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Sample records for cell signaling network

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  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. Cell Identification based on Received Signal Strength Fingerprints: Concept and Application towards Energy Saving in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Elke Roth-Mandutz

    2014-09-01

    Full Text Available The increasing deployment of small cells aimed at off-loading data traffic from macrocells in heterogeneous networks has resulted in a drastic increase in energy consumption in cellular networks. Energy consumption can be optimized in a selforganized way by adapting the number of active cells in response to the current traffic demand. In this paper we concentrate on the complex problem of how to identify small cells to be reactivated in situations where multiple cells are concurrently inactive. Solely based on the received signal strength, we present cell-specific patterns for the generation of unique cell fingerprints. The cell fingerprints of the deactivated cells are matched with measurements from a high data rate demanding mobile device to identify the most appropriate candidate. Our scheme results in a matching success rate of up to 100% to identify the best cell depending on the number of cells to be activated.

  18. 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.

  19. 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

  20. Transforming growth factor-beta signaling network regulates plasticity and lineage commitment of lung cancer cells

    OpenAIRE

    Ischenko, I; Liu, J.; Petrenko, O; Hayman, M J

    2014-01-01

    Identification of target cells in lung tumorigenesis and characterization of the signals that control their behavior is an important step toward improving early cancer diagnosis and predicting tumor behavior. We identified a population of cells in the adult lung that bear the EpCAM+CD104+CD49f+CD44+CD24loSCA1+ phenotype and can be clonally expanded in culture, consistent with the properties of early progenitor cells. We show that these cells, rather than being restricted to one tumor type, ca...

  1. 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.

  2. Signaling networks and cell motility: a computational approach using a phase field description.

    Science.gov (United States)

    Marth, Wieland; Voigt, Axel

    2014-07-01

    The processes of protrusion and retraction during cell movement are driven by the turnover and reorganization of the actin cytoskeleton. Within a reaction-diffusion model which combines processes along the cell membrane with processes within the cytoplasm a Turing type instability is used to form the necessary polarity to distinguish between cell front and rear and to initiate the formation of different organizational arrays within the cytoplasm leading to protrusion and retraction. A simplified biochemical network model for the activation of GTPase which accounts for the different dimensionality of the cell membrane and the cytoplasm is used for this purpose and combined with a classical Helfrich type model to account for bending and stiffness effects of the cell membrane. In addition streaming within the cytoplasm and the extracellular matrix is taken into account. Combining these phenomena allows to simulate the dynamics of cells and to reproduce the primary phenomenology of cell motility. The coupled model is formulated within a phase field approach and solved using adaptive finite elements. PMID:23835784

  3. Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles.

    Science.gov (United States)

    Rezza, Amélie; Wang, Zichen; Sennett, Rachel; Qiao, Wenlian; Wang, Dongmei; Heitman, Nicholas; Mok, Ka Wai; Clavel, Carlos; Yi, Rui; Zandstra, Peter; Ma'ayan, Avi; Rendl, Michael

    2016-03-29

    The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplifying cell (TAC) progenitors that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing, we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs, and the DP niche express a plethora of ligands and receptors. Signaling interaction network analysis reveals a bird's-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach, this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth. PMID:27009580

  4. Cell signaling review series

    Institute of Scientific and Technical Information of China (English)

    Aiming Lin; Zhenggang Liu

    2008-01-01

    @@ Signal transduction is pivotal for many, if not all, fundamental cellular functions including proliferation, differentiation, transformation and programmed cell death. Deregulation of cell signaling may result in certain types of cancers and other human diseases.

  5. Functional characterization of FLT3 receptor signaling deregulation in acute myeloid leukemia by single cell network profiling (SCNP.

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    David B Rosen

    Full Text Available BACKGROUND: Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3 in cytogenetically normal acute myeloid leukemia (AML has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative. METHODOLOGY/PRINCIPAL FINDINGS: Using single cell network profiling (SCNP, cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L, including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling

  6. Chronic morphine treatment attenuates cell growth of human BT474 breast cancer cells by rearrangement of the ErbB signalling network.

    Directory of Open Access Journals (Sweden)

    Inka Regine Weingaertner

    Full Text Available There is increasing evidence that opioid analgesics may interfere with tumour growth. It is currently thought that these effects are mediated by transactivation of receptor tyrosine kinase (RTK-controlled ERK1/2 and Akt signalling. The growth of many breast cancer cells is dependent on hyperactive ErbB receptor networks and one of the most successful approaches in antineoplastic therapy during the last decade was the development of ErbB-targeted therapies. However, the response rates of single therapies are often poor and resistance mechanisms evolve rapidly. To date there is no information about the ability of opioid analgesics to interfere with the growth of ErbB-driven cancers.Here we demonstrate that ErbB2 overexpressing BT474 human breast cancer cells carry fully functional endogenous µ-opioid receptors. Most interestingly, the acute opioid effects on basal and Heregulin-stimulated ERK1/2 and Akt phosphorylation changed considerably during chronic Morphine treatment. Investigation of the underlying mechanism by the use of protein kinase inhibitors and co-immunoprecipitation studies revealed that chronic Morphine treatment results in rearrangement of the ErbB signalling network leading to dissociation of ERK1/2 from Akt signalling and a switch from ErbB1/ErbB3 to ErbB1/ErbB2-dependent cell growth. In chronically Morphine-treated cells Heregulin-stimulated ERK1/2 signalling is redirected via a newly established PI3K- and metalloproteinase-dependent feedback loop. Together, these alterations result in apoptosis of BT474 cells. A similar switch in Heregulin-stimulated ERK1/2 signalling from an ErbB2-independent to an ErbB2-, PI3K- and metalloproteinase-dependent mechanism was also observed in κ-opioid receptor expressing SKBR3 human mammary adenocarcinoma cells.The present data demonstrate that the ErbB receptor network of human breast cancer cells represents a target for chronic Morphine treatment. Rearrangement of ErbB signalling by chronic

  7. Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells

    Science.gov (United States)

    Kulbe, Hagen; Iorio, Francesco; Chakravarty, Probir; Milagre, Carla S.; Moore, Robert; Thompson, Richard G.; Everitt, Gemma; Canosa, Monica; Montoya, Alexander; Drygin, Denis; Braicu, Ioana; Sehouli, Jalid; Saez-Rodriguez, Julio; Cutillas, Pedro R.; Balkwill, Frances R.

    2016-01-01

    We previously showed how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in ovarian cancer. This network, which we named the “TNF network”, has paracrine actions within the tumor microenvironment, influencing angiogenesis and the immune cell infiltrate. The aim of this study was to identify critical regulators in the signaling pathways of the TNF network in ovarian cancer cells that might be therapeutic targets. To achieve our aim, we used a systems biology approach, combining data from phospho-proteomic mass spectrometry and gene expression array analysis. Among the potential therapeutic kinase targets identified was the protein kinase Casein kinase II (CK2). Knockdown of CK2 expression in malignant cells by siRNA or treatment with the specific CK2 inhibitor CX-4945 significantly decreased Notch signaling and reduced constitutive cytokine release in ovarian cancer cell lines that expressed the TNF network as well as malignant cells isolated from high grade serous ovarian cancer ascites. The expression of the same cytokines was also inhibited after treatment with CX-4945 in a 3D organotypic model. CK2 inhibition was associated with concomitant inhibition of proliferative activity, reduced angiogenesis and experimental peritoneal ovarian tumor growth. In conclusion, we have identified kinases, particularly CK2, associated with the TNF network that may play a central role in sustaining the cytokine network and/or mediating its effects in ovarian cancer. PMID:26871292

  8. 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.)

  9. Retrograde signaling: Organelles go networking.

    Science.gov (United States)

    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

  10. 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.

  11. Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network.

    Science.gov (United States)

    Yang, Jiajia; Hou, Yixuan; Zhou, Mingli; Wen, Siyang; Zhou, Jian; Xu, Liyun; Tang, Xi; Du, Yan-e; Hu, Ping; Liu, Manran

    2016-02-01

    Twist, a highly conserved basic Helix-Loop-Helix transcription factor, functions as a major regulator of epithelial-mesenchymal transition (EMT) and tumor metastasis. In different cell models, signaling pathways such as TGF-β, MAPK/ERK, WNT, AKT, JAK/STAT, Notch, and P53 have also been shown to play key roles in the EMT process, yet little is known about the signaling pathways regulated by Twist in tumor cells. Using iTRAQ-labeling combined with 2D LC-MS/MS analysis, we identified 194 proteins with significant changes of expression in MCF10A-Twist cells. These proteins reportedly play roles in EMT, cell junction organization, cell adhesion, and cell migration and invasion. ECM-receptor interaction, MAPK, PI3K/AKT, P53 and WNT signaling were found to be aberrantly activated in MCF10A-Twist cells. Ingenuity Pathways Analysis showed that integrin β1 (ITGB1) acts as a core regulator in linking integrin-linked kinase (ILK), Focal-adhesion kinase (FAK), MAPK/ERK, PI3K/AKT, and WNT signaling. Increased Twist and ITGB1 are associated with breast tumor progression. Twist transcriptionally regulates ITGB1 expression. Over-expression of ITGB1 or Twist in MCF10A led to EMT, activation of FAK/ILK, MAPK/ERK, PI3K/AKT, and WNT signaling. Knockdown of Twist or ITGB1 in BT549 and Hs578T cells decreased activity of FAK, ILK, and their downstream signaling, thus specifically impeding EMT and cell invasion. Knocking down ILK or inhibiting FAK, MAPK/ERK, or PI3K/AKT signaling also suppressed Twist-driven EMT and cell invasion. Thus, the Twist-ITGB1-FAK/ILK pathway and their downstream signaling network dictate the Twist-induced EMT process in human mammary epithelial cells and breast cancer cells. PMID:26693891

  12. The cancer stem-cell signaling network and resistance to therapy.

    Science.gov (United States)

    Carnero, A; Garcia-Mayea, Y; Mir, C; Lorente, J; Rubio, I T; LLeonart, M E

    2016-09-01

    The study of cancer stem cells (CSCs) has shown that tumors are driven by a subpopulation of self-renewing CSCs that retain the capacity to engender the various differentiated cell populations that form tumors. The characterization of CSCs has indicated that CSCs are remarkably resistant to conventional radio- and chemo-therapy. Clinically, the remaining populations of CSC are responsible for metastasis and recurrence in patients with cancer, which can lead to the disease becoming chronic and incurable. Therefore, the elimination of CSCs is an important goal of cancer treatments. Furthermore, CSCs are subject to strong regulation by the surrounding microenvironment, which also impacts tumor responses. In this review, we discuss the mechanisms by which pathways that are defective in CSCs influence ultimately therapeutic and clinical outcomes. PMID:27434881

  13. Stem Cell Networks

    OpenAIRE

    Werner, Eric

    2016-01-01

    We present a general computational theory of stem cell networks and their developmental dynamics. Stem cell networks are special cases of developmental control networks. Our theory generates a natural classification of all possible stem cell networks based on their network architecture. Each stem cell network has a unique topology and semantics and developmental dynamics that result in distinct phenotypes. We show that the ideal growth dynamics of multicellular systems generated by stem cell ...

  14. 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...

  15. A Cell-Signaling Network Temporally Resolves Specific versus Promiscuous Phosphorylation

    Directory of Open Access Journals (Sweden)

    Evgeny Kanshin

    2015-02-01

    Full Text Available If specific and functional kinase- or phosphatase-substrate interactions are optimized for binding compared to promiscuous interactions, then changes in phosphorylation should occur faster on functional versus promiscuous substrates. To test this hypothesis, we designed a high temporal resolution global phosphoproteomics protocol to study the high-osmolarity glycerol (HOG response in the budding yeast Saccharomyces cerevisiae. The method provides accurate, stimulus-specific measurement of phosphoproteome changes, quantitative analysis of phosphodynamics at sub-minute temporal resolution, and detection of more phosphosites. Rates of evolution of dynamic phosphosites were comparable to those of known functional phosphosites and significantly lower than static or longer-time-frame dynamic phosphosites. Kinetic profile analyses indicated that putatively functional kinase- or phosphatase-substrate interactions occur more rapidly, within 60 s, than promiscuous interactions. Finally, we report many changes in phosphorylation of proteins implicated in cytoskeletal and mitotic spindle dynamics that may underlie regulation of cell cycle and morphogenesis.

  16. 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.

  17. 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...

  18. 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.

  19. Evaluation of phosphopeptide enrichment strategies for quantitative TMT analysis of complex network dynamics in cancer-associated cell signalling

    OpenAIRE

    Benedetta Lombardi; Nigel Rendell; Mina Edwards; Matilda Katan; Jasminka Godovac Zimmermann

    2015-01-01

    Defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics. A number of different approaches have been established to isolate, identify and quantify phosphorylated proteins and peptides. In the current report, a comparison between SCX prefractionation versus an antibody based approach, both coupled to TiO2 enrichment and applied to TMT labelled cellular lysates, is described. The antibody strategy was more complete for enriching phosphope...

  20. The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system

    OpenAIRE

    Nicola Bernabò; Barbara Barboni; Mauro Maccarrone

    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 ma...

  1. 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....

  2. 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...

  3. 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....

  4. Evaluation of phosphopeptide enrichment strategies for quantitative TMT analysis of complex network dynamics in cancer-associated cell signalling

    Directory of Open Access Journals (Sweden)

    Benedetta Lombardi

    2015-03-01

    Full Text Available Defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics. A number of different approaches have been established to isolate, identify and quantify phosphorylated proteins and peptides. In the current report, a comparison between SCX prefractionation versus an antibody based approach, both coupled to TiO2 enrichment and applied to TMT labelled cellular lysates, is described. The antibody strategy was more complete for enriching phosphopeptides and allowed the identification of a large set of proteins known to be phosphorylated (715 protein groups with a minimum number of not previously known phosphorylated proteins (2.

  5. Origin of cells and network information

    Institute of Scientific and Technical Information of China (English)

    Shihori Tanabe

    2015-01-01

    All cells are derived from one cell, and the origin ofdifferent cell types is a subject of curiosity. Cells constructlife through appropriately timed networks at each stageof development. Communication among cells andintracellular signaling are essential for cell differentiationand for life processes. Cellular molecular networksestablish cell diversity and life. The investigation ofthe regulation of each gene in the genome within thecellular network is therefore of interest. Stem cellsproduce various cells that are suitable for specificpurposes. The dynamics of the information in thecellular network changes as the status of cells isaltered. The components of each cell are subject toinvestigation.

  6. 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

  7. 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.

  8. Profiling Signaling Polarity in Chemotactic Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yingchun; Ding, Shi-Jian; Wang, Wei; Jacobs, Jon M.; Qian, Weijun; Moore, Ronald J.; Yang, Feng; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2007-05-15

    While directional movement requires morphological polarization characterized by formation of a leading pseudopodium at the front and a trailing rear at the back, little is known about how protein networks are spatially integrated to regulate this process. Here, we utilize a unique pseudopodial purification system and quantitative proteomics and phosphoproteomics to map the spatial relationship of 3509 proteins and 228 distinct sites of phosphorylation in polarized cells. Networks of signaling proteins, metabolic pathways, actin regulatory proteins, and kinase-substrate cascades were found to partition to different poles of the cell including components of the Ras/ERK pathway. Also, several novel proteins were found to be differentially phosphorylated at the front or rear of polarized cells and to localize to distinct subcellular structures. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive profile of proteins and their sites of phosphorylation that control cell polarization.

  9. 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...

  10. 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...

  11. 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

  12. Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State.

    Science.gov (United States)

    Sacco, Francesca; Silvestri, Alessandra; Posca, Daniela; Pirrò, Stefano; Gherardini, Pier Federico; Castagnoli, Luisa; Mann, Matthias; Cesareni, Gianni

    2016-03-23

    Metformin is the most frequently prescribed drug for type 2 diabetes. In addition to its hypoglycemic effects, metformin also lowers cancer incidence. This anti-cancer activity is incompletely understood. Here, we profiled the metformin-dependent changes in the proteome and phosphoproteome of breast cancer cells using high-resolution mass spectrometry. In total, we quantified changes of 7,875 proteins and 15,813 phosphosites after metformin changes. To interpret these datasets, we developed a generally applicable strategy that overlays metformin-dependent changes in the proteome and phosphoproteome onto a literature-derived network. This approach suggested that metformin treatment makes cancer cells more sensitive to apoptotic stimuli and less sensitive to pro-growth stimuli. These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner. In conclusion, analysis of deep proteomics reveals both detailed and global mechanisms that contribute to the anti-cancer activity of metformin. PMID:27135362

  13. 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.

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Learning robust cell signalling models from high throughput proteomic data

    OpenAIRE

    Koch, Mitchell; Broom, Bradley M.; Subramanian, Devika

    2009-01-01

    We propose a framework for learning robust Bayesian network models of cell signalling from high-throughput proteomic data. We show that model averaging using Bayesian bootstrap resampling generates more robust structures than procedures that learn structures using all of the data. We also develop an algorithm for ranking the importance of network features using bootstrap resample data. We apply our algorithms to derive the T-cell signalling network from the flow cytometry data of Sachs et al....

  17. 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

  18. 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

  19. 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...

  20. 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

  1. 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.'

  2. 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

  3. 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

  4. Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines

    Directory of Open Access Journals (Sweden)

    Emmanuelle Berger

    2015-01-01

    Full Text Available Cancer progression may be affected by metabolism. In this study, we aimed to analyze the effect of glucose on the proliferation and/or survival of human hepatocellular carcinoma (HCC cells. Human gene datasets regulated by glucose were compared to gene datasets either dysregulated in HCC or regulated by other signaling pathways. Significant numbers of common genes suggested putative involvement in transcriptional regulations by glucose. Real-time proliferation assays using high (4.5 g/L versus low (1 g/L glucose on two human HCC cell lines and specific inhibitors of selected pathways were used for experimental validations. High glucose promoted HuH7 cell proliferation but not that of HepG2 cell line. Gene network analyses suggest that gene transcription by glucose could be mediated at 92% through ChREBP in HepG2 cells, compared to 40% in either other human cells or rodent healthy liver, with alteration of LKB1 (serine/threonine kinase 11 and NOX (NADPH oxidases signaling pathways and loss of transcriptional regulation of PPARGC1A (peroxisome-proliferator activated receptors gamma coactivator 1 target genes by high glucose. Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression.

  5. T cell traffic signals

    OpenAIRE

    Van Epps, Heather L.

    2005-01-01

    In 1990, Charles Mackay and colleagues combined classical physiology with modern molecular biology to provide the first concrete evidence that naive and memory T cells follow distinct migratory routes out of the bloodstream— a discovery that helped invigorate the field of lymphocyte homing.

  6. 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...

  7. 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.

  8. Non-Invasive Green Small Cell Network

    OpenAIRE

    Mawlawi, Baher; Bastug, Ejder; Nerguizian, Chahé; Azarian, Sylvain; Debbah, Mérouane

    2011-01-01

    Future low cost wireless networks are expected to provide high data rates with low power consumption. A dense deployment of distributed small-cells, within the existing network infrastructure, is one of the candidate solutions to achieve this goal. Unfortunately, the aggregate signal resulting from the transmission of these multiples small cells can be considered as an electromagnetic (EM) pollution for passive users who do not carry wireless devices. These users are victim of primary electro...

  9. Cell signalling and phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-01-01

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Syndecans, signaling, and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1996-01-01

    structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link with the...... transmembrane signaling from matrix to cytoskeleton, as proposed for other classes of adhesion receptors....

  15. A positive feedback cell signaling nucleation model of astrocyte dynamics

    Directory of Open Access Journals (Sweden)

    Gabriel A Silva

    2013-07-01

    Full Text Available We constructed a model of calcium signaling in astrocyte neural glial cells that incorporates a positive feedback nucleation mechanism, whereby small microdomain increases in local calcium can stochastically produce global cellular and intercellular network scale dynamics. The model is able to simultaneously capture dynamic spatial and temporal heterogeneities associated with intracellular calcium transients in individual cells and intercellular calcium waves (ICW in spatially realistic networks of astrocytes, i.e. networks where the positions of cells were taken from real in vitro experimental data of spontaneously forming sparse networks, as opposed to artificially constructed grid networks or other non-realistic geometries. This is the first work we are aware of where an intracellular model of calcium signaling that reproduces intracellular dynamics inherently accounts for intercellular network dynamics. These results suggest that a nucleation type mechanism should be further investigated experimentally in order to test its contribution to calcium signaling in astrocytes and in other cells more broadly. It may also be of interest in engineered neuromimetic network systems that attempt to emulate biological signaling and information processing properties in synthetic hardwired neuromorphometric circuits or coded algorithms.

  16. 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...

  17. 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.

  18. 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.

