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Sample records for amp signaling networks

  1. Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

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    Andre Terzic

    2009-04-01

    Full Text Available Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7 are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network.

  2. Genetic association of cyclic AMP signaling genes with bipolar disorder

    OpenAIRE

    McDonald, M-L; MacMullen, C.; Liu, D. J.; Leal, S M; Davis, R L

    2012-01-01

    The genetic basis for bipolar disorder (BPD) is complex with the involvement of multiple genes. As it is well established that cyclic adenosine monophosphate (cAMP) signaling regulates behavior, we tested variants in 29 genes that encode components of this signaling pathway for associations with BPD type I (BPD I) and BPD type II (BPD II). A total of 1172 individuals with BPD I, 516 individuals with BPD II and 1728 controls were analyzed. Single SNP (single-nucleotide polymorphism), haplotype...

  3. cAMP signaling in cortisol-producing adrenal adenoma.

    Science.gov (United States)

    Calebiro, Davide; Di Dalmazi, Guido; Bathon, Kerstin; Ronchi, Cristina L; Beuschlein, Felix

    2015-10-01

    The cAMP signaling pathway is one of the major players in the regulation of growth and hormonal secretion in adrenocortical cells. Although its role in the pathogenesis of adrenocortical hyperplasia associated with Cushing's syndrome has been clarified, a clear involvement of the cAMP signaling pathway and of one of its major downstream effectors, the protein kinase A (PKA), in sporadic adrenocortical adenomas remained elusive until recently. During the last year, a report by our group and three additional independent groups showed that somatic mutations of PRKACA, the gene coding for the catalytic subunit α of PKA, are a common genetic alteration in patients with Cushing's syndrome due to adrenal adenomas, occurring in 35-65% of the patients. In vitro studies revealed that those mutations are able to disrupt the association between catalytic and regulatory subunits of PKA, leading to a cAMP-independent activity of the enzyme. Despite somatic PRKACA mutations being a common finding in patients with clinically manifest Cushing's syndrome, the pathogenesis of adrenocortical adenomas associated with subclinical hypercortisolism seems to rely on a different molecular background. In this review, the role of cAMP/PKA signaling in the regulation of adrenocortical cell function and its alterations in cortisol-producing adrenocortical adenomas will be summarized, with particular focus on recent developments. PMID:26139209

  4. Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

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    Martina Schmidt

    2012-11-01

    Full Text Available Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD. Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myofibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP superfamily and IQ motif containing GTPase activating protein (IQGAPs. In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target.

  5. Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling.

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    Krishnamurthy, Srinath; Moorthy, Balakrishnan Shenbaga; Xin Xiang, Lim; Xin Shan, Lim; Bharatham, Kavitha; Tulsian, Nikhil Kumar; Mihalek, Ivana; Anand, Ganesh S

    2014-09-16

    Cyclic 3'5' adenosine monophosphate (cAMP)-dependent-protein kinase (PKA) signaling is a fundamental regulatory pathway for mediating cellular responses to hormonal stimuli. The pathway is activated by high-affinity association of cAMP with the regulatory subunit of PKA and signal termination is achieved upon cAMP dissociation from PKA. Although steps in the activation phase are well understood, little is known on how signal termination/resetting occurs. Due to the high affinity of cAMP to PKA (KD ∼ low nM), bound cAMP does not readily dissociate from PKA, thus begging the question of how tightly bound cAMP is released from PKA to reset its signaling state to respond to subsequent stimuli. It has been recently shown that phosphodiesterases (PDEs) can catalyze dissociation of bound cAMP and thereby play an active role in cAMP signal desensitization/termination. This is achieved through direct interactions with the regulatory subunit of PKA, thereby facilitating cAMP dissociation and hydrolysis. In this study, we have mapped direct interactions between a specific cyclic nucleotide phosphodiesterase (PDE8A) and a PKA regulatory subunit (RIα isoform) in mammalian cAMP signaling, by a combination of amide hydrogen/deuterium exchange mass spectrometry, peptide array, and computational docking. The interaction interface of the PDE8A:RIα complex, probed by peptide array and hydrogen/deuterium exchange mass spectrometry, brings together regions spanning the phosphodiesterase active site and cAMP-binding sites of RIα. Computational docking combined with amide hydrogen/deuterium exchange mass spectrometry provided a model for parallel dissociation of bound cAMP from the two tandem cAMP-binding domains of RIα. Active site coupling suggests a role for substrate channeling in the PDE-dependent dissociation and hydrolysis of cAMP bound to PKA. This is the first instance, to our knowledge, of PDEs directly interacting with a cAMP-receptor protein in a mammalian system, and

  6. 78 FR 1264 - CalAmp Wireless Networks Corporation, Waseca, MN; Notice of Negative Determination Regarding...

    Science.gov (United States)

    2013-01-08

    ... Employment and Training Administration CalAmp Wireless Networks Corporation, Waseca, MN; Notice of Negative... workers of the subject firm (TA-W-80,399A; CalAmp Wireless Networks Corporation, Waseca, Minnesota... Wireless Networks Corporation, Waseca, Minnesota to apply for TAA, the Department determines that...

  7. Mathematical model of cAMP-dependent signaling pathway in constitutive and UV-induced melanogenesis

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    Stolnitz, Mikhail M.; Peshkova, Anna Y.

    2002-07-01

    Cascade of reactions of cAMP-dependent signaling pathway in melanocytes is investigated by mathematical modeling. Model takes into account (alpha) -melanocyte stimulating hormone binding to melanocortin-1 receptor, adenylate cyclase activation by G-protein, increase of the intracellular cAMP concentration, PKA activation by cAMP, CREB phosphorylation by PKA, microphthalmia gene expression, microphthalmia binding to tyrosinase gene promoter, increase of tyrosinase synthesis. Positive and negative feedback loops of this system are analyzed.

  8. Cross-Talk between Signaling Pathways Can Generate Robust Oscillations in Calcium and cAMP

    OpenAIRE

    Siso-Nadal, Fernando; Fox, Jeffrey J.; Laporte, Stéphane A.; Hébert, Terence E.; Swain, Peter S

    2009-01-01

    Background To control and manipulate cellular signaling, we need to understand cellular strategies for information transfer, integration, and decision-making. A key feature of signal transduction is the generation of only a few intracellular messengers by many extracellular stimuli. Methodology/Principal Findings Here we model molecular cross-talk between two classic second messengers, cyclic AMP (cAMP) and calcium, and show that the dynamical complexity of the response of both messengers inc...

  9. Persistent cAMP Signaling by Internalized LH Receptors in Ovarian Follicles.

    Science.gov (United States)

    Lyga, Sandra; Volpe, Silvia; Werthmann, Ruth C; Götz, Konrad; Sungkaworn, Titiwat; Lohse, Martin J; Calebiro, Davide

    2016-04-01

    A crucial event in female reproduction occurs at midcycle, when a LH peak induces the final maturation of ovarian follicles. LH signals via a G protein-coupled receptor selectively expressed in the outermost follicular cell layers. However, how LH signals are relayed inside these cells and finally to the oocyte is incompletely understood. Here, we monitored LH signaling in intact ovarian follicles of transgenic mice expressing a fluorescent cAMP sensor. We found that LH stimulation induces 2 phases of cAMP signaling in all cell layers surrounding the oocyte. Interfering with LH receptor internalization abolished the second, persistent cAMP phase and partially inhibited oocyte meiosis resumption. These data suggest that persistent cAMP signals from internalized LH receptors contribute to transmitting LH effects inside follicle cells and ultimately to the oocyte. Thus, this study indicates that the recently proposed paradigm of cAMP signaling by internalized G protein-coupled receptors is implicated in receptor function and is physiologically relevant. PMID:26828746

  10. Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation.

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    Gundlach, Jan; Rath, Hermann; Herzberg, Christina; Mäder, Ulrike; Stülke, Jörg

    2016-01-01

    The Gram-positive model organism Bacillus subtilis produces the essential second messenger signaling nucleotide cyclic di-AMP. In B. subtilis and other bacteria, c-di-AMP has been implicated in diverse functions such as control of metabolism, cell division and cell wall synthesis, and potassium transport. To enhance our understanding of the multiple functions of this second messenger, we have studied the consequences of c-di-AMP accumulation at a global level by a transcriptome analysis. C-di-AMP accumulation affected the expression of about 700 genes, among them the two major operons required for biofilm formation. The expression of both operons was severely reduced both in the laboratory and a non-domesticated strain upon accumulation of c-di-AMP. In excellent agreement, the corresponding strain was unable to form complex colonies. In B. subtilis, the transcription factor SinR controls the expression of biofilm genes by binding to their promoter regions resulting in transcription repression. Inactivation of the sinR gene restored biofilm formation even at high intracellular c-di-AMP concentrations suggesting that the second messenger acts upstream of SinR in the signal transduction pathway. As c-di-AMP accumulation did not affect the intracellular levels of SinR, we conclude that the nucleotide affects the activity of SinR. PMID:27252699

  11. Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation

    Science.gov (United States)

    Gundlach, Jan; Rath, Hermann; Herzberg, Christina; Mäder, Ulrike; Stülke, Jörg

    2016-01-01

    The Gram-positive model organism Bacillus subtilis produces the essential second messenger signaling nucleotide cyclic di-AMP. In B. subtilis and other bacteria, c-di-AMP has been implicated in diverse functions such as control of metabolism, cell division and cell wall synthesis, and potassium transport. To enhance our understanding of the multiple functions of this second messenger, we have studied the consequences of c-di-AMP accumulation at a global level by a transcriptome analysis. C-di-AMP accumulation affected the expression of about 700 genes, among them the two major operons required for biofilm formation. The expression of both operons was severely reduced both in the laboratory and a non-domesticated strain upon accumulation of c-di-AMP. In excellent agreement, the corresponding strain was unable to form complex colonies. In B. subtilis, the transcription factor SinR controls the expression of biofilm genes by binding to their promoter regions resulting in transcription repression. Inactivation of the sinR gene restored biofilm formation even at high intracellular c-di-AMP concentrations suggesting that the second messenger acts upstream of SinR in the signal transduction pathway. As c-di-AMP accumulation did not affect the intracellular levels of SinR, we conclude that the nucleotide affects the activity of SinR. PMID:27252699

  12. Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline.

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    Hansen, Rolf T; Zhang, Han-Ting

    2013-06-21

    It is well known that alongside senescence there is a gradual decline in cognitive ability, most noticeably certain kinds of memory such as working, episodic, spatial, and long term memory. However, until recently, not much has been known regarding the specific mechanisms responsible for the decline in cognitive ability with age. Over the past decades, researchers have become more interested in cAMP signaling, and its downstream transcription factor cAMP response element binding protein (CREB) in the context of senescence. However, there is still a lack of understanding on what ultimately causes the cognitive deficits observed with senescence. This review will focus on the changes in intracellular signaling in the brain, more specifically, alterations in cAMP/CREB signaling in aging. In addition, the downstream effects of altered cAMP signaling on cognitive ability with age will be further discussed. Overall, understanding the senescent-related changes that occur in cAMP/CREB signaling could be important for the development of novel drug targets for both healthy aging, and pathological aging such as Alzheimer's disease. PMID:23623816

  13. cAMP/PKA signaling inhibits osteogenic differentiation and bone formation in rodent models.

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    Siddappa, Ramakrishnaiah; Mulder, Winfried; Steeghs, Ilse; van de Klundert, Christine; Fernandes, Hugo; Liu, Jun; Arends, Roel; van Blitterswijk, Clemens; de Boer, Jan

    2009-08-01

    We previously demonstrated that cAMP-mediated protein kinase A (PKA) activation induces in vitro osteogenesis and in vivo bone formation by human mesenchymal stem cells (hMSCs). To analyze the species-specific response of this phenomenon and to translate our findings into a clinical trial, suitable animal models and cell lines are desirable. In this report, we assessed whether PKA plays a similar proosteogenic role played by two commonly used PKA activators-N6,2'-O-dibutyryl-cAMP (db-cAMP) and 8-bromo cAMP (8b-cAMP)-in a number of model systems. To this end, we treated MC3T3-E1 cells, mouse calvarial osteoblasts, mouse MSCs, and rat MSCs with cAMP. We demonstrate that cAMP inhibits osteogenesis in rodent cell types, evidenced by inhibition of osteogenic markers such as alkaline phosphatase (ALP), osteocalcin (BGLAP), and collagen type 1 (COL1A1). In support of this, ex vivo-cultured mouse calvaria exposed to db-cAMP showed a reduction in bone volume. Interestingly, cAMP even stimulated adipogenic differentiation in rat MSCs. Taken together, our data demonstrate that cAMP inhibits osteogenesis in vitro and bone formation ex vivo in rodent models in contrast to our earlier findings in hMSCs. The species discrepancy in response to various osteogenic signals is a critical need to be tested in clinically relevant models to translate the fundamental findings in lower species level to clinical applications. PMID:19231969

  14. Coronin 1 regulates cognition and behavior through modulation of cAMP/protein kinase A signaling.

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    Rajesh Jayachandran

    2014-03-01

    Full Text Available Cognitive and behavioral disorders are thought to be a result of neuronal dysfunction, but the underlying molecular defects remain largely unknown. An important signaling pathway involved in the regulation of neuronal function is the cyclic AMP/Protein kinase A pathway. We here show an essential role for coronin 1, which is encoded in a genomic region associated with neurobehavioral dysfunction, in the modulation of cyclic AMP/PKA signaling. We found that coronin 1 is specifically expressed in excitatory but not inhibitory neurons and that coronin 1 deficiency results in loss of excitatory synapses and severe neurobehavioral disabilities, including reduced anxiety, social deficits, increased aggression, and learning defects. Electrophysiological analysis of excitatory synaptic transmission in amygdala revealed that coronin 1 was essential for cyclic-AMP-protein kinase A-dependent presynaptic plasticity. We further show that upon cell surface stimulation, coronin 1 interacted with the G protein subtype Gαs to stimulate the cAMP/PKA pathway. The absence of coronin 1 or expression of coronin 1 mutants unable to interact with Gαs resulted in a marked reduction in cAMP signaling. Strikingly, synaptic plasticity and behavioral defects of coronin 1-deficient mice were restored by in vivo infusion of a membrane-permeable cAMP analogue. Together these results identify coronin 1 as being important for cognition and behavior through its activity in promoting cAMP/PKA-dependent synaptic plasticity and may open novel avenues for the dissection of signal transduction pathways involved in neurobehavioral processes.

  15. Alterations of cAMP-dependent signaling in dystrophic skeletal muscle

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    Rüdiger eRudolf

    2013-10-01

    Full Text Available Autonomic regulation processes in striated muscles are largely mediated by cAMP/PKA-signaling. In order to achieve specificity of signaling its spatial-temporal compartmentation plays a critical role. We discuss here how specificity of cAMP/PKA-signaling can be achieved in skeletal muscle by spatio-temporal compartmentation. While a microdomain containing PKA type I in the region of the neuromuscular junction is important for post-synaptic, activity-dependent stabilization of the nicotinic acetylcholine receptor, PKA type I and II microdomains in the sarcomeric part of skeletal muscle are likely to play different roles, including the regulation of muscle homeostasis. These microdomains are due to specific A-kinase anchoring proteins, like rapsyn and myospryn. Importantly, recent evidence indicates that compartmentation of the cAMP/PKA-dependent signaling pathway and pharmacological activation of cAMP production are aberrant in different skeletal muscles disorders. Thus, we discuss here their potential as targets for palliative treatment of certain forms of dystrophy and myasthenia. Under physiological conditions, the neuropeptide, α-calcitonin-related peptide, as well as beta-adrenergic agonists are the most-mentioned natural triggers for activating cAMP/PKA signaling in skeletal muscle. While the precise domains and functions of these first messengers are still under investigation, agonists of β2-adrenoceptors clearly exhibit anabolic activity under normal conditions and reduce protein degradation during atrophic periods. Past and recent studies suggest direct sympathetic innervation of skeletal muscle fibers. In summary, the organization and roles of cAMP-dependent signaling in skeletal muscle are increasingly understood, revealing crucial functions in processes like nerve-muscle interaction and muscle trophicity.

  16. Cooperation between cAMP signalling and sulfonylurea in insulin secretion.

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    Shibasaki, T; Takahashi, T; Takahashi, H; Seino, S

    2014-09-01

    Although glucose is physiologically the most important regulator of insulin secretion, glucose-induced insulin secretion is modulated by hormonal and neural inputs to pancreatic β-cells. Most of the hormones and neurotransmitters evoke intracellular signals such as cAMP, Ca²⁺ , and phospholipid-derived molecules by activating G protein-coupled receptors (GPCRs). In particular, cAMP is a key second messenger that amplifies insulin secretion in a glucose concentration-dependent manner. The action of cAMP on insulin secretion is mediated by both protein kinase A (PKA)-dependent and Epac2A-dependent mechanisms. Many of the proteins expressed in β-cells are phosphorylated by PKA in vitro, but only a few proteins in which PKA phosphorylation directly affects insulin secretion have been identified. On the other hand, Epac2A activates the Ras-like small G protein Rap in a cAMP-dependent manner. Epac2A is also directly activated by various sulfonylureas, except for gliclazide. 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analogue, and glibenclamide, a sulfonylurea, synergistically activate Epac2A and Rap1, whereas adrenaline, which suppresses cAMP production in pancreatic β-cells, blocks activation of Epac2A and Rap1 by glibenclamide. Thus, cAMP signalling and sulfonylurea cooperatively activate Epac2A and Rap1. This interaction could account, at least in part, for the synergistic effects of incretin-related drugs and sulfonylureas in insulin secretion. Accordingly, clarification of the mechanism of Epac2A activation may provide therapeutic strategies to improve insulin secretion in diabetes. PMID:25200305

  17. Neural networks in signal processing

    International Nuclear Information System (INIS)

    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.)

  18. Involvement of the second messenger cAMP in gravity-signal transduction in physarum

    Science.gov (United States)

    Block, I.; Rabien, H.; Ivanova, K.

    The aim of the investigation was to clarify, whether cellular signal processing following graviperception involves second messenger pathways. The test object was a most gravisensitive free-living ameboid cell, the myxomycete (acellular slime mold) Physarum polycephalum. It was demonstrated that the motor response is related to acceleration-dependent changes in the levels of the cellular second messenger cyclic adenosine monophosphate (cAMP). Rotating Physarum plasmodia in the gravity field of the Earth about a horizontal axis increased their cAMP concentration. Depriving the cells for a few days of the acceleration stimulus (near weightlessness in a space experiment on STS-69) slightly lowered plasmodial cAMP levels. Thus, the results provide first indications that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

  19. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

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    Ghania Ramdani

    2015-05-01

    Full Text Available Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.

  20. Allostery through the computational microscope: cAMP activation of a canonical signalling domain

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    Malmstrom, Robert D.; Kornev, Alexandr P.; Taylor, Susan S.; Amaro, Rommie E.

    2015-07-01

    Ligand-induced protein allostery plays a central role in modulating cellular signalling pathways. Here using the conserved cyclic nucleotide-binding domain of protein kinase A's (PKA) regulatory subunit as a prototype signalling unit, we combine long-timescale, all-atom molecular dynamics simulations with Markov state models to elucidate the conformational ensembles of PKA's cyclic nucleotide-binding domain A for the cAMP-free (apo) and cAMP-bound states. We find that both systems exhibit shallow free-energy landscapes that link functional states through multiple transition pathways. This observation suggests conformational selection as the general mechanism of allostery in this canonical signalling domain. Further, we expose the propagation of the allosteric signal through key structural motifs in the cyclic nucleotide-binding domain and explore the role of kinetics in its function. Our approach integrates disparate lines of experimental data into one cohesive framework to understand structure, dynamics and function in complex biological systems.

  1. Human cellular differences in cAMP - CREB signaling correlate with light-dependent melatonin suppression and bipolar disorder

    NARCIS (Netherlands)

    Gaspar, Ludmila; van de Werken, Maan; Johansson, Anne-Sophie; Moriggi, Ermanno; Owe-Larsson, Bjorn; Kocks, Janwillem W. H.; Lundkvist, Gabriella B.; Gordijn, Marijke C. M.; Brown, Steven A.

    2014-01-01

    Various lines of evidence suggest a mechanistic role for altered cAMP-CREB (cAMP response element - binding protein) signaling in depressive and affective disorders. However, the establishment and validation of human inter-individual differences in this and other major signaling pathways has proven

  2. Communication of cAMP by connexin43 gap junctions regulates osteoblast signaling and gene expression.

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    Gupta, Aditi; Anderson, Hidayah; Buo, Atum M; Moorer, Megan C; Ren, Margaret; Stains, Joseph P

    2016-08-01

    Connexin43 (Cx43) containing gap junctions play an important role in bone homeostasis, yet little is known about the second messengers communicated by Cx43 among bone cells. Here, we used MC3T3-E1 pre-osteoblasts and UMR106 rat osteosarcoma cells to test the hypothesis that cAMP is a second messenger communicated by bone cells through Cx43 containing gap junctions in a manner that is sufficient to impact osteoblast function. Overexpression of Cx43 markedly enhanced the activity of a cAMP-response element driven transcriptional luciferase reporter (CRE-luc) and increased phospho-CREB and phospho-ERK1/2 levels following expression of a constitutively active Gsα or by treatment with prostaglandin E2 (PGE2), 3-Isobutyl-1-methyl xanthine (IBMX) or forskolin. The Cx43-dependent potentiation of signaling in PGE2 treated cells was not accompanied by a further increase in cAMP levels, suggesting that the cAMP was shared between cells rather than Cx43 enhancing cAMP production. To support this, we developed a novel assay in which one set of cells expressing constitutively active Gsα (donor cells) were co-cultured with a second set of cells expressing a CRE-luc reporter (acceptor cells). Using this assay, activation of a CRE-luc reporter in the acceptor cells was both Cx43- and cell contact-dependent, indicating communication of cAMP among cells. Finally, we showed that Cx43 increased the cAMP-dependent mRNA expression of receptor activator of nuclear factor kappa B ligand (RANKL) and enhanced the repression of the sclerostin mRNA, implying a potential mechanism for the modulation of tissue remodeling. In total, these data demonstrate that Cx43 can communicate cAMP between cells and, more importantly, that the communicated cAMP is sufficient to impact signal transduction cascades and the expression of key bone effector molecules between interconnected cells. PMID:27156839

  3. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

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    Ketty Bacallao

    Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

  4. Retrograde signaling: Organelles go networking.

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    Kleine, Tatjana; Leister, Dario

    2016-08-01

    The term retrograde signaling refers to the fact that chloroplasts and mitochondria utilize specific signaling molecules to convey information on their developmental and physiological states to the nucleus and modulate the expression of nuclear genes accordingly. Signals emanating from plastids have been associated with two main networks: 'Biogenic control' is active during early stages of chloroplast development, while 'operational' control functions in response to environmental fluctuations. Early work focused on the former and its major players, the GUN proteins. However, our view of retrograde signaling has since been extended and revised. Elements of several 'operational' signaling circuits have come to light, including metabolites, signaling cascades in the cytosol and transcription factors. Here, we review recent advances in the identification and characterization of retrograde signaling components. We place particular emphasis on the strategies employed to define signaling components, spanning the entire spectrum of genetic screens, metabolite profiling and bioinformatics. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID:26997501

  5. Mathematical Modelling Plant Signalling Networks

    KAUST Repository

    Muraro, D.

    2013-01-01

    During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This mathematical analysis of sub-cellular molecular mechanisms paves the way for more comprehensive modelling studies of hormonal transport and signalling in a multi-scale setting. © EDP Sciences, 2013.

  6. Adenyl cyclases and cAMP in plant signaling - Past and present

    KAUST Repository

    Gehring, Christoph A

    2010-06-25

    In lower eukaryotes and animals 3\\'-5\\'-cyclic adenosine monophosphate (cAMP) and adenyl cyclases (ACs), enzymes that catalyse the formation of cAMP from ATP, have long been established as key components and second messengers in many signaling pathways. In contrast, in plants, both the presence and biological role of cAMP have been a matter of ongoing debate and some controversy. Here we shall focus firstly on the discovery of cellular cAMP in plants and evidence for a role of this second messenger in plant signal transduction. Secondly, we shall review current evidence of plant ACs, analyse aspects of their domain organisations and the biological roles of candidate molecules. In addition, we shall assess different approaches based on search motifs consisting of functionally assigned amino acids in the catalytic centre of annotated and/or experimentally tested nucleotide cyclases that can contribute to the identification of novel candidate molecules with AC activity such as F-box and TIR proteins. 2010 Gehring; licensee BioMed Central Ltd.

  7. PACAP signaling to DREAM: a cAMP-dependent pathway that regulates cortical astrogliogenesis.

    Science.gov (United States)

    Vallejo, Mario

    2009-04-01

    Astrocytes constitute a very abundant cell type in the mammalian central nervous system and play critical roles in brain function. During development, astrocytes are generated from neural progenitor cells only after these cells have generated neurons. This so called gliogenic switch is tightly regulated by intrinsic factors that inhibit the generation of astrocytes during the neurogenic period. Once neural progenitors acquire gliogenic competence, they differentiate into astrocytes in response to specific extracellular signals. Some of these signals are delivered by neurotrophic cytokines via activation of the gp130-JAK-signal transducer and activator of transcription system, whereas others depend on the activity of pituitary adenylate cyclase-activating polypeptide (PACAP) on specific PAC1 receptors that stimulate the production of cAMP. This results in the activation of the small GTPases Rap1 and Ras, and in the cAMP-dependent entry of extracellular calcium into the cell. Calcium, in turn, stimulates the transcription factor downstream regulatory element antagonist modulator (DREAM), which is bound to specific sites of the promoter of the glial fibrillary acidic protein gene, stimulating its expression during astrocyte differentiation. Lack of DREAM in vivo results in alterations in the number of neurons and astrocytes generated during development. Thus, the PACAP-cAMP-Ca(2+)-DREAM signaling cascade constitutes an important pathway to activate glial-specific gene expression during astrocyte differentiation. PMID:19238593

  8. Cross-talk between signaling pathways can generate robust oscillations in calcium and cAMP.

    Directory of Open Access Journals (Sweden)

    Fernando Siso-Nadal

    Full Text Available BACKGROUND: To control and manipulate cellular signaling, we need to understand cellular strategies for information transfer, integration, and decision-making. A key feature of signal transduction is the generation of only a few intracellular messengers by many extracellular stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Here we model molecular cross-talk between two classic second messengers, cyclic AMP (cAMP and calcium, and show that the dynamical complexity of the response of both messengers increases substantially through their interaction. In our model of a non-excitable cell, both cAMP and calcium concentrations can oscillate. If mutually inhibitory, cross-talk between the two second messengers can increase the range of agonist concentrations for which oscillations occur. If mutually activating, cross-talk decreases the oscillation range, but can generate 'bursting' oscillations of calcium and may enable better filtering of noise. CONCLUSION: We postulate that this increased dynamical complexity allows the cell to encode more information, particularly if both second messengers encode signals. In their native environments, it is unlikely that cells are exposed to one stimulus at a time, and cross-talk may help generate sufficiently complex responses to allow the cell to discriminate between different combinations and concentrations of extracellular agonists.

  9. Signal integration in the galactose network of Escherichia coli.

    Science.gov (United States)

    Semsey, Szabolcs; Krishna, Sandeep; Sneppen, Kim; Adhya, Sankar

    2007-07-01

    The gal regulon of Escherichia coli contains genes involved in galactose transport and metabolism. Transcription of the gal regulon genes is regulated in different ways by two iso-regulatory proteins, Gal repressor (GalR) and Gal isorepressor (GalS), which recognize the same binding sites in the absence of d-galactose. DNA binding by both GalR and GalS is inhibited in the presence of d-galactose. Many of the gal regulon genes are activated in the presence of the adenosine cyclic-3',5'-monophosphate (cAMP)-cAMP receptor protein (CRP) complex. We studied transcriptional regulation of the gal regulon promoters simultaneously in a purified system and attempted to integrate the two small molecule signals, d-galactose and cAMP, that modulate the isoregulators and CRP respectively, at each promoter, using Boolean logic. Results show that similarly organized promoters can have different input functions. We also found that in some cases the activity of the promoter and the cognate gene can be described by different logic gates. We combined the transcriptional network of the galactose regulon, obtained from our experiments, with literature data to construct an integrated map of the galactose network. Structural analysis of the network shows that at the interface of the genetic and metabolic network, feedback loops are by far the most common motif. PMID:17630975

  10. cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation

    Directory of Open Access Journals (Sweden)

    Gourlay Campbell W

    2010-11-01

    Full Text Available Abstract Background Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. Results We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. Conclusions We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast.

  11. Bioinformatics analyses for signal transduction networks

    Institute of Scientific and Technical Information of China (English)

    LIU Wei; LI Dong; ZHU YunPing; HE FuChu

    2008-01-01

    Research in signaling networks contributes to a deeper understanding of organism living activities. With the development of experimental methods in the signal transduction field, more and more mechanisms of signaling pathways have been discovered. This paper introduces such popular bioin-formatics analysis methods for signaling networks as the common mechanism of signaling pathways and database resource on the Internet, summerizes the methods of analyzing the structural properties of networks, including structural Motif finding and automated pathways generation, and discusses the modeling and simulation of signaling networks in detail, as well as the research situation and tendency in this area. Now the investigation of signal transduction is developing from small-scale experiments to large-scale network analysis, and dynamic simulation of networks is closer to the real system. With the investigation going deeper than ever, the bioinformatics analysis of signal transduction would have immense space for development and application.

  12. Protein evolution on a human signaling network

    OpenAIRE

    Purisima Enrico O; Cui Qinghua; Wang Edwin

    2009-01-01

    Abstract Background The architectural structure of cellular networks provides a framework for innovations as well as constraints for protein evolution. This issue has previously been studied extensively by analyzing protein interaction networks. However, it is unclear how signaling networks influence and constrain protein evolution and conversely, how protein evolution modifies and shapes the functional consequences of signaling networks. In this study, we constructed a human signaling networ...

  13. Ca2+-regulated-cAMP/PKA signaling in cardiac pacemaker cells links ATP supply to demand

    Science.gov (United States)

    Yaniv, Yael; Juhaszova, Magdalena; Lyashkov, Alexey E.; Spurgeon, Harold A.; Sollott, Steven J.; Lakatta, Edward G.

    2011-01-01

    Rationale In sinoatrial node cells (SANC), Ca2+ activates adenylate cyclase (AC) to generate a high basal level of cAMP-mediated/protein kinase A (PKA)-dependent phosphorylation of Ca2+ cycling proteins. These result in spontaneous sarcoplasmic-reticulum (SR) generated rhythmic Ca2+ oscillations during diastolic depolarization, that not only trigger the surface membrane to generate rhythmic action potentials (APs), but, in a feed-forward manner, also activate AC/PKA signaling. ATP is consumed to pump Ca2+ to the SR, to produce cAMP, to support contraction and to maintain cell ionic homeostasis. Objective Since a negative feedback mechanism links ATP-demand to ATP production, we hypothesized that (1) both basal ATP supply and demand in SANC would be Ca2+-cAMP/PKA dependent; and (2) due to its feed–forward nature, a decrease in flux through the Ca2+-cAMP/PKA signaling axis will reduce the basal ATP production rate. Methods and Results O2 consumption in spontaneous beating SANC was comparable to ventricular myocytes (VM) stimulated at 3 Hz. Graded reduction of basal Ca2+-cAMP/PKA signaling to reduce ATP demand in rabbit SANC produced graded ATP depletion (r2=0.96), and reduced O2 consumption and flavoprotein fluorescence. Neither inhibition of glycolysis, selectively blocking contraction nor specific inhibition of mitochondrial Ca2+ flux reduced the ATP level. Conclusions Feed-forward basal Ca2+-cAMP/PKA signaling both consumes ATP to drive spontaneous APs in SANC and is tightly linked to mitochondrial ATP production. Interfering with Ca2+-cAMP/PKA signaling not only slows the firing rate and reduces ATP consumption, but also appears to reduce ATP production so that ATP levels fall. This distinctly differs from VM, which lack this feed-forward basal cAMP/PKA signaling, and in which ATP level remains constant when the demand changes. PMID:21835182

  14. Twitching motility and cAMP levels: signal transduction through a single methyl-accepting chemotaxis protein.

    Science.gov (United States)

    Jansari, Vibhuti H; Potharla, Vishwakanth Y; Riddell, Geoff T; Bardy, Sonia L

    2016-06-01

    The Pseudomonas aeruginosa Chp chemosensory system regulates twitching motility, intracellular adenosine 3('') 5(')-cyclic monophosphate (cAMP) levels and is postulated to be involved in directional twitching towards phosphatidylethanolamine (PE). Because PilJ is the only methyl-accepting chemotaxis protein (MCP) identified in the Chp system, we determined the role of PilJ in mediating signal transduction for the distinct outputs of this system. Mutants that lack the periplasmic domain of PilJ (pilJΔ74-273) showed lower levels of cAMP but retained directional twitching towards PE. While initial studies revealed reduced twitching motility by PilJΔ74-273, this was due to decreased cAMP levels. Our data illustrate the importance of the periplasmic domain of PilJ in regulating cAMP. This is the first time a defined domain within PilJ has been identified as having a distinct role in signal transduction. PMID:27190147

  15. 78 FR 1252 - CalAmp Wireless Networks Corporation (CWNC), Satellite Products Division, Including On-Site...

    Science.gov (United States)

    2013-01-08

    ... December 13, 2011 (76 FR 77556). At the request of the State of Minnesota, the Department reviewed the... Employment and Training Administration CalAmp Wireless Networks Corporation (CWNC), Satellite Products Division, Including On-Site Leased Workers From Select Staffing, Oxnard, CA; CalAmp Wireless...

  16. Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion

    OpenAIRE

    Ghupurjan Gheni; Masahito Ogura; Masahiro Iwasaki; Norihide Yokoi; Kohtaro Minami; Yasumune Nakayama; Kazuo Harada; Benoit Hastoy; Xichen Wu; Harumi Takahashi; Kazushi Kimura; Toshiya Matsubara; Ritsuko Hoshikawa; Naoya Hatano; Kenji Sugawara

    2014-01-01

    Summary Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shu...

  17. cAMP-dependent proteolysis of GATA-6 is linked to JNK-signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan); Maeda, Masatomo, E-mail: mmaeda@iwate-med.ac.jp [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6. Black-Right-Pointing-Pointer Effect of a JNK activator anisomycin on the proteolysis was examined. Black-Right-Pointing-Pointer Anisomycin stimulated the export of nuclear GATA-6 into the cytoplasm. Black-Right-Pointing-Pointer JNK activated the CRM1 mediated nuclear export of GATA-6. Black-Right-Pointing-Pointer JNK further stimulated slowly the degradation of GATA-6 by cytoplasmic proteasomes. -- Abstract: A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6 by proteasomes around its IC50. We further examined the effects of SP600125 on the degradation of GATA-6 in detail, since an activator of JNK (anisomycin) is available. Interestingly, anisomycin immediately stimulated the export of nuclear GATA-6 into the cytoplasm, and then the cytoplasmic content of GATA-6 decreased slowly through degradation by proteasomes. Such an effect of anisomycin was inhibited by SP600125, indicating that the observed phenomenon might be linked to the JNK signaling pathway. The inhibitory effect of SP600125 could not be ascribed to the inhibition of PKA, since phosphorylation of CREB occurred in the presence of dbcAMP and SP600125. The nuclear export of GATA-6 was inhibited by leptomycin B, suggesting that CRM1-mediated export could be activated by anisomycin. Furthermore, it seems likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA-6 through CRM1 but also the degradation of GATA-6 by cytoplasmic proteasomes. In contrast, A-kinase might activate only the latter process through JNK.

  18. Signaling in large-scale neural networks

    DEFF Research Database (Denmark)

    Berg, Rune W; Hounsgaard, Jørn

    2009-01-01

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

  19. cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

    Science.gov (United States)

    Peng, Li-qun; Li, Ping; Zhang, Qiu-li; Hong, Lan; Liu, Li-ping

    2016-01-01

    Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na+-K+-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 µmol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 (3.0 µmol/L), an inhibitor for reverse mode of Na+-Ca2+ exchangers (NCX), but did not by L-type Ca2+ channel blocker nifedipine (1.0 µmol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 µmol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 µmol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 µmol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 µmol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds. PMID:26807018

  20. Organisation of signal flow in directed networks

    CERN Document Server

    Bányai, M; Négyessy, L; Bazsó, F

    2010-01-01

    Structure of signal flow in the network is mapped using the notion of convergence degree (CD), introduced in N\\'egyessy et al 2008 Proc. Roy. Soc. B, vol. 275 p. 2403. We refine the definition of convergence degree and complement it with the notion of the overlapping set of an edge. Definitions of the edge measures are based on the notion of shortest paths, thus they encapsulate global network properties. Using the defining notions of convergence degree and overlapping set we clarify the meaning of network causality. Properties of CD are explored on two model graphs, convergence degree values are calculated for regular oriented trees and its probability density function for networks grown with preferential attachment mechanism. Based on the node-reduced convergence degree representation of the network we distinguish nodes according to their local and global signal transmitting and processing properties. In case of real-world networks, local and global signal transmitting and processing properties differ, exhi...

  1. Signal Propagation in Cortical Networks: A Digital Signal Processing Approach

    OpenAIRE

    Rodrigues, Francisco A.

    2009-01-01

    This work reports a digital signal processing approach to representing and modeling transmission and combination of signals in cortical networks. The signal dynamics is modeled in terms of diffusion, which allows the information processing undergone between any pair of nodes to be fully characterized in terms of a finite impulse response (FIR) filter. Diffusion without and with time decay are investigated. All filters underlying the cat and macaque cortical organization are found to be of l...

  2. Interaction between cAMP and intracellular Ca(2+)-signaling pathways during odor-perception and adaptation in Drosophila.

    Science.gov (United States)

    Murmu, Meena Sriti; Martin, Jean-René

    2016-09-01

    Binding of an odorant to olfactory receptors triggers cascades of second messenger systems in olfactory receptor neurons (ORNs). Biochemical studies indicate that the transduction mechanism at ORNs is mediated by cyclic adenosine monophosphate (cAMP) and/or inositol,1,4,5-triphosphate (InsP3)-signaling pathways in an odorant-dependent manner. However, the interaction between these two second messenger systems during olfactory perception or adaptation processes is much less understood. Here, we used interfering-RNAi to disrupt the level of cAMP alone or in combination with the InsP3-signaling pathway cellular targets, InsP3 receptor (InsP3R) or ryanodine receptor (RyR) in ORNs, and quantify at ORN axon terminals in the antennal lobe, the odor-induced Ca(2+)-response. In-vivo functional bioluminescence Ca(2+)-imaging indicates that a single 5s application of an odor increased Ca(2+)-transients at ORN axon terminals. However, compared to wild-type controls, the magnitude and duration of ORN Ca(2+)-response was significantly diminished in cAMP-defective flies. In a behavioral assay, perception of odorants was defective in flies with a disrupted cAMP level suggesting that the ability of flies to correctly detect an odor depends on cAMP. Simultaneous disruption of cAMP level and InsP3R or RyR further diminished the magnitude and duration of ORN response to odorants and affected the flies' ability to detect an odor. In conclusion, this study provides functional evidence that cAMP and InsP3-signaling pathways act in synergy to mediate odor processing within the ORN axon terminals, which is encoded in the magnitude and duration of ORN response. PMID:27212269

  3. Organization of signal flow in directed networks

    International Nuclear Information System (INIS)

    Confining an answer to the question of whether and how the coherent operation of network elements is determined by the network structure is the topic of our work. We map the structure of signal flow in directed networks by analysing the degree of edge convergence and the overlap between the in- and output sets of an edge. Definitions of convergence degree and overlap are based on the shortest paths, thus they encapsulate global network properties. Using the defining notions of convergence degree and overlapping set we clarify the meaning of network causality and demonstrate the crucial role of chordless circles. In real-world networks the flow representation distinguishes nodes according to their signal transmitting, processing and control properties. The analysis of real-world networks in terms of flow representation was in accordance with the known functional properties of the network nodes. It is shown that nodes with different signal processing, transmitting and control properties are randomly connected at the global scale, while local connectivity patterns depart from randomness. The grouping of network nodes according to their signal flow properties was unrelated to the network's community structure. We present evidence that the signal flow properties of small-world-like, real-world networks cannot be reconstructed by algorithms used to generate small-world networks. Convergence degree values were calculated for regular oriented trees, and the probability density function for networks grown with the preferential attachment mechanism. For Erdos–Rényi graphs we calculated the probability density function of both convergence degrees and overlaps

  4. Signal processing devices and networks

    Science.gov (United States)

    Graveline, S. W.

    1985-02-01

    According to an axiom employed with respect to electronic warfare (EW) behavior, system effectiveness increases directly with the amount of information recovered from an intercepted signal. The evolution in EW signal processing capability has proceeded accordingly. After an initiation of EW systems as broadband receivers, the most significant advance was related to the development of digital instantaneous frequency measurement (DIFM) devices. The use of such devices provides significant improvements regarding signal identification and RF measurement to within a few MHz. An even more accurate processing device, the digital RF memory (DRFM), allows frequency characterization to within a few Hz. This invention was made in response to the need to process coherent pulse signals. Attention is given to the generic EW system, the modern EW system, and the generic receiver function for a modern EW system showing typical output signals.

  5. Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling.

    Science.gov (United States)

    Bachmann, Verena A; Mayrhofer, Johanna E; Ilouz, Ronit; Tschaikner, Philipp; Raffeiner, Philipp; Röck, Ruth; Courcelles, Mathieu; Apelt, Federico; Lu, Tsan-Wen; Baillie, George S; Thibault, Pierre; Aanstad, Pia; Stelzl, Ulrich; Taylor, Susan S; Stefan, Eduard

    2016-07-12

    Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein-protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl-terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions. PMID:27357676

  6. Metabolic Basis for Thyroid Hormone Liver Preconditioning: Upregulation of AMP-Activated Protein Kinase Signaling

    Directory of Open Access Journals (Sweden)

    Luis A. Videla

    2012-01-01

    Full Text Available The liver is a major organ responsible for most functions of cellular metabolism and a mediator between dietary and endogenous sources of energy for extrahepatic tissues. In this context, adenosine-monophosphate- (AMP- activated protein kinase (AMPK constitutes an intrahepatic energy sensor regulating physiological energy dynamics by limiting anabolism and stimulating catabolism, thus increasing ATP availability. This is achieved by mechanisms involving direct allosteric activation and reversible phosphorylation of AMPK, in response to signals such as energy status, serum insulin/glucagon ratio, nutritional stresses, pharmacological and natural compounds, and oxidative stress status. Reactive oxygen species (ROS lead to cellular AMPK activation and downstream signaling under several experimental conditions. Thyroid hormone (L-3,3′,5-triiodothyronine, T3 administration, a condition that enhances liver ROS generation, triggers the redox upregulation of cytoprotective proteins affording preconditioning against ischemia-reperfusion (IR liver injury. Data discussed in this work suggest that T3-induced liver activation of AMPK may be of importance in the promotion of metabolic processes favouring energy supply for the induction and operation of preconditioning mechanisms. These include antioxidant, antiapoptotic, and anti-inflammatory mechanisms, repair or resynthesis of altered biomolecules, induction of the homeostatic acute-phase response, and stimulation of liver cell proliferation, which are required to cope with the damaging processes set in by IR.

  7. Hypoxia regulates the cAMP- and Ca2+/calmodulin signaling systems in PC12 cells.

    Science.gov (United States)

    Beitner-Johnson, D; Leibold, J; Millhorn, D E

    1998-01-01

    Hypoxic/ischemic trauma is a primary factor in the pathology of various disease states. Yet, very little is known about the molecular mechanisms involved in cellular responses and adaptations to hypoxia. As a means of identifying intracellular signaling systems that are regulated in response to hypoxia, the effects of acute and chronic hypoxia on the activity of protein kinase A (PKA) and Ca2+/CaM-dependent protein kinase II (CaMK-II) were evaluated in rat pheochromocytoma (PC12) cells. Chronic (> 6 hr), but not acute exposure to hypoxia (5% O2) significantly decreased both PKA enzyme activity and immunoreactivity compared to control levels. This effect was not due to hypoxia-induced alterations in cell number or viability. Similarly, chronic hypoxia significantly decreased CaMK-II enzyme activity and protein levels in PC12 cells. These data demonstrate that down-regulation of the cAMP and Ca2+/CaM-signaling systems is a mechanism by which PC12 cells adapt to long-term hypoxia. PMID:9439610

  8. Signalling in voice over IP Networks

    OpenAIRE

    Moreno, José Ignacio; Soto, Ignacio; Larrabeiti, David

    2001-01-01

    Voice signalling protocols have evolved, keeping with the prevalent move from circuit to packet switched networks. Standardization bodies have provided solutions for carrying voice traffic over packet networks while the main manufacturers are already providing products in workgroup, enterprise, or operator portfolio. This trend will accrue in next years due to the evolution of UMTS mobile networks to an “all-IP” environment. In this paper we present the various architectures that are proposed...

  9. Regulation patterns in signaling networks of cancer

    Directory of Open Access Journals (Sweden)

    Kannabiran Nandakumar

    2010-11-01

    Full Text Available Abstract Background Formation of cellular malignancy results from the disruption of fine tuned signaling homeostasis for proliferation, accompanied by mal-functional signals for differentiation, cell cycle and apoptosis. We wanted to observe central signaling characteristics on a global view of malignant cells which have evolved to selfishness and independence in comparison to their non-malignant counterparts that fulfill well defined tasks in their sample. Results We investigated the regulation of signaling networks with twenty microarray datasets from eleven different tumor types and their corresponding non-malignant tissue samples. Proteins were represented by their coding genes and regulatory distances were defined by correlating the gene-regulation between neighboring proteins in the network (high correlation = small distance. In cancer cells we observed shorter pathways, larger extension of the networks, a lower signaling frequency of central proteins and links and a higher information content of the network. Proteins of high signaling frequency were enriched with cancer mutations. These proteins showed motifs of regulatory integration in normal cells which was disrupted in tumor cells. Conclusion Our global analysis revealed a distinct formation of signaling-regulation in cancer cells when compared to cells of normal samples. From these cancer-specific regulation patterns novel signaling motifs are proposed.

  10. Biasing vector network analyzers using variable frequency and amplitude signals

    Science.gov (United States)

    Nobles, J. E.; Zagorodnii, V.; Hutchison, A.; Celinski, Z.

    2016-08-01

    We report the development of a test setup designed to provide a variable frequency biasing signal to a vector network analyzer (VNA). The test setup is currently used for the testing of liquid crystal (LC) based devices in the microwave region. The use of an AC bias for LC based devices minimizes the negative effects associated with ionic impurities in the media encountered with DC biasing. The test setup utilizes bias tees on the VNA test station to inject the bias signal. The square wave biasing signal is variable from 0.5 to 36.0 V peak-to-peak (VPP) with a frequency range of DC to 10 kHz. The test setup protects the VNA from transient processes, voltage spikes, and high-frequency leakage. Additionally, the signals to the VNA are fused to ½ amp and clipped to a maximum of 36 VPP based on bias tee limitations. This setup allows us to measure S-parameters as a function of both the voltage and the frequency of the applied bias signal.

  11. Regulatory Roles of Metabolites in Cell Signaling Networks

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Wei Xu; Shimin Zhao

    2013-01-01

    Mounting evidence suggests that cellular metabolites,in addition to being sources of fuel and macromolecular substrates,are actively involved in signaling and epigenetic regulation.Many metabolites,such as cyclic AMP,which regulates phosphorylation/dephosphorylation,have been identified to modulate DNA and histone methylation and protein stability.Metabolite-driven cellular regulation occurs through two distinct mechanisms:proteins allosterically bind or serve as substrates for protein signaling pathways,and metabolites covalently modify proteins to regulate their functions.Such novel protein metabolites include fumarate,succinyl-CoA,propionyl-CoA,butyryl-CoA and crontonyl-CoA.Other metabolites,including α-ketoglutarate,succinate and fumarate,regulate epigenetic processes and cell signaling via protein binding.Here,we summarize recent progress in metabolite-derived post-translational protein modification and metabolite-binding associated signaling regulation.Uncovering metabolites upstream of cell signaling and epigenetic networks permits the linkage of metabolic disorders and human diseases,and suggests that metabolite modulation may be a strategy for innovative therapeutics and disease prevention techniques.

  12. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids

    NARCIS (Netherlands)

    Madsen, L.; Pedersen, L.M.; Liaset, B.; Ma, T.; Petersen, R.K.; Berg, S. van den; Pan, J.; Müller-Decker, K.M.; Dülsner, E.D.; Kleemann, R.; Kooistra, T.; Døskeland, S.O.; Kristiansen, K.

    2008-01-01

    The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti-ad

  13. Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

    Directory of Open Access Journals (Sweden)

    Jong Hyun Kim

    Full Text Available BACKGROUND: Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation. CONCLUSIONS/SIGNIFICANCE: These results

  14. Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Ghupurjan Gheni

    2014-10-01

    Full Text Available Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shuttle upon glucose stimulation underlies the stimulatory effect of incretins and that glutamate uptake into insulin granules mediated by cAMP/PKA signaling amplifies insulin release. Glutamate production is diminished in an incretin-unresponsive, insulin-secreting β cell line and pancreatic islets of animal models of human diabetes and obesity. Conversely, a membrane-permeable glutamate precursor restores amplification of insulin secretion in these models. Thus, cytosolic glutamate represents the elusive link between glucose metabolism and cAMP action in incretin-induced insulin secretion.

  15. Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

    Science.gov (United States)

    Gao, Jun; Joseph, Nadine; Xie, Zhigang; Zhou, Ying; Durak, Omer; Zhang, Lei; Zhu, J. Julius; Clauser, Karl R.; Carr, Steven A.; Tsai, Li-Huei

    2011-01-01

    Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation. PMID:21984943

  16. Hydrogen peroxide induces activation of insulin signaling pathway via AMP-dependent kinase in podocytes

    Energy Technology Data Exchange (ETDEWEB)

    Piwkowska, Agnieszka, E-mail: apiwkowska@cmdik.pan.pl [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Rogacka, Dorota; Angielski, Stefan [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Jankowski, Maciej [Mossakowski Medical Research Centre, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdansk (Poland); Medical University of Gdansk, Department of Therapy Monitoring and Pharmacogenetics (Poland)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer H{sub 2}O{sub 2} activates the insulin signaling pathway and glucose uptake in podocytes. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} induces time-dependent changes in AMPK phosphorylation. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} enhances insulin signaling pathways via AMPK activation. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} stimulation of glucose uptake is AMPK-dependent. -- Abstract: Podocytes are cells that form the glomerular filtration barrier in the kidney. Insulin signaling in podocytes is critical for normal kidney function. Insulin signaling is regulated by oxidative stress and intracellular energy levels. We cultured rat podocytes to investigate the effects of hydrogen peroxide (H{sub 2}O{sub 2}) on the phosphorylation of proximal and distal elements of insulin signaling. We also investigated H{sub 2}O{sub 2}-induced intracellular changes in the distribution of protein kinase B (Akt). Western blots showed that H{sub 2}O{sub 2} (100 {mu}M) induced rapid, transient phosphorylation of the insulin receptor (IR), the IR substrate-1 (IRS1), and Akt with peak activities at 5 min ({Delta} 183%, P < 0.05), 3 min ({Delta} 414%, P < 0.05), and 10 min ({Delta} 35%, P < 0.05), respectively. Immunostaining cells with an Akt-specific antibody showed increased intensity at the plasma membrane after treatment with H{sub 2}O{sub 2}>. Furthermore, H{sub 2}O{sub 2} inhibited phosphorylation of the phosphatase and tensin homologue (PTEN; peak activity at 10 min; {Delta} -32%, P < 0.05) and stimulated phosphorylation of the AMP-dependent kinase alpha subunit (AMPK{alpha}; 78% at 3 min and 244% at 10 min). The stimulation of AMPK was abolished with an AMPK inhibitor, Compound C (100 {mu}M, 2 h). Moreover, Compound C significantly reduced the effect of H{sub 2}O{sub 2} on IR phosphorylation by about 40% (from 2.07 {+-} 0.28 to 1.28 {+-} 0.12, P < 0.05). In addition, H{sub 2}O{sub 2} increased glucose uptake in podocytes

  17. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Madsen, Lise; Pedersen, Lone Møller; Liaset, Bjørn;

    2008-01-01

    The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti...... pivotal in regulating the adipogenic effect of n-6 PUFAs and that diet-induced differences in cAMP levels may explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity....

  18. Studying mechanisms of cAMP and cyclic nucleotide phosphodiesterase signaling in Leydig cell function with phosphoproteomics.

