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Sample records for domain-dependent signaling complex

  1. Chansporter complexes in cell signaling.

    Science.gov (United States)

    Abbott, Geoffrey W

    2017-09-01

    Ion channels facilitate diffusion of ions across cell membranes for such diverse purposes as neuronal signaling, muscular contraction, and fluid homeostasis. Solute transporters often utilize ionic gradients to move aqueous solutes up their concentration gradient, also fulfilling a wide variety of tasks. Recently, an increasing number of ion channel-transporter ('chansporter') complexes have been discovered. Chansporter complex formation may overcome what could otherwise be considerable spatial barriers to rapid signal integration and feedback between channels and transporters, the ions and other substrates they transport, and environmental factors to which they must respond. Here, current knowledge in this field is summarized, covering both heterologous expression structure/function findings and potential mechanisms by which chansporter complexes fulfill contrasting roles in cell signaling in vivo. © 2017 Federation of European Biochemical Societies.

  2. Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner

    DEFF Research Database (Denmark)

    Kny, Melanie; Standera, Sybille; Hartmann-Petersen, Rasmus

    2011-01-01

    in ER-associated protein degradation (ERAD) and interacts directly with the ubiquitin ligase Hrd1, which is found in high molecular mass complexes of the ER membrane. Here we present the first evidence that Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like (UBL) domain-dependent manner. We...

  3. A Signal-Interleaving Complex Bandpass Sigma-Delta Converter

    DEFF Research Database (Denmark)

    Wad, Paul Emmanuel

    1997-01-01

    Complex or quadrature Sigma-Delta converters operate on complex signals, i.e. signals consisting of a real and an imaginary component, whereas conventional converters operate only on real signals. The advantage of complex signal processing in the discrete-time domain is that the entire sampling...

  4. Exome localization of complex disease association signals

    Directory of Open Access Journals (Sweden)

    Lewis Cathryn M

    2011-02-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS of common diseases have had a tremendous impact on genetic research over the last five years; the field is now moving from microarray-based technology towards next-generation sequencing. To evaluate the potential of association studies for complex diseases based on exome sequencing we analysed the distribution of association signal with respect to protein-coding genes based on GWAS data for seven diseases from the Wellcome Trust Case Control Consortium. Results We find significant concentration of association signal in exons and genes for Crohn's Disease, Type 1 Diabetes and Bipolar Disorder, but also observe enrichment from up to 40 kilobases upstream to 40 kilobases downstream of protein-coding genes for Crohn's Disease and Type 1 Diabetes; the exact extent of the distribution is disease dependent. Conclusions Our work suggests that exome sequencing may be a feasible approach to find genetic variation associated with complex disease. Extending the exome sequencing to include flanking regions therefore promises further improvement of covering disease-relevant variants.

  5. Sequence distance via parsing complexity: Heartbeat signals

    International Nuclear Information System (INIS)

    Degli Esposti, M.; Farinelli, C.; Menconi, G.

    2009-01-01

    We compare and discuss the use of different symbolic codings of electrocardiogram (ECG) signals in order to distinguish healthy patients from hospitalized ones. To this aim, we recall a parsing-based similarity distance and compare the performances of several methods of classification of data.

  6. Selective disruption of the AKAP signaling complexes.

    Science.gov (United States)

    Kennedy, Eileen J; Scott, John D

    2015-01-01

    Synthesis of the second messenger cAMP activates a variety of signaling pathways critical for all facets of intracellular regulation. Protein kinase A (PKA) is the major cAMP-responsive effector. Where and when this enzyme is activated has profound implications on the cellular role of PKA. A-Kinase Anchoring Proteins (AKAPs) play a critical role in this process by orchestrating spatial and temporal aspects of PKA action. A popular means of evaluating the impact of these anchored signaling events is to biochemically interfere with the PKA-AKAP interface. Hence, peptide disruptors of PKA anchoring are valuable tools in the investigation of local PKA action. This article outlines the development of PKA isoform-selective disruptor peptides, documents the optimization of cell-soluble peptide derivatives, and introduces alternative cell-based approaches that interrogate other aspects of the PKA-AKAP interface.

  7. Astrocyte Ca2+ signalling: an unexpected complexity

    OpenAIRE

    Volterra, Andrea; Liaudet, Nicolas; Savtchouk, Iaroslav

    2014-01-01

    Astrocyte Ca(2+) signalling has been proposed to link neuronal information in different spatial-temporal dimensions to achieve a higher level of brain integration. However, some discrepancies in the results of recent studies challenge this view and highlight key insufficiencies in our current understanding. In parallel, new experimental approaches that enable the study of astrocyte physiology at higher spatial-temporal resolution in intact brain preparations are beginning to reveal an unexpec...

  8. Modulation of EEG Theta Band Signal Complexity by Music Therapy

    Science.gov (United States)

    Bhattacharya, Joydeep; Lee, Eun-Jeong

    The primary goal of this study was to investigate the impact of monochord (MC) sounds, a type of archaic sounds used in music therapy, on the neural complexity of EEG signals obtained from patients undergoing chemotherapy. The secondary goal was to compare the EEG signal complexity values for monochords with those for progressive muscle relaxation (PMR), an alternative therapy for relaxation. Forty cancer patients were randomly allocated to one of the two relaxation groups, MC and PMR, over a period of six months; continuous EEG signals were recorded during the first and last sessions. EEG signals were analyzed by applying signal mode complexity, a measure of complexity of neuronal oscillations. Across sessions, both groups showed a modulation of complexity of beta-2 band (20-29Hz) at midfrontal regions, but only MC group showed a modulation of complexity of theta band (3.5-7.5Hz) at posterior regions. Therefore, the neuronal complexity patterns showed different changes in EEG frequency band specific complexity resulting in two different types of interventions. Moreover, the different neural responses to listening to monochords and PMR were observed after regular relaxation interventions over a short time span.

  9. Brain signal complexity rises with repetition suppression in visual learning.

    Science.gov (United States)

    Lafontaine, Marc Philippe; Lacourse, Karine; Lina, Jean-Marc; McIntosh, Anthony R; Gosselin, Frédéric; Théoret, Hugo; Lippé, Sarah

    2016-06-21

    Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual

  10. Fractal Complexity-Based Feature Extraction Algorithm of Communication Signals

    Science.gov (United States)

    Wang, Hui; Li, Jingchao; Guo, Lili; Dou, Zheng; Lin, Yun; Zhou, Ruolin

    How to analyze and identify the characteristics of radiation sources and estimate the threat level by means of detecting, intercepting and locating has been the central issue of electronic support in the electronic warfare, and communication signal recognition is one of the key points to solve this issue. Aiming at accurately extracting the individual characteristics of the radiation source for the increasingly complex communication electromagnetic environment, a novel feature extraction algorithm for individual characteristics of the communication radiation source based on the fractal complexity of the signal is proposed. According to the complexity of the received signal and the situation of environmental noise, use the fractal dimension characteristics of different complexity to depict the subtle characteristics of the signal to establish the characteristic database, and then identify different broadcasting station by gray relation theory system. The simulation results demonstrate that the algorithm can achieve recognition rate of 94% even in the environment with SNR of -10dB, and this provides an important theoretical basis for the accurate identification of the subtle features of the signal at low SNR in the field of information confrontation.

  11. Nonlinear complexity analysis of brain FMRI signals in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Moses O Sokunbi

    Full Text Available We investigated the differences in brain fMRI signal complexity in patients with schizophrenia while performing the Cyberball social exclusion task, using measures of Sample entropy and Hurst exponent (H. 13 patients meeting diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV criteria for schizophrenia and 16 healthy controls underwent fMRI scanning at 1.5 T. The fMRI data of both groups of participants were pre-processed, the entropy characterized and the Hurst exponent extracted. Whole brain entropy and H maps of the groups were generated and analysed. The results after adjusting for age and sex differences together show that patients with schizophrenia exhibited higher complexity than healthy controls, at mean whole brain and regional levels. Also, both Sample entropy and Hurst exponent agree that patients with schizophrenia have more complex fMRI signals than healthy controls. These results suggest that schizophrenia is associated with more complex signal patterns when compared to healthy controls, supporting the increase in complexity hypothesis, where system complexity increases with age or disease, and also consistent with the notion that schizophrenia is characterised by a dysregulation of the nonlinear dynamics of underlying neuronal systems.

  12. Aliasing in the Complex Cepstrum of Linear-Phase Signals

    DEFF Research Database (Denmark)

    Bysted, Tommy Kristensen

    1997-01-01

    Assuming linear-phase of the associated time signal, this paper presents an approximated analytical description of the unavoidable aliasing in practical use of complex cepstrums. The linear-phase assumption covers two major applications of complex cepstrums which are linear- to minimum-phase FIR......-filter transformation and minimum-phase estimation from amplitude specifications. The description is made in the cepstrum domain, the Fourier transform of the complex cepstrum and in the frequency domain. Two examples are given, one for verification of the derived equations and one using the description to reduce...... aliasing in minimum-phase estimation...

  13. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    Science.gov (United States)

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  14. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    OpenAIRE

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show ...

  15. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    Science.gov (United States)

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

  16. Assembly of oligomeric death domain complexes during Toll receptor signaling.

    Science.gov (United States)

    Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

    2008-11-28

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

  17. Simulation of Weak Signals of Nanotechnology Innovation in Complex System

    Directory of Open Access Journals (Sweden)

    Sun Hi Yoo

    2018-02-01

    Full Text Available It is especially indispensable for new businesses or industries to predict the innovation of new technologies. This requires an understanding of how the complex process of innovation, which is accomplished through more efficient products, processes, services, technologies, or ideas, is adopted and diffused in the market, government, and society. Furthermore, detecting “weak signals” (signs of change in science and technology (S&T is also important to foretell events associated with innovations in technology. Thus, we explore the dynamic behavior of weak signals of a specific technological innovation using the agent-based simulating tool NetLogo. This study provides a deeper understanding of the early stages of complex technology innovation, and the models are capable of analyzing initial complex interaction structures between components of technologies and between agents engaged in collective invention.

  18. Entropy for the Complexity of Physiological Signal Dynamics.

    Science.gov (United States)

    Zhang, Xiaohua Douglas

    2017-01-01

    Recently, the rapid development of large data storage technologies, mobile network technology, and portable medical devices makes it possible to measure, record, store, and track analysis of biological dynamics. Portable noninvasive medical devices are crucial to capture individual characteristics of biological dynamics. The wearable noninvasive medical devices and the analysis/management of related digital medical data will revolutionize the management and treatment of diseases, subsequently resulting in the establishment of a new healthcare system. One of the key features that can be extracted from the data obtained by wearable noninvasive medical device is the complexity of physiological signals, which can be represented by entropy of biological dynamics contained in the physiological signals measured by these continuous monitoring medical devices. Thus, in this chapter I present the major concepts of entropy that are commonly used to measure the complexity of biological dynamics. The concepts include Shannon entropy, Kolmogorov entropy, Renyi entropy, approximate entropy, sample entropy, and multiscale entropy. I also demonstrate an example of using entropy for the complexity of glucose dynamics.

  19. Complex Interplay of Hormonal Signals during Grape Berry Ripening

    Directory of Open Access Journals (Sweden)

    Ana Margarida Fortes

    2015-05-01

    Full Text Available Grape and wine production and quality is extremely dependent on the fruit ripening process. Sensory and nutritional characteristics are important aspects for consumers and their development during fruit ripening involves complex hormonal control. In this review, we explored data already published on grape ripening and compared it with the hormonal regulation of ripening of other climacteric and non-climacteric fruits. The roles of abscisic acid, ethylene, and brassinosteroids as promoters of ripening are discussed, as well as the role of auxins, cytokinins, gibberellins, jasmonates, and polyamines as inhibitors of ripening. In particular, the recently described role of polyamine catabolism in grape ripening is discussed, together with its putative interaction with other hormones. Furthermore, other recent examples of cross-talk among the different hormones are presented, revealing a complex interplay of signals during grape development and ripening.

  20. Design principles of nuclear receptor signaling: how complex networking improves signal transduction

    Science.gov (United States)

    Kolodkin, Alexey N; Bruggeman, Frank J; Plant, Nick; Moné, Martijn J; Bakker, Barbara M; Campbell, Moray J; van Leeuwen, Johannes P T M; Carlberg, Carsten; Snoep, Jacky L; Westerhoff, Hans V

    2010-01-01

    The topology of nuclear receptor (NR) signaling is captured in a systems biological graphical notation. This enables us to identify a number of ‘design' aspects of the topology of these networks that might appear unnecessarily complex or even functionally paradoxical. In realistic kinetic models of increasing complexity, calculations show how these features correspond to potentially important design principles, e.g.: (i) cytosolic ‘nuclear' receptor may shuttle signal molecules to the nucleus, (ii) the active export of NRs may ensure that there is sufficient receptor protein to capture ligand at the cytoplasmic membrane, (iii) a three conveyor belts design dissipating GTP-free energy, greatly aids response, (iv) the active export of importins may prevent sequestration of NRs by importins in the nucleus and (v) the unspecific nature of the nuclear pore may ensure signal-flux robustness. In addition, the models developed are suitable for implementation in specific cases of NR-mediated signaling, to predict individual receptor functions and differential sensitivity toward physiological and pharmacological ligands. PMID:21179018

  1. Association between increased EEG signal complexity and cannabis dependence.

    Science.gov (United States)

    Laprevote, Vincent; Bon, Laura; Krieg, Julien; Schwitzer, Thomas; Bourion-Bedes, Stéphanie; Maillard, Louis; Schwan, Raymund

    2017-12-01

    Both acute and regular cannabis use affects the functioning of the brain. While several studies have demonstrated that regular cannabis use can impair the capacity to synchronize neural assemblies during specific tasks, less is known about spontaneous brain activity. This can be explored by measuring EEG complexity, which reflects the spontaneous variability of human brain activity. A recent study has shown that acute cannabis use can affect that complexity. Since the characteristics of cannabis use can affect the impact on brain functioning, this study sets out to measure EEG complexity in regular cannabis users with or without dependence, in comparison with healthy controls. We recruited 26 healthy controls, 25 cannabis users without cannabis dependence and 14 cannabis users with cannabis dependence, based on DSM IV TR criteria. The EEG signal was extracted from at least 250 epochs of the 500ms pre-stimulation phase during a visual evoked potential paradigm. Brain complexity was estimated using Lempel-Ziv Complexity (LZC), which was compared across groups by non-parametric Kruskall-Wallis ANOVA. The analysis revealed a significant difference between the groups, with higher LZC in participants with cannabis dependence than in non-dependent cannabis users. There was no specific localization of this effect across electrodes. We showed that cannabis dependence is associated to an increased spontaneous brain complexity in regular users. This result is in line with previous results in acute cannabis users. It may reflect increased randomness of neural activity in cannabis dependence. Future studies should explore whether this effect is permanent or diminishes with cannabis cessation. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  2. Age-Related Changes in Electroencephalographic Signal Complexity

    Science.gov (United States)

    Zappasodi, Filippo; Marzetti, Laura; Olejarczyk, Elzbieta; Tecchio, Franca; Pizzella, Vittorio

    2015-01-01

    The study of active and healthy aging is a primary focus for social and neuroscientific communities. Here, we move a step forward in assessing electrophysiological neuronal activity changes in the brain with healthy aging. To this end, electroencephalographic (EEG) resting state activity was acquired in 40 healthy subjects (age 16–85). We evaluated Fractal Dimension (FD) according to the Higuchi algorithm, a measure which quantifies the presence of statistical similarity at different scales in temporal fluctuations of EEG signals. Our results showed that FD increases from age twenty to age fifty and then decreases. The curve that best fits the changes in FD values across age over the whole sample is a parabola, with the vertex located around age fifty. Moreover, FD changes are site specific, with interhemispheric FD asymmetry being pronounced in elderly individuals in the frontal and central regions. The present results indicate that fractal dimension well describes the modulations of brain activity with age. Since fractal dimension has been proposed to be related to the complexity of the signal dynamics, our data demonstrate that the complexity of neuronal electric activity changes across the life span of an individual, with a steady increase during young adulthood and a decrease in the elderly population. PMID:26536036

  3. Enabling complex genetic circuits to respond to extrinsic environmental signals.

    Science.gov (United States)

    Hoynes-O'Connor, Allison; Shopera, Tatenda; Hinman, Kristina; Creamer, John Philip; Moon, Tae Seok

    2017-07-01

    Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real-world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real-world applications. A previously identified pH-responsive promoter and a temperature-responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23-fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168-fold change. These circuits provide the first demonstration of complex pH- and temperature-responsive genetic circuits, and lay the groundwork for the use of similar circuits in real-world applications. Biotechnol. Bioeng. 2017;114: 1626-1631. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    KAUST Repository

    Kuwahara, Hiroyuki; Gao, Xin

    2013-01-01

    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

  5. Assembly of Slx4 signaling complexes behind DNA replication forks.

    Science.gov (United States)

    Balint, Attila; Kim, TaeHyung; Gallo, David; Cussiol, Jose Renato; Bastos de Oliveira, Francisco M; Yimit, Askar; Ou, Jiongwen; Nakato, Ryuichiro; Gurevich, Alexey; Shirahige, Katsuhiko; Smolka, Marcus B; Zhang, Zhaolei; Brown, Grant W

    2015-08-13

    Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress. © 2015 The Authors.

  6. Integrative curriculum reform, domain dependent knowing, and teachers` epistemological theories: Implications for middle-level teaching

    Energy Technology Data Exchange (ETDEWEB)

    Powell, R.R. [Texas Tech Univ., Lubbock, TX (United States). College of Education

    1998-12-01

    Integrative curriculum as both a theoretical construct and a practical reality, and as a theme-based, problem-centered, democratic way of schooling, is becoming more widely considered as a feasible alternative to traditional middle-level curricula. Importantly for teaching and learning, domain dependence requires teachers to view one area of knowledge as fully interdependent with other areas of knowledge during the learning process. This requires teachers to adopt personal epistemological theories that reflect integrative, domain dependent knowing. This study explored what happened when teachers from highly traditional domain independent school settings encountered an ambitious college-level curriculum project that was designed to help the teachers understand the potential that integrative, domain dependent teaching holds for precollege settings. This study asked: What influence does an integrative, domain dependent curriculum project have on teachers` domain independent, epistemological theories for teaching and learning? Finding an answer to this question is essential if we, as an educational community, are to understand how integrative curriculum theory is transformed by teachers into systemic curriculum reform. The results suggest that the integrative curriculum project that teachers participated in did not explicitly alter their classroom practices in a wholesale manner. Personal epistemological theories of teachers collectively precluded teachers from making any wholesale changes in their individual classroom teaching. However, teachers became aware of integrative curriculum as an alternative, and they expressed interest in infusing integrative practices into their classrooms as opportunities arise.

  7. Modelling of Context: Designing Mobile Systems from Domain-Dependent Models

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Stage, Jan

    2009-01-01

    Modelling of domain-dependent aspects is a key prerequisite for the design of software for mobile systems. Most mobile systems include a more or less advanced model of selected aspects of the domain in which they are used. This paper discusses the creation of such a model and its relevance for te...

  8. Blind identification and separation of complex-valued signals

    CERN Document Server

    Moreau, Eric

    2013-01-01

    Blind identification consists of estimating a multi-dimensional system only through the use of its output, and source separation, the blind estimation of the inverse of the system. Estimation is generally carried out using different statistics of the output. The authors of this book consider the blind identification and source separation problem in the complex-domain, where the available statistical properties are richer and include non-circularity of the sources - underlying components. They define identifiability conditions and present state-of-the-art algorithms that are based on algebraic methods as well as iterative algorithms based on maximum likelihood theory. Contents 1. Mathematical Preliminaries. 2. Estimation by Joint Diagonalization. 3. Maximum Likelihood ICA. About the Authors Eric Moreau is Professor of Electrical Engineering at the University of Toulon, France. His research interests concern statistical signal processing, high order statistics and matrix/tensor decompositions with applic...