  19. Networks in Cell Biology = Modelling cell biology with networks

    OpenAIRE

    Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, M.

    2010-01-01

    The science of complex biological networks is transforming research in areas ranging from evolutionary biology to medicine. This is the first book on the subject, providing a comprehensive introduction to complex network science and its biological applications. With contributions from key leaders in both network theory and modern cell biology, this book discusses the network science that is increasingly foundational for systems biology and the quantitative understanding of living systems. It ...

  20. 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...

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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...

  9. 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...

  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. 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...

  12. Cell Wall Integrity Signaling in Saccharomyces cerevisiae

    OpenAIRE

    Levin, David E.

    2005-01-01

    The yeast cell wall is a highly dynamic structure that is responsible for protecting the cell from rapid changes in external osmotic potential. The wall is also critical for cell expansion during growth and morphogenesis. This review discusses recent advances in understanding the various signal transduction pathways that allow cells to monitor the state of the cell wall and respond to environmental challenges to this structure. The cell wall integrity signaling pathway controlled by the small...

  13. 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...

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  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. 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

  4. 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

  5. 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)

  6. A positive feedback cell signaling nucleation model of astrocyte dynamics

    OpenAIRE

    MacDonald, Christopher L.; Silva, Gabriel A.

    2013-01-01

    We constructed a model of calcium signaling in astrocyte neural glial cells that incorporates a positive feedback nucleation mechanism, whereby small microdomain increases in local calcium can stochastically produce global cellular and intercellular network scale dynamics. The model is able to simultaneously capture dynamic spatial and temporal heterogeneities associated with intracellular calcium transients in individual cells and intercellular calcium waves (ICW) in spatially realistic netw...

  7. Wnt signalling pathway parameters for mammalian cells.

    Science.gov (United States)

    Tan, Chin Wee; Gardiner, Bruce S; Hirokawa, Yumiko; Layton, Meredith J; Smith, David W; Burgess, Antony W

    2012-01-01

    Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated with the parameters

  8. Wnt signalling pathway parameters for mammalian cells.

    Directory of Open Access Journals (Sweden)

    Chin Wee Tan

    Full Text Available Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated

  9. 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.

  10. 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...

  11. 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

  12. Wnt Signaling in Cancer Stem Cell Biology

    Science.gov (United States)

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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)

  18. 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.

  19. 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.

  20. 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...

  1. 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

  2. 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....

  3. 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

  4. The AII Amacrine Cell Connectome: A Dense Network Hub

    OpenAIRE

    Marc, Robert E.; James Russell Anderson; Bryan William Jones; Crystal Lynn Sigulinsky; James Scott Lauritzen

    2014-01-01

    The mammalian AII retinal amacrine cell is a narrow-field, multistratified glycinergic neuron best known for its role in collecting scotopic signals from rod bipolar cells and distributing them to ON and OFF cone pathways in a crossover network via a combination of inhibitory synapses and heterocellular AII::ON cone bipolar cell gap junctions. Long considered a simple cell, a full connectomics analysis shows that AII cells possess the most complex interaction repertoire of any known vertebrat...

  5. 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...

  6. 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 ...

  7. Articular cartilage stem cell signalling

    OpenAIRE

    Karlsson, Camilla; Lindahl, Anders

    2009-01-01

    The view of articular cartilage as a non-regeneration organ has been challenged in recent years. The articular cartilage consists of distinct zones with different cellular and molecular phenotypes, and the superficial zone has been hypothesized to harbour stem cells. Furthermore, the articular cartilage demonstrates a distinct pattern regarding stem cell markers (that is, Notch-1, Stro-1, and vascular cell adhesion molecule-1). These results, in combination with the positive identification of...

  8. 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.

  9. Wnt signaling and stem cell control

    Institute of Scientific and Technical Information of China (English)

    Roel Nusse

    2008-01-01

    Wnt signaling has been implicated in the control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state.As currently understood,Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface.Through several cytoplasmic relay components,the signal is transduced to B-catenin,which then enters the nucleus and forms a complex with TCF to activate transcription of Wnt target genes.Wnts can also signal through tyrosine kinase receptors,in particular the ROR and RYK receptors,leading to alternative modes of Wnt signaling.During the growth of tissues,these ligands and receptors are dynamically expressed,often transcriptionally controlled by Wnt signals themselves,to ensure the right balance between proliferation and differentiation.Isolated Wnt proteins are active on a variety of stem cells,including neural,mammary and embryonic stem cells.In general,Wnt proteins act to maintain the undifferentiated state of stem cells,while other growth factors instruct the cells to proliferate.These other factors include FGF and EGF,signaling through tyrosine kinase pathways.

  10. 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

  11. Ceramide signaling in cancer and stem cells

    OpenAIRE

    Bieberich, Erhard

    2008-01-01

    Most of the previous work on the sphingolipid ceramide has been devoted to its function as an apoptosis inducer. Recent studies, however, have shown that in stem cells, ceramide has additional nonapoptotic functions. In this article, ceramide signaling will be reviewed in light of ‘systems interface biology’: as an interconnection of sphingolipid metabolism, membrane biophysics and cell signaling. The focus will be on the metabolic interconversion of ceramide and sphingomyelin or sphingosine-...

  12. N-Acetylglucosamine Functions in Cell Signaling

    Directory of Open Access Journals (Sweden)

    James B. Konopka

    2012-01-01

    Full Text Available The amino sugar N-acetylglucosamine (GlcNAc is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli responds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.

  13. 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...

  14. Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution.

    Science.gov (United States)

    Lin, Xiukun; Farooqi, Ammad Ahmad; Qureshi, Muhammad Zahid; Romero, Mirna Azalea; Tabassum, Sobia; Ismail, Muhammad

    2016-06-01

    It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with "stem cell" like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as "cancer stem cells". Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network. PMID:26846602

  15. Janus kinases in immune cell signaling

    OpenAIRE

    Ghoreschi, Kamran; Laurence, Arian; O’Shea, John J.

    2009-01-01

    The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jak in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical dis...

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. Cell cycle and cell signal transduction in marine phytoplankton

    Institute of Scientific and Technical Information of China (English)

    LIU Jingwen; JIAO Nianzhi; CAI Huinong

    2006-01-01

    As unicellular phytoplankton, the growth of a marine phytoplankton population results directly from the completion of a cell cycle, therefore, cell-environment communication is an important way which involves signal transduction pathways to regulate cell cycle progression and contribute to growth, metabolism and primary production and respond to their surrounding environment in marine phytoplankton. Cyclin-CDK and CaM/Ca2+ are essentially key regulators in control of cell cycle and signal transduction pathway, which has important values on both basic research and applied biotechnology. This paper reviews progress made in this research field, which involves the identification and characterization of cyclins and cell signal transduction system, cell cycle control mechanisms in marine phytoplankton cells, cell cycle proteins as a marker of a terminal event to estimate the growth rate of phytoplankton at the species level, cell cycle-dependent toxin production of toxic algae and cell cycle progression regulated by environmental factors.

  1. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Signal transduction and chemotaxis in mast cells.

    Science.gov (United States)

    Draber, Petr; Halova, Ivana; Polakovicova, Iva; Kawakami, Toshiaki

    2016-05-01

    Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis. PMID:25941081

  7. 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.

  8. New Twists in Drosophila Cell Signaling.

    Science.gov (United States)

    Shilo, Ben-Zion

    2016-04-01

    The discovery of a handful of conserved signaling pathways that dictate most aspects of embryonic and post-embryonic development of multicellular organisms has generated a universal view of animal development (Perrimon, N., Pitsouli, C., and Shilo, B. Z. (2012)Cold Spring Harb. Perspect. Biol.4, a005975). Although we have at hand most of the "hardware" elements that mediate cell communication events that dictate cell fate choices, we are still far from a comprehensive mechanistic understanding of these processes. One of the next challenges entails an analysis of developmental signaling pathways from the cell biology perspective. Where in the cell does signaling take place, and how do general cellular machineries and structures contribute to the regulation of developmental signaling? Another challenge is to examine these signaling pathways from a quantitative perspective, rather than as crude on/off switches. This requires more precise measurements, and incorporation of the time element to generate a dynamic sequence instead of frozen snapshots of the process. The quantitative outlook also brings up the issue of precision, and the unknown mechanisms that buffer variability in signaling between embryos, to produce a robust and reproducible output. Although these issues are universal to all multicellular organisms, they can be effectively tackled in theDrosophilamodel, by a combination of genetic manipulations, biochemical analyses, and a variety of imaging techniques. This review will present some of the recent advances that were accomplished by utilizing the versatility of theDrosophilasystem. PMID:26907691

  9. Cell signalling and phospholipid metabolism. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-12-31

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Tracking hypoxic signaling within encapsulated cell aggregates.

    Science.gov (United States)

    Skiles, Matthew L; Sahai, Suchit; Blanchette, James O

    2011-01-01

    In Diabetes mellitus type 1, autoimmune destruction of the pancreatic β-cells results in loss of insulin production and potentially lethal hyperglycemia. As an alternative treatment option to exogenous insulin injection, transplantation of functional pancreatic tissue has been explored. This approach offers the promise of a more natural, long-term restoration of normoglycemia. Protection of the donor tissue from the host's immune system is required to prevent rejection and encapsulation is a method used to help achieve this aim. Biologically-derived materials, such as alginate and agarose, have been the traditional choice for capsule construction but may induce inflammation or fibrotic overgrowth which can impede nutrient and oxygen transport. Alternatively, synthetic poly(ethylene glycol) (PEG)-based hydrogels are non-degrading, easily functionalized, available at high purity, have controllable pore size, and are extremely biocompatible. As an additional benefit, PEG hydrogels may be formed rapidly in a simple photo-crosslinking reaction that does not require application of non-physiological temperatures. Such a procedure is described here. In the crosslinking reaction, UV degradation of the photoinitiator, 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), produces free radicals which attack the vinyl carbon-carbon double bonds of dimethacrylated PEG (PEGDM) inducing crosslinking at the chain ends. Crosslinking can be achieved within 10 minutes. PEG hydrogels constructed in such a manner have been shown to favorably support cells, and the low photoinitiator concentration and brief exposure to UV irradiation is not detrimental to viability and function of the encapsulated tissue. While we methacrylate our PEG with the method described below, PEGDM can also be directly purchased from vendors such as Sigma. An inherent consequence of encapsulation is isolation of the cells from a vascular network. Supply of nutrients, notably oxygen

  15. Wnt Signalling Pathway Parameters for Mammalian Cells

    OpenAIRE

    Tan, Chin Wee; Gardiner, Bruce S.; Hirokawa, Yumiko; Layton, Meredith J.; Smith, David W.; Burgess, Antony W.

    2012-01-01

    Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a c...

  16. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  17. A special issue on cell signaling, disease, and stem cells

    Institute of Scientific and Technical Information of China (English)

    Dangsheng Li

    2012-01-01

    As the basic unit of life,cells utilize signaling pathways to receive inputs from the environment and translate such information into appropriate cellular behaviors and responses.Cell signaling is also pivotal for multicellular organisms such as mammals,as cells need to communicate extensively among each other and with the environment in order to orchestrate appropriate actions,which are in turn integrated at the system level for the proper functioning and well-being of the organism.Thus,understanding the molecular mechanisms of cell signaling constitutes a fundamental quest of today's life science research.Not surprisingly,dysregulation of cell signaling causes many diseases such as cancer,and in such cases,a thorough understanding of the nature of cell signaling under disease states would provide an important basis to the efforts of developing novel therapeutic strategies.In this context,we are pleased to present this 2012 Cell Research Special Issue focusing on "Cell signaling,disease,and stem cells".

  18. 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...

  19. 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.

  20. Small Cell Network Topology Comparison

    Directory of Open Access Journals (Sweden)

    Jan Oppolzer

    2013-01-01

    Full Text Available One of the essential problems in a mobile network with small cells is that there is only a limited number of (PCIs available. Due to this fact, operators face the inevitable need for reusing (PCIs. In our contribution, we are dealing with a (PCI assignment to FAPs in three different topologies. The first model places FAPs randomly within the network while respecting overlapping defined. The second model places FAPs in a grid without other restrictions. The third model forms a grid as well, although buildings and roads are taken into account and (FAPs are always inside buildings. The proposed models are compared and a conclusion is made based on simulation results.

  1. 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

  2. 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.

  3. Regulation of Akt/FOXO3a/GSK-3β/AR Signaling Network by Isoflavone in Prostate Cancer Cells*

    OpenAIRE

    Li, Yiwei; Wang, Zhiwei; Kong, Dejuan; Li, Ran; Sarkar, Sanila H.; Sarkar, Fazlul H

    2008-01-01

    We have previously shown that genistein could inhibit Akt activation and down-regulate AR (androgen receptor) and PSA (prostate-specific antigen) expression in prostate cancer (PCa) cells. However, pure genistein showed increased lymph node metastasis in an animal model, but such an adverse effect was not seen with isoflavone, suggesting that further mechanistic studies are needed for elucidating the role of isoflavone in PCa. It is known that FOXO3a and GSK-3β, target...

  4. 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

  5. A Cell Phone Positioning Method Based on the Intelligent Received Signal Strength Pattern Recognition in GSM Network for Implementing Mobile Advertisement Services

    Directory of Open Access Journals (Sweden)

    M. F Sabahi

    2013-06-01

    Full Text Available Cellular positioning methods in urban environments suffer from a significant error due to multipath and fading phenomena. In this paper, regarding the implementation location-based services, one pattern recognition positioning method based on the signal strength is presented, which provides proper results in urban areas. Although many works have been done in this field, the main challenge is to create and to update the database and heavy calculation to estimate the position .In this paper, some practical and intelligent solutions for overcoming the mentioned problems, enhancing the accuracy and reducing the computational load of this positioning method are presented. Specially, some intelligent filtering methods are presented for reducing the search region in the database and also increasing the accuracy of position estimation. Real measurements obtained in Isfahan, illustrate the high accuracy of the proposed techniques. In addition, an advertising service based on the proposed method is presented. User’s interest and local time is considered as well as him/her position for enhancing the efficiency of the mentioned service.

  6. 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

  7. 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

  8. Erythropoietin signaling promotes transplanted progenitor cell survival

    OpenAIRE

    Jia, Yi; Warin, Renaud; Yu, Xiaobing; Epstein, Reed; Noguchi, Constance Tom

    2009-01-01

    We examine the potential for erythropoietin signaling to promote donor cell survival in a model of myoblast transplantation. Expression of a truncated erythropoietin receptor in hematopoietic stem cells has been shown to promote selective engraftment in mice. We previously demonstrated expression of endogenous erythropoietin receptor on murine myoblasts, and erythropoietin treatment can stimulate myoblast proliferation and delay differentiation. Here, we report that enhanced erythropoietin re...

  9. 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

  10. Designer cell signal processing circuits for biotechnology

    Science.gov (United States)

    Bradley, Robert W.; Wang, Baojun

    2015-01-01

    Microorganisms are able to respond effectively to diverse signals from their environment and internal metabolism owing to their inherent sophisticated information processing capacity. A central aim of synthetic biology is to control and reprogramme the signal processing pathways within living cells so as to realise repurposed, beneficial applications ranging from disease diagnosis and environmental sensing to chemical bioproduction. To date most examples of synthetic biological signal processing have been built based on digital information flow, though analogue computing is being developed to cope with more complex operations and larger sets of variables. Great progress has been made in expanding the categories of characterised biological components that can be used for cellular signal manipulation, thereby allowing synthetic biologists to more rationally programme increasingly complex behaviours into living cells. Here we present a current overview of the components and strategies that exist for designer cell signal processing and decision making, discuss how these have been implemented in prototype systems for therapeutic, environmental, and industrial biotechnological applications, and examine emerging challenges in this promising field. PMID:25579192

  11. Designer cell signal processing circuits for biotechnology.

    Science.gov (United States)

    Bradley, Robert W; Wang, Baojun

    2015-12-25

    Microorganisms are able to respond effectively to diverse signals from their environment and internal metabolism owing to their inherent sophisticated information processing capacity. A central aim of synthetic biology is to control and reprogramme the signal processing pathways within living cells so as to realise repurposed, beneficial applications ranging from disease diagnosis and environmental sensing to chemical bioproduction. To date most examples of synthetic biological signal processing have been built based on digital information flow, though analogue computing is being developed to cope with more complex operations and larger sets of variables. Great progress has been made in expanding the categories of characterised biological components that can be used for cellular signal manipulation, thereby allowing synthetic biologists to more rationally programme increasingly complex behaviours into living cells. Here we present a current overview of the components and strategies that exist for designer cell signal processing and decision making, discuss how these have been implemented in prototype systems for therapeutic, environmental, and industrial biotechnological applications, and examine emerging challenges in this promising field. PMID:25579192

  12. 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

  13. MAPK Cascades in Guard Cell Signal Transduction.

    Science.gov (United States)

    Lee, Yuree; Kim, Yun Ju; Kim, Myung-Hee; Kwak, June M

    2016-01-01

    Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK) cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions. PMID:26904052

  14. Signaling involved in stem cell reprogramming and differentiation

    Institute of Scientific and Technical Information of China (English)

    Shihori; Tanabe

    2015-01-01

    Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have reve-aled that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell pro-gramming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review,the molecular interactions and signaling pathways related to stem cell differentiation are discussed.

  15. FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells.

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2006-03-01

    WNT, FGF and Hedgehog signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis. FGF16, FGF18, and FGF20 genes are targets of WNT-mediated TCF/LEF-beta-catenin-BCL9/BCL9L-PYGO transcriptional complex. SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members. Here, transcriptional regulation of SPRY1, SPRY2, SPRY3, SPRY4, SPRED1, SPRED2, and SPRED3 genes by WNT/beta-catenin signaling cascade was investigated by using bioinformatics and human intelligence (humint). Because double TCF/LEF-binding sites were identified within the 5'-promoter region of human SPRY4 gene, comparative genomics analyses on SPRY4 orthologs were further performed. SPRY4-FGF1 locus at human chromosome 5q31.3 and FGF2-NUDT6-SPATA5-SPRY1 locus at human chromosome 4q27-q28.1 were paralogous regions within the human genome. Chimpanzee SPRY4 gene was identified within NW_107083.1 genome sequence. Human, chimpanzee, rat and mouse SPRY4 orthologs, consisting of three exons, were well conserved. SPRY4 gene was identified as the evolutionarily conserved target of WNT/beta-catenin signaling pathway based on the conservation of double TCF/LEF-binding sites within 5'-promoter region of mammalian SPRY4 orthologs. Human SPRY4 mRNA was expressed in embryonic stem (ES) cells, brain, pancreatic islet, colon cancer, head and neck tumor, melanoma, and pancreatic cancer. WNT signaling activation in progenitor cells leads to the growth regulation of progenitor cells themselves through SPRY4 induction, and also to the growth stimulation of proliferating cells through FGF secretion. Epigenetic silencing and loss-of-function mutations of SPRY4 gene in progenitor cells could lead to carcinogenesis. SPRY4 is the pharmacogenomics target in the fields of oncology and regenerative medicine. PMID:16465403

  16. 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

  17. 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

  18. 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...

  19. 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

  20. 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

  1. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

    Science.gov (United States)

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary; Zhu, Hongwen; Zhang, Jun; Liu, Jie; Liu, Hailiang; deVellis, Jean; Horvath, Steve; Sun, Yi Eve; Li, Siguang

    2015-05-21

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation. PMID:26000486

  2. 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.

  3. 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.

  4. 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.

  5. Homeostatic interplay between bacterial cell-cell signaling and iron in virulence.

    Directory of Open Access Journals (Sweden)

    Ronen Hazan

    2010-03-01

    Full Text Available Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.

  6. 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.

  7. [Neural stem cells and Notch signalling].

    Science.gov (United States)

    Traiffort, Elisabeth; Ferent, Julien

    2015-12-01

    Development and repair of the nervous system are based on the existence of neural stem cells (NSCs) able to generate neurons and glial cells. Among the mechanisms that are involved in the control of embryo or adult NSCs, the Notch signalling plays a major role. In embryo, the pathway participates in the maintenance of NSCs during all steps of development of the central nervous system which starts with the production of neurons also called neurogenesis and continues with gliogenesis giving rise to astrocytes and oligodendrocytes. During the postnatal and adult period, Notch signalling is still present in the major neurogenic areas, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus. In these regions, Notch maintains NSC quiescence, contributes to the heterogeneity of these cells and displays pleiotropic effects during the regeneration process occurring after a lesion. PMID:26672665

  8. Intracellular Signals of T Cell Costimulation

    Institute of Scientific and Technical Information of China (English)

    Jianxun Song; Fengyang Tylan Lei; Xiaofang Xiong; Rizwanul Haque

    2008-01-01

    Ligation of T cell receptor (TCR) alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions (costimulation) on antigen presenting cells (APCs) and T cells are required. T cell costimulation has been shown to be essential for eliciting efficient T cell responses, involving all phases during T cell development. However, the mechanisms by which costimulation affects the function of T cells still need to be elucidated. In recent years, advances have been made in studies of costimulation as potential therapies in cancer, infectious disease as well as autoimmune disease. In this review, we discussed intracellular costimulation signals that regulate T cell proliferation, cell cycle progression, cytokine production, survival, and memory development. In general, the pathway of phosphoinositide-3 kinase (PBK)/protein kinase B (PKB, also known as Akt)/nuclear factor κB (NF-κB) might be central to many costimulatory effects. Through these pathways, costimulation controls T-cell expansion and proliferation by maintenance of survivin and aurora B expression, and sustains long-term T-cell survival and memory development by regulating the expression of bci-2 family members. Cellular & Molecular Immunology.2008;5(4):239-247.