    Science.gov (United States)

    Golkowski, Martin; Shimizu-Albergine, Masami; Suh, Hyong Won; Beavo, Joseph A; Ong, Shao-En

    2016-07-01

    Many cellular processes are modulated by cyclic AMP and nucleotide phosphodiesterases (PDEs) regulate this second messenger by catalyzing its breakdown. The major unique function of testicular Leydig cells is to produce testosterone in response to luteinizing hormone (LH). Treatment of Leydig cells with PDE inhibitors increases cAMP levels and the activity of its downstream effector, cAMP-dependent protein kinase (PKA), leading to a series of kinase-dependent signaling and transcription events that ultimately increase testosterone release. We have recently shown that PDE4B and PDE4C as well as PDE8A and PDE8B are expressed in rodent Leydig cells and that combined inhibition of PDE4 and PDE8 leads to dramatically increased steroid biosynthesis. Here we investigated the effect of PDE4 and PDE8 inhibition on the molecular mechanisms of cAMP actions in a mouse MA10 Leydig cell line model with SILAC mass spectrometry-based phosphoproteomics. We treated MA10 cells either with PDE4 family specific inhibitor (Rolipram) and PDE8 family specific inhibitor (PF-04957325) alone or in combination and quantified the resulting phosphorylation changes at five different time points between 0 and 180min. We identified 28,336 phosphosites from 4837 proteins and observed significant regulation of 749 sites in response to PDE4 and PDE8 inhibitor treatment. Of these, 132 phosphosites were consensus PKA sites. Our data strongly suggest that PDE4 and PDE8 inhibitors synergistically regulate phosphorylation of proteins required for many different cellular processes, including cell cycle progression, lipid and glucose metabolism, transcription, endocytosis and vesicle transport. Our data suggests that cAMP, PDE4 and PDE8 coordinate steroidogenesis by acting on not one rate-limiting step but rather multiple pathways. Moreover, the pools of cAMP controlled by these PDEs also coordinate many other metabolic processes that may be regulated to assure timely and sufficient testosterone secretion

  19. Neural networks for intelligent signal processing

    CERN Document Server

    Zaknich, Anthony

    2003-01-01

    This book provides a thorough theoretical and practical introduction to the application of neural networks to pattern recognition and intelligent signal processing. It has been tested on students, unfamiliar with neural networks, who were able to pick up enough details to successfully complete their masters or final year undergraduate projects. The text also presents a comprehensive treatment of a class of neural networks called common bandwidth spherical basis function NNs, including the probabilistic NN, the modified probabilistic NN and the general regression NN. Contents: A Brief Historica

  20. GATA-Dependent Glutaminolysis Drives Appressorium Formation in Magnaporthe oryzae by Suppressing TOR Inhibition of cAMP/PKA Signaling

    OpenAIRE

    Marroquin-Guzman, Margarita; Richard A. Wilson

    2015-01-01

    Fungal plant pathogens are persistent and global food security threats. To invade their hosts they often form highly specialized infection structures, known as appressoria. The cAMP/ PKA- and MAP kinase-signaling cascades have been functionally delineated as positive-acting pathways required for appressorium development. Negative-acting regulatory pathways that block appressorial development are not known. Here, we present the first detailed evidence that the conserved Target of Rapamycin (TO...

  1. Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP signaling to inhibit steroidogenesis in human granulosa cells

    Directory of Open Access Journals (Sweden)

    HoYuen Basil

    2009-10-01

    Full Text Available Abstract Background Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells. Methods The effect of leptin on progesterone production in simian virus 40 immortalized granulosa (SVOG cells was examined by Enzyme linked immunosorbent assay (ELISA. The effect of leptin on the expression of the steroidogenic enzymes (StAR, P450scc, 3betaHSD in SVOG cells was examined by real-time PCR and Western blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were examined by using PCR. SVOG cells were co-treated with leptin and specific pharmacological inhibitors to identify the signaling pathways involved in leptin-reduced progesterone production. Silencing RNA against leptin receptor was used to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts in a leptin receptor-dependent manner. Results and Conclusion In the present study, we investigated the cellular mechanisms underlying leptin-regulated steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo cAMP-stimulated progesterone production in a concentration-dependent manner. Furthermore, we show that leptin inhibits expression of the cAMP-stimulated steroidogenic acute regulatory (StAR protein, the rate limiting de novo protein in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK but only the ERK1/2 (PD98059 and p38 (SB203580 inhibitors attenuate the leptin-induced inhibition of cAMP-stimulated StAR protein expression and progesterone production. These data suggest that the leptin-induced MAPK signal transduction pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor attenuates the effect of leptin on cAMP-induced StAR protein expression and progesterone

  2. Quantitative phosphoproteomics to characterize signaling networks

    DEFF Research Database (Denmark)

    Rigbolt, Kristoffer T G; Blagoev, Blagoy

    2012-01-01

    Reversible protein phosphorylation is involved in the regulation of most, if not all, major cellular processes via dynamic signal transduction pathways. During the last decade quantitative phosphoproteomics have evolved from a highly specialized area to a powerful and versatile platform for...... analyzing protein phosphorylation at a system-wide scale and has become the intuitive strategy for comprehensive characterization of signaling networks. Contemporary phosphoproteomics use highly optimized procedures for sample preparation, mass spectrometry and data analysis algorithms to identify and...... quantify thousands of phosphorylations, thus providing extensive overviews of the cellular signaling networks. As a result of these developments quantitative phosphoproteomics have been applied to study processes as diverse as immunology, stem cell biology and DNA damage. Here we review the developments in...

  3. Diatom acclimation to elevated CO2 via cAMP signalling and coordinated gene expression

    Science.gov (United States)

    Hennon, Gwenn M. M.; Ashworth, Justin; Groussman, Ryan D.; Berthiaume, Chris; Morales, Rhonda L.; Baliga, Nitin S.; Orellana, Mónica V.; Armbrust, E. V.

    2015-08-01

    Diatoms are responsible for ~40% of marine primary productivity, fuelling the oceanic carbon cycle and contributing to natural carbon sequestration in the deep ocean. Diatoms rely on energetically expensive carbon concentrating mechanisms (CCMs) to fix carbon efficiently at modern levels of CO2 (refs , , ). How diatoms may respond over the short and long term to rising atmospheric CO2 remains an open question. Here we use nitrate-limited chemostats to show that the model diatom Thalassiosira pseudonana rapidly responds to increasing CO2 by differentially expressing gene clusters that regulate transcription and chromosome folding, and subsequently reduces transcription of photosynthesis and respiration gene clusters under steady-state elevated CO2. These results suggest that exposure to elevated CO2 first causes a shift in regulation, and then a metabolic rearrangement. Genes in one CO2-responsive cluster included CCM and photorespiration genes that share a putative cAMP-responsive cis-regulatory sequence, implying these genes are co-regulated in response to CO2, with cAMP as an intermediate messenger. We verified cAMP-induced downregulation of CCM gene δ-CA3 in nutrient-replete diatom cultures by inhibiting the hydrolysis of cAMP. These results indicate an important role for cAMP in downregulating CCM and photorespiration genes under elevated CO2 and provide insights into mechanisms of diatom acclimation in response to climate change.

  4. cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila.

    Science.gov (United States)

    Hong, Sung-Tae; Bang, Sunhoe; Hyun, Seogang; Kang, Jongkyun; Jeong, Kyunghwa; Paik, Donggi; Chung, Jongkyeong; Kim, Jaeseob

    2008-08-01

    Homoiotherms, for example mammals, regulate their body temperature with physiological responses such as a change of metabolic rate and sweating. In contrast, the body temperature of poikilotherms, for example Drosophila, is the result of heat exchange with the surrounding environment as a result of the large ratio of surface area to volume of their bodies. Accordingly, these animals must instinctively move to places with an environmental temperature as close as possible to their genetically determined desired temperature. The temperature that Drosophila instinctively prefers has a function equivalent to the 'set point' temperature in mammals. Although various temperature-gated TRP channels have been discovered, molecular and cellular components in Drosophila brain responsible for determining the desired temperature remain unknown. We identified these components by performing a large-scale genetic screen of temperature preference behaviour (TPB) in Drosophila. In parallel, we mapped areas of the Drosophila brain controlling TPB by targeted inactivation of neurons with tetanus toxin and a potassium channel (Kir2.1) driven with various brain-specific GAL4s. Here we show that mushroom bodies (MBs) and the cyclic AMP-cAMP-dependent protein kinase A (cAMP-PKA) pathway are essential for controlling TPB. Furthermore, targeted expression of cAMP-PKA pathway components in only the MB was sufficient to rescue abnormal TPB of the corresponding mutants. Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants. PMID:18594510

  5. Modulation of adhesion-dependent cAMP signaling by echistatin and alendronate

    Science.gov (United States)

    Fong, J. H.; Ingber, D. E.

    1996-01-01

    We measured intracellular cAMP levels in cells during attachment and spreading on different extracellular matrix (ECM) proteins. Increases in cAMP were observed within minutes when cells attached to fibronectin, vitronectin, and a synthetic RGD-containing fibronectin peptide (Petite 2000), but not when they adhered to another integrin alpha nu beta 3 ligand, echistatin. Because echistatin also inhibits bone resorption, we measured the effects of adding another osteoporosis inhibitor, alendronate, in this system. Alendronate inhibited the cAMP increase induced by ligands that primarily utilize integrin alpha nu beta 3 (vitronectin, Peptite 2000), but not by fibronectin which can also use integrin alpha 5 beta 1. These results show that cell adhesion to ECM can increase intracellular cAPM levels and raise the possibility that inhibitors of osteoporosis may act, in part, by preventing activation of this pathway by integrins.

  6. Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models

    Science.gov (United States)

    Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Joseph; Rosenfelt, Cory; Gertner, Michael J.; Campbell, Sean R.; Emerson, Danielle; Hinchey, Paul; Kollaros, Maria; Ferrick, Neal J.; Chambers, Daniel B.; Langer, Steven; Sust, Steven; Malik, Aatika; Terlizzi, Allison M.; Liebelt, David A.; Ferreiro, David; Sharma, Ali; Koenigsberg, Eric; Choi, Richard J.; Louneva, Natalia; Arnold, Steven E.; Featherstone, Robert E.; Siegel, Steven J.; Zukin, R. Suzanne; McDonald, Thomas V.; Bolduc, Francois V.; Jongens, Thomas A.; McBride, Sean M. J.

    2016-01-01

    Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model. PMID:27445731

  7. cAMP/PKA Signaling Inhibits Osteogenic Differentiation and Bone Formation in Rodent Models

    NARCIS (Netherlands)

    Siddappa, Ramakrishnaiah; Mulder, Winfried; Steeghs, Ilse; Klundert, van de Christine; Fernandes, Hugo; Liu, Jun; Arends, Roel; Blitterswijk, van Clemens; Boer, de Jan

    2009-01-01

    We previously demonstrated that cAMP-mediated protein kinase A (PKA) activation induces in vitro osteogenesis and in vivo bone formation by human mesenchymal stem cells (hMSCs). To analyze the species-specific response of this phenomenon and to translate our findings into a clinical trial, suitable

  8. Signaling governed by G proteins and cAMP is crucial for growth, secondary metabolism and sexual development in Fusarium fujikuroi.

    Directory of Open Access Journals (Sweden)

    Lena Studt

    Full Text Available The plant-pathogenic fungus Fusarium fujikuroi is a notorious rice pathogen causing hyper-elongation of infected plants due to the production of gibberellic acids (GAs. In addition to GAs, F. fujikuroi produces a wide range of other secondary metabolites, such as fusarins, fusaric acid or the red polyketides bikaverins and fusarubins. The recent availability of the fungal genome sequence for this species has revealed the potential of many more putative secondary metabolite gene clusters whose products remain to be identified. However, the complex regulation of secondary metabolism is far from being understood. Here we studied the impact of the heterotrimeric G protein and the cAMP-mediated signaling network, including the regulatory subunits of the cAMP-dependent protein kinase (PKA, to study their effect on colony morphology, sexual development and regulation of bikaverins, fusarubins and GAs. We demonstrated that fusarubin biosynthesis is negatively regulated by at least two Gα subunits, FfG1 and FfG3, which both function as stimulators of the adenylyl cyclase FfAC. Surprisingly, the primary downstream target of the adenylyl cyclase, the PKA, is not involved in the regulation of fusarubins, suggesting that additional, yet unidentified, cAMP-binding protein(s exist. In contrast, bikaverin biosynthesis is significantly reduced in ffg1 and ffg3 deletion mutants and positively regulated by FfAC and FfPKA1, while GA biosynthesis depends on the active FfAC and FfPKA2 in an FfG1- and FfG3-independent manner. In addition, we provide evidence that G Protein-mediated/cAMP signaling is important for growth in F. fujikuroi because deletion of ffg3, ffac and ffpka1 resulted in impaired growth on minimal and rich media. Finally, sexual crosses of ffg1 mutants showed the importance of a functional FfG1 protein for development of perithecia in the mating strain that carries the MAT1-1 idiomorph.

  9. Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation.

    Science.gov (United States)

    Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung; Wang, Hongbing

    2016-08-01

    Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca(2+)-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca(2+)-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca(2+)-stimulated cAMP can affect the molecular outcome of physical exercise. PMID:27421897

  10. Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Zequn Jiang; Shasha Li; Yunyi Liu; Pengyi Deng; Jianguo Huang; Guangyuan He

    2011-01-01

    In this study,we confirmed that sesamin,an active lignan isolated from sesame seed and oil,is a novel skin-tanning compound.The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells.The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin.Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmiaassociated transcription factor (MITF).Sesamin could activate cAMP response element (CRE) binding protein (CREB),but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt.Moreover,sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway.Consistent with these results,sesamin-mediated increase of melanin synthesis was reduced significantly by H-89,a PKA inhibitor,but not by SB203580,a p38 MAPK inhibitor or by LY294002,a phosphatidylinositol-3-kinase (PI3K) inhibitor.Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89.These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase,which was,in turn,due to the activation of cAMP signaling.

  11. Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway.

    Science.gov (United States)

    Jiang, Zequn; Li, Shasha; Liu, Yunyi; Deng, Pengyi; Huang, Jianguo; He, Guangyuan

    2011-10-01

    In this study, we confirmed that sesamin, an active lignan isolated from sesame seed and oil, is a novel skin-tanning compound. The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin. Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmia-associated transcription factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor, but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89. These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase, which was, in turn, due to the activation of cAMP signaling. PMID:21896570

  12. Phospholipase D1 Mediates AMP-Activated Protein Kinase Signaling for Glucose Uptake

    OpenAIRE

    Kim, Jong Hyun; Park, Ji-Man; Yea, Kyungmoo; Kim, Hyun Wook; Suh, Pann-Ghill; Ryu, Sung Ho

    2010-01-01

    Background Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK) is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of gluc...

  13. AMP-Activated Protein Kinase alpha1 Dependent Signaling in Renal Tissue Fibrosis

    OpenAIRE

    Mia, Sobuj

    2016-01-01

    Tubulointerstitial fibrosis is a common hallmark of chronic kidney disease caused by diabetes, hypertension, ischemia, renal injury and obstructive uropathy. The hetereotrimeric AMP-activated protein kinase (AMPK) consists of three subunits (α, β, γ) and is a master sensor of cellular energy status. Activation of AMPK contributes to monocyte-fibroblast transition and production of matrix protein even though accumulating evidence suggests that activated AMPK inhibits tissue fibrosis, which may...

  14. Phospholipase D1 Mediates AMP-Activated Protein Kinase Signaling for Glucose Uptake

    OpenAIRE

    Jong Hyun Kim; Ji-Man Park; Kyungmoo Yea; Hyun Wook Kim; Pann-Ghill Suh; Sung Ho Ryu

    2010-01-01

    BACKGROUND: Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK) is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glu...

  15. Metabolic Basis for Thyroid Hormone Liver Preconditioning: Upregulation of AMP-Activated Protein Kinase Signaling

    OpenAIRE

    Videla, Luis A; Virginia Fernández; Pamela Cornejo; Romina Vargas

    2012-01-01

    The liver is a major organ responsible for most functions of cellular metabolism and a mediator between dietary and endogenous sources of energy for extrahepatic tissues. In this context, adenosine-monophosphate- (AMP-) activated protein kinase (AMPK) constitutes an intrahepatic energy sensor regulating physiological energy dynamics by limiting anabolism and stimulating catabolism, thus increasing ATP availability. This is achieved by mechanisms involving direct allosteric activation and reve...

  16. Qualitative networks: a symbolic approach to analyze biological signaling networks

    Directory of Open Access Journals (Sweden)

    Henzinger Thomas A

    2007-01-01

    Full Text Available Abstract Background A central goal of Systems Biology is to model and analyze biological signaling pathways that interact with one another to form complex networks. Here we introduce Qualitative networks, an extension of Boolean networks. With this framework, we use formal verification methods to check whether a model is consistent with the laboratory experimental observations on which it is based. If the model does not conform to the data, we suggest a revised model and the new hypotheses are tested in-silico. Results We consider networks in which elements range over a small finite domain allowing more flexibility than Boolean values, and add target functions that allow to model a rich set of behaviors. We propose a symbolic algorithm for analyzing the steady state of these networks, allowing us to scale up to a system consisting of 144 elements and state spaces of approximately 1086 states. We illustrate the usefulness of this approach through a model of the interaction between the Notch and the Wnt signaling pathways in mammalian skin, and its extensive analysis. Conclusion We introduce an approach for constructing computational models of biological systems that extends the framework of Boolean networks and uses formal verification methods for the analysis of the model. This approach can scale to multicellular models of complex pathways, and is therefore a useful tool for the analysis of complex biological systems. The hypotheses formulated during in-silico testing suggest new avenues to explore experimentally. Hence, this approach has the potential to efficiently complement experimental studies in biology.

  17. Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats

    International Nuclear Information System (INIS)

    Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle–box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus

  18. The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons

    Directory of Open Access Journals (Sweden)

    Marina ePolito

    2013-11-01

    Full Text Available The NO-cGMP signaling plays an important role in the regulation of striatal function although the mechanisms of action of cGMP specifically in medium spiny neurons (MSNs remain unclear. Using genetically encoded fluorescent biosensors, including a novel Epac-based sensor (EPAC-SH150 with increased sensitivity for cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO donors in both striatonigral and striatopallidal MSNs, and this cGMP signal was controlled partially by PDE2. At the level of cAMP brief forskolin stimulations produced transient cAMP signals which differed between D1 and D2 medium spiny neurons. NO inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect that was translated and magnified downstream of cAMP, at the level of PKA. PDE2 thus appears as a critical effector of NO which modulates the post-synaptic response of MSNs to dopaminergic transmission.

  19. cAMP-dependent protein kinase A and the dynamics of epithelial cell surface domains : moving membranes to keep in shape

    NARCIS (Netherlands)

    Wojtal, Kacper A.; Hoekstra, Dick; van IJzendoorn, Sven C. D.

    2008-01-01

    Cyclic adenosine monophosphate (cAMP) and cAMP-dependent protein kinase A (PKA) are evolutionary conserved molecules with a well-established position in the complex network of signal transduction pathways. cAMP/PKA-mediated signaling pathways are implicated in many biological processes that cooperat

  20. Coordinated induction of GST and MRP2 by cAMP in Caco-2 cells: Role of protein kinase A signaling pathway and toxicological relevance

    Energy Technology Data Exchange (ETDEWEB)

    Arana, Maite Rocío, E-mail: arana@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Tocchetti, Guillermo Nicolás, E-mail: gtocchetti@live.com.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Domizi, Pablo, E-mail: domizi@ibr-conicet.gov.ar [Instituto de Biología Molecular y Celular de Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Arias, Agostina, E-mail: agoarias@yahoo.com.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Rigalli, Juan Pablo, E-mail: jprigalli@gmail.com [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Ruiz, María Laura, E-mail: ruiz@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); and others

    2015-09-01

    The cAMP pathway is a universal signaling pathway regulating many cellular processes including metabolic routes, growth and differentiation. However, its effects on xenobiotic biotransformation and transport systems are poorly characterized. The effect of cAMP on expression and activity of GST and MRP2 was evaluated in Caco-2 cells, a model of intestinal epithelium. Cells incubated with the cAMP permeable analog dibutyryl cyclic AMP (db-cAMP: 1,10,100 μM) for 48 h exhibited a dose–response increase in GST class α and MRP2 protein expression. Incubation with forskolin, an activator of adenylyl cyclase, confirmed the association between intracellular cAMP and upregulation of MRP2. Consistent with increased expression of GSTα and MRP2, db-cAMP enhanced their activities, as well as cytoprotection against the common substrate 1-chloro-2,4-dinitrobenzene. Pretreatment with protein kinase A (PKA) inhibitors totally abolished upregulation of MRP2 and GSTα induced by db-cAMP. In silico analysis together with experiments consisting of treatment with db-cAMP of Caco-2 cells transfected with a reporter construct containing CRE and AP-1 sites evidenced participation of these sites in MRP2 upregulation. Further studies involving the transcription factors CREB and AP-1 (c-JUN, c-FOS and ATF2) demonstrated increased levels of total c-JUN and phosphorylation of c-JUN and ATF2 by db-cAMP, which were suppressed by a PKA inhibitor. Co-immunoprecipitation and ChIP assay studies demonstrated that db-cAMP increased c-JUN/ATF2 interaction, with further recruitment to the region of the MRP2 promoter containing CRE and AP-1 sites. We conclude that cAMP induces GSTα and MRP2 expression and activity in Caco-2 cells via the PKA pathway, thus regulating detoxification of specific xenobiotics. - Highlights: • cAMP positively modulates the expression and activity of GST and MRP2 in Caco-2 cells. • Such induction resulted in increased cytoprotection against chemical injury. • PKA

  1. Coordinated induction of GST and MRP2 by cAMP in Caco-2 cells: Role of protein kinase A signaling pathway and toxicological relevance

    International Nuclear Information System (INIS)

    The cAMP pathway is a universal signaling pathway regulating many cellular processes including metabolic routes, growth and differentiation. However, its effects on xenobiotic biotransformation and transport systems are poorly characterized. The effect of cAMP on expression and activity of GST and MRP2 was evaluated in Caco-2 cells, a model of intestinal epithelium. Cells incubated with the cAMP permeable analog dibutyryl cyclic AMP (db-cAMP: 1,10,100 μM) for 48 h exhibited a dose–response increase in GST class α and MRP2 protein expression. Incubation with forskolin, an activator of adenylyl cyclase, confirmed the association between intracellular cAMP and upregulation of MRP2. Consistent with increased expression of GSTα and MRP2, db-cAMP enhanced their activities, as well as cytoprotection against the common substrate 1-chloro-2,4-dinitrobenzene. Pretreatment with protein kinase A (PKA) inhibitors totally abolished upregulation of MRP2 and GSTα induced by db-cAMP. In silico analysis together with experiments consisting of treatment with db-cAMP of Caco-2 cells transfected with a reporter construct containing CRE and AP-1 sites evidenced participation of these sites in MRP2 upregulation. Further studies involving the transcription factors CREB and AP-1 (c-JUN, c-FOS and ATF2) demonstrated increased levels of total c-JUN and phosphorylation of c-JUN and ATF2 by db-cAMP, which were suppressed by a PKA inhibitor. Co-immunoprecipitation and ChIP assay studies demonstrated that db-cAMP increased c-JUN/ATF2 interaction, with further recruitment to the region of the MRP2 promoter containing CRE and AP-1 sites. We conclude that cAMP induces GSTα and MRP2 expression and activity in Caco-2 cells via the PKA pathway, thus regulating detoxification of specific xenobiotics. - Highlights: • cAMP positively modulates the expression and activity of GST and MRP2 in Caco-2 cells. • Such induction resulted in increased cytoprotection against chemical injury. • PKA

  2. Cyclic AMP-Rap1A signaling mediates cell surface translocation of microvascular smooth muscle α2C-adrenoceptors through the actin-binding protein filamin-2

    OpenAIRE

    Motawea, Hanaa K. B.; Selvi C. Jeyaraj; Eid, Ali H; Mitra, Srabani; Unger, Nicholas T.; Ahmed, Amany A. E.; Flavahan, Nicholas A.; Chotani, Maqsood A.

    2013-01-01

    The second messenger cyclic AMP (cAMP) plays a vital role in vascular physiology, including vasodilation of large blood vessels. We recently demonstrated cAMP activation of Epac-Rap1A and RhoA-Rho-associated kinase (ROCK)-F-actin signaling in arteriolar-derived smooth muscle cells increases expression and cell surface translocation of functional α2C-adrenoceptors (α2C-ARs) that mediate vasoconstriction in small blood vessels (arterioles). The Ras-related small GTPAse Rap1A increased expressio...

  3. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Mingyuan [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Department of Radiation Oncology, China–Japan Union Hospital of Jilin University, Changchun 130033 (China); Dong, Chen; Xie, Yuexia; Li, Jitao; Yuan, Dexiao; Bai, Yang [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2014-05-15

    Highlights: • α-Irradiation induced reciprocal effects between macrophage and hepatocyte cells. • cAMP played a protective role in regulating the reverse bystander effect. • cAMP communication contributed to the reciprocal effects via membrane signaling. • p53 was required for cAMP-regulated bystander effect in the recipient cells. - Abstract: Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6 h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in

  4. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway

    International Nuclear Information System (INIS)

    Highlights: • α-Irradiation induced reciprocal effects between macrophage and hepatocyte cells. • cAMP played a protective role in regulating the reverse bystander effect. • cAMP communication contributed to the reciprocal effects via membrane signaling. • p53 was required for cAMP-regulated bystander effect in the recipient cells. - Abstract: Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6 h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in

  5. Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signaltransduction pathway in depressive disorder

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Yingquan Zhang; Mingqi Qiao

    2013-01-01

    The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression.

  6. Schizosaccharomyces pombe Git7p, a Member of the Saccharomyces cerevisiae Sgt1p Family, Is Required for Glucose and Cyclic AMP Signaling, Cell Wall Integrity, and Septation

    OpenAIRE

    Schadick, Kevin; Fourcade, H. Matthew; Boumenot, Peter; Seitz, Jeffrey J.; Morrell, Jennifer L.; Chang, Louise; Gould, Kathleen L.; Partridge, Janet F.; Allshire, Robin C.; Kitagawa, Katsumi; Hieter, Phil; Hoffman, Charles S.

    2002-01-01

    The Schizosaccharomyces pombe fbp1 gene, encoding fructose-1,6-bisphosphatase, is transcriptionally repressed by glucose. Mutations that confer constitutive fbp1 transcription identify git (glucose-insensitive transcription) genes that encode components of a cyclic AMP (cAMP) signaling pathway required for adenylate cyclase activation. Four of these genes encode the three subunits of a heterotrimeric G protein (gpa2, git5, and git11) and a G protein-coupled receptor (git3). Three additional g...

  7. T3-induced liver AMP-activated protein kinase signaling: Redox dependency and upregulation of downstream targets

    Science.gov (United States)

    Videla, Luis A; Fernández, Virginia; Cornejo, Pamela; Vargas, Romina; Morales, Paula; Ceballo, Juan; Fischer, Alvaro; Escudero, Nicolás; Escobar, Oscar

    2014-01-01

    AIM: To investigate the redox dependency and promotion of downstream targets in thyroid hormone (T3)-induced AMP-activated protein kinase (AMPK) signaling as cellular energy sensor to limit metabolic stresses in the liver. METHODS: Fed male Sprague-Dawley rats were given a single ip dose of 0.1 mg T3/kg or T3 vehicle (NaOH 0.1 N; controls) and studied at 8 or 24 h after treatment. Separate groups of animals received 500 mg N-acetylcysteine (NAC)/kg or saline ip 30 min prior T3. Measurements included plasma and liver 8-isoprostane and serum β-hydroxybutyrate levels (ELISA), hepatic levels of mRNAs (qPCR), proteins (Western blot), and phosphorylated AMPK (ELISA). RESULTS: T3 upregulates AMPK signaling, including the upstream kinases Ca2+-calmodulin-dependent protein kinase kinase-β and transforming growth factor-β-activated kinase-1, with T3-induced reactive oxygen species having a causal role due to its suppression by pretreatment with the antioxidant NAC. Accordingly, AMPK targets acetyl-CoA carboxylase and cyclic AMP response element binding protein are phosphorylated, with the concomitant carnitine palmitoyltransferase-1α (CPT-1α) activation and higher expression of peroxisome proliferator-activated receptor-γ co-activator-1α and that of the fatty acid oxidation (FAO)-related enzymes CPT-1α, acyl-CoA oxidase 1, and acyl-CoA thioesterase 2. Under these conditions, T3 induced a significant increase in the serum levels of β-hydroxybutyrate, a surrogate marker for hepatic FAO. CONCLUSION: T3 administration activates liver AMPK signaling in a redox-dependent manner, leading to FAO enhancement as evidenced by the consequent ketogenic response, which may constitute a key molecular mechanism regulating energy dynamics to support T3 preconditioning against ischemia-reperfusion injury. PMID:25516653

  8. Activation of the cAMP-dependent protein kinase signaling pathway by luteinizing hormone in trout theca layers.

    Science.gov (United States)

    Méndez, Eva; Maeland, Mari; Skålhegg, Bjørn S; Planas, Josep V

    2003-07-31

    In the fish ovary, LH is the main factor regulating the production of steroids during the periovulatory period and its effects are believed to be mediated, at least partially, through the cAMP-dependent protein kinase (PKA) signaling pathway. However, there is no direct evidence for the presence of PKA in the fish ovary nor on the regulation of its activity by fish LH. Here, we show the identification of regulatory (R) and catalytic (C) subunits of PKA in trout theca cells by immunoblotting. DEAE-cellulose chromatography of theca cell extracts indicated the presence of PKA type I and II and showed that trout theca cells display PKA-specific phosphotransferase and cAMP-binding activities. Salmon LH (sLH) stimulated PKA activity and increased the levels of immunoreactive RIIalpha, RIIbeta and C subunits in trout theca layers. These observations, coupled with the sLH-dependent decrease in the half-life of the C subunit, as shown by pulse-chase experiments, strongly suggest that sLH activates PKA in trout theca cells. Furthermore, our results suggest that ovarian PKA activity and its regulation by LH has been well conserved from fish to humans. PMID:12890563

  9. Magnetoencephalography from signals to dynamic cortical networks

    CERN Document Server

    Aine, Cheryl

    2014-01-01

    "Magnetoencephalography (MEG) provides a time-accurate view into human brain function. The concerted action of neurons generates minute magnetic fields that can be detected---totally noninvasively---by sensitive multichannel magnetometers. The obtained millisecond accuracycomplements information obtained by other modern brain-imaging tools. Accurate timing is quintessential in normal brain function, often distorted in brain disorders. The noninvasiveness and time-sensitivityof MEG are great assets to developmental studies, as well. This multiauthored book covers an ambitiously wide range of MEG research from introductory to advanced level, from sensors to signals, and from focal sources to the dynamics of cortical networks. Written by active practioners of this multidisciplinary field, the book contains tutorials for newcomers and chapters of new challenging methods and emerging technologies to advanced MEG users. The reader will obtain a firm grasp of the possibilities of MEG in the study of audition, vision...

  10. Global Optimization for Transport Network Expansion and Signal Setting

    Directory of Open Access Journals (Sweden)

    Haoxiang Liu

    2015-01-01

    Full Text Available This paper proposes a model to address an urban transport planning problem involving combined network design and signal setting in a saturated network. Conventional transport planning models usually deal with the network design problem and signal setting problem separately. However, the fact that network capacity design and capacity allocation determined by network signal setting combine to govern the transport network performance requires the optimal transport planning to consider the two problems simultaneously. In this study, a combined network capacity expansion and signal setting model with consideration of vehicle queuing on approaching legs of intersection is developed to consider their mutual interactions so that best transport network performance can be guaranteed. We formulate the model as a bilevel program and design an approximated global optimization solution method based on mixed-integer linearization approach to solve the problem, which is inherently nnonlinear and nonconvex. Numerical experiments are conducted to demonstrate the model application and the efficiency of solution algorithm.

  11. Using Artificial Neural Networks for ECG Signals Denoising

    OpenAIRE

    Zoltán Germán-Salló; Katalin György

    2010-01-01

    The authors have investigated some potential applications of artificial neural networks in electrocardiografic (ECG) signal prediction. For this, the authors used an adaptive multilayer perceptron structure to predict the signal. The proposed procedure uses an artificial neural network based learning structure to estimate the (n+1)th sample from n previous samples To train and adjust the network weights, the backpropagation (BP) algorithm was used. In this paper, prediction of ECG signals (as...

  12. Hydrogen peroxide induces activation of insulin signaling pathway via AMP-dependent kinase in podocytes

    International Nuclear Information System (INIS)

    Highlights: ► H2O2 activates the insulin signaling pathway and glucose uptake in podocytes. ► H2O2 induces time-dependent changes in AMPK phosphorylation. ► H2O2 enhances insulin signaling pathways via AMPK activation. ► H2O2 stimulation of glucose uptake is AMPK-dependent. -- Abstract: Podocytes are cells that form the glomerular filtration barrier in the kidney. Insulin signaling in podocytes is critical for normal kidney function. Insulin signaling is regulated by oxidative stress and intracellular energy levels. We cultured rat podocytes to investigate the effects of hydrogen peroxide (H2O2) on the phosphorylation of proximal and distal elements of insulin signaling. We also investigated H2O2-induced intracellular changes in the distribution of protein kinase B (Akt). Western blots showed that H2O2 (100 μM) induced rapid, transient phosphorylation of the insulin receptor (IR), the IR substrate-1 (IRS1), and Akt with peak activities at 5 min (Δ 183%, P 2O2>. Furthermore, H2O2 inhibited phosphorylation of the phosphatase and tensin homologue (PTEN; peak activity at 10 min; Δ −32%, P 2O2 on IR phosphorylation by about 40% (from 2.07 ± 0.28 to 1.28 ± 0.12, P 2O2 increased glucose uptake in podocytes (from 0.88 ± 0.04 to 1.29 ± 0.12 nmol/min/mg protein, P 2O2 activated the insulin signaling pathway and glucose uptake via AMPK in cultured rat podocytes. This signaling may play a potential role in the prevention of insulin resistance under conditions associated with oxidative stress.

  13. Hypoxia induces phosphorylation of the cyclic AMP response element-binding protein by a novel signaling mechanism.

    Science.gov (United States)

    Beitner-Johnson, D; Millhorn, D E

    1998-07-31

    To investigate signaling mechanisms by which hypoxia regulates gene expression, we examined the effect of hypoxia on the cyclic AMP response element-binding protein (CREB) in PC12 cells. Exposure to physiological levels of hypoxia (5% O2, approximately 50 mm Hg) rapidly induced a persistent phosphorylation of CREB on Ser133, an event that is required for CREB-mediated transcriptional activation. Hypoxia-induced phosphorylation of CREB was more robust than that induced by any other stimulus tested, including forskolin, depolarization, and osmotic stress. Furthermore, this effect was not mediated by any of the previously known signaling pathways that lead to phosphorylation of CREB, including protein kinase A, calcium/calmodulin-dependent protein kinase, protein kinase C, ribosomal S6 kinase-2, and mitogen-activated protein kinase-activated protein kinase-2. Hypoxic activation of a CRE-containing reporter (derived from the 5'-flanking region of the tyrosine hydroxylase gene) was attenuated markedly by mutation of the CRE. Thus, a physiological reduction in O2 levels induces a functional phosphorylation of CREB at Ser133 via a novel signaling pathway. PMID:9677418

  14. Application of Neutral Network by EEG Signal Classification

    Directory of Open Access Journals (Sweden)

    Michal Gala

    2008-01-01

    Full Text Available Analysis of long-term EEG requires that it is segmented into piece-wise stationary sections and classified. Neural network architecture is introduced for the problem of classification of EEG signals. This paper deals with basic signal classification into two classes. This work is a ground towards creating an algorithm to sleep status analysis. Signal is first worked by signal segmentation and then is used a neural network to classification into two class.

  15. RMOD: a tool for regulatory motif detection in signaling network.

    Science.gov (United States)

    Kim, Jinki; Yi, Gwan-Su

    2013-01-01

    Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod. PMID:23874612

  16. RMOD: a tool for regulatory motif detection in signaling network.

    Directory of Open Access Journals (Sweden)

    Jinki Kim

    Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

  17. HPRT-deficiency dysregulates cAMP-PKA signaling and phosphodiesterase 10A expression: mechanistic insight and potential target for Lesch-Nyhan Disease?

    Directory of Open Access Journals (Sweden)

    Ghiabe-Henri Guibinga

    Full Text Available Lesch-Nyhan Disease (LND is the result of mutations in the X-linked gene encoding the purine metabolic enzyme, hypoxanthine guanine phosphoribosyl transferase (HPRT. LND gives rise to severe neurological anomalies including mental retardation, dystonia, chorea, pyramidal signs and a compulsive and aggressive behavior to self injure. The neurological phenotype in LND has been shown to reflect aberrant dopaminergic signaling in the basal ganglia, however there are little data correlating the defect in purine metabolism to the neural-related abnormalities. In the present studies, we find that HPRT-deficient neuronal cell lines have reduced CREB (cAMP response element-binding protein expression and intracellular cyclic AMP (cAMP, which correlates with attenuated CREB-dependent transcriptional activity and a reduced phosphorylation of protein kinase A (PKA substrates such as synapsin (p-syn I. Of interest, we found increased expression of phosphodiesterase 10A (PDE10A in HPRT-deficient cell lines and that the PDE10 inhibitor papaverine and PDE10A siRNA restored cAMP/PKA signaling. Furthermore, reconstitution of HPRT expression in mutant cells partly increased cAMP signaling synapsin phosphorylation. In conclusion, our data show that HPRT-deficiency alters cAMP/PKA signaling pathway, which is in part due to the increased of PDE10A expression and activity. These findings suggest a mechanistic insight into the possible causes of LND and highlight PDE10A as a possible therapeutic target for this intractable neurological disease.

  18. Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals.

    Science.gov (United States)

    Li, Chun-Chun; Le, Kang; Kato, Jiro; Moss, Joel; Vaughan, Martha

    2016-05-24

    Multifunctional β-catenin, with critical roles in both cell-cell adhesion and Wnt-signaling pathways, was among HeLa cell proteins coimmunoprecipitated by antibodies against brefeldin A-inhibited guanine nucleotide-exchange factors 1 and 2 (BIG1 or BIG2) that activate ADP-ribosylation factors (Arfs) by accelerating the replacement of bound GDP with GTP. BIG proteins also contain A-kinase anchoring protein (AKAP) sequences that can act as scaffolds for multimolecular assemblies that facilitate and limit cAMP signaling temporally and spatially. Direct interaction of BIG1 N-terminal sequence with β-catenin was confirmed using yeast two-hybrid assays and in vitro synthesized proteins. Depletion of BIG1 and/or BIG2 or overexpression of guanine nucleotide-exchange factor inactive mutant, but not wild-type, proteins interfered with β-catenin trafficking, leading to accumulation at perinuclear Golgi structures. Both phospholipase D activity and vesicular trafficking were required for effects of BIG1 and BIG2 on β-catenin activation. Levels of PKA-phosphorylated β-catenin S675 and β-catenin association with PKA, BIG1, and BIG2 were also diminished after BIG1/BIG2 depletion. Inferring a requirement for BIG1 and/or BIG2 AKAP sequence in PKA modification of β-catenin and its effect on transcription activation, we confirmed dependence of S675 phosphorylation and transcription coactivator function on BIG2 AKAP-C sequence. PMID:27162341

  19. AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

    Science.gov (United States)

    Mahboubi, Hicham; Koromilas, Antonis E; Stochaj, Ursula

    2016-10-01

    Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. PMID:27430620

  20. 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

  1. Defining a Modular Signalling Network from the Fly Interactome

    Directory of Open Access Journals (Sweden)

    Jacq Bernard

    2008-05-01

    Full Text Available Abstract Background Signalling pathways relay information by transmitting signals from cell surface receptors to intracellular effectors that eventually activate the transcription of target genes. Since signalling pathways involve several types of molecular interactions including protein-protein interactions, we postulated that investigating their organization in the context of the global protein-protein interaction network could provide a new integrated view of signalling mechanisms. Results Using a graph-theory based method to analyse the fly protein-protein interaction network, we found that each signalling pathway is organized in two to three different signalling modules. These modules contain canonical proteins of the signalling pathways, known regulators as well as other proteins thereby predicted to participate to the signalling mechanisms. Connections between the signalling modules are prominent as compared to the other network's modules and interactions within and between signalling modules are among the more central routes of the interaction network. Conclusion Altogether, these modules form an interactome sub-network devoted to signalling with particular topological properties: modularity, density and centrality. This finding reflects the integration of the signalling system into cell functioning and its important role connecting and coordinating different biological processes at the level of the interactome.

  2. A fuzzy neural network for sensor signal estimation

    International Nuclear Information System (INIS)

    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

  3. Autonomous and nonautonomous regulation of axis formation by antagonistic signaling via 7-span cAMP receptors and GSK3 in Dictyostelium

    OpenAIRE

    Ginsburg, Gail T.; Alan R. Kimmel

    1997-01-01

    Early during Dictyostelium development a fundamental cell-fate decision establishes the anteroposterior (prestalk/prespore) axis. Signaling via the 7-transmembrane cAMP receptor CAR4 is essential for creating and maintaining a normal pattern; car4-null alleles have decreased levels of prestalk-specific mRNAs but enhanced expression of prespore genes. car4− cells produce all of the signals required for prestalk differentiation but lack an extracellular factor necessary for prespore differentia...

  4. Using Artificial Neural Networks for ECG Signals Denoising

    Directory of Open Access Journals (Sweden)

    Zoltán Germán-Salló

    2010-12-01

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

  5. The EEG signal prediction bz using neural network

    OpenAIRE

    Babušiak, B.; Mohylová, J.

    2008-01-01

    The neural network is computational model based on the features abstraction of biological neural systems. The neural networks have many ways of usage in technical field. They have been applied successfully to speech recognition, image analysis and adaptive control, in order to construct software agents or autonomous robots. In this paper is described usage of neural networks for ECG signal prediction. The ECG signal prediction can be used for automated detection of irregular heart...

  6. An approach to evolving cell signaling networks in silico

    OpenAIRE

    Decraene, James; Mitchell, George G.; Kelly, Ciaran; McMullin, Barry

    2006-01-01

    Cell Signaling Networks(CSN) are complex bio-chemical networks which, through evolution, have become highly efficient for governing critical control processes such as immunological responses, cell cycle control or homeostasis. From a computational point of view, modeling Artificial Cell Signaling Networks (ACSNs) in silico may provide new ways to design computer systems which may have specialized application areas. To investigate these new opportunities, we review the key issues of mod...

  7. The EEG Signal Prediction by Using Neural Network

    OpenAIRE

    Branko Babusiak; Jitka Mohylova

    2008-01-01

    The neural network is computational model based on the features abstraction of biological neural systems. The neural networks have many ways of usage in technical field. They have been applied successfully to speech recognition, image analysis and adaptive control, in order to construct software agents or autonomous robots. In this paper is described usage of neural networks for ECG signal prediction. The ECG signal prediction can be used for  automated detection of irregular heartbeat – extr...

  8. Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation

    Directory of Open Access Journals (Sweden)

    Dandekar Thomas

    2011-10-01

    Full Text Available Abstract Background Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG activation. In turn, platelet phosphodiesterases (PDEs and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation. Results We modeled dynamically concentration-dependent responses of pathway effectors (inhibitors, activators, drug combinations to cyclic nucleotide signaling as well as to downstream signaling events and verified resulting model predictions by experimental data. Experiments with various cAMP affecting compounds including anti-platelet drugs and their combinations revealed a high fidelity, fine-tuned cAMP signaling in platelets without cross-talk to the cGMP pathway. The model and the data provide evidence for two independent feedback loops: PKA, which is activated by elevated cAMP levels in the platelet, subsequently inhibits adenylyl cyclase (AC but as well activates PDE3. By multi-experiment fitting, we established a comprehensive dynamic model with one predictive, optimized and validated set of parameters. Different pharmacological conditions (inhibition, activation, drug combinations, permanent and transient perturbations are successfully tested and simulated, including statistical validation and sensitivity analysis

  9. The cAMP-dependent protein kinase inhibitor H-89 attenuates the bioluminescence signal produced by Renilla Luciferase.

    Directory of Open Access Journals (Sweden)

    Katie J Herbst

    Full Text Available BACKGROUND: Investigations into the regulation and functional roles of kinases such as cAMP-dependent protein kinase (PKA increasingly rely on cellular assays. Currently, there are a number of bioluminescence-based assays, for example reporter gene assays, that allow the study of the regulation, activity, and functional effects of PKA in the cellular context. Additionally there are continuing efforts to engineer improved biosensors that are capable of detecting real-time PKA signaling dynamics in cells. These cell-based assays are often utilized to test the involvement of PKA-dependent processes by using H-89, a reversible competitive inhibitor of PKA. PRINCIPAL FINDINGS: We present here data to show that H-89, in addition to being a competitive PKA inhibitor, attenuates the bioluminescence signal produced by Renilla luciferase (RLuc variants in a population of cells and also in single cells. Using 10 microM of luciferase substrate and 10 microM H-89, we observed that the signal from RLuc and RLuc8, an eight-point mutation variant of RLuc, in cells was reduced to 50% (+/-15% and 54% (+/-14% of controls exposed to the vehicle alone, respectively. In vitro, we showed that H-89 decreased the RLuc8 bioluminescence signal but did not compete with coelenterazine-h for the RLuc8 active site, and also did not affect the activity of Firefly luciferase. By contrast, another competitive inhibitor of PKA, KT5720, did not affect the activity of RLuc8. SIGNIFICANCE: The identification and characterization of the adverse effect of H-89 on RLuc signal will help deconvolute data previously generated from RLuc-based assays looking at the functional effects of PKA signaling. In addition, for the current application and future development of bioluminscence assays, KT5720 is identified as a more suitable PKA inhibitor to be used in conjunction with RLuc-based assays. These principal findings also provide an important lesson to fully consider all of the potential

  10. Neural network signal understanding for instrumentation

    DEFF Research Database (Denmark)

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

    1990-01-01

    A report is presented on the use of neural signal interpretation theory and techniques for the purpose of classifying the shapes of a set of instrumentation signals, in order to calibrate devices, diagnose anomalies, generate tuning/settings, and interpret the measurement results. Neural signal......, and an explanation facility designed to help neural signal understanding is described. The results are compared to those obtained with a knowledge-based signal interpretation system using the same instrument and data...

  11. GATA-Dependent Glutaminolysis Drives Appressorium Formation in Magnaporthe oryzae by Suppressing TOR Inhibition of cAMP/PKA Signaling.

    Directory of Open Access Journals (Sweden)

    Margarita Marroquin-Guzman

    2015-04-01

    Full Text Available Fungal plant pathogens are persistent and global food security threats. To invade their hosts they often form highly specialized infection structures, known as appressoria. The cAMP/ PKA- and MAP kinase-signaling cascades have been functionally delineated as positive-acting pathways required for appressorium development. Negative-acting regulatory pathways that block appressorial development are not known. Here, we present the first detailed evidence that the conserved Target of Rapamycin (TOR signaling pathway is a powerful inhibitor of appressorium formation by the rice blast fungus Magnaporthe oryzae. We determined TOR signaling was activated in an M. oryzae mutant strain lacking a functional copy of the GATA transcription factor-encoding gene ASD4. Δasd4 mutant strains could not form appressoria and expressed GLN1, a glutamine synthetase-encoding orthologue silenced in wild type. Inappropriate expression of GLN1 increased the intracellular steady-state levels of glutamine in Δasd4 mutant strains during axenic growth when compared to wild type. Deleting GLN1 lowered glutamine levels and promoted appressorium formation by Δasd4 strains. Furthermore, glutamine is an agonist of TOR. Treating Δasd4 mutant strains with the specific TOR kinase inhibitor rapamycin restored appressorium development. Rapamycin was also shown to induce appressorium formation by wild type and Δcpka mutant strains on non-inductive hydrophilic surfaces but had no effect on the MAP kinase mutant Δpmk1. When taken together, we implicate Asd4 in regulating intracellular glutamine levels in order to modulate TOR inhibition of appressorium formation downstream of cPKA. This study thus provides novel insight into the metabolic mechanisms that underpin the highly regulated process of appressorium development.

  12. Subsurface Event Detection and Classification Using Wireless Signal Networks

    OpenAIRE

    Suleiman, Muhannad T.; Sibel Pamukcu; Liang Cheng; Ehsan Ghazanfari; Suk-Un Yoon

    2012-01-01

    Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs). The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for even...

  13. Intelligent sensor networks the integration of sensor networks, signal processing and machine learning

    CERN Document Server

    Hu, Fei

    2012-01-01

    Although governments worldwide have invested significantly in intelligent sensor network research and applications, few books cover intelligent sensor networks from a machine learning and signal processing perspective. Filling this void, Intelligent Sensor Networks: The Integration of Sensor Networks, Signal Processing and Machine Learning focuses on the close integration of sensing, networking, and smart signal processing via machine learning. Based on the world-class research of award-winning authors, the book provides a firm grounding in the fundamentals of intelligent sensor networks, incl

  14. Interleukin-7 Receptor Signaling Network: An Integrated Systems Perspective

    Institute of Scientific and Technical Information of China (English)

    Megan J. Palmer; Vinay S. Mahajan; Lily C. Trajman; Darrell J. Irvine; Douglas A.Lauffenburger; Jianzhu Chen

    2008-01-01

    Interleukin-7 (IL-7) is an essential cytokine for the development and homeostatic maintenance of T and B lymphocytes. Binding of IL-7 to its cognate receptor, the IL-7 receptor (IL-7R), activates multiple pathways that regulate lymphocyte survival, glucose uptake, proliferation and differentiation. There has been much interest in understanding how IL-7 receptor signaling is modulated at multiple interconnected network levels. This review examines how the strength of the signal through the IL-7 receptor is modulated in T and B cells, including the use of shared receptor components, signaling crosstaik, shared interaction domains, feedback loops, integrated gene regulation, muitimerization and ligand competition. We discuss how these network control mechanisms could integrate to govern the properties of IL-7R signaling in lymphocytes in health and disease. Analysis of IL-7receptor signaling at a network level in a systematic manner will allow for a comprehensive approach to understanding the impact of multiple signaling pathways on lymphocyte biology.

  15. Decoding signalling networks by mass spectrometry-based proteomics

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Mann, Matthias

    2010-01-01

    Signalling networks regulate essentially all of the biology of cells and organisms in normal and disease states. Signalling is often studied using antibody-based techniques such as western blots. Large-scale 'precision proteomics' based on mass spectrometry now enables the system-wide characteriz......Signalling networks regulate essentially all of the biology of cells and organisms in normal and disease states. Signalling is often studied using antibody-based techniques such as western blots. Large-scale 'precision proteomics' based on mass spectrometry now enables the system...... perturbation. Current studies focus on phosphorylation, but acetylation, methylation, glycosylation and ubiquitylation are also becoming amenable to investigation. Large-scale proteomics-based signalling research will fundamentally change our understanding of signalling networks....

  16. Defining a Modular Signalling Network from the Fly Interactome

    OpenAIRE

    Jacq Bernard; Guénoche Alain; Angelelli Jean-Baptiste; Baudot Anaïs; Brun Christine

    2008-01-01

    Abstract Background Signalling pathways relay information by transmitting signals from cell surface receptors to intracellular effectors that eventually activate the transcription of target genes. Since signalling pathways involve several types of molecular interactions including protein-protein interactions, we postulated that investigating their organization in the context of the global protein-protein interaction network could provide a new integrated view of signalling mechanisms. Results...

  17. An extended signal control strategy for urban network traffic flow

    Science.gov (United States)

    Yan, Fei; Tian, Fuli; Shi, Zhongke

    2016-03-01

    Traffic flow patterns are in general repeated on a daily or weekly basis. To improve the traffic conditions by using the inherent repeatability of traffic flow, a novel signal control strategy for urban networks was developed via iterative learning control (ILC) approach. Rigorous analysis shows that the proposed learning control method can guarantee the asymptotic convergence. The impacts of the ILC-based signal control strategy on the macroscopic fundamental diagram (MFD) were analyzed by simulations on a test road network. The results show that the proposed ILC strategy can evenly distribute the accumulation in the network and improve the network mobility.

  18. Differences in the control of basal L-type Ca(2+) current by the cyclic AMP signaling cascade in frog, rat, and human cardiac myocytes.

    Science.gov (United States)

    Treinys, Rimantas; Bogdelis, Andrius; Rimkutė, Lina; Jurevičius, Jonas; Skeberdis, Vytenis Arvydas

    2016-07-01

    β-adrenergic receptors (β-ARs) mediate the positive inotropic effects of catecholamines by cAMP-dependent phosphorylation of the L-type Ca(2+) channels (LTCCs), which provide Ca(2+) for the initiation and regulation of cell contraction. The overall effect of cAMP-modulating agents on cardiac calcium current (I Ca,L) and contraction depends on the basal activity of LTCCs which, in turn, depends on the basal activities of key enzymes involved in the cAMP signaling cascade. Our current work is a comparative study demonstrating the differences in the basal activities of β-ARs, adenylyl cyclase, phosphodiesterases, phosphatases, and LTCCs in the frog and rat ventricular and human atrial myocytes. The main conclusion is that the basal I Ca,L, and consequently the contractile function of the heart, is secured from unnecessary elevation of its activity and energy consumption at the several "checking-points" of cAMP-dependent signaling cascade and the loading of these "checking-points" may vary in different species and tissues. PMID:26676115

  19. Processing of seismic signals from a seismometer network

    International Nuclear Information System (INIS)

    A description is given of the Seismometer Network Analysis Computer (SNAC) which processes short period data from a network of seismometers (UKNET). The nine stations of the network are distributed throughout the UK and their outputs are transmitted to a control laboratory (Blacknest) where SNAC monitors the data for seismic signals. The computer gives an estimate of the source location of the detected signals and stores the waveforms. The detection logic is designed to maintain high sensitivity without excessive ''false alarms''. It is demonstrated that the system is able to detect seismic signals at an amplitude level consistent with a network of single stations and, within the limitations of signal onset time measurements made by machine, can locate the source of the seismic disturbance. (author)

  20. Detection of Gaussian signals via hexagonal sensor networks

    OpenAIRE

    Frasca, Paolo; Mason, Paolo; Piccoli, Benedetto

    2009-01-01

    This paper considers a special case of the problem of identifying a static scalar signal, depending on the location, using a planar network of sensors in a distributed fashion. Motivated by the application to monitoring wild-fires spreading and pollutants dispersion, we assume the signal to be Gaussian in space. Using a network of sensors positioned to form a regular hexagonal tessellation, we prove that each node can estimate the parameters of the Gaussian from local measurements. Moreover, ...

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

    International Nuclear Information System (INIS)

    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

  2. Signaling Over Protocols Gateways in Next-Generation Networks

    OpenAIRE

    Akinwande, Gbenga Segun

    2009-01-01

    In this thesis, I examined various signalling both in wired and mobile networks, with more emphasis on SIGTRAN. The SIGTRAN is the protocol suite applicable in the current new generation and next-generation networks, most especially as it enables service provider to be able to interpolate both wireline and wireless services within the same architecture. This concept is an important component in today’s Triple-play communication, and hence this thesis has provided a broad view on Signalling an...