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

    Science.gov (United States)

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

    2014-10-01

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

  10. Is there any need for domain-dependent control information? A reply

    Energy Technology Data Exchange (ETDEWEB)

    Minton, S. [USC Information Sciences Inst., Marina del Rey, CA (United States)

    1996-12-31

    In this paper, we consider the role that domain-dependent control knowledge plays in problem solving systems. Ginsberg and Geddis have claimed that domain-dependent control information has no place in declarative systems; instead, they say, such information should be derived from declarative facts about the domain plus domain-independent principles. We dispute their conclusion, arguing that it is impractical to generate control knowledge solely on the basis of logical derivations. We propose that simplifying abstractions are crucial for deriving control knowledge, and, as a result, empirical utility evaluation of the resulting rules will frequently be necessary to validate the utility of derived control knowledge. We illustrate our arguments with examples from two implemented systems.

  11. A Unified Framework for Creating Domain Dependent Polarity Lexicons from User Generated Reviews.

    Directory of Open Access Journals (Sweden)

    Muhammad Zubair Asghar

    Full Text Available The exponential increase in the explosion of Web-based user generated reviews has resulted in the emergence of Opinion Mining (OM applications for analyzing the users' opinions toward products, services, and policies. The polarity lexicons often play a pivotal role in the OM, indicating the positivity and negativity of a term along with the numeric score. However, the commonly available domain independent lexicons are not an optimal choice for all of the domains within the OM applications. The aforementioned is due to the fact that the polarity of a term changes from one domain to other and such lexicons do not contain the correct polarity of a term for every domain. In this work, we focus on the problem of adapting a domain dependent polarity lexicon from set of labeled user reviews and domain independent lexicon to propose a unified learning framework based on the information theory concepts that can assign the terms with correct polarity (+ive, -ive scores. The benchmarking on three datasets (car, hotel, and drug reviews shows that our approach improves the performance of the polarity classification by achieving higher accuracy. Moreover, using the derived domain dependent lexicon changed the polarity of terms, and the experimental results show that our approach is more effective than the base line methods.

  12. NSP-CAS Protein Complexes: Emerging Signaling Modules in Cancer.

    Science.gov (United States)

    Wallez, Yann; Mace, Peter D; Pasquale, Elena B; Riedl, Stefan J

    2012-05-01

    The CAS (CRK-associated substrate) family of adaptor proteins comprises 4 members, which share a conserved modular domain structure that enables multiple protein-protein interactions, leading to the assembly of intracellular signaling platforms. Besides their physiological role in signal transduction downstream of a variety of cell surface receptors, CAS proteins are also critical for oncogenic transformation and cancer cell malignancy through associations with a variety of regulatory proteins and downstream effectors. Among the regulatory partners, the 3 recently identified adaptor proteins constituting the NSP (novel SH2-containing protein) family avidly bind to the conserved carboxy-terminal focal adhesion-targeting (FAT) domain of CAS proteins. NSP proteins use an anomalous nucleotide exchange factor domain that lacks catalytic activity to form NSP-CAS signaling modules. Additionally, the NSP SH2 domain can link NSP-CAS signaling assemblies to tyrosine-phosphorylated cell surface receptors. NSP proteins can potentiate CAS function by affecting key CAS attributes such as expression levels, phosphorylation state, and subcellular localization, leading to effects on cell adhesion, migration, and invasion as well as cell growth. The consequences of these activities are well exemplified by the role that members of both families play in promoting breast cancer cell invasiveness and resistance to antiestrogens. In this review, we discuss the intriguing interplay between the NSP and CAS families, with a particular focus on cancer signaling networks.

  13. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, A E; Skov, Svend; Bregenholt, S

    1999-01-01

    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...... and functioning, MHC-I molecules might be of importance for the maintenance of cellular homeostasis not only within the immune system, but also in the interplay between the immune system and other organ systems....

  14. Nonlinear signal processing for ultrasonic imaging of material complexity

    Czech Academy of Sciences Publication Activity Database

    Dos Santos, S.; Vejvodová, Šárka; Převorovský, Zdeněk

    2010-01-01

    Roč. 59, č. 2 (2010), s. 108-117 ISSN 1736-6046 Institutional research plan: CEZ:AV0Z20760514 Keywords : nonlinear signal processing * TR-NEWS * symmetry analysis * DORT Subject RIV: BI - Acoustics Impact factor: 0.464, year: 2010 www.eap.ee/proceedings

  15. Machines vs. ensembles: effective MAPK signaling through heterogeneous sets of protein complexes.

    Directory of Open Access Journals (Sweden)

    Ryan Suderman

    Full Text Available Despite the importance of intracellular signaling networks, there is currently no consensus regarding the fundamental nature of the protein complexes such networks employ. One prominent view involves stable signaling machines with well-defined quaternary structures. The combinatorial complexity of signaling networks has led to an opposing perspective, namely that signaling proceeds via heterogeneous pleiomorphic ensembles of transient complexes. Since many hypotheses regarding network function rely on how we conceptualize signaling complexes, resolving this issue is a central problem in systems biology. Unfortunately, direct experimental characterization of these complexes has proven technologically difficult, while combinatorial complexity has prevented traditional modeling methods from approaching this question. Here we employ rule-based modeling, a technique that overcomes these limitations, to construct a model of the yeast pheromone signaling network. We found that this model exhibits significant ensemble character while generating reliable responses that match experimental observations. To contrast the ensemble behavior, we constructed a model that employs hierarchical assembly pathways to produce scaffold-based signaling machines. We found that this machine model could not replicate the experimentally observed combinatorial inhibition that arises when the scaffold is overexpressed. This finding provides evidence against the hierarchical assembly of machines in the pheromone signaling network and suggests that machines and ensembles may serve distinct purposes in vivo. In some cases, e.g. core enzymatic activities like protein synthesis and degradation, machines assembled via hierarchical energy landscapes may provide functional stability for the cell. In other cases, such as signaling, ensembles may represent a form of weak linkage, facilitating variation and plasticity in network evolution. The capacity of ensembles to signal effectively

  16. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-01-01

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

  17. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-03-21

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

  18. SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes

    Directory of Open Access Journals (Sweden)

    Sebastian Kupka

    2016-08-01

    Full Text Available Recruitment of the deubiquitinase CYLD to signaling complexes is mediated by its interaction with HOIP, the catalytically active component of the linear ubiquitin chain assembly complex (LUBAC. Here, we identify SPATA2 as a constitutive direct binding partner of HOIP that bridges the interaction between CYLD and HOIP. SPATA2 recruitment to TNFR1- and NOD2-signaling complexes is dependent on HOIP, and loss of SPATA2 abolishes CYLD recruitment. Deficiency in SPATA2 exerts limited effects on gene activation pathways but diminishes necroptosis induced by tumor necrosis factor (TNF, resembling loss of CYLD. In summary, we describe SPATA2 as a previously unrecognized factor in LUBAC-dependent signaling pathways that serves as an adaptor between HOIP and CYLD, thereby enabling recruitment of CYLD to signaling complexes.

  19. Improved Empirical Mode Decomposition Algorithm of Processing Complex Signal for IoT Application

    OpenAIRE

    Yang, Xianzhao; Cheng, Gengguo; Liu, Huikang

    2015-01-01

    Hilbert-Huang transform is widely used in signal analysis. However, due to its inadequacy in estimating both the maximum and the minimum values of the signals at both ends of the border, traditional HHT is easy to produce boundary error in empirical mode decomposition (EMD) process. To overcome this deficiency, this paper proposes an enhanced empirical mode decomposition algorithm for processing complex signal. Our work mainly focuses on two aspects. On one hand, we develop a technique to obt...

  20. Unraveling the Complexities of Androgen Receptor Signaling in Prostate Cancer Cells

    OpenAIRE

    Heemers, Hannelore V.; Tindall, Donald J.

    2009-01-01

    Androgen signaling is critical for proliferation of prostate cancer cells but cannot be fully inhibited by current androgen deprivation therapies. A study by Xu et al. in this issue of Cancer Cell provides insights into the complexities of androgen signaling in prostate cancer and suggests avenues to target a subset of androgen-sensitive genes.

  1. Normalization of informatisation parameter on airfield light-signal bar at flights in complex meteorological conditions

    Directory of Open Access Journals (Sweden)

    П.В. Попов

    2005-03-01

    Full Text Available  The technique of maintenance of the set level of flights safetivness is developed by normalization of informatisation parameters functional groups of light-signal lightings at technological stages of interaction of crew of the airplane with the airfield light-signals bar at flights in a complex weathercast conditions.

  2. Complex Signal Kurtosis and Independent Component Analysis for Wideband Radio Frequency Interference Detection

    Science.gov (United States)

    Schoenwald, Adam; Mohammed, Priscilla; Bradley, Damon; Piepmeier, Jeffrey; Wong, Englin; Gholian, Armen

    2016-01-01

    Radio-frequency interference (RFI) has negatively implicated scientific measurements across a wide variation passive remote sensing satellites. This has been observed in the L-band radiometers SMOS, Aquarius and more recently, SMAP [1, 2]. RFI has also been observed at higher frequencies such as K band [3]. Improvements in technology have allowed wider bandwidth digital back ends for passive microwave radiometry. A complex signal kurtosis radio frequency interference detector was developed to help identify corrupted measurements [4]. This work explores the use of ICA (Independent Component Analysis) as a blind source separation technique to pre-process radiometric signals for use with the previously developed real and complex signal kurtosis detectors.

  3. The effect of hypobaric hypoxia on multichannel EEG signal complexity.

    Science.gov (United States)

    Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Maglaveras, Nikos; Pappas, Konstantinos

    2007-01-01

    The objective of this study was the development and evaluation of nonlinear electroencephalography parameters which assess hypoxia-induced EEG alterations, and describe the temporal characteristics of different hypoxic levels' residual effect upon the brain electrical activity. Multichannel EEG, pO2, pCO2, ECG, and respiration measurements were recorded from 10 subjects exposed to three experimental conditions (100% oxygen, hypoxia, recovery) at three-levels of reduced barometric pressure. The mean spectral power of EEG under each session and altitude were estimated for the standard bands. Approximate Entropy (ApEn) of EEG segments was calculated, and the ApEn's time-courses were smoothed by a moving average filter. On the smoothed diagrams, parameters were defined. A significant increase in total power and power of theta and alpha bands was observed during hypoxia. Visual interpretation of ApEn time-courses revealed a characteristic pattern (decreasing during hypoxia and recovering after oxygen re-administration). The introduced qEEG parameters S1 and K1 distinguished successfully the three hypoxic conditions. The introduced parameters based on ApEn time-courses are assessing reliably and effectively the different hypoxic levels. ApEn decrease may be explained by neurons' functional isolation due to hypoxia since decreased complexity corresponds to greater autonomy of components, although this interpretation should be further supported by electrocorticographic animal studies. The introduced qEEG parameters seem to be appropriate for assessing the hypoxia-related neurophysiological state of patients in the hyperbaric chambers in the treatment of decompression sickness, carbon dioxide poisoning, and mountaineering.

  4. Use of multiple singular value decompositions to analyze complex intracellular calcium ion signals

    KAUST Repository

    Martinez, Josue G.; Huang, Jianhua Z.; Burghardt, Robert C.; Barhoumi, Rola; Carroll, Raymond J.

    2009-01-01

    ) to extract the signals from such movies, in a way that is semi-automatic and tuned closely to the actual data and their many complexities. These complexities include the following. First, the images themselves are of no interest: all interest focuses

  5. A simple iterative independent component analysis algorithm for vibration source signal identification of complex structures

    Directory of Open Access Journals (Sweden)

    Dong-Sup Lee

    2015-01-01

    Full Text Available Independent Component Analysis (ICA, one of the blind source separation methods, can be applied for extracting unknown source signals only from received signals. This is accomplished by finding statistical independence of signal mixtures and has been successfully applied to myriad fields such as medical science, image processing, and numerous others. Nevertheless, there are inherent problems that have been reported when using this technique: insta- bility and invalid ordering of separated signals, particularly when using a conventional ICA technique in vibratory source signal identification of complex structures. In this study, a simple iterative algorithm of the conventional ICA has been proposed to mitigate these problems. The proposed method to extract more stable source signals having valid order includes an iterative and reordering process of extracted mixing matrix to reconstruct finally converged source signals, referring to the magnitudes of correlation coefficients between the intermediately separated signals and the signals measured on or nearby sources. In order to review the problems of the conventional ICA technique and to vali- date the proposed method, numerical analyses have been carried out for a virtual response model and a 30 m class submarine model. Moreover, in order to investigate applicability of the proposed method to real problem of complex structure, an experiment has been carried out for a scaled submarine mockup. The results show that the proposed method could resolve the inherent problems of a conventional ICA technique.

  6. Aiding the Detection of QRS Complex in ECG Signals by Detecting S Peaks Independently.

    Science.gov (United States)

    Sabherwal, Pooja; Singh, Latika; Agrawal, Monika

    2018-03-30

    In this paper, a novel algorithm for the accurate detection of QRS complex by combining the independent detection of R and S peaks, using fusion algorithm is proposed. R peak detection has been extensively studied and is being used to detect the QRS complex. Whereas, S peaks, which is also part of QRS complex can be independently detected to aid the detection of QRS complex. In this paper, we suggest a method to first estimate S peak from raw ECG signal and then use them to aid the detection of QRS complex. The amplitude of S peak in ECG signal is relatively weak than corresponding R peak, which is traditionally used for the detection of QRS complex, therefore, an appropriate digital filter is designed to enhance the S peaks. These enhanced S peaks are then detected by adaptive thresholding. The algorithm is validated on all the signals of MIT-BIH arrhythmia database and noise stress database taken from physionet.org. The algorithm performs reasonably well even for the signals highly corrupted by noise. The algorithm performance is confirmed by sensitivity and positive predictivity of 99.99% and the detection accuracy of 99.98% for QRS complex detection. The number of false positives and false negatives resulted while analysis has been drastically reduced to 80 and 42 against the 98 and 84 the best results reported so far.

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

    Science.gov (United States)

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

    2008-09-01

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

  8. Hydrogen Exchange Differences between Chemoreceptor Signaling Complexes Localize to Functionally Important Subdomains

    Science.gov (United States)

    2015-01-01

    The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes. PMID:25420045

  9. 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.

  10. Complexity of EEG-signal in Time Domain - Possible Biomedical Application

    Science.gov (United States)

    Klonowski, Wlodzimierz; Olejarczyk, Elzbieta; Stepien, Robert

    2002-07-01

    Human brain is a highly complex nonlinear system. So it is not surprising that in analysis of EEG-signal, which represents overall activity of the brain, the methods of Nonlinear Dynamics (or Chaos Theory as it is commonly called) can be used. Even if the signal is not chaotic these methods are a motivating tool to explore changes in brain activity due to different functional activation states, e.g. different sleep stages, or to applied therapy, e.g. exposure to chemical agents (drugs) and physical factors (light, magnetic field). The methods supplied by Nonlinear Dynamics reveal signal characteristics that are not revealed by linear methods like FFT. Better understanding of principles that govern dynamics and complexity of EEG-signal can help to find `the signatures' of different physiological and pathological states of human brain, quantitative characteristics that may find applications in medical diagnostics.

  11. Bio-Signal Complexity Analysis in Epileptic Seizure Monitoring: A Topic Review

    Directory of Open Access Journals (Sweden)

    Zhenning Mei

    2018-05-01

    Full Text Available Complexity science has provided new perspectives and opportunities for understanding a variety of complex natural or social phenomena, including brain dysfunctions like epilepsy. By delving into the complexity in electrophysiological signals and neuroimaging, new insights have emerged. These discoveries have revealed that complexity is a fundamental aspect of physiological processes. The inherent nonlinearity and non-stationarity of physiological processes limits the methods based on simpler underlying assumptions to point out the pathway to a more comprehensive understanding of their behavior and relation with certain diseases. The perspective of complexity may benefit both the research and clinical practice through providing novel data analytics tools devoted for the understanding of and the intervention about epilepsies. This review aims to provide a sketchy overview of the methods derived from different disciplines lucubrating to the complexity of bio-signals in the field of epilepsy monitoring. Although the complexity of bio-signals is still not fully understood, bundles of new insights have been already obtained. Despite the promising results about epileptic seizure detection and prediction through offline analysis, we are still lacking robust, tried-and-true real-time applications. Multidisciplinary collaborations and more high-quality data accessible to the whole community are needed for reproducible research and the development of such applications.

  12. Receptor density balances signal stimulation and attenuation in membrane-assembled complexes of bacterial chemotaxis signaling proteins

    Science.gov (United States)

    Besschetnova, Tatiana Y.; Montefusco, David J.; Asinas, Abdalin E.; Shrout, Anthony L.; Antommattei, Frances M.; Weis, Robert M.

    2008-01-01

    All cells possess transmembrane signaling systems that function in the environment of the lipid bilayer. In the Escherichia coli chemotaxis pathway, the binding of attractants to a two-dimensional array of receptors and signaling proteins simultaneously inhibits an associated kinase and stimulates receptor methylation—a slower process that restores kinase activity. These two opposing effects lead to robust adaptation toward stimuli through a physical mechanism that is not understood. Here, we provide evidence of a counterbalancing influence exerted by receptor density on kinase stimulation and receptor methylation. Receptor signaling complexes were reconstituted over a range of defined surface concentrations by using a template-directed assembly method, and the kinase and receptor methylation activities were measured. Kinase activity and methylation rates were both found to vary significantly with surface concentration—yet in opposite ways: samples prepared at high surface densities stimulated kinase activity more effectively than low-density samples, whereas lower surface densities produced greater methylation rates than higher densities. FRET experiments demonstrated that the cooperative change in kinase activity coincided with a change in the arrangement of the membrane-associated receptor domains. The counterbalancing influence of density on receptor methylation and kinase stimulation leads naturally to a model for signal regulation that is compatible with the known logic of the E. coli pathway. Density-dependent mechanisms are likely to be general and may operate when two or more membrane-related processes are influenced differently by the two-dimensional concentration of pathway elements. PMID:18711126

  13. Fuzzy approximate entropy analysis of chaotic and natural complex systems: detecting muscle fatigue using electromyography signals.

    Science.gov (United States)

    Xie, Hong-Bo; Guo, Jing-Yi; Zheng, Yong-Ping

    2010-04-01

    In the present contribution, a complexity measure is proposed to assess surface electromyography (EMG) in the study of muscle fatigue during sustained, isometric muscle contractions. Approximate entropy (ApEn) is believed to provide quantitative information about the complexity of experimental data that is often corrupted with noise, short data length, and in many cases, has inherent dynamics that exhibit both deterministic and stochastic behaviors. We developed an improved ApEn measure, i.e., fuzzy approximate entropy (fApEn), which utilizes the fuzzy membership function to define the vectors' similarity. Tests were conducted on independent, identically distributed (i.i.d.) Gaussian and uniform noises, a chirp signal, MIX processes, Rossler equation, and Henon map. Compared with the standard ApEn, the fApEn showed better monotonicity, relative consistency, and more robustness to noise when characterizing signals with different complexities. Performance analysis on experimental EMG signals demonstrated that the fApEn significantly decreased during the development of muscle fatigue, which is a similar trend to that of the mean frequency (MNF) of the EMG signal, while the standard ApEn failed to detect this change. Moreover, fApEn of EMG demonstrated a better robustness to the length of the analysis window in comparison with the MNF of EMG. The results suggest that the fApEn of an EMG signal may potentially become a new reliable method for muscle fatigue assessment and be applicable to other short noisy physiological signal analysis.