  9. 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.

  10. 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

  11. 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

  12. Signaling involved in stem cell reprogramming and differentiation

    OpenAIRE

    Tanabe, Shihori

    2015-01-01

    Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have revealed that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell programming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review, the molecular interactions and signaling pathways related to s...

  13. 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.

  14. 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.

  15. 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.

  16. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo

    OpenAIRE

    Simmons, Alan J; Banerjee, Amrita; McKinley, Eliot T; Scurrah, Cherie' R; Herring, Charles A; Gewin, Leslie S; Masuzaki, Ryota; Karp, Seth J.; Franklin, Jeffrey L.; Gerdes, Michael J.; Irish, Jonathan M.; Coffey, Robert J.; Lau, Ken S.

    2015-01-01

    Understanding heterogeneous cellular behaviors in a complex tissue requires the evaluation of signaling networks at single-cell resolution. However, probing signaling in epithelial tissues using cytometry-based single-cell analysis has been confounded by the necessity of single-cell dissociation, where disrupting cell-to-cell connections inherently perturbs native cell signaling states. Here, we demonstrate a novel strategy (Disaggregation for Intracellular Signaling in Single Epithelial Cell...

  17. 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

  18. Fuel cells for telephone networks

    International Nuclear Information System (INIS)

    Critical telephone network systems are currently protected from electric utility power failures by a backup system consisting of lead-acid batteries and an engine-alternator. It is considered here an alternate power system where less expensive off-peak commercial electricity electrolyses water, while fuel cells draw continuously on the stored gas products to provide direct current for the protected equipment. The lead acid batteries are eliminated. The benefits and costs of the existing and alternate systems in scenarios with various system efficiencies, capital costs, and electric utility rates and incentives, are compared. In today's conditions, the alternate system is not economical; however, cost and performance feasibility domains are identified. 2 figs., 4 tabs., 12 refs

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Cell Signalling Through Covalent Modification and Allostery

    Science.gov (United States)

    Johnson, Louise N.

    Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases catalyze the transfer of the γ-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. This covalent modification allows activation or inhibition of enzyme activity, creates recognition sites for other proteins and promotes order/disorder or disorder/order transitions. These properties regulate ­signalling pathways and cellular processes that mediate metabolism, transcription, cell cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. In this lecture I shall review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase and the cell cycle cyclin dependent protein kinases as illustrations. Regulation of protein phosphorylation may be disrupted in the diseased state and protein kinases have become high profile targets for drug development. To date there are 11 compounds that have been approved for clinical use in the treatment of cancer.

  5. Molecular signal transduction in vascular cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.

  6. Phosphatidylinositol 3-phosphates-at the interface between cell signalling and membrane traffic.

    Science.gov (United States)

    Marat, Andrea L; Haucke, Volker

    2016-03-15

    Phosphoinositides (PIs) form a minor class of phospholipids with crucial functions in cell physiology, ranging from cell signalling and motility to a role as signposts of compartmental membrane identity. Phosphatidylinositol 3-phosphates are present at the plasma membrane and within the endolysosomal system, where they serve as key regulators of both cell signalling and of intracellular membrane traffic. Here, we provide an overview of the metabolic pathways that regulate cellular synthesis of PI 3-phosphates at distinct intracellular sites and discuss the mechanisms by which these lipids regulate cell signalling and membrane traffic. Finally, we provide a framework for how PI 3-phosphate metabolism is integrated into the cellular network. PMID:26888746

  7. Cell fate reprogramming by control of intracellular network dynamics

    Science.gov (United States)

    Zanudo, Jorge G. T.; Albert, Reka

    Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

  8. 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

  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. Lipid rafts: cell surface platforms for T cell signaling

    Directory of Open Access Journals (Sweden)

    TONY MAGEE

    2002-01-01

    Full Text Available The Src family tyrosine kinase Lck is essential for T cell development and T cell receptor (TCR* signaling. Lck is post-translationally fatty acylated at its N-terminus conferring membrane targeting and concentration in plasma membrane lipid rafts, which are lipid-based organisational platforms. Confocal fluorescence microscopy shows that Lck colocalises in rafts with GPI-linked proteins, the adaptor protein LAT and Ras, but not with non-raft membrane proteins including the protein tyrosine phosphatase CD45. The TCR also associates with lipid rafts and its cross-linking causes coaggregation of raft-associated proteins including Lck, but not of CD45. Cross-linking of either the TCR or rafts strongly induces specific tyrosine phosphorylation of the TCR in the rafts. Remarkably, raft patching alone induces signalling events analogous to TCR stimulation, with the same dependence on expression of key TCR signalling molecules. Our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts, which facilitates colocalisation of signaling proteins including Lck, LAT, and the TCR, while excluding CD45, thereby potentiating protein tyrosine phosphorylation and downstream signaling. We are currently testing this hypothesis as well as using imaging techniques such as fluorescence resonance energy transfer (FRET microscopy to study the dynamics of proteins and lipids in lipid rafts in living cells undergoing signaling events. Recent data show that the key phosphoinositide PI(4,5P2 is concentrated in T cell lipid rafts and that on stimulation of the cells it is rapidly converted to PI(3,4,5P3 and diacylglycerol within rafts. Thus rafts are hotspots for both protein and lipid signalling pathways.

  11. 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.

  12. 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.

  13. 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

  14. Dynamical Adaptation in Terrorist Cells/Networks

    DEFF Research Database (Denmark)

    Hussain, Dil Muhammad Akbar; Ahmed, Zaki

    2010-01-01

    followers etc. In this research we analyze and predict the most likely role a particular node can adapt once a member of the network is either killed or caught. The adaptation is based on computing Bayes posteriori probability of each node and the level of the said node in the network structure.......Typical terrorist cells/networks have dynamical structure as they evolve or adapt to changes which may occur due to capturing or killing of a member of the cell/network. Analytical measures in graph theory like degree centrality, betweenness and closeness centralities are very common and have long...

  15. Microrheology of keratin networks in cancer cells

    International Nuclear Information System (INIS)

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a deceasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. (paper)

  16. Microrheology of keratin networks in cancer cells.

    Science.gov (United States)

    Paust, T; Paschke, S; Beil, M; Marti, O

    2013-12-01

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a decreasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. PMID:24305115

  17. 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...

  18. 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.

  19. Single cell analysis of signaling molecules

    Czech Academy of Sciences Publication Activity Database

    Klepárník, Karel; Luksch, Jaroslav; Adamová, Eva; Potáčová, Anna; Matalová, E.; Foret, František

    Grupo VLS Print Solution, 2014 - (Guzman, N.; Taveres, M.). s. 49-49 [International Symposium on Electro- and Liquid Phase-Separation Techniques /21./ and Latin-American Symposium on Biotechnology, Biomedical, Biopharmaceutical, and Industrial Applications of Capillary Electrophoresis and Microchip Technology /21./. 04.10.2014-08.10.2014, Natal] R&D Projects: GA ČR(CZ) GA14-28254S Institutional support: RVO:68081715 ; RVO:67985904 Keywords : single cell analysis * signaling molecules * caspase Subject RIV: CB - Analytical Chemistry, Separation

  20. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Rodriguez-Zas Sandra L

    2009-11-01

    Full Text Available Abstract Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis (S. uberis that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare, and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection (IMI with S. uberis and relate these with other physiological measurements associated with immune and/or metabolic responses to mastitis challenge with S. uberis O140J. Results Streptococcus uberis IMI resulted in 2,102 (1,939 annotated differentially expressed genes (DEG. Within this set of DEG, we uncovered 20 significantly enriched canonical pathways (with 20 to 61 genes each, the majority of which were signaling pathways. Among the most inhibited were LXR/RXR Signaling and PPARα/RXRα Signaling. Pathways activated by IMI were IL-10 Signaling and IL-6 Signaling which likely reflected counter mechanisms of mammary tissue to respond to infection. Of the 2,102 DEG, 1,082 were up-regulated during IMI and were primarily involved with the immune response, e.g., IL6, TNF, IL8, IL10, SELL, LYZ, and SAA3. Genes down-regulated (1,020 included those associated with milk fat synthesis, e.g., LPIN1, LPL, CD36, and BTN1A1. Network analysis of DEG indicated that TNF had positive relationships with genes involved with immune system function (e.g., CD14, IL8, IL1B, and TLR2 and negative relationships with genes involved with lipid metabolism (e.g., GPAM, SCD, FABP4, CD36, and LPL and antioxidant activity (SOD1. Conclusion Results provided novel information into the early signaling and metabolic pathways in mammary tissue that are associated with the innate immune response to S. uberis infection. Our study indicated that IMI challenge with S. uberis (strain O140J elicited

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Chemokines: a new dendritic cell signal for T cell activation

    Directory of Open Access Journals (Sweden)

    Christoph A Thaiss

    2011-08-01

    Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

  11. 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.

  12. 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 ...

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Semantic Mining based on graph theory and ontologies. Case Study: Cell Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Carlos R. Rangel

    2016-08-01

    Full Text Available In this paper we use concepts from graph theory and cellular biology represented as ontologies, to carry out semantic mining tasks on signaling pathway networks. Specifically, the paper describes the semantic enrichment of signaling pathway networks. A cell signaling network describes the basic cellular activities and their interactions. The main contribution of this paper is in the signaling pathway research area, it proposes a new technique to analyze and understand how changes in these networks may affect the transmission and flow of information, which produce diseases such as cancer and diabetes. Our approach is based on three concepts from graph theory (modularity, clustering and centrality frequently used on social networks analysis. Our approach consists into two phases: the first uses the graph theory concepts to determine the cellular groups in the network, which we will call them communities; the second uses ontologies for the semantic enrichment of the cellular communities. The measures used from the graph theory allow us to determine the set of cells that are close (for example, in a disease, and the main cells in each community. We analyze our approach in two cases: TGF-ß and the Alzheimer Disease.

  18. 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

  19. Oscillations and temporal signalling in cells.

    Science.gov (United States)

    Tiana, G; Krishna, S; Pigolotti, S; Jensen, M H; Sneppen, K

    2007-06-01

    The development of new techniques to quantitatively measure gene expression in cells has shed light on a number of systems that display oscillations in protein concentration. Here we review the different mechanisms which can produce oscillations in gene expression or protein concentration using a framework of simple mathematical models. We focus on three eukaryotic genetic regulatory networks which show 'ultradian' oscillations, with a time period of the order of hours, and involve, respectively, proteins important for development (Hes1), apoptosis (p53) and immune response (NF-kappaB). We argue that underlying all three is a common design consisting of a negative feedback loop with time delay which is responsible for the oscillatory behaviour. PMID:17664651

  20. Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation.

    Science.gov (United States)

    Tape, Christopher J; Ling, Stephanie; Dimitriadi, Maria; McMahon, Kelly M; Worboys, Jonathan D; Leong, Hui Sun; Norrie, Ida C; Miller, Crispin J; Poulogiannis, George; Lauffenburger, Douglas A; Jørgensen, Claus

    2016-05-01

    Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRAS(G12D)) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRAS(G12D) signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRAS(G12D) engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRAS(G12D). Consequently, reciprocal KRAS(G12D) produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRAS(G12D) alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. VIDEO ABSTRACT. PMID:27087446

  1. 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...

  2. Sunitinib activates Axl signaling in renal cell cancer.

    Science.gov (United States)

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID:26815723

  3. Role of inositol phospholipid signaling in natural killer cell biology

    OpenAIRE

    Gumbleton, Matthew; Kerr, William G.

    2013-01-01

    Natural killer (NK) cells are important for host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the inositol ph...

  4. Construction of a computable cell proliferation network focused on non-diseased lung cells

    Directory of Open Access Journals (Sweden)

    Veljkovic Emilija

    2011-07-01

    Full Text Available Abstract Background Critical to advancing the systems-level evaluation of complex biological processes is the development of comprehensive networks and computational methods to apply to the analysis of systems biology data (transcriptomics, proteomics/phosphoproteomics, metabolomics, etc.. Ideally, these networks will be specifically designed to capture the normal, non-diseased biology of the tissue or cell types under investigation, and can be used with experimentally generated systems biology data to assess the biological impact of perturbations like xenobiotics and other cellular stresses. Lung cell proliferation is a key biological process to capture in such a network model, given the pivotal role that proliferation plays in lung diseases including cancer, chronic obstructive pulmonary disease (COPD, and fibrosis. Unfortunately, no such network has been available prior to this work. Results To further a systems-level assessment of the biological impact of perturbations on non-diseased mammalian lung cells, we constructed a lung-focused network for cell proliferation. The network encompasses diverse biological areas that lead to the regulation of normal lung cell proliferation (Cell Cycle, Growth Factors, Cell Interaction, Intra- and Extracellular Signaling, and Epigenetics, and contains a total of 848 nodes (biological entities and 1597 edges (relationships between biological entities. The network was verified using four published gene expression profiling data sets associated with measured cell proliferation endpoints in lung and lung-related cell types. Predicted changes in the activity of core machinery involved in cell cycle regulation (RB1, CDKN1A, and MYC/MYCN are statistically supported across multiple data sets, underscoring the general applicability of this approach for a network-wide biological impact assessment using systems biology data. Conclusions To the best of our knowledge, this lung-focused Cell Proliferation Network

  5. Integrative Network Analysis of Signaling in Human CD34+ Hematopoietic Progenitor Cells by Global Phosphoproteomic Profiling Using TiO2 Enrichment Combined with 2D LC-MS/MS and Pathway Mapping

    OpenAIRE

    Guo, Hongbo; Isserlin, Ruth; Chen, Xiaoji; Wang, Weijia; Phanse, Sadhna; Zandstra, Peter W.; Bader, Gary; Paddison, Patrick; Emili, Andrew

    2013-01-01

    Protein kinase signaling regulates human hematopoietic stem/progenitor cell (HSPC) fate, yet little is known about critical pathway substrates. To address this, we have developed and applied a large-scale, empirically-optimized phosphopeptide affinity enrichment strategy with high-throughput 2D LC-MS/MS screening to evaluate the phosphoproteome of an isolated human CD34+ HSPC population. We first used hydrophilic interaction chromatography (HILIC) as a first dimension separation to separate a...

  6. 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.

  7. 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.

  8. Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

    OpenAIRE

    Torday, John S.; Rehan, V.K.

    2009-01-01

    Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been “deconvoluted” (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, ho...

  9. 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.

  10. Epigenetic disruption of cell signaling in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Li Li; Xing-Sheng Shu; Zhao-Hui Wang; Ya Cao; Qian Tao

    2011-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia. Alternative to genetic changes, aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/ or histone modifications. These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC. In this review, we summariye the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research. Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.

  11. 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

  12. 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.

  13. GLYCINE AND GLYCINE RECEPTOR SIGNALING IN IMMUNE CELLS

    OpenAIRE

    Van den Eynden, Jimmy

    2010-01-01

    The central nervous system (CNS) is an integration center for signal processing, receiving signals from the different sensory systems and transmitting signals to the motor system. The main cells conducting signals are neurons, and for the largest part of the 20th century most attention of neuroscientist was focused on neurons. A role of glial cells, for a long time considered as passive connective tissue elements, in normal physiology and pathophysiology is now becoming increasingly appreciat...

  14. Wnt signaling in adult intestinal stem cells and cancer

    OpenAIRE

    Krausová, M. (Michaela); Kořínek, V. (Vladimír)

    2014-01-01

    Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physi...

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. Regulation of embryonic stem cell self-renewal and differentiation by TGF-β family signaling

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Embryonic stem (ES) cells are characterized by their ability to indefinitely self-renew and potential to differentiate into all the cell lineages of the body. ES cells are considered to have potential applications in regenerative medicine. In particular, the emergence of an ES cell analogue-induced pluripotent stem (iPS) cells via somatic cell reprogramming by co-expressing a limited number of critical stemness-related transcriptional factors has solved the problem of obtaining patient-specific pluripotent cells, encouraging researchers to develop more specific and functional cell lineages from ES or iPS cells for broad therapeutic applications. ES cell fate choice is delicately controlled by a core transcriptional network, epigenetic modification profiles and complex signaling cascades both intrinsically and extrinsically. Of these signals, transforming growth factor β (TGF-β) family members, including TGF-β, bone morphogenetic protein (BMP), Activin and Nodal, have been reported to influence cell self-renewal and a broad spectrum of lineage differentiation in ES cells, in accordance with the key roles of TGF-β family signaling in early embryo development. In this review, the roles of TGF-β family signals in coordinating ES cell fate determination are summarized.

  3. Hybrid modeling of cell signaling and transcriptional reprogramming and its application in C. elegans development

    Directory of Open Access Journals (Sweden)

    Elana J Fertig

    2011-11-01

    Full Text Available Modeling of signal driven transcriptional reprogramming is critical for understanding of organism development, human disease, and cell biology. Many current modeling techniques discount key features of the biological sub-systems when modeling multi-scale, organism level processes. We present a mechanistic hybrid model, GESSA, which integrates a novel pooled probabilistic Boolean network model of cell signaling and a stochastic simulation of transcription and translation responding to a diffusion model of extra-cellular signals. We apply the model to simulate the well studied cell fate decision process of the vulval precursor cells (VPCs in C. elegans, using experimentally derived rate constants wherever possible and shared parameters to avoid overfitting. We demonstrate that GESSA recovers (1 the effects of varying scaffold protein concentration on signal strength, (2 amplification of signals in expression, (3 the relative external ligand concentration in a known geometry, and (4 feedback in biochemical networks. We demonstrate that setting model parameters based on wild-type and LIN-12 loss-of-function mutants in C. elegans leads to correct prediction of a wide variety of mutants including partial penetrance of phenotypes. Moreover, the model is relatively insensitive to parameters, retaining the wild-type phenotype for a wide range of cell signaling rate parameters.

  4. 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...

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Encoding network states by striatal cell assemblies.

    Science.gov (United States)

    Carrillo-Reid, Luis; Tecuapetla, Fatuel; Tapia, Dagoberto; Hernández-Cruz, Arturo; Galarraga, Elvira; Drucker-Colin, René; Bargas, José

    2008-03-01

    Correlated activity in cortico-basal ganglia circuits plays a key role in the encoding of movement, associative learning and procedural memory. How correlated activity is assembled by striatal microcircuits is not understood. Calcium imaging of striatal neuronal populations, with single-cell resolution, reveals sporadic and asynchronous activity under control conditions. However, N-methyl-d-aspartate (NMDA) application induces bistability and correlated activity in striatal neurons. Widespread neurons within the field of observation present burst firing. Sets of neurons exhibit episodes of recurrent and synchronized bursting. Dimensionality reduction of network dynamics reveals functional states defined by cell assemblies that alternate their activity and display spatiotemporal pattern generation. Recurrent synchronous activity travels from one cell assembly to the other often returning to the original assembly; suggesting a robust structure. An initial search into the factors that sustain correlated activity of neuronal assemblies showed a critical dependence on both intrinsic and synaptic mechanisms: blockage of fast glutamatergic transmission annihilates all correlated firing, whereas blockage of GABAergic transmission locked the network into a single dominant state that eliminates assembly diversity. Reduction of L-type Ca(2+)-current restrains synchronization. Each cell assembly comprised different cells, but a small set of neurons was shared by different assemblies. A great proportion of the shared neurons was local interneurons with pacemaking properties. The network dynamics set into action by NMDA in the striatal network may reveal important properties of striatal microcircuits under normal and pathological conditions. PMID:18184883

  11. Cytokine signaling in the differentiation of innate effector cells

    OpenAIRE

    Huang, Hua; Li, Yapeng; Qi, Xiaopeng

    2013-01-01

    Innate effector cells, including innate effector cells of myeloid and lymphoid lineages, are crucial components of various types of immune responses. Bone marrow progenitors differentiate into many subsets of innate effector cells after receiving instructional signals often provided by cytokines. Signal transducer and activator of transcription (STATs) have been shown to be essential in the differentiation of various types of innate effector cells. In this review, we focus specifically on the...