  3. Crosstalk between pathways enhances the controllability of signalling networks.

    Science.gov (United States)

    Wang, Dingjie; Jin, Suoqin; Zou, Xiufen

    2016-02-01

    The control of complex networks is one of the most challenging problems in the fields of biology and engineering. In this study, the authors explored the controllability and control energy of several signalling networks, which consisted of many interconnected pathways, including networks with a bow-tie architecture. On the basis of the theory of structure controllability, they revealed that biological mechanisms, such as cross-pathway interactions, compartmentalisation and so on make the networks easier to fully control. Furthermore, using numerical simulations for two realistic examples, they demonstrated that the control energy of normal networks with crosstalk is lower than in networks without crosstalk. These results indicate that the biological networks are optimally designed to achieve their normal functions from the viewpoint of the control theory. The authors' work provides a comprehensive understanding of the impact of network structures and properties on controllability. PMID:26816393

  4. Enhanced photoacoustic signal from DNA assembled gold nanoparticle networks

    International Nuclear Information System (INIS)

    We report an experimental finding of photoacoustic signal enhancement from finite sized DNA–gold nanoparticle networks. We synthesized DNA-functionalized hollow and solid gold nanospheres (AuNS) to form finite sized networks, which were characterized by means of optical extinction spectroscopy, dynamic light scattering, and scanning electron microscopy in transmission mode. It is shown that the signal amplification scales with network size for networks comprising either hollow or solid AuNS as well as networks consisting of both types of nanoparticles. The laser intensities applied in our multispectral setup (λ = 650 nm, 850 nm, 905 nm) were low enough to maintain the structural integrity of the networks. This reflects that the binding and recognition properties of the temperature-sensitive cross-linking DNA-molecules are retained. (paper)

  5. Caffeine Modulates Vesicle Release and Recovery at Cerebellar Parallel Fibre Terminals, Independently of Calcium and Cyclic AMP Signalling.

    Directory of Open Access Journals (Sweden)

    Katharine L Dobson

    Full Text Available Cerebellar parallel fibres release glutamate at both the synaptic active zone and at extrasynaptic sites-a process known as ectopic release. These sites exhibit different short-term and long-term plasticity, the basis of which is incompletely understood but depends on the efficiency of vesicle release and recycling. To investigate whether release of calcium from internal stores contributes to these differences in plasticity, we tested the effects of the ryanodine receptor agonist caffeine on both synaptic and ectopic transmission.Whole cell patch clamp recordings from Purkinje neurons and Bergmann glia were carried out in transverse cerebellar slices from juvenile (P16-20 Wistar rats.Caffeine caused complex changes in transmission at both synaptic and ectopic sites. The amplitude of postsynaptic currents in Purkinje neurons and extrasynaptic currents in Bergmann glia were increased 2-fold and 4-fold respectively, but paired pulse ratio was substantially reduced, reversing the short-term facilitation observed under control conditions. Caffeine treatment also caused synaptic sites to depress during 1 Hz stimulation, consistent with inhibition of the usual mechanisms for replenishing vesicles at the active zone. Unexpectedly, pharmacological intervention at known targets for caffeine--intracellular calcium release, and cAMP signalling--had no impact on these effects.We conclude that caffeine increases release probability and inhibits vesicle recovery at parallel fibre synapses, independently of known pharmacological targets. This complex effect would lead to potentiation of transmission at fibres firing at low frequencies, but depression of transmission at high frequency connections.

  6. Signal propagation through feedforward neuronal networks with different operational modes

    Science.gov (United States)

    Li, Jie; Liu, Feng; Xu, Ding; Wang, Wei

    2009-02-01

    How neuronal activity is propagated across multiple layers of neurons is a fundamental issue in neuroscience. Using numerical simulations, we explored how the operational mode of neurons —coincidence detector or temporal integrator— could affect the propagation of rate signals through a 10-layer feedforward network with sparse connectivity. Our study was based on two kinds of neuron models. The Hodgkin-Huxley (HH) neuron can function as a coincidence detector, while the leaky integrate-and-fire (LIF) neuron can act as a temporal integrator. When white noise is afferent to the input layer, rate signals can be stably propagated through both networks, while neurons in deeper layers fire synchronously in the absence of background noise; but the underlying mechanism for the development of synchrony is different. When an aperiodic signal is presented, the network of HH neurons can represent the temporal structure of the signal in firing rate. Meanwhile, synchrony is well developed and is resistant to background noise. In contrast, rate signals are somewhat distorted during the propagation through the network of LIF neurons, and only weak synchrony occurs in deeper layers. That is, coincidence detectors have a performance advantage over temporal integrators in propagating rate signals. Therefore, given weak synaptic conductance and sparse connectivity between layers in both networks, synchrony does greatly subserve the propagation of rate signals with fidelity, and coincidence detection could be of considerable functional significance in cortical processing.

  7. cAMP signalling of Bordetella adenylate cyclase toxin through the SHP-1 phosphatase activates the BimEL-Bax pro-apoptotic cascade in phagocytes.

    Science.gov (United States)

    Ahmad, Jawid Nazir; Cerny, Ondrej; Linhartova, Irena; Masin, Jiri; Osicka, Radim; Sebo, Peter

    2016-03-01

    The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) plays a key role in virulence of Bordetella pertussis. CyaA penetrates myeloid cells expressing the complement receptor 3 (αM β2 integrin CD11b/CD18) and subverts bactericidal capacities of neutrophils and macrophages by catalysing unregulated conversion of cytosolic ATP to the key signalling molecule adenosine 3',5'-cyclic monophosphate (cAMP). We show that the signalling of CyaA-produced cAMP hijacks, by an as yet unknown mechanism, the activity of the tyrosine phosphatase SHP-1 and activates the pro-apoptotic BimEL-Bax cascade. Mitochondrial hyperpolarization occurred in human THP-1 macrophages within 10 min of exposure to low CyaA concentrations (e.g. 20 ng ml(-1) ) and was accompanied by accumulation of BimEL and association of the pro-apoptotic factor Bax with mitochondria. BimEL accumulation required cAMP/protein kinase A signalling, depended on SHP-1 activity and was selectively inhibited upon small interfering RNA knockdown of SHP-1 but not of the SHP-2 phosphatase. Moreover, signalling of CyaA-produced cAMP inhibited the AKT/protein kinase B pro-survival cascade, enhancing activity of the FoxO3a transcription factor and inducing Bim transcription. Synergy of FoxO3a activation with SHP-1 hijacking thus enables the toxin to rapidly trigger a persistent accumulation of BimEL, thereby activating the pro-apoptotic programme of macrophages and subverting the innate immunity of the host. PMID:26334669

  8. Type I Collagen Structure Regulates Cell Morphology and EGF Signaling in Primary Rat Hepatocytes through cAMP-dependent Protein Kinase A

    OpenAIRE

    Fassett, John; Tobolt, Diane; Hansen, Linda K.

    2006-01-01

    Adhesion to type 1 collagen elicits different responses dependent on whether the collagen is in fibrillar (gel) or monomeric form (film). Hepatocytes adherent to collagen film spread and proliferate, whereas those adherent to collagen gel remain rounded and growth arrested. To explore the role of potential intracellular inhibitory signals responsible for collagen gel-mediated growth arrest, cAMP-dependent protein kinase A (PKA) was examined in hepatocytes adherent to collagen film or gel. PKA...

  9. Dopamine- and cAMP-regulated phosphoprotein of 32-kDa (DARPP-32)-dependent activation of extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin complex 1 (mTORC1) signaling in experimental parkinsonism.

    Science.gov (United States)

    Santini, Emanuela; Feyder, Michael; Gangarossa, Giuseppe; Bateup, Helen S; Greengard, Paul; Fisone, Gilberto

    2012-08-10

    Dyskinesia, a motor complication caused by prolonged administration of the antiparkinsonian drug l-3,4-dihydroxyphenylalanine (l-DOPA), is accompanied by activation of cAMP signaling and hyperphosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). Here, we show that the abnormal phosphorylation of DARPP-32 occurs specifically in medium spiny neurons (MSNs) expressing dopamine D1 receptors (D1R). Using mice in which DARPP-32 is selectively deleted in D1R-expressing MSNs, we demonstrate that this protein is required for l-DOPA-induced activation of the extracellular signal-regulated protein kinases 1 and 2 and the mammalian target of rapamycin complex 1 (mTORC1) pathways, which are implicated in dyskinesia. We also show that mutation of the phosphorylation site for cAMP-dependent protein kinase on DARPP-32 attenuates l-DOPA-induced dyskinesia and reduces the concomitant activations of ERK and mTORC1 signaling. These studies demonstrate that, in D1R-expressing MSNs, l-DOPA-induced activation of ERK and mTORC1 requires DARPP-32 and indicates the importance of the cAMP/DARPP-32 signaling cascade in dyskinesia. PMID:22753408

  10. Dopamine- and cAMP-regulated Phosphoprotein of 32-kDa (DARPP-32)-dependent Activation of Extracellular Signal-regulated Kinase (ERK) and Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling in Experimental Parkinsonism*

    Science.gov (United States)

    Santini, Emanuela; Feyder, Michael; Gangarossa, Giuseppe; Bateup, Helen S.; Greengard, Paul; Fisone, Gilberto

    2012-01-01

    Dyskinesia, a motor complication caused by prolonged administration of the antiparkinsonian drug l-3,4-dihydroxyphenylalanine (l-DOPA), is accompanied by activation of cAMP signaling and hyperphosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). Here, we show that the abnormal phosphorylation of DARPP-32 occurs specifically in medium spiny neurons (MSNs) expressing dopamine D1 receptors (D1R). Using mice in which DARPP-32 is selectively deleted in D1R-expressing MSNs, we demonstrate that this protein is required for l-DOPA-induced activation of the extracellular signal-regulated protein kinases 1 and 2 and the mammalian target of rapamycin complex 1 (mTORC1) pathways, which are implicated in dyskinesia. We also show that mutation of the phosphorylation site for cAMP-dependent protein kinase on DARPP-32 attenuates l-DOPA-induced dyskinesia and reduces the concomitant activations of ERK and mTORC1 signaling. These studies demonstrate that, in D1R-expressing MSNs, l-DOPA-induced activation of ERK and mTORC1 requires DARPP-32 and indicates the importance of the cAMP/DARPP-32 signaling cascade in dyskinesia. PMID:22753408

  11. Energy Distribution of EEG Signals: EEG Signal Wavelet-Neural Network Classifier

    OpenAIRE

    Omerhodzic, Ibrahim; Avdakovic, Samir; Nuhanovic, Amir; Dizdarevic, Kemal

    2013-01-01

    In this paper, a wavelet-based neural network (WNN) classifier for recognizing EEG signals is implemented and tested under three sets EEG signals (healthy subjects, patients with epilepsy and patients with epileptic syndrome during the seizure). First, the Discrete Wavelet Transform (DWT) with the Multi-Resolution Analysis (MRA) is applied to decompose EEG signal at resolution levels of the components of the EEG signal (delta, theta, alpha, beta and gamma) and the Parsevals theorem are employ...

  12. Social multimedia signals a signal processing approach to social network phenomena

    CERN Document Server

    Roy, Suman Deb

    2014-01-01

    This book provides a comprehensive coverage of the state-of-the-art in understanding media popularity and trends in online social networks through social multimedia signals. With insights from the study of popularity and sharing patterns of online media, trend spread in social media, social network analysis for multimedia and visualizing diffusion of media in online social networks. In particular, the book will address the following important issues: Understanding social network phenomena from a signal processing point of view; The existence and popularity of multimedia as shared and social me

  13. The EEG Signal Prediction by Using Neural Network

    Directory of Open Access Journals (Sweden)

    Jitka Mohylova

    2008-01-01

    Full Text Available The neural network is computational model based on the features abstraction of biological neural systems. The neural networks have many ways of usage in technical field. They have been applied successfully to speech recognition, image analysis and adaptive control, in order to construct software agents or autonomous robots. In this paper is described usage of neural networks for ECG signal prediction. The ECG signal prediction can be used for  automated detection of irregular heartbeat – extrasystole. The automated detection system of unexpected abnormalities is also described in this paper

  14. Human Identification with Electrocardiogram Signals: a Neural Network Approach

    Science.gov (United States)

    Wan, Yongbo; Yao, Jianchu

    2009-05-01

    This paper presents a neural network developed to identify human subjects using electrocardiogram (ECG) signals collected from an "in-house" wearable electrocardiogram (ECG) sensor. In this project, noises were first removed from the raw signals with wavelet filters. ECG cycles were then extracted from the filtered signals and decomposed into wavelet coefficient structures. These coefficient structures were used as input vectors to a 3-layer feedforward neural network that generates the identification results. In the current study, 61 datasets collected from 23 subjects were utilized to train the neural network, which thereafter was tested with 15 new datasets from 15 different subjects. All the 15 subjects in the experiment were successfully identified. The testing results demonstrate that the neural network is effective.

  15. Amplified Signal Response by Neuronal Diversity on Complex Networks

    International Nuclear Information System (INIS)

    The effect of diversity on dynamics of coupled FitzHugh–Nagumo neurons on complex networks is numerically investigated, where each neuron is subjected to an external subthreshold signal. With the diversity the network is a mixture of excitable and oscillatory neurons, and the diversity is determined by the variance of the system's parameter. The complex network is constructed by randomly adding long-range connections (shortcuts) on a nearest-neighbouring coupled one-dimensional chain. Numerical results show that external signals are maximally magnified at an intermediate value of the diversity, as in the case of well-known stochastic resonance. Furthermore, the effects of the number of shortcuts and coupled strength on the diversity-induced phenomena are also discussed. These findings exhibit that the diversity may play a constructive role in response to external signal, and highlight the importance of the diversity on such complex networks. (general)

  16. Structural permeability of complex networks to control signals

    Science.gov (United States)

    Lo Iudice, Francesco; Garofalo, Franco; Sorrentino, Francesco

    2015-09-01

    Many biological, social and technological systems can be described as complex networks. The goal of affecting their behaviour has motivated recent work focusing on the relationship between the network structure and its propensity to be controlled. While this work has provided insight into several relevant problems, a comprehensive approach to address partial and complete controllability of networks is still lacking. Here, we bridge this gap by developing a framework to maximize the diffusion of the control signals through a network, while taking into account physical and economic constraints that inevitably arise in applications. This approach allows us to introduce the network permeability, a unified metric of the propensity of a network to be controllable. The analysis of the permeability of several synthetic and real networks enables us to extract some structural features that deepen our quantitative understanding of the ease with which specific controllability requirements can be met.

  17. SIMULATING BIOCHEMICAL SIGNALING NETWORKS IN COMPLEX MOVING GEOMETRIES.

    Science.gov (United States)

    Strychalski, Wanda; Adalsteinsson, David; Elston, Timothy C

    2010-01-01

    Signaling networks regulate cellular responses to environmental stimuli through cascades of protein interactions. External signals can trigger cells to polarize and move in a specific direction. During migration, spatially localized activity of proteins is maintained. To investigate the effects of morphological changes on intracellular signaling, we developed a numerical scheme consisting of a cut cell finite volume spatial discretization coupled with level set methods to simulate the resulting advection-reaction-diffusion system. We then apply the method to several biochemical reaction networks in changing geometries. We found that a Turing instability can develop exclusively by cell deformations that maintain constant area. For a Turing system with a geometry-dependent single or double peak solution, simulations in a dynamically changing geometry suggest that a single peak solution is the only stable one, independent of the oscillation frequency. The method is also applied to a model of a signaling network in a migrating fibroblast. PMID:24086102

  18. Prioritizing Signaling Information Transmission in Next Generation Networks

    Directory of Open Access Journals (Sweden)

    Jasmina Baraković

    2011-01-01

    Full Text Available Next generation transport network is characterized by the use of in-band signaling, where Internet Protocol (IP packets carrying signaling or media information are mixed in transmission. Since transport resources are limited, when any segment of access or core network is congested, IP packets carrying signaling information may be discarded. As a consequence, it may be impossible to implement reachability and quality of service (QoS. Since present approaches are insufficient to completely address this problem, a novel approach is proposed, which is based on prioritizing signaling information transmission. To proof the concept, a simulation study was performed using Network Simulator version 2 (ns-2 and independently developed Session Initiation Protocol (SIP module. The obtained results were statistically processed using Statistical Package for the Social Sciences (SPSS version 15.0. Summarizing our research results, several issues are identified for future work.

  19. Identification of melanoma biomarkers based on network modules by integrating the human signaling network with microarrays

    OpenAIRE

    Chunyun Huang; Youyu Sheng; Jack Jia; Lianjun Chen

    2014-01-01

    Background: Melanoma is a leading cause of cancer death. Thus, accurate prognostic biomarkers that will assist rational treatment planning need to be identified. Methods: Microarray analysis of melanoma and normal tissue samples was performed to identify differentially expressed modules (DEMs) from the signaling network and ultimately detect molecular markers to support histological examination. Network motifs were extracted from the human signaling network. Then, significant expression-c...

  20. Signaling network dynamics investigated by quantitative phosphoproteomics

    NARCIS (Netherlands)

    Giansanti, Piero

    2014-01-01

    This thesis describes the application of proteomics technologies to get insight into several aspects of phosphorylation signaling dynamics. The core tool in all performed experiments is mass spectrometry (MS)-based phosphoproteomics. In Chapter 1, a general introduction is given into proteomics and

  1. Techniques for labeling of optical signals in bust switched networks

    DEFF Research Database (Denmark)

    Tafur Monroy, Idelfonso; Koonen, A. M. J.; Zhang, Jianfeng; Chi, Nan; Holm-Nielsen, Pablo Villanueva; Peucheret, Christophe; Olmos, J. J. Vegas; Khoe, G. D.

    2003-01-01

    We present a review of significant issues related to labeled optical burst switched (LOBS) networks and technologies enabling future optical internet networks. Labeled optical burst switching provides a quick and efficient forwarding mechanism of IP packets/bursts over wavelength division...... multiplexed (WDM) networks due to its single forwarding algorithm, thus yielding low latency, and it enables scaling to terabit rates. Moreover, LOBS is compatible with the general multiprotocol label switching (GMPLS) framework for a unified control plane. We present a review on techniques for labeling of...... optical signals for LOBS networks, including experimental results, we discuss as well issues for further research....

  2. Network Non-Neutrality through Preferential Signaling

    OpenAIRE

    Hanawal, Manjesh Kumar; Altman, Eitan

    2013-01-01

    One of the central issues in the debate on network neutrality has been whether one should allow or prevent preferential treatment by an internet service provider (ISP) of traffic according to its origin. This raised the question of whether to allow an ISP to have exclusive agreement with a content provider (CP). In this paper we consider discrimination in the opposite direction. We study the impact that a CP can have on the benefits of several competing ISPs by sharing private information con...

  3. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE......-dependent regulation of signal transduction. Upon ligand-binding and activation in the cilium, TGFβ receptors accumulate and are internalized at the ciliary base together with Smad2/3 transcription factors that are phosphorylated here and translocated to the nucleus for target gene expression. These processes depend...... migration. A number of central Wnt components localize to the fibroblast primary cilium, including the Wnt5a-receptor, Fzd3, and Dvl proteins. Inversin-deficient MEFs have an elevated expression of canonical Wnt-associated genes and proteins, in addition to dysregulation of components in non-canonical Wnt...

  4. Emerging connections in the ethylene signaling network

    OpenAIRE

    Yoo, Sang-Dong; Cho, Younghee; Sheen, Jen

    2009-01-01

    The gaseous plant hormone ethylene acts as a pivotal mediator to respond to and coordinate internal and external cues in modulating plant growth dynamics and developmental programs. Genetic analysis of Arabidopsis thaliana has been used to identify key components and to build a linear ethylene-signaling pathway from the receptors through to the nuclear transcription factors. Studies applying integrative approaches have revealed new regulators, molecular connections and mechanisms in ethylene ...

  5. Quantitative analysis of the dynamic signaling pathway involved in the cAMP mediated induction of l-carnitine biosynthesis in E. coli cultures.

    Science.gov (United States)

    Hormiga, José; González-Alcón, Carlos; Sevilla, Angel; Cánovas, Manuel; Torres, Néstor V

    2010-04-01

    L-(-)-carnitine can be synthesized from waste bioprecursors in the form of crotonobetaine. Such biotransformation is carried out in E. coli by the enzymes encoded by operons regulated by the cAMP receptor proteins. Non-phosphorylated sugars, such as glycerol are used as energy and carbon source since glucose inhibits cAMP synthesis. Until now little attention has been paid to the regulatory signaling structure that operates during the transition from a glucose-consuming, non-l-carnitine producing steady state, to a glycerol-consuming l-carnitine producing steady state. In this work we aim to elucidate and quantify the underlying regulatory mechanisms operating in the abolition of the glucose inhibiting effect. For this purpose we make use of the systemic approach by integrating the available information and our own experimentally generated data to construct a mathematical model. The model is built using power-law representation and is used as a platform to make predictive simulations and to assess the consistency of the regulatory structure of the overall process. The model is subsequently checked for quality through stability and a special, dynamic sensitivity analysis. The results show that the model is able to deal with the observed system transient phase. The model is multi-hierarchical, comprising the metabolic, gene expression, signaling and bioreactor levels. It involves variables and parameters of a very different nature that develop in different time scales and orders of magnitude. Some of the most relevant conclusions obtained are: (i) the regulatory interactions among glucose, glycerol and cAMP metabolism are far stronger than those present in the l-carnitine transport, production and degradation processes; (ii) carnitine biosynthesis is very sensitive to the cAMP signaling system since it reacts at very low cAMP receptor concentrations, and (iii) ATP is a critical factor in the transient dynamics. All these model-derived observations have been

  6. Autonomous Traffic Signal Control Model with Neural Network Analogy

    CERN Document Server

    Ohira, T

    1997-01-01

    We propose here an autonomous traffic signal control model based on analogy with neural networks. In this model, the length of cycle time period of traffic lights at each signal is autonomously adapted. We find a self-organizing collective behavior of such a model through simulation on a one-dimensional lattice model road: traffic congestion is greatly diffused when traffic signals have such autonomous adaptability with suitably tuned parameters. We also find that effectiveness of the system emerges through interactions between units and shows a threshold transition as a function of proportion of adaptive signals in the model.

  7. Optical Performance Monitoring and Signal Optimization in Optical Networks

    DEFF Research Database (Denmark)

    Petersen, Martin Nordal

    2006-01-01

    The thesis studies performance monitoring for the next generation optical networks. The focus is on all-optical networks with bit-rates of 10 Gb/s or above. Next generation all-optical networks offer large challenges as the optical transmitted distance increases and the occurrence of electrical......-optical-electrical regeneration points decreases. This thesis evaluates the impact of signal degrading effects that are becoming of increasing concern in all-optical high-speed networks due to all-optical switching and higher bit-rates. Especially group-velocity-dispersion (GVD) and a number of nonlinear effects will require...... enhanced attention to avoid signal degradations. The requirements for optical performance monitoring features are discussed, and the thesis evaluates the advantages and necessity of increasing the level of performance monitoring parameters in the physical layer. In particular, methods for optical...

  8. The cAMP signaling system inhibits the repair of γ-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► cAMP signaling system inhibits repair of γ-ray-induced DNA damage. ► cAMP signaling system inhibits DNA damage repair by decreasing XRCC1 expression. ► cAMP signaling system decreases XRCC1 expression by promoting its proteasomal degradation. ► The promotion of XRCC1 degradation by cAMP signaling system is mediated by Epac1. -- Abstract: Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on γ-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (GαsQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of GαsQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after γ-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2′-O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2′-O-Me-cAMP and restored XRCC1 protein level following γ-ray irradiation. From these results, we conclude that the cAMP signaling system inhibits the repair of γ-ray-induced DNA damage by promoting the ubiquitin

  9. Detection of Gaussian signals via hexagonal sensor networks

    CERN Document Server

    Frasca, Paolo; Piccoli, Benedetto

    2009-01-01

    This paper considers a special case of the problem of identifying a static scalar signal, depending on the location, using a planar network of sensors in a distributed fashion. Motivated by the application to monitoring wildfires spreading and pollutants dispersion, we assume the signal to be Gaussian in space. Using a network of sensors positioned to form a regular hexagonal tessellation, we prove that the parameters of the Gaussian can be reconstructed from local measurements. We study the impact of the distance among sensors, and we show how a consensus algorithm can fuse the local estimates, effectively compensating additive errors in the measurements.

  10. Signal processing techniques for synchronization of wireless sensor networks

    Science.gov (United States)

    Lee, Jaehan; Wu, Yik-Chung; Chaudhari, Qasim; Qaraqe, Khalid; Serpedin, Erchin

    2010-11-01

    Clock synchronization is a critical component in wireless sensor networks, as it provides a common time frame to different nodes. It supports functions such as fusing voice and video data from different sensor nodes, time-based channel sharing, and sleep wake-up scheduling, etc. Early studies on clock synchronization for wireless sensor networks mainly focus on protocol design. However, clock synchronization problem is inherently related to parameter estimation, and recently, studies of clock synchronization from the signal processing viewpoint started to emerge. In this article, a survey of latest advances on clock synchronization is provided by adopting a signal processing viewpoint. We demonstrate that many existing and intuitive clock synchronization protocols can be interpreted by common statistical signal processing methods. Furthermore, the use of advanced signal processing techniques for deriving optimal clock synchronization algorithms under challenging scenarios will be illustrated.

  11. Hierarchical feedback modules and reaction hubs in cell signaling networks.

    Directory of Open Access Journals (Sweden)

    Jianfeng Xu

    Full Text Available Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks.

  12. Perturbation Biology: inferring signaling networks in cellular systems

    OpenAIRE

    Molinelli, Evan J.; Korkut, Anil; Wang, Weiqing; Miller, Martin L; Gauthier, Nicholas P.; Jing, Xiaohong; Kaushik, Poorvi; He, Qin; Mills, Gordon; Solit, David B.; Pratilas, Christine A.; Weigt, Martin; Braunstein, Alfredo; Pagnani, Andrea; Zecchina, Riccardo

    2013-01-01

    Author Summary Drugs that target specific effects of signaling proteins are promising agents for treating cancer. One of the many obstacles facing optimal drug design is inadequate quantitative understanding of the coordinated interactions between signaling proteins. De novo model inference of network or pathway models refers to the algorithmic construction of mathematical predictive models from experimental data without dependence on prior knowledge. De novo inference is difficult because of...

  13. Radar signal design problem with neural network processing

    Indian Academy of Sciences (India)

    C Krishnamohan Rao; P S Moharir

    2001-06-01

    Binary and ternary sequences with peaky autocorrelation, measured in terms of high discrimination and merit factor have been searched earlier, using optimization techniques. It is shown that the use of neural network processing of the return signal is much more advantageous. It opens up a new signal design problem, which is solved by an optimization technique called Hamming scan, for both binary and ternary sequences.

  14. The yeast Sks1p kinase signaling network regulates pseudohyphal growth and glucose response.

    Directory of Open Access Journals (Sweden)

    Cole Johnson

    2014-03-01

    Full Text Available The yeast Saccharomyces cerevisiae undergoes a dramatic growth transition from its unicellular form to a filamentous state, marked by the formation of pseudohyphal filaments of elongated and connected cells. Yeast pseudohyphal growth is regulated by signaling pathways responsive to reductions in the availability of nitrogen and glucose, but the molecular link between pseudohyphal filamentation and glucose signaling is not fully understood. Here, we identify the glucose-responsive Sks1p kinase as a signaling protein required for pseudohyphal growth induced by nitrogen limitation and coupled nitrogen/glucose limitation. To identify the Sks1p signaling network, we applied mass spectrometry-based quantitative phosphoproteomics, profiling over 900 phosphosites for phosphorylation changes dependent upon Sks1p kinase activity. From this analysis, we report a set of novel phosphorylation sites and highlight Sks1p-dependent phosphorylation in Bud6p, Itr1p, Lrg1p, Npr3p, and Pda1p. In particular, we analyzed the Y309 and S313 phosphosites in the pyruvate dehydrogenase subunit Pda1p; these residues are required for pseudohyphal growth, and Y309A mutants exhibit phenotypes indicative of impaired aerobic respiration and decreased mitochondrial number. Epistasis studies place SKS1 downstream of the G-protein coupled receptor GPR1 and the G-protein RAS2 but upstream of or at the level of cAMP-dependent PKA. The pseudohyphal growth and glucose signaling transcription factors Flo8p, Mss11p, and Rgt1p are required to achieve wild-type SKS1 transcript levels. SKS1 is conserved, and deletion of the SKS1 ortholog SHA3 in the pathogenic fungus Candida albicans results in abnormal colony morphology. Collectively, these results identify Sks1p as an important regulator of filamentation and glucose signaling, with additional relevance towards understanding stress-responsive signaling in C. albicans.

  15. Non-coding RNA LINC00473 mediates decidualization of human endometrial stromal cells in response to cAMP signaling.

    Science.gov (United States)

    Liang, Xiao-Huan; Deng, Wen-Bo; Liu, Yue-Fang; Liang, Yu-Xiang; Fan, Zong-Min; Gu, Xiao-Wei; Liu, Ji-Long; Sha, Ai-Guo; Diao, Hong-Lu; Yang, Zeng-Ming

    2016-01-01

    Decidualization is an essential step in the establishment of pregnancy. However, the functional contributions of long intergenic noncoding RNAs (LincRNAs) to decidualization have not been explored. To explore the regulation and role of LincRNAs during human decidualization, human endometrial stromal cells (HESCs) are induced to undergo in vitro decidualization by treating with estradiol-17β, db-cAMP and medroxyprogesterone acetate. LINC00473 (LINC473) expression is highly induced in HESCs after decidual stimulus. We found that cAMP-PKA pathway regulates the expression of LINC473 through IL-11-mediated STAT3 phosphorylation. RNA interference-mediated down-regulation of LINC473 inhibits in vitro decidualization. These results suggested that LINC473 might be functionally required for human decidualization. This is the first report demonstrating the presence of LincRNA during human decidualization. PMID:26947914

  16. Non-coding RNA LINC00473 mediates decidualization of human endometrial stromal cells in response to cAMP signaling

    Science.gov (United States)

    Liang, Xiao-Huan; Deng, Wen-Bo; Liu, Yue-Fang; Liang, Yu-Xiang; Fan, Zong-Min; Gu, Xiao-Wei; Liu, Ji-Long; Sha, Ai-Guo; Diao, Hong-Lu; Yang, Zeng-Ming

    2016-01-01

    Decidualization is an essential step in the establishment of pregnancy. However, the functional contributions of long intergenic noncoding RNAs (LincRNAs) to decidualization have not been explored. To explore the regulation and role of LincRNAs during human decidualization, human endometrial stromal cells (HESCs) are induced to undergo in vitro decidualization by treating with estradiol-17β, db-cAMP and medroxyprogesterone acetate. LINC00473 (LINC473) expression is highly induced in HESCs after decidual stimulus. We found that cAMP-PKA pathway regulates the expression of LINC473 through IL-11-mediated STAT3 phosphorylation. RNA interference-mediated down-regulation of LINC473 inhibits in vitro decidualization. These results suggested that LINC473 might be functionally required for human decidualization. This is the first report demonstrating the presence of LincRNA during human decidualization. PMID:26947914

  17. Autonomous and nonautonomous regulation of axis formation by antagonistic signaling via 7-span cAMP receptors and GSK3 in Dictyostelium.

    Science.gov (United States)

    Ginsburg, G T; Kimmel, A R

    1997-08-15

    Early during Dictyostelium development a fundamental cell-fate decision establishes the anteroposterior (prestalk/prespore) axis. Signaling via the 7-transmembrane cAMP receptor CAR4 is essential for creating and maintaining a normal pattern; car4-null alleles have decreased levels of prestalk-specific mRNAs but enhanced expression of prespore genes. car4- cells produce all of the signals required for prestalk differentiation but lack an extracellular factor necessary for prespore differentiation of wild-type cells. This secreted factor decreases the sensitivity of prespore cells to inhibition by the prestalk morphogen DIF-1. At the cell autonomous level, CAR4 is linked to intracellular circuits that activate prestalk but inhibit prespore differentiation. The autonomous action of CAR4 is antagonistic to the positive intracellular signals mediated by another cAMP receptor, CAR1 and/or CAR3. Additional data indicate that these CAR-mediated pathways converge at the serine/threonine protein kinase GSK3, suggesting that the anterior (prestalk)/posterior (prespore) axis of Dictyostelium is regulated by an ancient mechanism that is shared by the Wnt/Fz circuits for dorsoventral patterning during early Xenopus development and establishing Drosophila segment polarity. PMID:9284050

  18. Adiponectin Stimulates Angiogenesis by Promoting Cross-talk between AMP-activated Protein Kinase and Akt Signaling in Endothelial Cells*

    OpenAIRE

    Ouchi, Noriyuki; Kobayashi, Hideki; Kihara, Shinji; Kumada, Masahiro; Sato, Kaori; Inoue, Tatsuya; Funahashi, Tohru; Walsh, Kenneth

    2003-01-01

    Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase Akt/protein ...

  19. Subsurface Event Detection and Classification Using Wireless Signal Networks

    Directory of Open Access Journals (Sweden)

    Muhannad T. Suleiman

    2012-11-01

    Full Text Available Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs. The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events.

  20. Subsurface event detection and classification using Wireless Signal Networks.

    Science.gov (United States)

    Yoon, Suk-Un; Ghazanfari, Ehsan; Cheng, Liang; Pamukcu, Sibel; Suleiman, Muhannad T

    2012-01-01

    Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs). The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events. PMID:23202191

  1. Subsurface Event Detection and Classification Using Wireless Signal Networks

    Science.gov (United States)

    Yoon, Suk-Un; Ghazanfari, Ehsan; Cheng, Liang; Pamukcu, Sibel; Suleiman, Muhannad T.

    2012-01-01

    Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs). The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events. PMID:23202191

  2. Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus

    OpenAIRE

    Kim, Mun Hee; Leem, Yea Hyun

    2014-01-01

    [Purpose] Mood disorders such as anxiety and depression are prevalent psychiatric illness, but the role of 5HT1A in the anti-depressive effects of exercise has been rarely known yet. We investigated whether long-term exercise affected a depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB signaling in depression mice model. [Methods] To induce depressive behaviors, mice were subjected to 14 consecutive days of restraint stress (2 hours/day). Depression-like behavio...

  3. An interplay between 2 signaling pathways: Melatonin-cAMP and IP{sub 3}–Ca{sup 2+} signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum

    Energy Technology Data Exchange (ETDEWEB)

    Furuyama, Wakako [National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan); Enomoto, Masahiro [Princess Margaret Cancer Centre, Department of Medical Biophysics, University of Toronto, M5G1L7 Toronto, Ontario (Canada); Mossaad, Ehab [National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan); Kawai, Satoru [Laboratory of Tropical Medicine and Parasitology, Dokkyo Medical University, Mibu, Tochigi 321-0293 (Japan); Mikoshiba, Katsuhiko [Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama 351-0198 (Japan); Kawazu, Shin-ichiro, E-mail: skawazu@obihiro.ac.jp [National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan)

    2014-03-28

    Highlights: • A melatonin receptor antagonist blocked Ca{sup 2+} oscillation in P. falciparum and inhibited parasite growth. • P. falciparum development is controlled by Ca{sup 2+}- and cAMP-signaling pathways. • The cAMP-signaling pathway at ring form and late trophozoite stages governs parasite growth of P. falciparum. - Abstract: Plasmodium falciparum spends most of its asexual life cycle within human erythrocytes, where proliferation and maturation occur. Development into the mature forms of P. falciparum causes severe symptoms due to its distinctive sequestration capability. However, the physiological roles and the molecular mechanisms of signaling pathways that govern development are poorly understood. Our previous study showed that P. falciparum exhibits stage-specific spontaneous Calcium (Ca{sup 2+}) oscillations in ring and early trophozoites, and the latter was essential for parasite development. In this study, we show that luzindole (LZ), a selective melatonin receptor antagonist, inhibits parasite growth. Analyses of development and morphology of LZ-treated P. falciparum revealed that LZ severely disrupted intraerythrocytic maturation, resulting in parasite death. When LZ was added at ring stage, the parasite could not undergo further development, whereas LZ added at the trophozoite stage inhibited development from early into late schizonts. Live-cell Ca{sup 2+} imaging showed that LZ treatment completely abolished Ca{sup 2+} oscillation in the ring forms while having little effect on early trophozoites. Further, the melatonin-induced cAMP increase observed at ring and late trophozoite stage was attenuated by LZ treatment. These suggest that a complex interplay between IP{sub 3}–Ca{sup 2+} and cAMP signaling pathways is involved in intraerythrocytic development of P. falciparum.

  4. Effects of fluorotelomer alcohol 8:2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade

    International Nuclear Information System (INIS)

    Previous studies have demonstrated that perfluorinated chemicals (PFCs) can affect reproduction by disruption of steroidogenesis in experimental animals. However, the underlying mechanism(s) of this disruption remain unknown. Here we investigated the effects and mechanisms of action of 1H, 1H, 2H, 2H-perfluoro-decan-1-ol (8:2 FTOH) on steroidogenesis using a human adrenocortical carcinoma cell line (H295R) as a model. H295R cells were exposed to 0, 7.4, 22.2 or 66.6 μM 8:2 FTOH for 24 h and productions of progesterone, 17α-OH-progesterone, androstenedione, testosterone, deoxycorticosterone, corticosterone and cortisol were quantified by HPLC-MS/MS. With the exception of progesterone, 8:2 FTOH treatment significantly decreased production of all hormones in the high dose group. Exposure to 8:2 FTOH significantly down-regulated cAMP-dependent mRNA expression and protein abundance of several key steroidogenic enzymes, including StAR, CYP11A, CYP11B1, CYP11B2, CYP17 and CYP21. Furthermore, a dose-dependent decrease of cellular cAMP levels was observed in H295R cells exposed to 8:2 FTOH. The observed responses are consistent with reduced cellular cAMP levels. Exposure to 8:2 FTOH resulted in significantly less basal (+ GTP) and isoproterenol-stimulated adenylate cyclase activities, but affected neither total cellular ATP level nor basal (-GTP) or NaF-stimulated adenylate cyclase activities, suggesting that inhibition of steroidogenesis may be due to an alteration in membrane properties. Metabolites of 8:2 FTOH were not detected by HPLC-MS/MS, suggesting that 8:2 FTOH was not metabolized by H295R cells. Overall, the results show that 8:2 FTOH may inhibit steroidogenesis by disrupting the cAMP signalling cascade.

  5. Signalling network in dental apoptosis: focused on caspase-3

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Sharpe, P. T.; Šetková, Jana; Míšek, Ivan; Tucker, A. S.

    Vancouver: Keystone Symposia, 2006. s. 45. [Signaling Networks 2006. 30.01.2006-04.02.2006, Vancouver] R&D Projects: GA AV ČR KJB500450503 Grant ostatní: Royal Society 2005/R1 Institutional research plan: CEZ:AV0Z50450515 Keywords : dental apoptosis Subject RIV: EA - Cell Biology

  6. Classification of Electroencephalograph (EEG Signals Using Quantum Neural Network

    Directory of Open Access Journals (Sweden)

    Ibtisam A. Aljazaery , Abduladhem Abdulkareem Ali, Hayder Mahdi Abdulridha

    2011-02-01

    Full Text Available In this paper, quantum neural network (QNN, which is a class of feedforwardneural networks (FFNN’s, is used to recognize (EEG signals. For thispurpose ,independent component analysis (ICA, wavelet transform (WT andFourier transform (FT are used as a feature extraction after normalization ofthese signals. The architecture of (QNN’s have inherently built in fuzzy. Thehidden units of these networks develop quantized representations of thesample information provided by the training data set in various graded levelsof certainty. Experimental results presented here show that (QNN’s arecapable of recognizing structures in data, a property that conventional(FFNN’s with sigmoidal hidden units lack . Finally, (QNN gave us kind of fastand realistic results compared with the (FFNN. Simulation results show that atotal classification of 81.33% for (ICA, 76.67% for (WT and 67.33% for (FT.

  7. Multiplexed Signal Distribution Using Fiber Network For Radar Applications

    Science.gov (United States)

    Meena, D.; Prakasam, L. G. M.; Pandey, D. C.; Shivaleela, E. S.; Srinivas, T.

    2011-10-01

    Most of the modern Active phased Array Radars consist of multiple receive modules in an Antenna array. This demands the distribution of various Local Oscillator Signals (LOs) for the down conversion of received signals to the Intermediate Frequency (IF) band signals. This is normally achieved through Radio Frequency (RF) cables with Complex distribution networks which adds additional weight to the Arrays. Similarly these kinds of receivers require Control/Clock signals which are digital in nature, for the synchronization of all receive modules of the radar system which are also distributed through electrical cables. In addition some of the control messages (Digital in nature) are distributed through Optical interfaces. During Transmit operation, the RF transmit Signal is also distributed through the same receiver modules which will in turn distribute to all the elements of the Array which require RF cables which are bulky in nature. So it is very essential to have a multiplexed Signal distribution scheme through the existing Optical Interface for distribution of these signals which are RF and Digital in nature. This paper discusses about various distribution schemes for the realization in detail. We propose a distribution network architecture where existing fibers can be further extended for the distribution of other types of signals also. In addition, it also briefs about a comparative analysis done on these schemes by considering the complexity and space constraint factors. Thus we bring out an optimum scheme which will lead to the reduction in both hardware complexity and weight of the array systems. In addition, being an Optical network it is free from Electromagnetic interference which is a crucial requirement in an array environment.

  8. Phosphoproteomics-based systems analysis of signal transduction networks

    Directory of Open Access Journals (Sweden)

    Hiroko eKozuka-Hata

    2012-01-01

    Full Text Available Signal transduction systems coordinate complex cellular information to regulate biological events such as cell proliferation and differentiation. Although the accumulating evidence on widespread association of signaling molecules has revealed essential contribution of phosphorylation-dependent interaction networks to cellular regulation, their dynamic behavior is mostly yet to be analyzed. Recent technological advances regarding mass spectrometry-based quantitative proteomics have enabled us to describe the comprehensive status of phosphorylated molecules in a time-resolved manner. Computational analyses based on the phosphoproteome dynamics accelerate generation of novel methodologies for mathematical analysis of cellular signaling. Phosphoproteomics-based numerical modeling can be used to evaluate regulatory network elements from a statistical point of view. Integration with transcriptome dynamics also uncovers regulatory hubs at the transcriptional level. These omics-based computational methodologies, which have firstly been applied to representative signaling systems such as the epidermal growth factor receptor pathway, have now opened up a gate for systems analysis of signaling networks involved in immune response and cancer.

  9. Reverse engineering GTPase programming languages with reconstituted signaling networks.

    Science.gov (United States)

    Coyle, Scott M

    2016-07-01

    The Ras superfamily GTPases represent one of the most prolific signaling currencies used in Eukaryotes. With these remarkable molecules, evolution has built GTPase networks that control diverse cellular processes such as growth, morphology, motility and trafficking. (1-4) Our knowledge of the individual players that underlie the function of these networks is deep; decades of biochemical and structural data has provided a mechanistic understanding of the molecules that turn GTPases ON and OFF, as well as how those GTPase states signal by controlling the assembly of downstream effectors. However, we know less about how these different activities work together as a system to specify complex dynamic signaling outcomes. Decoding this molecular "programming language" would help us understand how different species and cell types have used the same GTPase machinery in different ways to accomplish different tasks, and would also provide new insights as to how mutations to these networks can cause disease. We recently developed a bead-based microscopy assay to watch reconstituted H-Ras signaling systems at work under arbitrary configurations of regulators and effectors. (5) Here we highlight key observations and insights from this study and propose extensions to our method to further study this and other GTPase signaling systems. PMID:27128855

  10. Novel links in the plant TOR kinase signaling network.

    Science.gov (United States)

    Xiong, Yan; Sheen, Jen

    2015-12-01

    Nutrient and energy sensing and signaling mechanisms constitute the most ancient and fundamental regulatory networks to control growth and development in all life forms. The target of rapamycin (TOR) protein kinase is modulated by diverse nutrient, energy, hormone and stress inputs and plays a central role in regulating cell proliferation, growth, metabolism and stress responses from yeasts to plants and animals. Recent chemical, genetic, genomic and metabolomic analyses have enabled significant progress toward molecular understanding of the TOR signaling network in multicellular plants. This review discusses the applications of new chemical tools to probe plant TOR functions and highlights recent findings and predictions on TOR-mediate biological processes. Special focus is placed on novel and evolutionarily conserved TOR kinase effectors as positive and negative signaling regulators that control transcription, translation and metabolism to support cell proliferation, growth and maintenance from embryogenesis to senescence in the plant system. PMID:26476687

  11. Model calibration and uncertainty analysis in signaling networks.

    Science.gov (United States)

    Heinemann, Tim; Raue, Andreas

    2016-06-01

    For a long time the biggest challenges in modeling cellular signal transduction networks has been the inference of crucial pathway components and the qualitative description of their interactions. As a result of the emergence of powerful high-throughput experiments, it is now possible to measure data of high temporal and spatial resolution and to analyze signaling dynamics quantitatively. In addition, this increase of high-quality data is the basis for a better understanding of model limitations and their influence on the predictive power of models. We review established approaches in signal transduction network modeling with a focus on ordinary differential equation models as well as related developments in model calibration. As central aspects of the calibration process we discuss possibilities of model adaptation based on data-driven parameter optimization and the concomitant objective of reducing model uncertainties. PMID:27085224

  12. The statistical mechanics of complex signaling networks: nerve growth factor signaling

    Science.gov (United States)

    Brown, K. S.; Hill, C. C.; Calero, G. A.; Myers, C. R.; Lee, K. H.; Sethna, J. P.; Cerione, R. A.

    2004-10-01

    The inherent complexity of cellular signaling networks and their importance to a wide range of cellular functions necessitates the development of modeling methods that can be applied toward making predictions and highlighting the appropriate experiments to test our understanding of how these systems are designed and function. We use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. A key difficulty with signaling models is that, while significant effort is being made to experimentally measure the rate constants for individual steps in these networks, many of the parameters required to describe their behavior remain unknown or at best represent estimates. To establish the usefulness of our approach, we have applied our methods toward modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. In particular, we study the actions of NGF and mitogenic epidermal growth factor (EGF) in rat pheochromocytoma (PC12) cells. Through a network of intermediate signaling proteins, each of these growth factors stimulates extracellular regulated kinase (Erk) phosphorylation with distinct dynamical profiles. Using our modeling approach, we are able to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems that we call 'sloppiness.'

  13. Signalling network construction for modelling plant defence response.

    Directory of Open Access Journals (Sweden)

    Dragana Miljkovic

    Full Text Available Plant defence signalling response against various pathogens, including viruses, is a complex phenomenon. In resistant interaction a plant cell perceives the pathogen signal, transduces it within the cell and performs a reprogramming of the cell metabolism leading to the pathogen replication arrest. This work focuses on signalling pathways crucial for the plant defence response, i.e., the salicylic acid, jasmonic acid and ethylene signal transduction pathways, in the Arabidopsis thaliana model plant. The initial signalling network topology was constructed manually by defining the representation formalism, encoding the information from public databases and literature, and composing a pathway diagram. The manually constructed network structure consists of 175 components and 387 reactions. In order to complement the network topology with possibly missing relations, a new approach to automated information extraction from biological literature was developed. This approach, named Bio3graph, allows for automated extraction of biological relations from the literature, resulting in a set of (component1, reaction, component2 triplets and composing a graph structure which can be visualised, compared to the manually constructed topology and examined by the experts. Using a plant defence response vocabulary of components and reaction types, Bio3graph was applied to a set of 9,586 relevant full text articles, resulting in 137 newly detected reactions between the components. Finally, the manually constructed topology and the new reactions were merged to form a network structure consisting of 175 components and 524 reactions. The resulting pathway diagram of plant defence signalling represents a valuable source for further computational modelling and interpretation of omics data. The developed Bio3graph approach, implemented as an executable language processing and graph visualisation workflow, is publically available at http://ropot.ijs.si/bio3graph/and can be

  14. Signaling pathway networks mined from human pituitary adenoma proteomics data

    Directory of Open Access Journals (Sweden)

    Zhan Xianquan

    2010-04-01

    Full Text Available Abstract Background We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins, comparative proteomic data (56 differentially expressed proteins, and nitroproteomic data (17 nitroproteins. There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system. Methods The Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses. Results For the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a

  15. Unique Effects of Acute Aripiprazole Treatment on the Dopamine D2 Receptor Downstream cAMP-PKA and Akt-GSK3β Signalling Pathways in Rats

    Science.gov (United States)

    Pan, Bo; Chen, Jiezhong; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2015-01-01

    Aripiprazole is a wide-used antipsychotic drug with therapeutic effects on both positive and negative symptoms of schizophrenia, and reduced side-effects. Although aripiprazole was developed as a dopamine D2 receptor (D2R) partial agonist, all other D2R partial agonists that aimed to mimic aripiprazole failed to exert therapeutic effects in clinic. The present in vivo study aimed to investigate the effects of aripiprazole on the D2R downstream cAMP-PKA and Akt-GSK3β signalling pathways in comparison with a D2R antagonist – haloperidol and a D2R partial agonist – bifeprunox. Rats were injected once with aripiprazole (0.75mg/kg, i.p.), bifeprunox (0.8mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.) or vehicle. Five brain regions – the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), ventral tegmental area (VTA) and substantia nigra (SN) were collected. The protein levels of PKA, Akt and GSK3β were measured by Western Blotting; the cAMP levels were examined by ELISA tests. The results showed that aripiprazole presented similar acute effects on PKA expression to haloperidol, but not bifeprunox, in the CPU and VTA. Additionally, aripiprazole was able to increase the phosphorylation of GSK3β in the PFC, NAc, CPu and SN, respectively, which cannot be achieved by bifeprunox and haloperidol. These results suggested that acute treatment of aripiprazole had differential effects on the cAMP-PKA and Akt-GSK3β signalling pathways from haloperidol and bifeprunox in these brain areas. This study further indicated that, by comparison with bifeprunox, the unique pharmacological profile of aripiprazole may be attributed to the relatively lower intrinsic activity at D2R. PMID:26162083

  16. Early-warning signals of topological collapse in interbank networks

    CERN Document Server

    Squartini, Tiziano; Garlaschelli, Diego

    2013-01-01

    The financial crisis marked a paradigm shift, from traditional studies of individual risk to recent research on the "systemic risk" generated by whole networks of institutions. However, the reverse effects of realized defaults on network topology are poorly understood. Here we analyze the Dutch interbank network over the period 1998-2008, ending with the global crisis. We find that many topological properties, after controlling for overall density effects, display an abrupt change in 2008, thus providing a clear but unpredictable signature of the crisis. By contrast, if the intrinsic heterogeneity of banks is controlled for, the same properties undergo a slow and continuous transition, gradually connecting the crisis period to a much earlier stationary phase. This early-warning signal begins in 2005, and is preceded by an even earlier period of "risk autocatalysis" characterized by anomalous debt loops. These remarkable precursors are undetectable if the network is reconstructed from partial bank-specific inf...

  17. Classification of Epileptic EEG Signals using Time-Delay Neural Networks and Probabilistic Neural Networks

    Directory of Open Access Journals (Sweden)

    Ateke Goshvarpour

    2013-05-01

    Full Text Available The aim of this paper is to investigate the performance of time delay neural networks (TDNNs and the probabilistic neural networks (PNNs trained with nonlinear features (Lyapunov exponents and Entropy on electroencephalogram signals (EEG in a specific pathological state. For this purpose, two types of EEG signals (normal and partial epilepsy are analyzed. To evaluate the performance of the classifiers, mean square error (MSE and elapsed time of each classifier are examined. The results show that TDNN with 12 neurons in hidden layer result in a lower MSE with the training time of about 19.69 second. According to the results, when the sigma values are lower than 0.56, the best performance in the proposed probabilistic neural network structure is achieved. The results of present study show that applying the nonlinear features to train these networks can serve as useful tool in classifying of the EEG signals.

  18. Signal Processing in Periodically Forced Gradient Frequency Neural Networks

    Science.gov (United States)

    Kim, Ji Chul; Large, Edward W.

    2015-01-01

    Oscillatory instability at the Hopf bifurcation is a dynamical phenomenon that has been suggested to characterize active non-linear processes observed in the auditory system. Networks of oscillators poised near Hopf bifurcation points and tuned to tonotopically distributed frequencies have been used as models of auditory processing at various levels, but systematic investigation of the dynamical properties of such oscillatory networks is still lacking. Here we provide a dynamical systems analysis of a canonical model for gradient frequency neural networks driven by a periodic signal. We use linear stability analysis to identify various driven behaviors of canonical oscillators for all possible ranges of model and forcing parameters. The analysis shows that canonical oscillators exhibit qualitatively different sets of driven states and transitions for different regimes of model parameters. We classify the parameter regimes into four main categories based on their distinct signal processing capabilities. This analysis will lead to deeper understanding of the diverse behaviors of neural systems under periodic forcing and can inform the design of oscillatory network models of auditory signal processing. PMID:26733858

  19. 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.