  14. Complex motion of a vehicle through a series of signals controlled by power-law phase

    Science.gov (United States)

    Nagatani, Takashi

    2017-07-01

    We study the dynamic motion of a vehicle moving through the series of traffic signals controlled by the position-dependent phase of power law. All signals are controlled by both cycle time and position-dependent phase. The dynamic model of the vehicular motion is described in terms of the nonlinear map. The vehicular motion varies in a complex manner by varying cycle time for various values of the power of the position-dependent phase. The vehicle displays the periodic motion with a long cycle for the integer power of the phase, while the vehicular motion exhibits the very complex behavior for the non-integer power of the phase.

  15. Synthesis of high-complexity rhythmic signals for closed-loop electrical neuromodulation.

    Science.gov (United States)

    Zalay, Osbert C; Bardakjian, Berj L

    2013-06-01

    We propose an approach to synthesizing high-complexity rhythmic signals for closed-loop electrical neuromodulation using cognitive rhythm generator (CRG) networks, wherein the CRG is a hybrid oscillator comprised of (1) a bank of neuronal modes, (2) a ring device (clock), and (3) a static output nonlinearity (mapper). Networks of coupled CRGs have been previously implemented to simulate the electrical activity of biological neural networks, including in silico models of epilepsy, producing outputs of similar waveform and complexity to the biological system. This has enabled CRG network models to be used as platforms for testing seizure control strategies. Presently, we take the application one step further, envisioning therapeutic CRG networks as rhythmic signal generators creating neuromimetic signals for stimulation purposes, motivated by recent research indicating that stimulus complexity and waveform characteristics influence neuromodulation efficacy. To demonstrate this concept, an epileptiform CRG network generating spontaneous seizure-like events (SLEs) was coupled to a therapeutic CRG network, forming a closed-loop neuromodulation system. SLEs are associated with low-complexity dynamics and high phase coherence in the network. The tuned therapeutic network generated a high-complexity, multi-banded rhythmic stimulation signal with prominent theta and gamma-frequency power that suppressed SLEs and increased dynamic complexity in the epileptiform network, as measured by a relative increase in the maximum Lyapunov exponent and decrease in phase coherence. CRG-based neuromodulation outperformed both low and high-frequency periodic pulse stimulation, suggesting that neuromodulation using complex, biomimetic signals may provide an improvement over conventional electrical stimulation techniques for treating neurological disorders such as epilepsy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

    Science.gov (United States)

    Choi, B K; Hercules, D M; Gusev, A I

    2001-02-01

    The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

  17. Use of multiple singular value decompositions to analyze complex intracellular calcium ion signals

    KAUST Repository

    Martinez, Josue G.

    2009-12-01

    We compare calcium ion signaling (Ca(2+)) between two exposures; the data are present as movies, or, more prosaically, time series of images. This paper describes novel uses of singular value decompositions (SVD) and weighted versions of them (WSVD) to extract the signals from such movies, in a way that is semi-automatic and tuned closely to the actual data and their many complexities. These complexities include the following. First, the images themselves are of no interest: all interest focuses on the behavior of individual cells across time, and thus, the cells need to be segmented in an automated manner. Second, the cells themselves have 100+ pixels, so that they form 100+ curves measured over time, so that data compression is required to extract the features of these curves. Third, some of the pixels in some of the cells are subject to image saturation due to bit depth limits, and this saturation needs to be accounted for if one is to normalize the images in a reasonably un-biased manner. Finally, the Ca(2+) signals have oscillations or waves that vary with time and these signals need to be extracted. Thus, our aim is to show how to use multiple weighted and standard singular value decompositions to detect, extract and clarify the Ca(2+) signals. Our signal extraction methods then lead to simple although finely focused statistical methods to compare Ca(2+) signals across experimental conditions.

  18. Isolation and structure–function characterization of a signaling-active rhodopsin–G protein complex

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W.; Cerione, Richard A.; Skiniotis, Georgios; Ramachandran, Sekar

    2017-01-01

    The visual photo-transduction cascade is a prototypical G protein–coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (GT). This results in the dissociation of GT into its component αT–GTP and β1γ1 subunit complex. Structural information for the Rho*–GT complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (GT*) comprising a GαT/Gαi1 chimera (αT*) and β1γ1. The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to GαT* is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one GT*. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β2-adrenergic receptor–GS complex, including a flexible αT* helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. PMID:28655769

  19. Isolation and structure-function characterization of a signaling-active rhodopsin-G protein complex.

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W; Cerione, Richard A; Skiniotis, Georgios; Ramachandran, Sekar

    2017-08-25

    The visual photo-transduction cascade is a prototypical G protein-coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (G T ). This results in the dissociation of G T into its component α T -GTP and β 1 γ 1 subunit complex. Structural information for the Rho*-G T complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (G T *) comprising a Gα T /Gα i1 chimera (α T *) and β 1 γ 1 The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to Gα T * is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one G T *. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β 2 -adrenergic receptor-G S complex, including a flexible α T * helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. A functional TOC complex contributes to gravity signal transduction in Arabidopsis.

    Science.gov (United States)

    Strohm, Allison K; Barrett-Wilt, Greg A; Masson, Patrick H

    2014-01-01

    Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism.

  1. Identifying deterministic signals in simulated gravitational wave data: algorithmic complexity and the surrogate data method

    International Nuclear Information System (INIS)

    Zhao Yi; Small, Michael; Coward, David; Howell, Eric; Zhao Chunnong; Ju Li; Blair, David

    2006-01-01

    We describe the application of complexity estimation and the surrogate data method to identify deterministic dynamics in simulated gravitational wave (GW) data contaminated with white and coloured noises. The surrogate method uses algorithmic complexity as a discriminating statistic to decide if noisy data contain a statistically significant level of deterministic dynamics (the GW signal). The results illustrate that the complexity method is sensitive to a small amplitude simulated GW background (SNR down to 0.08 for white noise and 0.05 for coloured noise) and is also more robust than commonly used linear methods (autocorrelation or Fourier analysis)

  2. Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal

    OpenAIRE

    Hamidreza Namazi; Amin Akrami; Sina Nazeri; Vladimir V. Kulish

    2016-01-01

    An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally ...

  3. 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.

  4. 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.

  5. Disentangling the Complexity of HGF Signaling by Combining Qualitative and Quantitative Modeling.

    Directory of Open Access Journals (Sweden)

    Lorenza A D'Alessandro

    2015-04-01

    Full Text Available Signaling pathways are characterized by crosstalk, feedback and feedforward mechanisms giving rise to highly complex and cell-context specific signaling networks. Dissecting the underlying relations is crucial to predict the impact of targeted perturbations. However, a major challenge in identifying cell-context specific signaling networks is the enormous number of potentially possible interactions. Here, we report a novel hybrid mathematical modeling strategy to systematically unravel hepatocyte growth factor (HGF stimulated phosphoinositide-3-kinase (PI3K and mitogen activated protein kinase (MAPK signaling, which critically contribute to liver regeneration. By combining time-resolved quantitative experimental data generated in primary mouse hepatocytes with interaction graph and ordinary differential equation modeling, we identify and experimentally validate a network structure that represents the experimental data best and indicates specific crosstalk mechanisms. Whereas the identified network is robust against single perturbations, combinatorial inhibition strategies are predicted that result in strong reduction of Akt and ERK activation. Thus, by capitalizing on the advantages of the two modeling approaches, we reduce the high combinatorial complexity and identify cell-context specific signaling networks.

  6. Signaling and Adaptation Modulate the Dynamics of the Photosensoric Complex of Natronomonas pharaonis.

    Directory of Open Access Journals (Sweden)

    Philipp S Orekhov

    2015-10-01

    Full Text Available Motile bacteria and archaea respond to chemical and physical stimuli seeking optimal conditions for survival. To this end transmembrane chemo- and photoreceptors organized in large arrays initiate signaling cascades and ultimately regulate the rotation of flagellar motors. To unravel the molecular mechanism of signaling in an archaeal phototaxis complex we performed coarse-grained molecular dynamics simulations of a trimer of receptor/transducer dimers, namely NpSRII/NpHtrII from Natronomonas pharaonis. Signaling is regulated by a reversible methylation mechanism called adaptation, which also influences the level of basal receptor activation. Mimicking two extreme methylation states in our simulations we found conformational changes for the transmembrane region of NpSRII/NpHtrII which resemble experimentally observed light-induced changes. Further downstream in the cytoplasmic domain of the transducer the signal propagates via distinct changes in the dynamics of HAMP1, HAMP2, the adaptation domain and the binding region for the kinase CheA, where conformational rearrangements were found to be subtle. Overall these observations suggest a signaling mechanism based on dynamic allostery resembling models previously proposed for E. coli chemoreceptors, indicating similar properties of signal transduction for archaeal photoreceptors and bacterial chemoreceptors.

  7. Comparison of GFL–GFRα complexes: further evidence relating GFL bend angle to RET signalling

    International Nuclear Information System (INIS)

    Parkash, Vimal; Goldman, Adrian

    2009-01-01

    The second crystal structure of the GDNF-GFRα1 complex provides further evidence that GFL signalling through RET is determined by the bend angle in the GFL. Glial cell line-derived neurotrophic factor (GDNF) activates the receptor tyrosine kinase RET by binding to the GDNF-family receptor α1 (GFRα1) and forming the GDNF 2 –GFRα1 2 –RET 2 heterohexamer complex. A previous crystal structure of the GDNF 2 –GFRα1 2 complex suggested that differences in signalling in GDNF-family ligand (GFL) complexes might arise from differences in the bend angle between the two monomers in the GFL homodimer. Here, a 2.35 Å resolution structure of the GDNF 2 –GFRα1 2 complex crystallized with new cell dimensions is reported. The structure was refined to a final R factor of 22.5% (R free = 28%). The structures of both biological tetrameric complexes in the asymmetric unit are very similar to 2v5e and different from the artemin–GFRα3 structure, even though there is a small change in the structure of the GDNF. By comparison of all known GDNF and artemin structures, it is concluded that GDNF is more bent and more flexible than artemin and that this may be related to RET signalling. Comparisons also suggest that the differences between artemin and GDNF arise from the increased curvature of the artemin ‘fingers’, which both increases the buried surface area in the monomer–monomer interface and changes the intermonomer bend angle. From sequence comparison, it is suggested that neuturin (the second GFL) adopts an artemin-like conformation, while persephin has a different conformation to the other three

  8. Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

    Science.gov (United States)

    Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

    1993-06-25

    Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

  9. Characterizing scaling properties of complex signals with missed data segments using the multifractal analysis

    Science.gov (United States)

    Pavlov, A. N.; Pavlova, O. N.; Abdurashitov, A. S.; Sindeeva, O. A.; Semyachkina-Glushkovskaya, O. V.; Kurths, J.

    2018-01-01

    The scaling properties of complex processes may be highly influenced by the presence of various artifacts in experimental recordings. Their removal produces changes in the singularity spectra and the Hölder exponents as compared with the original artifacts-free data, and these changes are significantly different for positively correlated and anti-correlated signals. While signals with power-law correlations are nearly insensitive to the loss of significant parts of data, the removal of fragments of anti-correlated signals is more crucial for further data analysis. In this work, we study the ability of characterizing scaling features of chaotic and stochastic processes with distinct correlation properties using a wavelet-based multifractal analysis, and discuss differences between the effect of missed data for synchronous and asynchronous oscillatory regimes. We show that even an extreme data loss allows characterizing physiological processes such as the cerebral blood flow dynamics.

  10. Discrimination of Rock Fracture and Blast Events Based on Signal Complexity and Machine Learning

    Directory of Open Access Journals (Sweden)

    Zilong Zhou

    2018-01-01

    Full Text Available The automatic discrimination of rock fracture and blast events is complex and challenging due to the similar waveform characteristics. To solve this problem, a new method based on the signal complexity analysis and machine learning has been proposed in this paper. First, the permutation entropy values of signals at different scale factors are calculated to reflect complexity of signals and constructed into a feature vector set. Secondly, based on the feature vector set, back-propagation neural network (BPNN as a means of machine learning is applied to establish a discriminator for rock fracture and blast events. Then to evaluate the classification performances of the new method, the classifying accuracies of support vector machine (SVM, naive Bayes classifier, and the new method are compared, and the receiver operating characteristic (ROC curves are also analyzed. The results show the new method obtains the best classification performances. In addition, the influence of different scale factor q and number of training samples n on discrimination results is discussed. It is found that the classifying accuracy of the new method reaches the highest value when q = 8–15 or 8–20 and n=140.

  11. TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

    Directory of Open Access Journals (Sweden)

    Brad J. Niles

    2014-02-01

    Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

  12. Precise signal amplitude retrieval for a non-homogeneous diagnostic beam using complex interferometry approach

    Science.gov (United States)

    Krupka, M.; Kalal, M.; Dostal, J.; Dudzak, R.; Juha, L.

    2017-08-01

    Classical interferometry became widely used method of active optical diagnostics. Its more advanced version, allowing reconstruction of three sets of data from just one especially designed interferogram (so called complex interferogram) was developed in the past and became known as complex interferometry. Along with the phase shift, which can be also retrieved using classical interferometry, the amplitude modifications of the probing part of the diagnostic beam caused by the object under study (to be called the signal amplitude) as well as the contrast of the interference fringes can be retrieved using the complex interferometry approach. In order to partially compensate for errors in the reconstruction due to imperfections in the diagnostic beam intensity structure as well as for errors caused by a non-ideal optical setup of the interferometer itself (including the quality of its optical components), a reference interferogram can be put to a good use. This method of interferogram analysis of experimental data has been successfully implemented in practice. However, in majority of interferometer setups (especially in the case of the ones employing the wavefront division) the probe and the reference part of the diagnostic beam would feature different intensity distributions over their respective cross sections. This introduces additional error into the reconstruction of the signal amplitude and the fringe contrast, which cannot be resolved using the reference interferogram only. In order to deal with this error it was found that additional separately recorded images of the intensity distribution of the probe and the reference part of the diagnostic beam (with no signal present) are needed. For the best results a sufficient shot-to-shot stability of the whole diagnostic system is required. In this paper, efficiency of the complex interferometry approach for obtaining the highest possible accuracy of the signal amplitude reconstruction is verified using the computer

  13. Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

    Science.gov (United States)

    Sorokin, Andrey

    2016-01-01

    The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

  14. Hurst Exponent Analysis of Resting-State fMRI Signal Complexity across the Adult Lifespan

    Directory of Open Access Journals (Sweden)

    Jianxin Dong

    2018-02-01

    Full Text Available Exploring functional information among various brain regions across time enables understanding of healthy aging process and holds great promise for age-related brain disease diagnosis. This paper proposed a method to explore fractal complexity of the resting-state functional magnetic resonance imaging (rs-fMRI signal in the human brain across the adult lifespan using Hurst exponent (HE. We took advantage of the examined rs-fMRI data from 116 adults 19 to 85 years of age (44.3 ± 19.4 years, 49 females from NKI/Rockland sample. Region-wise and voxel-wise analyses were performed to investigate the effects of age, gender, and their interaction on complexity. In region-wise analysis, we found that the healthy aging is accompanied by a loss of complexity in frontal and parietal lobe and increased complexity in insula, limbic, and temporal lobe. Meanwhile, differences in HE between genders were found to be significant in parietal lobe (p = 0.04, corrected. However, there was no interaction between gender and age. In voxel-wise analysis, the significant complexity decrease with aging was found in frontal and parietal lobe, and complexity increase was found in insula, limbic lobe, occipital lobe, and temporal lobe with aging. Meanwhile, differences in HE between genders were found to be significant in frontal, parietal, and limbic lobe. Furthermore, we found age and sex interaction in right parahippocampal gyrus (p = 0.04, corrected. Our findings reveal HE variations of the rs-fMRI signal across the human adult lifespan and show that HE may serve as a new parameter to assess healthy aging process.

  15. Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-04-01

    The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

  16. Identification of Anisomerous Motor Imagery EEG Signals Based on Complex Algorithms

    Science.gov (United States)

    Zhang, Zhiwen; Duan, Feng; Zhou, Xin; Meng, Zixuan

    2017-01-01

    Motor imagery (MI) electroencephalograph (EEG) signals are widely applied in brain-computer interface (BCI). However, classified MI states are limited, and their classification accuracy rates are low because of the characteristics of nonlinearity and nonstationarity. This study proposes a novel MI pattern recognition system that is based on complex algorithms for classifying MI EEG signals. In electrooculogram (EOG) artifact preprocessing, band-pass filtering is performed to obtain the frequency band of MI-related signals, and then, canonical correlation analysis (CCA) combined with wavelet threshold denoising (WTD) is used for EOG artifact preprocessing. We propose a regularized common spatial pattern (R-CSP) algorithm for EEG feature extraction by incorporating the principle of generic learning. A new classifier combining the K-nearest neighbor (KNN) and support vector machine (SVM) approaches is used to classify four anisomerous states, namely, imaginary movements with the left hand, right foot, and right shoulder and the resting state. The highest classification accuracy rate is 92.5%, and the average classification accuracy rate is 87%. The proposed complex algorithm identification method can significantly improve the identification rate of the minority samples and the overall classification performance. PMID:28874909

  17. Identification of Anisomerous Motor Imagery EEG Signals Based on Complex Algorithms.

    Science.gov (United States)

    Liu, Rensong; Zhang, Zhiwen; Duan, Feng; Zhou, Xin; Meng, Zixuan

    2017-01-01

    Motor imagery (MI) electroencephalograph (EEG) signals are widely applied in brain-computer interface (BCI). However, classified MI states are limited, and their classification accuracy rates are low because of the characteristics of nonlinearity and nonstationarity. This study proposes a novel MI pattern recognition system that is based on complex algorithms for classifying MI EEG signals. In electrooculogram (EOG) artifact preprocessing, band-pass filtering is performed to obtain the frequency band of MI-related signals, and then, canonical correlation analysis (CCA) combined with wavelet threshold denoising (WTD) is used for EOG artifact preprocessing. We propose a regularized common spatial pattern (R-CSP) algorithm for EEG feature extraction by incorporating the principle of generic learning. A new classifier combining the K -nearest neighbor (KNN) and support vector machine (SVM) approaches is used to classify four anisomerous states, namely, imaginary movements with the left hand, right foot, and right shoulder and the resting state. The highest classification accuracy rate is 92.5%, and the average classification accuracy rate is 87%. The proposed complex algorithm identification method can significantly improve the identification rate of the minority samples and the overall classification performance.

  18. Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal.

    Science.gov (United States)

    Namazi, Hamidreza; Akrami, Amin; Nazeri, Sina; Kulish, Vladimir V

    2016-01-01

    An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal EEG signal. Also, odorant having higher entropy causes the EEG signal to have lower approximate entropy. The method discussed here can be applied and investigated in case of patients with brain diseases as the rehabilitation purpose.

  19. Multi-signal sedimentation velocity analysis with mass conservation for determining the stoichiometry of protein complexes.

    Directory of Open Access Journals (Sweden)

    Chad A Brautigam

    Full Text Available Multi-signal sedimentation velocity analytical ultracentrifugation (MSSV is a powerful tool for the determination of the number, stoichiometry, and hydrodynamic shape of reversible protein complexes in two- and three-component systems. In this method, the evolution of sedimentation profiles of macromolecular mixtures is recorded simultaneously using multiple absorbance and refractive index signals and globally transformed into both spectrally and diffusion-deconvoluted component sedimentation coefficient distributions. For reactions with complex lifetimes comparable to the time-scale of sedimentation, MSSV reveals the number and stoichiometry of co-existing complexes. For systems with short complex lifetimes, MSSV reveals the composition of the reaction boundary of the coupled reaction/migration process, which we show here may be used to directly determine an association constant. A prerequisite for MSSV is that the interacting components are spectrally distinguishable, which may be a result, for example, of extrinsic chromophores or of different abundances of aromatic amino acids contributing to the UV absorbance. For interacting components that are spectrally poorly resolved, here we introduce a method for additional regularization of the spectral deconvolution by exploiting approximate knowledge of the total loading concentrations. While this novel mass conservation principle does not discriminate contributions to different species, it can be effectively combined with constraints in the sedimentation coefficient range of uncomplexed species. We show in theory, computer simulations, and experiment, how mass conservation MSSV as implemented in SEDPHAT can enhance or even substitute for the spectral discrimination of components. This should broaden the applicability of MSSV to the analysis of the composition of reversible macromolecular complexes.