  12. 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 ...

  13. IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

    DEFF Research Database (Denmark)

    Hammer, Troels; Tritsaris, Katerina; Hübschmann, Martin V;

    2009-01-01

    IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon...... IL-20 induced phosphorylation of Erk1/2 and mTOR, and using the MEK inhibitor PD98059 and mTOR complex inhibitor rapamycin we demonstrated the importance of these signalling pathways in IL-20-mediated proliferation. IL-20 triggered actin polymerization and morphological changes resulting in elongated...... cell structures, and in matrigels, IL-20 caused tube formations of hTERT-HDLEC in a PI3K- and mTOR dependent way. In a sprouting assay we found that IL-20 caused cell migration within 24 h at a rate comparable to VEGF-C, and this migration could be inhibited by wortmannin and rapamycin. These data show...

  14. 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.

  15. Wnt signaling and the control of human stem cell fate.

    Science.gov (United States)

    Van Camp, J K; Beckers, S; Zegers, D; Van Hul, W

    2014-04-01

    Wnt signaling determines major developmental processes in the embryonic state and regulates maintenance, self-renewal and differentiation of adult mammalian tissue stem cells. Both β-catenin dependent and independent Wnt pathways exist, and both affect stem cell fate in developing and adult tissues. In this review, we debate the response to Wnt signal activation in embryonic stem cells and human, adult stem cells of mesenchymal, hematopoetic, intestinal, gastric, epidermal, mammary and neural lineages, and discuss the need for Wnt signaling in these cell types. Due to the vital actions of Wnt signaling in developmental and maintenance processes, deregulation of the pathway can culminate into a broad spectrum of developmental and genetic diseases, including cancer. The way in which Wnt signals can feed tumors and maintain cancer stem stells is discussed as well. Manipulation of Wnt signals both in vivo and in vitro thus carries potential for therapeutic approaches such as tissue engineering for regenerative medicine and anti-cancer treatment. Although many questions remain regarding the complete Wnt signal cell-type specific response and interplay of Wnt signaling with pathways such as BMP, Hedgehog and Notch, we hereby provide an overview of current knowledge on Wnt signaling and its control over human stem cell fate. PMID:24323281

  16. Cytokine signaling for proliferation, survival, and death in hematopoietic cells.

    Science.gov (United States)

    Miyajima, A; Ito, Y; Kinoshita, T

    1999-04-01

    The survival, proliferation, and differentiation of hematopoietic cells are regulated by cytokines. In the absence of cytokines, hematopoietic cells not only stop proliferation, but undergo apoptosis. This strict dependency of hematopoietic cells on cytokines is an important mechanism that maintains the homeostasis of blood cells. Cytokines induce various intracellular signaling pathways by activating the receptor-associated Janus kinases (Jaks), and distinct signals are responsible for cell cycle progression and cell survival. Induction of signals for cell cycle progression without suppressing apoptosis results in apoptotic cell death, indicating the essential role of anti-apoptotic signaling for cell growth. In hematopoietic cells, Ras, a cellular protooncogen product, and phosphatidylinositol 3 kinase are involved in the suppression of apoptosis. Cytokine depletion not only turns off anti-apoptotic signaling, but also actively induces cell death by activating caspases, a distinct family of cysteine proteases. Alterations in the mechanisms of cytokine signaling for cell cycle progression and anti-apoptotic function are implicated in hematological disorders. PMID:10222650

  17. Excellence in cell signaling research recognized with major new award.

    Science.gov (United States)

    Feller, Stephan M

    2013-01-01

    The newly installed Life Sciences Breakthrough Prize (http://www.breakthroughprizeinlifesciences.org/), which comes with more than double the financial reward of the Nobel Prize, has been awarded to several world-leaders in the field of cancer-related cell signaling and therapy research: Lewis C. Cantley (PI3 kinase), Hans Clevers (Wnt signaling), Charles L. Sawyers (signaling-targeted cancer therapy), Bert Vogelstein (colorectal cancer signaling) and Robert Weinberg (Ras & other cancer-relevant genes). They have all made remarkable contributions to our understanding of cell communication and malignancies over the last decades. Needless to say that virtually all other awardees of the 11 scientists honored in 2013 have also, in one way or another, touched upon signaling molecules, highlighting the fundamental interdisciplinarity and significance of signal transduction for living cells in general. For example, Shinya Yamanaka's exciting work was built on the four transcriptional signaling proteins, Oct3/4, Sox2, Klf4 and c-Myc. PMID:23497077

  18. The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells

    DEFF Research Database (Denmark)

    Rønn, Sif G; Hansen, Johnny A; Lindberg, Karen;

    2002-01-01

    . Furthermore, using Northern blot analysis it was shown that SOCS-3 can completely inhibit GH-induced insulin production in these cells. Finally, 5-bromodeoxyuridine incorporation followed by fluorescence-activated cell sorting analysis showed that SOCS-3 inhibits GH-induced proliferation of INS-1 cells. These......GH is an important regulator of cell growth and metabolism. In the pancreas, GH stimulates mitogenesis as well as insulin production in beta-cells. The cellular effects of GH are exerted mainly through activation of the Janus kinase-signal transducer and activator of transcription (STAT) pathway....... Recently it has been found that suppressors of cytokine signaling (SOCS) proteins are able to inhibit GH-induced signal transduction. In the present study, the role of SOCS-3 in GH signaling was investigated in the pancreatic beta-cell lines RIN-5AH and INS-1 by means of inducible expression systems. Via...

  19. Calcium signals and calcium channels in osteoblastic cells

    Science.gov (United States)

    Duncan, R. L.; Akanbi, K. A.; Farach-Carson, M. C.

    1998-01-01

    Calcium (Ca2+) channels are present in non-excitable as well as in excitable cells. In bone cells of the osteoblast lineage, Ca2+ channels play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. They are also proposed to modulate paracrine signaling between bone-forming osteoblasts and bone-resorbing osteoclasts at local sites of bone remodeling. Calcium signals are characterized by transient increases in intracellular Ca2+ levels that are associated with activation of intracellular signaling pathways that control cell behavior and phenotype, including patterns of gene expression. Development of Ca2+ signals is a tightly regulated cellular process that involves the concerted actions of plasma membrane and intracellular Ca2+ channels, along with Ca2+ pumps and exchangers. This review summarizes the current state of knowledge concerning the structure, function, and role of Ca2+ channels and Ca2+ signals in bone cells, focusing on the osteoblast.

  20. Diffusion wave and signal transduction in biological live cells

    CERN Document Server

    Fan, Tian You

    2012-01-01

    Transduction of mechanical stimuli into biochemical signals is a fundamental subject for cell physics. In the experiments of FRET signal in cells a wave propagation in nanoscope was observed. We here develop a diffusion wave concept and try to give an explanation to the experimental observation. The theoretical prediction is in good agreement to result of the experiment.

  1. Cells in Multidimensional Recurrent Neural Networks

    OpenAIRE

    Leifert, G.; Strauß, T.; Grüning, T; Labahn, R.

    2014-01-01

    The transcription of handwritten text on images is one task in machine learning and one solution to solve it is using multi-dimensional recurrent neural networks (MDRNN) with connectionist temporal classification (CTC). The RNNs can contain special units, the long short-term memory (LSTM) cells. They are able to learn long term dependencies but they get unstable when the dimension is chosen greater than one. We defined some useful and necessary properties for the one-dimensional LSTM cell and...

  2. 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

  3. NMU signaling promotes endometrial cancer cell progression by modulating adhesion signaling.

    Science.gov (United States)

    Lin, Ting-Yu; Wu, Fang-Ju; Chang, Chia-Lin; Li, Zhongyou; Luo, Ching-Wei

    2016-03-01

    Neuromedin U (NMU) was originally named based on its strong uterine contractile activity, but little is known regarding its signaling/functions in utero. We identified that NMU and one of its receptors, NMUR2, are not only present in normal uterine endometrium but also co-expressed in endometrial cancer tissues, where the NMU level is correlated with the malignant grades and survival of patients. Cell-based assays further confirmed that NMU signaling can promote cell motility and proliferation of endometrial cancer cells derived from grade II tumors. Activation of NMU pathway in these endometrial cancer cells is required in order to sustain expression of various adhesion molecules, such as CD44 and integrin alpha1, as well as production of their corresponding extracellular matrix ligands, hyaluronan and collagen IV; it also increased the activity of SRC and its downstream proteins RHOA and RAC1. Thus, it is concluded that NMU pathway positively controls the adhesion signaling-SRC-Rho GTPase axis in the tested endometrial cancer cells and that changes in cell motility and proliferation can occur when there is manipulation of NMU signaling in these cells either in vitro or in vivo. Intriguingly, this novel mechanism also explains how NMU signaling promotes the EGFR-driven and TGFβ receptor-driven mesenchymal transitions. Through the above axis, NMU signaling not only can promote malignancy of the tested endometrial cancer cells directly, but also helps these cells to become more sensitive to niche growth factors in their microenvironment. PMID:26849234

  4. 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.

  5. 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...

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

    Directory of Open Access Journals (Sweden)

    Natalia Polouliakh

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

  7. 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.

  8. 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.

  9. Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process.

    Science.gov (United States)

    Wu, Danielle; Schaffler, Mitchell B; Weinbaum, Sheldon; Spray, David C

    2013-07-16

    Osteocytes are bone cells that form cellular networks that sense mechanical loads distributed throughout the bone tissue. Interstitial fluid flow in the lacunar canalicular system produces focal strains at localized attachment sites around the osteocyte cell process. These regions of periodic attachment between the osteocyte cell membrane and its canalicular wall are sites where pN-level fluid-flow induced forces are generated in vivo. In this study, we show that focally applied forces of this magnitude using a newly developed Stokesian fluid stimulus probe initiate rapid and transient intercellular electrical signals in vitro. Our experiments demonstrate both direct gap junction coupling and extracellular purinergic P2 receptor signaling between MLO-Y4 cells in a connected bone cell network. Intercellular signaling was initiated by pN-level forces applied at integrin attachment sites along both appositional and distal unapposed cell processes, but not initiated at their cell bodies with equivalent forces. Electrical coupling was evident in 58% of all cell pairs tested with appositional connections; coupling strength increased with the increasing number of junctional connections. Apyrase, a nucleotide-degrading enzyme, suppressed and abolished force-induced effector responses, indicating a contribution from ATP released by the stimulated cell. This work extends the understanding of how osteocytes modulate their microenvironment in response to mechanical signals and highlights mechanisms of intercellular relay of mechanoresponsive signals in the bone network. PMID:23818616

  10. 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.

  11. 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

  12. 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

  13. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Mark A.; Pfeiffer, Janet R. (University of New Mexico, Albuquerque, NM); Wilson, Bridget S. (University of New Mexico, Albuquerque, NM); Timlin, Jerilyn Ann; Thomas, James L. (University of New Mexico, Albuquerque, NM); Lidke, Keith A. (University of New Mexico, Albuquerque, NM); Spendier, Kathrin (University of New Mexico, Albuquerque, NM); Oliver, Janet M. (University of New Mexico, Albuquerque, NM); Carroll-Portillo, Amanda (University of New Mexico, Albuquerque, NM); Aaron, Jesse S.; Mirijanian, Dina T.; Carson, Bryan D.; Burns, Alan Richard; Rebeil, Roberto

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effort to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.

  14. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  15. 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...

  16. 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.

  17. 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)

  18. 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...

  19. 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

  20. Microtubule networks for plant cell division.

    Science.gov (United States)

    de Keijzer, Jeroen; Mulder, Bela M; Janson, Marcel E

    2014-09-01

    During cytokinesis the cytoplasm of a cell is divided to form two daughter cells. In animal cells, the existing plasma membrane is first constricted and then abscised to generate two individual plasma membranes. Plant cells on the other hand divide by forming an interior dividing wall, the so-called cell plate, which is constructed by localized deposition of membrane and cell wall material. Construction starts in the centre of the cell at the locus of the mitotic spindle and continues radially towards the existing plasma membrane. Finally the membrane of the cell plate and plasma membrane fuse to form two individual plasma membranes. Two microtubule-based cytoskeletal networks, the phragmoplast and the pre-prophase band (PPB), jointly control cytokinesis in plants. The bipolar microtubule array of the phragmoplast regulates cell plate deposition towards a cortical position that is templated by the ring-shaped microtubule array of the PPB. In contrast to most animal cells, plants do not use centrosomes as foci of microtubule growth initiation. Instead, plant microtubule networks are striking examples of self-organizing systems that emerge from physically constrained interactions of dispersed microtubules. Here we will discuss how microtubule-based activities including growth, shrinkage, severing, sliding, nucleation and bundling interrelate to jointly generate the required ordered structures. Evidence mounts that adapter proteins sense the local geometry of microtubules to locally modulate the activity of proteins involved in microtubule growth regulation and severing. Many of the proteins and mechanisms involved have roles in other microtubule assemblies as well, bestowing broader relevance to insights gained from plants. PMID:25136380

  1. KLF7 Regulates Satellite Cell Quiescence in Response to Extracellular Signaling.

    Science.gov (United States)

    Wang, Xiaobin; Shen, Qingwu W; Wang, Jie; Zhang, Zhiguo; Feng, Fu; Chen, Ting; Zhang, Yanyan; Wei, Huan; Li, Zhongwen; Wang, Xinxia; Wang, Yizhen

    2016-05-01

    Retaining muscle stem satellite cell (SC) quiescence is important for the maintenance of stem cell population and tissue regeneration. Accumulating evidence supports the model where key extracellular signals play crucial roles in maintaining SC quiescence or activation, however, the intracellular mechanisms that mediate niche signals to control SC behavior are not fully understood. Here, we reported that KLF7 functioned as a key mediator involved in low-level TGF-β signaling and canonical Notch signaling-induced SC quiescence and myoblast arrest. The data obtained showed that KLF7 was upregulated in quiescent SCs and nonproliferating myoblasts. Silence of KLF7 promoted SCs activation and myoblasts proliferation, but overexpression of KLF7 induced myogenic cell arrest. Notably, the expression of KLF7 was regulated by TGF-β and Notch3 signaling. Knockdown of KLF7 diminished low-level TGF-β and canonical Notch signaling-induced SC quiescence. Investigation into the mechanism revealed that KLF7 regulation of SC function was dependent on p21 and acetylation of Lys227 and/or 231 in the DNA binding domain of KLF7. Our study provides new insights into the regulatory network of muscle stem cell quiescence. Stem Cells 2016;34:1310-1320. PMID:26930448

  2. 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

  3. 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

  4. 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...

  5. 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....

  6. 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.

  7. 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...

  8. Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

    Science.gov (United States)

    Corso, Jasmin; Pan, Kuan-Ting; Walter, Roland; Doebele, Carmen; Mohr, Sebastian; Bohnenberger, Hanibal; Ströbel, Philipp; Lenz, Christof; Slabicki, Mikolaj; Hüllein, Jennifer; Comoglio, Federico; Rieger, Michael A; Zenz, Thorsten; Wienands, Jürgen; Engelke, Michael; Serve, Hubert; Urlaub, Henning; Oellerich, Thomas

    2016-05-17

    Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments. PMID:27155012

  9. Cell death signalling mechanisms in heart failure

    OpenAIRE

    Mughal, Wajihah; Kirshenbaum, Lorrie A.

    2011-01-01

    In 2003, cardiovascular disease was the most costly disease in Canada, and it is still on the rise. The loss of properly functioning cardiomyocytes leads to cardiac impairment, which is a consequence of heart failure. Therefore, understanding the pathways of cell death (necrosis and apoptosis) has potential implications for the development of therapeutic strategies. In addition, the role of B-cell lymphoma-2 family members is discussed and the importance of mitochondria in directing cell deat...

  10. Suprachiasmatic Nucleus: Cell Autonomy and Network Properties

    Science.gov (United States)

    Welsh, David K.; Takahashi, Joseph S.; Kay, Steve A.

    2013-01-01

    The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Individual SCN neurons in dispersed culture can generate independent circadian oscillations of clock gene expression and neuronal firing. However, SCN rhythmicity depends on sufficient membrane depolarization and levels of intracellular calcium and cAMP. In the intact SCN, cellular oscillations are synchronized and reinforced by rhythmic synaptic input from other cells, resulting in a reproducible topographic pattern of distinct phases and amplitudes specified by SCN circuit organization. The SCN network synchronizes its component cellular oscillators, reinforces their oscillations, responds to light input by altering their phase distribution, increases their robustness to genetic perturbations, and enhances their precision. Thus, even though individual SCN neurons can be cell-autonomous circadian oscillators, neuronal network properties are integral to normal function of the SCN. PMID:20148688

  11. 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...

  12. 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...

  13. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    KAUST Repository

    Muraro, D.

    2013-12-31

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

  14. Cell Multiprocessor Communication Network: Built for Speed

    International Nuclear Information System (INIS)

    The existence of major obstacles to the traditional path to processor performance improvement has led chip manufacturers to consider multi-core designs. These architectural solutions promise a variety of power/performance and area/performance benefits. But additional care must be taken to ensure that these benefits are not lost due to inadequate design of the on-chip communication network. This paper presents the design challenges of the on-chip network of the Cell Broadband Engine (Cell BE) processor, and describes in detail its architectural design and the network, communication and synchronization protocols. In the experimental evaluation, performed on an early prototype, we analyze the communication characteristics of the Cell BE processor, using a series of microbenchmarks involving various DMA traffic patterns and synchronization protocols. We find that the on-chip communication subsystem is well matched to the to computational capacity of the processor. A Synergistic Processing Element (SPE) can issue an internal direct memory access (DMA) operation in less than 4 nanoseconds, and a DMA of a single cache line can be executed in less the than 100 nanoseconds. SPEs can achieve the optimal bandwidth of 25.6 GB/second in point to point communication with surprisingly small messages ?only a few KB, using batches of non-blocking DMAs. The aggregate network behavior under heavy load is also remarkably efficient, reaching almost 200 GB/second with collective patterns and optimal contention resolution under hot-spot traffic. Additionally, we demonstrate the consistency of these hardware results with identical experiments carried out using the Mambo simulator software for Cell BE

  15. Nitric oxide functions in both methyl jasmonate signaling and abscisic acid signaling in Arabidopsis guard cells

    OpenAIRE

    Saito, Naoki; Nakamura, Yoshimasa; Mori, Izumi C.; Murata, Yoshiyuki

    2009-01-01

    Intracellular components in methyl jasmonate (MeJA) signaling remain largely unknown, to compare those in well-understood abscisic acid (ABA) signaling. We have reported that nitric oxide (NO) is a signaling component in MeJA-induced stomatal closure, as well as ABA-induced stomatal closure in the previous study. To gain further information about the role of NO in the guard cell signaling, NO production was examined in an ABA- and MeJA-insensitive Arabidopsis mutant, rcn1. Neither MeJA nor AB...

  16. 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...

  17. 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

  18. 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).

  19. Retinoic acid signalling in thymocytes regulates T cell development

    DEFF Research Database (Denmark)

    Wendland, Kerstin; Sitnik, Katarzyna Maria; Kotarsky, Knut;

    The Vitamin A derivative retinoic acid (RA) has emerged as an important regulator of peripheral T cell responses. However, whether there is endogenous retinoic acid receptor (RAR) signaling in developing thymocytes and the potential impact of such signals in thymocyte development remains unclear...

  20. 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.

  1. 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....

  2. 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.

  3. 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

  4. 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...

  5. Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

    NARCIS (Netherlands)

    Clevers, Hans; Loh, Kyle M; Nusse, Roel

    2014-01-01

    Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

  6. Wnt signaling control of bone cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Peter V N Bodine

    2008-01-01

    Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morphogenesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled (FZD) G-protein-coupled receptor and a low-density , lipoprotein (LDL) receptor-related protein (LRP). The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density (BMD) and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects of osteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-1, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3p support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.

  7. Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling

    Science.gov (United States)

    Gibson, Daniel; Chang, Frederick; Gnad, Florian; Gunawardena, Jeremy

    2016-01-01

    The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell’s environment. This suggests that the external environment may be harnessed to interrogate the cell’s internal molecular architecture. Cells, however, are not only nonlinear and non-stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a “correct” model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology. PMID:27367445

  8. 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.

  9. Stimulation of vascular cells by extracellular signals - A biophysical analysis

    OpenAIRE

    Biela, Sarah A.

    2009-01-01

    Stimulation of vascular cells by extracellullar signals Treatment of vascular diseases often requires the selective addressing of endothelial (ECs) and smooth muscle cells (SMCs). The two vascular cell types are important for the wound healing after stent implantation. Recent research designs new materials and coatings for stents to improve the complex healing process. The aim of my work was to find and investigate different reactions in the two vascular cell types (ECs and SMCs) through surf...