  20. Image and signal processing for networked eHealth applications

    CERN Document Server

    Maglogiannis, Ilias

    2006-01-01

    E-health is closely related with networks and telecommunications when dealing with applications of collecting or transferring medical data from distant locations for performing remote medical collaborations and diagnosis. In this book we provide an overview of the fields of image and signal processing for networked and distributed e-health applications and their supporting technologies. The book is structured in 10 chapters, starting the discussion from the lower end, that of acquisition and processing of biosignals and medical images and ending in complex virtual reality systems and technique

  1. A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in β-globin disorders

    Directory of Open Access Journals (Sweden)

    Ikuta T

    2013-12-01

    Full Text Available Tohru Ikuta,1 Yuichi Kuroyanagi,1 Nadine Odo,1 Siyang Liu21Department of Anesthesiology and Perioperative Medicine, 2Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USABackground: Although erythroid cells prepared from fetal liver, cord blood, or blood from β-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and β-thalassemia.Methods: The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with β-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control.Results: We found that intracellular cAMP levels were higher in erythroid cells from cord blood and β-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or β-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or β-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the β-globin gene.Conclusion: These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to

  2. Distributed Signal Processing for Wireless EEG Sensor Networks.

    Science.gov (United States)

    Bertrand, Alexander

    2015-11-01

    Inspired by ongoing evolutions in the field of wireless body area networks (WBANs), this tutorial paper presents a conceptual and exploratory study of wireless electroencephalography (EEG) sensor networks (WESNs), with an emphasis on distributed signal processing aspects. A WESN is conceived as a modular neuromonitoring platform for high-density EEG recordings, in which each node is equipped with an electrode array, a signal processing unit, and facilities for wireless communication. We first address the advantages of such a modular approach, and we explain how distributed signal processing algorithms make WESNs more power-efficient, in particular by avoiding data centralization. We provide an overview of distributed signal processing algorithms that are potentially applicable in WESNs, and for illustration purposes, we also provide a more detailed case study of a distributed eye blink artifact removal algorithm. Finally, we study the power efficiency of these distributed algorithms in comparison to their centralized counterparts in which all the raw sensor signals are centralized in a near-end or far-end fusion center. PMID:25850092

  3. cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b in rats

    Directory of Open Access Journals (Sweden)

    Liu X

    2016-01-01

    accompanied by a significant increased GLT, decreased cAMP, PKAca, pCREB activities in hippocampus. However, repeated GEBR-7b administration significantly reversed CUS-induced depression-like behavior and changes of cAMP/PKA/CREB/GLT1 signaling. No alteration was observed in locomotor activity in open field test.Conclusion: These findings indicate that GEBR-7b reversed the depression-like behaviors induced by CUS in rats, which is at least in part mediated by modulating cAMP, PKAca, pCREB, and GLT1 levels in the hippocampus of rats, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by CUS. Keywords: phosphodiesterase 4D, GEBR-7b, cyclic adenosine monophosphate, protein kinase Aca, cAMP response element-binding protein, phosphorylation of CREB, glutamate transporter 1 

  4. Cancer signaling networks and their implications for personalized medicine

    DEFF Research Database (Denmark)

    Creixell, Pau

    of the articles that are part of this PhD thesis (part II). In part III, we illustrate with an article that has been submitted recently, how next-generation sequencing data and mass spectrometry data can be combined to uncover genome-specific signaling networks. In part IV, I describe the two computational......) based on the integration of these cues; this integration and consequently the cellular decisions taken by cancer cells are arguably very distinct from the decisions that would be expected from non-cancer cells. Since cellular signaling networks and its different states are the computational circuits......Amongst the unique features of cancer cells perhaps the most crucial one is the change in the cellular decision-making process. While both non-cancer and cancer cells are constantly integrating different external cues that reach them and computing cellular decisions (e.g. proliferation or apoptosis...

  5. Neural Network AE Source Location Based on Extracted Signal Features

    Czech Academy of Sciences Publication Activity Database

    Chlada, Milan; Blaháček, Michal; Převorovský, Zdeněk

    Brno : VUT Brno, 2005 - (Mazal, P.), s. 55-62 ISBN 80-214-2996-8. [NDT in Progress. Praha (CZ), 10.10.2005-12.10.2005] R&D Projects: GA ČR(CZ) GA201/04/2102; GA MPO FT-TA/026 Institutional research plan: CEZ:AV0Z20760514 Keywords : AE source location * neural network s * signal features Subject RIV: BI - Acoustics

  6. Neural Network Nonlinear Factor Analysis of High Dimensional Binary Signal

    Czech Academy of Sciences Publication Activity Database

    Húsek, Dušan; Řezanková, H.; Snášel, Václav; Frolov, A. A.; Polyakov, P.Y.

    IEEE, 2005 - (Chbeir, R.; Dipanda, A.; Vétongnon, K.), s. 86-89 ISBN 2-9525435-0. [IEEE SITIS 2005. International Conference on Signal & Image Technology and Internet Based Systems /1./. Yaoundé (CM), 27.11.2005-01.12.2005] R&D Projects: GA MŠk 1M0567; GA MŠk 1M0554 Keywords : neural networks * associative memory * Boolean factor analysis * text mining Subject RIV: BA - General Mathematics

  7. Feasibility of RFID signal denoising using neural network

    OpenAIRE

    Vojtěch, Lukáš

    2010-01-01

    Radio Frequency Identification signal denoising can be a perspective method for the future intelligent Radio Frequency Identification readers with high reading distances capability. This paper deals with the Group Method of Data Handling neural network denoising filter experiments. Capability of the probability learning of the Group Method of Data Handling filters is an effective instrument in more exacting applications in comparison with classical Finite Impulse Respo...

  8. Wireless sensor networks for monitoring physiological signals of multiple patients.

    Science.gov (United States)

    Dilmaghani, R S; Bobarshad, H; Ghavami, M; Choobkar, S; Wolfe, C

    2011-08-01

    This paper presents the design of a novel wireless sensor network structure to monitor patients with chronic diseases in their own homes through a remote monitoring system of physiological signals. Currently, most of the monitoring systems send patients' data to a hospital with the aid of personal computers (PC) located in the patients' home. Here, we present a new design which eliminates the need for a PC. The proposed remote monitoring system is a wireless sensor network with the nodes of the network installed in the patients' homes. These nodes are then connected to a central node located at a hospital through an Internet connection. The nodes of the proposed wireless sensor network are created by using a combination of ECG sensors, MSP430 microcontrollers, a CC2500 low-power wireless radio, and a network protocol called the SimpliciTI protocol. ECG signals are first sampled by a small portable device which each patient carries. The captured signals are then wirelessly transmitted to an access point located within the patients' home. This connectivity is based on wireless data transmission at 2.4-GHz frequency. The access point is also a small box attached to the Internet through a home asynchronous digital subscriber line router. Afterwards, the data are sent to the hospital via the Internet in real time for analysis and/or storage. The benefits of this remote monitoring are wide ranging: the patients can continue their normal lives, they do not need a PC all of the time, their risk of infection is reduced, costs significantly decrease for the hospital, and clinicians can check data in a short time. PMID:23851949

  9. Seismic signals detection and classification using artiricial neural networks

    Directory of Open Access Journals (Sweden)

    G. Romeo

    1994-06-01

    Full Text Available Pattern recognition belongs to a class of Problems which are easily solved by humans, but difficult for computers. It is sometimes difficult to formalize a problem which a human operator can casily understand by using examples. Neural networks are useful in solving this kind of problem. A neural network may, under certain conditions, simulate a well trained human operator in recognizing different types of earthquakes or in detecting the presence of a seismic event. It is then shown how a fully connected multi layer perceptron may perform a recognition task. It is shown how a self training auto associative neural network may detect an earthquake occurrence analysing the change in signal characteristics.

  10. Monitoring Breathing via Signal Strength in Wireless Networks

    CERN Document Server

    Patwari, Neal; R., Sai Ananthanarayanan P; Kasera, Sneha K; Westenskow, Dwayne

    2011-01-01

    This paper shows experimentally that standard wireless networks which measure received signal strength (RSS) can be used to reliably detect human breathing and estimate the breathing rate, an application we call "BreathTaking". We show that although an individual link cannot reliably detect breathing, the collective spectral content of a network of devices reliably indicates the presence and rate of breathing. We present a maximum likelihood estimator (MLE) of breathing rate, amplitude, and phase, which uses the RSS data from many links simultaneously. We show experimental results which demonstrate that reliable detection and frequency estimation is possible with 30 seconds of data, within 0.3 breaths per minute (bpm) RMS error. Use of directional antennas is shown to improve robustness to motion near the network.

  11. Modeling of cortical signals using echo state networks

    Science.gov (United States)

    Zhou, Hanying; Wang, Yongji; Huang, Jiangshuai

    2009-10-01

    Diverse modeling frameworks have been utilized with the ultimate goal of translating brain cortical signals into prediction of visible behavior. The inputs to these models are usually multidimensional neural recordings collected from relevant regions of a monkey's brain while the outputs are the associated behavior which is typically the 2-D or 3-D hand position of a primate. Here our task is to set up a proper model in order to figure out the move trajectories by input the neural signals which are simultaneously collected in the experiment. In this paper, we propose to use Echo State Networks (ESN) to map the neural firing activities into hand positions. ESN is a newly developed recurrent neural network(RNN) model. Besides its dynamic property and short term memory just as other recurrent neural networks have, it has a special echo state property which endows it with the ability to model nonlinear dynamic systems powerfully. What distinguished it from transitional recurrent neural networks most significantly is its special learning method. In this paper we train this net with a refined version of its typical training method and get a better model.

  12. Sweet Taste Receptor Signaling Network: Possible Implication for Cognitive Functioning

    Directory of Open Access Journals (Sweden)

    Menizibeya O. Welcome

    2015-01-01

    Full Text Available Sweet taste receptors are transmembrane protein network specialized in the transmission of information from special “sweet” molecules into the intracellular domain. These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism. Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization. Due to their pleiotropic signaling properties and multisubstrate ligand affinity, sweet taste receptors are able to cooperatively bind multiple substances and mediate signaling by other receptors. Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning.

  13. Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

    Science.gov (United States)

    Walia, Mannu K; Ho, Patricia MW; Taylor, Scott; Ng, Alvin JM; Gupte, Ankita; Chalk, Alistair M; Zannettino, Andrew CW; Martin, T John; Walkley, Carl R

    2016-01-01

    Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS. DOI: http://dx.doi.org/10.7554/eLife.13446.001 PMID:27070462

  14. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Directory of Open Access Journals (Sweden)

    Marcio Luis Acencio

    Full Text Available Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI. This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved

  15. NT2 derived neuronal and astrocytic network signalling.

    Directory of Open Access Journals (Sweden)

    Eric J Hill

    Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

  16. Analysis on Design of Kohonen-network System Based on Classification of Complex Signals

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The key methods of detection and classification of the electroencephalogram(EEG) used in recent years are introduced . Taking EEG for example, the design plan of Kohonen neural network system based on detection and classification of complex signals is proposed, and both the network design and signal processing are analyzed, including pre-processing of signals, extraction of signal features, classification of signal and network topology, etc.

  17. Dual Role of Signaling Pathways Leading to Ca2+ and Cyclic AMP Elevation in Host Cell Invasion by Trypanosoma cruzi

    OpenAIRE

    Caler, Elisabet V.; Morty, Rory E; Burleigh, Barbara A.; Andrews, Norma W.

    2000-01-01

    Cell invasion by the protozoan parasite Trypanosoma cruzi involves activation of host signaling pathways and the recruitment and fusion of lysosomes at the parasite entry site. A major signaling pathway regulating invasion of fibroblasts, epithelial cells, and myoblasts involves mobilization of Ca2+ from intracellular stores and requires the activity of a T. cruzi serine peptidase, oligopeptidase B (OPB). Deletion of the OPB gene results in a marked defect in trypomastigote virulence, consist...

  18. Identification of melanoma biomarkers based on network modules by integrating the human signaling network with microarrays

    Directory of Open Access Journals (Sweden)

    Chunyun Huang

    2014-01-01

    Full Text Available Background: Melanoma is a leading cause of cancer death. Thus, accurate prognostic biomarkers that will assist rational treatment planning need to be identified. Methods: Microarray analysis of melanoma and normal tissue samples was performed to identify differentially expressed modules (DEMs from the signaling network and ultimately detect molecular markers to support histological examination. Network motifs were extracted from the human signaling network. Then, significant expression-correlation differential modules were identified by comparing the network module expression-correlation differential scores under normal and disease conditions using the gene expression datasets. Finally, we obtained DEMs by the Wilcoxon rank test and considered the average gene expression level in these modules as the classification features for diagnosing melanoma. Results: In total, 99 functional DEMs were identified from the signaling network and gene expression profiles. The area under the curve scores for cancer module genes, melanoma module genes, and whole network modules are 92.4%, 90.44%, and 88.45%, respectively. The classification efficiency rates for nonmodule features are 71.04% and 79.38%, which correspond to the features of cancer genes and melanoma cancer genes, respectively. Finally, we acquired six significant molecular biomarkers, namely, module 10 (CALM3, Ca 2+ , PKC, PDGFRA, phospholipase-g, PIB5PA, and phosphatidylinositol-3-kinase, module 14 (SRC, Src homology 2 domain-containing [SHC], SAM68, GIT1, transcription factor-4, CBLB, GRB2, VAV2, LCK, YES, PTCH2, downstream of tyrosine kinase [DOK], and KIT, module 16 (ELK3, p85beta, SHC, ZFYVE9, TGFBR1, TGFBR2, CITED1, SH3KBP1, HCK, DOK, and KIT, module 45 (RB, CCND3, CCNA2, CDK4, and CDK6, module 75 (PCNA, CDK4, and CCND1, and module 114 (PSD93, NMDAR, and FYN. Conclusion: We explored the gene expression profile and signaling network in a global view and identified DEMs that can be used as

  19. The Ballistocardiogram Signal Monitoring System Based on the GSM Network

    Institute of Scientific and Technical Information of China (English)

    WANG Chun-wu; WANG Xu; LONG Zhe; ZHANG Ke-xin; YANG Dan

    2015-01-01

    Ballistocardiogram signal monitoring system based on GSM network was put forward in this paper. The system included a BCG signal acquisition module, a data processing module, a display module and a GSM module. The STM32F103VB microprocessor was used as the controlling core of the signal acquisition module. BCG signal acquisition, amplification, filtering and A/D conversion were completed by the resistance strain sensor and high precision A/D conversion chip of TM7708; VB6.0 software was used to realize the BCG signal analysis and processing;the SD card and LCD completed data storage and waveform display; the BCG data remote transmission and alarm function were realized through the GSM module. The system cannot only real-time monitor the changes of heart rate of patients by non-contact means, and can process data automatically, timely detection of arrhythmia and automatic alarm. The system is particularly suitable for heart disease patients receiving long-term home care;therefore, it has a broad application prospect.

  20. Microglia Control Neuronal Network Excitability via BDNF Signalling

    Directory of Open Access Journals (Sweden)

    Francesco Ferrini

    2013-01-01

    Full Text Available Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF released by microglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played by microglial BDNF in controlling neuronal excitability by causing disinhibition. The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF from microglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K+-Cl− cotransporter KCC2, dysrupting Cl−homeostasis, and hence the strength of GABAA- and glycine receptor-mediated inhibition. The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions.

  1. AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of β-catenin at Ser 552

    International Nuclear Information System (INIS)

    AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent studies show that AMPK involves in cell differentiation but the underlying mechanism remains undefined. Wingless Int-1 (Wnt)/β-catenin signaling pathway regulates the differentiation of mesenchymal stem cells through enhancing β-catenin/T-cell transcription factor 1 (TCF) mediated transcription. The objective of this study was to determine whether AMPK cross-talks with Wnt/β-catenin signaling through phosphorylation of β-catenin. C3H10T1/2 mesenchymal cells were used. Chemical inhibition of AMPK and the expression of a dominant negative AMPK decreased phosphorylation of β-catenin at Ser 552. The β-catenin/TCF mediated transcription was correlated with AMPK activity. In vitro, pure AMPK phosphorylated β-catenin at Ser 552 and the mutation of Ser 552 to Ala prevented such phosphorylation, which was further confirmed using [γ-32P]ATP autoradiography. In conclusion, AMPK phosphorylates β-catenin at Ser 552, which stabilizes β-catenin, enhances β-catenin/TCF mediated transcription, expanding AMPK from regulation of energy metabolism to cell differentiation and development via cross-talking with the Wnt/β-catenin signaling pathway.

  2. Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling.

    Directory of Open Access Journals (Sweden)

    Yan Shen

    Full Text Available We previously demonstrated that cinnamon extract (CE ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4 translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK.

  3. Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis

    Science.gov (United States)

    Wang, Hai; Zhao, Miaoyun; Sud, Neetu; Christian, Patricia; Shen, Jing; Song, Yongyan; Pashaj, Anjeza; Zhang, Kezhong; Carr, Timothy; Su, Qiaozhu

    2016-01-01

    Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia. PMID:27582413

  4. RECEIVED SIGNAL STRENGTH INDICATION MODELING IN INDOOR WIRELESS SENSOR NETWORKS

    Directory of Open Access Journals (Sweden)

    Edson Taira Procopio

    2013-01-01

    Full Text Available This study aims to identify mathematical models that represent the relation between Received Signal Strength Indication (RSSI and objects in an indoor Wireless Sensor Network (WSN. Using the Least Squares Method, four linear models have been identified: The first one relates uplink RSSI and objects; the second one relates downlink RSSI and objects; the third one relates uplink RSSI and obstacles and the fourth one relates downlink RSSI and obstacles. The obtained results, characterized by small residual values, attest the validation of all four models.

  5. 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.

  6. Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling

    DEFF Research Database (Denmark)

    Bailey, Michael J; Coon, Steven L; Carter, John David;

    2009-01-01

    The pineal gland plays an essential role in vertebrate chronobiology by converting time into a hormonal signal, melatonin, which is always elevated at night. Here we have analyzed the rodent pineal transcriptome using Affymetrix GeneChip(R) technology to obtain a more complete description of pineal...

  7. Prunetin signals via G-protein-coupled receptor, GPR30(GPER1): Stimulation of adenylyl cyclase and cAMP-mediated activation of MAPK signaling induces Runx2 expression in osteoblasts to promote bone regeneration.

    Science.gov (United States)

    Khan, Kainat; Pal, Subhashis; Yadav, Manisha; Maurya, Rakesh; Trivedi, Arun Kumar; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2015-12-01

    Prunetin is found in red clover and fruit of Prunus avium (red cherry). The effect of prunetin on osteoblast function, its mode of action and bone regeneration in vivo were investigated. Cultures of primary osteoblasts, osteoblastic cell line and HEK293T cells were used for various in vitro studies. Adult female rats received drill-hole injury at the femur diaphysis to assess the bone regenerative effect of prunetin. Prunetin at 10nM significantly (a) increased proliferation and differentiation of primary cultures of osteoblasts harvested from rats and (b) promoted formation of mineralized nodules by bone marrow stromal/osteoprogenitor cells. At this concentration, prunetin did not activate any of the two nuclear estrogen receptors (α and β). However, prunetin triggered signaling via a G-protein-coupled receptor, GPR30/GPER1, and enhanced cAMP levels in osteoblasts. G15, a selective GPR30 antagonist, abolished prunetin-induced increases in osteoblast proliferation, differentiation and intracellular cAMP. In osteoblasts, prunetin up-regulated runt-related transcription factor 2 (Runx2) protein through cAMP-dependent Erk/MAP kinase activation that ultimately resulted in the up-regulation of GPR30. Administration of prunetin at 0.25mg/kg given to rats stimulated bone regeneration at the site of drill hole and up-regulated Runx2 expression in the fractured callus and the effect was comparable to human parathyroid hormone, the only clinically used osteogenic therapy. We conclude that prunetin promotes osteoinduction in vivo and the mechanism is defined by signaling through GPR30 resulting in the up-regulation of the key osteogenic gene Runx2 that in turn up-regulates GPR30. PMID:26345541

  8. A modular analysis of the auxin signalling network.

    Directory of Open Access Journals (Sweden)

    Etienne Farcot

    Full Text Available Auxin is essential for plant development from embryogenesis onwards. Auxin acts in large part through regulation of transcription. The proteins acting in the signalling pathway regulating transcription downstream of auxin have been identified as well as the interactions between these proteins, thus identifying the topology of this network implicating 54 Auxin Response Factor (ARF and Aux/IAA (IAA transcriptional regulators. Here, we study the auxin signalling pathway by means of mathematical modeling at the single cell level. We proceed analytically, by considering the role played by five functional modules into which the auxin pathway can be decomposed: the sequestration of ARF by IAA, the transcriptional repression by IAA, the dimer formation amongst ARFs and IAAs, the feedback loop on IAA and the auxin induced degradation of IAA proteins. Focusing on these modules allows assessing their function within the dynamics of auxin signalling. One key outcome of this analysis is that there are both specific and overlapping functions between all the major modules of the signaling pathway. This suggests a combinatorial function of the modules in optimizing the speed and amplitude of auxin-induced transcription. Our work allows identifying potential functions for homo- and hetero-dimerization of transcriptional regulators, with ARF:IAA, IAA:IAA and ARF:ARF dimerization respectively controlling the amplitude, speed and sensitivity of the response and a synergistic effect of the interaction of IAA with transcriptional repressors on these characteristics of the signaling pathway. Finally, we also suggest experiments which might allow disentangling the structure of the auxin signaling pathway and analysing further its function in plants.

  9. Identification of EPAC (Exchange Protein Activated by cAMP) bioinformatically as a potential signalling biomarker in Cardiovascular Disease (CVD) and its molecular docking by a lead molecule.

    Science.gov (United States)

    Bala, Saranya; Pathak, Ravi Kant; Mishra, Vachaspati

    2011-01-01

    The present work delineates the combinatorial approach of firstly, creation of a centralized data-set comprising signalling proteins identified on the basis of altered expression, such as over-expression or repression of a set of signalling protein(s) leading to the cause of the disease, which is based on published reports screened through Pubmed and secondly, in the in silico creation of novel lead (drug) molecules and docking of identified signalling biomarkers using such drugs to investigate possibility of their future application in the model systems eventually. EPAC (Exchange Protein Activated by cAMP) emerges as a signalling biomarker in cases studied presently. Brefeldin, the known inhibitor of EPAC, though the mechanism yet unexplored, has been the molecule used as the pharmacophore for creation of lead drug molecule. Various modifications have been incorporated into the pharmacophore to increase the hydrophobic interactions for increasing the binding efficiency of the generated lead molecule. Side-chain modifications of the pharmacophore and refinement of data through firedock upon docking of EPAC with the modified pharmacophore yielded best results on the bases of atomic contact energy, van der Waal and partial electrostatic interactions as well as additional estimations of the binding free energy. Modifications of CH3 at C15 with COOH and H at C2 with OH in brefeldin showed the best docking results on the basis of protein-drug interaction parameters. The present work provides a clue in rational design of EPAC inhibitors which could be developed as drug lead in combating CVD. PMID:21738308

  10. Nesfatin-1 induces the phosphorylation levels of cAMP response element-binding protein for intracellular signaling in a neural cell line.

    Directory of Open Access Journals (Sweden)

    Emi Ishida

    Full Text Available Nesfatin-1 is a novel anorexic peptide that reduces the food intake of rodents when administered either intraventricularly or intraperitoneally. However, the molecular mechanism of intracellular signaling via Nesfatin-1 is yet to be resolved. In the current study, we investigated the ability of different neuronal cell lines to respond to Nesfatin-1 and further elucidated the signal transduction pathway of Nesfatin-1. To achieve this, we transfected several cell lines with various combinations of reporter vectors containing different kinds of response elements and performed reporter assays with Nesfatin-1, its active midsegment encoding 30 amino acid residues (M30 and M30-derived mutants. Notably, we found that both Nesfatin-1 as well as M30, significantly increased cAMP response element (CRE reporter activity in a mouse neuroblastoma cell line, NB41A3. An antagonist of Melanocortin 3/4 receptor, SHU9119, aborted the promoter activity, and a mutant M30, which exerts no anorexic effect in vivo did not induce the CRE reporter activity in NB41A3 cells. Western blotting analyses revealed that Nesfatin-1 and M30 significantly increased the phosphorylation levels of CRE-binding protein (CREB, without altering the intracellular cAMP levels. Further, our study showed that a mitogen-activated protein kinase (MAPK kinase inhibitor and an L-type Calcium (Ca(2+ channel blocker abolished the M30-induced CREB phosphorylation. Furthermore, the radio-receptor assay revealed that (125I-Nesfatin-1 binds in a saturable fashion to the membrane fractions of the mouse hypothalamus and NB41A3 cells, with Kd values of 0.79 nM and 0.17 nM, respectively. Collectively, our findings indicate the presence of a Nesfatin-1-specific receptor on the cell surface of NB41A3 cells and mouse hypothalamus. Our study highlights that Nesfatin-1, via its receptor, induces the phosphorylation of CREB, thus activating the intracellular signaling cascade in neurons.

  11. Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling.

    Science.gov (United States)

    Avanzato, D; Genova, T; Fiorio Pla, A; Bernardini, M; Bianco, S; Bussolati, B; Mancardi, D; Giraudo, E; Maione, F; Cassoni, P; Castellano, I; Munaron, L

    2016-01-01

    Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1-10 mm result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium. PMID:27586846

  12. L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Xiang-Zhu Xie

    2016-01-01

    Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

  13. Automated Measurement and Signaling Systems for the Transactional Network

    Energy Technology Data Exchange (ETDEWEB)

    Piette, Mary Ann; Brown, Richard; Price, Phillip; Page, Janie; Granderson, Jessica; Riess, David; Czarnecki, Stephen; Ghatikar, Girish; Lanzisera, Steven

    2013-12-31

    The Transactional Network Project is a multi-lab activity funded by the US Department of Energy?s Building Technologies Office. The project team included staff from Lawrence Berkeley National Laboratory, Pacific Northwest National Laboratory and Oak Ridge National Laboratory. The team designed, prototyped and tested a transactional network (TN) platform to support energy, operational and financial transactions between any networked entities (equipment, organizations, buildings, grid, etc.). PNNL was responsible for the development of the TN platform, with agents for this platform developed by each of the three labs. LBNL contributed applications to measure the whole-building electric load response to various changes in building operations, particularly energy efficiency improvements and demand response events. We also provide a demand response signaling agent and an agent for cost savings analysis. LBNL and PNNL demonstrated actual transactions between packaged rooftop units and the electric grid using the platform and selected agents. This document describes the agents and applications developed by the LBNL team, and associated tests of the applications.

  14. Pattern recognition for electroencephalographic signals based on continuous neural networks.

    Science.gov (United States)

    Alfaro-Ponce, M; Argüelles, A; Chairez, I

    2016-07-01

    This study reports the design and implementation of a pattern recognition algorithm to classify electroencephalographic (EEG) signals based on artificial neural networks (NN) described by ordinary differential equations (ODEs). The training method for this kind of continuous NN (CNN) was developed according to the Lyapunov theory stability analysis. A parallel structure with fixed weights was proposed to perform the classification stage. The pattern recognition efficiency was validated by two methods, a generalization-regularization and a k-fold cross validation (k=5). The classifier was applied on two different databases. The first one was made up by signals collected from patients suffering of epilepsy and it is divided in five different classes. The second database was made up by 90 single EEG trials, divided in three classes. Each class corresponds to a different visual evoked potential. The pattern recognition algorithm achieved a maximum correct classification percentage of 97.2% using the information of the entire database. This value was similar to some results previously reported when this database was used for testing pattern classification. However, these results were obtained when only two classes were considered for the testing. The result reported in this study used the whole set of signals (five different classes). In comparison with similar pattern recognition methods that even considered less number of classes, the proposed CNN proved to achieve the same or even better correct classification results. PMID:27131469

  15. Weak signal transmission in complex networks and its application in detecting connectivity.

    Science.gov (United States)

    Liang, Xiaoming; Liu, Zonghua; Li, Baowen

    2009-10-01

    We present a network model of coupled oscillators to study how a weak signal is transmitted in complex networks. Through both theoretical analysis and numerical simulations, we find that the response of other nodes to the weak signal decays exponentially with their topological distance to the signal source and the coupling strength between two neighboring nodes can be figured out by the responses. This finding can be conveniently used to detect the topology of unknown network, such as the degree distribution, clustering coefficient and community structure, etc., by repeatedly choosing different nodes as the signal source. Through four typical networks, i.e., the regular one dimensional, small world, random, and scale-free networks, we show that the features of network can be approximately given by investigating many fewer nodes than the network size, thus our approach to detect the topology of unknown network may be efficient in practical situations with large network size. PMID:19905385

  16. Computational study of noise in a large signal transduction network

    Directory of Open Access Journals (Sweden)

    Ruohonen Keijo

    2011-06-01

    Full Text Available Abstract Background Biochemical systems are inherently noisy due to the discrete reaction events that occur in a random manner. Although noise is often perceived as a disturbing factor, the system might actually benefit from it. In order to understand the role of noise better, its quality must be studied in a quantitative manner. Computational analysis and modeling play an essential role in this demanding endeavor. Results We implemented a large nonlinear signal transduction network combining protein kinase C, mitogen-activated protein kinase, phospholipase A2, and β isoform of phospholipase C networks. We simulated the network in 300 different cellular volumes using the exact Gillespie stochastic simulation algorithm and analyzed the results in both the time and frequency domain. In order to perform simulations in a reasonable time, we used modern parallel computing techniques. The analysis revealed that time and frequency domain characteristics depend on the system volume. The simulation results also indicated that there are several kinds of noise processes in the network, all of them representing different kinds of low-frequency fluctuations. In the simulations, the power of noise decreased on all frequencies when the system volume was increased. Conclusions We concluded that basic frequency domain techniques can be applied to the analysis of simulation results produced by the Gillespie stochastic simulation algorithm. This approach is suited not only to the study of fluctuations but also to the study of pure noise processes. Noise seems to have an important role in biochemical systems and its properties can be numerically studied by simulating the reacting system in different cellular volumes. Parallel computing techniques make it possible to run massive simulations in hundreds of volumes and, as a result, accurate statistics can be obtained from computational studies.

  17. Seismic Signal Classification with Offshore/Amphibious Networks Using an Artificial Neural Network

    Science.gov (United States)

    Williams, M. C.; Trehu, A. M.

    2011-12-01

    The amphibious Central Oregon Locked Zone Array (COLZA) of seismic stations was deployed from 2007-2009 to record earthquakes occurring in the seismogenic zone offshore central Oregon. This array included two year-long deployments of ocean bottom seismometers (OBS's) from the NSF OBSIP. In addition to local and distant earthquakes, the OBS array recorded thousands of impulsive local signals, which are not easily filtered out by a standard STA/LTA detection algorithm. Many of these signals are likely of biological origin (informally referred to as "bio-bumps"). These signals have a wide range of amplitudes, can mask local earthquake phase arrivals, and make automatic detection more difficult. We show that signal characteristics derived from 3-component seismic data at each station can be used to filter out event detections that are unlikely to be earthquake-generated. A decision-making algorithm is run using a joint set of signal characteristics to identify possible local events and classify detections that are likely to be "bumps". We present results on the effectiveness of this classification technique using various combinations of input parameters applied to the onshore/offshore COLZA array dataset. The classification algorithm is a multilayer perceptron (MLP) artificial neural network, trained through backpropagation using human-identified examples of both earthquake phases and impulsive "bumps". The effectiveness of a neural network is highly dependent on the data space consisting of the inputs calculated for each signal, which represent its main characteristics and differentiate it from other events. As inputs to the neural network, for each event detection, in addition to the STA/LTA value, we determine three signal characteristics from 3-component waveform data: the variance of the power cepstrum calculated from a portion of the signal spectrum, the rectilinearity of particle motion, and the ratio of particle motion orthogonal to the principle direction of

  18. Traffic Signal Synchronization in the Saturated High-Density Grid Road Network

    OpenAIRE

    Xiaojian Hu; Jian Lu; Wei Wang,; Ye Zhirui

    2015-01-01

    Most existing traffic signal synchronization strategies do not perform well in the saturated high-density grid road network (HGRN). Traffic congestion often occurs in the saturated HGRN, and the mobility of the network is difficult to restore. In order to alleviate traffic congestion and to improve traffic efficiency in the network, the study proposes a regional traffic signal synchronization strategy, named the long green and long red (LGLR) traffic signal synchronization strategy. The essen...

  19. Signal detection, modularity and the correlation between extrinsic and intrinsic noise in biochemical networks

    OpenAIRE

    Tanase-Nicola, Sorin; Warren, Patrick B.; Wolde, Pieter Rein ten

    2005-01-01

    Understanding cell function requires an accurate description of how noise is transmitted through biochemical networks. We present an analytical result for the power spectrum of the output signal of a biochemical network that takes into account the correlations between the noise in the input signal (the extrinsic noise) and the noise in the reactions that constitute the network (the intrinsic noise). These correlations arise from the fact that the reactions by which biochemical signals are det...

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

    Directory of Open Access Journals (Sweden)

    Shi Zhiqiang

    2003-01-01

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

  1. An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence

    Science.gov (United States)

    Huynh, TuAnh Ngoc; Luo, Shukun; Pensinger, Daniel; Sauer, John-Demian; Tong, Liang; Woodward, Joshua J.

    2015-01-01

    The nucleotide cyclic di-3′,5′- adenosine monophosphate (c-di-AMP) was recently identified as an essential and widespread second messenger in bacterial signaling. Among c-di-AMP–producing bacteria, altered nucleotide levels result in several physiological defects and attenuated virulence. Thus, a detailed molecular understanding of c-di-AMP metabolism is of both fundamental and practical interest. Currently, c-di-AMP degradation is recognized solely among DHH-DHHA1 domain-containing phosphodiesterases. Using chemical proteomics, we identified the Listeria monocytogenes protein PgpH as a molecular target of c-di-AMP. Biochemical and structural studies revealed that the PgpH His-Asp (HD) domain bound c-di-AMP with high affinity and specifically hydrolyzed this nucleotide to 5′-pApA. PgpH hydrolysis activity was inhibited by ppGpp, indicating a cross-talk between c-di-AMP signaling and the stringent response. Genetic analyses supported coordinated regulation of c-di-AMP levels in and out of the host. Intriguingly, a L. monocytogenes mutant that lacks c-di-AMP phosphodiesterases exhibited elevated c-di-AMP levels, hyperinduced a host type-I IFN response, and was significantly attenuated for infection. Furthermore, PgpH homologs, which belong to the 7TMR-HD family, are widespread among hundreds of c-di-AMP synthesizing microorganisms. Thus, PgpH represents a broadly conserved class of c-di-AMP phosphodiesterase with possibly other physiological functions in this crucial signaling network. PMID:25583510

  2. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  3. Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

    Science.gov (United States)

    Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

    2015-01-01

    Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways. PMID:25836921

  4. Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows.

    Science.gov (United States)

    Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

    2015-06-01

    Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (Pbiomarkers to supplement the THI and evaluate moderate heat stress in dairy cows in the future. PMID:26055916

  5. β-Hydroxybutyric Sodium Salt Inhibition of Growth Hormone and Prolactin Secretion via the cAMP/PKA/CREB and AMPK Signaling Pathways in Dairy Cow Anterior Pituitary Cells

    OpenAIRE

    Shou-Peng Fu; Wei Wang(College of William and Mary); Bing-Run Liu; Huan-Min Yang; Hong Ji; Zhan-Qing Yang; Bin Guo; Ju-Xiong Liu; Jian-Fa Wang

    2015-01-01

    β-hydroxybutyric acid (BHBA) regulates the synthesis and secretion of growth hormone (GH) and prolactin (PRL), but its mechanism is unknown. In this study, we detected the effects of BHBA on the activities of G protein signaling pathways, AMPK-α activity, GH, and PRL gene transcription, and GH and PRL secretion in dairy cow anterior pituitary cells (DCAPCs). The results showed that BHBA decreased intracellular cAMP levels and a subsequent reduction in protein kinase A (PKA) activity. Inhibit...

  6. A fuzzy neural network combining wavelet denoising and PCA for sensor signal estimation

    International Nuclear Information System (INIS)

    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

  7. Research on Characteristics of RC Polyphase Network for Quadrature Signal Generator

    Directory of Open Access Journals (Sweden)

    Hu Yi-ming

    2013-12-01

    Full Text Available The quadrature signal generator is widely used in devices such as the quadrature modulator and image rejection frequency converter. An RC polyphase network is commonly used as a quadrature signal generator because of its simple structure and perfect linear performance. This study derives explicit transfer functions for the RC polyphase network based on the complex signal properties and the matrix theory. Moreover, build-related parameters are determined to analyze the I/Q amplitude and phase balance characteristic of the RC polyphase network, thus providing a theoretical guideline for the design of a high-balance quadrature signal generator.

  8. Spatiotemporal Properties of Intracellular Calcium Signaling in Osteocytic and Osteoblastic Cell Networks under Fluid Flow

    OpenAIRE

    Jing, Da; Lu, X. Lucas; Luo, Erping; Sajda, Paul; Leong, Pui L.; Guo, X. Edward

    2013-01-01

    Mechanical stimuli can trigger intracellular calcium (Ca2+) responses in osteocytes and osteoblasts. Successful construction of bone cell networks necessitates more elaborate and systematic analysis for the spatiotemporal properties of Ca2+ signaling in the networks. In the present study, an unsupervised algorithm based on independent component analysis (ICA) was employed to extract the Ca2+ signals of bone cells in the network. We demonstrated that the ICA-based technology could yield higher...

  9. Research on Characteristics of RC Polyphase Network for Quadrature Signal Generator

    OpenAIRE

    Hu Yi-ming; Yu Guo-wen; Zhang Yuan-fa

    2013-01-01

    The quadrature signal generator is widely used in devices such as the quadrature modulator and image rejection frequency converter. An RC polyphase network is commonly used as a quadrature signal generator because of its simple structure and perfect linear performance. This study derives explicit transfer functions for the RC polyphase network based on the complex signal properties and the matrix theory. Moreover, build-related parameters are determined to analyze the I/Q amplitude and phase ...

  10. The alterations in biochemical signaling of hippocampal network activity in the autism brain The alterations in biochemical signaling of hippocampal network activity in the autism brain The alterations in biochemical signaling of hippocampal network activity in the autism brain

    Institute of Scientific and Technical Information of China (English)

    田允; 黄继云; 王锐; 陶蓉蓉; 卢应梅; 廖美华; 陆楠楠; 李静; 芦博; 韩峰

    2012-01-01

    Autism is a highly heritable neurodevelopmental condition characterized by impaired social interaction and communication. However, the role of synaptic dysfunction during development of autism remains unclear. In the present study, we address the alterations of biochemical signaling in hippocampal network following induction of the autism in experimental animals. Here, the an- imal disease model and DNA array being used to investigate the differences in transcriptome or- ganization between autistic and normal brain by gene co--expression network analysis.

  11. Genetic and logic networks with the signal-inhibitor-activator structure are dynamically robust

    Institute of Scientific and Technical Information of China (English)

    LI Fangting; TAN Ning

    2006-01-01

    The proteins, DNA and RNA interaction networks govern various biological functions in living cells, these networks should be dynamically robust in the intracellular and environmental fluctuations. Here, we use Boolean network to study the robust structure of both genetic and logic networks. First, SOS network in bacteria E. coli, which regulates cell survival and repair after DNA damage, is shown to be dynamically robust. Comparing with cell cycle network in budding yeast and flagella network in E. coli, we find the signal-inhibitor-activator (SIA) structure in transcription regulatory networks. Second, under the dynamical rule that inhibition is much stronger than activation, we have searched 3-node non-self-loop logical networks that are dynamically robust, and that if the attractive basin of a final attractor is as large as seven, and the final attractor has only one active node, then the active node acts as inhibitor, and the SIA and signal-inhibitor (SI) structures are fundamental architectures of robust networks. SIA and SI networks with dynamic robustness against environment uncertainties may be selected and maintained over the course of evolution, rather than blind trial-error testing and be ing an accidental consequence of particular evolutionary history. SIA network can perform a more complex process than SI network, andSIA might be used to design robust artificial genetic network. Our results provide dynamical support for why the inhibitors and SIA/SI structures are frequently employed in cellular regulatory networks.

  12. In vivo selective binding of (R)-[11C]rolipram to phosphodiesterase-4 provides the basis for studying intracellular cAMP signaling in the myocardium and other peripheral tissues

    International Nuclear Information System (INIS)

    Introduction: Phosphodiesterase-4 (PDE4) enzymes specifically break down the second messenger cAMP, thereby terminating the intracellular signaling cascade that plays an essential role in neurohormonal modulation of many physiological systems. PDE4 activity and expression are regulated by cAMP levels, suggesting that measurement of PDE4 provides an index of intracellular cAMP signaling. Methods: Male Sprague-Dawley rats were administered (R)- or the less active enantiomer (S)-[11C]rolipram and sacrificed 30 min later with tracer retention measured in various tissues. Co-injections with saturating doses of unlabeled (R)-rolipram (S)-rolipram and Ro 20-1724, as well as subtype-selective PDE inhibitors vinpocetine, Bay 60-7550, cilostazol and zaprinast were used to establish binding selectivity for PDE4 over PDE1, PDE2, PDE3 and PDE5 subtypes, respectively. Autoradiography was performed to substantiate results of biodistribution studies in the myocardium. Results: In vivo (R)-[11C]rolipram retention was dose-dependently reduced by co-injections of (R)-rolipram and (S)-rolipram (ED50 values of 0.03 mg/kg and 0.2 mg/kg, respectively). Vinpocetine, Bay 60-7550, cilostazol and zaprinast had no effect on (R)-[11C]rolipram binding, while (R)-rolipram and Ro 20-1724 reduced the tracer uptake to nonspecific levels in PDE4-rich tissues. Conclusions: In addition to the brain (R)-[11C]rolipram binds selectively to PDE4 across all cardiac regions, skeletal muscle, lungs and pancreas, but not in the adipose tissues. In vivo findings were confirmed by in vitro autoradiography studies, suggesting that (R)-[11C]rolipram can be applied to evaluate alterations in central and peripheral PDE4 levels and cAMP-mediated signaling

  13. In vivo selective binding of (R)-[{sup 11}C]rolipram to phosphodiesterase-4 provides the basis for studying intracellular cAMP signaling in the myocardium and other peripheral tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kenk, Miran [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Greene, Michael [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Thackeray, James [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Kemp, Robert A. de [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Lortie, Mireille [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Thorn, Stephanie [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); Beanlands, Rob S. [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada); DaSilva, Jean N. [Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y 4W7 (Canada) and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 (Canada)]. E-mail: jdasilva@ottawaheart.ca

    2007-01-15

    Introduction: Phosphodiesterase-4 (PDE4) enzymes specifically break down the second messenger cAMP, thereby terminating the intracellular signaling cascade that plays an essential role in neurohormonal modulation of many physiological systems. PDE4 activity and expression are regulated by cAMP levels, suggesting that measurement of PDE4 provides an index of intracellular cAMP signaling. Methods: Male Sprague-Dawley rats were administered (R)- or the less active enantiomer (S)-[{sup 11}C]rolipram and sacrificed 30 min later with tracer retention measured in various tissues. Co-injections with saturating doses of unlabeled (R)-rolipram (S)-rolipram and Ro 20-1724, as well as subtype-selective PDE inhibitors vinpocetine, Bay 60-7550, cilostazol and zaprinast were used to establish binding selectivity for PDE4 over PDE1, PDE2, PDE3 and PDE5 subtypes, respectively. Autoradiography was performed to substantiate results of biodistribution studies in the myocardium. Results: In vivo (R)-[{sup 11}C]rolipram retention was dose-dependently reduced by co-injections of (R)-rolipram and (S)-rolipram (ED{sub 50} values of 0.03 mg/kg and 0.2 mg/kg, respectively). Vinpocetine, Bay 60-7550, cilostazol and zaprinast had no effect on (R)-[{sup 11}C]rolipram binding, while (R)-rolipram and Ro 20-1724 reduced the tracer uptake to nonspecific levels in PDE4-rich tissues. Conclusions: In addition to the brain (R)-[{sup 11}C]rolipram binds selectively to PDE4 across all cardiac regions, skeletal muscle, lungs and pancreas, but not in the adipose tissues. In vivo findings were confirmed by in vitro autoradiography studies, suggesting that (R)-[{sup 11}C]rolipram can be applied to evaluate alterations in central and peripheral PDE4 levels and cAMP-mediated signaling.

  14. Stochastic effects as a force to increase the complexity of signaling networks

    KAUST Repository

    Kuwahara, Hiroyuki

    2013-07-29

    Cellular signaling networks are complex and appear to include many nonfunctional elements. Recently, it was suggested that nonfunctional interactions of proteins cause signaling noise, which, perhaps, shapes the signal transduction mechanism. However, the conditions under which molecular noise influences cellular information processing remain unclear. Here, we explore a large number of simple biological models of varying network sizes to understand the architectural conditions under which the interactions of signaling proteins can exhibit specific stochastic effects - called deviant effects - in which the average behavior of a biological system is substantially altered in the presence of molecular noise. We find that a small fraction of these networks does exhibit deviant effects and shares a common architectural feature whereas most of the networks show only insignificant levels of deviations. Interestingly, addition of seemingly unimportant interactions into protein networks gives rise to deviant effects.

  15. Detection of Emergency Signal in Hearing Aids using Neural Networks

    OpenAIRE

    Lakum, Vamshi Krishna; Gubbala, Arshini

    2014-01-01

    ABSTRACT The detection of an emergency signal can be estimated by the cancellation of surrounding noise and achieving the desired signal in order to alert the automobilist. The aim of the thesis is to detect the emergency signal arriving nearer to the automobilist carrying hearing aids. Recent studies show that this can be achieved by designing various kinds of fixed and adaptive beam formers. A beam former does spatial filtering in the sense that it separates two signals with overlapping fre...

  16. Proteomics, pathway array and signaling network-based medicine in cancer

    Directory of Open Access Journals (Sweden)

    Xu Hong

    2009-10-01

    Full Text Available Abstract Cancer is a multifaceted disease that results from dysregulated normal cellular signaling networks caused by genetic, genomic and epigenetic alterations at cell or tissue levels. Uncovering the underlying protein signaling network changes, including cell cycle gene networks in cancer, aids in understanding the molecular mechanism of carcinogenesis and identifies the characteristic signaling network signatures unique for different cancers and specific cancer subtypes. The identified signatures can be used for cancer diagnosis, prognosis, and personalized treatment. During the past several decades, the available technology to study signaling networks has significantly evolved to include such platforms as genomic microarray (expression array, SNP array, CGH array, etc. and proteomic analysis, which globally assesses genetic, epigenetic, and proteomic alterations in cancer. In this review, we compared Pathway Array analysis with other proteomic approaches in analyzing protein network involved in cancer and its utility serving as cancer biomarkers in diagnosis, prognosis and therapeutic target identification. With the advent of bioinformatics, constructing high complexity signaling networks is possible. As the use of signaling network-based cancer diagnosis, prognosis and treatment is anticipated in the near future, medical and scientific communities should be prepared to apply these techniques to further enhance personalized medicine.

  17. Energy Efficiency of Distributed Signal Processing in Wireless Networks: A Cross-Layer Analysis

    Science.gov (United States)

    Geraci, Giovanni; Wildemeersch, Matthias; Quek, Tony Q. S.

    2016-02-01

    In order to meet the growing mobile data demand, future wireless networks will be equipped with a multitude of access points (APs). Besides the important implications for the energy consumption, the trend towards densification requires the development of decentralized and sustainable radio resource management techniques. It is critically important to understand how the distribution of signal processing operations affects the energy efficiency of wireless networks. In this paper, we provide a cross-layer framework to evaluate and compare the energy efficiency of wireless networks under different levels of distribution of the signal processing load: (i) hybrid, where the signal processing operations are shared between nodes and APs, (ii) centralized, where signal processing is entirely implemented at the APs, and (iii) fully distributed, where all operations are performed by the nodes. We find that in practical wireless networks, hybrid signal processing exhibits a significant energy efficiency gain over both centralized and fully distributed approaches.

  18. Impulse-Induced Optimum Signal Amplification in Scale-Free Networks

    CERN Document Server

    Martínez, Pedro J

    2015-01-01

    Optimizing information transmission across a network is an essential task for controlling and manipulating generic information-processing systems. Here, we show how topological amplification effects in scale-free networks of signaling devices are optimally enhanced when the $\\it{impulse}$ transmitted by periodic external signals (time integral over two consecutive zeros) is maximum. This is demonstrated theoretically by means of a star-like network of overdamped bistable systems subjected to $\\it{generic}$ zero-mean periodic signals, and confirmed numerically by simulations of scale-free networks of such systems. Our results show that the enhancer effect of increasing values of the signal's impulse is due to a correlative increase of the energy transmitted by the periodic signals, while it is found to be resonant-like with respect to the topology-induced amplification mechanism.

  19. The translation start signal region of TEM beta-lactamase mRNA is responsible for heat shock-induced repression of amp gene expression in Escherichia coli.

    OpenAIRE

    Kuriki, Y

    1989-01-01

    pBR322 contains the amp gene encoding beta-lactamase. When Escherichia coli carrying this plasmid is exposed to heat shock, beta-lactamase synthesis is repressed transiently at the translational level. To identify the DNA element responsible for this translational repression, DNA segments containing the translation start region of the amp gene were excised from pAT153 and fused in frame with the lacZ reading frame in the open reading frame vector pORF1. These constructs were introduced into E...

  20. Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

    OpenAIRE

    Nakagawa, Yuko; Nagasawa, Masahiro; Yamada, Satoko; Hara, Akemi; Mogami, Hideo; Nikolaev, Viacheslav O.; Lohse, Martin J.; Shigemura, Noriatsu; Ninomiya, Yuzo; Kojima, Itaru

    2009-01-01

    Background Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. Methodology/Principal Findings The expression of the sweet taste receptor was determined by RT–PCR and immunohistochemistry. Changes in cytoplasmic Ca2+ ([Ca2+]c) and cAMP ([cAMP]c) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was mo...

  1. 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.

  2. Digital Signal Processing and Control for the Study of Gene Networks

    Science.gov (United States)

    Shin, Yong-Jun

    2016-01-01

    Thanks to the digital revolution, digital signal processing and control has been widely used in many areas of science and engineering today. It provides practical and powerful tools to model, simulate, analyze, design, measure, and control complex and dynamic systems such as robots and aircrafts. Gene networks are also complex dynamic systems which can be studied via digital signal processing and control. Unlike conventional computational methods, this approach is capable of not only modeling but also controlling gene networks since the experimental environment is mostly digital today. The overall aim of this article is to introduce digital signal processing and control as a useful tool for the study of gene networks. PMID:27102828

  3. Digital Signal Processing and Control for the Study of Gene Networks.

    Science.gov (United States)

    Shin, Yong-Jun

    2016-01-01

    Thanks to the digital revolution, digital signal processing and control has been widely used in many areas of science and engineering today. It provides practical and powerful tools to model, simulate, analyze, design, measure, and control complex and dynamic systems such as robots and aircrafts. Gene networks are also complex dynamic systems which can be studied via digital signal processing and control. Unlike conventional computational methods, this approach is capable of not only modeling but also controlling gene networks since the experimental environment is mostly digital today. The overall aim of this article is to introduce digital signal processing and control as a useful tool for the study of gene networks. PMID:27102828

  4. Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats.

    Science.gov (United States)

    Stojkov, N J; Janjic, M M; Kostic, T S; Andric, S A

    2013-03-01

    Doxazosin (Doxa) is an α1-selective adrenergic receptor (ADR) antagonist widely used, alone or in combination, to treat high blood pressure, benign prostatic hyperplasia symptoms, and recently has been suggested as a potential drug for prostate cancer prevention/treatment. This study was designed to evaluate the effect of in vivo Doxa po-application, in clinically relevant dose, on: (i) steroidogenic machinery homeostasis; (ii) cAMP/cGMP signalling; (iii) transcription profile of ADR in Leydig cells of adult rats. The results showed that po-application of Doxa for once (1×Doxa), or for two (2×Doxa) or 10 (10×Doxa) consecutive days significantly disturbed steroidogenic machinery homeostasis in Leydig cells. Doxa po-application significantly decreased circulating luteinizing hormone and androgens levels. The level of androgens in testicular interstitial fluid and that extracted from testes obtained from 1×Doxa/2×Doxa rats decreased, although it remained unchanged in 10×Doxa rats. Similarly, the ex vivo basal androgen production followed in testes isolated from 1×Doxa/2×Doxa rats decreased, while remained unchanged in 10×Doxa rats. Differently, ex vivo testosterone production and steroidogenic capacity of Leydig cells isolated from 1×Doxa/2×Doxa rats was stimulated, while 10×Doxa had opposite effect. In the same cells, cAMP content/release showed similar stimulatory effect, but back to control level in Leydig cells of 10×Doxa. 1×Doxa/2×Doxa decreased transcripts for cAMP specific phosphodiesterases Pde7b/Pde8b, whereas 10×Doxa increased Pde4d. All types of treatment reduced the expression of genes encoding protein kinase A (PRKA) regulatory subunit (Prkar2b), whereas only 10×Doxa stimulated catalytic subunit (Prkaca). Doxa application more affected cGMP signalling: stimulated transcription of constitutive nitric oxide synthases (Nos1, Nos3) in time-dependent manner, whereas reduced inducible Nos2. 10×Doxa increased guanylyl cyclase 1 transcript and

  5. ECG Signals Classification Based on Wavelet Transform and Probabilistic Neural Networks

    OpenAIRE

    Iman Moazen; Mohamadreza Ahmadzadeh

    2009-01-01

    In this paper a very intelligent tool with low computational complexity is presented for Electroencephalogram (ECG) signal classification. The proposed classifier is based on Discrete Wavelet Transform (DWT) and Probabilistic Neural Network (PNN). The novelty of this approach is that signal statistics, morphological analysis and DWT of the histogram of signal (density estimation) altogether have been used to achieve a higher recognition rate. ECG signals and their density estimation are decom...

  6. Elimination of spiral waves and spatiotemporal chaos by the synchronization transmission technology of network signals

    Institute of Scientific and Technical Information of China (English)

    Zhang Qing-Ling; Lu Ling; Zhang Yi

    2011-01-01

    A method to eliminate spiral waves and spatiotemporal chaos by using the synchronization transmission technology of network signals is proposed in this paper. The character of the spiral waves and the spatiotemporal chaos in the Fitzhugh-Nagumo model is presented. The network error evolution equation with spatiotemporal variables and the corresponding eigenvalue equation are determined based on the stability theory,and the global synchronization condition is obtained. Simulations are made in a complex network with Fitzhugh-Nagumo models as the nodes to verify the effectiveness of the synchronization transmission principle of the network signal.

  7. Elimination of spiral waves and spatiotemporal chaos by the synchronization transmission technology of network signals

    International Nuclear Information System (INIS)

    A method to eliminate spiral waves and spatiotemporal chaos by using the synchronization transmission technology of network signals is proposed in this paper. The character of the spiral waves and the spatiotemporal chaos in the Fitzhugh—Nagumo model is presented. The network error evolution equation with spatiotemporal variables and the corresponding eigenvalue equation are determined based on the stability theory, and the global synchronization condition is obtained. Simulations are made in a complex network with Fitzhugh—Nagumo models as the nodes to verify the effectiveness of the synchronization transmission principle of the network signal. (general)

  8. The Steroid Hormone 20-Hydroxyecdysone Enhances Gene Transcription through the cAMP Response Element-binding Protein (CREB) Signaling Pathway.