  20. Ethylene Regulates Levels of Ethylene Receptor/CTR1 Signaling Complexes in Arabidopsis thaliana*

    Science.gov (United States)

    Shakeel, Samina N.; Gao, Zhiyong; Amir, Madiha; Chen, Yi-Feng; Rai, Muneeza Iqbal; Haq, Noor Ul; Schaller, G. Eric

    2015-01-01

    The plant hormone ethylene is perceived by a five-member family of receptors in Arabidopsis thaliana. The receptors function in conjunction with the Raf-like kinase CTR1 to negatively regulate ethylene signal transduction. CTR1 interacts with multiple members of the receptor family based on co-purification analysis, interacting more strongly with receptors containing a receiver domain. Levels of membrane-associated CTR1 vary in response to ethylene, doing so in a post-transcriptional manner that correlates with ethylene-mediated changes in levels of the ethylene receptors ERS1, ERS2, EIN4, and ETR2. Interactions between CTR1 and the receptor ETR1 protect ETR1 from ethylene-induced turnover. Kinetic and dose-response analyses support a model in which two opposing factors control levels of the ethylene receptor/CTR1 complexes. Ethylene stimulates the production of new complexes largely through transcriptional induction of the receptors. However, ethylene also induces turnover of receptors, such that levels of ethylene receptor/CTR1 complexes decrease at higher ethylene concentrations. Implications of this model for ethylene signaling are discussed. PMID:25814663

  1. The mediator complex in genomic and non-genomic signaling in cancer.

    Science.gov (United States)

    Weber, Hannah; Garabedian, Michael J

    2018-05-01

    Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Jasmonate signalling in Arabidopsis involves SGT1b-HSP70-HSP90 chaperone complexes.

    Science.gov (United States)

    Zhang, Xue-Cheng; Millet, Yves A; Cheng, Zhenyu; Bush, Jenifer; Ausubel, Frederick M

    Plant hormones play pivotal roles in growth, development and stress responses. Although it is essential to our understanding of hormone signalling, how plants maintain a steady state level of hormone receptors is poorly understood. We show that mutation of the Arabidopsis thaliana co-chaperone SGT1b impairs responses to the plant hormones jasmonate, auxin and gibberellic acid, but not brassinolide and abscisic acid, and that SGT1b and its homologue SGT1a are involved in maintaining the steady state levels of the F-box proteins COI1 and TIR1, receptors for jasmonate and auxin, respectively. The association of SGT1b with COI1 is direct and is independent of the Arabidopsis SKP1 protein, ASK1. We further show that COI1 is a client protein of SGT1b-HSP70-HSP90 chaperone complexes and that the complexes function in hormone signalling by stabilizing the COI1 protein. This study extends the SGT1b-HSP90 client protein list and broadens the functional scope of SGT1b-HSP70-HSP90 chaperone complexes.

  3. A complex symbol signal-to-noise ratio estimator and its performance

    Science.gov (United States)

    Feria, Y.

    1994-01-01

    This article presents an algorithm for estimating the signal-to-noise ratio (SNR) of signals that contain data on a downconverted suppressed carrier or the first harmonic of a square-wave subcarrier. This algorithm can be used to determine the performance of the full-spectrum combiner for the Galileo S-band (2.2- to 2.3-GHz) mission by measuring the input and output symbol SNR. A performance analysis of the algorithm shows that the estimator can estimate the complex symbol SNR using 10,000 symbols at a true symbol SNR of -5 dB with a mean of -4.9985 dB and a standard deviation of 0.2454 dB, and these analytical results are checked by simulations of 100 runs with a mean of -5.06 dB and a standard deviation of 0.2506 dB.

  4. Phase dynamics of complex-valued neural networks and its application to traffic signal control.

    Science.gov (United States)

    Nishikawa, Ikuko; Iritani, Takeshi; Sakakibara, Kazutoshi; Kuroe, Yasuaki

    2005-01-01

    Complex-valued Hopfield networks which possess the energy function are analyzed. The dynamics of the network with certain forms of an activation function is de-composable into the dynamics of the amplitude and phase of each neuron. Then the phase dynamics is described as a coupled system of phase oscillators with a pair-wise sinusoidal interaction. Therefore its phase synchronization mechanism is useful for the area-wide offset control of the traffic signals. The computer simulations show the effectiveness under the various traffic conditions.

  5. Application of «Sensor signal analysis network» complex for distributed, time synchronized analysis of electromagnetic radiation

    Science.gov (United States)

    Mochalov, Vladimir; Mochalova, Anastasia

    2017-10-01

    The paper considers a developing software-hardware complex «Sensor signal analysis network» for distributed and time synchronized analysis of electromagnetic radiations. The areas of application and the main features of the complex are described. An example of application of the complex to monitor natural electromagnetic radiation sources is considered based on the data recorded in VLF range. A generalized functional scheme of stream analysis of signals by a complex functional node is suggested and its application for stream detection of atmospherics, whistlers and tweaks is considered.

  6. The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation.

    Science.gov (United States)

    Sun, X J; Pons, S; Asano, T; Myers, M G; Glasheen, E; White, M F

    1996-05-03

    Irs-proteins link the receptors for insulin/IGF-1, growth hormones, and several interleukins and interferons to signaling proteins that contain Src homology-2 (SH2). To identify new Irs-1-binding proteins, we screened a mouse embryo expression library with recombinant [32P]Irs-1, which revealed a specific association between p59fyn and Irs-1. The SH2 domain in p59fyn bound to phosphorylated Tyr895 and Tyr1172, which are located in YXX(L/I) motifs. Mutation of p59fyn at the COOH-terminal tyrosine phosphorylation site (Tyr531) enhanced its binding to Irs-1 during insulin stimulation. Binding experiments with various SH2 protein revealed that Grb-2 was largely excluded from Irs-1 complexes containing p59fyn, whereas Grb-2 and p85 occurred in the same Irs-1 complex. By comparison with the insulin receptor, p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. These results outline a role for p59fyn or other related Src-kinases during insulin and cytokine signaling.

  7. Design Implementation and Testing of a VLSI High Performance ASIC for Extracting the Phase of a Complex Signal

    National Research Council Canada - National Science Library

    Altmeyer, Ronald

    2002-01-01

    This thesis documents the research, circuit design, and simulation testing of a VLSI ASIC which extracts phase angle information from a complex sampled signal using the arctangent relationship: (phi=tan/-1 (Q/1...

  8. Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

    Science.gov (United States)

    Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

    2016-10-24

    The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Generation of Long-time Complex Signals for Testing the Instruments for Detection of Voltage Quality Disturbances

    Science.gov (United States)

    Živanović, Dragan; Simić, Milan; Kokolanski, Zivko; Denić, Dragan; Dimcev, Vladimir

    2018-04-01

    Software supported procedure for generation of long-time complex test sentences, suitable for testing the instruments for detection of standard voltage quality (VQ) disturbances is presented in this paper. This solution for test signal generation includes significant improvements of computer-based signal generator presented and described in the previously published paper [1]. The generator is based on virtual instrumentation software for defining the basic signal parameters, data acquisition card NI 6343, and power amplifier for amplification of output voltage level to the nominal RMS voltage value of 230 V. Definition of basic signal parameters in LabVIEW application software is supported using Script files, which allows simple repetition of specific test signals and combination of more different test sequences in the complex composite test waveform. The basic advantage of this generator compared to the similar solutions for signal generation is the possibility for long-time test sequence generation according to predefined complex test scenarios, including various combinations of VQ disturbances defined in accordance with the European standard EN50160. Experimental verification of the presented signal generator capability is performed by testing the commercial power quality analyzer Fluke 435 Series II. In this paper are shown some characteristic complex test signals with various disturbances and logged data obtained from the tested power quality analyzer.

  10. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

    Science.gov (United States)

    Zeke, András; Misheva, Mariya

    2016-01-01

    SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. PMID:27466283

  11. Binding of Signal Recognition Particle Gives Ribosome/Nascent Chain Complexes a Competitive Advantage in Endoplasmic Reticulum Membrane Interaction

    Science.gov (United States)

    Neuhof, Andrea; Rolls, Melissa M.; Jungnickel, Berit; Kalies, Kai-Uwe; Rapoport, Tom A.

    1998-01-01

    Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC–SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes. PMID:9436994

  12. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants

    Directory of Open Access Journals (Sweden)

    Subhasis eSamanta

    2015-09-01

    Full Text Available Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channelling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic and molecular analyses have unravelled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator’s involvement in these processes.

  13. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants.

    Science.gov (United States)

    Samanta, Subhasis; Thakur, Jitendra K

    2015-01-01

    Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channeling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator's involvement in these processes.

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

    Science.gov (United States)

    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, homeostasis, and regeneration based on evolutionary principles. This cell–cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such

  15. The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development.

    Directory of Open Access Journals (Sweden)

    Hélène Chanut-Delalande

    Full Text Available BACKGROUND: Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. PRINCIPAL FINDINGS: Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. CONCLUSIONS/SIGNIFICANCE: Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development.

  16. Employing the Hilbert-Huang Transform to analyze observed natural complex signals: Calm wind meandering cases

    Science.gov (United States)

    Martins, Luis Gustavo Nogueira; Stefanello, Michel Baptistella; Degrazia, Gervásio Annes; Acevedo, Otávio Costa; Puhales, Franciano Scremin; Demarco, Giuliano; Mortarini, Luca; Anfossi, Domenico; Roberti, Débora Regina; Costa, Felipe Denardin; Maldaner, Silvana

    2016-11-01

    In this study we analyze natural complex signals employing the Hilbert-Huang spectral analysis. Specifically, low wind meandering meteorological data are decomposed into turbulent and non turbulent components. These non turbulent movements, responsible for the absence of a preferential direction of the horizontal wind, provoke negative lobes in the meandering autocorrelation functions. The meandering characteristic time scales (meandering periods) are determined from the spectral peak provided by the Hilbert-Huang marginal spectrum. The magnitudes of the temperature and horizontal wind meandering period obtained agree with the results found from the best fit of the heuristic meandering autocorrelation functions. Therefore, the new method represents a new procedure to evaluate meandering periods that does not employ mathematical expressions to represent observed meandering autocorrelation functions.

  17. Ant Queen Egg-Marking Signals: Matching Deceptive Laboratory Simplicity with Natural Complexity

    DEFF Research Database (Denmark)

    van Zweden, Jelle Stijn; Heinze, Jürgen; Boomsma, Jacobus Jan

    2009-01-01

    Background Experiments under controlled laboratory conditions can produce decisive evidence for testing biological hypotheses, provided they are representative of the more complex natural conditions. However, whether this requirement is fulfilled is seldom tested explicitly. Here we provide a lab....../field comparison to investigate the identity of an egg-marking signal of ant queens. Our study was based on ant workers resolving conflict over male production by destroying each other's eggs, but leaving queen eggs unharmed. For this, the workers need a proximate cue to discriminate between the two egg types...... that this compound by itself is not the natural queen egg-marking pheromone. We subsequently investigated the overall differences of entire chemical profiles of eggs, and found that queen-laid eggs in field colonies are more distinct from worker-laid eggs than in lab colonies, have more variation in profiles...

  18. Low-complexity camera digital signal imaging for video document projection system

    Science.gov (United States)

    Hsia, Shih-Chang; Tsai, Po-Shien

    2011-04-01

    We present high-performance and low-complexity algorithms for real-time camera imaging applications. The main functions of the proposed camera digital signal processing (DSP) involve color interpolation, white balance, adaptive binary processing, auto gain control, and edge and color enhancement for video projection systems. A series of simulations demonstrate that the proposed method can achieve good image quality while keeping computation cost and memory requirements low. On the basis of the proposed algorithms, the cost-effective hardware core is developed using Verilog HDL. The prototype chip has been verified with one low-cost programmable device. The real-time camera system can achieve 1270 × 792 resolution with the combination of extra components and can demonstrate each DSP function.

  19. Optimal sensor configuration for complex systems with application to signal detection in structures

    DEFF Research Database (Denmark)

    Sadegh, Payman; Spall, J. C.

    2000-01-01

    sensor outputs. Secondly, we describe an efficient and practical algorithm to achieve the optimization goals, based on simultaneous perturbation stochastic approximation (SPSA). SPSA avoids the need for detailed modeling of the sensor response by simply relying on observed responses as obtained......The paper considers the problem of sensor configuration for complex systems. The contribution of the paper is twofold. Firstly, we define an appropriate criterion that is based on maximizing overall sensor responses while minimizing redundant information as measured by correlations between multiple...... by limited experimentation with test sensor configurations. We illustrate the application of the approach to optimal placement of acoustic sensors for signal detection in structures. This includes both a computer simulation study for an aluminum plate, and real experimentations on a steel I-beam....

  20. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins

    Science.gov (United States)

    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.

    2013-01-01

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320

  1. Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

    Science.gov (United States)

    Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

    2018-01-24

    Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

  2. Micro-earthquake signal analysis and hypocenter determination around Lokon volcano complex

    Energy Technology Data Exchange (ETDEWEB)

    Firmansyah, Rizky, E-mail: rizkyfirmansyah@hotmail.com [Geophysical Engineering, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Nugraha, Andri Dian, E-mail: nugraha@gf.itb.ac.id [Global Geophysical Group, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Kristianto, E-mail: kris@vsi.esdm.go.id [Center for Volcanology and Geological Hazard Mitigation (CVGHM), Geological Agency, Bandung, 40122 (Indonesia)

    2015-04-24

    Mount Lokon is one of five active volcanoes which is located in the North Sulawesi region. Since June 26{sup th}, 2011, standby alert set by the Center for Volcanology and Geological Hazard Mitigation (CVGHM) for this mountain. The Mount Lokon volcano erupted on July 4{sup th}, 2011 and still continuously erupted until August 28{sup th}, 2011. Due to its high seismic activity, this study is focused to analysis of micro-earthquake signal and determine the micro-earthquake hypocenter location around the complex area of Lokon-Empung Volcano before eruption phase in 2011 (time periods of January, 2009 up to March, 2010). Determination of the hypocenter location was conducted with Geiger Adaptive Damping (GAD) method. We used initial model from previous study in Volcan de Colima, Mexico. The reason behind the model selection was based on the same characteristics that shared between Mount Lokon and Colima including andesitic stratovolcano and small-plinian explosions volcanian types. In this study, a picking events was limited to the volcano-tectonics of A and B types, hybrid, long-period that has a clear signal onset, and local tectonic with different maximum S – P time are not more than three seconds. As a result, we observed the micro-earthquakes occurred in the area north-west of Mount Lokon region.

  3. Micro-earthquake signal analysis and hypocenter determination around Lokon volcano complex

    International Nuclear Information System (INIS)

    Firmansyah, Rizky; Nugraha, Andri Dian; Kristianto

    2015-01-01

    Mount Lokon is one of five active volcanoes which is located in the North Sulawesi region. Since June 26 th , 2011, standby alert set by the Center for Volcanology and Geological Hazard Mitigation (CVGHM) for this mountain. The Mount Lokon volcano erupted on July 4 th , 2011 and still continuously erupted until August 28 th , 2011. Due to its high seismic activity, this study is focused to analysis of micro-earthquake signal and determine the micro-earthquake hypocenter location around the complex area of Lokon-Empung Volcano before eruption phase in 2011 (time periods of January, 2009 up to March, 2010). Determination of the hypocenter location was conducted with Geiger Adaptive Damping (GAD) method. We used initial model from previous study in Volcan de Colima, Mexico. The reason behind the model selection was based on the same characteristics that shared between Mount Lokon and Colima including andesitic stratovolcano and small-plinian explosions volcanian types. In this study, a picking events was limited to the volcano-tectonics of A and B types, hybrid, long-period that has a clear signal onset, and local tectonic with different maximum S – P time are not more than three seconds. As a result, we observed the micro-earthquakes occurred in the area north-west of Mount Lokon region

  4. Efficient transmission of subthreshold signals in complex networks of spiking neurons.

    Science.gov (United States)

    Torres, Joaquin J; Elices, Irene; Marro, J

    2015-01-01

    We investigate the efficient transmission and processing of weak, subthreshold signals in a realistic neural medium in the presence of different levels of the underlying noise. Assuming Hebbian weights for maximal synaptic conductances--that naturally balances the network with excitatory and inhibitory synapses--and considering short-term synaptic plasticity affecting such conductances, we found different dynamic phases in the system. This includes a memory phase where population of neurons remain synchronized, an oscillatory phase where transitions between different synchronized populations of neurons appears and an asynchronous or noisy phase. When a weak stimulus input is applied to each neuron, increasing the level of noise in the medium we found an efficient transmission of such stimuli around the transition and critical points separating different phases for well-defined different levels of stochasticity in the system. We proved that this intriguing phenomenon is quite robust, as it occurs in different situations including several types of synaptic plasticity, different type and number of stored patterns and diverse network topologies, namely, diluted networks and complex topologies such as scale-free and small-world networks. We conclude that the robustness of the phenomenon in different realistic scenarios, including spiking neurons, short-term synaptic plasticity and complex networks topologies, make very likely that it could also occur in actual neural systems as recent psycho-physical experiments suggest.

  5. Efficient transmission of subthreshold signals in complex networks of spiking neurons.

    Directory of Open Access Journals (Sweden)

    Joaquin J Torres

    Full Text Available We investigate the efficient transmission and processing of weak, subthreshold signals in a realistic neural medium in the presence of different levels of the underlying noise. Assuming Hebbian weights for maximal synaptic conductances--that naturally balances the network with excitatory and inhibitory synapses--and considering short-term synaptic plasticity affecting such conductances, we found different dynamic phases in the system. This includes a memory phase where population of neurons remain synchronized, an oscillatory phase where transitions between different synchronized populations of neurons appears and an asynchronous or noisy phase. When a weak stimulus input is applied to each neuron, increasing the level of noise in the medium we found an efficient transmission of such stimuli around the transition and critical points separating different phases for well-defined different levels of stochasticity in the system. We proved that this intriguing phenomenon is quite robust, as it occurs in different situations including several types of synaptic plasticity, different type and number of stored patterns and diverse network topologies, namely, diluted networks and complex topologies such as scale-free and small-world networks. We conclude that the robustness of the phenomenon in different realistic scenarios, including spiking neurons, short-term synaptic plasticity and complex networks topologies, make very likely that it could also occur in actual neural systems as recent psycho-physical experiments suggest.

  6. Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling.

    Science.gov (United States)

    Kourtidis, Antonis; Necela, Brian; Lin, Wan-Hsin; Lu, Ruifeng; Feathers, Ryan W; Asmann, Yan W; Thompson, E Aubrey; Anastasiadis, Panos Z

    2017-10-02

    Cumulative evidence demonstrates that most RNAs exhibit specific subcellular distribution. However, the mechanisms regulating this phenomenon and its functional consequences are still under investigation. Here, we reveal that cadherin complexes at the apical zonula adherens (ZA) of epithelial adherens junctions recruit the core components of the RNA-induced silencing complex (RISC) Ago2, GW182, and PABPC1, as well as a set of 522 messenger RNAs (mRNAs) and 28 mature microRNAs (miRNAs or miRs), via PLEKHA7. Top canonical pathways represented by these mRNAs include Wnt/β-catenin, TGF-β, and stem cell signaling. We specifically demonstrate the presence and silencing of MYC, JUN, and SOX2 mRNAs by miR-24 and miR-200c at the ZA. PLEKHA7 knockdown dissociates RISC from the ZA, decreases loading of the ZA-associated mRNAs and miRNAs to Ago2, and results in a corresponding increase of MYC, JUN, and SOX2 protein expression. The present work reveals a mechanism that directly links junction integrity to the silencing of a set of mRNAs that critically affect epithelial homeostasis. © 2017 Kourtidis et al.