  10. Shape-dependent control of cell growth, differentiation, and apoptosis: switching between attractors in cell regulatory networks

    Science.gov (United States)

    Huang, S.; Ingber, D. E.

    2000-01-01

    Development of characteristic tissue patterns requires that individual cells be switched locally between different phenotypes or "fates;" while one cell may proliferate, its neighbors may differentiate or die. Recent studies have revealed that local switching between these different gene programs is controlled through interplay between soluble growth factors, insoluble extracellular matrix molecules, and mechanical forces which produce cell shape distortion. Although the precise molecular basis remains unknown, shape-dependent control of cell growth and function appears to be mediated by tension-dependent changes in the actin cytoskeleton. However, the question remains: how can a generalized physical stimulus, such as cell distortion, activate the same set of genes and signaling proteins that are triggered by molecules which bind to specific cell surface receptors. In this article, we use computer simulations based on dynamic Boolean networks to show that the different cell fates that a particular cell can exhibit may represent a preprogrammed set of common end programs or "attractors" which self-organize within the cell's regulatory networks. In this type of dynamic network model of information processing, generalized stimuli (e.g., mechanical forces) and specific molecular cues elicit signals which follow different trajectories, but eventually converge onto one of a small set of common end programs (growth, quiescence, differentiation, apoptosis, etc.). In other words, if cells use this type of information processing system, then control of cell function would involve selection of preexisting (latent) behavioral modes of the cell, rather than instruction by specific binding molecules. Importantly, the results of the computer simulation closely mimic experimental data obtained with living endothelial cells. The major implication of this finding is that current methods used for analysis of cell function that rely on characterization of linear signaling pathways or

  11. Paper-based microreactor array for rapid screening of cell signaling cascades.

    Science.gov (United States)

    Huang, Chia-Hao; Lei, Kin Fong; Tsang, Ngan-Ming

    2016-08-01

    Investigation of cell signaling pathways is important for the study of pathogenesis of cancer. However, the related operations used in these studies are time consuming and labor intensive. Thus, the development of effective therapeutic strategies may be hampered. In this work, gel-free cell culture and subsequent immunoassay has been successfully integrated and conducted in a paper-based microreactor array. Study of the activation level of different kinases of cells stimulated by different conditions, i.e., IL-6 stimulation, starvation, and hypoxia, was demonstrated. Moreover, rapid screening of cell signaling cascades after the stimulations of HGF, doxorubicin, and UVB irradiation was respectively conducted to simultaneously screen 40 kinases and transcription factors. Activation of multi-signaling pathways could be identified and the correlation between signaling pathways was discussed to provide further information to investigate the entire signaling network. The present technique integrates most of the tedious operations using a single paper substrate, reduces sample and reagent consumption, and shortens the time required by the entire process. Therefore, it provides a first-tier rapid screening tool for the study of complicated signaling cascades. It is expected that the technique can be developed for routine protocol in conventional biological research laboratories. PMID:27377153

  12. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling

    Directory of Open Access Journals (Sweden)

    Abraham Libin

    2012-12-01

    Full Text Available Abstract Nef, an accessory protein of the Human Immunodeficiency Virus type 1 (HIV-1, is dispensable for viral replication in cell culture, but promotes virus replication and pathogenesis in the infected host. Acting as protein-interaction adaptor, HIV-1 Nef modulates numerous target cell activities including cell surface receptor expression, cytoskeletal remodeling, vesicular transport, and signal transduction. In infected T-lymphocytes, altering T-cell antigen receptor (TCR signaling has long been recognized as one key function of the viral protein. However, reported effects of Nef range from inhibition to activation of this cascade. Recent advances in the field begin to explain these seemingly contradictory observations and suggest that Nef alters intracellular trafficking of TCR proximal machinery to disrupt plasma membrane bound TCR signaling while at the same time, the viral protein induces localized signal transduction at the trans-Golgi network. This review summarizes these new findings on how HIV-1 Nef reprograms TCR signalling output from a broad response to selective activation of the RAS-Erk pathway. We also discuss the implications of these alterations in the context of HIV-1 infection and in light of current concepts of TCR signal transduction.

  13. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression

    KAUST Repository

    Onesto, Valentina

    2016-05-10

    Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect.

  14. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression

    Science.gov (United States)

    Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo; Cesarelli, Mario; Amato, Francesco; Gentile, Francesco

    2016-01-01

    Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect.

  15. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression

    Directory of Open Access Journals (Sweden)

    Valentina Onesto

    2016-01-01

    Full Text Available Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect.

  16. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression.

    Science.gov (United States)

    Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo; Cesarelli, Mario; Amato, Francesco; Gentile, Francesco

    2016-01-01

    Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect. PMID:27403421

  17. Optimal Cell Load and Throughput in Green Small Cell Networks with Generalized Cell Association

    OpenAIRE

    Liu, Chun-Hung; Wang, Li-Chun

    2015-01-01

    This paper thoroughly explored the fundamental interactions between cell association, cell load and throughput in a green (energy-efficient) small cell network in which all base stations form a homogeneous Poisson point process (PPP) of intensity $\\lambda_B$ and all users form another independent PPP of intensity $\\lambda_U$. Cell voidness, usually disregarded due to rarity in cellular network modeling, is first theoretically analyzed under generalized (channel-aware) cell association (GCA). ...

  18. 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.

  19. Two-stage Recognition of Raw Acceleration Signals for 3-D Gesture-Understanding Cell Phones

    OpenAIRE

    Cho, Sung-Jung; Choi, Eunseok; Bang, Won-Chul; YANG Jing; Sohn, Junil; Kim, Dong Yoon; Lee, Young-Bum; Kim, Sangryong

    2006-01-01

    As many functionalities like cameras and MP3 players are converged to cell phones, more intuitive interaction methods are essential beyond tiny keypads. In this paper, we present gesture-based interactions and their two-stage recognition algorithm. Acceleration signals are generated from accelerometer. At the first stage, they are hierarchically modelled and matched as basic component and their relationships by Bayesian networks. At the second stage, they are further classified by SVMs for re...

  20. Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

    OpenAIRE

    Levin, David E.

    2011-01-01

    The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to...

  1. Single-Cell Transcriptome Analyses Reveal Signals to Activate Dormant Neural Stem Cells

    OpenAIRE

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary

    2015-01-01

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133+/GFAP− ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133+/GFAP− quiescent cells were enriched...

  2. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer.

    Science.gov (United States)

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh'd; Singh, Ajay P

    2016-01-01

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer. PMID:27354262

  3. Three-Dimensional Gradients of Cytokine Signaling between T Cells.

    Directory of Open Access Journals (Sweden)

    Kevin Thurley

    2015-04-01

    Full Text Available Immune responses are regulated by diffusible mediators, the cytokines, which act at sub-nanomolar concentrations. The spatial range of cytokine communication is a crucial, yet poorly understood, functional property. Both containment of cytokine action in narrow junctions between immune cells (immunological synapses and global signaling throughout entire lymph nodes have been proposed, but the conditions under which they might occur are not clear. Here we analyze spatially three-dimensional reaction-diffusion models for the dynamics of cytokine signaling at two successive scales: in immunological synapses and in dense multicellular environments. For realistic parameter values, we observe local spatial gradients, with the cytokine concentration around secreting cells decaying sharply across only a few cell diameters. Focusing on the well-characterized T-cell cytokine interleukin-2, we show how cytokine secretion and competitive uptake determine this signaling range. Uptake is shaped locally by the geometry of the immunological synapse. However, even for narrow synapses, which favor intrasynaptic cytokine consumption, escape fluxes into the extrasynaptic space are expected to be substantial (≥20% of secretion. Hence paracrine signaling will generally extend beyond the synapse but can be limited to cellular microenvironments through uptake by target cells or strong competitors, such as regulatory T cells. By contrast, long-range cytokine signaling requires a high density of cytokine producers or weak consumption (e.g., by sparsely distributed target cells. Thus in a physiological setting, cytokine gradients between cells, and not bulk-phase concentrations, are crucial for cell-to-cell communication, emphasizing the need for spatially resolved data on cytokine signaling.

  4. Wound signaling of regenerative cell reprogramming.

    Science.gov (United States)

    Lup, Samuel Daniel; Tian, Xin; Xu, Jian; Pérez-Pérez, José Manuel

    2016-09-01

    Plants are sessile organisms that must deal with various threats resulting in tissue damage, such as herbivore feeding, and physical wounding by wind, snow or crushing by animals. During wound healing, phytohormone crosstalk orchestrates cellular regeneration through the establishment of tissue-specific asymmetries. In turn, hormone-regulated transcription factors and their downstream targets coordinate cellular responses, including dedifferentiation, cell cycle reactivation and vascular regeneration. By comparing different examples of wound-induced tissue regeneration in the model plant Arabidopsis thaliana, a number of key regulators of developmental plasticity of plant cells have been identified. We present the relevance of these findings and of the dynamic establishment of differential auxin gradients for cell reprogramming after wounding. PMID:27457994

  5. Shared signaling pathways in normal and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Gautam K Malhotra

    2011-01-01

    Full Text Available Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs. These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog; with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.

  6. New Modeling Approaches to Investigate Cell Signaling in Radiation Response

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.

    2011-01-01

    Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine

  7. 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.

  8. Dynamic Trk and G Protein Signalings Regulate Dopaminergic Neurodifferentiation in Human Trophoblast Stem Cells

    Science.gov (United States)

    Lee, Tony Tung-Yin; Tsai, Cheng-Fang; Chen, Hung-Sheng; Lai, Feng-Jie; Yokoyama, Kazunari K.; Hsieh, Tsung-Hsun; Wu, Ruey-Meei; Lee, Jau-nan

    2015-01-01

    Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells. Intracranial implantation of such neural progenitor cells into the 6-OHDA-lesioned substantia nigra pars compacta successfully regenerates dopaminergic neurons and integrity of the nigrostriatal pathway, ameliorating the behavioral deficits in the Parkinson’s disease rat model. Here, we demonstrated a dynamic molecular network in systematic analysis by addressing spatiotemporal molecular expression, intracellular protein-protein interaction and inhibition, imaging study, and genetic expression to explore the regulatory mechanisms of RA induction in the differentiation of human trophoblast stem cells to DA committed progenitor cells. We focused on the tyrosine receptor kinase (Trk), G proteins, canonical Wnt2B/β-catenin, genomic and non-genomic RA signaling transductions with Tyrosine hydroxylase (TH) gene expression as the differentiation endpoint. We found that at the early stage, integration of TrkA and G protein signalings aims for axonogenesis and morphogenesis, involving the novel RXRα/Gαq/11 and RARβ/Gβ signaling pathways. While at the later stage, five distinct signaling pathways together with epigenetic histone modifications emerged to regulate expression of TH, a precursor of dopamine. RA induction generated DA committed progenitor cells in one day. Our results provided substantial mechanistic

  9. 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

  10. Regulation of Hedgehog Signalling Inside and Outside the Cell

    Science.gov (United States)

    Ramsbottom, Simon A.; Pownall, Mary E.

    2016-01-01

    The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis. Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known to act as a morphogen that diffuses to elicit pattern formation. Heparan sulfate proteoglycans (HSPGs) play a major role in the regulation of Hh distribution outside the cell. Inside the cell, the primary cilium provides an important hub for processing the Hh signal in vertebrates. This review will summarise the current understanding of how the Hh pathway is regulated from ligand production, release, and diffusion, through to signal reception and intracellular transduction.

  11. 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.

  12. Surface code—biophysical signals for apoptotic cell clearance

    International Nuclear Information System (INIS)

    Apoptotic cell death and the clearance of dying cells play an important and physiological role in embryonic development and normal tissue turnover. In contrast to necrosis, apoptosis proceeds in an anti-inflammatory manner. It is orchestrated by the timed release and/or exposure of so-called ‘find-me’, ‘eat me’ and ‘tolerate me’ signals. Mononuclear phagocytes are attracted by various ‘find-me’ signals, including proteins, nucleotides, and phospholipids released by the dying cell, whereas the involvement of granulocytes is prevented via ‘stay away’ signals. The exposure of anionic phospholipids like phosphatidylserine (PS) by apoptotic cells on the outer leaflet of the plasma membrane is one of the main ‘eat me’ signals. PS is recognized by a number of innate receptors as well as by soluble bridging molecules on the surface of phagocytes. Importantly, phagocytes are able to discriminate between viable and apoptotic cells both exposing PS. Due to cytoskeleton remodeling PS has a higher lateral mobility on the surfaces of apoptotic cells thereby promoting receptor clustering on the phagocyte. PS not only plays an important role in the engulfment process, but also acts as ‘tolerate me’ signal inducing the release of anti-inflammatory cytokines by phagocytes. An efficient and fast clearance of apoptotic cells is required to prevent secondary necrosis and leakage of intracellular danger signals into the surrounding tissue. Failure or prolongation of the clearance process leads to the release of intracellular antigens into the periphery provoking inflammation and development of systemic inflammatory autoimmune disease like systemic lupus erythematosus. Here we review the current findings concerning apoptosis-inducing pathways, important players of apoptotic cell recognition and clearance as well as the role of membrane remodeling in the engulfment of apoptotic cells by phagocytes. (paper)

  13. Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    William L Riles; Jason Erickson; Sanjay Nayyar; Mary Jo Atten; Bashar M Attar; Oksana Holian

    2006-01-01

    AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-Ⅲ) with deleted p53.METHODS: Nuclear fragmentation was used to quantitate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression.RESULTS: Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP, Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bclxl, Bax, Bid or Smac/Diablo, and did not promote subcellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines.SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-Ⅲ cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities.CONCLUSION: These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells.

  14. BMP2 Transfer to Neighboring Cells and Activation of Signaling.

    Science.gov (United States)

    Alborzinia, Hamed; Shaikhkarami, Marjan; Hortschansky, Peter; Wölfl, Stefan

    2016-09-01

    Morphogen gradients and concentration are critical features during early embryonic development and cellular differentiation. Previously we reported the preparation of biologically active, fluorescently labeled BMP2 and quantitatively analyzed their binding to the cell surface and followed BMP2 endocytosis over time on the level of single endosomes. Here we show that this internalized BMP2 can be transferred to neighboring cells and, moreover, also activates downstream BMP signaling in adjacent cells, indicated by Smad1/5/8 phosphorylation and activation of the downstream target gene id1. Using a 3D matrix to modulate cell-cell contacts in culture we could show that direct cell-cell contact significantly increased BMP2 transfer. Using inhibitors of vesicular transport, transfer was strongly inhibited. Interestingly, cotreatment with the physiological BMP inhibitor Noggin increased BMP2 uptake and transfer, albeit activation of Smad signaling in neighboring cells was completely suppressed. Our findings present a novel and interesting mechanism by which morphogens such as BMP2 can be transferred between cells and how this is modulated by BMP antagonists such as Noggin, and how this influences activation of Smad signaling by BMP2 in neighboring cells. PMID:27306974

  15. Mast cell chemotaxis - chemoattractants and signaling pathways

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2012-01-01

    Roč. 3, May (2012), s. 119. ISSN 1664-3224 R&D Projects: GA MŠk LD12073; GA ČR GA301/09/1826; GA ČR GAP302/10/1759 Grant ostatní: ECST(XE) BM1007; AV ČR(CZ) MC200520901 Institutional support: RVO:68378050 Keywords : mast cell * IgE receptor * plasma membrane Subject RIV: EB - Genetics ; Molecular Biology

  16. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma.

    Science.gov (United States)

    Wei, Wei; Shin, Young Shik; Xue, Min; Matsutani, Tomoo; Masui, Kenta; Yang, Huijun; Ikegami, Shiro; Gu, Yuchao; Herrmann, Ken; Johnson, Dazy; Ding, Xiangming; Hwang, Kiwook; Kim, Jungwoo; Zhou, Jian; Su, Yapeng; Li, Xinmin; Bonetti, Bruno; Chopra, Rajesh; James, C David; Cavenee, Webster K; Cloughesy, Timothy F; Mischel, Paul S; Heath, James R; Gini, Beatrice

    2016-04-11

    Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations. PMID:27070703

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. Cytokinin signaling regulates pavement cell morphogenesis in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Hongjiang Li; Tongda Xu; Deshu Lin; Mingzhang Wen; Mingtang Xie; Jér(o)me Duclercq; Agnieszka Bielach

    2013-01-01

    The puzzle piece-shaped Arabidopsis leaf pavement cells (PCs) with interdigitated lobes and indents is a good model system to investigate the mechanisms that coordinate cell polarity and shape formation within a tissue.Auxin has been shown to coordinate the interdigitation by activating ROP GTPase-dependent signaling pathways.To identify additional components or mechanisms,we screened for mutants with abnormal PC morphogenesis and found that cytokinin signaling regulates the PC interdigitation pattern.Reduction in cytokinin accumulation and defects in cytokinin signaling (such as in ARR7-over-expressing lines,the ahk3cre1 cytokinin receptor mutant,and the ahp12345 cytokinin signaling mutant) enhanced PC interdigitation,whereas over-production of cytokinin and over-activation of cytokinin signaling in an ARR20 over-expression line delayed or abolished PC interdigitation throughout the cotyledon.Genetic and biochemical analyses suggest that cytokinin signaling acts upstream of ROPs to suppress the formation of interdigitated pattern.Our results provide novel mechanistic understanding of the pathways controlling PC shape and uncover a new role for cytokinin signaling in cell morphogenesis.

  2. ELMO1 signaling in apoptotic germ cell clearance and spermatogenesis.

    Science.gov (United States)

    Elliott, Michael R; Ravichandran, Kodi S

    2010-10-01

    Apoptosis and the subsequent removal of dying cells are crucial processes for tissue development and maintenance. Although we are beginning to understand the signaling pathways that control the phagocytic clearance of apoptotic cells, the physiological relevance of these pathways is lacking. During spermatogenesis, over half of the developing germ cells eventually die by apoptosis, yet the signaling pathways that regulate the phagocytic clearance of these dying cells or the impact of this clearance on development and maintenance of the germ cell population is not well understood. The ELMO1/Dock180 proteins form an evolutionarily conserved signaling module that functions as a bipartite guanine nucleotide exchange factor for the small GTPase Rac. The subsequent Rac-dependent cytoskeletal changes play an important role in the physical engulfment of apoptotic cells. Recent findings demonstrate an in vivo role for ELMO1-dependent clearance in the testes, with implications for spermatogenesis. Here we will discuss the role of apoptotic cell clearance during spermatogenesis, with a particular emphasis on ELMO1/Dock180 signaling. PMID:20958313

  3. 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 ...

  4. Determinants of Cell-to-Cell Variability in Protein Kinase Signaling

    OpenAIRE

    Matthias Jeschke; Stephan Baumgärtner; Stefan Legewie

    2013-01-01

    Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity') and the maximal act...

  5. Radioresistance-related signaling pathways in nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Objective: To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2, and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma. Methods: The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2. CNE-2R and CNE-2 cells were cultured and administered with 60Co γ-ray irradiation at the dose of 400 cGy for 15 times. Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes. Bioinformatic analysis was used to identify the pathways related to radioresistance. Results: The number of the differentially expressed genes that were found in these 2 experiments was 374. The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN, MYD88, CCL5, CXCL10, STAT1, LY96, FOS, CCL3, IL-6, IL-8, IL-1α, IL-1β, and IRAK2 (t=13.47-66.57, P<0.05). Conclusions: Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance. (authors)

  6. 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.

  7. Control and Communication Network in Hybrid Fuel Cell Vehicles

    Institute of Scientific and Technical Information of China (English)

    朱元; 吴昊; 田光宇; 阳宪惠; 赵立安; 周伟波

    2004-01-01

    This paper describes the control and communication network in fuel cell vehicles, including both the protocol and the hardware.Based on the current protocol (ISO-11898 and SAE J1939), a new practical protocol is proposed and implemented for the control and communication network in fuel cell vehicles.To improve the reliability of data communication and to unify the network management, a new network system based on dual-port RAM is also implemented.

  8. Lipid rafts in T cell receptor signalling (Review)

    OpenAIRE

    KABOURIDIS, PANAGIOTIS S.

    2006-01-01

    The molecular events and the protein components that are involved in signalling by the T cell receptor (TCR) for antigen have been extensively studied. Activation of signalling cascades following TCR stimulation depends on the phosphorylation of the receptor by the tyrosine kinase Lck, which localizes to the cytoplasmic face of the plasma membrane by virtue of its post-translational modification. However, the precise order of events during TCR phosphorylation at the plasma membrane, remains t...