    Science.gov (United States)

    Jing, Yu-Pu; Wang, Di; Han, Xiao-Lin; Dong, Du-Juan; Wang, Jin-Xing; Zhao, Xiao-Fan

    2016-06-10

    Animal steroid hormones regulate gene transcription through genomic pathways by binding to nuclear receptors. These steroid hormones also rapidly increase intracellular calcium and cyclic adenosine monophosphate (cAMP) levels and activate the protein kinase C (PKC) and protein kinase A (PKA) nongenomic pathways. However, the function and mechanism of the nongenomic pathways of the steroid hormones are unclear, and the relationship between the PKC and PKA pathways is also unclear. We propose that the steroid hormone 20-hydroxyecdysone (20E) activates the PKA pathway to enhance 20E-induced gene transcription in the lepidopteran insect Helicoverpa armigera The expression of the catalytic subunit 1 of PKA (PKAC1) increased during metamorphosis, and PKAC1 knockdown blocked pupation and repressed 20E-responsive gene expression. 20E regulated PKAC1 phosphorylation at threonine 200 and nuclear translocation through an ecdysone-responsive G-protein-coupled receptor 2. PKAC1 induced cAMP response element-binding protein (CREB) phosphorylation at serine 143, which bound to the cAMP response element on DNA to enhance 20E-responsive gene transcription. Through ecdysone-responsive G-protein-coupled receptor 2, 20E increased cAMP levels, which induced CREB PKA phosphorylation and 20E-responsive gene expression. This study demonstrates that the PKA/CREB pathway tightly and critically regulates 20E-induced gene transcription as well as its relationship with the 20E-induced PKC pathway. PMID:27129227

  9. The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP

    DEFF Research Database (Denmark)

    Almblad, Henrik; Harrison, Joe J; Rybtke, Morten;

    2015-01-01

    a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (c...

  10. Speech Subvocal Signal Processing using Packet Wavelet and Neuronal Network

    OpenAIRE

    Luis E. Mendoza; Jesus Peña; Luis A. Muñoz-Bedoya; Hernando J. Velandia-Villamizar

    2013-01-01

    This paper presents the results obtained from the recording, processing and classification of words in the Spanish language by means of the analysis of subvocal speech signals. The processed database has six words (forward, backward, right, left, start and stop). In this work, the signals were sensed with surface electrodes placed on the surface of the throat and acquired with a sampling frequency of 50 kHz. The signal conditioning consisted in: the location of area of interest using energy a...

  11. An integrated signal transduction network of macrophage migration inhibitory factor.

    Science.gov (United States)

    Subbannayya, Tejaswini; Variar, Prathyaksha; Advani, Jayshree; Nair, Bipin; Shankar, Subramanian; Gowda, Harsha; Saussez, Sven; Chatterjee, Aditi; Prasad, T S Keshava

    2016-06-01

    Macrophage migration inhibitory factor (MIF) is a glycosylated multi-functional protein that acts as an enzyme as well as a cytokine. MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7. MIF has been implicated in the pathogenesis of several acute and chronic inflammatory diseases. Although MIF is a molecule of biomedical importance, a public resource of MIF signaling pathway is currently lacking. In view of this, we carried out detailed data mining and documentation of the signaling events pertaining to MIF from published literature and developed an integrated reaction map of MIF signaling. This resulted in the cataloguing of 68 molecules belonging to MIF signaling pathway, which includes 24 protein-protein interactions, 44 post-translational modifications, 11 protein translocation events and 8 activation/inhibition events. In addition, 65 gene regulation events at the mRNA levels induced by MIF signaling have also been catalogued. This signaling pathway has been integrated into NetPath ( http://www.netpath.org ), a freely available human signaling pathway resource developed previously by our group. The MIF pathway data is freely available online in various community standard data exchange formats. We expect that data on signaling events and a detailed signaling map of MIF will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on MIF. PMID:27139435

  12. The cost and capacity of signaling in the Escherichia coli protein reaction network

    International Nuclear Information System (INIS)

    In systems biology new ways are required to analyze the large amount of existing data on regulation of cellular processes. Recent work can be roughly classified into either dynamical models of well-described subsystems, or coarse-grained descriptions of the topology of the molecular networks at the scale of the whole organism. In order to bridge these two disparate approaches one needs to develop simplified descriptions of dynamics and topological measures which address the propagation of signals in molecular networks. Transmission of a signal across a reaction node depends on the presence of other reactants. It will typically be more demanding to transmit a signal across a reaction node with more input links. Sending signals along a path with several subsequent reaction nodes also increases the constraints on the presence of other proteins in the overall network. Therefore counting in and out links along reactions of a potential pathway can give insight into the signaling properties of a particular molecular network. Here, we consider the directed network of protein regulation in E. coli, characterizing its modularity in terms of its potential to transmit signals. We demonstrate that the simplest measure based on identifying subnetworks of strong components, within which each node could send a signal to every other node, does indeed partition the network into functional modules. We suggest that the total number of reactants needed to send a signal between two nodes in the network can be considered as the cost associated with transmitting this signal. Similarly we define spread as the number of reaction products that could be influenced by transmission of a successful signal. Our considerations open for a new class of network measures that implicitly utilize the constrained repertoire of chemical modifications of any biological molecule. The counting of cost and spread connects the topology of networks to the specificity of signaling across the network. Thereby, we

  13. Signaling pathways in ascidian oocyte maturation: the roles of cAMP/Epac, intracellular calcium levels, and calmodulin kinase in regulating GVBD.

    Science.gov (United States)

    Lambert, Charles C

    2011-01-01

    Most mature ascidian oocytes undergo germinal vesicle breakdown (GVBD) when released by the ovary into sea water (SW). Acidic SW blocks this but they can be stimulated by raising the pH, increasing intracellular cAMP levels by cell permeant forms, inhibiting its breakdown or causing synthesis. Boltenia villosa oocytes undergo GVBD in response to these drugs. However, the cAMP receptor protein kinase A (PKA) does not appear to be involved, as oocytes are not affected by the kinase inhibitor H-89. Also, the PKA independent Epac agonist 8CPT-2Me-cAMP stimulates GVBD in acidic SW. GVBD is inhibited in calcium free sea water (CaFSW). The intracellular calcium chelator BAPTA-AM blocks GVBD at 10 µM. GVBD is also inhibited when the ryanodine receptors (RYR) are blocked by tetracaine or ruthenium red but not by the IP(3) inhibitor D-609. However, dimethylbenzanthracene (DMBA), a protein kinase activator, stimulates GVBD in BAPTA, tetracaine or ruthenium red blocked oocytes. The calmodulin kinase inhibitor KN-93 blocks GVBD at 10 µM. This and preceding papers support the hypothesis that the maturation inducing substance (MIS) produced by the follicle cells in response to increased pH causes activation of a G protein which triggers cAMP synthesis. The cAMP then activates an Epac molecule, which causes an increase in intracellular calcium from the endoplasmic reticulum ryanodine receptor. The increased intracellular calcium subsequently activates calmodulin kinase, which causes an increase in cdc25 phosphatase activity, activating MPF and the progression of the oocyte into meiosis. PMID:21774024

  14. Model-based design of self-Adapting networked signal processing systems

    NARCIS (Netherlands)

    Oliveira Filho, J.A. de; Papp, Z.; Djapic, R.; Oostveen, J.C.

    2013-01-01

    The paper describes a model based approach for architecture design of runtime reconfigurable, large-scale, networked signal processing applications. A graph based modeling formalism is introduced to describe all relevant aspects of the design (functional, concurrency, hardware, communication, energy

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

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

    Larsen, Jan

    This proceeding contains refereed papers presented at the thirteenth IEEE Workshop on Neural Networks for Signal Processing (NNSP’2003), held at the Atria-Mercure Conference Center, Toulouse, France, September 17-19, 2003. The Neural Networks for Signal Processing Technical Committee of the IEEE...... Signal Processing Society organized the workshop with sponsorship of the Signal Processing Society and the co-operation of the IEEE Neural Networks Society. The IEEE Press published the previous twelve volumes of the NNSP Workshop proceedings in a hardbound volume. This year, the bound volume is to be...... published by IEEE following the workshop, and we are pleased to inaugurate a new CDROM electronic format, which maintains the same standard as the printed version and facilitates the reading and searching of the papers. In recent years, the field of neural networks has matured considerably in both...

  17. Experimental Demonstration of Mixed Formats and Bit Rates Signal Allocation for Spectrum-flexible Optical Networking

    DEFF Research Database (Denmark)

    Borkowski, Robert; Karinou, Fotini; Angelou, Marianna; Arlunno, Valeria; Zibar, Darko; Klonidis, Dimitrios; Guerrero Gonzalez, Neil; Caballero Jambrina, Antonio; Tomkos, Ioannis; Monroy, Idelfonso Tafur

    2012-01-01

    We report on an extensive experimental study for adaptive allocation of 16-QAM and QPSK signals inside spectrum flexible heterogeneous superchannel. Physical-layer performance parameters are extracted for use in resource allocation mechanisms of future flexible networks....

  18. Experimental Demonstration of Mixed Formats and Bit Rates Signal Allocation for Spectrum-flexible Optical Networking

    OpenAIRE

    Borkowski, Robert; Karinou, Fotini; Angelou, Marianna; Arlunno, Valeria; Zibar, Darko; Klonidis, Dimitrios; Guerrero Gonzalez, Neil; Caballero Jambrina, Antonio; Tomkos, Ioannis; Monroy, Idelfonso Tafur

    2012-01-01

    We report on an extensive experimental study for adaptive allocation of 16-QAM and QPSK signals inside spectrum flexible heterogeneous superchannel. Physical-layer performance parameters are extracted for use in resource allocation mechanisms of future flexible networks.

  19. Methods for the Analysis of Protein Phosphorylation–Mediated Cellular Signaling Networks

    Science.gov (United States)

    White, Forest M.; Wolf-Yadlin, Alejandro

    2016-06-01

    Protein phosphorylation–mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

  20. Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks.

    Science.gov (United States)

    White, Forest M; Wolf-Yadlin, Alejandro

    2016-06-12

    Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks. PMID:27049636

  1. Experimental and computational tools for analysis of signaling networks in primary cells

    DEFF Research Database (Denmark)

    Schoof, Erwin M; Linding, Rune

    2014-01-01

    Cellular information processing in signaling networks forms the basis of responses to environmental stimuli. At any given time, cells receive multiple simultaneous input cues, which are processed and integrated to determine cellular responses such as migration, proliferation, apoptosis, or differ...

  2. Traffic analysis and signal processing in optical packet switched networks

    DEFF Research Database (Denmark)

    Fjelde, Tina

    2002-01-01

    /s optical packet switched network exploiting the best of optics and electronics, is used as a thread throughout the thesis. An overview of the DAVID network architecture is given, focussing on the MAN and WAN architecture as well as the MPLS-based network hierarchy. Subsequently, the traffic performance...... into an MI. Moreover, logic XOR is demonstrated in an MZI at 10 and 20 Gbit/s with good results. Using an MI, the excellent performance of a novel scheme for MPLS label swapping exploiting logic XOR is demonstrated at 10 Gbit/s with a negligible 0.4 dB penalty. Finally, three novel schemes are described...

  3. Inferring signalling networks from longitudinal data using sampling based approaches in the R-package 'ddepn'

    Directory of Open Access Journals (Sweden)

    Korf Ulrike

    2011-07-01

    Full Text Available Abstract Background Network inference from high-throughput data has become an important means of current analysis of biological systems. For instance, in cancer research, the functional relationships of cancer related proteins, summarised into signalling networks are of central interest for the identification of pathways that influence tumour development. Cancer cell lines can be used as model systems to study the cellular response to drug treatments in a time-resolved way. Based on these kind of data, modelling approaches for the signalling relationships are needed, that allow to generate hypotheses on potential interference points in the networks. Results We present the R-package 'ddepn' that implements our recent approach on network reconstruction from longitudinal data generated after external perturbation of network components. We extend our approach by two novel methods: a Markov Chain Monte Carlo method for sampling network structures with two edge types (activation and inhibition and an extension of a prior model that penalises deviances from a given reference network while incorporating these two types of edges. Further, as alternative prior we include a model that learns signalling networks with the scale-free property. Conclusions The package 'ddepn' is freely available on R-Forge and CRAN http://ddepn.r-forge.r-project.org, http://cran.r-project.org. It allows to conveniently perform network inference from longitudinal high-throughput data using two different sampling based network structure search algorithms.

  4. The function of AK and AMP signaling in body energy sensing and balance%腺苷酸激酶与AMP信号在感知及维持机体能量中的作用

    Institute of Scientific and Technical Information of China (English)

    张盈; 夏琳; 逢文强; 王涛; 张建法

    2011-01-01

    Adenylate kinase(AK) is a phosphotransferase en yme that catalyzes the interconversion of adenine nucleotides, and plays an important role in cellular energy homeostasis.The enzyme has seven isoforms, and plays a critical role in energy transfer and distribution between mitochondria, cytosol and nucleus.AMP levels in cellular,interstitial and blood are potential metabolic signals associated with body energy sensing, sleep, hibernation and food intake.Either low or excess AMP signaling has been linked to human disease.AK and downstream AMP signaling is an integrated metabolic monitoring system, which reads the cellular energy state in order to tune and report signals to metabolic sensors.The function of AK and AMP signaling in body energy sensing and balance is reviewed in details here.%腺苷酸激酶(AK)是催化各种腺嘌呤核苷酸相互转化的一种磷酸转移酶,其在维持细胞能量平衡中起着重要的作用.AK有七种亚型,在线粒体、胞浆、细胞核之间的能量转移和分布中起着至关重要的作用.细胞内、细胞外和血液中的AMP水平是机体能量感知、睡眠、冬眠和食物摄取的代谢信号.高于或低于正常水平的AMP信号与人类疾病相关.AK及其下游的AMP信号组成了一个完整的代谢监测系统,通过榆测细胞能量状态变化,从而调整对代谢感受器传递的信号.详细阐述了AK和AMP在感知及维持机体能量中的作用.

  5. Topological basis of signal integration in the transcriptional-regulatory network of the yeast, Saccharomyces cerevisiae

    OpenAIRE

    Chennubhotla Chakra; Wu Chuang; Farkas Illés J; Bahar Ivet; Oltvai Zoltán N

    2006-01-01

    Abstract Background Signal recognition and information processing is a fundamental cellular function, which in part involves comprehensive transcriptional regulatory (TR) mechanisms carried out in response to complex environmental signals in the context of the cell's own internal state. However, the network topological basis of developing such integrated responses remains poorly understood. Results By studying the TR network of the yeast Saccharomyces cerevisiae we show that an intermediate l...

  6. A comprehensive map of the toll-like receptor signaling network

    OpenAIRE

    Oda, Kanae; Kitano, Hiroaki

    2006-01-01

    Recognition of pathogen-associated molecular signatures is critically important in proper activation of the immune system. The toll-like receptor (TLR) signaling network is responsible for innate immune response. In mammalians, there are 11 TLRs that recognize a variety of ligands from pathogens to trigger immunological responses. In this paper, we present a comprehensive map of TLRs and interleukin 1 receptor signaling networks based on papers published so far. The map illustrates the possib...

  7. Energy-Efficient Distributed Signal Processing in Mobile Wireless Sensor Networks

    OpenAIRE

    ARIENZO LOREDANA

    2009-01-01

    Wireless mobile sensor networks are important for a number of strategic applications such as surveillance, fire detection, outlier detection. Energy is a critical resource in wireless sensor networks and system lifetime needs to be prolonged through the use of energy-efficient signal processing during system operation. We present an overview of statistical prediction frameworks for tracking dynamic targets in range-based signal processing. The single mobile target algorithm has been evaluated...

  8. Microglia Control Neuronal Network Excitability via BDNF Signalling

    OpenAIRE

    Francesco Ferrini; Yves De Koninck

    2013-01-01

    Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophi...

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

    CERN Document Server

    Hussain, A; Shim, I

    1999-01-01

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

  10. Frequency Sensitivity of Signal Detection in Scale-Free Networks

    Institute of Scientific and Technical Information of China (English)

    LU Fa-Ming; LIU Zong-Hua

    2009-01-01

    @@ It has been recently reported that scale-free topology favors the detection of a weak signal because of the higher amplification at the hub node than that at other nodes [Phys. Ref. E 78 (2008)046111]. We investigate the corresponding synchronization behaviors and find that the favorite detection depends not only on the coupling and noise strengths but also on the frequency of the external signal. We reveal theoretically and numerically that the amplification effect of the hub node will decrease monotonously with the externai frequency, which is useful to understand the high sensitivity of animal visual and auditory systems to weak external signals.

  11. Dynamical patterns of calcium signaling in a functional model of neuron-astrocyte networks

    DEFF Research Database (Denmark)

    Postnov, D.E.; Koreshkov, R.N.; Brazhe, N.A.;

    2009-01-01

    We propose a functional mathematical model for neuron-astrocyte networks. The model incorporates elements of the tripartite synapse and the spatial branching structure of coupled astrocytes. We consider glutamate-induced calcium signaling as a specific mode of excitability and transmission in...... astrocytic-neuronal networks. We reproduce local and global dynamical patterns observed experimentally....

  12. Dynamical patterns of calcium signaling in a functional model of neuron–astrocyte networks

    OpenAIRE

    Postnov, D. E.; Koreshkov, R. N.; Brazhe, N. A.; Brazhe, A. R.; Sosnovtseva, O. V.

    2009-01-01

    We propose a functional mathematical model for neuron-astrocyte networks. The model incorporates elements of the tripartite synapse and the spatial branching structure of coupled astrocytes. We consider glutamate-induced calcium signaling as a specific mode of excitability and transmission in astrocytic–neuronal networks. We reproduce local and global dynamical patterns observed experimentally.

  13. Modeling of inclined fracture network and calculation of fracture effect on seismic signal spectrum

    International Nuclear Information System (INIS)

    The paper considers modeling technique for the medium with a network of inclined fractures and calculations for completing seismic tasks for such a medium. The network of plane-parallel fractures has controlled dip angle and fluid saturation. The time section for a model with water-saturated fractures is produced. The comparison of incident and transmitted signal spectra is made

  14. 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...

  15. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells

    Directory of Open Access Journals (Sweden)

    Yeo Cho Yoon

    2015-12-01

    Full Text Available Limonin, one of the major components in dictamni radicis cortex (DRC, has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB.

  16. Involvement of hippocampal AMPA glutamate receptor changes and the cAMP/protein kinase A/CREB-P signalling pathway in memory consolidation of an avoidance task in rats

    Directory of Open Access Journals (Sweden)

    Bernabeu R.

    1997-01-01

    Full Text Available Training in step-down inhibitory avoidance (0.3-mA footshock is followed by biochemical changes in rat hippocampus that strongly suggest an involvement of quantitative changes in glutamate AMPA receptors, followed by changes in the dopamine D1 receptor/cAMP/protein kinase A (PKA/CREB-P signalling pathway in memory consolidation. AMPA binding to its receptor and levels of the AMPA receptor-specific subunit GluR1 increase in the hippocampus within the first 3 h after training (20-70%. Binding of the specific D1 receptor ligand, SCH23390, and cAMP levels increase within 3 or 6 h after training (30-100%. PKA activity and CREB-P levels show two peaks: a 35-40% increase 0 h after training, and a second increase 3-6 h later (35-60%. The results correlate with pharmacological findings showing an early post-training involvement of AMPA receptors, and a late involvement of the D1/cAMP/PKA/CREB-P pathway in memory consolidation of this task

  17. Stability of multispecies bacterial communities: signaling networks may stabilize microbiomes.

    Directory of Open Access Journals (Sweden)

    Ádám Kerényi

    Full Text Available Multispecies bacterial communities can be remarkably stable and resilient even though they consist of cells and species that compete for environmental resources. In silico models suggest that common signals released into the environment may help selected bacterial species cluster at common locations and that sharing of public goods (i.e. molecules produced and released for mutual benefit can stabilize this coexistence. In contrast, unilateral eavesdropping on signals produced by a potentially invading species may protect a community by keeping invaders away from limited resources. Shared bacterial signals, such as those found in quorum sensing systems, may thus play a key role in fine tuning competition and cooperation within multi-bacterial communities. We suggest that in addition to metabolic complementarity, signaling dynamics may be important in further understanding complex bacterial communities such as the human, animal as well as plant microbiomes.

  18. Array signal processing in the NASA Deep Space Network

    Science.gov (United States)

    Pham, Timothy T.; Jongeling, Andre P.

    2004-01-01

    In this paper, we will describe the benefits of arraying and past as well as expected future use of this application. The signal processing aspects of array system are described. Field measurements via actual tracking spacecraft are also presented.

  19. Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.

    Directory of Open Access Journals (Sweden)

    Yuko Nakagawa

    Full Text Available BACKGROUND: Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS: The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+ ([Ca(2+](c and cAMP ([cAMP](c were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+](c. The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+](c response. The effect of sucralose on [Ca(2+](c was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q inhibitor. Sucralose also induced sustained elevation of [cAMP](c, which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. CONCLUSIONS: Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+ and cAMP-dependent mechanisms.

  20. Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans.

    OpenAIRE

    Shimizu, K; Keller, N P

    2001-01-01

    In the filamentous fungus Aspergillus nidulans, a heterotrimeric G protein alpha-subunit and an RGS domain protein, encoded by fadA and flbA, respectively, regulate production of the carcinogenic metabolite sterigmatocystin (ST) and asexual spores (i.e., conidia). We investigated the genetic involvement of the cAMP-dependent protein kinase catalytic subunit (PkaA), a potential downstream target of FadA activity, in ST production and conidiation. Relative to wild type, sporulation was decrease...

  1. cAMP and EPAC are key players in the regulation of the signal transduction pathway involved in the α-hemolysin autophagic response.

    Directory of Open Access Journals (Sweden)

    María Belén Mestre

    Full Text Available Staphylococcus aureus is a microorganism that causes serious diseases in the human being. This microorganism is able to escape the phagolysosomal pathway, increasing intracellular bacterial survival and killing the eukaryotic host cell to spread the infection. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. We have shown that the pore-forming toxin α-hemolysin (Hla is the S. aureus-secreted factor responsible for the activation of the autophagic pathway and that this response occurs through a PI3K/Beclin1-independent form. In the present report we demonstrate that cAMP has a key role in the regulation of this autophagic response. Our results indicate that cAMP is able to inhibit the autophagy induced by Hla and that PKA, the classical cAMP effector, does not participate in this regulation. We present evidence that EPAC and Rap2b, through calpain activation, are the proteins involved in the regulation of Hla-induced autophagy. Similar results were obtained in cells infected with different S. aureus strains. Interestingly, in this report we show, for the first time to our knowledge, that both EPAC and Rap2b are recruited to the S. aureus-containing phagosome. We believe that our findings have important implications in understanding innate immune processes involved in intracellular pathogen invasion of the host cell.

  2. Estimation of azimuth and slowness of teleseismic signals recorded by a local seismic network

    Institute of Scientific and Technical Information of China (English)

    靳平; 潘常周

    2002-01-01

    A new method that is applicable to local seismic networks to estimate the azimuth and slowness of teleseismic signals is introduced in the paper. The method is based on the correlation between the arrival times and station positions. The analyzed results indicate that the azimuth and slowness of teleseismic signals can be accurately estimated by the method. Average errors for azimuth and slowness measurements obtained by this method using data of Xi(an Digital Telemetry Seismic Network are 2.0o and 0.34 s/(o), respectively. The conclusions drawn from this study indicate that this method may be very useful to interpret teleseismic records of local seismic networks.

  3. A network map of Interleukin-10 signaling pathway.

    Science.gov (United States)

    Verma, Renu; Balakrishnan, Lavanya; Sharma, Kusum; Khan, Aafaque Ahmad; Advani, Jayshree; Gowda, Harsha; Tripathy, Srikanth Prasad; Suar, Mrutyunjay; Pandey, Akhilesh; Gandotra, Sheetal; Prasad, T S Keshava; Shankar, Subramanian

    2016-03-01

    Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important immunoregulatory functions. It is primarily secreted by antigen-presenting cells such as activated T-cells, monocytes, B-cells and macrophages. In biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer IL-10 receptor and induces downstream signaling. IL-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as Burkitt lymphoma, non-Hodgkins lymphoma and non-small scell lung cancer. In addition, it plays a central role in survival and persistence of intracellular pathogens such as Leishmania donovani, Mycobacterium tuberculosis and Trypanosoma cruzi inside the host. The signaling mechanisms of IL-10 cytokine are not well explored and a well annotated pathway map has been lacking. To this end, we developed a pathway resource by manually annotating the IL-10 induced signaling molecules derived from literature. The reactions were categorized under molecular associations, activation/inhibition, catalysis, transport and gene regulation. In all, 37 molecules and 76 reactions were annotated. The IL-10 signaling pathway can be freely accessed through NetPath, a resource of signal transduction pathways previously developed by our group. PMID:26253919

  4. 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.

  5. Integrating in silico resources to map a signaling network.

    Science.gov (United States)

    Liu, Hanqing; Beck, Tim N; Golemis, Erica A; Serebriiskii, Ilya G

    2014-01-01

    The abundance of publicly available life science databases offers a wealth of information that can support interpretation of experimentally derived data and greatly enhance hypothesis generation. Protein interaction and functional networks are not simply new renditions of existing data: they provide the opportunity to gain insights into the specific physical and functional role a protein plays as part of the biological system. In this chapter, we describe different in silico tools that can quickly and conveniently retrieve data from existing data repositories and we discuss how the available tools are best utilized for different purposes. While emphasizing protein-protein interaction databases (e.g., BioGrid and IntAct), we also introduce metasearch platforms such as STRING and GeneMANIA, pathway databases (e.g., BioCarta and Pathway Commons), text mining approaches (e.g., PubMed and Chilibot), and resources for drug-protein interactions, genetic information for model organisms and gene expression information based on microarray data mining. Furthermore, we provide a simple step-by-step protocol for building customized protein-protein interaction networks in Cytoscape, a powerful network assembly and visualization program, integrating data retrieved from these various databases. As we illustrate, generation of composite interaction networks enables investigators to extract significantly more information about a given biological system than utilization of a single database or sole reliance on primary literature. PMID:24233784

  6. Insights into biological information processing: structural and dynamical analysis of a human protein signalling network

    International Nuclear Information System (INIS)

    We present an investigation on the structural and dynamical properties of a 'human protein signalling network' (HPSN). This biological network is composed of nodes that correspond to proteins and directed edges that represent signal flows. In order to gain insight into the organization of cell information processing this network is analysed taking into account explicitly the edge directions. We explore the topological properties of the HPSN at the global and the local scale, further applying the generating function formalism to provide a suitable comparative model. The relationship between the node degrees and the distribution of signals through the network is characterized using degree correlation profiles. Finally, we analyse the dynamical properties of small sub-graphs showing high correlation between their occurrence and dynamic stability

  7. Signaling-based path-segment protection in mesh optical networks

    Institute of Scientific and Technical Information of China (English)

    Yueming Lu; Chao Zou; Qiushi Wang; Yuefeng Ji

    2011-01-01

    Path protections have become increasingly important for current mesh optical networks because fast restorations in generalized multiprotocol label switching (GMPLS) networks are uncertain. However, setting up additional disjoint paths to protect connections leads to more path setup blocking and signaling collisions. We analyze signaling collisions, path blocking and blocking probability, as well as calculate node-to-node blocking probabilities. A signaling-based path-segment protection (PSP) is proposed, which integrates segment protections and path protections as well as enhances the performance of path protections and ring protections. The setup of PSP connections causes less blocking probability than the setup of path protection connections in the simulations.%Path protections have become increasingly important for current mesh optical networks because fast restorations in generalized multiprotocol label switching (GMPLS) networks are uncertain.However,setting up additional disjoint paths to protect connections leads to more path setup blocking and signaling collisions.We analyze signaling collisions,path blocking and blocking probability,as well as calculate node-to-node blocking probabilities.A signaling-based path-segment protection (PSP) is proposed,which integrates segment protections and path protections as well as enhances the performance of path protections and ring protections.The setup of PSP connections causes less blocking probability than the setup of path protection connections in the simulations.Recently,with the emergence of new protection and restoration methods,mesh topologies have gradually replaced ring topologies,especially in optical transport networks (OTNs)[1],automatically switched optical networks (ASONs)[2],generalized multiprotocol label switching (GMPLS) protocol networks[3,4],and packet transport networks (PTNs)[5].However,fast restoration methods currently face some challenges in China.

  8. Towards the systematic discovery of signal transduction networks using phosphorylation dynamics data

    Directory of Open Access Journals (Sweden)

    Yachie Nozomu

    2010-05-01

    Full Text Available Abstract Background Phosphorylation is a ubiquitous and fundamental regulatory mechanism that controls signal transduction in living cells. The number of identified phosphoproteins and their phosphosites is rapidly increasing as a result of recent mass spectrometry-based approaches. Results We analyzed time-course phosphoproteome data obtained previously by liquid chromatography mass spectrometry with the stable isotope labeling using amino acids in cell culture (SILAC method. This provides the relative phosphorylation activities of digested peptides at each of five time points after stimulating HeLa cells with epidermal growth factor (EGF. We initially calculated the correlations between the phosphorylation dynamics patterns of every pair of peptides and connected the strongly correlated pairs to construct a network. We found that peptides extracted from the same intracellular fraction (nucleus vs. cytoplasm tended to be close together within this phosphorylation dynamics-based network. The network was then analyzed using graph theory and compared with five known signal-transduction pathways. The dynamics-based network was correlated with known signaling pathways in the NetPath and Phospho.ELM databases, and especially with the EGF receptor (EGFR signaling pathway. Although the phosphorylation patterns of many proteins were drastically changed by the EGF stimulation, our results suggest that only EGFR signaling transduction was both strongly activated and precisely controlled. Conclusions The construction of a phosphorylation dynamics-based network provides a useful overview of condition-specific intracellular signal transduction using quantitative time-course phosphoproteome data under specific experimental conditions. Detailed prediction of signal transduction based on phosphoproteome dynamics remains challenging. However, since the phosphorylation profiles of kinase-substrate pairs on the specific pathway were localized in the dynamics

  9. Integrating In Silico Resources to Map a Signaling Network

    OpenAIRE

    Liu, Hanqing; Beck, Tim N.; Golemis, Erica A.; Serebriiskii, Ilya G.

    2014-01-01

    The abundance of publicly available life science databases offer a wealth of information that can support interpretation of experimentally derived data and greatly enhance hypothesis generation. Protein interaction and functional networks are not simply new renditions of existing data: they provide the opportunity to gain insights into the specific physical and functional role a protein plays as part of the biological system. In this chapter, we describe different in silico tools that can qui...

  10. Signaling and Transcriptional Networks in Heart Development and Regeneration

    OpenAIRE

    Bruneau, Benoit G.

    2013-01-01

    The mammalian heart is the first functional organ, the first indicator of life. Its normal formation and function are essential for fetal life. Defects in heart formation lead to congenital heart defects, underscoring the finesse with which the heart is assembled. Understanding the regulatory networks controlling heart development have led to significant insights into its lineage origins and morphogenesis and illuminated important aspects of mammalian embryology, while providing insights into...

  11. Signaling and transcriptional networks in heart development and regeneration

    OpenAIRE

    Bruneau, BG

    2013-01-01

    The mammalian heart is the first functional organ, the first indicator of life. Its normal formation and function are essential for fetal life. Defects in heart formation lead to congenital heart defects, underscoring the finesse with which the heart is assembled. Understanding the reg-ulatory networks controlling heart development have led to significant insights into its lineage origins and morphogenesis and illuminated important aspects of mammalian embryology, while providing insights int...

  12. AE SOURCE RECOGNITION BY NEURAL NETWORKS WITH OPTIMIZED SIGNAL PARAMETERS

    Czech Academy of Sciences Publication Activity Database

    Chlada, Milan; Převorovský, Zdeněk

    Krakow: University of Technology Krakov, 2008 - (Kanji, O.), s. 250-255 ISBN 978-83-7242-478-5. [European Conference on Acoustic Emission Testing EWGAE /28./. Krakow (PL), 17.09.2008-19.09.2008] R&D Projects: GA ČR GA101/07/1518; GA ČR GA106/07/1393 Institutional research plan: CEZ:AV0Z20760514 Keywords : AE source recognition * artificial neural network Subject RIV: BI - Acoustics

  13. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Science.gov (United States)

    Tullet, Jennifer M A; Araiz, Caroline; Sanders, Matthew J; Au, Catherine; Benedetto, Alexandre; Papatheodorou, Irene; Clark, Emily; Schmeisser, Kathrin; Jones, Daniel; Schuster, Eugene F; Thornton, Janet M; Gems, David

    2014-02-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved

  14. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jennifer M A Tullet

    2014-02-01

    Full Text Available The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK, which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be

  15. β-Hydroxybutyric sodium salt inhibition of growth hormone and prolactin secretion via the cAMP/PKA/CREB and AMPK signaling pathways in dairy cow anterior pituitary cells.

    Science.gov (United States)

    Fu, Shou-Peng; Wang, Wei; Liu, Bing-Run; Yang, Huan-Min; Ji, Hong; Yang, Zhan-Qing; Guo, Bin; Liu, Ju-Xiong; Wang, Jian-Fa

    2015-01-01

    β-hydroxybutyric acid (BHBA) regulates the synthesis and secretion of growth hormone (GH) and prolactin (PRL), but its mechanism is unknown. In this study, we detected the effects of BHBA on the activities of G protein signaling pathways, AMPK-α activity, GH, and PRL gene transcription, and GH and PRL secretion in dairy cow anterior pituitary cells (DCAPCs). The results showed that BHBA decreased intracellular cAMP levels and a subsequent reduction in protein kinase A (PKA) activity. Inhibition of PKA activity reduced cAMP response element-binding protein (CREB) phosphorylation, thereby inhibiting GH and PRL transcription and secretion. The effects of BHBA were attenuated by a specific Gαi inhibitor, pertussis toxin (PTX). In addition, intracellular BHBA uptake mediated by monocarboxylate transporter 1 (MCT1) could trigger AMPK signaling and result in the decrease in GH and PRL mRNA translation in DCAPCs cultured under low-glucose and non-glucose condition when compared with the high-glucose group. This study identifies a biochemical mechanism for the regulatory action of BHBA on GH and PRL gene transcription, translation, and secretion in DCAPCs, which may be one of the factors that regulate pituitary function during the transition period in dairy cows. PMID:25690038

  16. β-Hydroxybutyric Sodium Salt Inhibition of Growth Hormone and Prolactin Secretion via the cAMP/PKA/CREB and AMPK Signaling Pathways in Dairy Cow Anterior Pituitary Cells

    Directory of Open Access Journals (Sweden)

    Shou-Peng Fu

    2015-02-01

    Full Text Available β-hydroxybutyric acid (BHBA regulates the synthesis and secretion of growth hormone (GH and prolactin (PRL, but its mechanism is unknown. In this study, we detected the effects of BHBA on the activities of G protein signaling pathways, AMPK-α activity, GH, and PRL gene transcription, and GH and PRL secretion in dairy cow anterior pituitary cells (DCAPCs. The results showed that BHBA decreased intracellular cAMP levels and a subsequent reduction in protein kinase A (PKA activity. Inhibition of PKA activity reduced cAMP response element-binding protein (CREB phosphorylation, thereby inhibiting GH and PRL transcription and secretion. The effects of BHBA were attenuated by a specific Gαi inhibitor, pertussis toxin (PTX. In addition, intracellular BHBA uptake mediated by monocarboxylate transporter 1 (MCT1 could trigger AMPK signaling and result in the decrease in GH and PRL mRNA translation in DCAPCs cultured under low-glucose and non-glucose condition when compared with the high-glucose group. This study identifies a biochemical mechanism for the regulatory action of BHBA on GH and PRL gene transcription, translation, and secretion in DCAPCs, which may be one of the factors that regulate pituitary function during the transition period in dairy cows.

  17. Creating and analyzing pathway and protein interaction compendia for modelling signal transduction networks

    Directory of Open Access Journals (Sweden)

    Kirouac Daniel C

    2012-05-01

    Full Text Available Abstract Background Understanding the information-processing capabilities of signal transduction networks, how those networks are disrupted in disease, and rationally designing therapies to manipulate diseased states require systematic and accurate reconstruction of network topology. Data on networks central to human physiology, such as the inflammatory signalling networks analyzed here, are found in a multiplicity of on-line resources of pathway and interactome databases (Cancer CellMap, GeneGo, KEGG, NCI-Pathway Interactome Database (NCI-PID, PANTHER, Reactome, I2D, and STRING. We sought to determine whether these databases contain overlapping information and whether they can be used to construct high reliability prior knowledge networks for subsequent modeling of experimental data. Results We have assembled an ensemble network from multiple on-line sources representing a significant portion of all machine-readable and reconcilable human knowledge on proteins and protein interactions involved in inflammation. This ensemble network has many features expected of complex signalling networks assembled from high-throughput data: a power law distribution of both node degree and edge annotations, and topological features of a “bow tie” architecture in which diverse pathways converge on a highly conserved set of enzymatic cascades focused around PI3K/AKT, MAPK/ERK, JAK/STAT, NFκB, and apoptotic signaling. Individual pathways exhibit “fuzzy” modularity that is statistically significant but still involving a majority of “cross-talk” interactions. However, we find that the most widely used pathway databases are highly inconsistent with respect to the actual constituents and interactions in this network. Using a set of growth factor signalling networks as examples (epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, and wingless, we find a multiplicity of network topologies in which receptors couple to downstream

  18. A Signaling Network of Thyroid-Stimulating Hormone

    OpenAIRE

    Goel, Renu; Raju, Rajesh; Maharudraiah, Jagadeesha; Sameer Kumar, Ghantasala S.; Ghosh, Krishna; Kumar, Amit; Lakshmi, T. Pragna; Sharma, Jyoti; Sharma, Rakesh; Balakrishnan, Lavanya; Pan, Archana; Kandasamy, Kumaran; Christopher, Rita; V. Krishna; Mohan, S. Sujatha

    2011-01-01

    Human thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland. TSH plays an important physiological role in the regulation of hypothalamic-pituitary-thyroid axis by modulating the release of the thyroid hormones from the thyroid gland. It induces iodine uptake by the thyroid, promotes thyroid epithelial differentiation and growth, and protects thyroid cells from apoptosis. Impairment of TSH signal transduction pathway leads to thyroid disorders...

  19. Mapping Complex Networks: Exploring Boolean Modeling of Signal Transduction Pathways

    OpenAIRE

    Bhardwaj, Gaurav; Wells, Christine P.; Albert, Reka; van Rossum, Damian B.; Patterson, Randen L

    2009-01-01

    In this study, we explored the utility of a descriptive and predictive bionetwork model for phospholipase C-coupled calcium signaling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP3R) and the plasma-membrane resident canonical transient receptor potential channel 3 (TRPC3). These results are specific as randomization of ...

  20. Patterns of human gene expression variance show strong associations with signaling network hierarchy

    Directory of Open Access Journals (Sweden)

    Ram Prahlad T

    2010-11-01

    Full Text Available Abstract Background Understanding organizational principles of cellular networks is one of the central goals of systems biology. Although much has been learnt about gene expression programs under specific conditions, global patterns of expressional variation (EV of genes and their relationship to cellular functions and physiological responses is poorly understood. Results To understand global principles of relationship between transcriptional regulation of human genes and their functions, we have leveraged large-scale datasets of human gene expression measurements across a wide spectrum of cell conditions. We report that human genes are highly diverse in terms of their EV; while some genes have highly variable expression pattern, some seem to be relatively ubiquitously expressed across a wide range of conditions. The wide spectrum of gene EV strongly correlates with the positioning of proteins within the signaling network hierarchy, such that, secreted extracellular receptor ligands and membrane receptors have the highest EV, and intracellular signaling proteins have the lowest EV in the genome. Our analysis shows that this pattern of EV reflects functional centrality: proteins with highly specific signaling functions are modulated more frequently than those with highly central functions in the network, which is also consistent with previous studies on tissue-specific gene expression. Interestingly, these patterns of EV along the signaling network hierarchy have significant correlations with promoter architectures of respective genes. Conclusion Our analyses suggest a generic systems level mechanism of regulation of the cellular signaling network at the transcriptional level.

  1. On the propagation of diel signals in river networks using analytic solutions of flow equations

    Science.gov (United States)

    Fonley, M.; Mantilla, R.; Small, S. J.; Curtu, R.

    2015-08-01

    Two hypotheses have been put forth to explain the magnitude and timing of diel streamflow oscillations during low flow conditions. The first suggests that delays between the peaks and troughs of streamflow and daily evapotranspiration are due to processes occurring in the soil as water moves toward the channels in the river network. The second posits that they are due to the propagation of the signal through the channels as water makes its way to the outlet of the basin. In this paper, we design and implement a theoretical experiment to test these hypotheses. We impose a baseflow signal entering the river network and use a linear transport equation to represent flow along the network. We develop analytic streamflow solutions for two cases: uniform and nonuniform velocities in space over all river links. We then use our analytic solutions to simulate streamflows along a self-similar river network for different flow velocities. Our results show that the amplitude and time delay of the streamflow solution are heavily influenced by transport in the river network. Moreover, our equations show that the geomorphology and topology of the river network play important roles in determining how amplitude and signal delay are reflected in streamflow signals. Finally, our results are consistent with empirical observations that delays are more significant as low flow decreases.

  2. Truncated Glucagon-like Peptide-1 and Exendin-4 α-Conotoxin pl14a Peptide Chimeras Maintain Potency and α-Helicity and Reveal Interactions Vital for cAMP Signaling in Vitro.

    Science.gov (United States)

    Swedberg, Joakim E; Schroeder, Christina I; Mitchell, Justin M; Fairlie, David P; Edmonds, David J; Griffith, David A; Ruggeri, Roger B; Derksen, David R; Loria, Paula M; Price, David A; Liras, Spiros; Craik, David J

    2016-07-22

    Glucagon-like peptide-1 (GLP-1) signaling through the glucagon-like peptide 1 receptor (GLP-1R) is a key regulator of normal glucose metabolism, and exogenous GLP-1R agonist therapy is a promising avenue for the treatment of type 2 diabetes mellitus. To date, the development of therapeutic GLP-1R agonists has focused on producing drugs with an extended serum half-life. This has been achieved by engineering synthetic analogs of GLP-1 or the more stable exogenous GLP-1R agonist exendin-4 (Ex-4). These synthetic peptide hormones share the overall structure of GLP-1 and Ex-4, with a C-terminal helical segment and a flexible N-terminal tail. Although numerous studies have investigated the molecular determinants underpinning GLP-1 and Ex-4 binding and signaling through the GLP-1R, these have primarily focused on the length and composition of the N-terminal tail or on how to modulate the helicity of the full-length peptides. Here, we investigate the effect of C-terminal truncation in GLP-1 and Ex-4 on the cAMP pathway. To ensure helical C-terminal regions in the truncated peptides, we produced a series of chimeric peptides combining the N-terminal portion of GLP-1 or Ex-4 and the C-terminal segment of the helix-promoting peptide α-conotoxin pl14a. The helicity and structures of the chimeric peptides were confirmed using circular dichroism and NMR, respectively. We found no direct correlation between the fractional helicity and potency in signaling via the cAMP pathway. Rather, the most important feature for efficient receptor binding and signaling was the C-terminal helical segment (residues 22-27) directing the binding of Phe(22) into a hydrophobic pocket on the GLP-1R. PMID:27226591

  3. Spatiotemporal properties of intracellular calcium signaling in osteocytic and osteoblastic cell networks under fluid flow.

    Science.gov (United States)

    Jing, Da; Lu, X Lucas; Luo, Erping; Sajda, Paul; Leong, Pui L; Guo, X Edward

    2013-04-01

    Mechanical stimuli can trigger intracellular calcium (Ca(2+)) responses in osteocytes and osteoblasts. Successful construction of bone cell networks necessitates more elaborate and systematic analysis for the spatiotemporal properties of Ca(2+) signaling in the networks. In the present study, an unsupervised algorithm based on independent component analysis (ICA) was employed to extract the Ca(2+) signals of bone cells in the network. We demonstrated that the ICA-based technology could yield higher signal fidelity than the manual region of interest (ROI) method. Second, the spatiotemporal properties of Ca(2+) signaling in osteocyte-like MLO-Y4 and osteoblast-like MC3T3-E1 cell networks under laminar and steady fluid flow stimulation were systematically analyzed and compared. MLO-Y4 cells exhibited much more active Ca(2+) transients than MC3T3-E1 cells, evidenced by more Ca(2+) peaks, less time to the 1st peak and less time between the 1st and 2nd peaks. With respect to temporal properties, MLO-Y4 cells demonstrated higher spike rate and Ca(2+) oscillating frequency. The spatial intercellular synchronous activities of Ca(2+) signaling in MLO-Y4 cell networks were higher than those in MC3T3-E1 cell networks and also negatively correlated with the intercellular distance, revealing faster Ca(2+) wave propagation in MLO-Y4 cell networks. Our findings show that the unsupervised ICA-based technique results in more sensitive and quantitative signal extraction than traditional ROI analysis, with the potential to be widely employed in Ca(2+) signaling extraction in the cell networks. The present study also revealed a dramatic spatiotemporal difference in Ca(2+) signaling for osteocytic and osteoblastic cell networks in processing the mechanical stimulus. The higher intracellular Ca(2+) oscillatory behaviors and intercellular coordination of MLO-Y4 cells provided further evidences that osteocytes may behave as the major mechanical sensor in bone modeling and remodeling

  4. Traffic signal synchronization in the saturated high-density grid road network.

    Science.gov (United States)

    Hu, Xiaojian; Lu, Jian; Wang, Wei; Zhirui, Ye

    2015-01-01

    Most existing traffic signal synchronization strategies do not perform well in the saturated high-density grid road network (HGRN). Traffic congestion often occurs in the saturated HGRN, and the mobility of the network is difficult to restore. In order to alleviate traffic congestion and to improve traffic efficiency in the network, the study proposes a regional traffic signal synchronization strategy, named the long green and long red (LGLR) traffic signal synchronization strategy. The essence of the strategy is to control the formation and dissipation of queues and to maximize the efficiency of traffic flows at signalized intersections in the saturated HGRN. With this strategy, the same signal control timing plan is used at all signalized intersections in the HGRN, and the straight phase of the control timing plan has a long green time and a long red time. Therefore, continuous traffic flows can be maintained when vehicles travel, and traffic congestion can be alleviated when vehicles stop. Using the strategy, the LGLR traffic signal synchronization model is developed, with the objective of minimizing the number of stops. Finally, the simulation is executed to analyze the performance of the model by comparing it to other models, and the superiority of the LGLR model is evident in terms of delay, number of stops, queue length, and overall performance in the saturated HGRN. PMID:25663835

  5. Topological basis of signal integration in the transcriptional-regulatory network of the yeast, Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Chennubhotla Chakra

    2006-10-01

    Full Text Available Abstract Background Signal recognition and information processing is a fundamental cellular function, which in part involves comprehensive transcriptional regulatory (TR mechanisms carried out in response to complex environmental signals in the context of the cell's own internal state. However, the network topological basis of developing such integrated responses remains poorly understood. Results By studying the TR network of the yeast Saccharomyces cerevisiae we show that an intermediate layer of transcription factors naturally segregates into distinct subnetworks. In these topological units transcription factors are densely interlinked in a largely hierarchical manner and respond to external signals by utilizing a fraction of these subnets. Conclusion As transcriptional regulation represents the 'slow' component of overall information processing, the identified topology suggests a model in which successive waves of transcriptional regulation originating from distinct fractions of the TR network control robust integrated responses to complex stimuli.

  6. Multimodal signalling in the North American barn swallow: a phenotype network approach.

    Science.gov (United States)

    Wilkins, Matthew R; Shizuka, Daizaburo; Joseph, Maxwell B; Hubbard, Joanna K; Safran, Rebecca J

    2015-10-01

    Complex signals, involving multiple components within and across modalities, are common in animal communication. However, decomposing complex signals into traits and their interactions remains a fundamental challenge for studies of phenotype evolution. We apply a novel phenotype network approach for studying complex signal evolution in the North American barn swallow (Hirundo rustica erythrogaster). We integrate model testing with correlation-based phenotype networks to infer the contributions of female mate choice and male-male competition to the evolution of barn swallow communication. Overall, the best predictors of mate choice were distinct from those for competition, while moderate functional overlap suggests males and females use some of the same traits to assess potential mates and rivals. We interpret model results in the context of a network of traits, and suggest this approach allows researchers a more nuanced view of trait clustering patterns that informs new hypotheses about the evolution of communication systems. PMID:26423842

  7. Method for analyzing signaling networks in complex cellular systems.

    Science.gov (United States)

    Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie; Wang, Yuker; Dajee, Maya; Melrose, Jennifer; Nakao, Brian; Hytopoulos, Evangelos; Berg, Ellen L; Butcher, Eugene C

    2004-02-01

    Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-kappaBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. PMID:14745015

  8. Adaptive coded spreading OFDM signal for dynamic-λ optical access network

    Science.gov (United States)

    Liu, Bo; Zhang, Lijia; Xin, Xiangjun

    2015-12-01

    This paper proposes and experimentally demonstrates a novel adaptive coded spreading (ACS) orthogonal frequency division multiplexing (OFDM) signal for dynamic distributed optical ring-based access network. The wavelength can be assigned to different remote nodes (RNs) according to the traffic demand of optical network unit (ONU). The ACS can provide dynamic spreading gain to different signals according to the split ratio or transmission length, which offers flexible power budget for the network. A 10×13.12 Gb/s OFDM access with ACS is successfully demonstrated over two RNs and 120 km transmission in the experiment. The demonstrated method may be viewed as one promising for future optical metro access network.

  9. Drastic disorder-induced reduction of signal amplification in scale-free networks.

    Science.gov (United States)

    Chacón, Ricardo; Martínez, Pedro J

    2015-07-01

    Understanding information transmission across a network is a fundamental task for controlling and manipulating both biological and manmade information-processing systems. Here we show how topological resonant-like amplification effects in scale-free networks of signaling devices are drastically reduced when phase disorder in the external signals is considered. This is demonstrated theoretically by means of a starlike network of overdamped bistable systems, and confirmed numerically by simulations of scale-free networks of such systems. The taming effect of the phase disorder is found to be sensitive to the amplification's strength, while the topology-induced amplification mechanism is robust against this kind of quenched disorder in the sense that it does not significantly change the values of the coupling strength where amplification is maximum in its absence. PMID:26274239

  10. Neural Network Analysis of Acoustic Emission Signals for Drill Wear Monitoring

    International Nuclear Information System (INIS)

    The objective of the proposed study is to produce a tool-condition monitoring (TCM) strategy that will lead to a more efficient and economical drilling tool usage. Drill-wear monitoring is an important attribute in the automatic cutting processes as it can help preventing damages of the tools and workpieces and optimizing the tool usage. This study presents the architectures of a multi-layer feed-forward neural network with back-propagation training algorithm for the monitoring of drill wear. The input features to the neural networks were extracted from the AE signals using the wavelet transform analysis. Training and testing were performed under a moderate range of cutting conditions in the dry drilling of steel plates. The results indicated that the extracted input features from AE signals to the supervised neural networks were effective for drill wear monitoring and the output of the neural networks could be utilized for the tool life management planning.

  11. Reduced-Dimension Linear Transform Coding of Correlated Signals in Networks

    CERN Document Server

    Goela, Naveen

    2012-01-01

    A model, called the linear transform network (LTN), is proposed to analyze the compression and estimation of correlated signals transmitted over directed acyclic graphs (DAGs). An LTN is a DAG network with multiple source and receiver nodes. Source nodes transmit subspace projections of random correlated signals by applying reduced-dimension linear transforms. The subspace projections are linearly processed by multiple relays and routed to intended receivers. Each receiver applies a linear estimator to approximate a subset of the sources with minimum mean squared error (MSE) distortion. The model is extended to include noisy networks with power constraints on transmitters. A key task is to compute all local compression matrices and linear estimators in the network to minimize end-to-end distortion. The non-convex problem is solved iteratively within an optimization framework using constrained quadratic programs (QPs). The proposed algorithm recovers as special cases the regular and distributed Karhunen-Loeve ...

  12. Molecular signaling networks in regulation of immunity and disease

    DEFF Research Database (Denmark)

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

    The gut microbiota, host tissues, and the immune system form a complex network where extensive crosstalk and molecular interactions substantially impact the overall state of the system. Concomitantly, modulation of host immune function is recurrently a result of the interaction of complex 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...

  13. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Cédric eBOULARAN; Céline eGALES

    2015-01-01

    Cyclic adenosine 3’,5’-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  14. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  15. The behaviour of basic autocatalytic signalling modules in isolation and embedded in networks

    International Nuclear Information System (INIS)

    In this paper, we examine the behaviour of basic autocatalytic feedback modules involving a species catalyzing its own production, either directly or indirectly. We first perform a systematic study of the autocatalytic feedback module in isolation, examining the effect of different factors, showing how this module is capable of exhibiting monostable threshold and bistable switch-like behaviour. We then study the behaviour of this module embedded in different kinds of basic networks including (essentially) irreversible cycles, open and closed reversible chains, and networks with additional feedback. We study the behaviour of the networks deterministically and also stochastically, using simulations, analytical work, and bifurcation analysis. We find that (i) there are significant differences between the behaviour of this module in isolation and in a network: thresholds may be altered or destroyed and bistability may be destroyed or even induced, even when the ambient network is simple. The global characteristics and topology of this network and the position of the module in the ambient network can play important and unexpected roles. (ii) There can be important differences between the deterministic and stochastic dynamics of the module embedded in networks, which may be accentuated by the ambient network. This provides new insights into the functioning of such enzymatic modules individually and as part of networks, with relevance to other enzymatic signalling modules as well

  16. Clustering of ECG Signals Based on Fuzzy Neural Network with Initial Weights Generated by Genetic Algorithm

    OpenAIRE

    Elaheh Sayari; Mahdi Yaghoobi

    2014-01-01

    Early detection of heart diseases/abnormalities can prolong life and enhance the quality of living through appropriate treatment. Whereas clustering of electrocardiogram (ECG) signals will help to identify the heart diseases as soon as possible. In this regard, neural network and fuzzy logic have been used in many application areas while each of them has the advantages and disadvantages. Thus, the present paper utilizes the proposed fuzzy neural network (FNN) with initial weights generated by...

  17. Regulation of rhythm genesis by volume-limited, astroglia-like signals in neural networks

    OpenAIRE

    Savtchenko, L P; Rusakov, D. A.