  7. Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

    Science.gov (United States)

    Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

    2014-01-17

    The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

  8. β-Catenin destruction complex-independent regulation of Hippo–YAP signaling by APC in intestinal tumorigenesis

    Science.gov (United States)

    Cai, Jing; Maitra, Anirban; Anders, Robert A.; Taketo, Makoto M.; Pan, Duojia

    2015-01-01

    Mutations in Adenomatous polyposis coli (APC) underlie familial adenomatous polyposis (FAP), an inherited cancer syndrome characterized by the widespread development of colorectal polyps. APC is best known as a scaffold protein in the β-catenin destruction complex, whose activity is antagonized by canonical Wnt signaling. Whether other effector pathways mediate APC's tumor suppressor function is less clear. Here we report that activation of YAP, the downstream effector of the Hippo signaling pathway, is a general hallmark of tubular adenomas from FAP patients. We show that APC functions as a scaffold protein that facilitates the Hippo kinase cascade by interacting with Sav1 and Lats1. Consistent with the molecular link between APC and the Hippo signaling pathway, genetic analysis reveals that YAP is absolutely required for the development of APC-deficient adenomas. These findings establish Hippo–YAP signaling as a critical effector pathway downstream from APC, independent from its involvement in the β-catenin destruction complex. PMID:26193883

  9. Kurtosis based blind source extraction of complex noncircular signals with application in EEG artifact removal in real-time

    Directory of Open Access Journals (Sweden)

    Soroush eJavidi

    2011-10-01

    Full Text Available A new class of complex domain blind source extraction (BSE algorithms suitable for the extraction of both circular and noncircular complex signals is proposed. This is achieved through sequential extraction based on the degree of kurtosis and in the presence of noncircular measurement noise. The existence and uniqueness analysis of the solution is followed by a study of fast converging variants of the algorithm. The performance is first assessed through simulations on well understood benchmark signals, followed by a case study on real-time artifact removal from EEG signals, verified using both qualitative and quantitative metrics. The results illustrate the power of the proposed approach in real-time blind extraction of general complex-valued sources.

  10. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    OpenAIRE

    Tukachinsky, Hanna; Lopez, Lyle V.; Salic, Adrian

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in wh...

  11. Complex on the base of the ISKRA 226.6 personal computer for nuclear quadrupole resonance signal processing

    International Nuclear Information System (INIS)

    Morgunov, V.G.; Kravchenko, Eh.A.

    1988-01-01

    Complex, designed to conduct investigations by means of nuclear quadrupole resonance (NQR) method, which includes radiospectrometer, multichannel spectrum analyzer and ISKRA 226.6 personal computer, is developed. Analog-to-digital converter (ADC) with buffer storage device, interface and microcomputer are used to process NQR-signals. ADS conversion time is no more, than 50 ns, linearity - 1%. Programs on Fourier analysis of NQR-signals and calculation of relaxation times are developed

  12. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V; Salic, Adrian

    2010-10-18

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu-Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu-Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu-Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu-Gli complexes, a process inhibited by PKA.

  13. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    Science.gov (United States)

    Tukachinsky, Hanna; Lopez, Lyle V.

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu–Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu–Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu–Gli complexes, a process inhibited by PKA. PMID:20956384

  14. Rheb may complex with RASSF1A to coordinate Hippo and TOR signaling.

    Science.gov (United States)

    Nelson, Nicholas; Clark, Geoffrey J

    2016-06-07

    The TOR pathway is a vital component of cellular homeostasis that controls the synthesis of proteins, nucleic acids and lipids. Its core is the TOR kinase. Activation of the TOR pathway suppresses autophagy, which plays a vital but complex role in tumorigenesis. The TOR pathway is regulated by activation of the Ras-related protein Rheb, which can bind mTOR. The Hippo pathway is a major growth control module that regulates cell growth, differentiation and apoptosis. Its core consists of an MST/LATS kinase cascade that can be activated by the RASSF1A tumor suppressor. The TOR and Hippo pathways may be coordinately regulated to promote cellular homeostasis. However, the links between the pathways remain only partially understood. We now demonstrate that in addition to mTOR regulation, Rheb also impacts the Hippo pathway by forming a complex with RASSF1A. Using stable clones of two human lung tumor cell lines (NCI-H1792 and NCI-H1299) with shRNA-mediated silencing or ectopic overexpression of RASSF1A, we show that activated Rheb stimulates the Hippo pathway, but is suppressed in its ability to stimulate the TOR pathway. Moreover, by selectively labeling autophagic vacuoles we show that RASSF1A inhibits the ability of Rheb to suppress autophagy and enhance cell growth. Thus, we identify a new connection that impacts coordination of Hippo and TOR signaling. As RASSF1A expression is frequently lost in human tumors, the RASSF1A status of a tumor may impact not just its Hippo pathway status, but also its TOR pathway status.

  15. Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema.

    Science.gov (United States)

    Ruwanpura, Saleela M; McLeod, Louise; Dousha, Lovisa F; Seow, Huei J; Alhayyani, Sultan; Tate, Michelle D; Deswaerte, Virginie; Brooks, Gavin D; Bozinovski, Steven; MacDonald, Martin; Garbers, Christoph; King, Paul T; Bardin, Philip G; Vlahos, Ross; Rose-John, Stefan; Anderson, Gary P; Jenkins, Brendan J

    2016-12-15

    The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL-6R), and trans-signaling via a naturally occurring soluble IL-6R. To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. We used the gp130 F/F genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  18. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv's Distribution for Quadratic Frequency Modulation Signals.

    Science.gov (United States)

    Jing, Fulong; Jiao, Shuhong; Hou, Changbo; Si, Weijian; Wang, Yu

    2017-06-21

    For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM) signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR) and the quadratic chirp rate (QCR) are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF) and modified scaled Fourier transform (mSFT), an effective parameter estimation algorithm is proposed-referred to as the Two-Dimensional product modified Lv's distribution (2D-PMLVD)-for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT) and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  19. Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway.

    Science.gov (United States)

    Nakada, Daisuke; Hirano, Yukinori; Sugimoto, Katsunori

    2004-11-01

    The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex consists of two highly related proteins, Mre11 and Rad50, and a third protein, Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction. We show here that the Mre11 complex functions together with exonuclease 1 (Exo1) in activation of the Mec1 signaling pathway after DNA damage and replication block. Mec1 controls the checkpoint responses following UV irradiation as well as DSB induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1 collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well. Accordingly, the Mre11 complex and Exo1 contribute to activation of the replication checkpoint pathway. Our results provide a model in which the Mre11 complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate Mec1 association with sites of DNA damage or replication block.

  20. A lossless multichannel bio-signal compression based on low-complexity joint coding scheme for portable medical devices.

    Science.gov (United States)

    Kim, Dong-Sun; Kwon, Jin-San

    2014-09-18

    Research on real-time health systems have received great attention during recent years and the needs of high-quality personal multichannel medical signal compression for personal medical product applications are increasing. The international MPEG-4 audio lossless coding (ALS) standard supports a joint channel-coding scheme for improving compression performance of multichannel signals and it is very efficient compression method for multi-channel biosignals. However, the computational complexity of such a multichannel coding scheme is significantly greater than that of other lossless audio encoders. In this paper, we present a multichannel hardware encoder based on a low-complexity joint-coding technique and shared multiplier scheme for portable devices. A joint-coding decision method and a reference channel selection scheme are modified for a low-complexity joint coder. The proposed joint coding decision method determines the optimized joint-coding operation based on the relationship between the cross correlation of residual signals and the compression ratio. The reference channel selection is designed to select a channel for the entropy coding of the joint coding. The hardware encoder operates at a 40 MHz clock frequency and supports two-channel parallel encoding for the multichannel monitoring system. Experimental results show that the compression ratio increases by 0.06%, whereas the computational complexity decreases by 20.72% compared to the MPEG-4 ALS reference software encoder. In addition, the compression ratio increases by about 11.92%, compared to the single channel based bio-signal lossless data compressor.

  1. Fixed-Point Algorithms for the Blind Separation of Arbitrary Complex-Valued Non-Gaussian Signal Mixtures

    Directory of Open Access Journals (Sweden)

    Douglas Scott C

    2007-01-01

    Full Text Available We derive new fixed-point algorithms for the blind separation of complex-valued mixtures of independent, noncircularly symmetric, and non-Gaussian source signals. Leveraging recently developed results on the separability of complex-valued signal mixtures, we systematically construct iterative procedures on a kurtosis-based contrast whose evolutionary characteristics are identical to those of the FastICA algorithm of Hyvarinen and Oja in the real-valued mixture case. Thus, our methods inherit the fast convergence properties, computational simplicity, and ease of use of the FastICA algorithm while at the same time extending this class of techniques to complex signal mixtures. For extracting multiple sources, symmetric and asymmetric signal deflation procedures can be employed. Simulations for both noiseless and noisy mixtures indicate that the proposed algorithms have superior finite-sample performance in data-starved scenarios as compared to existing complex ICA methods while performing about as well as the best of these techniques for larger data-record lengths.

  2. Bcl-xL acts downstream of caspase-8 activation by the CD95 death-inducing signaling complex

    NARCIS (Netherlands)

    Medema, J. P.; Scaffidi, C.; Krammer, P. H.; Peter, M. E.

    1998-01-01

    The Bcl-2 family member Bcl-xL has often been correlated with apoptosis resistance. We have shown recently that in peripheral human T cells resistance to CD95-mediated apoptosis is characterized by a lack of caspase-8 recruitment to the CD95 death-inducing signaling complex (DISC) and by increased

  3. Pseudo-stokes vector from complex signal representation of a speckle pattern and its applications to micro-displacement measurement

    DEFF Research Database (Denmark)

    Wang, W.; Ishijima, R.; Matsuda, A.

    2010-01-01

    As an improvement of the intensity correlation used widely in conventional electronic speckle photography, we propose a new technique for displacement measurement based on correlating Stokes-like parameters derivatives for transformed speckle patterns. The method is based on a Riesz transform of ...... are presented that demonstrate the validity and advantage of the proposed pseudo-Stokes vector correlation technique over conventional intensity correlation technique....... of the intensity speckle pattern, which converts the original real-valued signal into a complex signal. In closest analogy to the polarisation of a vector wave, the Stokes-like vector constructed from the spatial derivative of the generated complex signal has been applied for correlation. Experimental results...

  4. Analysis of progression of fatigue conditions in biceps brachii muscles using surface electromyography signals and complexity based features.

    Science.gov (United States)

    Karthick, P A; Makaram, Navaneethakrishna; Ramakrishnan, S

    2014-01-01

    Muscle fatigue is a neuromuscular condition where muscle performance decreases due to sustained or intense contraction. It is experienced by both normal and abnormal subjects. In this work, an attempt has been made to analyze the progression of muscle fatigue in biceps brachii muscles using surface electromyography (sEMG) signals. The sEMG signals are recorded from fifty healthy volunteers during dynamic contractions under well defined protocol. The acquired signals are preprocessed and segmented in to six equal parts for further analysis. The features, such as activity, mobility, complexity, sample entropy and spectral entropy are extracted from all six zones. The results are found showing that the extracted features except complexity feature have significant variations in differentiating non-fatigue and fatigue zone respectively. Thus, it appears that, these features are useful in automated analysis of various neuromuscular activities in normal and pathological conditions.

  5. An Adaptive Noise Cancellation System Based on Linear and Widely Linear Complex Valued Least Mean Square Algorithms for Removing Electrooculography Artifacts from Electroencephalography Signals

    Directory of Open Access Journals (Sweden)

    Engin Cemal MENGÜÇ

    2018-03-01

    Full Text Available In this study, an adaptive noise cancellation (ANC system based on linear and widely linear (WL complex valued least mean square (LMS algorithms is designed for removing electrooculography (EOG artifacts from electroencephalography (EEG signals. The real valued EOG and EEG signals (Fp1 and Fp2 given in dataset are primarily expressed as a complex valued signal in the complex domain. Then, using the proposed ANC system, the EOG artifacts are eliminated in the complex domain from the EEG signals. Expression of these signals in the complex domain allows us to remove EOG artifacts from two EEG channels simultaneously. Moreover, in this study, it has been shown that the complex valued EEG signal exhibits noncircular behavior, and in the case, the WL-CLMS algorithm enhances the performance of the ANC system compared to real-valued LMS and CLMS algorithms. Simulation results support the proposed approach.

  6. n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

    Science.gov (United States)

    Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

    2015-09-01

    This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling.

    Science.gov (United States)

    Wang, Hongzhong; Zou, Xinle; Wei, Zhuang; Wu, Yuan; Li, Rongxia; Zeng, Rong; Chen, Zhengjun; Liao, Kan

    2015-01-01

    The primary cilium is composed of an axoneme that protrudes from the cell surface, a basal body beneath the membrane and a transition neck in between. It is a sensory organelle on the plasma membrane, involved in mediating extracellular signals. In the transition neck region of the cilium, the microtubules change from triplet to doublet microtubules. This region also contains the transition fibres that crosslink the axoneme with the membrane and the necklace proteins that regulate molecules being transported into and out of the cilium. In this protein-enriched, complex area it is important to maintain the correct assembly of all of these proteins. Here, through immunofluorescent staining and protein isolation, we identify the molecular chaperone Hsp90α clustered at the periciliary base. At the transition neck region, phosphorylated Hsp90α forms a stable ring around the axoneme. Heat shock treatment causes Hsp90α to dissipate and induces resorption of cilia. We further identify that Hsp90α at the transition neck region represents a signalling platform on which IRS-1 interacts with intracellular downstream signalling molecules involved in IGF-1 receptor signalling. © 2015. Published by The Company of Biologists Ltd.

  8. Low complexity iterative MLSE equalization of M-QAM signals in extremely long rayleigh fading channels

    CSIR Research Space (South Africa)

    Myburgh, HC

    2009-05-01

    Full Text Available long channels. Its computational complexity is linear in the data block length and approximately independent of the channel memory length, whereas conventional equalization algorithms have computational complexity linear in the data block length...

  9. From PII signaling to metabolite sensing: a novel 2-oxoglutarate sensor that details PII-NAGK complex formation.

    Directory of Open Access Journals (Sweden)

    Jan Lüddecke

    Full Text Available The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specifically responded to 2-oxoglutarate. The impact of the fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon resonance spectroscopy and isothermal calorimetric experiments. The developed FRET sensor provides real-time data on PII - NAGK interaction and its modulation by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel insights into PII - NAGK complex formation: (i It revealed the formation of an encounter-complex between PII and NAGK, which holds the proteins in proximity even in the presence of inhibitors of complex formation; (ii It revealed that the PII T-loop residue Ser49 is neither essential for complex formation with NAGK nor for activation of the enzyme but necessary to form a stable complex and efficiently relieve NAGK from arginine inhibition; (iii It showed that arginine stabilizes the NAGK hexamer and stimulates PII - NAGK interaction.

  10. Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target of rapamycin complex 1 (mTORC1.

    Directory of Open Access Journals (Sweden)

    Gokhan Demirkan

    Full Text Available Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR complex 1 (mTORC1, which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2 affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo.

  11. ALGORITHM OF CARDIO COMPLEX DETECTION AND SORTING FOR PROCESSING THE DATA OF CONTINUOUS CARDIO SIGNAL MONITORING.

    Science.gov (United States)

    Krasichkov, A S; Grigoriev, E B; Nifontov, E M; Shapovalov, V V

    The paper presents an algorithm of cardio complex classification as part of processing the data of continuous cardiac monitoring. R-wave detection concurrently with cardio complex sorting is discussed. The core of this approach is the use of prior information about. cardio complex forms, segmental structure, and degree of kindness. Results of the sorting algorithm testing are provided.

  12. Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

    Science.gov (United States)

    Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

    2018-05-16

    Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

  13. Correlations between the signal complexity of cerebral and cardiac electrical activity: a multiscale entropy analysis.

    Directory of Open Access Journals (Sweden)

    Pei-Feng Lin

    Full Text Available The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG and a 19-channel eye-closed routine electroencephalography (EEG. Multiscale entropy (MSE analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS, and photic stimulation of slow frequencies (slow-PS of EEG in the 1-58 Hz frequency range, and three RR interval (RRI time series (awake-state, sleep and that concomitant with the EEG for each subject. The low-to-high frequency power (LF/HF ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse at Fp2, C4, T6 and T4; (b the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration.

  14. Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se [Department of Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, SE-106 91 Stockholm (Sweden); Bottai, Matteo, E-mail: Matteo.Bottai@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Westerholm, Roger, E-mail: Roger.Westerholm@anchem.su.se [Department of Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, SE-106 91 Stockholm (Sweden); Stenius, Ulla, E-mail: Ulla.Stenius@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Dreij, Kristian, E-mail: Kristian.Dreij@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden)

    2013-02-01

    Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

  15. Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

    International Nuclear Information System (INIS)

    Jarvis, Ian W.H.; Bergvall, Christoffer; Bottai, Matteo; Westerholm, Roger; Stenius, Ulla; Dreij, Kristian

    2013-01-01

    Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

  16. Maize and Arabidopsis ARGOS Proteins Interact with Ethylene Receptor Signaling Complex, Supporting a Regulatory Role for ARGOS in Ethylene Signal Transduction[OPEN

    Science.gov (United States)

    Shi, Jinrui; Wang, Hongyu; Habben, Jeffrey E.

    2016-01-01

    The phytohormone ethylene regulates plant growth and development as well as plant response to environmental cues. ARGOS genes reduce plant sensitivity to ethylene when overexpressed in transgenic Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). A previous genetic study suggested that the endoplasmic reticulum and Golgi-localized maize ARGOS1 targets the ethylene signal transduction components at or upstream of CONSTITUTIVE TRIPLE RESPONSE1, but the mechanism of ARGOS modulating ethylene signaling is unknown. Here, we demonstrate in Arabidopsis that ZmARGOS1, as well as the Arabidopsis ARGOS homolog ORGAN SIZE RELATED1, physically interacts with Arabidopsis REVERSION-TO-ETHYLENE SENSITIVITY1 (RTE1), an ethylene receptor interacting protein that regulates the activity of ETHYLENE RESPONSE1. The protein-protein interaction was also detected with the yeast split-ubiquitin two-hybrid system. Using the same yeast assay, we found that maize RTE1 homolog REVERSION-TO-ETHYLENE SENSITIVITY1 LIKE4 (ZmRTL4) and ZmRTL2 also interact with maize and Arabidopsis ARGOS proteins. Like AtRTE1 in Arabidopsis, ZmRTL4 and ZmRTL2 reduce ethylene responses when overexpressed in maize, indicating a similar mechanism for ARGOS regulating ethylene signaling in maize. A polypeptide fragment derived from ZmARGOS8, consisting of a Pro-rich motif flanked by two transmembrane helices that are conserved among members of the ARGOS family, can interact with AtRTE1 and maize RTL proteins in Arabidopsis. The conserved domain is necessary and sufficient to reduce ethylene sensitivity in Arabidopsis and maize. Overall, these results suggest a physical association between ARGOS and the ethylene receptor signaling complex via AtRTE1 and maize RTL proteins, supporting a role for ARGOS in regulating ethylene perception and the early steps of signal transduction in Arabidopsis and maize. PMID:27268962

  17. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade.