  9. Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

    Science.gov (United States)

    Unachukwu, Uchenna John; Warren, Alice; Li, Ze; Mishra, Shawn; Zhou, Jing; Sauane, Moira; Lim, Hyungsik; Vazquez, Maribel; Redenti, Stephen

    2016-03-01

    To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

  10. Keeping Signals Straight: How Cells Process Information and Make Decisions.

    Science.gov (United States)

    Laub, Michael T

    2016-07-01

    As we become increasingly dependent on electronic information-processing systems at home and work, it's easy to lose sight of the fact that our very survival depends on highly complex biological information-processing systems. Each of the trillions of cells that form the human body has the ability to detect and respond to a wide range of stimuli and inputs, using an extraordinary set of signaling proteins to process this information and make decisions accordingly. Indeed, cells in all organisms rely on these signaling proteins to survive and proliferate in unpredictable and sometimes rapidly changing environments. But how exactly do these proteins relay information within cells, and how do they keep a multitude of incoming signals straight? Here, I describe recent efforts to understand the fidelity of information flow inside cells. This work is providing fundamental insight into how cells function. Additionally, it may lead to the design of novel antibiotics that disrupt the signaling of pathogenic bacteria or it could help to guide the treatment of cancer, which often involves information-processing gone awry inside human cells. PMID:27427909

  11. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.

    Directory of Open Access Journals (Sweden)

    Martin H Schaefer

    2014-06-01

    Full Text Available Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors and the output (transcription factors layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.

  12. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.

    Science.gov (United States)

    Schaefer, Martin H; Yang, Jae-Seong; Serrano, Luis; Kiel, Christina

    2014-06-01

    Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors) and the output (transcription factors) layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types. PMID:24922536

  13. Plasma membrane rafts engaged in T cell signalling: new developments in an old concept

    Directory of Open Access Journals (Sweden)

    Sangani Dhaval

    2009-09-01

    Full Text Available Abstract Considerable controversy arose over the concept that cholesterol/sphingolipid-rich rafts in the T cell plasma membrane serve as a platform for TCR signalling reactions. This controversy was founded on the initial definition of rafts as detergent resistant membranes which later turned out to misrepresent many features of cell membrane organisation under physiological conditions. Raft-organisation was subsequently studied using a number of detergent-free experimental approaches. The results led to a refined perception of membrane rafts which resolves the controversies. Here we review new biophysical and biochemical data which provide an updated picture of the highly dynamic nanometer-sized cholesterol/sphingolipid-rich raft domains stabilised by protein-networks to form TCR signalling platforms in the T cell plasma membrane.

  14. Cell wall integrity signalling in human pathogenic fungi.

    Science.gov (United States)

    Dichtl, Karl; Samantaray, Sweta; Wagener, Johannes

    2016-09-01

    Fungi are surrounded by a rigid structure, the fungal cell wall. Its plasticity and composition depend on active regulation of the underlying biosynthesis and restructuring processes. This involves specialised signalling pathways that control gene expression and activities of biosynthetic enzymes. The cell wall integrity (CWI) pathway is the central signalling cascade required for the adaptation to a wide spectrum of cell wall perturbing conditions, including heat, oxidative stress and antifungals. In the recent years, great efforts were made to analyse the CWI pathway of diverse fungi. It turned out that the CWI signalling cascade is mostly conserved in the fungal kingdom. In this review, we summarise as well as compare the current knowledge on the canonical CWI pathway in the human pathogenic fungi Candida albicans, Candida glabrata, Aspergillus fumigatus and Cryptococcus neoformans. Understanding the differences and similarities in the stress responses of these organisms could become a key to improving existing or developing new antifungal therapies. PMID:27155139

  15. AlliedSignal solid oxide fuel cell technology

    Energy Technology Data Exchange (ETDEWEB)

    Minh, N.; Barr, K.; Kelly, P.; Montgomery, K. [AlliedSignal Aerospace Equipment Systems, Torrance, CA (United States)

    1996-12-31

    AlliedSignal has been developing high-performance, lightweight solid oxide fuel cell (SOFC) technology for a broad spectrum of electric power generation applications. This technology is well suited for use in a variety of power systems, ranging from commercial cogeneration to military mobile power sources. The AlliedSignal SOFC is based on stacking high-performance thin-electrolyte cells with lightweight metallic interconnect assemblies to form a compact structure. The fuel cell can be operated at reduced temperatures (600{degrees} to 800{degrees}C). SOFC stacks based on this design has the potential of producing 1 kW/kg and 1 ML. This paper summarizes the technical status of the design, manufacture, and operation of AlliedSignal SOFCs.

  16. 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

  17. 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

  18. Cell to Cell Signalling via Exosomes Through esRNA

    OpenAIRE

    Lotvall, Jan; Valadi, Hadi

    2007-01-01

    Exosomes are small vesicles of endosomal origin that can be released by many different cells to the microenvironment. Exosomes have been shown to participate in the immune system, by mediating antigen presentation. We have recently shown the presence of both mRNA and microRNA in exosomes, specifically in exosomes derived from mast cells. This RNA can be transferred between one mast cell to another, most likely through fusion of the exosome to the recipient cell membrane. The delivered RNA is ...

  19. Self-Organization in Disaster Resilient Heterogeneous Small Cell Networks

    OpenAIRE

    Zhang, Haijun; Jiang, Chunxiao; Hu, Rose Qingyang; Qian, Yi

    2015-01-01

    Heterogeneous small cell networks with overlay femtocells and macrocell is a promising solution for future heterogeneous wireless cellular communications. However, great resilience is needed in heterogeneous small cells in case of accidents, attacks and natural disasters. In this article, we first describe the network architecture of disaster resilient heterogeneous small cell networks (DRHSCNs), where several self-organization inspired approaches are applied. Based on the proposed resilient ...

  20. The Primary Cilium in Cell Signaling and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michaud III, Edward J [ORNL; Yoder, Bradley [University of Alabama, Birmingham

    2006-01-01

    The primary cilium is a microtubule-based antenna-like structure that emanates from the surface of virtually all cells in the mammalian body. It is anchored to the cell by the basal body, which develops from the mother centriole of the centrosome in a manner that is coordinately regulated with the cell cycle. The primary cilium is a sensory organelle that receives both mechanical and chemical signals from other cells and the environment, and transmits these signals to the nucleus to elicit a cellular response. Recent studies revealed that multiple components of the Sonic hedgehog and plateletderived growth factor receptor-A signal transduction pathways localize to the primary cilium, and that loss of the cilium blocks ligand-induced signaling by both pathways. In light of the major role that these pathways play in numerous types of cancer, we anticipate that the emerging discoveries being made about the function of the primary cilium in signaling pathways that are critical for embryonic development and tissue homeostasis in adults will also provide novel insights into the molecular mechanisms of carcinogenesis. (Cancer Res 2006; 66 13): 6463-7)

  1. Vitamin D cell signalling in health and disease.

    Science.gov (United States)

    Berridge, Michael J

    2015-04-24

    Vitamin D deficiency has been linked to many human diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), hypertension and cardiovascular disease. A Vitamin D phenotypic stability hypothesis, which is developed in this review, attempts to describe how this vital hormone acts to maintain healthy cellular functions. This role of Vitamin D as a guardian of phenotypic stability seems to depend on its ability to maintain the redox and Ca(2+) signalling systems. It is argued that its primary action is to maintain the expression of those signalling components responsible for stabilizing the low resting state of these two signalling pathways. This phenotypic stability role is facilitated through the ability of vitamin D to increase the expression of both Nrf2 and the anti-ageing protein Klotho, which are also major regulators of Ca(2+) and redox signalling. A decline in Vitamin D levels will lead to a decline in the stability of this regulatory signalling network and may account for why so many of the major diseases in man, which have been linked to vitamin D deficiency, are associated with a dysregulation in both ROS and Ca(2+) signalling. PMID:25998734

  2. 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.

  3. 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

  4. 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.

  5. 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 ...

  6. Plant Cell and Signaling Biology Blooms in the Wuyi Mountain

    Institute of Scientific and Technical Information of China (English)

    Jianping Hu

    2011-01-01

    @@ INTRODUCTION The Eighth International Conference on Plant Biology Fron-tiers, organized by Zhenbiao Yang, Chentao Lin, and Xing-wang Deng, was convened in the Wuyi Mountain Yeohwa Resort in Fujian, China, 23-27 September 2010.The meeting's main theme was Cells and Signals, featuring four keynote speeches, 45 plenary talks, and over 40 poster presentations that covered a wide range of topics, from dynamic cellular structures to how developmental and environmental signals control various plant processes at the juncture of cells.

  7. Extracellular ATP signaling and homeostasis in plant cells

    OpenAIRE

    Sun, Jian; Zhang, Chunlan; Zhang, Xuan; Deng, Shurong; Zhao, Rui; Shen, Xin; Chen, Shaoliang

    2012-01-01

    Extracellular ATP (eATP) is now recognized as an important signaling agent in plant growth and defense response to environmental stimuli. eATP has dual functions in plant cell signaling, which is largely dependent on its concentration in the extracellular matrix (ECM). A lethal level of eATP (extremely low or high) causes cell death, whereas a moderate level of eATP benefits plant growth and development. Ecto-apyrases (Nucleoside Triphosphate-Diphosphohydrolase) help control the eATP concentr...

  8. G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells

    OpenAIRE

    Natalia Polouliakh; Richard Nock; Frank Nielsen; Hiroaki Kitano

    2009-01-01

    A series of recent studies on large-scale networks of signaling and metabolic systems revealed that a certain network structure often called "bow-tie network" are observed. In signaling systems, bow-tie network takes a form with diverse and redundant inputs and outputs connected via a small numbers of core molecules. While arguments have been made that such network architecture enhances robustness and evolvability of biological systems, its functional role at a cellular level remains obscure....

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. Cell responses to FGFR3 signalling: growth, differentiation and apoptosis

    International Nuclear Information System (INIS)

    FGFR3 is a receptor tyrosine kinase (RTK) of the FGF receptor family, known to have a negative regulatory effect on long bone growth. Fgfr3 knockout mice display longer bones and, accordingly, most germline-activating mutations in man are associated with dwarfism. Somatically, some of the same activating mutations are associated with the human cancers multiple myeloma, cervical carcinoma and carcinoma of the bladder. How signalling through FGFR3 can lead to either chondrocyte apoptosis or cancer cell proliferation is not fully understood. Although FGFR3 can be expressed as two main splice isoforms (IIIb or IIIc), there is no apparent link with specific cell responses, which may rather be associated with the cell type or its differentiation status. Depending on cell type, differential activation of STAT proteins has been observed. STAT1 phosphorylation seems to be involved in inhibition of chondrocyte proliferation while activation of the ERK pathway inhibits chondrocyte differentiation and B-cell proliferation (as in multiple myeloma). The role of FGFR3 in epithelial cancers (bladder and cervix) is not known. Some of the cell specificity may arise via modulation of signalling by crosstalk with other signalling pathways. Recently, inhibition of the ERK pathway in achondroplastic mice has provided hope for an approach to the treatment of dwarfism. Further understanding of the ability of FGFR3 to trigger different responses depending on cell type and cellular context may lead to treatments for both skeletal dysplasias and cancer

  16. Apoptosis and signalling in acid sphingomyelinase deficient cells

    Directory of Open Access Journals (Sweden)

    Sillence Dan J

    2001-11-01

    Full Text Available Abstract Background Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis. Hypothesis An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function. Testing the hypothesis It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes / lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype. Implications of the hypothesis If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis.

  17. Lipid body accumulation alters calcium signaling dynamics in immune cells

    Science.gov (United States)

    Greineisen, William E.; Speck, Mark; Shimoda, Lori M.N.; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J.; Turner, Helen

    2014-01-01

    Summary There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcεRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signalling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcεRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signalling pathway and its downstream targets. PMID:25016314

  18. 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

  19. 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...

  20. 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.

  1. 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.

  2. 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)

  3. 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

  4. 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

  5. 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.

  6. Turing instabilities in a mathematical model for signaling networks

    CERN Document Server

    Rätz, Andreas

    2011-01-01

    GTPase molecules are important regulators in cells that continuously run through an activation/deactivation and membrane-attachment/membrane-detachment cycle. Activated GTPase is able to localize in parts of the membranes and to induce cell polarity. As feedback loops contribute to the GTPase cycle and as the coupling between membrane-bound and cytoplasmic processes introduces different diffusion coefficients a Turing mechanism is a natural candidate for this symmetry breaking. We formulate a mathematical model that couples a reaction-diffusion system in the inner volume to a reaction-diffusion system on the membrane via a flux condition and an attachment/detachment law at the membrane. We present a reduction to a simpler non-local reaction-diffusion model and perform a stability analysis and numerical simulations for this reduction. Our model in principle does support Turing instabilities but only if the lateral diffusion of inactivated GTPase is much faster than the diffusion of activated GTPase.

  7. 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 ...

  8. 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...

  9. 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...

  10. Targeting glioma stem cells via the Hedgehog signaling pathway

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2014-09-01

    Full Text Available Cancer is one of the leading causes of death worldwide. Gliomas are among the most devastating tumor types, and current clinical therapies are unsatisfactory. Recent reports revealed the importance of glioma-propagating cells in the malignancy of gliomas. These cells, also referred to as glioma stem cells (GSCs, share similarities with neural stem cells (NSCs. The Hedgehog (Hh signaling pathway controls tissue polarity, patterning maintenance, and maintenance of NSCs during embryonic development. Aberrant activation of the Hh pathway resulting from mutation and deregulation has recently been recognized to cause tumorigenesis in a wide variety of tissues, including gliomas and GSCs. In this review, we explore the role of the Hh signaling pathway in GSCs and its potential as a therapeutic strategy.

  11. Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

    International Nuclear Information System (INIS)

    Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

  12. Inquiry into Chemotherapy-Induced P53 Activation in Cancer Cells as a Model for Teaching Signal Transduction

    Science.gov (United States)

    Srougi, Melissa C.; Carson, Susan

    2013-01-01

    Intracellular and extracellular communication is conducted through an intricate and interwoven network of signal transduction pathways. The mechanisms for how cells speak with one another are of significant biological importance to both basic and industrial scientists from a number of different disciplines. We have therefore developed and…

  13. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    OpenAIRE

    Rodriguez-Zas Sandra L; Bionaz Massimo; Morin Dawn E; Drackley James K; Moyes Kasey M; Everts Robin E; Lewin Harris A; Loor Juan J

    2009-01-01

    Abstract Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis (S. uberis) that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare, and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection...

  14. 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

  15. 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.

  16. The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis

    OpenAIRE

    Wang, Fei

    2009-01-01

    Chemotaxis—the directed movement of cells in a gradient of chemoattractant—is essential for neutrophils to crawl to sites of inflammation and infection and for Dictyostelium discoideum (D. discoideum) to aggregate during morphogenesis. Chemoattractant-induced activation of spatially localized cellular signals causes cells to polarize and move toward the highest concentration of the chemoattractant. Extensive studies have been devoted to achieving a better understanding of the mechanism(s) use...

  17. Modulation of host-cell MAPkinase signaling during fungal infection

    OpenAIRE

    Nir Osherov

    2015-01-01

    Fungal infections contribute substantially to human suffering and mortality. The interaction between fungal pathogens and their host involves the invasion and penetration of the surface epithelium, activation of cells of the innate immune system and the generation of an effective response to block infection. Numerous host-cell signaling pathways are activated during fungal infection. This review will focus on the main fungal pathogens Aspergillus fumigatus, Candida albicans and Cryptococcus n...

  18. Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Thomas Kalinski

    Full Text Available Interleukin (IL-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

  19. 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.

  20. Signal transduction underlying ionizing radiation dose effects on cell growth

    International Nuclear Information System (INIS)

    Phosphorylation/dephosphorylation is commonly utilized in the irradiated cells to transmit intracellular information, such as that monitoring the severity of lesions, effectiveness of repair of damages, and fate of cells. Thus, the radiation dose effects on the flow of information through these intracellular networks should reveal the mechanisms underlying the cellular radiosensitivity, which needs to be monitored before performing radiation therapy on cancer patients. Antibodies that specifically recognize phosphorylated state of amino acids can be utilized to detect phosphorylation/dephosphorylation networks. It will be necessary to identify the antigenic proteins of the anti-phosphorylated amino acid antibody for further understanding. Mass spectrometry, which can determine the amino acid sequence of small peptide, will be important for this purpose. The radiation sensitivity measured by the flow of intracellular information will have general applications as a biomarker reflecting the state of homeostasis of cells in patients affected by various diseases or healthy aging individuals. (authors)

  1. 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.

  2. Microbe Associated Molecular Pattern Signaling in Guard Cells.

    Science.gov (United States)

    Ye, Wenxiu; Murata, Yoshiyuki

    2016-01-01

    Stomata, formed by pairs of guard cells in the epidermis of terrestrial plants, regulate gas exchange, thus playing a critical role in plant growth and stress responses. As natural openings, stomata are exploited by microbes as an entry route. Recent studies reveal that plants close stomata upon guard cell perception of molecular signatures from microbes, microbe associated molecular patterns (MAMPs), to prevent microbe invasion. The perception of MAMPs induces signal transduction including recruitment of second messengers, such as Ca(2+) and H2O2, phosphorylation events, and change of transporter activity, leading to stomatal movement. In the present review, we summarize recent findings in signaling underlying MAMP-induced stomatal movement by comparing with other signalings. PMID:27200056

  3. New results on anti-synchronization of switched neural networks with time-varying delays and lag signals.

    Science.gov (United States)

    Cao, Yuting; Wen, Shiping; Chen, Michael Z Q; Huang, Tingwen; Zeng, Zhigang

    2016-09-01

    This paper investigates the problem of global exponential anti-synchronization of a class of switched neural networks with time-varying delays and lag signals. Considering the packed circuits, the controller is dependent on the output of the system as the inner states are very hard to measure. Therefore, it is necessary to investigate the controller based on the output of the neuron cell. Through theoretical analysis, it is obvious that the obtained ones improve and generalize the results derived in the previous literature. To illustrate the effectiveness, a simulation example with applications in image encryptions is also presented in the paper. PMID:27295505

  4. Signal transduction events in aluminum-induced cell death in tomato suspension cells

    NARCIS (Netherlands)

    Iakimova, E.T.; Kapchina-Toteva, V.M.; Woltering, E.J.

    2007-01-01

    In this study, some of the signal transduction events involved in AlCl3-induced cell death in tomato (Lycopersicon esculentum Mill.) suspension cells were elucidated. Cells treated with 100 ¿M AlCl3 showed typical features of programmed cell death (PCD) such as nuclear and cytoplasmic condensation.

  5. Proteomes and Neural Stem Cells: cellular signalling during differentiation

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Halada, Petr; Vodička, Petr; Motlík, Jan; Horning, O.; Jensen, O. N.; Gadher, S. J.; Pelech, S.; Kovářová, Hana

    Cambridge : -, 2007, s. 1-1. [BSPR-EBI Meeting: Integrative Proteomics: From Molecules to Systems,. Cambridge (GB), 25.07.2007-27.07.2007] Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : neural stem cells * differentiation * signalling * proteome Subject RIV: EB - Genetics ; Molecular Biology

  6. A signal processing analysis of Purkinje cells in vitro

    Directory of Open Access Journals (Sweden)

    Ze'ev R Abrams

    2010-05-01

    Full Text Available Cerebellar Purkinje cells in vitro fire recurrent sequences of Sodium and Calcium spikes. Here, we analyze the Purkinje cell using harmonic analysis, and our experiments reveal that its output signal is comprised of three distinct frequency bands, which are combined using Amplitude and Frequency Modulation (AM/FM. We find that the three characteristic frequencies - Sodium, Calcium and Switching – occur in various combinations in all waveforms observed using whole-cell current clamp recordings. We found that the Calcium frequency can display a frequency doubling of its frequency mode, and the Switching frequency can act as a possible generator of pauses that are typically seen in Purkinje output recordings. Using a reversibly photo-switchable kainate receptor agonist, we demonstrate the external modulation of the Calcium and Switching frequencies. These experiments and Fourier analysis suggest that the Purkinje cell can be understood as a harmonic signal oscillator, enabling a higher level of interpretation of Purkinje signaling based on modern signal processing techniques.

  7. WNT antagonist, DKK2, is a Notch signaling target in intestinal stem cells: augmentation of a negative regulation system for canonical WNT signaling pathway by the Notch-DKK2 signaling loop in primates.