    2014-01-01

    Rhythmic activity of the brain often depends on synchronized spiking of interneuronal networks interacting with principal neurons. The quest for physiological mechanisms regulating network synchronization has therefore been firmly focused on synaptic circuits. However, it has recently emerged that synaptic efficacy could be influenced by astrocytes that release signalling molecules into their macroscopic vicinity. To understand how this volume-limited synaptic regulation can affect oscillatio...

  18. Power network transient stability electronics emulator using mixed-signal calibration

    OpenAIRE

    Lanz, Guillaume; Fabre, Laurent; Lilis, Georgios; Kyriakidis, Theodoros; Sallin, Denis; Cherkaoui, Rachid; Kayal, Maher

    2013-01-01

    The emerging field of power system emulation for real time smart grid management is very demanding in terms of speed and accuracy. This paper provides detailed information about the electronics calibration process of a high-speed power network emulator dedicated to the transient stability analysis of power systems. This emulator uses mixed-signal hardware to model the dynamic behavior of a power network. Special design allows the self-calibration of the analog electronics through successive m...

  19. Design of Transparent Distributed IMS Network: Security Challenges Risk and Signaling Analysis

    OpenAIRE

    Hamid Allouch; Mostafa Belkasmi

    2013-01-01

    The IP Multimedia subsystem (IMS) based on SIP as mechanism signalling and interfaces with otherservers using OSA (Open Service Access) and CAMEL (Customized Applications for Mobile networkEnhanced Logic).Is responsible for the interconnection of IP packets with other network, IMS support datacommunication services, voice, video, messaging and web-based technologies. In this work we present adistributed design of architecture that turns up some challenges of transparent mobility on the secure...

  20. Chemokine Signaling Directs Trunk Lymphatic Network Formation along the Preexisting Blood Vasculature

    OpenAIRE

    Cha, Young Ryun; Fujita, Misato; Butler, Matthew; Isogai, Sumio; Kochhan, Eva; Siekmann, Arndt F; Weinstein, Brant M

    2012-01-01

    The lymphatic system is crucial for fluid homeostasis, immune responses, and numerous pathological processes. However, the molecular mechanisms responsible for establishing the anatomical form of the lymphatic vascular network remain largely unknown. Here, we show that chemokine signaling provides critical guidance cues directing early trunk lymphatic network assembly and patterning. The chemokine receptors Cxcr4a and Cxcr4b are expressed in lymphatic endothelium, while chemokine ligands Cxcl...

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

    International Nuclear Information System (INIS)

    Neural networks are used to help distinguish the ZZ→l+l--jet-jet signal produced by the decay of a 400 GeV Higgs boson at a proton-proton collider energy of 15 TeV from the open-quote open-quote ordinary close-quote close-quote QCD Z+jets background. The ideal case where only one event at a time enters the detector (no pileup) and the case of multiple interactions per beam crossing (pileup) are examined. In both cases, when used in conjunction with the standard cuts, neural networks provide an additional signal-to-background enhancement. copyright 1996 The American Physical Society

  2. Common corruption of the mTOR signaling network in human tumors

    Science.gov (United States)

    Menon, Suchithra; Manning, Brendan D.

    2013-01-01

    Summary The mammalian Target of Rapamycin (mTOR) is responsive to numerous extracellular and intracellular cues and, through the formation of two physically and functionally distinct complexes, plays a central role in the homeostatic control of cell growth, proliferation and survival. Through aberrant activation of mTOR signaling, the perception of cellular growth signals becomes disconnected from the processes promoting cell growth, and this underlies the pathophysiology of a number of genetic tumor syndromes and cancers. Here, we review the oncogenes and tumor suppressors comprising the regulatory network upstream of mTOR, highlight the human cancers in which mTOR is activated, and discuss how dysregulated mTOR signaling gives tumors a selective growth advantage. In addition, we discuss why activation of mTOR, as a consequence of distinct oncogenic events, results in diverse clinical outcomes, and how the complexity of the mTOR signaling network might dictate therapeutic approaches. PMID:19956179

  3. Neighbor Discovery in a Wireless Sensor Network: Multipacket Reception Capability and Physical-Layer Signal Processing

    CERN Document Server

    Jeon, Jeongho

    2011-01-01

    In randomly deployed networks, such as sensor networks, an important problem for each node is to discover its \\textit{neighbor} nodes so that the connectivity amongst nodes can be established. In this paper, we consider this problem by incorporating the physical layer parameters in contrast to the most of the previous work which assumed a collision channel. Specifically, the pilot signals that nodes transmit are successfully decoded if the strength of the received signal relative to the interference is sufficiently high. Thus, each node must extract signal parameter information from the superposition of an unknown number of received signals. This problem falls naturally in the purview of random set theory (RST) which generalizes standard probability theory by assigning \\textit{sets}, rather than values, to random outcomes. The contributions in the paper are twofold: first, we introduce the realistic effect of physical layer considerations in the evaluation of the performance of \\textit{logical} discovery algo...

  4. Research of Crossbar Switch of High Performance Network of Signal Processing System

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The new type of embedded signal processing system based on the packet switched network is achieved. According to the application field and the characteristics of signal processing system, the RapidIO protocol is used to solve the high-speed interconnection of multi-digital signal processor (DSP). Based on this protocol, a kind of crossbar switch module which is used to interconnect multi-DSP in the system is introduced. A route strategy, some flow control rules and error control rules, which adapt to different RapidIO network topology are also introduced. Crossbar switch performance is analyzed in detail by the probability module. By researching the technique of crossbar switch and analyzing the system performance, it has a significant meaning for building the general signal processing system.

  5. ECG Signals Classification Based on Wavelet Transform and Probabilistic Neural Networks

    Directory of Open Access Journals (Sweden)

    Iman Moazen

    2009-09-01

    Full Text Available In this paper a very intelligent tool with low computational complexity is presented for Electroencephalogram (ECG signal classification. The proposed classifier is based on Discrete Wavelet Transform (DWT and Probabilistic Neural Network (PNN. The novelty of this approach is that signal statistics, morphological analysis and DWT of the histogram of signal (density estimation altogether have been used to achieve a higher recognition rate. ECG signals and their density estimation are decomposed into sub-classes using DWT. A PNN is used to classify ECG signals using statistical discriminating features which are extracted from ECG and its sub-classes. Experimental results on five classes of ECG signals from MIT-BIH arrhythmia database show that the proposed method learns very fast, low computational complexity, and a very high performance compared to the previous methods.

  6. Signal reconstruction in wireless sensor networks based on a cubature Kalman particle filter

    International Nuclear Information System (INIS)

    For solving the issues of the signal reconstruction of nonlinear non-Gaussian signals in wireless sensor networks (WSNs), a new signal reconstruction algorithm based on a cubature Kalman particle filter (CKPF) is proposed in this paper. We model the reconstruction signal first and then use the CKPF to estimate the signal. The CKPF uses a cubature Kalman filter (CKF) to generate the importance proposal distribution of the particle filter and integrates the latest observation, which can approximate the true posterior distribution better. It can improve the estimation accuracy. CKPF uses fewer cubature points than the unscented Kalman particle filter (UKPF) and has less computational overheads. Meanwhile, CKPF uses the square root of the error covariance for iterating and is more stable and accurate than the UKPF counterpart. Simulation results show that the algorithm can reconstruct the observed signals quickly and effectively, at the same time consuming less computational time and with more accuracy than the method based on UKPF. (general)

  7. Reconstruction of physiological signals using iterative retraining and accumulated averaging of neural network models.

    Science.gov (United States)

    McBride, Joseph; Sullivan, Adam; Xia, Henian; Petrie, Adam; Zhao, Xiaopeng

    2011-06-01

    Real-time monitoring of vital physiological signals is of significant clinical relevance. Disruptions in the signals are frequently encountered and make it difficult for precise diagnosis. Thus, the ability to accurately predict/recover the lost signals could greatly impact medical research and application. We have developed new techniques of signal reconstructions based on iterative retraining and accumulated averaging of neural networks. The effectiveness and robustness of these techniques are demonstrated using data records from the Computing in Cardiology/PhysioNet Challenge 2010. The average correlation coefficient between prediction and target for 100 records of various target signals is about 0.9. We have also explored influences of a few important parameters on the accuracy of reconstructions. The developed techniques may be used to detect changes in patient state and to recognize intervals of signal corruption. PMID:21566268

  8. Reconstruction of physiological signals using iterative retraining and accumulated averaging of neural network models

    International Nuclear Information System (INIS)

    Real-time monitoring of vital physiological signals is of significant clinical relevance. Disruptions in the signals are frequently encountered and make it difficult for precise diagnosis. Thus, the ability to accurately predict/recover the lost signals could greatly impact medical research and application. We have developed new techniques of signal reconstructions based on iterative retraining and accumulated averaging of neural networks. The effectiveness and robustness of these techniques are demonstrated using data records from the Computing in Cardiology/PhysioNet Challenge 2010. The average correlation coefficient between prediction and target for 100 records of various target signals is about 0.9. We have also explored influences of a few important parameters on the accuracy of reconstructions. The developed techniques may be used to detect changes in patient state and to recognize intervals of signal corruption

  9. Network Signaling Channel for Improving ZigBee Performance in Dynamic Cluster-Tree Networks

    Directory of Open Access Journals (Sweden)

    D. Hämäläinen

    2008-03-01

    Full Text Available ZigBee is one of the most potential standardized technologies for wireless sensor networks (WSNs. Yet, sufficient energy-efficiency for the lowest power WSNs is achieved only in rather static networks. This severely limits the applicability of ZigBee in outdoor and mobile applications, where operation environment is harsh and link failures are common. This paper proposes a network channel beaconing (NCB algorithm for improving ZigBee performance in dynamic cluster-tree networks. NCB reduces the energy consumption of passive scans by dedicating one frequency channel for network beacon transmissions and by energy optimizing their transmission rate. According to an energy analysis, the power consumption of network maintenance operations reduces by 70%–76% in dynamic networks. In static networks, energy overhead is negligible. Moreover, the service time for data routing increases up to 37%. The performance of NCB is validated by ns-2 simulations. NCB can be implemented as an extension on MAC and NWK layers and it is fully compatible with ZigBee.

  10. Development of a high throughput screen for allosteric modulators of melanocortin-4 receptor signaling using a real time cAMP assay.

    Science.gov (United States)

    Pantel, Jacques; Williams, Savannah Y; Mi, Dehui; Sebag, Julien; Corbin, Jackie D; Weaver, C David; Cone, Roger D

    2011-06-11

    The melanocortin MC(4) receptor is a potential target for the development of drugs for both obesity and cachexia. Melanocortin MC(4) receptor ligands known thus far are orthosteric agonists or antagonists, however the agonists, in particular, have generally exhibited unwanted side effects. For some receptors, allosteric modulators are expected to reduce side-effect profiles. To identify allosteric modulators of the melanocortin MC(4) receptor, we created HEK293 cell lines coexpressing the human melanocortin MC(4) receptor and a modified luciferase-based cAMP sensor. Monitoring luminescence as a readout of real-time intracellular cAMP concentration, we demonstrate that this cell line is able to report melanocortin agonist responses, as well as inverse agonist response to the physiological AgRP peptide. Based on the MC4R-GLO cell line, we developed an assay that was shown to meet HTS standards (Z'=0.50). A pilot screen run on the Microsource Spectrum compound library (n=2000) successfully identified 62 positive modulators. This screen identified predicted families of compounds: β(2)AR agonists - the β(2)AR being endogenously expressed in HEK293 cells, an adenylyl cyclase activator and finally a distribution of phosphodiesterase (PDE) inhibitors well characterized or recently identified. In this last category, we identified a structural family of coumarin-derived compounds (imperatorin, osthol and prenyletin), along with deracoxib, a drug in veterinary use for its COX2 inhibitory properties. This latter finding unveiled a new off-target mechanism of action for deracoxib as a PDE inhibitor. Overall, these data are the first report of a HTS for allosteric modulators for a Gs protein coupled receptor. PMID:21296065

  11. MONITORING NETWORK STRUCTURE AND CONTENT QUALITY OF SIGNAL PROCESSING ARTICLES ON WIKIPEDIA

    OpenAIRE

    Lee, Tao-Chun; Unnikrishnan, Jayakrishnan

    2013-01-01

    Wikipedia has become a widely-used resource on signal processing. However, the freelance-editing model of Wikipedia makes it challenging to maintain a high content quality. We develop techniques to monitor the network structure and content quality of Signal Processing (SP) articles on Wikipedia. Using metrics to quantify the importance and quality of articles, we generate a list of SP articles on Wikipedia arranged in the order of their need for improvement. The tools we use include the HITS ...

  12. Wireless Body Area Network in a Ubiquitous Healthcare System for Physiological Signal Monitoring and Health Consulting

    OpenAIRE

    Joonyoung Jung; Kiryong Ha; Jeonwoo Lee; Youngsung Kim; Daeyoung Kim

    2008-01-01

    We developed a ubiquitous healthcare system consisted of aphysiological signal devices, a mobile system, a device provider system, a healthcare service provider system, a physician system, and a healthcare personal system. In this system, wireless body area network (WBAN) such as ZigBee is used to communicate between physiological signal devices and the mobile system. WBAN device needs a specific function for ubiquitous healthcare application. We propose a scanning algorithm, dynamic discover...

  13. Deciphering the hormonal signalling network behind the systemic resistance induced by Trichoderma harzianum in tomato

    OpenAIRE

    Martínez-Medina, Ainhoa; Fernández, Iván; Sánchez-Guzmán, María J.; Jung, Sabine C.; Pascual, Jose A.; Pozo, María J.

    2013-01-01

    Root colonization by selected Trichoderma isolates can activate in the plant a systemic defense response that is effective against a broad-spectrum of plant pathogens. Diverse plant hormones play pivotal roles in the regulation of the defense signaling network that leads to the induction of systemic resistance triggered by beneficial organisms [induced systemic resistance (ISR)]. Among them, jasmonic acid (JA) and ethylene (ET) signaling pathways are generally essential for ISR. However, Tric...

  14. Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo.

    Science.gov (United States)

    Deignan, Lisa; Pinheiro, Marco T; Sutcliffe, Catherine; Saunders, Abbie; Wilcockson, Scott G; Zeef, Leo A H; Donaldson, Ian J; Ashe, Hilary L

    2016-07-01

    The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA-seq with Mad and Brinker ChIP-seq to decipher the BMP-responsive transcriptional network underpinning differentiation of the dorsal ectoderm during dorsal-ventral axis patterning. We identify multiple new BMP target genes, including positive and negative regulators of EGF signaling. Manipulation of EGF signaling levels by loss- and gain-of-function studies reveals that EGF signaling negatively regulates embryonic BMP-responsive transcription. Therefore, the BMP gene network has a self-regulating property in that it establishes a balance between its activity and that of the antagonistic EGF signaling pathway to facilitate correct patterning. In terms of BMP-dependent transcription, we identify key roles for the Zelda and Zerknüllt transcription factors in establishing the resulting expression domain, and find widespread binding of insulator proteins to the Mad and Brinker-bound genomic regions. Analysis of embryos lacking the BEAF-32 insulator protein shows reduced transcription of a peak BMP target gene and a reduction in the number of amnioserosa cells, the fate specified by peak BMP signaling. We incorporate our findings into a model for Mad-dependent activation, and discuss its relevance to BMP signal interpretation in vertebrates. PMID:27379389

  15. Nuclease-Resistant c-di-AMP Derivatives That Differentially Recognize RNA and Protein Receptors.

    Science.gov (United States)

    Meehan, Robert E; Torgerson, Chad D; Gaffney, Barbara L; Jones, Roger A; Strobel, Scott A

    2016-02-16

    The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3'-5'-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activates specific pathways and mediates phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogues, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position more than a carbonyl at the C6 position. We also identified phosphate-modified analogues that bind both the ydaO RNA and GdpP protein with high affinity, whereas symmetrically modified ribose analogues exhibited a substantial decrease in ydaO affinity but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogues could be useful as chemical tools to specifically target subsections of second-messenger signaling pathways. PMID:26789423

  16. Signal Network Analysis of Plant Genes Responding to Ionizing Radiation

    International Nuclear Information System (INIS)

    In this project, we irradiated Arabidopsis plants with various doses of gamma-rays at the vegetative and reproductive stages to assess their radiation sensitivity. After the gene expression profiles and an analysis of the antioxidant response, we selected several Arabidopsis genes for uses of 'Radio marker genes (RMG)' and conducted over-expression and knock-down experiments to confirm the radio sensitivity. Based on these results, we applied two patents for the detection of two RMG (At3g28210 and At4g37990) and development of transgenic plants. Also, we developed a Genechip for use of high-throughput screening of Arabidopsis genes responding only to ionizing radiation and identified RMG to detect radiation leaks. Based on these results, we applied two patents associated with the use of Genechip for different types of radiation and different growth stages. Also, we conducted co-expression network study of specific expressed probes against gamma-ray stress and identified expressed patterns of duplicated genes formed by whole/500kb segmental genome duplication

  17. A wireless sensor network for monitoring volcano-seismic signals

    Science.gov (United States)

    Lopes Pereira, R.; Trindade, J.; Gonçalves, F.; Suresh, L.; Barbosa, D.; Vazão, T.

    2014-12-01

    Monitoring of volcanic activity is important for learning about the properties of each volcano and for providing early warning systems to the population. Monitoring equipment can be expensive, and thus the degree of monitoring varies from volcano to volcano and from country to country, with many volcanoes not being monitored at all. This paper describes the development of a wireless sensor network (WSN) capable of collecting geophysical measurements on remote active volcanoes. Our main goals were to create a flexible, easy-to-deploy and easy-to-maintain, adaptable, low-cost WSN for temporary or permanent monitoring of seismic tremor. The WSN enables the easy installation of a sensor array in an area of tens of thousands of m2, allowing the location of the magma movements causing the seismic tremor to be calculated. This WSN can be used by recording data locally for later analysis or by continuously transmitting it in real time to a remote laboratory for real-time analyses. We present a set of tests that validate different aspects of our WSN, including a deployment on a suspended bridge for measuring its vibration.

  18. 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.

  19. CLASSIFICATIONS OF EEG SIGNALS FOR MENTAL TASKS USING ADAPTIVE RBF NETWORK

    Institute of Scientific and Technical Information of China (English)

    薛建中; 郑崇勋; 闫相国

    2004-01-01

    Objective This paper presents classifications of mental tasks based on EEG signals using an adaptive Radial Basis Function (RBF) network with optimal centers and widths for the Brain-Computer Interface (BCI) schemes. Methods Initial centers and widths of the network are selected by a cluster estimation method based on the distribution of the training set. Using a conjugate gradient descent method, they are optimized during training phase according to a regularized error function considering the influence of their changes to output values. Results The optimizing process improves the performance of RBF network, and its best cognition rate of three task pairs over four subjects achieves 87.0%. Moreover, this network runs fast due to the fewer hidden layer neurons. Conclusion The adaptive RBF network with optimal centers and widths has high recognition rate and runs fast. It may be a promising classifier for on-line BCI scheme.

  20. Transduction motif analysis of gastric cancer based on a human signaling network

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  1. Transduction motif analysis of gastric cancer based on a human signaling network

    International Nuclear Information System (INIS)

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs

  2. 平性药桃仁对寒热不同血瘀证大鼠cAMP-PKA信号通路的影响%Study on the Regulation Role of Semen Persicae to cAMP-PKA Signal Pathway in the Rats with Cold and Heat Blood Stasis Syndrome

    Institute of Scientific and Technical Information of China (English)

    郝二伟; 邓家刚; 杜正彩; 包传红; 芦晓燕; 邓秀琼; 唐志玲

    2013-01-01

    model control groups were orally given water,2 times/day,20 mL/kg,for 7 days.Experiments in rats with cold and heat blood stasis syndromes were carried on respectiverly.In heat blood stasis syndromes,except normal control group,the other groups were intraperitoneally injected 10% carrageenan,5 mL/kg,1 times/day,for 3 days;24 hours after the last injection,subcutaneously injected 20% dry yeast suspension,10 mL/kg.In cold blood stasis syndromes,except normal control group,the other groups were put into fridge,temperature-(18 ± 2) ℃,2 hours/ times,2 times/day,for 7 days.Separately draw 5ml abdominal aortic blood and taken abdominal aorta,6 hours and 12 hours after finishing the model in the two syndromes.Tested the cAMP content by elisa,tested the PKA protein expression by Western blot.Results:Semen Persicae with neutral property,could decrease the content of cAMP in plasma(P < 0.01),inhibit the expression of protein PKA (P < 0.05) in rats with heat stagnation and blood stasis syndrome,increase the plasma content of cAMP(P < 0.01) and increase the expression of protein PKA (P <0.01)in rats with cold stagnation and blood stasis syndrome.Semen Persicae had two-way adjustment action on CAMP-PKA signal pathway.Conclusion:In different internal environment of heat stagnation and blood stasis syndrome,cold stagnation and blood stasis syndrome,Semen Persicae with neutral property has two-way adjustment to cAMP-PKA signaling channel,which may be one of the mechanism of it's two-way application.

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

    International Nuclear Information System (INIS)

    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.

  4. Towards convergence of wireless and wireline signal transport in broadband access networks

    DEFF Research Database (Denmark)

    Yu, Xianbin; Prince, Kamau; Tafur Monroy, Idelfonso

    2010-01-01

    Hybrid optical wireless access networks are to play an important role in the realization of the vision of delivery of broadband services to the end-user any time, anywhere and at affordable costs. We present results of experiments conducted over a field deployed optical fibre links we successfull...... demonstrated converged wireless and wireline signal transport over a common fibre infrastructure. The type of signal used in this field deployed experiments cover WiMax, Impulse-radio ultra-wideband (UWB) and coherent transmission of baseband QPSK and radio-over-fibre signals....

  5. A network signal amplification strategy of ultrasensitive photoelectrochemical immunosensing carcinoembryonic antigen based on CdSe/melamine network as label.

    Science.gov (United States)

    Li, Jiaojiao; Zhang, Yong; Kuang, Xuan; Wang, Zhiling; Wei, Qin

    2016-11-15

    Taking advantage of CdSe/melamine network as label and Au-TiO2 as substrate, this work developed a novel kind of signal amplification strategy for fabricating photoelectrochemical (PEC) immunoassay. The melamine, a star-shaped triamino molecule, was firstly used for readily capturing CdSe QDs and forming a CdSe/melamine network, which was formed through strong interactions between the carboxyl groups of TGA-stabilized CdSe QDs and the three amino groups of each melamine molecule. In this strategy, the primary antibody (Ab1) was immobilized onto Au-TiO2 substrate, which made the photoelectric conversion efficiency increase significantly. After the formed Ab2-CdSe/melamine network labels were captured onto the electrode surface via the specific antibody-antigen interaction, the photoelectric activity could be further enhanced via the interaction between the Au-TiO2 substrate and CdSe/melamine network. Due to this amplification of PEC signals and the special structure of the label, the fabricated PEC immunosensor was applied for sensitive and specific detection of cancer biomarker carcinoembryonic antigen (CEA), and displayed a wide linear range (0.005-1000ngmL(-1)) and low detection limit (5pgmL(-1)). In addition, the immunosensor was performed with good stability and reproducibility, and the results to analyze human serum samples were satisfactory. PMID:27281106

  6. Neural network approach of active ultrasonic signals for structural health monitoring analysis

    Science.gov (United States)

    Kral, Zachary; Horn, Walter; Steck, James

    2009-03-01

    Maintenance is an important issue for aerospace systems, since they are in service beyond their designed lifetime. This requires scheduled inspections and damage repair before failure. Research is in progress to develop a structural health monitoring system (SHMS) to improve this maintenance routine. Ultrasonic testing, utilizing a system of piezoelectric actuators and sensors, is a promising concept Measured wave signals are compared with signals for previously scanned states. Changes to the signal could be the result of damage to the component. This paper focuses on analyzing the differences of states, using artificial neural networks. Neural network analysis has the potential of creating a SHMS of greater ability and processing. Experiments were performed on a thin, flat aluminum panel. Ultrasonic actuators and sensors were installed and a baseline scan was performed on the undamaged panel. Simulated damage was introduced in specific areas, and scans were conducted for several damaged states. Neural networks were created to assess the changing conditions of the panel. The system was later tested on a lap joint specimen to confirm the abilities of the neural network. This form of analysis performed well at locating and quantifying areas of change within the structure. The neural network performance indicated that it has a role in the SHMS of aerospace structures.

  7. The interplay between cyclic AMP and insulin during obesity development

    DEFF Research Database (Denmark)

    Borkowski, Kamil

    Insulin and cAMP signalling are related to two opposite metabolic responses. Insulin secretion is elicited in response to food availability and trigger catabolic processes like lipogenesis and glycogen synthesis with a purpose of energy storage. On the other hand cAMP signalling is associated wit...... insulin signalling. Moreover, I am investigating how increased insulin secretion caused by sucrose consumption, affects insulin signaling in peripheral tissues....

  8. Spontaneous calcium signals induced by gap junctions in a network model of astrocytes

    Science.gov (United States)

    Kazantsev, V. B.

    2009-01-01

    The dynamics of a network model of astrocytes coupled by gap junctions is investigated. Calcium dynamics of the single cell is described by the biophysical model comprising the set of three nonlinear differential equations. Intercellular dynamics is provided by the diffusion of inositol 1,4,5-trisphosphate (IP3) through gap junctions between neighboring astrocytes. It is found that the diffusion induces the appearance of spontaneous activity patterns in the network. Stability of the network steady state is analyzed. It is proved that the increase of the diffusion coefficient above a certain critical value yields the generation of low-amplitude subthreshold oscillatory signals in a certain frequency range. It is shown that such spontaneous oscillations can facilitate calcium pulse generation and provide a certain time scale in astrocyte signaling.

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

    International Nuclear Information System (INIS)

    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

  10. Signaling and Gene Regulatory Networks Governing Definitive Endoderm Derivation From Pluripotent Stem Cells.

    Science.gov (United States)

    Mohammadnia, Abdulshakour; Yaqubi, Moein; Pourasgari, Farzaneh; Neely, Eric; Fallahi, Hossein; Massumi, Mohammad

    2016-09-01

    The generation of definitive endoderm (DE) from pluripotent stem cells (PSCs) is a fundamental stage in the formation of highly organized visceral organs, such as the liver and pancreas. Currently, there is a need for a comprehensive study that illustrates the involvement of different signaling pathways and their interactions in the derivation of DE cells from PSCs. This study aimed to identify signaling pathways that have the greatest influence on DE formation using analyses of transcriptional profiles, protein-protein interactions, protein-DNA interactions, and protein localization data. Using this approach, signaling networks involved in DE formation were constructed using systems biology and data mining tools, and the validity of the predicted networks was confirmed experimentally by measuring the mRNA levels of hub genes in several PSCs-derived DE cell lines. Based on our analyses, seven signaling pathways, including the BMP, ERK1-ERK2, FGF, TGF-beta, MAPK, Wnt, and PIP signaling pathways and their interactions, were found to play a role in the derivation of DE cells from PSCs. Lastly, the core gene regulatory network governing this differentiation process was constructed. The results of this study could improve our understanding surrounding the efficient generation of DE cells for the regeneration of visceral organs. J. Cell. Physiol. 231: 1994-2006, 2016. © 2016 Wiley Periodicals, Inc. PMID:26755186

  11. The Signal Extraction of Fetal Heart Rate Based on Wavelet Transform and BP Neural Network

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-hong; ZHANG Bang-cheng; FU Hu-dai

    2005-01-01

    This paper briefly introduces the collection and recognition of biomedical signals, designs the method to collect FM signals. A detailed discussion on the system hardware, structure and functions is also given. Under LabWindows/CVI, the hardware and the driver do compatible, the hardware equipment work properly actively. The paper adopts multi threading technology for real-time analysis and makes use of latency time of CPU effectively, expedites program reflect speed, improves the program to perform efficiency. One threading is collecting data; the other threading is analyzing data. Using the method, it is broaden to analyze the signal in real-time. Wavelet transform to remove the main interference in the FM and by adding time-window to recognize with BP network; Finally the results of collecting signals and BP networks are discussed. 8 pregnant women' s signals of FM were collected successfully by using the sensor. The correct of BP network recognition is about 83.3% by using the above measure.

  12. Multitask learning of signaling and regulatory networks with application to studying human response to flu.

    Directory of Open Access Journals (Sweden)

    Siddhartha Jain

    2014-12-01

    Full Text Available Reconstructing regulatory and signaling response networks is one of the major goals of systems biology. While several successful methods have been suggested for this task, some integrating large and diverse datasets, these methods have so far been applied to reconstruct a single response network at a time, even when studying and modeling related conditions. To improve network reconstruction we developed MT-SDREM, a multi-task learning method which jointly models networks for several related conditions. In MT-SDREM, parameters are jointly constrained across the networks while still allowing for condition-specific pathways and regulation. We formulate the multi-task learning problem and discuss methods for optimizing the joint target function. We applied MT-SDREM to reconstruct dynamic human response networks for three flu strains: H1N1, H5N1 and H3N2. Our multi-task learning method was able to identify known and novel factors and genes, improving upon prior methods that model each condition independently. The MT-SDREM networks were also better at identifying proteins whose removal affects viral load indicating that joint learning can still lead to accurate, condition-specific, networks. Supporting website with MT-SDREM implementation: http://sb.cs.cmu.edu/mtsdrem.

  13. Multitask Learning of Signaling and Regulatory Networks with Application to Studying Human Response to Flu

    Science.gov (United States)

    Jain, Siddhartha; Gitter, Anthony; Bar-Joseph, Ziv

    2014-01-01

    Reconstructing regulatory and signaling response networks is one of the major goals of systems biology. While several successful methods have been suggested for this task, some integrating large and diverse datasets, these methods have so far been applied to reconstruct a single response network at a time, even when studying and modeling related conditions. To improve network reconstruction we developed MT-SDREM, a multi-task learning method which jointly models networks for several related conditions. In MT-SDREM, parameters are jointly constrained across the networks while still allowing for condition-specific pathways and regulation. We formulate the multi-task learning problem and discuss methods for optimizing the joint target function. We applied MT-SDREM to reconstruct dynamic human response networks for three flu strains: H1N1, H5N1 and H3N2. Our multi-task learning method was able to identify known and novel factors and genes, improving upon prior methods that model each condition independently. The MT-SDREM networks were also better at identifying proteins whose removal affects viral load indicating that joint learning can still lead to accurate, condition-specific, networks. Supporting website with MT-SDREM implementation: http://sb.cs.cmu.edu/mtsdrem PMID:25522349

  14. Cardiac cAMP: production, hydrolysis, modulation and detection.

    Science.gov (United States)

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability. PMID:26483685

  15. Insulin-like growth factor-1 (IGF-1 induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB by activating different signaling pathways in PC12 cells

    Directory of Open Access Journals (Sweden)

    Zheng Wen-Hua

    2006-06-01

    Full Text Available Abstract Background Insulin-like growth factor-1 (IGF-1 is a polypeptide growth factor with a variety of functions in both neuronal and non-neuronal cells. IGF-1 plays anti-apoptotic and other functions by activating multiple signaling pathways including Akt kinase, a serine/threonine kinase essential for cell survival. The nuclear transcription factor cAMP response element-binding protein (CREB may also be involved although relationships between these two proteins in IGF-1 receptor signaling and protection is not clear, especially in neuronal cells. Results IGF-1, in a concentration- and time-dependent manner, induces the activation/phosphorylation of Akt and CREB in PC12 cells by activating different signaling pathways. IGF-1 induced a sustained phosphorylation of Akt while only a transient one was seen for CREB. The phosphorylation of Akt is mediated by the PI3 kinase pathway while that of CREB is dependent on the activation of both MAPK kinase and p38 MAPK. Moreover, the stimulation of PKC attenuated the phosphorylation of Akt induced by IGF-1 while enhancing that of CREB. Survival assays with various kinase inhibitors suggested that the activation/phosphorylation of both Akt and CREB contributes to IGF-1 mediated cell survival in PC12 cells. Conclusion These data suggest that IGF-1 induced the activation of Akt and CREB using distinct pathways in PC12 cells.

  16. DMPD: The interferon signaling network and transcription factor C/EBP-beta. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18163952 The interferon signaling network and transcription factor C/EBP-beta. Li H..., Gade P, Xiao W, Kalvakolanu DV. Cell Mol Immunol. 2007 Dec;4(6):407-18. (.png) (.svg) (.html) (.csml) Show The... interferon signaling network and transcription factor C/EBP-beta. PubmedID 18163952 Title The interfero

  17. Detection and classification of cardiac ischemia using vectorcardiogram signal via neural network

    Directory of Open Access Journals (Sweden)

    Ali Reza Mehri Dehnavi

    2011-01-01

    Full Text Available Background: Various techniques are used in diagnosing cardiac diseases. The electrocardiogram is one of these tools in common use. In this study vectorcardiogram (VCG signals are used as a tool for detection of cardiac ischemia. Methods: VCG signals used in this study were obtained form 60 patients suspected to have ischemia disease and 10 normal candidates. Verification of the ischemia had done by the cardiologist during strain test by the evaluation of electrocardiogram (ECG records and patient′s clinical history. The recorder device was Cardiax digital recorder system. The VCG signals were recorded in Frank lead configuration system. Results: Extracted ischemia VCG signals have been configured with 22 features. Feature dimensionalities were reduced by the use of Independent Components Analysis and Principal Component Analysis tools. Results obtained from strain test indicated that among 60 subjects, 50 had negative results and 10 had positive results. Ischemia detection of neural network using VCG parameters indicates 86% accuracy. Classification result on neural network using ECG ischemia detection parameters is 73% accurate. Accumulative evaluation including VCG analysis and strain test indicates 90% consistency. Conclusions: Regarding the obtained results in this study, VCG has higher accuracy than ECG, so that in cases which ECG signal cannot provide certain diagnosis of existence or non-existence of ischemia, VCG signal can help in a wider range. We suggest the use of VCG as an auxiliary low cost tool in ischemia detection.

  18. Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Neves-dos-Santos Sandra

    2010-01-01

    Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

  19. A signal combining technique based on channel shortening for cooperative sensor networks

    KAUST Repository

    Hussain, Syed Imtiaz

    2010-06-01

    The cooperative relaying process needs proper coordination among the communicating and the relaying nodes. This coordination and the required capabilities may not be available in some wireless systems, e.g. wireless sensor networks where the nodes are equipped with very basic communication hardware. In this paper, we consider a scenario where the source node transmits its signal to the destination through multiple relays in an uncoordinated fashion. The destination can capture the multiple copies of the transmitted signal through a Rake receiver. We analyze a situation where the number of Rake fingers N is less than that of the relaying nodes L. In this case, the receiver can combine N strongest signals out of L. The remaining signals will be lost and act as interference to the desired signal components. To tackle this problem, we develop a novel signal combining technique based on channel shortening. This technique proposes a processing block before the Rake reception which compresses the energy of L signal components over N branches while keeping the noise level at its minimum. The proposed scheme saves the system resources and makes the received signal compatible to the available hardware. Simulation results show that it outperforms the selection combining scheme. ©2010 IEEE.

  20. High-throughput mathematical analysis identifies Turing networks for patterning with equally diffusing signals

    Science.gov (United States)

    Marcon, Luciano; Diego, Xavier; Sharpe, James; Müller, Patrick

    2016-01-01

    The Turing reaction-diffusion model explains how identical cells can self-organize to form spatial patterns. It has been suggested that extracellular signaling molecules with different diffusion coefficients underlie this model, but the contribution of cell-autonomous signaling components is largely unknown. We developed an automated mathematical analysis to derive a catalog of realistic Turing networks. This analysis reveals that in the presence of cell-autonomous factors, networks can form a pattern with equally diffusing signals and even for any combination of diffusion coefficients. We provide a software (available at http://www.RDNets.com) to explore these networks and to constrain topologies with qualitative and quantitative experimental data. We use the software to examine the self-organizing networks that control embryonic axis specification and digit patterning. Finally, we demonstrate how existing synthetic circuits can be extended with additional feedbacks to form Turing reaction-diffusion systems. Our study offers a new theoretical framework to understand multicellular pattern formation and enables the wide-spread use of mathematical biology to engineer synthetic patterning systems. DOI: http://dx.doi.org/10.7554/eLife.14022.001 PMID:27058171

  1. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks

    Science.gov (United States)

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-03-01

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains.

  2. High-throughput mathematical analysis identifies Turing networks for patterning with equally diffusing signals.

    Science.gov (United States)

    Marcon, Luciano; Diego, Xavier; Sharpe, James; Müller, Patrick

    2016-01-01

    The Turing reaction-diffusion model explains how identical cells can self-organize to form spatial patterns. It has been suggested that extracellular signaling molecules with different diffusion coefficients underlie this model, but the contribution of cell-autonomous signaling components is largely unknown. We developed an automated mathematical analysis to derive a catalog of realistic Turing networks. This analysis reveals that in the presence of cell-autonomous factors, networks can form a pattern with equally diffusing signals and even for any combination of diffusion coefficients. We provide a software (available at http://www.RDNets.com) to explore these networks and to constrain topologies with qualitative and quantitative experimental data. We use the software to examine the self-organizing networks that control embryonic axis specification and digit patterning. Finally, we demonstrate how existing synthetic circuits can be extended with additional feedbacks to form Turing reaction-diffusion systems. Our study offers a new theoretical framework to understand multicellular pattern formation and enables the wide-spread use of mathematical biology to engineer synthetic patterning systems. PMID:27058171

  3. Interrogating cAMP-dependent kinase signaling in jurkat T cells via a protein kinase A targeted immune-precipitation phosphoproteomics approach

    NARCIS (Netherlands)

    Giansanti, P.; Stokes, M.P.; Silva, J.C.; Scholten, A.; Heck, A.J.R.

    2013-01-01

    In the past decade, mass-spectrometry-based methods have emerged for the quantitative profiling of dynamic changes in protein phosphorylation, allowing the behavior of thousands of phosphorylation sites to be monitored in a single experiment. However, when one is interested in specific signaling pat

  4. Plant morphogenesis, auxin, and the signal-trafficking network incompleteness theorem

    Directory of Open Access Journals (Sweden)

    Karl J. Niklas

    2012-03-01

    Full Text Available Plant morphogenesis (the development of form and function requires signal-trafficking and cross-talking among all levels of organization to coordinate the operation of metabolic and genomic networked systems. Many if not all of these biological features can be rendered as logic circuits supervising the operation of one or more signal-activated metabolic or genome networks. This approach simplifies complex morphogenetic phenomena and allows for their aggregation into diagrams of larger, more "global" networked systems. This conceptualization is illustrated for morphogenesis in model plants such as maize (Zea mays and Thale cress (Arabidopsis thaliana from an evolutionary perspective. The phytohormone indole-acetic acid (IAA is used as an example for a well-known signaling chemical and discussed in terms of the logic circuits and signal-activated sub-systems for hormone-mediated wall loosening and cell expansion as well as polar/lateral intercellular IAA transport. For each of these phenomena, a circuit/sub-system diagram highlights missing components, either in the logic circuit or in the sub-system it supervises, that must be identified experimentally if each of these basic phenomena is to be fully understood within a phylogen

  5. Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis.

    Science.gov (United States)

    Newaz, Khalique; Sriram, K; Bera, Debajyoti

    2015-01-01

    Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC) to protease-resistant isofrom (rPrPSc). Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are) the prime network pathway(s) that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes) potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs) of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that these

  6. Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis.

    Directory of Open Access Journals (Sweden)

    Khalique Newaz

    Full Text Available Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC to protease-resistant isofrom (rPrPSc. Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are the prime network pathway(s that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that

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

    International Nuclear Information System (INIS)

    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)

  8. 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.

  9. Coded Single-Tone Signaling for Resource Coordination and Interference Management in Femtocell Networks

    CERN Document Server

    Yang, Chunliang

    2011-01-01

    Resource coordination and interference management is the key to achieving the benefits of femtocell networks. Over-the-air signaling is one of the most effective means for distributed dynamic resource coordination and interference management. However, the design of this type of signal is challenging. In this letter, we address the challenges and propose an effective solution, referred to as coded single-tone signaling (STS). The proposed coded STS scheme possesses certain highly desirable properties, such as no dedicated resource requirement (no overhead), no near-and-far effect, no inter-signal interference (no multi-user interference), low peak-to-average power ratio (deep coverage). In addition, the proposed coded STS can fully exploit frequency diversity and provides a means for high quality wideband channel estimation. The coded STS design is demonstrated through a concrete numerical example. Performance of the proposed coded STS is evaluated through simulations.

  10. Emerging roles of microRNAs in the Wnt signaling network.

    Science.gov (United States)

    Schepeler, Troels

    2013-01-01

    The Wnt signaling network is known to regulate many cellular processes and is of crucial importance during development and in pathological conditions, including cancer. Small noncoding RNAs from the microRNA family (miRNAs) are important elements in the post-transcriptional control of gene expression. In this work, I review the cross talk between miRNAs and the canonical Wnt signaling pathway in various biological processes with particular emphasis on carcinogenesis. Because alterations of miRNA activity and aberrant Wnt signaling are each intimately linked to tumor biology, deciphering the complex interplay between these two regulatory modules is essential to advance our understanding of the integrated functions of miRNAs in signal transduction cascades and develop rational treatment regimens against cancer. PMID:23614621

  11. 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.

  12. 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.

  13. Information Feedback Strategies in a Signal Controlled Network with Overlapped Routes

    Institute of Scientific and Technical Information of China (English)

    TIAN Li-Jun; HUANG Hai-Jun; LIU Tian-Liang

    2009-01-01

    We investigate the effects of four different information feedback strategies on the dynamics of traffic, travel-ers' route choice and the resultant system performance in a signal controlled network with overlapped routes.Simulation results given by the cellular automaton model show that the system purpose-based mean velocity feedback strategy and the congestion coefficient feedback strategy have more advantages in improving network utilization efficiency and reducing travelers' travel times. The travel time feedback strategy and the individual purposed-based mean velocity feedback strategy behave slightly better to ensure user equity.

  14. dNSP: a biologically inspired dynamic Neural network approach to Signal Processing.

    Science.gov (United States)

    Cano-Izquierdo, José Manuel; Ibarrola, Julio; Pinzolas, Miguel; Almonacid, Miguel

    2008-09-01

    The arriving order of data is one of the intrinsic properties of a signal. Therefore, techniques dealing with this temporal relation are required for identification and signal processing tasks. To perform a classification of the signal according with its temporal characteristics, it would be useful to find a feature vector in which the temporal attributes were embedded. The correlation and power density spectrum functions are suitable tools to manage this issue. These functions are usually defined with statistical formulation. On the other hand, in biology there can be found numerous processes in which signals are processed to give a feature vector; for example, the processing of sound by the auditory system. In this work, the dNSP (dynamic Neural Signal Processing) architecture is proposed. This architecture allows representing a time-varying signal by a spatial (thus statical) vector. Inspired by the aforementioned biological processes, the dNSP performs frequency decomposition using an analogical parallel algorithm carried out by simple processing units. The architecture has been developed under the paradigm of a multilayer neural network, where the different layers are composed by units whose activation functions have been extracted from the theory of Neural Dynamic [Grossberg, S. (1988). Nonlinear neural networks principles, mechanisms and architectures. Neural Networks, 1, 17-61]. A theoretical study of the behavior of the dynamic equations of the units and their relationship with some statistical functions allows establishing a parallelism between the unit activations and correlation and power density spectrum functions. To test the capabilities of the proposed approach, several testbeds have been employed, i.e. the frequencial study of mathematical functions. As a possible application of the architecture, a highly interesting problem in the field of automatic control is addressed: the recognition of a controlled DC motor operating state. PMID:18579344

  15. Simulation study on effects of signaling network structure on the developmental increase in complexity

    Energy Technology Data Exchange (ETDEWEB)

    Keranen, Soile V.E.

    2003-04-02

    The developmental increase in structural complexity in multicellular life forms depends on local, often non-periodic differences in gene expression. These depend on a network of gene-gene interactions coded within the organismal genome. To better understand how genomic information generates complex expression patterns, I have modeled the pattern forming behavior of small artificial genomes in virtual blastoderm embryos. I varied several basic properties of these genomic signaling networks, such as the number of genes, the distributions of positive (inductive) and negative (repressive) interactions, and the strengths of gene-gene interactions, and analyzed their effects on developmental pattern formation. The results show how even simple genomes can generate complex non-periodic patterns under suitable conditions. They also show how the frequency of complex patterns depended on the numbers and relative arrangements of positive and negative interactions. For example, negative co-regulation of signaling pathway components increased the likelihood of (complex) patterns relative to differential negative regulation of the pathway components. Interestingly, neither quantitative differences either in strengths of signaling interactions nor multiple response thresholds to signal concentration (as in morphogen gradients) were essential for formation of multiple, spatially unique cell types. Thus, with combinatorial code of gene regulation and hierarchical signaling interactions, it is theoretically possible to organize metazoan embryogenesis with just a small fraction of the metazoan genome. Because even small networks can generate complex patterns when they contain a suitable set of connections, evolution of metazoan complexity may have depended more on selection for favourable configurations of signaling interactions than on the increase in numbers of regulatory genes.

  16. Hypoxia induces a phase transition within a kinase signaling network in cancer cells.

    Science.gov (United States)

    Wei, Wei; Shi, Qihui; Remacle, Francoise; Qin, Lidong; Shackelford, David B; Shin, Young Shik; Mischel, Paul S; Levine, R D; Heath, James R

    2013-04-01

    Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)--a critical component of hypoxic signaling and a compelling cancer drug target--is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier's principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles. PMID:23530221

  17. Traffic Signals Control with Adaptive Fuzzy Controller in Urban Road Network

    Institute of Scientific and Technical Information of China (English)

    LI Yan; FAN Xiao-ping

    2008-01-01

    An adaptive fuzzy logic controller (AFC) is presented for the signal control of the urban traffic network.The AFC is composed of the signal control system-oriented control level and the signal controller-oriented fuzzy rules regulation level.The control level decides the signal tunings in an intersection with a fuzzy logic controller.The regulation level optimizes the fuzzy rules by the Adaptive Rule Module in AFC according to both the system performance index in current control period and the traffic flows in the last one.Consequently the system performances are improved.A weight coefficient controller (WCC) is also developed to describe the interactions of traffic flow among the adjacent intersections.So the AFC combined with the WCC can be applied in a road network for signal timings.Simulations of the AFC on a real traffic scenario have been conducted.Simulation results indicate that the adaptive controller for traffic control shows better performance than the actuated one.

  18. Wireless Network of Collaborative Physiological Signal Devices in a U-Healthcare System

    Science.gov (United States)

    Jung, Joonyoung; Kim, Daeyoung

    We designed and implemented collaborative physiological signal devices in a u-healthcare(ubiquitous healthcare) system. In this system, wireless body area network (WBAN) such as ZigBee is used to communicate between physiological signal devices and the mobile system. WBAN device needs a specific function for ubiquitous healthcare application. We show several collaborative physiological devices and propose WBAN mechanism such as a fast scanning algorithm, a dynamic discovery and installation mechanism, a reliable data transmission, a device access control for security, and a healthcare profile for u-healthcare system.

  19. Wireless Body Area Network in a Ubiquitous Healthcare System for Physiological Signal Monitoring and Health Consulting

    Directory of Open Access Journals (Sweden)

    Joonyoung Jung

    2008-12-01

    Full Text Available We developed a ubiquitous healthcare system consisted of aphysiological signal devices, a mobile system, a device provider system, a healthcare service provider system, a physician system, and a healthcare personal system. In this system, wireless body area network (WBAN such as ZigBee is used to communicate between physiological signal devices and the mobile system. WBAN device needs a specific function for ubiquitous healthcare application. We propose a scanning algorithm, dynamic discovery and installation, reliable data transmission, device access control, and a healthcare profile for ubiquitous healthcare system.

  20. The Applied Mathematics for Power Systems (AMPS)

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, Michael [Los Alamos National Laboratory

    2012-07-24

    Increased deployment of new technologies, e.g., renewable generation and electric vehicles, is rapidly transforming electrical power networks by crossing previously distinct spatiotemporal scales and invalidating many traditional approaches for designing, analyzing, and operating power grids. This trend is expected to accelerate over the coming years, bringing the disruptive challenge of complexity, but also opportunities to deliver unprecedented efficiency and reliability. Our Applied Mathematics for Power Systems (AMPS) Center will discover, enable, and solve emerging mathematics challenges arising in power systems and, more generally, in complex engineered networks. We will develop foundational applied mathematics resulting in rigorous algorithms and simulation toolboxes for modern and future engineered networks. The AMPS Center deconstruction/reconstruction approach 'deconstructs' complex networks into sub-problems within non-separable spatiotemporal scales, a missing step in 20th century modeling of engineered networks. These sub-problems are addressed within the appropriate AMPS foundational pillar - complex systems, control theory, and optimization theory - and merged or 'reconstructed' at their boundaries into more general mathematical descriptions of complex engineered networks where important new questions are formulated and attacked. These two steps, iterated multiple times, will bridge the growing chasm between the legacy power grid and its future as a complex engineered network.

  1. Wnt-signalling pathways and microRNAs network in carcinogenesis: experimental and bioinformatics approaches.

    Science.gov (United States)

    Onyido, Emenike K; Sweeney, Eloise; Nateri, Abdolrahman Shams

    2016-01-01

    Over the past few years, microRNAs (miRNAs) have not only emerged as integral regulators of gene expression at the post-transcriptional level but also respond to signalling molecules to affect cell function(s). miRNAs crosstalk with a variety of the key cellular signalling networks such as Wnt, transforming growth factor-β and Notch, control stem cell activity in maintaining tissue homeostasis, while if dysregulated contributes to the initiation and progression of cancer. Herein, we overview the molecular mechanism(s) underlying the crosstalk between Wnt-signalling components (canonical and non-canonical) and miRNAs, as well as changes in the miRNA/Wnt-signalling components observed in the different forms of cancer. Furthermore, the fundamental understanding of miRNA-mediated regulation of Wnt-signalling pathway and vice versa has been significantly improved by high-throughput genomics and bioinformatics technologies. Whilst, these approaches have identified a number of specific miRNA(s) that function as oncogenes or tumour suppressors, additional analyses will be necessary to fully unravel the links among conserved cellular signalling pathways and miRNAs and their potential associated components in cancer, thereby creating therapeutic avenues against tumours. Hence, we also discuss the current challenges associated with Wnt-signalling/miRNAs complex and the analysis using the biomedical experimental and bioinformatics approaches. PMID:27590724

  2. Cutting force signal pattern recognition using hybrid neural network in end milling

    Institute of Scientific and Technical Information of China (English)

    Song-Tae SEONG; Ko-Tae JO; Young-Moon LEE

    2009-01-01

    Under certain cutting conditions in end milling, the signs of cutting forces change from positive to negative during a revolution of the tool. The change of force direction causes the cutting dynamics to be unstable which results in chatter vibration. Therefore, cutting force signal monitoring and classification are needed to determine the optimal cutting conditions and to improve the efficiency of cut. Artificial neural networks are powerful tools for solving highly complex and nonlinear problems. It can be divided into supervised and unsupervised learning machines based on the availability of a teacher. Hybrid neural network was introduced with both of functions of multilayer perceptron (MLP) trained with the back-propagation algorithm for monitoring and detecting abnormal state, and self organizing feature map (SOFM) for treating huge datum such as image processing and pattern recognition, for predicting and classifying cutting force signal patterns simultaneously. The validity of the results is verified with cutting experiments and simulation tests.

  3. Implementation of an Antenna Array Signal Processing Breadboard for the Deep Space Network

    Science.gov (United States)

    Navarro, Robert

    2006-01-01

    The Deep Space Network Large Array will replace/augment 34 and 70 meter antenna assets. The array will mainly be used to support NASA's deep space telemetry, radio science, and navigation requirements. The array project will deploy three complexes in the western U.S., Australia, and European longitude each with 400 12m downlink antennas and a DSN central facility at JPL. THis facility will remotely conduct all real-time monitor and control for the network. Signal processing objectives include: provide a means to evaluate the performance of the Breadboard Array's antenna subsystem; design and build prototype hardware; demonstrate and evaluate proposed signal processing techniques; and gain experience with various technologies that may be used in the Large Array. Results are summarized..

  4. Novel scheme enabling broadcast signal transmission in WDM passive optical network

    Institute of Scientific and Technical Information of China (English)

    Xuejiao Ma; Chaoqin Gan

    2011-01-01

    @@ We present a novel method for providing broadcast signal transmission in a wavelength division multiplex-ing passive optical network (WDM-PON).An unmodulated optical carrier for downstream transmission and a pair of unmodulated single-side band subcarriers are utilized for broadcast delivery and upstream transmission, respectively.System performance at 2.5-Gb/s downlupstream and 2.5-Gb/s broadcast trans-mission is also investigated.%We present a novel method for providing broadcast signal transmission in a wavelength division multiplexing passive optical network (WDM-PON).An unmodulated optical carrier for downstream transmission and a pair of unmodulated single-side band subcarriers are utilized for broadcast delivery and upstream transmission, respectively.System performance at 2.5-Gb/s down/upstream and 2.5-Gb/s broadcast transmission is also investigated.

  5. A new cellular nonlinear network emulation on FPGA for EEG signal processing in epilepsy

    Science.gov (United States)

    Müller, Jens; Müller, Jan; Tetzlaff, Ronald

    2011-05-01

    For processing of EEG signals, we propose a new architecture for the hardware emulation of discrete-time Cellular Nonlinear Networks (DT-CNN). Our results show the importance of a high computational accuracy in EEG signal prediction that cannot be achieved with existing analogue VLSI circuits. The refined architecture of the processing elements and its resource schedule, the cellular network structure with local couplings, the FPGA-based embedded system containing the DT-CNN, and the data flow in the entire system will be discussed in detail. The proposed DT-CNN design has been implemented and tested on an Xilinx FPGA development platform. The embedded co-processor with a multi-threading kernel is utilised for control and pre-processing tasks and data exchange to the host via Ethernet. The performance of the implemented DT-CNN has been determined for a popular example and compared to that of a conventional computer.