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-28

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  18. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-01

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  19. Investigating complex patterns of blocked intestinal artery blood pressure signals by empirical mode decomposition and linguistic analysis

    International Nuclear Information System (INIS)

    Yeh, J-R; Lin, T-Y; Shieh, J-S; Chen, Y; Huang, N E; Wu, Z; Peng, C-K

    2008-01-01

    In this investigation, surgical operations of blocked intestinal artery have been conducted on pigs to simulate the condition of acute mesenteric arterial occlusion. The empirical mode decomposition method and the algorithm of linguistic analysis were applied to verify the blood pressure signals in simulated situation. We assumed that there was some information hidden in the high-frequency part of the blood pressure signal when an intestinal artery is blocked. The empirical mode decomposition method (EMD) has been applied to decompose the intrinsic mode functions (IMF) from a complex time series. But, the end effects and phenomenon of intermittence damage the consistence of each IMF. Thus, we proposed the complementary ensemble empirical mode decomposition method (CEEMD) to solve the problems of end effects and the phenomenon of intermittence. The main wave of blood pressure signals can be reconstructed by the main components, identified by Monte Carlo verification, and removed from the original signal to derive a riding wave. Furthermore, the concept of linguistic analysis was applied to design the blocking index to verify the pattern of riding wave of blood pressure using the measurements of dissimilarity. Blocking index works well to identify the situation in which the sampled time series of blood pressure signal was recorded. Here, these two totally different algorithms are successfully integrated and the existence of the existence of information hidden in high-frequency part of blood pressure signal has been proven

  20. Investigating complex patterns of blocked intestinal artery blood pressure signals by empirical mode decomposition and linguistic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, J-R; Lin, T-Y; Shieh, J-S [Department of Mechanical Engineering, Yuan Ze University, 135 Far-East Road, Chung-Li, Taoyuan, Taiwan (China); Chen, Y [Far Eastern Memorial Hospital, Taiwan (China); Huang, N E [Research Center for Adaptive Data Analysis, National Central University, Taiwan (China); Wu, Z [Center for Ocean-Land-Atmosphere Studies (United States); Peng, C-K [Beth Israel Deaconess Medical Center, Harvard Medical School (United States)], E-mail: s939205@ mail.yzu.edu.tw

    2008-02-15

    In this investigation, surgical operations of blocked intestinal artery have been conducted on pigs to simulate the condition of acute mesenteric arterial occlusion. The empirical mode decomposition method and the algorithm of linguistic analysis were applied to verify the blood pressure signals in simulated situation. We assumed that there was some information hidden in the high-frequency part of the blood pressure signal when an intestinal artery is blocked. The empirical mode decomposition method (EMD) has been applied to decompose the intrinsic mode functions (IMF) from a complex time series. But, the end effects and phenomenon of intermittence damage the consistence of each IMF. Thus, we proposed the complementary ensemble empirical mode decomposition method (CEEMD) to solve the problems of end effects and the phenomenon of intermittence. The main wave of blood pressure signals can be reconstructed by the main components, identified by Monte Carlo verification, and removed from the original signal to derive a riding wave. Furthermore, the concept of linguistic analysis was applied to design the blocking index to verify the pattern of riding wave of blood pressure using the measurements of dissimilarity. Blocking index works well to identify the situation in which the sampled time series of blood pressure signal was recorded. Here, these two totally different algorithms are successfully integrated and the existence of the existence of information hidden in high-frequency part of blood pressure signal has been proven.

  1. Preprotein import into chloroplasts via the Toc and Tic complexes is regulated by redox signals in Pisum sativum.

    Science.gov (United States)

    Stengel, Anna; Benz, J Philipp; Buchanan, Bob B; Soll, Jürgen; Bölter, Bettina

    2009-11-01

    The import of nuclear-encoded preproteins is necessary to maintain chloroplast function. The recognition and transfer of most precursor proteins across the chloroplast envelopes are facilitated by two membrane-inserted protein complexes, the translocons of the chloroplast outer and inner envelope (Toc and Tic complexes, respectively). Several signals have been invoked to regulate the import of preproteins. In our study, we were interested in redox-based import regulation mediated by two signals: regulation based on thiols and on the metabolic NADP+/NADPH ratio. We sought to identify the proteins participating in the regulation of these transport pathways and to characterize the preprotein subgroups whose import is redox-dependent. Our results provide evidence that the formation and reduction of disulfide bridges in the Toc receptors and Toc translocation channel have a strong influence on import yield of all tested preproteins that depend on the Toc complex for translocation. Furthermore, the metabolic NADP+/NADPH ratio influences not only the composition of the Tic complex, but also the import efficiency of most, but not all, preproteins tested. Thus, several Tic subcomplexes appear to participate in the translocation of different preprotein subgroups, and the redox-active components of these complexes likely play a role in regulating transport.

  2. Effect of harmonicity on the detection of a signal in a complex masker and on spatial release from masking.

    Directory of Open Access Journals (Sweden)

    Astrid Klinge

    Full Text Available The amount of masking of sounds from one source (signals by sounds from a competing source (maskers heavily depends on the sound characteristics of the masker and the signal and on their relative spatial location. Numerous studies investigated the ability to detect a signal in a speech or a noise masker or the effect of spatial separation of signal and masker on the amount of masking, but there is a lack of studies investigating the combined effects of many cues on the masking as is typical for natural listening situations. The current study using free-field listening systematically evaluates the combined effects of harmonicity and inharmonicity cues in multi-tone maskers and cues resulting from spatial separation of target signal and masker on the detection of a pure tone in a multi-tone or a noise masker. A linear binaural processing model was implemented to predict the masked thresholds in order to estimate whether the observed thresholds can be accounted for by energetic masking in the auditory periphery or whether other effects are involved. Thresholds were determined for combinations of two target frequencies (1 and 8 kHz, two spatial configurations (masker and target either co-located or spatially separated by 90 degrees azimuth, and five different masker types (four complex multi-tone stimuli, one noise masker. A spatial separation of target and masker resulted in a release from masking for all masker types. The amount of masking significantly depended on the masker type and frequency range. The various harmonic and inharmonic relations between target and masker or between components of the masker resulted in a complex pattern of increased or decreased masked thresholds in comparison to the predicted energetic masking. The results indicate that harmonicity cues affect the detectability of a tonal target in a complex masker.

  3. Entamoeba histolytica: a beta 1 integrin-like fibronectin receptor assembles a signaling complex similar to those of mammalian cells.

    Science.gov (United States)

    Flores-Robles, Donaciano; Rosales, Carlos; Rosales-Encina, José Luis; Talamás-Rohana, Patricia

    2003-01-01

    During tissue invasion, Entamoeba histolytica trophozoites interact with endothelial cells and extracellular matrix (ECM) proteins such as fibronectin (FN), collagen, and laminin. It has been demonstrated that trophozoites interact with FN through a beta1 integrin-like FN receptor (beta 1EhFNR), activating tyrosine kinases. In order to characterize the signaling process triggered by the amoebic receptor, activation, and association of tyrosine kinases and structural proteins were determined. As a result of FN binding by the beta 1EhFNR, the receptor itself, FAK, and paxillin were phosphorylated in tyrosine. Co-immunoprecipitation experiments showed that a multimolecular signaling complex was formed by the amoebic FN receptor, FAK, paxillin, and vinculin. These results strongly suggest that a signaling pathway, similar to the one used in mammalian cells, is activated when E. histolytica trophozoites adhere to FN.

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

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

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

  5. CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

    Directory of Open Access Journals (Sweden)

    Matous Hrdinka

    2016-03-01

    Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

  6. Conformational coupling between receptor and kinase binding sites through a conserved salt bridge in a signaling complex scaffold protein.

    Directory of Open Access Journals (Sweden)

    Davi R Ortega

    Full Text Available Bacterial chemotaxis is one of the best studied signal transduction pathways. CheW is a scaffold protein that mediates the association of the chemoreceptors and the CheA kinase in a ternary signaling complex. The effects of replacing conserved Arg62 of CheW with other residues suggested that the scaffold protein plays a more complex role than simply binding its partner proteins. Although R62A CheW had essentially the same affinity for chemoreceptors and CheA, cells expressing the mutant protein are impaired in chemotaxis. Using a combination of molecular dynamics simulations (MD, NMR spectroscopy, and circular dichroism (CD, we addressed the role of Arg62. Here we show that Arg62 forms a salt bridge with another highly conserved residue, Glu38. Although this interaction is unimportant for overall protein stability, it is essential to maintain the correct alignment of the chemoreceptor and kinase binding sites of CheW. Computational and experimental data suggest that the role of the salt bridge in maintaining the alignment of the two partner binding sites is fundamental to the function of the signaling complex but not to its assembly. We conclude that a key feature of CheW is to maintain the specific geometry between the two interaction sites required for its function as a scaffold.

  7. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Madsen, Mette; Moestrup, Søren K

    2002-01-01

    as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular...

  8. Wing, tail, and vocal contributions to the complex acoustic signals of courting Calliope hummingbirds

    Directory of Open Access Journals (Sweden)

    Christopher James CLARK

    2011-04-01

    Full Text Available Multi-component signals contain multiple signal parts expressed in the same physical modality. One way to identify individual components is if they are produced by different physical mechanisms. Here, I studied the mechanisms generating acoustic signals in the courtship displays of the Calliope hummingbird Stellula calliope. Display dives consisted of three synchronized sound elements, a high-frequency tone (hft, a low frequency tone (lft, and atonal sound pulses (asp, which were then followed by a frequency-modulated fall. Manipulating any of the rectrices (tail-feathers of wild males impaired production of the lft and asp but not the hft or fall, which are apparently vocal. I tested the sound production capabilities of the rectrices in a wind tunnel. Single rectrices could generate the lft but not the asp, whereas multiple rectrices tested together produced sounds similar to the asp when they fluttered and collided with their neighbors percussively, representing a previously unknown mechanism of sound production. During the shuttle display, a trill is generated by the wings during pulses in which the wingbeat frequency is elevated to 95 Hz, 40% higher than the typical hovering wingbeat frequency. The Calliope hummingbird courtship displays include sounds produced by three independent mechanisms, and thus include a minimum of three acoustic signal components. These acoustic mechanisms have different constraints and thus potentially contain different messages. Producing multiple acoustic signals via multiple mechanisms may be a way to escape the constraints present in any single mechanism [Current Zoology 57 (2: 187–196, 2011].

  9. Precise Temporal Profiling of Signaling Complexes in Primary Cells Using SWATH Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Etienne Caron

    2017-03-01

    Full Text Available Spatiotemporal organization of protein interactions in cell signaling is a fundamental process that drives cellular functions. Given differential protein expression across tissues and developmental stages, the architecture and dynamics of signaling interaction proteomes is, likely, highly context dependent. However, current interaction information has been almost exclusively obtained from transformed cells. In this study, we applied an advanced and robust workflow combining mouse genetics and affinity purification (AP-SWATH mass spectrometry to profile the dynamics of 53 high-confidence protein interactions in primary T cells, using the scaffold protein GRB2 as a model. The workflow also provided a sufficient level of robustness to pinpoint differential interaction dynamics between two similar, but functionally distinct, primary T cell populations. Altogether, we demonstrated that precise and reproducible quantitative measurements of protein interaction dynamics can be achieved in primary cells isolated from mammalian tissues, allowing resolution of the tissue-specific context of cell-signaling events.

  10. The biology of skin wetness perception and its implications in manual function and for reproducing complex somatosensory signals in neuroprosthetics

    Science.gov (United States)

    Ackerley, Rochelle

    2017-01-01

    Our perception of skin wetness is generated readily, yet humans have no known receptor (hygroreceptor) to signal this directly. It is easy to imagine the sensation of water running over our hands or the feel of rain on our skin. The synthetic sensation of wetness is thought to be produced from a combination of specific skin thermal and tactile inputs, registered through thermoreceptors and mechanoreceptors, respectively. The present review explores how thermal and tactile afference from the periphery can generate the percept of wetness centrally. We propose that the main signals include information about skin cooling, signaled primarily by thinly myelinated thermoreceptors, and rapid changes in touch, through fast-conducting, myelinated mechanoreceptors. Potential central sites for integration of these signals, and thus the perception of skin wetness, include the primary and secondary somatosensory cortices and the insula cortex. The interactions underlying these processes can also be modeled to aid in understanding and engineering the mechanisms. Furthermore, we discuss the role that sensing wetness could play in precision grip and the dexterous manipulation of objects. We expand on these lines of inquiry to the application of the knowledge in designing and creating skin sensory feedback in prosthetics. The addition of real-time, complex sensory signals would mark a significant advance in the use and incorporation of prosthetic body parts for amputees in everyday life. PMID:28123008

  11. Stream computing for biomedical signal processing: A QRS complex detection case-study.

    Science.gov (United States)

    Murphy, B M; O'Driscoll, C; Boylan, G B; Lightbody, G; Marnane, W P

    2015-01-01

    Recent developments in "Big Data" have brought significant gains in the ability to process large amounts of data on commodity server hardware. Stream computing is a relatively new paradigm in this area, addressing the need to process data in real time with very low latency. While this approach has been developed for dealing with large scale data from the world of business, security and finance, there is a natural overlap with clinical needs for physiological signal processing. In this work we present a case study of streams processing applied to a typical physiological signal processing problem: QRS detection from ECG data.

  12. [Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

    Science.gov (United States)

    Vanin, A F

    2004-01-01

    The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

  13. The quantitative evaluation of complex defect signals from eddy current testings with multi-frequency methods

    International Nuclear Information System (INIS)

    Naegele, W.

    1982-01-01

    The usual formulation of multi-frequency eddy current signals of large defects by linearized impedance diagrams may lead to misinterpretations. Here a developement of the linear superposition principle is proposed, which takes into account also the curvature of the impedance diagrams thus allowing to identify even large defects in an unambiguous way. (orig.) [de

  14. Temporal signal energy correction and low-complexity encoder feedback for lossy scalable video coding

    NARCIS (Netherlands)

    Loomans, M.J.H.; Koeleman, C.J.; With, de P.H.N.

    2010-01-01

    In this paper, we address two problems found in embedded implementations of Scalable Video Codecs (SVCs): the temporal signal energy distribution and frame-to-frame quality fluctuations. The unequal energy distribution between the low- and high-pass band with integer-based wavelets leads to

  15. Conceptualization of the Complex Outcomes of Sexual Abuse: A Signal Detection Analysis

    Science.gov (United States)

    Pechtel, Pia; Evans, Ian M.; Podd, John V.

    2011-01-01

    Eighty-five New Zealand based practitioners experienced in treating adults with a history of child sexual abuse participated in an online judgment study of child sexual abuse outcomes using signal detection theory methodology. Participants' level of sensitivity was assessed independent of their degree of response bias when discriminating (a) known…

  16. Signal-to-Noise ratio and design complexity based on Unified Loss ...

    African Journals Online (AJOL)

    Taguchi's quality loss function for larger-the-better performance characteristics uses a reciprocal transformation to compute quality loss. This paper suggests that reciprocal transformation unnecessarily complicates and may distort results. Examples of this distortion include the signal-to-noise ratio based on mean squared ...

  17. Cytoplasmic organelles determine complexity and specificity of calcium signalling in adrenal chromaffin cells

    Czech Academy of Sciences Publication Activity Database

    Garsia-Sancho, J.; Verkhratsky, Alexei

    2008-01-01

    Roč. 192, č. 2 (2008), s. 263-271 ISSN 1748-1708 Institutional research plan: CEZ:AV0Z50390512 Keywords : Ca2+ signalling * calcium microdomains * chromaffin cells Subject RIV: JE - Non-nuclear Energetics, Energy Consumption ; Use Impact factor: 2.455, year: 2008

  18. Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

    Science.gov (United States)

    Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

    2013-10-29

    In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

  19. Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex.

    Science.gov (United States)

    Campanello, Gregory C; Lofgren, Michael; Yokom, Adam L; Southworth, Daniel R; Banerjee, Ruma

    2017-10-27

    G-proteins regulate various processes ranging from DNA replication and protein synthesis to cytoskeletal dynamics and cofactor assimilation and serve as models for uncovering strategies deployed for allosteric signal transduction. MeaB is a multifunctional G-protein chaperone, which gates loading of the active 5'-deoxyadenosylcobalamin cofactor onto methylmalonyl-CoA mutase (MCM) and precludes loading of inactive cofactor forms. MeaB also safeguards MCM, which uses radical chemistry, against inactivation and rescues MCM inactivated during catalytic turnover by using the GTP-binding energy to offload inactive cofactor. The conserved switch I and II signaling motifs used by G-proteins are predicted to mediate allosteric regulation in response to nucleotide binding and hydrolysis in MeaB. Herein, we targeted conserved residues in the MeaB switch I motif to interrogate the function of this loop. Unexpectedly, the switch I mutations had only modest effects on GTP binding and on GTPase activity and did not perturb stability of the MCM-MeaB complex. However, these mutations disrupted multiple MeaB chaperone functions, including cofactor editing, loading, and offloading. Hence, although residues in the switch I motif are not essential for catalysis, they are important for allosteric regulation. Furthermore, single-particle EM analysis revealed, for the first time, the overall architecture of the MCM-MeaB complex, which exhibits a 2:1 stoichiometry. These EM studies also demonstrate that the complex exhibits considerable conformational flexibility. In conclusion, the switch I element does not significantly stabilize the MCM-MeaB complex or influence the affinity of MeaB for GTP but is required for transducing signals between MeaB and MCM. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Complex signal-based optical coherence tomography angiography enables in vivo visualization of choriocapillaris in human choroid

    Science.gov (United States)

    Chu, Zhongdi; Chen, Chieh-Li; Zhang, Qinqin; Pepple, Kathryn; Durbin, Mary; Gregori, Giovanni; Wang, Ruikang K.

    2017-12-01

    The choriocapillaris (CC) plays an essential role in maintaining the normal functions of the human eye. There is increasing interest in the community to develop an imaging technique for visualizing the CC, yet this remains underexplored due to technical limitations. We propose an approach for the visualization of the CC in humans via a complex signal-based optical microangiography (OMAG) algorithm, based on commercially available spectral domain optical coherence tomography (SD-OCT). We show that the complex signal-based OMAG was superior to both the phase and amplitude signal-based approaches in detailing the vascular lobules previously seen with histological analysis. With this improved ability to visualize the lobular vascular networks, it is possible to identify the feeding arterioles and draining venules around the lobules, which is important in understanding the role of the CC in the pathogenesis of ocular diseases. With built-in FastTrac™ and montage scanning capabilities, we also demonstrate wide-field SD-OCT angiograms of the CC with a field of view at 9×11 mm2.

  1. Influence of multi-microphone signal enhancement algorithms on auditory movement detection in acoustically complex situations

    DEFF Research Database (Denmark)

    Lundbeck, Micha; Hartog, Laura; Grimm, Giso

    2017-01-01

    The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that interfering sounds impaired the detectability of left-right source movements and reverberation that of near-far source...... movements for elderly hearing-impaired (EHI) listeners (Lundbeck et al., 2017). Here, we explored potential ways of improving these deficits with HAs. To that end, we carried out acoustic analyses to examine the impact of two beamforming algorithms and a binaural coherence-based noise reduction scheme...... on the cues underlying movement perception. While binaural cues remained mostly unchanged, there were greater monaural spectral changes and increases in signal-to-noise ratio and direct-to-reverberant sound ratio as a result of the applied processing. Based on these findings, we conducted a listening test...

  2. Acoustic wave focusing in complex media using Nonlinear Time Reversal coded signal processing

    Czech Academy of Sciences Publication Activity Database

    Dos Santos, S.; Dvořáková, Zuzana; Lints, M.; Kůs, V.; Salupere, A.; Převorovský, Zdeněk

    2014-01-01

    Roč. 19, č. 12 (2014) ISSN 1435-4934. [European Conference on Non-Destructive Testing (ECNDT 2014) /11./. Praha, 06.10.2014-10.10.2014] Institutional support: RVO:61388998 Keywords : ultrasonic testing (UT) * signal processing * TR- NEWS * nonlinear time reversal * NDT * nonlinear acoustics Subject RIV: BI - Acoustics http://www.ndt.net/events/ECNDT2014/app/content/Slides/590_DosSantos_Rev1.pdf

  3. Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.