    Science.gov (United States)

    Katoh, Masuko; Katoh, Masaru

    2007-01-01

    Notch and WNT signaling pathways are key components of the stem cell signaling network. Canonical WNT signaling to intestinal progenitor cells leads to transcriptional activation of the JAG1 gene, encoding Serrate-type Notch ligand. JAG1 then binds to the Notch receptor on adjacent stem cells to induce Notch receptor proteolyses for the release of Notch intracellular domain (NICD). NICD is associated with CSL/RBPSUH and Mastermind (MAML1, MAML2, or MAML3) to activate Notch target genes, such as HES1 and HES5. Although WNT-dependent Notch signaling activation in intestinal stem cells is clarified, the effects of Notch signaling activation on WNT signaling in progenitor cells remain unclear. We searched for Notch-response element (NRE) in the promoter region of genes encoding secreted WNT signaling inhibitors, including DKK1, DKK2, DKK3, DKK4, SFRP1, SFRP2, SFRP3, SFRP4, SFRP5 and WIF1. Double NREs were identified within human DKK2 promoter by bioinformatics and human intelligence (Humint). The human DKK2 gene was characterized as Notch signaling target in intestinal stem cells. Because DKK2 is a key player in the stem cell signaling network, the DKK2 gene at human chromosome 4q25 is a candidate tumor suppressor gene inactivated due to epigenetic silencing and/or deletion. The chimpanzee DKK2 gene was identified within the NW_105990.1 genome sequence, while the cow Dkk2 gene was identified within the AC156664.2 and AC158038.2 genome sequences. Chimpanzee DKK2 and cow Dkk2 showed 98.5% and 95.8% total-amino-acid identity with human DKK2, respectively. Double NREs in human DKK2 promoter were conserved in chimpanzee DKK2 promoter, partially in rat Dkk2 promoter, but not in cow and mouse Dkk2 promoters. The Notch-DKK2 signaling loop, created or potentiated in primates, was complementary to WNT-DKK1 and BMP-IHH-SFRP1 signaling loops for negative regulation of canonical WNT signaling pathway. Together, these facts indicate that DKK2 promoter evolution resulted in the

  8. Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers.

    Science.gov (United States)

    Pramparo, Tiziano; Lombardo, Michael V; Campbell, Kathleen; Barnes, Cynthia Carter; Marinero, Steven; Solso, Stephanie; Young, Julia; Mayo, Maisi; Dale, Anders; Ahrens-Barbeau, Clelia; Murray, Sarah S; Lopez, Linda; Lewis, Nathan; Pierce, Karen; Courchesne, Eric

    2015-12-01

    Genetic mechanisms underlying abnormal early neural development in toddlers with Autism Spectrum Disorder (ASD) remain uncertain due to the impossibility of direct brain gene expression measurement during critical periods of early development. Recent findings from a multi-tissue study demonstrated high expression of many of the same gene networks between blood and brain tissues, in particular with cell cycle functions. We explored relationships between blood gene expression and total brain volume (TBV) in 142 ASD and control male toddlers. In control toddlers, TBV variation significantly correlated with cell cycle and protein folding gene networks, potentially impacting neuron number and synapse development. In ASD toddlers, their correlations with brain size were lost as a result of considerable changes in network organization, while cell adhesion gene networks significantly correlated with TBV variation. Cell cycle networks detected in blood are highly preserved in the human brain and are upregulated during prenatal states of development. Overall, alterations were more pronounced in bigger brains. We identified 23 candidate genes for brain maldevelopment linked to 32 genes frequently mutated in ASD. The integrated network includes genes that are dysregulated in leukocyte and/or postmortem brain tissue of ASD subjects and belong to signaling pathways regulating cell cycle G1/S and G2/M phase transition. Finally, analyses of the CHD8 subnetwork and altered transcript levels from an independent study of CHD8 suppression further confirmed the central role of genes regulating neurogenesis and cell adhesion processes in ASD brain maldevelopment. PMID:26668231

  9. 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.

  10. 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....

  11. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  12. 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

  13. Neuroprotection Signaling of Nuclear Akt in Neuronal Cells

    OpenAIRE

    Ahn, Jee-Yin

    2014-01-01

    Akt is one of the central kinases that perform a pivotal function in mediating survival signaling in a wide range of neuronal cell types in response to growth factor stimulation. The recent findings of a number of targets for Akt suggest that it prohibits neuronal death by both impinging on the cytoplasmic cell death machinery and by regulating nuclear proteins. The presence of active Akt in the nuclei of mammalian cells is no longer debatable, and this has been corroborated by the finding of...

  14. 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.

  15. Insulin signaling regulates mitochondrial function in pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Siming Liu

    Full Text Available Insulin/IGF-I signaling regulates the metabolism of most mammalian tissues including pancreatic islets. To dissect the mechanisms linking insulin signaling with mitochondrial function, we first identified a mitochondria-tethering complex in beta-cells that included glucokinase (GK, and the pro-apoptotic protein, BAD(S. Mitochondria isolated from beta-cells derived from beta-cell specific insulin receptor knockout (betaIRKO mice exhibited reduced BAD(S, GK and protein kinase A in the complex, and attenuated function. Similar alterations were evident in islets from patients with type 2 diabetes. Decreased mitochondrial GK activity in betaIRKOs could be explained, in part, by reduced expression and altered phosphorylation of BAD(S. The elevated phosphorylation of p70S6K and JNK1 was likely due to compensatory increase in IGF-1 receptor expression. Re-expression of insulin receptors in betaIRKO cells partially restored the stoichiometry of the complex and mitochondrial function. These data indicate that insulin signaling regulates mitochondrial function and have implications for beta-cell dysfunction in type 2 diabetes.

  16. Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    O.H. Petersen

    2009-01-01

    Full Text Available The pancreatic acinar cell is a classical model for studies of secretion and signal transduction mechanisms. Because of the extensive endoplasmic reticulum and the large granular compartment, it has been possible - by direct measurements - to obtain considerable insights into intracellular Ca2+ handling under both normal and pathological conditions. Recent studies have also revealed important characteristics of stimulus-secretion coupling mechanisms in isolated human pancreatic acinar cells. The acinar cells are potentially dangerous because of the high intra-granular concentration of proteases, which become inappropriately activated in the human disease acute pancreatitis. This disease is due to toxic Ca2+ signals generated by excessive liberation of Ca2+ from both the endoplasmic reticulum and the secretory granules.

  17. Human pluripotent stem cell culture density modulates YAP signaling.

    Science.gov (United States)

    Hsiao, Cheston; Lampe, Michael; Nillasithanukroh, Songkhun; Han, Wenqing; Lian, Xiaojun; Palecek, Sean P

    2016-05-01

    Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs. PMID:26766309

  18. SoftCell: Taking Control of Cellular Core Networks

    OpenAIRE

    Jin, Xin; Li, Li Erran; Vanbever, Laurent; Rexford, Jennifer

    2013-01-01

    Existing cellular networks suffer from inflexible and expensive equipment, and complex control-plane protocols. To address these challenges, we present SoftCell, a scalable architecture for supporting fine-grained policies for mobile devices in cellular core networks. The SoftCell controller realizes high-level service polices by directing traffic over paths that traverse a sequence of middleboxes, optimized to the network conditions and user locations. To ensure scalability, the core switche...

  19. LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Benoit Langlois

    Full Text Available BACKGROUND: The low-density lipoprotein receptor-related protein-1 (LRP-1 is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. METHODOLOGY/PRINCIPAL FINDINGS: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. CONCLUSIONS: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion.

  20. 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

  1. 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.

  2. 14-3-3 proteins in guard cell signaling

    Directory of Open Access Journals (Sweden)

    Valérie eCotelle

    2016-01-01

    Full Text Available Guard cells are specialized cells located at the leaf surface delimiting pores which control gas exchanges between the plant and the atmosphere. To optimize the CO2 uptake necessary for photosynthesis while minimizing water loss, guard cells integrate environmental signals to adjust stomatal aperture. The size of the stomatal pore is regulated by movements of the guard cells driven by variations in their volume and turgor. As guard cells perceive and transduce a wide array of environmental cues, they provide an ideal system to elucidate early events of plant signaling. Reversible protein phosphorylation events are known to play a crucial role in the regulation of stomatal movements. However, in some cases, phosphorylation alone is not sufficient to achieve complete protein regulation, but is necessary to mediate the binding of interactors that modulate protein function. Among the phosphopeptide-binding proteins, the 14-3-3 proteins are the best characterized in plants. The 14-3-3s are found as multiple isoforms in eukaryotes and have been shown to be involved in the regulation of stomatal movements. In this review, we describe the current knowledge about 14-3-3 roles in the regulation of their binding partners in guard cells: receptors, ion pumps, channels, protein kinases and some of their substrates. Regulation of these targets by 14-3-3 proteins is discussed and related to their function in guard cells during stomatal movements in response to abiotic or biotic stresses.

  3. 14-3-3 Proteins in Guard Cell Signaling

    Science.gov (United States)

    Cotelle, Valérie; Leonhardt, Nathalie

    2016-01-01

    Guard cells are specialized cells located at the leaf surface delimiting pores which control gas exchanges between the plant and the atmosphere. To optimize the CO2 uptake necessary for photosynthesis while minimizing water loss, guard cells integrate environmental signals to adjust stomatal aperture. The size of the stomatal pore is regulated by movements of the guard cells driven by variations in their volume and turgor. As guard cells perceive and transduce a wide array of environmental cues, they provide an ideal system to elucidate early events of plant signaling. Reversible protein phosphorylation events are known to play a crucial role in the regulation of stomatal movements. However, in some cases, phosphorylation alone is not sufficient to achieve complete protein regulation, but is necessary to mediate the binding of interactors that modulate protein function. Among the phosphopeptide-binding proteins, the 14-3-3 proteins are the best characterized in plants. The 14-3-3s are found as multiple isoforms in eukaryotes and have been shown to be involved in the regulation of stomatal movements. In this review, we describe the current knowledge about 14-3-3 roles in the regulation of their binding partners in guard cells: receptors, ion pumps, channels, protein kinases, and some of their substrates. Regulation of these targets by 14-3-3 proteins is discussed and related to their function in guard cells during stomatal movements in response to abiotic or biotic stresses. PMID:26858725

  4. MAPK signal pathways in the regulation of cell proliferation in mammalian cells

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    MAPK families play an important role in complex cellular programs like proliferation, differentiation,development, transformation, and apoptosis. At least three MAPK families have been characterized: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation.

  5. Observation and inverse problems in coupled cell networks

    International Nuclear Information System (INIS)

    A coupled cell network is a model for many situations such as food webs in ecosystems, cellular metabolism and economic networks. It consists in a directed graph G, each node (or cell) representing an agent of the network and each directed arrow representing which agent acts on which. It yields a system of differential equations .x(t)=f(x(t)), where the component i of f depends only on the cells xj(t) for which the arrow j → i exists in G. In this paper, we investigate the observation problems in coupled cell networks: can one deduce the behaviour of the whole network (oscillations, stabilization, etc) by observing only one of the cells? We show that the natural observation properties hold for almost all the interactions f

  6. Integrative modelling of the influence of MAPK network on cancer cell fate decision.

    Directory of Open Access Journals (Sweden)

    Luca Grieco

    2013-10-01

    Full Text Available The Mitogen-Activated Protein Kinase (MAPK network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3 activating mutations.

  7. Reconstruction of Protein-Protein Interaction Network of Insulin Signaling in Homo Sapiens

    OpenAIRE

    Saliha Durmuş Tekir; Pelin Ümit; Aysun Eren Toku; Kutlu Ö. Ülgen

    2010-01-01

    Diabetes is one of the most prevalent diseases in the world. Type 1 diabetes is characterized by the failure of synthesizing and secreting of insulin because of destroyed pancreatic β-cells. Type 2 diabetes, on the other hand, is described by the decreased synthesis and secretion of insulin because of the defect in pancreatic β-cells as well as by the failure of responding to insulin because of malfunctioning of insulin signaling. In order to understand the signaling mechanisms of responding ...

  8. 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.

  9. 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

  10. Hormone Signaling Pathways in Plants: The Role of Jasmonic Acid in Plant Cell Signaling

    OpenAIRE

    TİRYAKİ, İskender

    2004-01-01

    Plant growth and metabolism are affected by various biotic and abiotic stimuli including microorganisms and insects attack as well as light and environmental stresses. Such a diverse plant response requires a communication system that uses a group of chemical messengers called hormones. Hormones promote, inhibit, or qualitatively modify plant growth and development. This complex process requires a signal transduction that defines a specific information pathway within a cell that translat...

  11. Wnt signaling pathway in non-small cell lung cancer.

    Science.gov (United States)

    Stewart, David J

    2014-01-01

    Wnt/β-catenin alterations are prominent in human malignancies. In non-small cell lung cancer (NSCLC), β-catenin and APC mutations are uncommon, but Wnt signaling is important in NSCLC cell lines, and Wnt inhibition reduces proliferation. Overexpression of Wnt-1, -2, -3, and -5a and of Wnt-pathway components Frizzled-8, Dishevelled, Porcupine, and TCF-4 is common in resected NSCLC and is associated with poor prognosis. Conversely, noncanonical Wnt-7a suppresses NSCLC development and is often downregulated. Although β-catenin is often expressed in NSCLCs, it was paradoxically associated with improved prognosis in some series, possibly because of E-cadherin interactions. Downregulation of Wnt inhibitors (eg, by hypermethylation) is common in NSCLC tumor cell lines and resected samples; may be associated with high stage, dedifferentiation, and poor prognosis; and has been reported for AXIN, sFRPs 1-5, WIF-1, Dkk-1, Dkk-3, HDPR1, RUNX3, APC, CDX2, DACT2, TMEM88, Chibby, NKD1, EMX2, ING4, and miR-487b. AXIN is also destabilized by tankyrases, and GSK3β may be inactivated through phosphorylation by EGFR. Preclinically, restoration of Wnt inhibitor function is associated with reduced Wnt signaling, decreased cell proliferation, and increased apoptosis. Wnt signaling may also augment resistance to cisplatin, docetaxel, and radiotherapy, and Wnt inhibitors may restore sensitivity. Overall, available data indicate that Wnt signaling substantially impacts NSCLC tumorigenesis, prognosis, and resistance to therapy, with loss of Wnt signaling inhibitors by promoter hypermethylation or other mechanisms appearing to be particularly important. Wnt pathway antagonists warrant exploration clinically in NSCLC. Agents blocking selected specific β-catenin interactions and approaches to increase expression of downregulated Wnt inhibitors may be of particular interest. PMID:24309006

  12. Phosphorylation site dynamics of early T-cell receptor signaling

    DEFF Research Database (Denmark)

    Chylek, Lily A; Akimov, Vyacheslav; Dengjel, Jörn;

    2014-01-01

    systems-level understanding of how these components cooperate to control signaling dynamics, especially during the crucial first seconds of stimulation. Here, we used quantitative proteomics to characterize reshaping of the T-cell phosphoproteome in response to TCR/CD28 co-stimulation, and found that...... diverse dynamic patterns emerge within seconds. We detected phosphorylation dynamics as early as 5 s and observed widespread regulation of key TCR signaling proteins by 30 s. Development of a computational model pointed to the presence of novel regulatory mechanisms controlling phosphorylation of sites...

  13. TIM-1 signaling in B cells regulates antibody production

    International Nuclear Information System (INIS)

    Highlights: → TIM-1 is highly expressed on anti-IgM + anti-CD40-stimulated B cells. → Anti-TIM-1 mAb enhanced proliferation and Ig production on activated B cell in vitro. → TIM-1 signaling regulates Ab production by response to TI-2 and TD antigens in vivo. -- Abstract: Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-IgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressed on B cells and inducible on anti-CD3+ anti-CD28-stimulated CD4+ T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation.

  14. Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

    2016-06-01

    Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

  15. Unidirectional signal propagation in primary neurons micropatterned at a single-cell resolution

    Science.gov (United States)

    Yamamoto, H.; Matsumura, R.; Takaoki, H.; Katsurabayashi, S.; Hirano-Iwata, A.; Niwano, M.

    2016-07-01

    The structure and connectivity of cultured neuronal networks can be controlled by using micropatterned surfaces. Here, we demonstrate that the direction of signal propagation can be precisely controlled at a single-cell resolution by growing primary neurons on micropatterns. To achieve this, we first examined the process by which axons develop and how synapses form in micropatterned primary neurons using immunocytochemistry. By aligning asymmetric micropatterns with a marginal gap, it was possible to pattern primary neurons with a directed polarization axis at the single-cell level. We then examined how synapses develop on micropatterned hippocampal neurons. Three types of micropatterns with different numbers of short paths for dendrite growth were compared. A normal development in synapse density was observed when micropatterns with three or more short paths were used. Finally, we performed double patch clamp recordings on micropatterned neurons to confirm that these synapses are indeed functional, and that the neuronal signal is transmitted unidirectionally in the intended orientation. This work provides a practical guideline for patterning single neurons to design functional neuronal networks in vitro with the direction of signal propagation being controlled.

  16. Biomechanical Origins of Muscle Stem Cell Signal Transduction.

    Science.gov (United States)

    Morrissey, James B; Cheng, Richard Y; Davoudi, Sadegh; Gilbert, Penney M

    2016-04-10

    Skeletal muscle, the most abundant and widespread tissue in the human body, contracts upon receiving electrochemical signals from the nervous system to support essential functions such as thermoregulation, limb movement, blinking, swallowing and breathing. Reconstruction of adult muscle tissue relies on a pool of mononucleate, resident muscle stem cells, known as "satellite cells", expressing the paired-box transcription factor Pax7 necessary for their specification during embryonic development and long-term maintenance during adult life. Satellite cells are located around the myofibres in a niche at the interface of the basal lamina and the host fibre plasma membrane (i.e., sarcolemma), at a very low frequency. Upon damage to the myofibres, quiescent satellite cells are activated and give rise to a population of transient amplifying myogenic progenitor cells, which eventually exit the cell cycle permanently and fuse to form new myofibres and regenerate the tissue. A subpopulation of satellite cells self-renew and repopulate the niche, poised to respond to future demands. Harnessing the potential of satellite cells relies on a complete understanding of the molecular mechanisms guiding their regulation in vivo. Over the past several decades, studies revealed many signal transduction pathways responsible for satellite cell fate decisions, but the niche cues driving the activation and silencing of these pathways are less clear. Here we explore the scintillating possibility that considering the dynamic changes in the biophysical properties of the skeletal muscle, namely stiffness, and the stretch and shear forces to which a myofibre can be subjected to may provide missing information necessary to gain a full understanding of satellite cell niche regulation. PMID:26004541

  17. An alternative pathway for signal flow from rod photoreceptors to ganglion cells in mammalian retina.

    OpenAIRE

    DeVries, S H; Baylor, D A

    1995-01-01

    Rod signals in the mammalian retina are thought to reach ganglion cells over the circuit rod-->rod depolarizing bipolar cell-->AII amacrine cell-->cone bipolar cells-->ganglion cells. A possible alternative pathway involves gap junctions linking the rods and cones, the circuit being rod-->cone-->cone bipolar cells-->ganglion cells. It is not clear whether this second pathway indeed relays rod signals to ganglion cells. We studied signal flow in the isolated rabbit retina with a multielectrode...

  18. Role of Calcium Signaling in B Cell Activation and Biology.

    Science.gov (United States)

    Baba, Yoshihiro; Kurosaki, Tomohiro

    2016-01-01

    Increase in intracellular levels of calcium ions (Ca2+) is one of the key triggering signals for the development of B cell response to the antigen. The diverse Ca2+ signals finely controlled by multiple factors participate in the regulation of gene expression, B cell development, and effector functions. B cell receptor (BCR)-initiated Ca2+ mobilization is sourced from two pathways: one is the release of Ca2+ from the intracellular stores, endoplasmic reticulum (ER), and other is the prolonged influx of extracellular Ca2+ induced by depleting the stores via store-operated calcium entry (SOCE) and calcium release-activated calcium (CRAC) channels. The identification of stromal interaction molecule 1(STIM1), the ER Ca2+ sensor, and Orai1, a key subunit of the CRAC channel pore, has now provided the tools to understand the mode of Ca2+ influx regulation and physiological relevance. Herein, we discuss our current understanding of the molecular mechanisms underlying BCR-triggered Ca2+ signaling as well as its contribution to the B cell biological processes and diseases. PMID:26369772

  19. Ovarian cancer stem-like cells differentiate into endothelial cells and participate in tumor angiogenesis through autocrine CCL5 signaling.