  6. Network Analysis of Neurodegenerative Disease Highlights a Role of Toll-Like Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Thanh-Phuong Nguyen

    2014-01-01

    Full Text Available Despite significant advances in the study of the molecular mechanisms altered in the development and progression of neurodegenerative diseases (NDs, the etiology is still enigmatic and the distinctions between diseases are not always entirely clear. We present an efficient computational method based on protein-protein interaction network (PPI to model the functional network of NDs. The aim of this work is fourfold: (i reconstruction of a PPI network relating to the NDs, (ii construction of an association network between diseases based on proximity in the disease PPI network, (iii quantification of disease associations, and (iv inference of potential molecular mechanism involved in the diseases. The functional links of diseases not only showed overlap with the traditional classification in clinical settings, but also offered new insight into connections between diseases with limited clinical overlap. To gain an expanded view of the molecular mechanisms involved in NDs, both direct and indirect connector proteins were investigated. The method uncovered molecular relationships that are in common apparently distinct diseases and provided important insight into the molecular networks implicated in disease pathogenesis. In particular, the current analysis highlighted the Toll-like receptor signaling pathway as a potential candidate pathway to be targeted by therapy in neurodegeneration.

  7. A structured approach for the engineering of biochemical network models, illustrated for signalling pathways

    OpenAIRE

    Breitling, Rainer; Gilbert, David; Heiner, Monika; Orton, Richard

    2008-01-01

    Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also a...

  8. International Conference on VLSI, Communication, Advanced Devices, Signals & Systems and Networking

    CERN Document Server

    Shirur, Yasha; Prasad, Rekha

    2013-01-01

    This book is a collection of papers presented by renowned researchers, keynote speakers and academicians in the International Conference on VLSI, Communication, Analog Designs, Signals and Systems, and Networking (VCASAN-2013), organized by B.N.M. Institute of Technology, Bangalore, India during July 17-19, 2013. The book provides global trends in cutting-edge technologies in electronics and communication engineering. The content of the book is useful to engineers, researchers and academicians as well as industry professionals.

  9. Traffic Congestion Evaluation and Signal Control Optimization Based on Wireless Sensor Networks: Model and Algorithms

    OpenAIRE

    Wei Zhang; Guozhen Tan; Nan Ding; Guangyuan Wang

    2012-01-01

    This paper presents the model and algorithms for traffic flow data monitoring and optimal traffic light control based on wireless sensor networks. Given the scenario that sensor nodes are sparsely deployed along the segments between signalized intersections, an analytical model is built using continuum traffic equation and develops the method to estimate traffic parameter with the scattered sensor data. Based on the traffic data and principle of traffic congestion formation, we introduce the ...

  10. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  11. M3R介导的cAMP-PKA信号途径对L-型钙通道的调控作用研究%Effects of M3 Receptor on L-type Calcium Channels by cAMP-PKA Signal Pathway

    Institute of Scientific and Technical Information of China (English)

    栾海蓉; 董琦; 王得利; 李海林; 吴红

    2012-01-01

    Objective To investigate the effects of M3 receptor agonist choline on L-type calcium channels by cAMP-PKA signal pathway. Methods Whole cell patch clamp technique was used to record L-type calcium current. Laser scanning confocal microscope( LSCM )was employed to measure the concentration of intracellular free calcium. Results The application of choline reduced the density of peak Ica-L from( 9.07 ±0. 68)pA/pf to(5.58 ±0.62 )pA/pP( n =4,vs control,P <0.01 ),H89 with choline reduced the density of peak Ica-L to( 7.68 ±0.75 )pA/pF,whose amplitude was higher than that of choline group( n =4,vs choline, P< 0.01 ). LSCM recorded that KC1 induced determined by used[ Ca2 + ]I increasing could be depressed by choline, and also depressed by H89 with choline, whose amplitude is higher than that of choline group( n=30,vs choline,P<0.05 ). Conclusion Choline reduces[ Ca2 + ]I via inhibition of cAMP-PKA signal pathway of L-type calcium channel, which is possibly involved in the mechanism of its protective effects on myocardial injury.%目的 研究M3受体激动剂通过cAMP-PKA信号途径对L-型钙通道的影响.方法 应用全细胞膜片钳技术记录M3受体激动剂胆碱对大鼠单个心室肌细胞L-型钙通道电流(ICa-L)的影响;采用激光扫描共聚焦技术观察细胞内钙离子的变化.结果 胆碱使大鼠心室肌细胞ICa-L密度从(9.07±0.68)pA/pF减少至(5.58 ±0.62)pA/pF(n=4,与对照组相比,P<0.01),H89加胆碱组使ICa-L电流密度减少至(7.68±0.75),幅度明显高于胆碱组(n=4,与胆碱组相比,P<0.01).胆碱抑制KCl除极诱导的心肌细胞[Ca2+]i的升高,从(2.83±0.08)降至(1.17±0.09)FI/FI0(n=30,与KCl组相比,P<0.01),胆碱与H89组可使[Ca2+]i降至(1.65±0.17)FI/FI0,幅度高于胆碱组(n=30,与胆碱组相比,P<0.05).结论 M3受体激动剂胆碱通过抑制PKA活性调控L-型钙通道,使外钙内流减少,降低细胞[Ca2+]i,从而发挥抗心肌保护作用.

  12. Vestibular and Attractor Network Basis of the Head Direction Cell Signal in Subcortical Circuits

    Directory of Open Access Journals (Sweden)

    Benjamin J Clark

    2012-03-01

    Full Text Available Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animal’s directional orientation and location in space. Within this navigation system are head direction (HD cells, which fire persistently when an animal’s head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007. HD cells are widely thought to underlie an animal’s sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. Much of this work has been directed at understanding the functional organization of the HD cell circuitry, and precisely how this signal is generated from sensory and motor systems. The purpose of the present review is to summarize some of the recent studies arguing that the HD cell circuit is largely processed in a hierarchical fashion, following a pathway involving the dorsal tegmental nuclei → lateral mammillary nuclei → anterior thalamus → parahippocampal and retrosplenial cortical regions. We also review recent work identifying “bursting” cellular activity in the HD cell circuit after lesions of the vestibular system, and relate these observations to the long held view that attractor network mechanisms underlie HD signal generation. Finally, we summarize the work to date suggesting that this network architecture may reside within the tegmento-mammillary circuit.

  13. Nitric oxide:A potential key point of the signaling network leading to plant secondary metabolite biosynthesis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The endogenous signaling network of plants plays important roles in mediating the exogenous factor-induced biosynthesis of secondary metabolites.Nitric oxide (NO) has emerged as a key signaling molecule in plants recently.Numerous studies demonstrated that the main signaling molecules such as salicylic acid(SA),jasmonic acid (JA),reactive oxygen species(ROS),and NO were not only involved in regulating plant secondary metabolite biosynthesis but also interacted to form a complex signaling network by mutual inhibition and/or synergy.The recent progress in the signal network of plant secondary metabolite biosynthesis has been discussed in this paper.Furthermore,we propose a hypothetical model to show that NO might act as a potential molecular switch in the stgnaling network leading to plant secondary metabolite biosynthesis.

  14. Information theory in systems biology. Part II: protein-protein interaction and signaling networks.

    Science.gov (United States)

    Mousavian, Zaynab; Díaz, José; Masoudi-Nejad, Ali

    2016-03-01

    By the development of information theory in 1948 by Claude Shannon to address the problems in the field of data storage and data communication over (noisy) communication channel, it has been successfully applied in many other research areas such as bioinformatics and systems biology. In this manuscript, we attempt to review some of the existing literatures in systems biology, which are using the information theory measures in their calculations. As we have reviewed most of the existing information-theoretic methods in gene regulatory and metabolic networks in the first part of the review, so in the second part of our study, the application of information theory in other types of biological networks including protein-protein interaction and signaling networks will be surveyed. PMID:26691180

  15. Cognitive sensor networks for structure defect monitoring and classification using guided wave signals

    Science.gov (United States)

    Jin, Yuanwei; O'Donoughue, Nicholas; Moura, José M. F.; Harley, Joel; Garrett, James H.; Oppenheim, Irving J.; Soibelman, Lucio; Ying, Yujie; He, Lin

    2010-04-01

    This paper develops a framework of a cognitive sensor networks system for structure defect monitoring and classification using guided wave signals. Guided ultrasonic waves that can propagate long distances along civil structures have been widely studied for inspection and detection of structure damage. Smart ultrasonic sensors arranged as a spatially distributed cognitive sensor networks system can transmit and receive ultrasonic guided waves to interrogate structure defects such as cracks and corrosion. A distinguishing characteristic of the cognitive sensor networks system is that it adaptively probes and learns about the environment, which enables constant optimization in response to its changing understanding of the defect response. In this paper, we develop a sequential multiple hypothesis testing scheme combined with adaptive waveform transmission for defect monitoring and classification. The performance is verified using numerical simulations of guided elastic wave propagation on a pipe model and by Monte Carlo simulations for computing the probability of correct classification.

  16. Bifurcation mechanisms of regular and chaotic network signaling in brain astrocytes

    Science.gov (United States)

    Matrosov, V. V.; Kazantsev, V. B.

    2011-06-01

    Bifurcation mechanisms underlying calcium oscillations in the network of astrocytes are investigated. Network model includes the dynamics of intracellular calcium concentration and intercellular diffusion of inositol 1,4,5-trisphosphate through gap junctions. Bifurcation analysis of underlying nonlinear dynamical system is presented. Parameter regions and principle bifurcation boundaries have been delineated and described. We show how variations of the diffusion rate can lead to generation of network calcium oscillations in originally nonoscillating cells. Different scenarios of regular activity and its transitions to chaotic dynamics have been obtained. Then, the bifurcations have been associated with statistical characteristics of calcium signals showing that different bifurcation scenarios yield qualitative changes in experimentally measurable quantities of the astrocyte activity, e.g., statistics of calcium spikes.

  17. Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors

    Directory of Open Access Journals (Sweden)

    Rebaï Ahmed

    2010-10-01

    Full Text Available Abstract Background Nuclear receptors (NRs and Receptor tyrosine kinases (RTKs are essential proteins in many cellular processes and sequence variations in their genes have been reported to be involved in many diseases including cancer. Although crosstalk between RTK and NR signalling and their contribution to the development of endocrine regulated cancers have been areas of intense investigation, the direct coupling of their signalling pathways remains elusive. In our understanding of the role and function of nuclear receptors on the cell membrane the interactions between nuclear receptors and tyrosine kinase receptors deserve further attention. Results We constructed a human signalling network containing nuclear receptors and tyrosine kinase receptors that identified a network topology involving eleven highly connected hubs. We further developed an integrated knowledge database, denominated NR-RTK database dedicated to human RTKs and NRs and their vertebrate orthologs and their interactions. These interactions were inferred using computational tools and those supported by literature evidence are indicated. NR-RTK database contains links to other relevant resources and includes data on receptor ligands. It aims to provide a comprehensive interaction map that identifies complex dynamics and potential crosstalk involved. Availability: NR-RTK database is accessible at http://www.bioinfo-cbs.org/NR-RTK/ Conclusions We infer that the NR-RTK interaction network is scale-free topology. We also uncovered the key receptors mediating the signal transduction between these two types of receptors. Furthermore, NR-RTK database is expected to be useful for researchers working on various aspects of the molecular basis of signal transduction by RTKs and NRs. Reviewers This article was reviewed by Professor Paul Harrison (nominated by Dr. Mark Gerstein, Dr. Arcady Mushegian and Dr. Anthony Almudevar.

  18. Design of Transparent Distributed IMS Network: Security Challenges Risk and Signaling Analysis

    Directory of Open Access Journals (Sweden)

    Hamid Allouch

    2013-01-01

    Full Text Available The IP Multimedia subsystem (IMS based on SIP as mechanism signalling and interfaces with otherservers using OSA (Open Service Access and CAMEL (Customized Applications for Mobile networkEnhanced Logic.Is responsible for the interconnection of IP packets with other network, IMS support datacommunication services, voice, video, messaging and web-based technologies. In this work we present adistributed design of architecture that turns up some challenges of transparent mobility on the secured IMSarchitecture. We introduced the architecture with clustering database HSS and automatic storage of datafiles that give a secure access to database. This paper gives an overview of classification of security in IMSnetwork and we show delay analysis comparison in signalling interworking with and without securingGateway (SEG in the registration of any UE in access network based IMS. We show that there is a tradeoffbetween the level of increasing system security and the potential delay incurred by mobility in AccessNetwork .we conclude that this architecture is suitable for operators and services providers for the newbusiness models delivering ,the services based IMS Everywhere, anytime and with any terminals.

  19. Real-time synchronization of wireless sensor network by 1-PPS signal

    Science.gov (United States)

    Giammarini, Marco; Pieralisi, Marco; Isidori, Daniela; Concettoni, Enrico; Cristalli, Cristina; Fioravanti, Matteo

    2015-05-01

    The use of wireless sensor networks with different nodes is desirable in a smart environment, because the network setting up and installation on preexisting structures can be done without a fixed cabled infrastructure. The flexibility of the monitoring system is fundamental where the use of a considerable quantity of cables could compromise the normal exercise, could affect the quality of acquired signal and finally increase the cost of the materials and installation. The network is composed of several intelligent "nodes", which acquires data from different kind of sensors, and then store or transmit them to a central elaboration unit. The synchronization of data acquisition is the core of the real-time wireless sensor network (WSN). In this paper, we present a comparison between different methods proposed by literature for the real-time acquisition in a WSN and finally we present our solution based on 1-Pulse-Per-Second (1-PPS) signal generated by GPS systems. The sensor node developed is a small-embedded system based on ARM microcontroller that manages the acquisition, the timing and the post-processing of the data. The communications between the sensors and the master based on IEEE 802.15.4 protocol and managed by dedicated software. Finally, we present the preliminary results obtained on a 3 floor building simulator with the wireless sensors system developed.

  20. Adaptive Wavelet Neural Networks for Signal Detection in DS-CDMA System

    Institute of Scientific and Technical Information of China (English)

    WANGLing; JIAOLichengt; TAOHaihong; LIUFang

    2004-01-01

    The Multiple access interference (MAI) is the major factor that limits the performance and capacity of a nonorthogonal Direct sequence Code division multiple access (DS-CDMA) system. By using the adaptability of highly parallel structure neural networks and the excellent approximation ability of wavelets, two kinds of Adaptive wavelets neural networks (AWNN) signal detectors are proposed in the paper, in which the inputs of detectors are the received signal vector corresponding to a single interesting user sampled at the chip rate, named by AWNN single-user detector, respectively, and to all or partial active users sampled at the bit rate after passing through a matched filter, named by AWNN multiuser detector and partial users AWNN multiuser detector. The complexity of the multiuser detectors only depends on that of wavelet networks. The performance analysis of the proposed detectors compared with the matched filters under single-user and multiuser systems and the multiuser detector based on multilayer perceptrons are carried out by Monte Carlo simulations. Results show that the adaptive wavelet neural networks multiuser detectors are superior to other detectors mentioned above.

  1. MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish

    DEFF Research Database (Denmark)

    Lundegaard, Pia R.; Anastasaki, Corina; Grant, Nicola J.;

    2015-01-01

    adult zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders......Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors...... as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and...

  2. cAMP/PKA/CREB信号通路及相关调控蛋白PDE-4和ERK对学习记忆的影响%Influence of Learning and Memory on the Expression of Relevant Controlling Protein PDE-4 and Extracellular Signal Regulating Kinase

    Institute of Scientific and Technical Information of China (English)

    杨夏

    2011-01-01

    In recent years,a lot of learning and memory tests which have been done with animals are all prompted that cAMP / PKA / CREB signaling pathway and the proteins are related to the process of learning and memory. PKA phosphorylates and activates cAMP response element hinding protein( CREB ). The latter is an important nucleoprotein , and it regulates the gene transcription of a promoter that has cAMP. It has heen confirmed that PDE-4 and ERK are cAMP /PKA/CREB signaling pathway regulatory protein. The cAMP/PKA/CREB signaling pathway and its regulated protein : PDE-4 and ERK. and the relationship among them, and explore its impact on learning and memory were reviewed in this article.%近年来在动物身上进行了大量的学习记忆实验,均提示cAMP/PKA/CREB信号通路中的各蛋白均与学习记忆过程有关.环磷酸腺苷(cAMP)激活蛋白激酶A磷酸化并激活cAMP反应单元结合蛋白(CREB),后者是一种重要的核蛋白,其调节启动子中具有cAMP反应单元(CRE)的基因转录,这种核转录因子具有调节包括学习记忆在内的广泛的生物学功能.已有研究证实,PDE4和ERK为cAMP/PKA/CREB信号通路的调节蛋白.现对cAMP/PKA/CREB信号通路中的各蛋白及其调控蛋白PDE-4和ERK进行研究,阐述着三者之间的关系,并探讨其对学习记忆的影响.

  3. FPGA implementation of a ZigBee wireless network control interface to transmit biomedical signals

    International Nuclear Information System (INIS)

    In recent years, cardiac hemodynamic monitors have incorporated new technologies based on wireless sensor networks which can implement different types of communication protocols. More precisely, a digital conductance catheter system recently developed adds a wireless ZigBee module (IEEE 802.15.4 standards) to transmit cardiac signals (ECG, intraventricular pressure and volume) which would allow the physicians to evaluate the patient's cardiac status in a noninvasively way. The aim of this paper is to describe a control interface, implemented in a FPGA device, to manage a ZigBee wireless network. ZigBee technology is used due to its excellent performance including simplicity, low-power consumption, short-range transmission and low cost. FPGA internal memory stores 8-bit signals with which the control interface prepares the information packets. These data were send to the ZigBee END DEVICE module that receives and transmits wirelessly to the external COORDINATOR module. Using an USB port, the COORDINATOR sends the signals to a personal computer for displaying. Each functional block of control interface was assessed by means of temporal diagrams. Three biological signals, organized in packets and converted to RS232 serial protocol, were successfully transmitted and displayed in a PC screen. For this purpose, a custom-made graphical software was designed using LabView.

  4. The network of P(II) signalling protein interactions in unicellular cyanobacteria.

    Science.gov (United States)

    Forchhammer, Karl

    2010-01-01

    P(II) signalling proteins constitute a large superfamily of signal perception and transduction proteins, which is represented in all domains of life and whose members play central roles in coordinating nitrogen assimilation. Generally, P(II) proteins act as sensors of the cellular adenylylate energy charge and 2-oxoglutarate level, and in response to these signals, they regulate central nitrogen assimilatory processes at various levels of control (from nutrient transport to gene expression) through protein-protein interactions with P(II) receptor proteins. An examination of the phylogeny of cyanobacteria reveals that specific functions of P(II) signalling evolved in this microbial lineage, which are not found in other prokaryotes. At least one of these functions, regulation of arginine biosynthesis by controlling the key enzyme N-acetyl-L: -glutamate kinase (NAGK), was transmitted by the ancestral cyanobacterium, which gave rise to chloroplasts, into the eukaryotic domain and was conserved during the evolution of planta. We have investigated in some detail the P(II) signalling protein, its signal perception and its interactions with receptors in the unicellular cyanobacteria Synechococcus elongatus PCC 7942 and Synechocystis PCC 6803 and have performed comparative analysis with Arabidopsis thaliana P(II)-NAGK interaction. This chapter will summarize these studies and will describe the emerging picture of a complex network of P(II) protein interactions in the unicellular cyanobacteria. PMID:20532736

  5. Co-evolution of Hormone Metabolism and Signaling Networks Expands Plant Adaptive Plasticity.

    Science.gov (United States)

    Weng, Jing-Ke; Ye, Mingli; Li, Bin; Noel, Joseph P

    2016-08-11

    Classically, hormones elicit specific cellular responses by activating dedicated receptors. Nevertheless, the biosynthesis and turnover of many of these hormone molecules also produce chemically related metabolites. These molecules may also possess hormonal activities; therefore, one or more may contribute to the adaptive plasticity of signaling outcomes in host organisms. Here, we show that a catabolite of the plant hormone abscisic acid (ABA), namely phaseic acid (PA), likely emerged in seed plants as a signaling molecule that fine-tunes plant physiology, environmental adaptation, and development. This trait was facilitated by both the emergence-selection of a PA reductase that modulates PA concentrations and by the functional diversification of the ABA receptor family to perceive and respond to PA. Our results suggest that PA serves as a hormone in seed plants through activation of a subset of ABA receptors. This study demonstrates that the co-evolution of hormone metabolism and signaling networks can expand organismal resilience. PMID:27518563

  6. Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow

    CERN Document Server

    Buibas, Marius; Nizar, Krystal; Silva, Gabriel A

    2009-01-01

    An optical flow gradient algorithm was applied to spontaneously forming networks of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e. a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling patterns. We begin by briefly reviewing the mathematics of the optical flow algorithm, describe how to solve for the displacement vectors, and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the ...

  7. ICE: a scalable, low-cost FPGA-based telescope signal processing and networking system

    CERN Document Server

    Bandura, K; Cliche, J F; de Haan, T; Dobbs, M A; Gilbert, A J; Griffin, S; Hsyu, G; Ittah, D; Parra, J Mena; Montgomery, J; Pinsonneault-Marotte, T; Siegel, S; Smecher, G; Tang, Q Y; Vanderlinde, K; Whitehorn, N

    2016-01-01

    We present an overview of the 'ICE' hardware and software framework that implements large arrays of interconnected FPGA-based data acquisition, signal processing and networking nodes economically. The system was conceived for application to radio, millimeter and sub-millimeter telescope readout systems that have requirements beyond typical off-the-shelf processing systems, such as careful control of interference signals produced by the digital electronics, and clocking of all elements in the system from a single precise observatory-derived oscillator. A new generation of telescopes operating at these frequency bands and designed with a vastly increased emphasis on digital signal processing to support their detector multiplexing technology or high-bandwidth correlators---data rates exceeding a terabyte per second---are becoming common. The ICE system is built around a custom FPGA motherboard that makes use of an Xilinx Kintex-7 FPGA and ARM-based co-processor. The system is specialized for specific application...

  8. An integrated knowledge translation experience: use of the Network of Pediatric Audiologists of Canada to facilitate the development of the University of Western Ontario Pediatric Audiological Monitoring Protocol (UWO PedAMP v1.0).

    Science.gov (United States)

    Moodie, Sheila T; Bagatto, Marlene P; Miller, Linda T; Kothari, Anita; Seewald, Richard; Scollie, Susan D

    2011-01-01

    Pediatric audiologists lack evidence-based, age-appropriate outcome evaluation tools with well-developed normative data that could be used to evaluate the auditory development and performance of children aged birth to 6 years with permanent childhood hearing impairment. Bagatto and colleagues recommend a battery of outcome tools that may be used with this population. This article provides results of an evaluation of the individual components of the University of Western Ontario Pediatric Audiological Monitoring Protocol (UWO PedAMP) version 1.0 by the audiologists associated with the Network of Pediatric Audiologists of Canada. It also provides information regarding barriers and facilitators to implementing outcome measures in clinical practice. Results indicate that when compared to the Parents' Evaluation of Aural/Oral Performance of Children (PEACH) Diary, audiologists found the PEACH Rating Scale to be a more clinically feasible evaluation tool to implement in practice from a time, task, and consistency of use perspective. Results also indicate that the LittlEARS(®) Auditory Questionnaire could be used to evaluate the auditory development and performance of children aged birth to 6 years with permanent childhood hearing impairment (PCHI). The most cited barrier to implementation is time. The result of this social collaboration was the creation of a knowledge product, the UWO PedAMP v1.0, which has the potential to be useful to audiologists and the children and families they serve. PMID:22194315

  9. The signal synchronization transmission of a spatiotemporal chaos network constituted by a laser phase-conjugate wave

    Institute of Scientific and Technical Information of China (English)

    Li Wen-Lin; Li Shu-Feng; Li Gang

    2012-01-01

    The signal synchronization transmission of a spatiotemporal chaos network is investigated.The structure of the coupling function between connected nodes of the complex network and the value range of the linear term coefficient of the separated configuration in state equation of the node are obtained through constructing an appropriate Lyapunov function.Each node of the complex network is a laser spatiotemporal chaos model in which the phase-conjugate wave and the unilateral coupled map lattice are taken as a local function and a spatially extended system,respectively.The simulation results show the effectiveness of the signal synchronization transmission principle of the network.

  10. The signal synchronization transmission of a spatiotemporal chaos network constituted by a laser phase-conjugate wave

    International Nuclear Information System (INIS)

    The signal synchronization transmission of a spatiotemporal chaos network is investigated. The structure of the coupling function between connected nodes of the complex network and the value range of the linear term coefficient of the separated configuration in state equation of the node are obtained through constructing an appropriate Lyapunov function. Each node of the complex network is a laser spatiotemporal chaos model in which the phase-conjugate wave and the unilateral coupled map lattice are taken as a local function and a spatially extended system, respectively. The simulation results show the effectiveness of the signal synchronization transmission principle of the network. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  11. Food-Sharing Networks in Lamalera, Indonesia: Status, Sharing, and Signaling.

    Science.gov (United States)

    Nolin, David A

    2012-07-01

    Costly signaling has been proposed as a possible mechanism to explain food sharing in foraging populations. This sharing-as-signaling hypothesis predicts an association between sharing and status. Using exponential random graph modeling (ERGM), this prediction is tested on a social network of between-household food-sharing relationships in the fishing and sea-hunting village of Lamalera, Indonesia. Previous analyses (Nolin 2010) have shown that most sharing in Lamalera is consistent with reciprocal altruism. The question addressed here is whether any additional variation may be explained as sharing-as-signaling by high-status households. The results show that high-status households both give and receive more than other households, a pattern more consistent with reciprocal altruism than costly signaling. However, once the propensity to reciprocate and household productivity are controlled, households of men holding leadership positions show greater odds of unreciprocated giving when compared to households of non-leaders. This pattern of excessive giving by leaders is consistent with the sharing-as-signaling hypothesis. Wealthy households show the opposite pattern, giving less and receiving more than other households. These households may reciprocate in a currency other than food or their wealth may attract favor-seeking behavior from others. Overall, status covariates explain little variation in the sharing network as a whole, and much of the sharing observed by high-status households is best explained by the same factors that explain sharing by other households. This pattern suggests that multiple mechanisms may operate simultaneously to promote sharing in Lamalera and that signaling may motivate some sharing by some individuals even within sharing regimes primarily maintained by other mechanisms. PMID:22822299

  12. Dynamic Bayesian Network Modeling of the Interplay between EGFR and Hedgehog Signaling.

    Science.gov (United States)

    Fröhlich, Holger; Bahamondez, Gloria; Götschel, Frank; Korf, Ulrike

    2015-01-01

    Aberrant activation of sonic Hegdehog (SHH) signaling has been found to disrupt cellular differentiation in many human cancers and to increase proliferation. The SHH pathway is known to cross-talk with EGFR dependent signaling. Recent studies experimentally addressed this interplay in Daoy cells, which are presumable a model system for medulloblastoma, a highly malignant brain tumor that predominately occurs in children. Currently ongoing are several clinical trials for different solid cancers, which are designed to validate the clinical benefits of targeting the SHH in combination with other pathways. This has motivated us to investigate interactions between EGFR and SHH dependent signaling in greater depth. To our knowledge, there is no mathematical model describing the interplay between EGFR and SHH dependent signaling in medulloblastoma so far. Here we come up with a fully probabilistic approach using Dynamic Bayesian Networks (DBNs). To build our model, we made use of literature based knowledge describing SHH and EGFR signaling and integrated gene expression (Illumina) and cellular location dependent time series protein expression data (Reverse Phase Protein Arrays). We validated our model by sub-sampling training data and making Bayesian predictions on the left out test data. Our predictions focusing on key transcription factors and p70S6K, showed a high level of concordance with experimental data. Furthermore, the stability of our model was tested by a parametric bootstrap approach. Stable network features were in agreement with published data. Altogether we believe that our model improved our understanding of the interplay between two highly oncogenic signaling pathways in Daoy cells. This may open new perspectives for the future therapy of Hedghog/EGF-dependent solid tumors. PMID:26571415

  13. Dynamic Bayesian Network Modeling of the Interplay between EGFR and Hedgehog Signaling.

    Directory of Open Access Journals (Sweden)

    Holger Fröhlich

    Full Text Available Aberrant activation of sonic Hegdehog (SHH signaling has been found to disrupt cellular differentiation in many human cancers and to increase proliferation. The SHH pathway is known to cross-talk with EGFR dependent signaling. Recent studies experimentally addressed this interplay in Daoy cells, which are presumable a model system for medulloblastoma, a highly malignant brain tumor that predominately occurs in children. Currently ongoing are several clinical trials for different solid cancers, which are designed to validate the clinical benefits of targeting the SHH in combination with other pathways. This has motivated us to investigate interactions between EGFR and SHH dependent signaling in greater depth. To our knowledge, there is no mathematical model describing the interplay between EGFR and SHH dependent signaling in medulloblastoma so far. Here we come up with a fully probabilistic approach using Dynamic Bayesian Networks (DBNs. To build our model, we made use of literature based knowledge describing SHH and EGFR signaling and integrated gene expression (Illumina and cellular location dependent time series protein expression data (Reverse Phase Protein Arrays. We validated our model by sub-sampling training data and making Bayesian predictions on the left out test data. Our predictions focusing on key transcription factors and p70S6K, showed a high level of concordance with experimental data. Furthermore, the stability of our model was tested by a parametric bootstrap approach. Stable network features were in agreement with published data. Altogether we believe that our model improved our understanding of the interplay between two highly oncogenic signaling pathways in Daoy cells. This may open new perspectives for the future therapy of Hedghog/EGF-dependent solid tumors.

  14. Synaptic network activity induces neuronal differentiation of adult hippocampal precursor cells through BDNF signaling

    Directory of Open Access Journals (Sweden)

    HarishBabu

    2009-09-01

    Full Text Available Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potential (LTP-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg2+-free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine and Mg2+-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca2+ influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling.

  15. Cylinder pressure reconstruction based on complex radial basis function networks from vibration and speed signals

    Science.gov (United States)

    Johnsson, Roger

    2006-11-01

    Methods to measure and monitor the cylinder pressure in internal combustion engines can contribute to reduced fuel consumption, noise and exhaust emissions. As direct measurements of the cylinder pressure are expensive and not suitable for measurements in vehicles on the road indirect methods which measure cylinder pressure have great potential value. In this paper, a non-linear model based on complex radial basis function (RBF) networks is proposed for the reconstruction of in-cylinder pressure pulse waveforms. Input to the network is the Fourier transforms of both engine structure vibration and crankshaft speed fluctuation. The primary reason for the use of Fourier transforms is that different frequency regions of the signals are used for the reconstruction process. This approach also makes it easier to reduce the amount of information that is used as input to the RBF network. The complex RBF network was applied to measurements from a 6-cylinder ethanol powered diesel engine over a wide range of running conditions. Prediction accuracy was validated by comparing a number of parameters between the measured and predicted cylinder pressure waveform such as maximum pressure, maximum rate of pressure rise and indicated mean effective pressure. The performance of the network was also evaluated for a number of untrained running conditions that differ both in speed and load from the trained ones. The results for the validation set were comparable to the trained conditions.

  16. Efficient transmission of subthreshold signals in complex networks of spiking neurons.

    Directory of Open Access Journals (Sweden)

    Joaquin J Torres

    Full Text Available We investigate the efficient transmission and processing of weak, subthreshold signals in a realistic neural medium in the presence of different levels of the underlying noise. Assuming Hebbian weights for maximal synaptic conductances--that naturally balances the network with excitatory and inhibitory synapses--and considering short-term synaptic plasticity affecting such conductances, we found different dynamic phases in the system. This includes a memory phase where population of neurons remain synchronized, an oscillatory phase where transitions between different synchronized populations of neurons appears and an asynchronous or noisy phase. When a weak stimulus input is applied to each neuron, increasing the level of noise in the medium we found an efficient transmission of such stimuli around the transition and critical points separating different phases for well-defined different levels of stochasticity in the system. We proved that this intriguing phenomenon is quite robust, as it occurs in different situations including several types of synaptic plasticity, different type and number of stored patterns and diverse network topologies, namely, diluted networks and complex topologies such as scale-free and small-world networks. We conclude that the robustness of the phenomenon in different realistic scenarios, including spiking neurons, short-term synaptic plasticity and complex networks topologies, make very likely that it could also occur in actual neural systems as recent psycho-physical experiments suggest.

  17. Dissection of the cis-2-decenoic acid signaling network in Pseudomonas aeruginosa using microarray technique

    Directory of Open Access Journals (Sweden)

    Azadeh eRahmani-Badi

    2015-04-01

    Full Text Available Many bacterial pathogens use quorum-sensing (QS signaling to regulate the expression of factors contributing to virulence and persistence. Bacteria produce signals of different chemical classes. The signal molecule, known as diffusible signal factor (DSF, is a cis-unsaturated fatty acid that was first described in the plant pathogen Xanthomonas campestris. Previous works have shown that human pathogen, Pseudomonas aeruginosa, also synthesizes a structurally related molecule, characterized as cis-2-decenoic acid (C10: Δ2, CDA that induces biofilm dispersal by multiple types of bacteria. Furthermore, CDA has been shown to be involved in inter-kingdom signaling that modulates fungal behavior. Therefore, an understanding of its signaling mechanism could suggest strategies for interference, with consequences for disease control. To identify the components of CDA signaling pathway in this pathogen, a comparative transcritpome analysis was conducted, in the presence and absence of CDA. A protein-protein interaction (PPI network for differentially expressed (DE genes with known function was then constructed by STRING and Cytoscape. In addition, the effects of CDA in combination with antimicrobial agents on the biofilm surface area and bacteria viability were evaluated using fluorescence microscopy and digital image analysis. Microarray analysis identified 666 differentially expressed genes in the presence of CDA and gene ontology (GO analysis revealed that in P. aeruginosa, CDA mediates dispersion of biofilms through signaling pathways, including enhanced motility, virulence as well as persistence at different temperatures. PPI data suggested that a cluster of five genes (PA4978, PA4979, PA4980, PA4982, PA4983 is involved in the CDA synthesis and perception. Combined treatments using both CDA and antimicrobial agents showed that following exposure of the biofilms to CDA, remaining cells on the surface were easily removed and killed by antimicrobials.

  18. Identification and analysis of signaling networks potentially involved in breast carcinoma metastasis to the brain.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available Brain is a common site of breast cancer metastasis associated with significant neurologic morbidity, decreased quality of life, and greatly shortened survival. However, the molecular and cellular mechanisms underpinning brain colonization by breast carcinoma cells are poorly understood. Here, we used 2D-DIGE (Difference in Gel Electrophoresis proteomic analysis followed by LC-tandem mass spectrometry to identify the proteins differentially expressed in brain-targeting breast carcinoma cells (MB231-Br compared with parental MDA-MB-231 cell line. Between the two cell lines, we identified 12 proteins consistently exhibiting greater than 2-fold (p<0.05 difference in expression, which were associated by the Ingenuity Pathway Analysis (IPA with two major signaling networks involving TNFα/TGFβ-, NFκB-, HSP-70-, TP53-, and IFNγ-associated pathways. Remarkably, highly related networks were revealed by the IPA analysis of a list of 19 brain-metastasis-associated proteins identified recently by the group of Dr. A. Sierra using MDA-MB-435-based experimental system (Martin et al., J Proteome Res 2008 7:908-20, or a 17-gene classifier associated with breast cancer brain relapse reported by the group of Dr. J. Massague based on a microarray analysis of clinically annotated breast tumors from 368 patients (Bos et al., Nature 2009 459: 1005-9. These findings, showing that different experimental systems and approaches (2D-DIGE proteomics used on brain targeting cell lines or gene expression analysis of patient samples with documented brain relapse yield highly related signaling networks, suggest strongly that these signaling networks could be essential for a successful colonization of the brain by metastatic breast carcinoma cells.

  19. Secured operating regions of Slotted ALOHA in the presence of interfering signals from other networks and DoS attacking signals

    Directory of Open Access Journals (Sweden)

    Jahangir H. Sarker

    2011-07-01

    Full Text Available It is expected that many networks will be providing services at a time in near future and those will also produce different interfering signals for the current Slotted ALOHA based systems. A random packet destruction Denial of Service (DoS attacking signal can shut down the Slotted ALOHA based networks easily. Therefore, to keep up the services of Slotted ALOHA based systems by enhancing the secured operating regions in the presence of the interfering signals from other wireless systems and DoS attacking signals is an important issue and is investigated in this paper. We have presented four different techniques for secured operating regions enhancements of Slotted ALOHA protocol. Results show that the interfering signals from other wireless systems and the DoS attacking signals can produce similar detrimental effect on Slotted ALOHA. However, the most detrimental effect can be produced, if an artificial DoS attack can be launched using extra false packets arrival from the original network. All four proposed secured operating regions enhancement techniques are easy to implement and have the ability to prevent the shutdown of the Slotted ALOHA based networks.

  20. Identification of new signaling components in the sensory epithelium of human saccule

    OpenAIRE

    EvaDegerman; UweRauch; OlgaGöransson; SvenLindberg; MånsMagnusson

    2011-01-01

    Objective: To locate components and target proteins of relevance for the cAMP and cGMP signaling networks including cAMP and cGMP phosphodiesterases (PDEs), salt-inducible kinases (SIKs), subunits of N+, K+-ATPases and aquaporins (AQPs) in the human saccule. Methods: The human saccule was dissected out during the removal of vestibular schwannoma via the translabyrinthine approach and immediately fixed. Immunohistochemistry was performed using PDE, SIK, Na+, K+-ATPase and AQP antibodies. Resul...

  1. Identification of New Signaling Components in the Sensory Epithelium of Human Saccule

    OpenAIRE

    Degerman, Eva; Rauch, Uwe; Göransson, Olga; Lindberg, Sven; Hultgårdh, Anna; Magnusson, Måns

    2011-01-01

    Objective: To locate components and target proteins of relevance for the cAMP and cGMP signaling networks including cAMP and cGMP phosphodiesterases (PDEs), salt-inducible kinases (SIKs), subunits of Na+, K+-ATPases, and aquaporins (AQPs) in the human saccule. Methods: The human saccule was dissected out during the removal of vestibular schwannoma via the translabyrinthine approach and immediately fixed. Immunohistochemistry was performed using PDE, SIK, Na(+), K(+)-ATPase, and AQP antibodies...

  2. The Limitation of Primary Signals Entering DVB-T On-Channel-Repeater Working in SFN Network

    Directory of Open Access Journals (Sweden)

    Marek Dvorsky

    2013-01-01

    Full Text Available This paper considers an issue of signal coverage in uncovered places using a broadcasting device called a Gap Filler. The main focus is placed on the analysis of potential negative effects while signals from two and more primary transmitters simultaneously enter to the Gap Filler. In particular, in the measurements the impact of reception cross delayed signals received by the Gap Filler from two adjacent primary transmitters operating in the Single Frequency Network was analysed. The influence of different receive signal levels from two adjacent primary transmitters was also examined. In the conclusion, based on the experiments, the limiting factors useful for individual transmitters in the Single Frequency Network were determined. The analysis and finding the limit parameters can help bradcasters in further setting and debugging of the Gap Filler network. Finally, the described laboratory experiment was also verified under the real SFN network condition in border region Vsetinsko to verify the laboratory findings.

  3. An intelligent signal processing and pattern recognition technique for defect identification using an active sensor network

    Science.gov (United States)

    Su, Zhongqing; Ye, Lin

    2004-08-01

    The practical utilization of elastic waves, e.g. Rayleigh-Lamb waves, in high-performance structural health monitoring techniques is somewhat impeded due to the complicated wave dispersion phenomena, the existence of multiple wave modes, the high susceptibility to diverse interferences, the bulky sampled data and the difficulty in signal interpretation. An intelligent signal processing and pattern recognition (ISPPR) approach using the wavelet transform and artificial neural network algorithms was developed; this was actualized in a signal processing package (SPP). The ISPPR technique comprehensively functions as signal filtration, data compression, characteristic extraction, information mapping and pattern recognition, capable of extracting essential yet concise features from acquired raw wave signals and further assisting in structural health evaluation. For validation, the SPP was applied to the prediction of crack growth in an alloy structural beam and construction of a damage parameter database for defect identification in CF/EP composite structures. It was clearly apparent that the elastic wave propagation-based damage assessment could be dramatically streamlined by introduction of the ISPPR technique.

  4. Interaction between Calcium and Actin in Guard Cell and Pollen Signaling Networks

    Directory of Open Access Journals (Sweden)

    Dong-Hua Chen

    2013-10-01

    Full Text Available Calcium (Ca2+ plays important roles in plant growth, development, and signal transduction. It is a vital nutrient for plant physical design, such as cell wall and membrane, and also serves as a counter-cation for biochemical, inorganic, and organic anions, and more particularly, its concentration change in cytosol is a ubiquitous second messenger in plant physiological signaling in responses to developmental and environmental stimuli. Actin cytoskeleton is well known for its importance in cellular architecture maintenance and its significance in cytoplasmic streaming and cell division. In plant cell system, the actin dynamics is a process of polymerization and de-polymerization of globular actin and filamentous actin and that acts as an active regulator for calcium signaling by controlling calcium evoked physiological responses. The elucidation of the interaction between calcium and actin dynamics will be helpful for further investigation of plant cell signaling networks at molecular level. This review mainly focuses on the recent advances in understanding the interaction between the two aforementioned signaling components in two well-established model systems of plant, guard cell, and pollen.

  5. Information theory and signal transduction systems: from molecular information processing to network inference.

    Science.gov (United States)

    Mc Mahon, Siobhan S; Sim, Aaron; Filippi, Sarah; Johnson, Robert; Liepe, Juliane; Smith, Dominic; Stumpf, Michael P H

    2014-11-01

    Sensing and responding to the environment are two essential functions that all biological organisms need to master for survival and successful reproduction. Developmental processes are marshalled by a diverse set of signalling and control systems, ranging from systems with simple chemical inputs and outputs to complex molecular and cellular networks with non-linear dynamics. Information theory provides a powerful and convenient framework in which such systems can be studied; but it also provides the means to reconstruct the structure and dynamics of molecular interaction networks underlying physiological and developmental processes. Here we supply a brief description of its basic concepts and introduce some useful tools for systems and developmental biologists. Along with a brief but thorough theoretical primer, we demonstrate the wide applicability and biological application-specific nuances by way of different illustrative vignettes. In particular, we focus on the characterisation of biological information processing efficiency, examining cell-fate decision making processes, gene regulatory network reconstruction, and efficient signal transduction experimental design. PMID:24953199

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

    Directory of Open Access Journals (Sweden)

    JIDE JULIUS POPOOLA

    2014-04-01

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

  7. Modeling propagation of infrasound signals observed by a dense seismic network.

    Science.gov (United States)

    Chunchuzov, I; Kulichkov, S; Popov, O; Hedlin, M

    2014-01-01

    The long-range propagation of infrasound from a surface explosion with an explosive yield of about 17.6 t TNT that occurred on June 16, 2008 at the Utah Test and Training Range (UTTR) in the western United States is simulated using an atmospheric model that includes fine-scale layered structure of the wind velocity and temperature fields. Synthetic signal parameters (waveforms, amplitudes, and travel times) are calculated using parabolic equation and ray-tracing methods for a number of ranges between 100 and 800 km from the source. The simulation shows the evolution of several branches of stratospheric and thermospheric signals with increasing range from the source. Infrasound signals calculated using a G2S (ground-to-space) atmospheric model perturbed by small-scale layered wind velocity and temperature fluctuations are shown to agree well with recordings made by the dense High Lava Plains seismic network located at an azimuth of 300° from UTTR. The waveforms of calculated infrasound arrivals are compared with those of seismic recordings. This study illustrates the utility of dense seismic networks for mapping an infrasound field with high spatial resolution. The parabolic equation calculations capture both the effect of scattering of infrasound into geometric acoustic shadow zones and significant temporal broadening of the arrivals. PMID:24437743

  8. Identifying Network Motifs that Buffer Front-to-Back Signaling in Polarized Neutrophils

    Directory of Open Access Journals (Sweden)

    Yanqin Wang

    2013-05-01

    Full Text Available Neutrophil polarity relies on local, mutual inhibition to segregate incompatible signaling circuits to the leading and trailing edges. Mutual inhibition alone should lead to cells having strong fronts and weak backs or vice versa. However, analysis of cell-to-cell variation in human neutrophils revealed that back polarity remains consistent despite changes in front strength. How is this buffering achieved? Pharmacological perturbations and mathematical modeling revealed a functional role for microtubules in buffering back polarity by mediating positive, long-range crosstalk from front to back; loss of microtubules inhibits buffering and results in anticorrelation between front and back signaling. Furthermore, a systematic, computational search of network topologies found that a long-range, positive front-to-back link is necessary for back buffering. Our studies suggest a design principle that can be employed by polarity networks: short-range mutual inhibition establishes distinct signaling regions, after which directed long-range activation insulates one region from variations in the other.

  9. Fault Diagnosis of Mixed-Signal Analog Circuit using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Ashwani Kumar Narula

    2015-06-01

    Full Text Available This paper presents parametric fault diagnosis in mixed-signal analog circuit using artificial neural networks. Single parametric faults are considered in this study. A benchmark R2R digital to analog converter circuit has been used as an example circuit for experimental validations. The input test pattern required for testing are reduced to optimum value using sensitivity analysis of the circuit under test. The effect of component tolerances has also been taken care of by performing the Monte-Carlo analysis. In this study parametric fault models are defined for the R2R network of the digital to analog converter. The input test patterns are applied to the circuit under test and the output responses are measured for each fault model covering all the Monte-Carlo runs. The classification of the parametric faults is done using artificial neural networks. The fault diagnosis system is developed in LabVIEW environment in the form of a virtual instrument. The artificial neural network is designed using MATLAB and finally embedded in the virtual instrument. The fault diagnosis is validated with simulated data and with the actual data acquired from the circuit hardware.

  10. Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Liu, Tao; Quesenberry, Ryan D.; Willse, Alan R.; Bandyopadhyay, Somnath; Kathmann, Loel E.; Weber, Thomas J.; Smith, Richard D.; Wiley, H. S.; Thrall, Brian D.

    2012-03-29

    To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF) using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  11. Network analysis of epidermal growth factor signaling using integrated genomic, proteomic and phosphorylation data.

    Directory of Open Access Journals (Sweden)

    Katrina M Waters

    Full Text Available To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  12. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.

    Science.gov (United States)

    Coleman, Matthew A; Sasi, Sharath P; Onufrak, Jillian; Natarajan, Mohan; Manickam, Krishnan; Schwab, John; Muralidharan, Sujatha; Peterson, Leif E; Alekseyev, Yuriy O; Yan, Xinhua; Goukassian, David A

    2015-12-01

    There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton ((1)H) and 15 cGy, 1 GeV/nucleon iron ((56)Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with (56)Fe-IR showing the greatest level of gene modulation. (1)H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to (56)Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers. PMID:26408534

  13. Signal Quality Outage Analysis for Ultra-Reliable Communications in Cellular Networks

    DEFF Research Database (Denmark)

    Gerardino, Guillermo Andrés Pocovi; Alvarez, Beatriz Soret; Lauridsen, Mads; Pedersen, Klaus I.; Mogensen, Preben Elgaard

    Ultra-reliable communications over wireless will open the possibility for a wide range of novel use cases and applications. In cellular networks, achieving reliable communication is challenging due to many factors, particularly the fading of the desired signal and the interference. In this regard...... schemes must be complemented with macroscopic diversity as well as interference management techniques in order to ensure the necessary SINR outage performance. Based on the obtained performance results, it is discussed which of the feasible options fulfilling the ultra-reliable criteria are most promising...

  14. Recognizing the Taste Signals Using the Clustering-Based Fuzzy Neural Network

    Institute of Scientific and Technical Information of China (English)

    HUANGYanxin; ZHOUChunguang

    2005-01-01

    A fuzzy neural network system model for recognizing 11 kinds of mineral waters by its taste signals is proposed. In the model, an entropy-based clustering algorithm is used as structure learning to partition the fuzzy input space and extract fuzzy if-then rules, and the Gradient Descent optimization algorithm is used as parameter learning to refine the fuzzy rule parameters. Experimental results show that the system can obtain perfect interpretability, robustness, learning capability and the cor-rect classification rates by choosing two system parameters properly.

  15. Circadian period integrates network information through activation of the BMP signaling pathway.

    Directory of Open Access Journals (Sweden)

    Esteban J Beckwith

    2013-12-01

    Full Text Available Living organisms use biological clocks to maintain their internal temporal order and anticipate daily environmental changes. In Drosophila, circadian regulation of locomotor behavior is controlled by ∼150 neurons; among them, neurons expressing the PIGMENT DISPERSING FACTOR (PDF set the period of locomotor behavior under free-running conditions. To date, it remains unclear how individual circadian clusters integrate their activity to assemble a distinctive behavioral output. Here we show that the BONE MORPHOGENETIC PROTEIN (BMP signaling pathway plays a crucial role in setting the circadian period in PDF neurons in the adult brain. Acute deregulation of BMP signaling causes period lengthening through regulation of dClock transcription, providing evidence for a novel function of this pathway in the adult brain. We propose that coherence in the circadian network arises from integration in PDF neurons of both the pace of the cell-autonomous molecular clock and information derived from circadian-relevant neurons through release of BMP ligands.

  16. Circadian Period Integrates Network Information Through Activation of the BMP Signaling Pathway

    Science.gov (United States)

    Beckwith, Esteban J.; Gorostiza, E. Axel; Berni, Jimena; Rezával, Carolina; Pérez-Santángelo, Agustín; Nadra, Alejandro D.; Ceriani, María Fernanda

    2013-01-01

    Living organisms use biological clocks to maintain their internal temporal order and anticipate daily environmental changes. In Drosophila, circadian regulation of locomotor behavior is controlled by ∼150 neurons; among them, neurons expressing the PIGMENT DISPERSING FACTOR (PDF) set the period of locomotor behavior under free-running conditions. To date, it remains unclear how individual circadian clusters integrate their activity to assemble a distinctive behavioral output. Here we show that the BONE MORPHOGENETIC PROTEIN (BMP) signaling pathway plays a crucial role in setting the circadian period in PDF neurons in the adult brain. Acute deregulation of BMP signaling causes period lengthening through regulation of dClock transcription, providing evidence for a novel function of this pathway in the adult brain. We propose that coherence in the circadian network arises from integration in PDF neurons of both the pace of the cell-autonomous molecular clock and information derived from circadian-relevant neurons through release of BMP ligands. PMID:24339749

  17. "cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.

    Directory of Open Access Journals (Sweden)

    Konstantinos Lefkimmiatis

    Full Text Available BACKGROUND: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP. METHODS/PRINCIPAL FINDINGS: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RIbeta of protein kinase A (PKA. Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge" was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. CONCLUSIONS: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events.

  18. 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

    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...

  19. On the use of a crystal detector for a phase calibration of the large signal network analyzer

    International Nuclear Information System (INIS)

    This paper introduces a crystal detector as a new calibration standard for large signal analysis [1–4]. By means of the detector as a reference element one can calibrate the phase distortion of the large signal network analyser (LSNA) on a dense frequency grid. In this paper we estimate and validate a parametric black-box model for a crystal detector

  20. Deciphering the hormonal signalling network behind the systemic resistance induced by Trichoderma harzianum in tomato.

    Science.gov (United States)

    Martínez-Medina, Ainhoa; Fernández, Iván; Sánchez-Guzmán, María J; Jung, Sabine C; Pascual, Jose A; Pozo, María J

    2013-01-01

    Root colonization by selected Trichoderma isolates can activate in the plant a systemic defense response that is effective against a broad-spectrum of plant pathogens. Diverse plant hormones play pivotal roles in the regulation of the defense signaling network that leads to the induction of systemic resistance triggered by beneficial organisms [induced systemic resistance (ISR)]. Among them, jasmonic acid (JA) and ethylene (ET) signaling pathways are generally essential for ISR. However, Trichoderma ISR (TISR) is believed to involve a wider variety of signaling routes, interconnected in a complex network of cross-communicating hormone pathways. Using tomato as a model, an integrative analysis of the main mechanisms involved in the systemic resistance induced by Trichoderma harzianum against the necrotrophic leaf pathogen Botrytis cinerea was performed. Root colonization by T. harzianum rendered the leaves more resistant to B. cinerea independently of major effects on plant nutrition. The analysis of disease development in shoots of tomato mutant lines impaired in the synthesis of the key defense-related hormones JA, ET, salicylic acid (SA), and abscisic acid (ABA), and the peptide prosystemin (PS) evidenced the requirement of intact JA, SA, and ABA signaling pathways for a functional TISR. Expression analysis of several hormone-related marker genes point to the role of priming for enhanced JA-dependent defense responses upon pathogen infection. Together, our results indicate that although TISR induced in tomato against necrotrophs is mainly based on boosted JA-dependent responses, the pathways regulated by the plant hormones SA- and ABA are also required for successful TISR development. PMID:23805146

  1. Gene network homology in prokaryotes using a similarity search approach: queries of quorum sensing signal transduction.

    Directory of Open Access Journals (Sweden)

    David N Quan

    Full Text Available Bacterial cell-cell communication is mediated by small signaling molecules known as autoinducers. Importantly, autoinducer-2 (AI-2 is synthesized via the enzyme LuxS in over 80 species, some of which mediate their pathogenicity by recognizing and transducing this signal in a cell density dependent manner. AI-2 mediated phenotypes are not well understood however, as the means for signal transduction appears varied among species, while AI-2 synthesis processes appear conserved. Approaches to reveal the recognition pathways of AI-2 will shed light on pathogenicity as we believe recognition of the signal is likely as important, if not more, than the signal synthesis. LMNAST (Local Modular Network Alignment Similarity Tool uses a local similarity search heuristic to study gene order, generating homology hits for the genomic arrangement of a query gene sequence. We develop and apply this tool for the E. coli lac and LuxS regulated (Lsr systems. Lsr is of great interest as it mediates AI-2 uptake and processing. Both test searches generated results that were subsequently analyzed through a number of different lenses, each with its own level of granularity, from a binary phylogenetic representation down to trackback plots that preserve genomic organizational information. Through a survey of these results, we demonstrate the identification of orthologs, paralogs, hitchhiking genes, gene loss, gene rearrangement within an operon context, and also horizontal gene transfer (HGT. We found a variety of operon structures that are consistent with our hypothesis that the signal can be perceived and transduced by homologous protein complexes, while their regulation may be key to defining subsequent phenotypic behavior.