    Science.gov (United States)

    Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

    2008-01-04

    The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.

  4. Abnormal Cell Properties and Down-Regulated FAK-Src Complex Signaling in B Lymphoblasts of Autistic Subjects

    Science.gov (United States)

    Wei, Hongen; Malik, Mazhar; Sheikh, Ashfaq M.; Merz, George; Ted Brown, W.; Li, Xiaohong

    2011-01-01

    Recent studies suggest that one of the major pathways to the pathogenesis of autism is reduced cell migration. Focal adhesion kinase (FAK) has an important role in neural migration, dendritic morphological characteristics, axonal branching, and synapse formation. The FAK-Src complex, activated by upstream reelin and integrin β1, can initiate a cascade of phosphorylation events to trigger multiple intracellular pathways, including mitogen-activated protein kinase–extracellular signal–regulated kinase and phosphatidylinositol 3-kinase–Akt signaling. In this study, by using B lymphoblasts as a model, we tested whether integrin β1 and FAK-Src signaling are abnormally regulated in autism and whether abnormal FAK-Src signaling leads to defects in B-lymphoblast adhesion, migration, proliferation, and IgG production. To our knowledge, for the first time, we show that protein expression levels of both integrin β1 and FAK are significantly decreased in autistic lymphoblasts and that Src protein expression and the phosphorylation of an active site (Y416) are also significantly decreased. We also found that lymphoblasts from autistic subjects exhibit significantly decreased migration, increased adhesion properties, and an impaired capacity for IgG production. The overexpression of FAK in autistic lymphoblasts countered the adhesion and migration defects. In addition, we demonstrate that FAK mediates its effect through the activation of Src, phosphatidylinositol 3-kinase–Akt, and mitogen-activated protein kinase signaling cascades and that paxillin is also likely involved in the regulation of adhesion and migration in autistic lymphoblasts. PMID:21703394

  5. Improving the arterial input function in dynamic contrast enhanced MRI by fitting the signal in the complex plane.

    Science.gov (United States)

    Simonis, Frank F J; Sbrizzi, Alessandro; Beld, Ellis; Lagendijk, Jan J W; van den Berg, Cornelis A T

    2016-10-01

    Dynamic contrast enhanced (DCE) imaging is a widely used technique in oncologic imaging. An essential prerequisite for obtaining quantitative values from DCE-MRI is the determination of the arterial input function (AIF). However, it is very challenging to accurately estimate the AIF using MR. A comprehensive model, which uses complex data instead of either magnitude or phase, was developed to improve AIF estimation. The model was first applied to simulated data. Subsequently, the accuracy of the estimated contrast agent concentration was validated in a phantom. Finally the method was applied to existing DCE scans of 13 prostate cancer patients. The complex signal method combines the complementary strengths of the magnitude and phase method, increasing the precision and accuracy of concentration estimation in simulated and phantom data. The in vivo AIFs show a good agreement between arterial voxels (standard deviation in the peak and tail equal 0.4 mM and 0.12 mM, respectively). Furthermore, the dynamic behavior closely followed the AIF obtained with DCE-CT in the same patients (mean correlation coefficient: 0.92). By using the complex signal, the AIF estimation becomes more accurate and precise. This might enable patient specific AIFs, thereby improving the quantitative values obtained from DCE-MRI. Magn Reson Med 76:1236-1245, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. Price computation in electricity auctions with complex rules: An analysis of investment signals

    International Nuclear Information System (INIS)

    Vazquez, Carlos; Hallack, Michelle; Vazquez, Miguel

    2017-01-01

    This paper discusses the problem of defining marginal costs when integer variables are present, in the context of short-term power auctions. Most of the proposals for price computation existing in the literature are concerned with short-term competitive equilibrium (generators should not be willing to change the dispatch assigned to them by the auctioneer), which implies operational-cost recovery for all of the generators accepted in the auction. However, this is in general not enough to choose between the different pricing schemes. We propose to include an additional criterion in order to discriminate among different pricing schemes: prices have to be also signals for generation expansion. Using this condition, we arrive to a single solution to the problem of defining prices, where they are computed as the shadow prices of the balance equations in a linear version of the unit commitment problem. Importantly, not every linearization of the unit commitment is valid; we develop the conditions for this linear model to provide adequate investment signals. Compared to other proposals in the literature, our results provide a strong motivation for the pricing scheme and a simple method for price computation. - Highlights: • Pricing proposals in power markets often deal with just accounting-cost recovery. • Including opportunity costs is an additional property required for efficient pricing. • We develop a framework to analyze the pricing proposals found in the literature. • We propose a pricing mechanism to include the costs of short-run integer decisions. • As it includes short-run opportunity costs, it provides efficient long-term signals.

  7. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection

    DEFF Research Database (Denmark)

    Carson, Christian T; Orazio, Nicole I; Lee, Darwin V

    2009-01-01

    The protein kinases ataxia-telangiectasia mutated (ATM) and ATM-Rad3 related (ATR) are activated in response to DNA damage, genotoxic stress and virus infections. Here we show that during infection with wild-type adenovirus, ATR and its cofactors RPA32, ATRIP and TopBP1 accumulate at viral...... during virus infection, which is independent of Mre11 nuclease activity and recruitment of RPA/ATR/ATRIP/TopBP1. Unlike other damage scenarios, we found that ATM and ATR signaling are not dependent on each other during infection. We identify a region of the viral E4orf3 protein responsible...

  8. Low-Complexity Iterative Receiver for Space-Time Coded Signals over Frequency Selective Channels

    Directory of Open Access Journals (Sweden)

    Mohamed Siala

    2002-05-01

    Full Text Available We propose a low-complexity turbo-detector scheme for frequency selective multiple-input multiple-output channels. The detection part of the receiver is based on a List-type MAP equalizer which is a state-reduction algorithm of the MAP algorithm using per-survivor technique. This alternative achieves a good tradeoff between performance and complexity provided a small amount of the channel is neglected. In order to induce the good performance of this equalizer, we propose to use a whitened matched filter (WMF which leads to a white-noise “minimum phase” channel model. Simulation results show that the use of the WMF yields significant improvement, particularly over severe channels. Thanks to the iterative turbo processing (detection and decoding are iterated several times, the performance loss due to the use of the suboptimum List-type equalizer is recovered.

  9. Broad-Complex acts downstream of Met in juvenile hormone signaling to coordinate primitive holometabolan metamorphosis

    Czech Academy of Sciences Publication Activity Database

    Konopová, Barbora; Jindra, Marek

    2008-01-01

    Roč. 135, č. 3 (2008), s. 559-568 ISSN 0950-1991 R&D Projects: GA ČR(CZ) GA204/07/1032; GA AV ČR IAA5007305; GA MŠk LC07032 Institutional research plan: CEZ:AV0Z50070508 Keywords : metamorphosis * juvenile hormone * broad-complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.812, year: 2008

  10. Gold nanoparticle-mediated laser stimulation causes a complex stress signal in neuronal cells

    Science.gov (United States)

    Johannsmeier, Sonja; Heeger, Patrick; Terakawa, Mitsuhiro; Kalies, Stefan; Heisterkamp, Alexander; Ripken, Tammo; Heinemann, Dag

    2017-07-01

    Gold nanoparticle mediated laser stimulation of neuronal cells allows for cell activation on a single-cell level. It could therefore be considered an alternative to classical electric neurostimulation. The physiological impact of this new approach has not been intensively studied so far. Here, we investigate the targeted cell's reaction to a laser stimulus based on its calcium response. A complex cellular reaction involving multiple sources has been revealed.

  11. The biology of skin wetness perception and its implications in manual function and for reproducing complex somatosensory signals in neuroprosthetics.

    Science.gov (United States)

    Filingeri, Davide; Ackerley, Rochelle

    2017-04-01

    Our perception of skin wetness is generated readily, yet humans have no known receptor (hygroreceptor) to signal this directly. It is easy to imagine the sensation of water running over our hands or the feel of rain on our skin. The synthetic sensation of wetness is thought to be produced from a combination of specific skin thermal and tactile inputs, registered through thermoreceptors and mechanoreceptors, respectively. The present review explores how thermal and tactile afference from the periphery can generate the percept of wetness centrally. We propose that the main signals include information about skin cooling, signaled primarily by thinly myelinated thermoreceptors, and rapid changes in touch, through fast-conducting, myelinated mechanoreceptors. Potential central sites for integration of these signals, and thus the perception of skin wetness, include the primary and secondary somatosensory cortices and the insula cortex. The interactions underlying these processes can also be modeled to aid in understanding and engineering the mechanisms. Furthermore, we discuss the role that sensing wetness could play in precision grip and the dexterous manipulation of objects. We expand on these lines of inquiry to the application of the knowledge in designing and creating skin sensory feedback in prosthetics. The addition of real-time, complex sensory signals would mark a significant advance in the use and incorporation of prosthetic body parts for amputees in everyday life. NEW & NOTEWORTHY Little is known about the underlying mechanisms that generate the perception of skin wetness. Humans have no specific hygroreceptor, and thus temperature and touch information combine to produce wetness sensations. The present review covers the potential mechanisms leading to the perception of wetness, both peripherally and centrally, along with their implications for manual function. These insights are relevant to inform the design of neuroengineering interfaces, such as sensory

  12. Low-complexity R-peak detection in ECG signals: a preliminary step towards ambulatory fetal monitoring.

    Science.gov (United States)

    Rooijakkers, Michiel; Rabotti, Chiara; Bennebroek, Martijn; van Meerbergen, Jef; Mischi, Massimo

    2011-01-01

    Non-invasive fetal health monitoring during pregnancy has become increasingly important. Recent advances in signal processing technology have enabled fetal monitoring during pregnancy, using abdominal ECG recordings. Ubiquitous ambulatory monitoring for continuous fetal health measurement is however still unfeasible due to the computational complexity of noise robust solutions. In this paper an ECG R-peak detection algorithm for ambulatory R-peak detection is proposed, as part of a fetal ECG detection algorithm. The proposed algorithm is optimized to reduce computational complexity, while increasing the R-peak detection quality compared to existing R-peak detection schemes. Validation of the algorithm is performed on two manually annotated datasets, the MIT/BIH Arrhythmia database and an in-house abdominal database. Both R-peak detection quality and computational complexity are compared to state-of-the-art algorithms as described in the literature. With a detection error rate of 0.22% and 0.12% on the MIT/BIH Arrhythmia and in-house databases, respectively, the quality of the proposed algorithm is comparable to the best state-of-the-art algorithms, at a reduced computational complexity.

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

    Directory of Open Access Journals (Sweden)

    Isabelle George

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

  14. Design of complete software GPS signal simulator with low complexity and precise multipath channel model

    Directory of Open Access Journals (Sweden)

    G. Arul Elango

    2016-09-01

    Full Text Available The need for GPS data simulators have become important due to the tremendous growth in the design of versatile GPS receivers. Commercial hardware and software based GPS simulators are expensive and time consuming. In this work, a low cost simple novel GPS L1 signal simulator is designed for testing and evaluating the performance of software GPS receiver in a laboratory environment. A typical real time paradigm, similar to actual satellite derived GPS signal is created on a computer generated scenario. In this paper, a GPS software simulator is proposed that may offer a lot of analysis and testing flexibility to the researchers and developers as it is totally software based primarily running on a laptop/personal computer without the requirement of any hardware. The proposed GPS simulator allows provision for re-configurability and test repeatability and is developed in VC++ platform to minimize the simulation time. It also incorporates Rayleigh multipath channel fading model under non-line of sight (NLOS conditions. In this work, to efficiently design the simulator, several Rayleigh fading models viz. Inverse Discrete Fourier Transform (IDFT, Filtering White Gaussian Noise (FWFN and modified Sum of Sinusoidal (SOS simulators are tested and compared in terms of accuracy of its first and second order statistical metrics, execution time and the later one is found to be as the best appropriate Rayleigh multipath model suitable for incorporating with GPS simulator. The fading model written in ‘MATLAB’ engine has been linked with software GPS simulator module enable to test GPS receiver’s functionality in different fading environments.

  15. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Directory of Open Access Journals (Sweden)

    Tae Sik Goh

    2017-01-01

    Full Text Available IL-7 signaling via IL-7Rα and common γ-chain (γc is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα.

  16. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Science.gov (United States)

    Goh, Tae Sik; Jo, Yuna; Lee, Byunghyuk; Kim, Geona; Hwang, Hyunju; Ko, Eunhee; Kang, Seung Wan; Oh, Sae-Ock; Baek, Sun-Yong; Yoon, Sik; Lee, Jung Sub

    2017-01-01

    IL-7 signaling via IL-7Rα and common γ-chain (γc) is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα. PMID:28127156

  17. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    Science.gov (United States)

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

    2017-04-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

  18. Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis.

    Science.gov (United States)

    Hu, Fang; Xu, Yong; Liu, Feng

    2016-06-01

    Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes. Copyright © 2016 the American Physiological Society.

  19. Metal Dependence of Signal Transmission through MolecularQuantum-Dot Cellular Automata (QCA: A Theoretical Studyon Fe, Ru, and Os Mixed-Valence Complexes

    Directory of Open Access Journals (Sweden)

    Ken Tokunaga

    2010-08-01

    Full Text Available Dynamic behavior of signal transmission through metal complexes [L5M-BL-ML5]5+ (M=Fe, Ru, Os, BL=pyrazine (py, 4,4’-bipyridine (bpy, L=NH3, which are simplified models of the molecular quantum-dot cellular automata (molecular QCA, is discussed from the viewpoint of one-electron theory, density functional theory. It is found that for py complexes, the signal transmission time (tst is Fe(0.6 fs < Os(0.7 fs < Ru(1.1 fs and the signal amplitude (A is Fe(0.05 e < Os(0.06 e < Ru(0.10 e. For bpy complexes, tst and A are Fe(1.4 fs < Os(1.7 fs < Ru(2.5 fs and Os(0.11 e < Ru(0.12 e complexes generally have stronger signal amplitude, but waste longer time for signal transmission than py complexes. Among all complexes, Fe complex with bpy BL shows the best result. These results are discussed from overlap integral and energy gap of molecular orbitals.

  20. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

    Science.gov (United States)

    Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

    2014-07-22

    The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

  1. Close relationship between fMRI signals and transient heart rate changes accompanying K-complex. Simultaneous EEG/fMRI study

    International Nuclear Information System (INIS)

    Kan, Shigeyuki; Koike, Takahiko; Miyauchi, Satoru; Misaki, Masaya

    2009-01-01

    Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) allows the investigation of spontaneous activities in the human brain. Recently, by using this technique, increases in fMRI signal accompanying transient EEG activities such as sleep spindles and slow waves were reported. Although these fMRI signal increases appear to arise as a result of the neural activities being reflected in the EEG, when the influence of physiological activities upon fMRI signals are taken into consideration, it is highly controversial that fMRI signal increases accompanying transient EEG activities reflect actual neural activities. In the present study, we conducted simultaneous fMRI and polysomnograph recording of 18 normal adults, to study the effect of transient heart rate changes after a K-complex on fMRI signals. Significant fMRI signal increase was observed in the cerebellum, the ventral thalamus, the dorsal part of the brainstem, the periventricular white matter and the ventricle (quadrigeminal cistern). On the other hand, significant fMRI signal decrease was observed only in the right insula. Moreover, intensities of fMRI signal increase that was accompanied by a K-complex correlated positively with the magnitude of heart rate changes after a K-complex. Previous studies have reported that K-complex is closely related with sympathetic nervous activity and that the attributes of perfusion regulation in the brain differ during wakefulness and sleep. By taking these findings into consideration, our present results indicate that a close relationship exists between a K-complex and the changes in cardio- and neurovascular regulations that are mediated by the autonomic nervous system during sleep; further, these results indicate that transient heart rate changes after a K-complex can affect the fMRI signal generated in certain brain regions. (author)

  2. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex.

    Science.gov (United States)

    Wu, Rui; Kausar, Hina; Johnson, Paul; Montoya-Durango, Diego E; Merchant, Michael; Rane, Madhavi J

    2007-07-27

    We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK-activated protein kinase-2 (MK2), and heat shock protein 27 (Hsp27) and MK2 phosphorylates Akt on Ser-473. Additionally, dissociation of Hsp27 from Akt, prior to Akt activation, induced polymorphonuclear leukocyte (PMN) apoptosis. However, the role of Hsp27 in regulating Akt activation was not examined. This study tested the hypothesis that Hsp27 regulates Akt activation and promotes cell survival by scaffolding MK2 to the Akt signal complex. Here we show that loss of Akt/Hsp27 interaction by anti-Hsp27 antibody treatment resulted in loss of Akt/MK2 interaction, loss of Akt-Ser-473 phosphorylation, and induced PMN apoptosis. Transfection of myristoylated Akt (AktCA) in HK-11 cells induced Akt-Ser-473 phosphorylation, activation, and Hsp27-Ser-82 phosphorylation. Cotransfection of AktCA with Hsp27 short interfering RNA, but not scrambled short interfering RNA, silenced Hsp27 expression, without altering Akt expression in HK-11 cells. Silencing Hsp27 expression inhibited Akt/MK2 interaction, inhibited Akt phosphorylation and Akt activation, and induced HK-11 cell death. Deletion mutagenesis studies identified acidic linker region (amino acids 117-128) on Akt as an Hsp27 binding region. Deletion of amino acids 117-128 on Akt resulted in loss of its interaction with Hsp27 and MK2 but not with Hsp90 as demonstrated by immunoprecipitation and glutathione S-transferase pulldown studies. Co-transfection studies demonstrated that constitutively active MK2 (MK2EE) phosphorylated Aktwt (wild type) on Ser-473 but failed to phosphorylate Akt(Delta117-128) mutant in transfixed cells. These studies collectively define a novel role of Hsp27 in regulating Akt activation and cellular apoptosis by mediating interaction between Akt and its upstream activator MK2.

  4. Replicating the Ice-Volume Signal of the Early Pleistocene with a Complex Earth System Model

    Science.gov (United States)

    Tabor, C. R.; Poulsen, C. J.; Pollard, D.

    2013-12-01

    Milankovitch theory proposes high-latitude summer insolation intensity paces the ice ages by controlling perennial snow cover amounts (Milankovitch, 1941). According to theory, the ~21 kyr cycle of precession should dominate the ice-volume records since it has the greatest influence on high-latitude summer insolation. Modeling experiments frequently support Milankovitch theory by attributing the majority of Northern Hemisphere high-latitude summer snowmelt to changes in the cycle of precession (e.g. Jackson and Broccoli, 2003). However, ice-volume proxy records, especially those of the Early Pleistocene (2.6-0.8 Ma), display variability with a period of ~41 kyr (Raymo and Lisiecki, 2005), indicative of insolation forcing from obliquity, which has a much smaller influence on summer insolation intensity than precession. Several hypotheses attempt to explain the discrepancies between Milkankovitch theory and the proxy records by invoking phenomena such as insolation gradients (Raymo and Nisancioglu, 2003), hemispheric offset (Raymo et al., 2006; Lee and Poulsen, 2009), and integrated summer energy (Huybers, 2006); however, all of these hypotheses contain caveats (Ruddiman, 2006) and have yet to be supported by modeling studies that use a complex GCM. To explore potential solutions to this '41 kyr problem,' we use an Earth system model composed of the GENESIS GCM and Land Surface model, the BIOME4 vegetation model, and the Pennsylvania State ice-sheet model. Using an asynchronous coupling technique, we run four idealized transient combinations of obliquity and precession, representing the orbital extremes of the Pleistocene (Berger and Loutre, 1991). Each experiment is run through several complete orbital cycles with a dynamic ice domain spanning North America and Greenland, and fixed preindustrial greenhouse-gas concentrations. For all orbital configurations, model results produce greater ice-volume spectral power at the frequency of obliquity despite significantly

  5. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    Energy Technology Data Exchange (ETDEWEB)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald, E-mail: gerald.thiel@uks.eu

    2015-03-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified.