    Science.gov (United States)

    Tang, Shu; Xiang, Tong; Huang, Shuo; Zhou, Jie; Wang, Zhongyu; Xie, Rongkai; Long, Haixia; Zhu, Bo

    2016-06-28

    Cancer stem cells (CSCs) are well known for their self-regeneration and tumorigenesis potential. In addition, the multi-differentiation potential of CSCs has become a popular issue and continues to attract increased research attention. Recent studies demonstrated that CSCs are able to differentiate into functional endothelial cells and participate in tumor angiogenesis. In this study, we found that ovarian cancer stem-like cells (CSLCs) activate the NF-κB and STAT3 signal pathways through autocrine CCL5 signaling and mediate their own differentiation into endothelial cells (ECs). Our data demonstrate that CSLCs differentiate into ECs morphologically and functionally. Anti-CCL5 antibodies and CCL5-shRNA lead to markedly inhibit EC differentiation and the tube formation of CSLCs, both in vitro and in vivo. Recombinant human-CCL5 significantly promotes ovarian CSLCs that differentiate into ECs and form microtube network. The CCL5-mediated EC differentiation of CSLCs depends on binding to receptors, such as CCR1, CCR3, and CCR5. The results demonstrated that CCL5-CCR1/CCR3/CCR5 activates the NF-κB and STAT3 signal pathways, subsequently mediating the differentiation of CSLCs into ECs. Therefore, this study was conducted based on the theory that CSCs improve tumor angiogenesis and provides a novel strategy for anti-angiogenesis in ovarian cancer. PMID:27033454

  20. Erythropoietin regulates Treg cells in asthma through TGFβ receptor signaling.

    Science.gov (United States)

    Wan, Guoshi; Wei, Bing

    2015-01-01

    Asthma is a chronic inflammatory disorder of the airways, the development of which is suppressed by regulatory T cells (Treg). Erythropoietin (EPO) is originally defined as a hematopoietic growth factor. Recently, the anti-inflammatory effects of EPO in asthma have been acknowledged. However, the underlying mechanisms remain ill-defined. Here, we showed that EPO treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice, seemingly through promoting Foxp3-mediated activation of Treg cells in OVA-treated mouse lung. The activation of Treg cells resulted from increases in transforming growth factor β1 (TGFβ1), which were mainly produced by M2 macrophages (M2M). In vitro, Co-culture with M2M increased Foxp3 levels in Treg cells and the Treg cell number, in a TGFβ receptor signaling dependent manner. Moreover, elimination of macrophages abolished the therapeutic effects of EPO in vivo. Together, our data suggest that EPO may increase M2M, which activate Treg cells through TGFβ receptor signaling to mitigate the severity of asthma. PMID:26807178

  1. 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.

  2. Vitamin D controls T cell antigen receptor signaling and activation of human T cells

    DEFF Research Database (Denmark)

    von Essen, Marina Rode; Kongsbak, Martin; Schjerling, Peter;

    2010-01-01

    Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-gamma1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering...... led to an upregulation of approximately 75-fold in PLC-gamma1 expression, which correlated with greater TCR responsiveness. Induction of PLC-gamma1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR...... signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-gamma1, which are required for subsequent classical TCR signaling and T cell activation....

  3. Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

    Directory of Open Access Journals (Sweden)

    M Lia Palomba

    Full Text Available PURPOSE: Chronic Lymphocytic Leukemia (CLL is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR. Results from multidimensional modeling were validated using an independent test cohort of 38 patients. RESULTS: We identified a dynamic and variable imbalance between proximal (pSYK, pBTK and distal (pPLCγ2, pBLNK, ppERK phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. CONCLUSION: Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.

  4. Breast cancer stem cells, cytokine networks, and the tumor microenvironment

    OpenAIRE

    Korkaya, Hasan; Liu, Suling; Wicha, Max S.

    2011-01-01

    Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment — including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells — through networks of cytokines and growth factors. Since these components have a direct...

  5. Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Su; Li-Ying Wang; Yu-Long Liang; Xi-Liang Zha

    2005-01-01

    AIM: Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase)ILK, and β-catenin in hepatocellular carcinoma cell apoptosis.METHODS: We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and 1H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 μmol/L N,N-diphenyl-p-phenylenediamine,which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, β-catenin, and PKB in this apoptotic model by Western blot.RESULTS: We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and β-catenin or the damage of cell-matrix and cell-cell adhesion.CONCLUSION: Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and β-catenin,could induce hepatocellular carcinoma cell apoptosis.

  6. 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.

  7. Cell Counting Attack and Browser Attack against TOR Network

    OpenAIRE

    Swati

    2014-01-01

    The onion router (TOR) allows to hide your identity various software under this categories are available that allows online anonymity network, supporting TCP applications over the Internet. It doesn't allow network surveillance or traffic analysis to get tracked but most of these software used equal size of cells (512B). In this paper we are comparing cell-counting attacks and browser attacks against TOR. Different from cell-counting attacks, these attacks can confirm anonymou...

  8. Breakdown of cell-collagen networks through collagen remodeling

    OpenAIRE

    Iordan, Andreea; Duperray, Alain; Gérard, Anaïs; Grichine, Alexei; Verdier, Claude

    2010-01-01

    International audience Collagen model tissues are analyzed, which consist of cells embedded in a collagen matrix at different concentrations (of cells and collagen). Rheological properties are measured and complementary confocal microscopy analyses are carried out. An important feature is observed, corresponding to the breakdown of the collagen network (i.e. decrease in network elasticity) for high collagen concentrations, due to the presence of cells. Thanks to confocal microscopy, we sho...

  9. A New Cell Association Scheme In Heterogeneous Networks

    OpenAIRE

    Yang, Bin; Mao, Guoqiang; Ge, Xiaohu; Han, Tao

    2015-01-01

    Cell association scheme determines which base station (BS) and mobile user (MU) should be associated with and also plays a significant role in determining the average data rate a MU can achieve in heterogeneous networks. However, the explosion of digital devices and the scarcity of spectra collectively force us to carefully re-design cell association scheme which was kind of taken for granted before. To address this, we develop a new cell association scheme in heterogeneous networks based on ...

  10. Vitamin D Receptor Signaling and Pancreatic Cancer Cell EMT

    Science.gov (United States)

    Li, Zhiwei; Guo, Junli; Xie, Keping; Zheng, Shaojiang

    2016-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of human malignancies. Even in patients who undergo resection, long-term survival rates remain extremely low. A major contributor to the aggressiveness of pancreatic ductal adenocarcinoma is epithelial-to-mesenchymal transition (EMT), a physiologic process of morphological and genetic changes in carcinoma cells from an epithelial phenotype to a mesenchymal phenotype, which is the basis of the high metastatic potential of pancreatic cancer cells. EMT is triggered by various tumor microenvironmental factors, including cytokines, growth factors, and chemotherapeutic agents. This review highlights the growing evidence of the effect of EMT on pancreatic cancer progression, focusing on the interaction of EMT with other pathways central to cancer progression, especially vitamin D receptor signaling. Studies of the signaling pathways that lead to the inactivation of EMT programs during these disease processes are providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions. PMID:25506892

  11. Isoelectric focusing technology quantifies protein signaling in 25 cells

    Science.gov (United States)

    O'Neill, Roger A.; Bhamidipati, Arunashree; Bi, Xiahui; Deb-Basu, Debabrita; Cahill, Linda; Ferrante, Jason; Gentalen, Erik; Glazer, Marc; Gossett, John; Hacker, Kevin; Kirby, Celeste; Knittle, James; Loder, Robert; Mastroieni, Catherine; MacLaren, Michael; Mills, Thomas; Nguyen, Uyen; Parker, Nineveh; Rice, Audie; Roach, David; Suich, Daniel; Voehringer, David; Voss, Karl; Yang, Jade; Yang, Tom; Vander Horn, Peter B.

    2006-01-01

    A previously undescribed isoelectric focusing technology allows cell signaling to be quantitatively assessed in <25 cells. High-resolution capillary isoelectric focusing allows isoforms and individual phosphorylation forms to be resolved, often to baseline, in a 400-nl capillary. Key to the method is photochemical capture of the resolved protein forms. Once immobilized, the proteins can be probed with specific antibodies flowed through the capillary. Antibodies bound to their targets are detected by chemiluminescence. Because chemiluminescent substrates are flowed through the capillary during detection, localized substrate depletion is overcome, giving excellent linearity of response across several orders of magnitude. By analyzing pan-specific antibody signals from individual resolved forms of a protein, each of these can be quantified, without the problems associated with using multiple antibodies with different binding avidities to detect individual protein forms. PMID:17053065

  12. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

    International Nuclear Information System (INIS)

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  13. Role of TAZ in cancer stem cells and Wnt signaling

    OpenAIRE

    Azzolin, Luca

    2013-01-01

    The transcriptional co-activator TAZ, known Hippo transducer together with his paralogue YAP, has recently emerged as important player in processes like organ growth and tumorigenesis. Here we focused on two aspects of TAZ biology: the first regards the role of TAZ as molecular determinant of breast cancer stem cells (CSCs); the second is the characterization of TAZ as downstream mediator of Wnt signaling. Using a bioinformatic approach, we discovered that more-malignant/CSC-enriched prim...

  14. Cell volume homeostatic mechanisms: effectors and signalling pathways

    DEFF Research Database (Denmark)

    Hoffmann, E K; Pedersen, Stine Helene Falsig

    2011-01-01

    the historical context of studies of cell volume regulation, focusing on the lineage started by Krogh, Bodil Schmidt-Nielsen, Hans-Henrik Ussing, and their students. The early work was focused on understanding the functional behaviour, kinetics and thermodynamics of the volume-regulatory ion transport......Cell volume homeostasis and its fine-tuning to the specific physiological context at any given moment are processes fundamental to normal cell function. The understanding of cell volume regulation owes much to August Krogh, yet has advanced greatly over the last decades. In this review, we outline...... mechanisms. Later work addressed the mechanisms through which cellular signalling pathways regulate the volume regulatory effectors or flux pathways. These studies were facilitated by the molecular identification of most of the relevant channels and transporters, and more recently also by the increased...

  15. Using Multi-objective Optimization to Identify Dynamical Network Biomarkers as Early-warning Signals of Complex Diseases.

    Science.gov (United States)

    Vafaee, Fatemeh

    2016-01-01

    Biomarkers have gained immense scientific interest and clinical value in the practice of medicine. With unprecedented advances in high-throughput technologies, research interest in identifying novel and customized disease biomarkers for early detection, diagnosis, or drug responses is rapidly growing. Biomarkers can be identified in different levels of molecular biomarkers, networks biomarkers and dynamical network biomarkers (DNBs). The latter is a recently developed concept which relies on the idea that a cell is a complex system whose behavior is emerged from interplay of various molecules, and this network of molecules dynamically changes over time. A DNB can serve as an early-warning signal of disease progression, or as a leading network that drives the system into the disease state, and thus unravels mechanisms of disease initiation and progression. It is therefore of great importance to identify DNBs efficiently and reliably. In this work, the problem of DNB identification is defined as a multi-objective optimization problem, and a framework to identify DNBs out of time-course high-throughput data is proposed. Temporal gene expression data of a lung injury with carbonyl chloride inhalation exposure has been used as a case study, and the functional role of the discovered biomarker in the pathogenesis of lung injury has been thoroughly analyzed. PMID:26906975

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Inference of Transcriptional Network for Pluripotency in Mouse Embryonic Stem Cells

    International Nuclear Information System (INIS)

    In embryonic stem cells, various transcription factors (TFs) maintain pluripotency. To gain insights into the regulatory system controlling pluripotency, I inferred the regulatory relationships between the TFs expressed in ES cells. In this study, I applied a method based on structural equation modeling (SEM), combined with factor analysis, to 649 expression profiles of 19 TF genes measured in mouse Embryonic Stem Cells (ESCs). The factor analysis identified 19 TF genes that were regulated by several unmeasured factors. Since the known cell reprogramming TF genes (Pou5f1, Sox2 and Nanog) are regulated by different factors, each estimated factor is considered to be an input for signal transduction to control pluripotency in mouse ESCs. In the inferred network model, TF proteins were also arranged as unmeasured factors that control other TFs. The interpretation of the inferred network model revealed the regulatory mechanism for controlling pluripotency in ES cells

  2. 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.

  3. Gravity perception and signal transduction in single cells

    Science.gov (United States)

    Block, I.; Wolke, A.; Briegleb, W.; Ivanova, K.

    Cellular signal processing in multi-, as well as in unicellular organisms, has to rely on fundamentally similar mechanisms. Free-living single cells often use the gravity vector for their spatial orientation (gravitaxis) and show distinct gravisensitivities. In this investigation the gravisensitive giant ameboid cell Physarum polycephalum (Myxomycetes, acellular slime molds) is used. Its gravitaxis and the modulation of its intrinsic rhythmic contraction activity by gravity was demonstrated in 180 °turn experiments and in simulated, as well as in actual, near-weightlessness studies (fast-rotating clinostat; Spacelab D1, IML-1). The stimulus perception was addressed in an IML-2 experiment, which provided information on the gravireceptor itself by the determination of the cell's acceleration-sensitivity threshold. Ground-based experiments designed to elucidate the subsequent steps in signal transduction leading to a motor response, suggest that an acceleration stimulus induces changes in the level of second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), indicating also that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

  4. Substrates of protein kinases involved in cell signal transduction

    International Nuclear Information System (INIS)

    In this study substrates for protein-tyrosine kinases and protein kinase C are examined to gain a better understanding of the conditions of their phosphorylation, their functions, and their potential involvement in intracellular signaling pathways. The tissue, cell type, and intracellular distributions of two protein-tyrosine kinase substrates, termed p36 and p81, are determined by immunoblotting of murine tissues, indirect immunofluorescence and immunoperoxidase staining of frozen rat tissue sections, and biochemical fractionation and indirect immunofluorescence staining of tissue culture cells. Both p36 and p81 are constitutively phosphorylated to low levels in tissue culture cells. In 32P-labeled A431 cells, pp81 contains both phosphoserine and phosphothreonine. Following brief epidermal growth factor treatment of A431 cells, pp81 is more heavily phosphorylated on threonine and approximately 10% of p81 molecules become phosphorylated on tyrosine. Treatment of A431 cells with the potent tumor promoter and protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), does not alter the phosphorylation state of p81. However, TPA treatment of A431 cells and certain other cell types leads to augmented serine phosphorylation of p36

  5. 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.

  6. 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

  7. Role of topology in complex functional networks of beta cells.

    Science.gov (United States)

    Cherubini, Christian; Filippi, Simonetta; Gizzi, Alessio; Loppini, Alessandro

    2015-10-01

    The activity of pancreatic β cells can be described by biological networks of coupled nonlinear oscillators that, via electrochemical synchronization, release insulin in response to augmented glucose levels. In this work, we analyze the emergent behavior of regular and percolated β-cells clusters through a stochastic mathematical model where "functional" networks arise. We show that the emergence and robustness of the synchronized dynamics depend both on intrinsic and extrinsic parameters. In particular, cellular noise level, glucose concentration, network spatial architecture, and cell-to-cell coupling strength are the key factors for the generation of a rhythmic and robust activity. Their role in the functional network topology associated with β-cells clusters is analyzed and discussed. PMID:26565267

  8. Sorafenib Inhibits Signal Transducer and Activator of Transcription-3 Signaling in Cholangiocarcinoma Cells by Activating the Phosphatase Shatterproof 2

    OpenAIRE

    Blechacz, Boris R. A.; Smoot, Rory L.; Bronk, Steven F; Werneburg, Nathan W.; Sirica, Alphonse E.; Gores, Gregory J.

    2009-01-01

    The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is one of the key signaling cascades in cholangiocarcinoma (CCA) cells, mediating their resistance to apoptosis. Our aim was to ascertain if sorafenib, a multikinase inhibitor, may also inhibit JAK/STAT signaling and, therefore, be efficacious for CCA. Sorafenib treatment of three human CCA cell lines resulted in Tyr705 phospho-STAT3 dephosphorylation. Similar results were obtained with the Raf-kinase inhibit...

  9. An integrated gene regulatory network controls stem cell proliferation in teeth.

    Directory of Open Access Journals (Sweden)

    Xiu-Ping Wang

    2007-06-01

    Full Text Available Epithelial stem cells reside in specific niches that regulate their self-renewal and differentiation, and are responsible for the continuous regeneration of tissues such as hair, skin, and gut. Although the regenerative potential of mammalian teeth is limited, mouse incisors grow continuously throughout life and contain stem cells at their proximal ends in the cervical loops. In the labial cervical loop, the epithelial stem cells proliferate and migrate along the labial surface, differentiating into enamel-forming ameloblasts. In contrast, the lingual cervical loop contains fewer proliferating stem cells, and the lingual incisor surface lacks ameloblasts and enamel. Here we have used a combination of mouse mutant analyses, organ culture experiments, and expression studies to identify the key signaling molecules that regulate stem cell proliferation in the rodent incisor stem cell niche, and to elucidate their role in the generation of the intrinsic asymmetry of the incisors. We show that epithelial stem cell proliferation in the cervical loops is controlled by an integrated gene regulatory network consisting of Activin, bone morphogenetic protein (BMP, fibroblast growth factor (FGF, and Follistatin within the incisor stem cell niche. Mesenchymal FGF3 stimulates epithelial stem cell proliferation, and BMP4 represses Fgf3 expression. In turn, Activin, which is strongly expressed in labial mesenchyme, inhibits the repressive effect of BMP4 and restricts Fgf3 expression to labial dental mesenchyme, resulting in increased stem cell proliferation and a large, labial stem cell niche. Follistatin limits the number of lingual stem cells, further contributing to the characteristic asymmetry of mouse incisors, and on the basis of our findings, we suggest a model in which Follistatin antagonizes the activity of Activin. These results show how the spatially restricted and balanced effects of specific components of a signaling network can regulate stem cell

  10. 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.

  11. 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.

  12. 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.

  13. Solar ultraviolet radiation as a trigger of cell signal transduction

    International Nuclear Information System (INIS)

    Ultraviolet light radiation in sunlight is known to cause major alterations in growth and differentiation patterns of exposed human tissues. The specific effects depend on the wavelengths and doses of the light, and the nature of the exposed tissue. Both growth inhibition and proliferation are observed, as well as inflammation and immune suppression. Whereas in the clinical setting, these responses may be beneficial, for example, in the treatment of psoriasis and atopic dermatitis, as an environmental toxicant, ultraviolet light can induce significant tissue damage. Thus, in the eye, ultraviolet light causes cataracts, while in the skin, it induces premature aging and the development of cancer. Although ultraviolet light can damage many tissue components including membrane phospholipids, proteins, and nucleic acids, it is now recognized that many of its cellular effects are due to alterations in growth factor- and cytokine-mediated signal transduction pathways leading to aberrant gene expression. It is generally thought that reactive oxygen intermediates are mediators of some of the damage induced by ultraviolet light. Generated when ultraviolet light is absorbed by endogenous photosensitizers in the presence of molecular oxygen, reactive oxygen intermediates and their metabolites induce damage by reacting with cellular electrophiles, some of which can directly initiate cell signaling processes. In an additional layer of complexity, ultraviolet light-damaged nucleic acids initiate signaling during the activation of repair processes. Thus, mechanisms by which solar ultraviolet radiation triggers cell signal transduction are multifactorial. The present review summarizes some of the mechanisms by which ultraviolet light alters signaling pathways as well as the genes important in the beneficial and toxic effects of ultraviolet light

  14. Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: a computational study.

    Science.gov (United States)

    Ganguli, Piyali; Chowdhury, Saikat; Bhowmick, Rupa; Sarkar, Ram Rup

    2015-10-01

    Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell's functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune clearance and also maintaining the cell in a functionally active state. Any defect in these co-receptor signalling pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical equations and simulated using the published time series microarray expression data as inputs. After validating the model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted, which shows significant variations among the proteins expression and the signalling routes through which the response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to study the changes in protein expression patterns and helps to predict variations in the cellular behaviour. PMID:26564978

  15. Knr4: a disordered hub protein at the heart of fungal cell wall signalling.

    Science.gov (United States)

    Martin-Yken, Hélène; François, Jean Marie; Zerbib, Didier

    2016-09-01

    The most highly connected proteins in protein-protein interactions networks are called hubs; they generally connect signalling pathways. In Saccharomyces cerevisiae, Knr4 constitutes a connecting node between the two main signal transmission pathways involved in cell wall maintenance upon stress: the cell wall integrity and the calcium-calcineurin pathway. Knr4 is required to enable the cells to resist many cell wall-affecting stresses, and KNR4 gene deletion is synthetic lethal with the simultaneous deletion of numerous other genes involved in morphogenesis and cell wall biogenesis. Knr4 has been shown to engage in multiple physical interactions, an ability conferred by the intrinsic structural adaptability of major disordered regions present in the N-terminal and C-terminal parts of the protein. Taking all together, Knr4 is an intrinsically disordered hub protein. Available data from other fungi indicate the conservation of Knr4 homologs cellular function and localization at sites of polarized growth among fungal species, including pathogenic species. Because of their particular role in morphogenesis control and of their fungal specificity, these proteins could constitute interesting new pharmaceutical drug targets for antifungal combination therapy. PMID:27199081

  16. Aberrant signaling pathways in medulloblastomas: a stem cell connection

    Directory of Open Access Journals (Sweden)

    Carolina Oliveira Rodini

    2010-12-01

    Full Text Available Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio- and chemo-resistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFβ, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers.

  17. 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.

  18. 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..

  19. 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.

  20. 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.