  2. Application of signal processing techniques for islanding detection of distributed generation in distribution network: A review

    International Nuclear Information System (INIS)

    Highlights: • Pros & cons of conventional islanding detection techniques (IDTs) are discussed. • Signal processing techniques (SPTs) ability in detecting islanding is discussed. • SPTs ability in improving performance of passive techniques are discussed. • Fourier, s-transform, wavelet, HHT & tt-transform based IDTs are reviewed. • Intelligent classifiers (ANN, ANFIS, Fuzzy, SVM) application in SPT are discussed. - Abstract: High penetration of distributed generation resources (DGR) in distribution network provides many benefits in terms of high power quality, efficiency, and low carbon emissions in power system. However, efficient islanding detection and immediate disconnection of DGR is critical in order to avoid equipment damage, grid protection interference, and personnel safety hazards. Islanding detection techniques are mainly classified into remote, passive, active, and hybrid techniques. From these, passive techniques are more advantageous due to lower power quality degradation, lower cost, and widespread usage by power utilities. However, the main limitations of these techniques are that they possess a large non detection zones and require threshold setting. Various signal processing techniques and intelligent classifiers have been used to overcome the limitations of passive islanding. Signal processing techniques, in particular, are adopted due to their versatility, stability, cost effectiveness, and ease of modification. This paper presents a comprehensive overview of signal processing techniques used to improve common passive islanding detection techniques. A performance comparison between the signal processing based islanding detection techniques with existing techniques are also provided. Finally, this paper outlines the relative advantages and limitations of the signal processing techniques in order to provide basic guidelines for researchers and field engineers in determining the best method for their system

  3. Phytochrome and retrograde signalling pathways converge to antagonistically regulate a light-induced transcriptional network

    Science.gov (United States)

    Martín, Guiomar; Leivar, Pablo; Ludevid, Dolores; Tepperman, James M.; Quail, Peter H.; Monte, Elena

    2016-01-01

    Plastid-to-nucleus retrograde signals emitted by dysfunctional chloroplasts impact photomorphogenic development, but the molecular link between retrograde- and photosensory-receptor signalling has remained unclear. Here, we show that the phytochrome and retrograde signalling (RS) pathways converge antagonistically to regulate the expression of the nuclear-encoded transcription factor GLK1, a key regulator of a light-induced transcriptional network central to photomorphogenesis. GLK1 gene transcription is directly repressed by PHYTOCHROME-INTERACTING FACTOR (PIF)-class bHLH transcription factors in darkness, but light-activated phytochrome reverses this activity, thereby inducing expression. Conversely, we show that retrograde signals repress this induction by a mechanism independent of PIF mediation. Collectively, our data indicate that light at moderate levels acts through the plant's nuclear-localized sensory-photoreceptor system to induce appropriate photomorphogenic development, but at excessive levels, sensed through the separate plastid-localized RS system, acts to suppress such development, thus providing a mechanism for protection against photo-oxidative damage by minimizing the tissue exposure to deleterious radiation. PMID:27150909

  4. Applying Mathematical Processes (AMP)

    Science.gov (United States)

    Kathotia, Vinay

    2011-01-01

    This article provides insights into the "Applying Mathematical Processes" resources, developed by the Nuffield Foundation. It features Nuffield AMP activities--and related ones from Bowland Maths--that were designed to support the teaching and assessment of key processes in mathematics--representing a situation mathematically, analysing,…

  5. AMP language reference manual

    International Nuclear Information System (INIS)

    The use of a program for symbolic calculations named AMP (Algebraic Manipulation Program) is described. Its main features are: high speed heart for usual algebraic calculations; conversational capability; derivation, substitutions, matricial calculus, expansions, non commutative algebrae...; possibility to define new symbols and associated rules; possibility to create and use external libraries; written for IBM/370 like computers

  6. Using Differential Evolution to Optimize Learning from Signals and Enhance Network Security

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, Paul K [Air Force Institute of Technology; Temple, Michael A [Air Force Institute of Technology; Buckner, Mark A [ORNL; Farquhar, Ethan [ORNL

    2011-01-01

    Computer and communication network attacks are commonly orchestrated through Wireless Access Points (WAPs). This paper summarizes proof-of-concept research activity aimed at developing a physical layer Radio Frequency (RF) air monitoring capability to limit unauthorizedWAP access and mprove network security. This is done using Differential Evolution (DE) to optimize the performance of a Learning from Signals (LFS) classifier implemented with RF Distinct Native Attribute (RF-DNA) fingerprints. Performance of the resultant DE-optimized LFS classifier is demonstrated using 802.11a WiFi devices under the most challenging conditions of intra-manufacturer classification, i.e., using emissions of like-model devices that only differ in serial number. Using identical classifier input features, performance of the DE-optimized LFS classifier is assessed relative to a Multiple Discriminant Analysis / Maximum Likelihood (MDA/ML) classifier that has been used for previous demonstrations. The comparative assessment is made using both Time Domain (TD) and Spectral Domain (SD) fingerprint features. For all combinations of classifier type, feature type, and signal-to-noise ratio considered, results show that the DEoptimized LFS classifier with TD features is uperior and provides up to 20% improvement in classification accuracy with proper selection of DE parameters.

  7. Ionospheric Sounding Opportunities Using Signal Data From Preexisting Amateur Radio And Other Networks

    Science.gov (United States)

    Cushley, A. C.; Noel, J. M. A.

    2015-12-01

    Amateur radio and other transmissions used for dedicated purposes, such as the Automatic Packet Reporting System (APRS) and Automatic Dependent Surveillance Broadcast (ADS-B), are signals that exist for another reason, but can be used for ionospheric sounding. Whether mandated and government funded or voluntarily constructed and operated, these networks provide data that can be used for scientific and operational purposes which rely on space weather data. Given the current state of the global economic environment and fiscal consequences to scientific research funding in Canada, these types of networks offer an innovative solution with preexisting hardware for more real-time and archival space-weather data to supplement current methods, particularly for data assimilation, modelling and forecasting. Furthermore, mobile ground-based transmitters offer more flexibility for deployment than stationary receivers. Numerical modelling has demonstrated that APRS and ADS-B signals are subject to Faraday rotation (FR) as they pass through the ionosphere. Ray tracingtechniques were used to determine the characteristics of individual waves, including the wave path and the state of polarization. The modelled FR was computed and converted to total electron content (TEC) along the raypaths. TEC data can be used as input for computerized ionospheric tomography (CIT) in order to reconstruct electron density maps of the ionosphere.

  8. Two time-delay dynamic model on the transmission of malicious signals in wireless sensor network

    International Nuclear Information System (INIS)

    Highlights: • Role of time delay to reduce the adversary effect in WSN is explored. • Model with two time delays is proposed to analyse spread of malicious signal in WSN. • Dynamical behaviour of worm-free equilibrium and endemic equilibrium is shown. • Threshold condition for switch of stability are obtained analytically. • Relation between stability and the two time delays is also explored. - Abstract: Deployed in a hostile environment, motes of a Wireless sensor network (WSN) could be easily compromised by the attackers because of several constraints such as limited processing capabilities, memory space, and limited battery life time etc. While transmitting the data to their neighbour motes within the network, motes are easily compromised due to resource constraints. Here time delay can play an efficient role to reduce the adversary effect on motes. In this paper, we propose an epidemic model SEIR (Susceptible–Exposed–Infectious–Recovered) with two time delays to describe the transmission dynamics of malicious signals in wireless sensor network. The first delay accounts for an exposed (latent) period while the second delay is for the temporary immunity period due to multiple worm outbreaks. The dynamical behaviour of worm-free equilibrium and endemic equilibrium is shown from the point of stability which switches under some threshold condition specified by the basic reproduction number. Our results show that the global properties of equilibria also depends on the threshold condition and that latent and temporary immunity period in a mote does not affect the stability, but they play a positive role to control malicious attack. Moreover, numerical simulations are given to support the theoretical analysis

  9. Genome-Wide Analysis of the TORC1 and Osmotic Stress Signaling Network in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Jeremy Worley

    2016-02-01

    Full Text Available The Target of Rapamycin kinase Complex I (TORC1 is a master regulator of cell growth and metabolism in eukaryotes. Studies in yeast and human cells have shown that nitrogen/amino acid starvation signals act through Npr2/Npr3 and the small GTPases Gtr1/Gtr2 (Rags in humans to inhibit TORC1. However, it is unclear how other stress and starvation stimuli inhibit TORC1, and/or act in parallel with the TORC1 pathway, to control cell growth. To help answer these questions, we developed a novel automated pipeline and used it to measure the expression of a TORC1-dependent ribosome biogenesis gene (NSR1 during osmotic stress in 4700 Saccharomyces cerevisiae strains from the yeast knock-out collection. This led to the identification of 440 strains with significant and reproducible defects in NSR1 repression. The cell growth control and stress response proteins deleted in these strains form a highly connected network, including 56 proteins involved in vesicle trafficking and vacuolar function; 53 proteins that act downstream of TORC1 according to a rapamycin assay—including components of the HDAC Rpd3L, Elongator, and the INO80, CAF-1 and SWI/SNF chromatin remodeling complexes; over 100 proteins involved in signaling and metabolism; and 17 proteins that directly interact with TORC1. These data provide an important resource for labs studying cell growth control and stress signaling, and demonstrate the utility of our new, and easily adaptable, method for mapping gene regulatory networks.

  10. Identifying early-warning signals of critical transitions with strong noise by dynamical network markers

    Science.gov (United States)

    Liu, Rui; Chen, Pei; Aihara, Kazuyuki; Chen, Luonan

    2015-12-01

    Identifying early-warning signals of a critical transition for a complex system is difficult, especially when the target system is constantly perturbed by big noise, which makes the traditional methods fail due to the strong fluctuations of the observed data. In this work, we show that the critical transition is not traditional state-transition but probability distribution-transition when the noise is not sufficiently small, which, however, is a ubiquitous case in real systems. We present a model-free computational method to detect the warning signals before such transitions. The key idea behind is a strategy: “making big noise smaller” by a distribution-embedding scheme, which transforms the data from the observed state-variables with big noise to their distribution-variables with small noise, and thus makes the traditional criteria effective because of the significantly reduced fluctuations. Specifically, increasing the dimension of the observed data by moment expansion that changes the system from state-dynamics to probability distribution-dynamics, we derive new data in a higher-dimensional space but with much smaller noise. Then, we develop a criterion based on the dynamical network marker (DNM) to signal the impending critical transition using the transformed higher-dimensional data. We also demonstrate the effectiveness of our method in biological, ecological and financial systems.

  11. A RECURRENT ELMAN NEURAL NETWORK - BASED APPROACH TO DETECT THE PRESENCE OF EPILEPTIC ATTACK IN ELECTROENCEPHALOGRAM (EEG SIGNALS

    Directory of Open Access Journals (Sweden)

    Mr.S.Sundaram

    2014-10-01

    Full Text Available Epileptic attack persons are detected largely on the analysis of Electroencephalogram (EEG signals. The EEG signals recordings generate very bulk data which require a skilled and careful analysis. This method can be automated based on Elman Neural Network by using a time frequency domain characteristics of EEG signal called Approximate Entropy (ApEn. This method consists of EEG collection of data, extraction and classification. EEG data from normal persons and epileptic affected persons was collected, digitized and then fed into the Elman neural network. This proposed system proposes a neural-network-based automated epileptic EEG detection system that uses approximate entropy (ApEn as the input feature. Approximate Entropy (ApEn [1] is a statistical parameter that measures the predictability of the current amplitude values of a physiological signal based on its previous amplitude values. It is known that the value of the Approximate Entropy drops sharply during an epileptic attack[2]and this fact is used in the proposed system. Type of a neural network namely, Elman neural network is considered in this paper. The experimental results portray that this proposed approach efficiently detects the presence of epileptic seizures[3] in EEG signals and showed a reasonable accuracy.

  12. The Brassinosteroid Signaling Pathway—New Key Players and Interconnections with Other Signaling Networks Crucial for Plant Development and Stress Tolerance

    Directory of Open Access Journals (Sweden)

    Damian Gruszka

    2013-04-01

    Full Text Available Brassinosteroids (BRs are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance in the elucidation of the molecular mechanisms of BR signaling from perception by the transmembrane receptor complex to the regulation of transcription factors influencing expression of the target genes. Application of the new approaches shed light on the molecular functions of the key players regulating the BR signaling cascade and allowed identification of new factors. Recent studies clearly indicated that some of the components of BR signaling pathway act as multifunctional proteins involved in other signaling networks regulating diverse physiological processes, such as photomorphogenesis, cell death control, stomatal development, flowering, plant immunity to pathogens and metabolic responses to stress conditions, including salinity. Regulation of some of these processes is mediated through a crosstalk between BR signalosome and the signaling cascades of other hormones, including auxin, abscisic acid, ethylene and salicylic acid. Unravelling the complicated mechanisms of BR signaling and its interconnections with other molecular networks may be of great importance for future practical applications in agriculture.

  13. The brassinosteroid signaling pathway-new key players and interconnections with other signaling networks crucial for plant development and stress tolerance.

    Science.gov (United States)

    Gruszka, Damian

    2013-01-01

    Brassinosteroids (BRs) are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance in the elucidation of the molecular mechanisms of BR signaling from perception by the transmembrane receptor complex to the regulation of transcription factors influencing expression of the target genes. Application of the new approaches shed light on the molecular functions of the key players regulating the BR signaling cascade and allowed identification of new factors. Recent studies clearly indicated that some of the components of BR signaling pathway act as multifunctional proteins involved in other signaling networks regulating diverse physiological processes, such as photomorphogenesis, cell death control, stomatal development, flowering, plant immunity to pathogens and metabolic responses to stress conditions, including salinity. Regulation of some of these processes is mediated through a crosstalk between BR signalosome and the signaling cascades of other hormones, including auxin, abscisic acid, ethylene and salicylic acid. Unravelling the complicated mechanisms of BR signaling and its interconnections with other molecular networks may be of great importance for future practical applications in agriculture. PMID:23615468

  14. Neural network technique for identifying prognostic anomalies from low-frequency electromagnetic signals in the Kuril-Kamchatka region

    Science.gov (United States)

    Popova, I.; Rozhnoi, A.; Solovieva, M.; Levin, B.; Chebrov, V.

    2016-03-01

    In this paper, we suggest a technique for forecasting seismic events based on the very low and low frequency (VLF and LF) signals in the 10 to 50 Hz band using the neural network approach, specifically, the error back-propagation method (EBPM). In this method, the solution of the problem has two main stages: training and recognition (forecasting). The training set is constructed from the combined data, including the amplitudes and phases of the VLF/LF signals measured in the monitoring of the Kuril-Kamchatka region and the corresponding parameters of regional seismicity. Training the neural network establishes the internal relationship between the characteristic changes in the VLF/LF signals a few days before a seismic event and the corresponding level of seismicity. The trained neural network is then applied in a prognostic mode for automated detection of the anomalous changes in the signal which are associated with seismic activity exceeding the assumed threshold level. By the example of several time intervals in 2004, 2005, 2006, and 2007, we demonstrate the efficiency of the neural network approach in the short-term forecasting of earthquakes with magnitudes starting from M ≥ 5.5 from the nighttime variations in the amplitudes and phases of the LF signals on one radio path. We also discuss the results of the simultaneous analysis of the VLF/LF data measured on two partially overlapping paths aimed at revealing the correlations between the nighttime variations in the amplitude of the signal and seismic activity.

  15. Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems

    Science.gov (United States)

    Hook, Vivian; Bandeira, Nuno

    2015-12-01

    Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human

  16. Three-dimensional WS2 nanosheet networks for H2O2 produced for cell signaling

    Science.gov (United States)

    Tang, Jing; Quan, Yingzhou; Zhang, Yueyu; Jiang, Min; Al-Enizi, Abdullah M.; Kong, Biao; An, Tiance; Wang, Wenshuo; Xia, Limin; Gong, Xingao; Zheng, Gengfeng

    2016-03-01

    Hydrogen peroxide (H2O2) is an important molecular messenger for cellular signal transduction. The capability of direct probing of H2O2 in complex biological systems can offer potential for elucidating its manifold roles in living systems. Here we report the fabrication of three-dimensional (3D) WS2 nanosheet networks with flower-like morphologies on a variety of conducting substrates. The semiconducting WS2 nanosheets with largely exposed edge sites on flexible carbon fibers enable abundant catalytically active sites, excellent charge transfer, and high permeability to chemicals and biomaterials. Thus, the 3D WS2-based nano-bio-interface exhibits a wide detection range, high sensitivity and rapid response time for H2O2, and is capable of visualizing endogenous H2O2 produced in living RAW 264.7 macrophage cells and neurons. First-principles calculations further demonstrate that the enhanced sensitivity of probing H2O2 is attributed to the efficient and spontaneous H2O2 adsorption on WS2 nanosheet edge sites. The combined features of 3D WS2 nanosheet networks suggest attractive new opportunities for exploring the physiological roles of reactive oxygen species like H2O2 in living systems.Hydrogen peroxide (H2O2) is an important molecular messenger for cellular signal transduction. The capability of direct probing of H2O2 in complex biological systems can offer potential for elucidating its manifold roles in living systems. Here we report the fabrication of three-dimensional (3D) WS2 nanosheet networks with flower-like morphologies on a variety of conducting substrates. The semiconducting WS2 nanosheets with largely exposed edge sites on flexible carbon fibers enable abundant catalytically active sites, excellent charge transfer, and high permeability to chemicals and biomaterials. Thus, the 3D WS2-based nano-bio-interface exhibits a wide detection range, high sensitivity and rapid response time for H2O2, and is capable of visualizing endogenous H2O2 produced in

  17. Energy Analysis of Received Signal Strength Localization in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    D. Girbau

    2011-12-01

    Full Text Available This paper presents the investigation of energy demands during localization of wireless nodes in ad-hoc networks. We focus on the method based on the received signal strength (RSS to estimate the distances between the nodes. To deal with the uncertainty of this technique, statistical methods are used. It implies more measurement samples to be taken and consequently more energy to be spent. Therefore, we investigate the accuracy of localization and the consumed energy in the relation to the number of measurement samples. The experimental measurements were conducted with IRIS sensor motes and their results related to the proposed energy model. The results show that the expended energy is not related linearly to the localization error. First, improvement of the accuracy rises fast with more measurement samples. Then, adding more samples, the accuracy increase is moderate, which means that the marginal energy cost of the additional improvement is higher.

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

    Directory of Open Access Journals (Sweden)

    P. Dhanalakshmi

    2010-12-01

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

  19. Efficient transmission of subthreshold signals in complex networks of spiking neurons

    CERN Document Server

    Torres, Joaquin J; Marro, J

    2014-01-01

    We investigate the efficient transmission and processing of weak signals (subthreshold) in a realistic neural medium in the presence of different levels of the underlying noise. Assuming Hebbian weights for maximal synaptic conductances - that naturally balances the network with excitatory and inhibitory synapses - and considering short-term synaptic plasticity affecting such conductances, we found different dynamical phases in the system. This includes a memory phase where population of neurons remain synchronized, an oscillatory phase where transitions between different synchronized populations of neurons appears and an asynchronous or noisy phase. When a weak stimulus input is applied to each neuron and increasing the level of noise in the medium we found an efficient transmission of such stimuli around the transition and critical points separating different phases and therefore for quite well defined and different levels of stochasticity in the system. We proved that this intriguing phenomenon is quite ro...

  20. Using received signal strength indicator to detect node replacement and replication attacks in wireless sensor networks

    Science.gov (United States)

    Hussain, Sajid; Rahman, Md Shafayat

    2009-04-01

    With the advent of powerful and efficient wireless sensor nodes, the usage of wireless sensor networks (WSNs) has been greatly increased. However, various kinds of security breaches have also been introduced, which exposes the vulnerability of these nodes to defend the valuable data from some specific types of attacks. In this paper, we address node replication, replacement, and man-in-the-middle attacks. We analyze the feasibility of using received signal strength indicator (RSSI) values measured at the receiver node to detect these kinds of attacks. As RSSI value is readily available for every message received by a node, a successful utilization of this information in security breach detection can be a very important contribution.

  1. Efficient Signal Processing in Random Networks that Generate Variability: A Comparison of Internally Generated and Externally Induced Variability

    Science.gov (United States)

    Dasgupta, Sakyasingha; Nishikawa, Isao; Aihara, Kazuyuki; Toyoizumi, Taro

    Source of cortical variability and its influence on signal processing remain an open question. We address the latter, by studying two types of balanced randomly connected networks of quadratic I-F neurons, with irregular spontaneous activity: (a) a deterministic network with strong connections generating noise by chaotic dynamics (b) a stochastic network with weak connections receiving noisy input. They are analytically tractable in the limit of large network-size and channel time-constant. Despite different sources of noise, spontaneous activity of these networks are identical unless majority of neurons are simultaneously recorded. However, the two networks show remarkably different sensitivity to external stimuli. In the former, input reverberates internally and can be read out over long time, but in the latter, inputs rapidly decay. This is further enhanced with activity-dependent plasticity at input synapses producing marked difference in decoding inputs from neural activity. We show, this leads to distinct performance of the two networks to integrate temporally separate signals from multiple sources, with the deterministic chaotic network activity serving as reservoir for Monte Carlo sampling to perform near optimal Bayesian integration, unlike its stochastic counterpart.

  2. Clustering of ECG Signals Based on Fuzzy Neural Network with Initial Weights Generated by Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Elaheh Sayari

    2014-12-01

    Full Text Available Early detection of heart diseases/abnormalities can prolong life and enhance the quality of living through appropriate treatment. Whereas clustering of electrocardiogram (ECG signals will help to identify the heart diseases as soon as possible. In this regard, neural network and fuzzy logic have been used in many application areas while each of them has the advantages and disadvantages. Thus, the present paper utilizes the proposed fuzzy neural network (FNN with initial weights generated by genetic algorithm (GFNN for the sake of improvement testing speed, accuracy and for reducing the chance of the FNN getting stuck on a local minimum. Four types of ECG beats (normal beat, congestive heart failure beat, ventricular tachyarrhythmia beat and atrial fibrillation beat obtained from the Physio Bank databases were clustered by the proposed GFNN model. Model of evaluation results indicate that the proposed model can perform more accurately and it has less testing speed than the conventional statistical methods, a single ANN and FNN. The total clustering accuracy of the GFNN model is 98.23%.

  3. R2NA: Received Signal Strength (RSS Ratio-Based Node Authentication for Body Area Network

    Directory of Open Access Journals (Sweden)

    Yang Wu

    2013-12-01

    Full Text Available The body area network (BAN is an emerging branch of wireless sensor networks for personalized applications. The services in BAN usually have a high requirement on security, especially for the medical diagnosis. One of the fundamental directions to ensure security in BAN is how to provide node authentication. Traditional research using cryptography relies on prior secrets shared among nodes, which leads to high resource cost. In addition, most existing non-cryptographic solutions exploit out-of-band (OOB channels, but they need the help of additional hardware support or significant modifications to the system software. To avoid the above problems, this paper presents a proximity-based node authentication scheme, which only uses wireless modules equipped on sensors. With only one sensor and one control unit (CU in BAN, we could detect a unique physical layer characteristic, namely, the difference between the received signal strength (RSS measured on different devices in BAN. Through the above-mentioned particular difference, we can tell whether the sender is close enough to be legitimate. We validate our scheme through both theoretical analysis and experiments, which are conducted on the real Shimmer nodes. The results demonstrate that our proposed scheme has a good security performance.

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

    Directory of Open Access Journals (Sweden)

    M. Sreeshakthy

    2016-01-01

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

  5. In silico evidence of signaling pathways of notch mediated networks in leukemia

    Directory of Open Access Journals (Sweden)

    Raghunatha Rao

    2012-07-01

    Full Text Available Notch signaling plays a critical role in cell fate determination and maintenance of progenitors in many developmental systems. Notch receptors have been shown to be expressed on hematopoietic progenitor cells as well as to various degrees in peripheral blood T and B lymphocytes, monocytes, and neutrophils. Our aim was to understand the protein interaction network, using Notch1 protein name as query in STRING database and we generated a model to assess the significance of Notch1 associated proteins in Acute Lymphoblastic Leukemia (ALL. We further analyzed the expression levels of the genes encoding hub proteins, using Oncomine database, to determine their significance in leukemogenesis. Of the forty two hub genes, we observed that sixteen genes were underexpressed and eleven genes were overexpressed in T-cell Acute Lymphoblastic samples in comparison to their expression levels in normal cells. Of these, we found three novel genes which have not been reported earlier- KAT2B, PSEN1 (underexpressed and CDH2 (overexpressed.These three identified genes may provide new insights into the abnormal hematopoietic process observed in Leukemia as these genes are involved in Notch signaling and cell adhesion processes. It is evident that experimental validation of the protein interactors in leukemic cells could help in the identification of new diagnostic markers for leukemia.

  6. Electrical signal transmission in a bone cell network: the influence of a discrete gap junction

    Science.gov (United States)

    Zhang, D.; Weinbaum, S.; Cowin, S. C.

    1998-01-01

    A refined electrical cable model is formulated to investigate the role of a discrete gap junction in the intracellular transmission of electrical signals in an electrically coupled system of osteocytes and osteoblasts in an osteon. The model also examines the influence of the ratio q between the membrane's electrical time constant and the characteristic time of pore fluid pressure, the circular, cylindrical geometry of the osteon, and key simplifying assumptions in our earlier continuous cable model (see Zhang, D., S. C. Cowin, and S. Weinbaum. Electrical signal transmission and gap junction regulation in a bone cell network: A cable model for an osteon. Ann. Biomed. Eng. 25:379-396, 1997). Using this refined model, it is shown that (1) the intracellular potential amplitude at the osteoblastic end of the osteonal cable retains the character of a combination of a low-pass and a high-pass filter as the corner frequency varies in the physiological range; (2) the presence of a discrete gap junction near a resting osteoblast can lead to significant modulation of the intracellular potential and current in the osteoblast for measured values of the gap junction coupling strength; and (3) the circular, cylindrical geometry of the osteon is well simulated by the beam analogy used in Zhang et al.

  7. Signaling Network of Environmental Sensing and Adaptation in Plants:. Key Roles of Calcium Ion

    Science.gov (United States)

    Kurusu, Takamitsu; Kuchitsu, Kazuyuki

    2011-01-01

    Considering the important issues concerning food, environment, and energy that humans are facing in the 21st century, humans mostly depend on plants. Unlike animals which move from an inappropriate environment, plants do not move, but rapidly sense diverse environmental changes or invasion by other organisms such as pathogens and insects in the place they root, and adapt themselves by changing their own bodies, through which they developed adaptability. Whole genetic information corresponding to the blueprints of many biological systems has recently been analyzed, and comparative genomic studies facilitated tracing strategies of each organism in their evolutional processes. Comparison of factors involved in intracellular signal transduction between animals and plants indicated diversification of different gene sets. Reversible binding of Ca2+ to sensor proteins play key roles as a molecular switch both in animals and plants. Molecular mechanisms for signaling network of environmental sensing and adaptation in plants will be discussed with special reference to Ca2+ as a key element in information processing.

  8. Multi-modal signal acquisition using a synchronized wireless body sensor network in geriatric patients.

    Science.gov (United States)

    Pflugradt, Maik; Mann, Steffen; Tigges, Timo; Görnig, Matthias; Orglmeister, Reinhold

    2016-02-01

    Wearable home-monitoring devices acquiring various biosignals such as the electrocardiogram, photoplethysmogram, electromyogram, respirational activity and movements have become popular in many fields of research, medical diagnostics and commercial applications. Especially ambulatory settings introduce still unsolved challenges to the development of sensor hardware and smart signal processing approaches. This work gives a detailed insight into a novel wireless body sensor network and addresses critical aspects such as signal quality, synchronicity among multiple devices as well as the system's overall capabilities and limitations in cardiovascular monitoring. An early sign of typical cardiovascular diseases is often shown by disturbed autonomic regulations such as orthostatic intolerance. In that context, blood pressure measurements play an important role to observe abnormalities like hypo- or hypertensions. Non-invasive and unobtrusive blood pressure monitoring still poses a significant challenge, promoting alternative approaches including pulse wave velocity considerations. In the scope of this work, the presented hardware is applied to demonstrate the continuous extraction of multi modal parameters like pulse arrival time within a preliminary clinical study. A Schellong test to diagnose orthostatic hypotension which is typically based on blood pressure cuff measurements has been conducted, serving as an application that might significantly benefit from novel multi-modal measurement principles. It is further shown that the system's synchronicity is as precise as 30 μs and that the integrated analog preprocessing circuits and additional accelerometer data provide significant advantages in ambulatory measurement environments. PMID:26479338

  9. Traffic Congestion Evaluation and Signal Control Optimization Based on Wireless Sensor Networks: Model and Algorithms

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2012-01-01

    Full Text Available This paper presents the model and algorithms for traffic flow data monitoring and optimal traffic light control based on wireless sensor networks. Given the scenario that sensor nodes are sparsely deployed along the segments between signalized intersections, an analytical model is built using continuum traffic equation and develops the method to estimate traffic parameter with the scattered sensor data. Based on the traffic data and principle of traffic congestion formation, we introduce the congestion factor which can be used to evaluate the real-time traffic congestion status along the segment and to predict the subcritical state of traffic jams. The result is expected to support the timing phase optimization of traffic light control for the purpose of avoiding traffic congestion before its formation. We simulate the traffic monitoring based on the Mobile Century dataset and analyze the performance of traffic light control on VISSIM platform when congestion factor is introduced into the signal timing optimization model. The simulation result shows that this method can improve the spatial-temporal resolution of traffic data monitoring and evaluate traffic congestion status with high precision. It is helpful to remarkably alleviate urban traffic congestion and decrease the average traffic delays and maximum queue length.

  10. Cardiac cAMP: production, hydrolysis, modulation and detection

    Directory of Open Access Journals (Sweden)

    Cédric eBOULARAN

    2015-10-01

    Full Text Available Cyclic adenosine 3’,5’-monophosphate (cAMP modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.

  11. The Emerging Field of Signal Processing on Graphs: Extending High-Dimensional Data Analysis to Networks and Other Irregular Domains

    OpenAIRE

    Shuman, David I; Narang, Sunil K.; Frossard, Pascal; Ortega, Antonio; Vandergheynst, Pierre

    2012-01-01

    In applications such as social, energy, transportation, sensor, and neuronal networks, high-dimensional data naturally reside on the vertices of weighted graphs. The emerging field of signal processing on graphs merges algebraic and spectral graph theoretic concepts with computational harmonic analysis to process such signals on graphs. In this tutorial overview, we outline the main challenges of the area, discuss different ways to define graph spectral domains, which are the analogues to the...

  12. A blind hierarchical coherent search for gravitational-wave signals from coalescing compact binaries in a network of interferometric detectors

    OpenAIRE

    Bose., S; Dayanga, T.; S. Ghosh; Talukder, D.

    2011-01-01

    We describe a hierarchical data analysis pipeline for coherently searching for gravitational wave (GW) signals from non-spinning compact binary coalescences (CBCs) in the data of multiple earth-based detectors. It assumes no prior information on the sky position of the source or the time of occurrence of its transient signals and, hence, is termed "blind". The pipeline computes the coherent network search statistic that is optimal in stationary, Gaussian noise, and allows for the computation ...

  13. Regulatory Networks and Complex Interactions between the Insulin and Angiotensin II Signalling Systems: Models and Implications for Hypertension and Diabetes

    OpenAIRE

    Çizmeci, Deniz; Arkun, Yaman

    2013-01-01

    Regulatory Networks and Complex Interactions between the Insulin and Angiotensin II Signalling Systems: Models and Implications for Hypertension and Diabetes Deniz Cizmeci, Yaman Arkun* Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey Abstract The cross-talk between insulin and angiotensin II signalling pathways plays a significant role in the co-occurrence of diabetes and hypertension. We developed a mathematical model of the system of ...

  14. Imaging alterations of cardiomyocyte cAMP microdomains in disease

    Directory of Open Access Journals (Sweden)

    Alexander eFroese

    2015-08-01

    Full Text Available 3’,5’-cyclic adenosine monophosphate (cAMP is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques. We further compile the data from different studies into a bigger picture of so far uncovered alterations in cardiomyocyte cAMP microdomains which occur in compensated cardiac hypertrophy and chronic heart failure. Finally, future research directions and translational perspectives are briefly discussed.

  15. Constant change: dynamic regulation of membrane transport by calcium signalling networks keeps plants in tune with their environment.

    Science.gov (United States)

    Kleist, Thomas J; Luan, Sheng

    2016-03-01

    Despite substantial variation and irregularities in their environment, plants must conform to spatiotemporal demands on the molecular composition of their cytosol. Cell membranes are the major interface between organisms and their environment and the basis for controlling the contents and intracellular organization of the cell. Membrane transport proteins (MTPs) govern the flow of molecules across membranes, and their activities are closely monitored and regulated by cell signalling networks. By continuously adjusting MTP activities, plants can mitigate the effects of environmental perturbations, but effective implementation of this strategy is reliant on precise coordination among transport systems that reside in distinct cell types and membranes. Here, we examine the role of calcium signalling in the coordination of membrane transport, with an emphasis on potassium transport. Potassium is an exceptionally abundant and mobile ion in plants, and plant potassium transport has been intensively studied for decades. Classic and recent studies have underscored the importance of calcium in plant environmental responses and membrane transport regulation. In reviewing recent advances in our understanding of the coding and decoding of calcium signals, we highlight established and emerging roles of calcium signalling in coordinating membrane transport among multiple subcellular locations and distinct transport systems in plants, drawing examples from the CBL-CIPK signalling network. By synthesizing classical studies and recent findings, we aim to provide timely insights on the role of calcium signalling networks in the modulation of membrane transport and its importance in plant environmental responses. PMID:26139029

  16. Experiment on Synchronous Timing Signal Detection from ISDB-T Terrestrial Digital TV Signal with Application to Autonomous Distributed ITS-IVC Network

    Science.gov (United States)

    Karasawa, Yoshio; Kumagai, Taichi; Takemoto, Atsushi; Fujii, Takeo; Ito, Kenji; Suzuki, Noriyoshi

    A novel timing synchronizing scheme is proposed for use in inter-vehicle communication (IVC) with an autonomous distributed intelligent transport system (ITS). The scheme determines the timing of packet signal transmission in the IVC network and employs the guard interval (GI) timing in the orthogonal frequency divisional multiplexing (OFDM) signal currently used for terrestrial broadcasts in the Japanese digital television system (ISDB-T). This signal is used because it is expected that the automotive market will demand the capability for cars to receive terrestrial digital TV broadcasts in the near future. The use of broadcasts by automobiles presupposes that the on-board receivers are capable of accurately detecting the GI timing data in an extremely low carrier-to-noise ratio (CNR) condition regardless of a severe multipath environment which will introduce broad scatter in signal arrival times. Therefore, we analyzed actual broadcast signals received in a moving vehicle in a field experiment and showed that the GI timing signal is detected with the desired accuracy even in the case of extremely low-CNR environments. Some considerations were also given about how to use these findings.

  17. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    International Nuclear Information System (INIS)

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As2O3

  18. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  19. 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...

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

    Lifescience Database Archive (English)

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

  1. Investigations into the relationship between feedback loops and functional importance of a signal transduction network based on Boolean network modeling

    OpenAIRE

    Cho Kwang-Hyun; Choi Sun; Kwon Yung-Keun

    2007-01-01

    Abstract Background A number of studies on biological networks have been carried out to unravel the topological characteristics that can explain the functional importance of network nodes. For instance, connectivity, clustering coefficient, and shortest path length were previously proposed for this purpose. However, there is still a pressing need to investigate another topological measure that can better describe the functional importance of network nodes. In this respect, we considered a fee...

  2. Improving Throughput and Delay by Signaling Modification in Integrated 802.11 and 3G Heterogeneous Wireless Network

    Directory of Open Access Journals (Sweden)

    Majid Fouladian

    2016-02-01

    Full Text Available Current trends show that UMTS network and WLAN will co-exist and work together to support more users with higher data rate services over a wider area. However, this integration invokes many challenges such as mobility management and handoff decision making. Vertical handoff is switching process between heterogeneous wireless networks in a 3G/WLAN network. Vertical handoffs often fail due to the abrupt degrade of the WLAN signal strength. In this paper, proposed a new vertical handoff method for to decrease the number of signaling and registration processes, to examine the Special conditions such as WLAN black holes and to eliminate disconnecting effects. By estimating user locations related to WLAN position, interface on-times will be reduced which makes the power consuming of the system decreased. To indicate the efficiency of proposed approach the performance and the delay results are simulated.

  3. A membrane protein / signaling protein interaction network for Arabidopsis version AMPv2

    Directory of Open Access Journals (Sweden)

    Sylvie Lalonde

    2010-09-01

    Full Text Available Interactions between membrane proteins and the soluble fraction are essential for signal transduction and for regulating nutrient transport. To gain insights into the membrane-based interactome, 3,852 open reading frames (ORFs out of a target list of 8,383 representing membrane and signaling proteins from Arabidopsis thaliana were cloned into a Gateway compatible vector. The mating-based split-ubiquitin system was used to screen for potential protein-protein interactions (pPPIs among 490 Arabidopsis ORFs. A binary robotic screen between 142 receptor-like kinases, 72 transporters, 57 soluble protein kinases and phosphatases, 40 glycosyltransferases, 95 proteins of various functions and 89 proteins with unknown function detected 387 out of 90,370 possible PPIs. A secondary screen confirmed 343 (of 387 pPPIs between 179 proteins, yielding a scale-free network (r2=0.863. Eighty of 142 transmembrane receptor-like kinases (RLK tested positive, identifying three homomers, 63 heteromers and 80 pPPIs with other proteins. Thirty-one out of 142 RLK interactors (including RLKs had previously been found to be phosphorylated; thus interactors may be substrates for respective RLKs. None of the pPPIs described here had been reported in the major interactome databases, including potential interactors of G protein-coupled receptors, phospholipase C, and AMT ammonium transporters. Two RLKs found as putative interactors of AMT1;1 were independently confirmed using a split luciferase assay in Arabidopsis protoplasts. These RLKs may be involved in ammonium-dependent phosphorylation of the C-terminus and regulation of ammonium uptake activity. The robotic screening method established here will enable a systematic analysis of membrane protein interactions in fungi, plants and metazoa.

  4. Design of Flow Systems for Improved Networking and Reduced Noise in Biomolecular Signal Processing in Biocomputing and Biosensing Applications

    Directory of Open Access Journals (Sweden)

    Arjun Verma

    2016-07-01

    Full Text Available We consider flow systems that have been utilized for small-scale biomolecular computing and digital signal processing in binary-operating biosensors. Signal measurement is optimized by designing a flow-reversal cuvette and analyzing the experimental data to theoretically extract the pulse shape, as well as reveal the level of noise it possesses. Noise reduction is then carried out numerically. We conclude that this can be accomplished physically via the addition of properly designed well-mixing flow-reversal cell(s as an integral part of the flow system. This approach should enable improved networking capabilities and potentially not only digital but analog signal-processing in such systems. Possible applications in complex biocomputing networks and various sense-and-act systems are discussed.

  5. Design of Flow Systems for Improved Networking and Reduced Noise in Biomolecular Signal Processing in Biocomputing and Biosensing Applications.

    Science.gov (United States)

    Verma, Arjun; Fratto, Brian E; Privman, Vladimir; Katz, Evgeny

    2016-01-01

    We consider flow systems that have been utilized for small-scale biomolecular computing and digital signal processing in binary-operating biosensors. Signal measurement is optimized by designing a flow-reversal cuvette and analyzing the experimental data to theoretically extract the pulse shape, as well as reveal the level of noise it possesses. Noise reduction is then carried out numerically. We conclude that this can be accomplished physically via the addition of properly designed well-mixing flow-reversal cell(s) as an integral part of the flow system. This approach should enable improved networking capabilities and potentially not only digital but analog signal-processing in such systems. Possible applications in complex biocomputing networks and various sense-and-act systems are discussed. PMID:27399702

  6. RECEIVED SIGNAL STRENGTH ESTIMATION IN VEHICLE-TO-VEHICLE COMMUNICATIONS USING NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Zeinab Talepour

    2014-03-01

    Full Text Available Received signal strength (RSS is a major performance metric in vehicular communication system design. Experimental measurements of the RSS for vehicular communications are not cost effective. Therefore, off-the-shelf ray-tracing packages are deployed to substitute the costly measurements with RSS simulations. However, the simulation process is too time-consuming if the RSS is required over a long interval of time. We propose a new RSS estimation approach using neural network (NN to reduce the computation time. First, ray-tracing is used for simulating the RSS in some instances of time and training the NN. Then, the NN is deployed to estimate the RSS afterward. We apply the new approach to an antenna placement problem in vehicle-to-vehicle (V2V communications. The numerical results show that RSS computation time reduces significantly by using the proposed estimation approach, and the approach is as effective as ray-tracing in the RSS simulation for the antenna placement problem in vehicular communications.

  7. Exploring phospholipase C-coupled Ca(2+) signalling networks using Boolean modelling.

    Science.gov (United States)

    Bhardwaj, G; Wells, C P; Albert, R; van Rossum, D B; Patterson, R L

    2011-05-01

    In this study, the authors explored the utility of a descriptive and predictive bionetwork model for phospholipase C-coupled calcium signalling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP(3)R) and the plasma-membrane resident canonical transient receptor potential channel 3 (TRPC3). These results are specific as randomisation of the Boolean operators ablates oscillatory pattern formation. Furthermore, knock-out simulations of the IP(3)R, TRPC3 and multiple other proteins recapitulate experimentally derived results. The potential of this approach can be observed by its ability to predict previously undescribed cellular phenotypes using in vitro experimental data. Indeed, our cellular analysis of the developmental and calcium-regulatory protein, DANGER1a, confirms the counter-intuitive predictions from our Boolean models in two highly relevant cellular models. Based on these results, the authors theorise that with sufficient legacy knowledge and/or computational biology predictions, Boolean networks can provide a robust method for predictive modelling of any biological system. [Includes supplementary material]. PMID:21639591

  8. Multiobjective Reinforcement Learning for Traffic Signal Control Using Vehicular Ad Hoc Network

    Science.gov (United States)

    Houli, Duan; Zhiheng, Li; Yi, Zhang

    2010-12-01

    We propose a new multiobjective control algorithm based on reinforcement learning for urban traffic signal control, named multi-RL. A multiagent structure is used to describe the traffic system. A vehicular ad hoc network is used for the data exchange among agents. A reinforcement learning algorithm is applied to predict the overall value of the optimization objective given vehicles' states. The policy which minimizes the cumulative value of the optimization objective is regarded as the optimal one. In order to make the method adaptive to various traffic conditions, we also introduce a multiobjective control scheme in which the optimization objective is selected adaptively to real-time traffic states. The optimization objectives include the vehicle stops, the average waiting time, and the maximum queue length of the next intersection. In addition, we also accommodate a priority control to the buses and the emergency vehicles through our model. The simulation results indicated that our algorithm could perform more efficiently than traditional traffic light control methods.

  9. Multiobjective Reinforcement Learning for Traffic Signal Control Using Vehicular Ad Hoc Network

    Directory of Open Access Journals (Sweden)

    Houli Duan

    2010-01-01

    Full Text Available We propose a new multiobjective control algorithm based on reinforcement learning for urban traffic signal control, named multi-RL. A multiagent structure is used to describe the traffic system. A vehicular ad hoc network is used for the data exchange among agents. A reinforcement learning algorithm is applied to predict the overall value of the optimization objective given vehicles' states. The policy which minimizes the cumulative value of the optimization objective is regarded as the optimal one. In order to make the method adaptive to various traffic conditions, we also introduce a multiobjective control scheme in which the optimization objective is selected adaptively to real-time traffic states. The optimization objectives include the vehicle stops, the average waiting time, and the maximum queue length of the next intersection. In addition, we also accommodate a priority control to the buses and the emergency vehicles through our model. The simulation results indicated that our algorithm could perform more efficiently than traditional traffic light control methods.

  10. Statistical Modeling of Large-Scale Signal Path Loss in Underwater Acoustic Networks

    Directory of Open Access Journals (Sweden)

    Manuel Perez Malumbres

    2013-02-01

    Full Text Available In an underwater acoustic channel, the propagation conditions are known to vary in time, causing the deviation of the received signal strength from the nominal value predicted by a deterministic propagation model. To facilitate a large-scale system design in such conditions (e.g., power allocation, we have developed a statistical propagation model in which the transmission loss is treated as a random variable. By applying repetitive computation to the acoustic field, using ray tracing for a set of varying environmental conditions (surface height, wave activity, small node displacements around nominal locations, etc., an ensemble of transmission losses is compiled and later used to infer the statistical model parameters. A reasonable agreement is found with log-normal distribution, whose mean obeys a log-distance increases, and whose variance appears to be constant for a certain range of inter-node distances in a given deployment location. The statistical model is deemed useful for higher-level system planning, where simulation is needed to assess the performance of candidate network protocols under various resource allocation policies, i.e., to determine the transmit power and bandwidth allocation necessary to achieve a desired level of performance (connectivity, throughput, reliability, etc..

  11. DAF-16/FoxO Directly Regulates an Atypical AMP-Activated Protein Kinase Gamma Isoform to Mediate the Effects of Insulin/IGF-1 Signaling on Aging in Caenorhabditis elegans

    OpenAIRE

    Tullet, J. M.; Araiz, C.; Sanders, M J; Au, C.; Benedetto, A.; Papatheodorou, I.; Clark, E.; Schmeisser, K.; Jones, D.; Schuster, E F; Thornton, J M; Gems, D.

    2014-01-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, ...

  12. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    OpenAIRE

    Tullet, Jennifer M. A.; Caroline Araiz; Sanders, Matthew J.; Catherine Au; Alexandre Benedetto; Irene Papatheodorou; Emily Clark; Kathrin Schmeisser; Daniel Jones; Eugene F Schuster; Thornton, Janet M.; David Gems

    2014-01-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, ...

  13. Digital Signal Processing for a Sliceable Transceiver for Optical Access Networks

    DEFF Research Database (Denmark)

    Saldaña Cercos, Silvia; Wagner, Christoph; Vegas Olmos, Juan José; Fagertun, Anna Manolova; Tafur Monroy, Idelfonso

    2015-01-01

    also for implementing full signal path symmetry in real-time oscilloscopes to provide performance and signal fidelity (i.e. lower noise and jitter). In this paper the key digital signal processing (DSP) subsystems required to achieve signal slicing are surveyed. It also presents, for the first time, a...

  14. The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system

    Science.gov (United States)

    Bernabò, Nicola; Barboni, Barbara; Maccarrone, Mauro

    2014-01-01

    Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to manage the information with a computational modeling-based approach. In particular, the use of biological networks has allowed the making of huge progress in this field. Here we discuss two possible application of the use of biological networks to explore cell signaling: the study of the architecture of signaling systems that cooperate in determining the acquisition of a complex cellular function (as it is the case of the process of activation of spermatozoa) and the organization of a single specific signaling systems expressed by different cells in different tissues (i.e. the endocannabinoid system). In both the cases we have found that the networks follow a scale free and small world topology, likely due to the evolutionary advantage of robustness against random damages, fastness and specific of information processing, and easy navigability. PMID:25379139

  15. Interrogating a cell signalling network sensitively monitors cell fate transition during early differentiation of mouse embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU; Yi-Hsin; HO; Chih-ming

    2010-01-01

    The different cell types in an animal are often considered to be specified by combinations of transcription factors,and defined by marker gene expression.This paradigm is challenged,however,in stem cell research and application.Using a mouse embryonic stem cell(mESC) culture system,here we show that the expression level of many key stem cell marker genes/transcription factors such as Oct4,Sox2 and Nanog failed to monitor cell status transition during mESC differentiation.On the other hand,the response patterns of cell signalling network to external stimuli,as monitored by the dynamics of protein phosphorylation,changed dramatically.Our results also suggest that an irreversible alternation in the cell signalling network precedes the adjustment of transcription factor levels.This is consistent with the notion that signal transduction events regulate cell fate specification.We propose that interrogating a cell signalling network can assess the cell property more precisely,and provide a sensitive measurement for the early events in cell fate transition.We wish to bring attention to the potential problem of cell identification using a few marker genes,and suggest a novel methodology to address this issue.

  16. Towards systematic discovery of signaling networks in budding yeast filamentous growth stress response using interventional phosphorylation data.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available Reversible phosphorylation is one of the major mechanisms of signal transduction, and signaling networks are critical regulators of cell growth and development. However, few of these networks have been delineated completely. Towards this end, quantitative phosphoproteomics is emerging as a useful tool enabling large-scale determination of relative phosphorylation levels. However, phosphoproteomics differs from classical proteomics by a more extensive sampling limitation due to the limited number of detectable sites per protein. Here, we propose a comprehensive quantitative analysis pipeline customized for phosphoproteome data from interventional experiments for identifying key proteins in specific pathways, discovering the protein-protein interactions and inferring the signaling network. We also made an effort to partially compensate for the missing value problem, a chronic issue for proteomics studies. The dataset used for this study was generated using SILAC (Stable Isotope Labeling with Amino acids in Cell culture technique with interventional experiments (kinase-dead mutations. The major components of the pipeline include phosphopeptide meta-analysis, correlation network analysis and causal relationship discovery. We have successfully applied our pipeline to interventional experiments identifying phosphorylation events underlying the transition to a filamentous growth form in Saccharomyces cerevisiae. We identified 5 high-confidence proteins from meta-analysis, and 19 hub proteins from correlation analysis (Pbi2p and Hsp42p were identified by both analyses. All these proteins are involved in stress responses. Nine of them have direct or indirect evidence of involvement in filamentous growth. In addition, we tested four of our predicted proteins, Nth1p, Pbi2p, Pdr12p and Rcn2p, by interventional phenotypic experiments and all of them present differential invasive growth, providing prospective validation of our approach. This comprehensive

  17. Coded Single-Tone Signaling and Its Application to Resource Coordination and Interference Management in Femtocell Networks

    CERN Document Server

    Yang, C; Wang, J

    2011-01-01

    Resource coordination and interference management is the key to achieving the benefits of femtocell networks. Over-the-air signaling is one of the most effective means for distributed dynamic resource coordination and interference management. However, the design of this type of signal is challenging. In this paper, we address the challenges and propose an effective solution, referred to as coded single-tone signaling (STS). The proposed coded STS scheme possesses certain highly desirable properties, such as no dedicated resource requirement (no overhead), no near-and-far effect, no inter-signal interference (no multi-user interference), low peak-to-average power ratio (deep coverage). In addition, the proposed coded STS can fully exploit frequency diversity and provides a means for high quality wideband channel estimation. The coded STS design is demonstrated through a concrete numerical example. Performance of the proposed coded STS and its effect on cochannel traffic channels are evaluated through simulatio...

  18. Acceptance of evidence-supported hypotheses generates a stronger signal from an underlying functionally-connected network.

    Science.gov (United States)

    Whitman, J C; Takane, Y; Cheung, T P L; Moiseev, A; Ribary, U; Ward, L M; Woodward, T S

    2016-02-15

    Choosing one's preferred hypothesis requires multiple brain regions to work in concert as a functionally connected network. We predicted that a stronger network signal would underlie cognitive coherence between a hypothesis and the available evidence. In order to identify such functionally connected networks in magnetoencephalography (MEG) data, we first localized the generators of changes in oscillatory power within three frequency bands, namely alpha (7-13Hz), beta (18-24Hz), and theta (3-7Hz), with a spatial resolution of 5mm and temporal resolution of 50ms. We then used principal component analysis (PCA) to identify functionally connected networks reflecting co-varying post-stimulus changes in power. As predicted, PCA revealed a functionally connected network with a stronger signal when the evidence supported accepting the hypothesis being judged. This difference was driven by beta-band power decreases in the left dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), posterior cingulate cortex (PCC), and midline occipital cortex. PMID:26702776

  19. Efficient Hybrid Grid Synthesis Method Based on Genetic Algorithm for Power/Ground Network Optimization with Dynamic Signal Consideration

    Science.gov (United States)

    Yang, Yun; Kimura, Shinji

    This paper proposes an efficient design algorithm for power/ground (P/G) network synthesis with dynamic signal consideration, which is mainly caused by Ldi/dt noise and Cdv/dt decoupling capacitance (DECAP) current in the distribution network. To deal with the nonlinear global optimization under synthesis constraints directly, the genetic algorithm (GA) is introduced. The proposed GA-based synthesis method can avoid the linear transformation loss and the restraint condition complexity in current SLP, SQP, ICG, and random-walk methods. In the proposed Hybrid Grid Synthesis algorithm, the dynamic signal is simulated in the gene disturbance process, and Trapezoidal Modified Euler (TME) method is introduced to realize the precise dynamic time step process. We also use a hybrid-SLP method to reduce the genetic execute time and increase the network synthesis efficiency. Experimental results on given power distribution network show the reduction on layout area and execution time compared with current P/G network synthesis methods.

  20. The classification of oximetry signals using Bayesian neural networks to assist in the detection of obstructive sleep apnoea syndrome

    International Nuclear Information System (INIS)

    In the present study, multilayer perceptron (MLP) neural networks were applied to help in the diagnosis of obstructive sleep apnoea syndrome (OSAS). Oxygen saturation (SaO2) recordings from nocturnal pulse oximetry were used for this purpose. We performed time and spectral analysis of these signals to extract 14 features related to OSAS. The performance of two different MLP classifiers was compared: maximum likelihood (ML) and Bayesian (BY) MLP networks. A total of 187 subjects suspected of suffering from OSAS took part in the study. Their SaO2 signals were divided into a training set with 74 recordings and a test set with 113 recordings. BY-MLP networks achieved the best performance on the test set with 85.58% accuracy (87.76% sensitivity and 82.39% specificity). These results were substantially better than those provided by ML-MLP networks, which were affected by overfitting and achieved an accuracy of 76.81% (86.42% sensitivity and 62.83% specificity). Our results suggest that the Bayesian framework is preferred to implement our MLP classifiers. The proposed BY-MLP networks could be used for early OSAS detection. They could contribute to overcome the difficulties of nocturnal polysomnography (PSG) and thus reduce the demand for these studies