  6. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    International Nuclear Information System (INIS)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald

    2015-01-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified

  7. Unilateral vestibular deafferentation-induced changes in calcium signaling-related molecules in the rat vestibular nuclear complex.

    Science.gov (United States)

    Masumura, Chisako; Horii, Arata; Mitani, Kenji; Kitahara, Tadashi; Uno, Atsuhiko; Kubo, Takeshi

    2007-03-23

    Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca(2+) ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the alpha2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca(2+) influx into the ipsilateral VNC neurons via up-regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca(2+) pump, would increase an efflux of Ca

  8. Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

    Science.gov (United States)

    Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

    2016-10-01

    Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

  9. CDIP1-BAP31 Complex Transduces Apoptotic Signals from Endoplasmic Reticulum to Mitochondria under Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Takushi Namba

    2013-10-01

    Full Text Available Resolved endoplasmic reticulum (ER stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a proapoptotic p53 target, CDIP1, acts as a key signal transducer of ER-stress-mediated apoptosis. We identify B-cell-receptor-associated protein 31 (BAP31 as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent truncated Bid (tBid and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER-stress-mediated apoptosis. Altogether, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a mechanism for establishing an ER-mitochondrial crosstalk for ER-stress-mediated apoptosis signaling.

  10. Klotho Regulates 14-3-3ζ Monomerization and Binding to the ASK1 Signaling Complex in Response to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Reynolds K Brobey

    Full Text Available The reactive oxygen species (ROS-sensitive apoptosis signal-regulating kinase 1 (ASK1 signaling complex is a key regulator of p38 MAPK activity, a major modulator of stress-associated with aging disorders. We recently reported that the ratio of free ASK1 to the complex-bound ASK1 is significantly decreased in Klotho-responsive manner and that Klotho-deficient tissues have elevated levels of free ASK1 which coincides with increased oxidative stress. Here, we tested the hypothesis that: 1 covalent interactions exist among three identified proteins constituting the ASK1 signaling complex; 2 in normal unstressed cells the ASK1, 14-3-3ζ and thioredoxin (Trx proteins simultaneously engage in a tripartite complex formation; 3 Klotho's stabilizing effect on the complex relied solely on 14-3-3ζ expression and its apparent phosphorylation and dimerization changes. To verify the hypothesis, we performed 14-3-3ζ siRNA knock-down experiments in conjunction with cell-based assays to measure ASK1-client protein interactions in the presence and absence of Klotho, and with or without an oxidant such as rotenone. Our results show that Klotho activity induces posttranslational modifications in the complex targeting 14-3-3ζ monomer/dimer changes to effectively protect against ASK1 oxidation and dissociation. This is the first observation implicating all three proteins constituting the ASK1 signaling complex in close proximity.

  11. A Complex Signal

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The removal of Taiwan from the common strategic objectives of the U.S.-Japan alliance could mean much more than a change of wording While U.S.and Japanese top diplomats and defense officials celebrated closer cooperation forged by their annual meeting in

  12. Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Bender, C L; Otamendi, A; Calfa, G D; Molina, V A

    2018-04-20

    Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Estrogen/ERα signaling axis participates in osteoblast maturation via upregulating chromosomal and mitochondrial complex gene expressions

    Science.gov (United States)

    Lin, Pei-I; Tai, Yu-Ting; Chan, Wing P.; Lin, Yi-Ling; Liao, Mei-Hsiu; Chen, Ruei-Ming

    2018-01-01

    Estrogen deficiency usually leads to bone loss and osteoporosis in postmenopausal women. Osteoblasts play crucial roles in bone formation. However, osteoblast functions are influenced by mitochondrial bioenergetic conditions. In this study, we investigated the roles of the estrogen and estrogen receptor alpha (ERα) axis in mitochondrial energy metabolism and subsequent osteoblast mineralization. Exposure of rat calvarial osteoblasts to estradiol caused substantial improvements in alkaline phosphatase activities and cell calcification. In parallel, treatment of human osteoblast-like U2OS cells, derived from a female osteosarcoma patient, with estradiol specifically augmented ERα levels. Sequentially, estradiol stimulated translocation of ERα to nuclei in human osteoblasts and induced expressions of genomic respiratory chain complex NDUFA10, UQCRC1, cytochrome c oxidase (COX)8A, COX6A2, COX8C, COX6C, COX6B2, COX412, and ATP12A genes. Concurrently, estradiol stimulated translocation of ERα to mitochondria from the cytoplasm. A bioinformatic search found the existence of four estrogen response elements in the 5’-promoter region of the mitochondrial cox i gene. Interestingly, estradiol induced COX I mRNA and protein expressions in human osteoblasts or rat calvarial osteoblasts. Knocking-down ERα translation concurrently downregulated estradiol-induced COX I mRNA expression. Consequently, exposure to estradiol led to successive increases in the mitochondrial membrane potential, the mitochondrial enzyme activity, and cellular adenosine triphosphate levels. Taken together, this study showed the roles of the estradiol/ERα signaling axis in improving osteoblast maturation through upregulating the mitochondrial bioenergetic system due to induction of definite chromosomal and mitochondrial complex gene expressions. Our results provide novel insights elucidating the roles of the estrogen/ERα alliance in regulating bone formation. PMID:29416685

  14. Structure of the Regulator of G Protein Signaling 8 (RGS8)-Gαq Complex: MOLECULAR BASIS FOR Gα SELECTIVITY.

    Science.gov (United States)

    Taylor, Veronica G; Bommarito, Paige A; Tesmer, John J G

    2016-03-04

    Regulator of G protein signaling (RGS) proteins interact with activated Gα subunits via their RGS domains and accelerate the hydrolysis of GTP. Although the R4 subfamily of RGS proteins generally accepts both Gαi/o and Gαq/11 subunits as substrates, the R7 and R12 subfamilies select against Gαq/11. In contrast, only one RGS protein, RGS2, is known to be selective for Gαq/11. The molecular basis for this selectivity is not clear. Previously, the crystal structure of RGS2 in complex with Gαq revealed a non-canonical interaction that could be due to interfacial differences imposed by RGS2, the Gα subunit, or both. To resolve this ambiguity, the 2.6 Å crystal structure of RGS8, an R4 subfamily member, was determined in complex with Gαq. RGS8 adopts the same pose on Gαq as it does when bound to Gαi3, indicating that the non-canonical interaction of RGS2 with Gαq is due to unique features of RGS2. Based on the RGS8-Gαq structure, residues in RGS8 that contact a unique α-helical domain loop of Gαq were converted to those typically found in R12 subfamily members, and the reverse substitutions were introduced into RGS10, an R12 subfamily member. Although these substitutions perturbed their ability to stimulate GTP hydrolysis, they did not reverse selectivity. Instead, selectivity for Gαq seems more likely determined by whether strong contacts can be maintained between α6 of the RGS domain and Switch III of Gαq, regions of high sequence and conformational diversity in both protein families. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    Directory of Open Access Journals (Sweden)

    Kia J Langford-Smith

    Full Text Available Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM:blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan. We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  16. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    Science.gov (United States)

    Langford-Smith, Kia J; Sandiford, Zara; Langford-Smith, Alex; Wilkinson, Fiona L; Jones, Simon A; Wraith, J Ed; Wynn, Robert F; Bigger, Brian W

    2013-01-01

    Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  17. Hippocampal dendritic spines remodeling and fear memory are modulated by GABAergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D; Molina, Victor A

    2015-05-01

    GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial role on the modulation of the stress influence on fear memory. Moreover, accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream target of BLA neurons in contextual fear. Given that hippocampal structural plasticity is proposed to provide a substrate for the storage of long-term memories, the main aim of this study is to evaluate the modulation of GABA neurotransmission in the BLA on spine density in the DH following stress on contextual fear learning. The present findings show that prior stressful experience promoted contextual fear memory and enhanced spine density in the DH. Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented the facilitating influence of stress on both fear retention and hippocampal dendritic spine remodeling. Similarly to the stress-induced effects, the blockade of GABAa sites within the BLA ameliorated fear memory emergence and induced structural remodeling in the DH. These findings suggest that GABAergic transmission in BLA modulates the structural changes in DH associated to the influence of stress on fear memory. © 2015 Wiley Periodicals, Inc.

  18. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation*

    Science.gov (United States)

    Ramírez, Valerie T.; Ramos-Fernández, Eva; Henríquez, Juan Pablo; Lorenzo, Alfredo; Inestrosa, Nibaldo C.

    2016-01-01

    Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Gαo under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Gαo appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gβγ is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. PMID:27402827

  19. Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling.

    Science.gov (United States)

    Deloose, Eveline; Tack, Jan

    2016-02-15

    During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine. Historically this pattern was designated to be the housekeeper of the gut since disturbances in the pattern were associated with small intestinal bacterial overgrowth; however, its role in the involvement of hunger sensations was already hinted in the beginning of the 20th century by both Cannon (Cannon W, Washburn A. Am J Physiol 29: 441-454, 1912) and Carlson (Carlson A. The Control of Hunger in Health and Disease. Chicago, IL: Univ. of Chicago Press, 1916). The discovery of motilin in 1973 shed more light on the control mechanisms of the MMC. Motilin plasma levels fluctuate together with the phases of the MMC and induce phase III contractions with a gastric onset. Recent research suggests that these motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients. This minireview describes the functions of the MMC in the gut and its regulatory role in controlling hunger sensations. Copyright © 2016 the American Physiological Society.

  20. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv’s Distribution for Quadratic Frequency Modulation Signals

    Directory of Open Access Journals (Sweden)

    Fulong Jing

    2017-06-01

    Full Text Available For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR and the quadratic chirp rate (QCR are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF and modified scaled Fourier transform (mSFT, an effective parameter estimation algorithm is proposed—referred to as the Two-Dimensional product modified Lv’s distribution (2D-PMLVD—for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  1. Formation and biochemical characterization of tube/pelle death domain complexes: critical regulators of postreceptor signaling by the Drosophila toll receptor.

    Science.gov (United States)

    Schiffmann, D A; White, J H; Cooper, A; Nutley, M A; Harding, S E; Jumel, K; Solari, R; Ray, K P; Gay, N J

    1999-09-07

    In Drosophila, the Toll receptor signaling pathway is required for embryonic dorso-ventral patterning and at later developmental stages for innate immune responses. It is thought that dimerization of the receptor by binding of the ligand spätzle causes the formation of a postreceptor activation complex at the cytoplasmic surface of the membrane. Two components of this complex are the adaptor tube and protein kinase pelle. These proteins both have "death domains", protein interaction motifs found in a number of signaling pathways, particularly those involved in apoptotic cell death. It is thought that pelle is bound by tube during formation of the activation complexes, and that this interaction is mediated by the death domains. In this paper, we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together. Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. We have purified proteins corresponding to the death domains of tube and pelle and show that these form corresponding heterodimeric complexes in vitro. Partial proteolysis reveals a smaller core consisting of the minimal death domain sequences. We have studied the tube/pelle interaction with the techniques of surface plasmon resonance, analytical ultracentrifugation and isothermal titration calorimetry. These measurements produce a value of K(d) for the complex of about 0.5 microM.

  2. Complex-enhanced chaotic signals with time-delay signature suppression based on vertical-cavity surface-emitting lasers subject to chaotic optical injection

    Science.gov (United States)

    Chen, Jianjun; Duan, Yingni; Zhong, Zhuqiang

    2018-03-01

    A chaotic system is constructed on the basis of vertical-cavity surface-emitting lasers (VCSELs), where a slave VCSEL subject to chaotic optical injection (COI) from a master VCSEL with the external feedback. The complex degree (CD) and time-delay signature (TDS) of chaotic signals generated by this chaotic system are investigated numerically via permutation entropy (PE) and self-correlation function (SF) methods, respectively. The results show that, compared with master VCSEL subject to optical feedback, complex-enhanced chaotic signals with TDS suppression can be achieved for S-VCSEL subject to COI. Meanwhile, the influences of several controllable parameters on the evolution maps of CD of chaotic signals are carefully considered. It is shown that the CD of chaotic signals for S-VCSEL is always higher than that for M-VCSEL due to the CIO effect. The TDS of chaotic signals can be significantly suppressed by choosing the reasonable parameters in this system. Furthermore, TDS suppression and high CD chaos can be obtained simultaneously in the specific parameter ranges. The results confirm that this chaotic system may effectively improve the security of a chaos-based communication scheme.

  3. Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling

    Science.gov (United States)

    Honda, Kenya; Yanai, Hideyuki; Mizutani, Tatsuaki; Negishi, Hideo; Shimada, Naoya; Suzuki, Nobutaka; Ohba, Yusuke; Takaoka, Akinori; Yeh, Wen-Chen; Taniguchi, Tadatsugu

    2004-01-01

    Toll-like receptor (TLR) activation is central to immunity, wherein the activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust induction of type I IFNs (IFN-α/β) by means of the MyD88 adaptor protein. However, it remains unknown how the TLR signal “input” can be processed through MyD88 to “output” the induction of the IFN genes. Here, we demonstrate that the transcription factor IRF-7 interacts with MyD88 to form a complex in the cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6 and provides the foundation for the TLR9-dependent activation of the IFN genes. The complex defined in this study represents an example of how the coupling of the signaling adaptor and effector kinase molecules together with the transcription factor regulate the processing of an extracellular signal to evoke its versatile downstream transcriptional events in a cell. Thus, we propose that this molecular complex may function as a cytoplasmic transductional-transcriptional processor. PMID:15492225

  4. A Complex Interplay between Wnt/β-Catenin Signalling and the Cell Cycle in the Adult Liver

    Directory of Open Access Journals (Sweden)

    Angélique Gougelet

    2012-01-01

    Full Text Available Canonical Wnt signalling, governed by its effector β-catenin, is known for a long time as playing an important role in development, tissue homeostasis, and cancer. In the liver, it was unravelled as both an oncogenic pathway involved in a subset of liver cancers and a physiological signalling identified as the “zonation-keeper” of the quiescent liver lobule. This duality has encouraged to explore the role of canonical Wnt in liver regeneration and liver-cell proliferation mainly using murine genetic models of β-catenin overactivation or inactivation. These studies definitely integrate Wnt signalling within the hepatic network driving regeneration and proliferation. We will review here the current knowledge concerning the mitogenic effect of Wnt, to switch on its specific role in the liver, which is quiescent but with a great capacity to regenerate. The duality of β-catenin signalling, associated both with liver quiescence and liver-cell proliferation, will be brought forward.

  5. A Complex Interplay between Wnt/β-Catenin Signalling and the Cell Cycle in the Adult Liver.

    Science.gov (United States)

    Gougelet, Angélique; Colnot, Sabine

    2012-01-01

    Canonical Wnt signalling, governed by its effector β-catenin, is known for a long time as playing an important role in development, tissue homeostasis, and cancer. In the liver, it was unravelled as both an oncogenic pathway involved in a subset of liver cancers and a physiological signalling identified as the "zonation-keeper" of the quiescent liver lobule. This duality has encouraged to explore the role of canonical Wnt in liver regeneration and liver-cell proliferation mainly using murine genetic models of β-catenin overactivation or inactivation. These studies definitely integrate Wnt signalling within the hepatic network driving regeneration and proliferation. We will review here the current knowledge concerning the mitogenic effect of Wnt, to switch on its specific role in the liver, which is quiescent but with a great capacity to regenerate. The duality of β-catenin signalling, associated both with liver quiescence and liver-cell proliferation, will be brought forward.

  6. Low-complexity R-peak detection in ECG signals : a preliminary step towards ambulatory fetal monitoring

    NARCIS (Netherlands)

    Rooijakkers, M.J.; Rabotti, C.; Bennebroek, M.; Meerbergen, van J.; Mischi, M.

    2011-01-01

    Non-invasive fetal health monitoring during pregnancy has become increasingly important. Recent advances in signal processing technology have enabled fetal monitoring during pregnancy, using abdominal ECG recordings. Ubiquitous ambulatory monitoring for continuous fetal health measurement is however

  7. A new inhibitor of the ?-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    OpenAIRE

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, St?phane A.

    2017-01-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, ?-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of ?-arrestin recruitment to the receptor and ?-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecul...

  8. Statistics of the derivatives of complex signal derived from Riesz transform and its application to pseudo-Stokes vector correlation for speckle displacement measurement

    DEFF Research Database (Denmark)

    Zhang, Shun; Yang, Yi; Hanson, Steen Grüner

    2015-01-01

    for the superiority of the proposed PSVC technique, we study the statistical properties of the spatial derivatives of the complex signal representation generated from the Riesz transform. Under the assumption of a Gaussian random process, a theoretical analysis for the pseudo Stokes vector correlation has been...... provided. Based on these results, we show mathematically that PSVC has a performance advantage over conventional intensity-based correlation technique....

  9. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes

    Directory of Open Access Journals (Sweden)

    Peter Draber

    2015-12-01

    Full Text Available Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1 ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC, at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC’s M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors.

  10. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    Science.gov (United States)

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  11. Investigation of the effects of different carotenoids on the absorption and CD signals of light harvesting 1 complexes

    NARCIS (Netherlands)

    Georgakopoulou, S.; van der Zwan, G.; Olsen, J.D.; Hunter, C.N.; Niederman, R.A.; van Grondelle, R.

    2006-01-01

    Absorption and circular dichroism (CD) spectra of light-harvesting (LH)1 complexes from the purple bacteria Rhodobacter (Rba.) sphaeroides and Rhodospirillum (Rsp.) rubrum are presented. The complexes exhibit very low intensity, highly nonconservative, near-infrared (NIR) CD spectra. Absorption and

  12. Signal complexity and modular organization of the courtship behaviours of two sibling species of wolf spiders (Araneae: Lycosidae).

    Science.gov (United States)

    Chiarle, Alberto; Isaia, Marco

    2013-07-01

    In this study, we compare the courtship behaviours of Pardosa proxima and P. vlijmi, two species of wolf spiders up to now regarded as "ethospecies", by means of motion analysis methodologies. In particular, we investigate the features of the signals, aiming at understanding the evolution of the courtship and its role in species delimitation and speciation processes. In our model, we highlight a modular structure of the behaviours and the presence of recurring units and phases. According to other similar cases concerning animal communication, we observed one highly variable and one stereotyped phase for both species. The stereotyped phase is here regarded as a signal related to species identity or an honest signal linked directly to the quality of the signaler. On the contrary, the variable phase aims to facilitate signal detection and assessment by the female reducing choice costs or errors. Variable phases include cues arisen from Fisherian runaway selection, female sensory exploitation and remaining of past selections. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Ancient Origin of the CARD–Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions

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    Jens Staal

    2018-05-01

    Full Text Available The CARD–coiled coil (CC/Bcl10/MALT1-like paracaspase (CBM signaling complexes composed of a CARD–CC family member (CARD-9, -10, -11, or -14, Bcl10, and the type 1 paracaspase MALT1 (PCASP1 play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is known about the evolutionary origin and the original functions of the CBM complex. Type 1 paracaspases originated before the last common ancestor of planulozoa (bilaterians and cnidarians. Notably in bilaterians, Ecdysozoa (e.g., nematodes and insects lacks Bcl10, whereas other lineages have a Bcl10 homolog. A survey of invertebrate CARD–CC homologs revealed such homologs only in species with Bcl10, indicating an ancient common origin of the entire CBM complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were only found in invertebrate organisms with CARD–CC/Bcl10, indicating that this pathway might be related to the original function of the CBM complex. Moreover, the type 1 paracaspase sequences from invertebrate organisms that have CARD–CC/Bcl10 are more similar to vertebrate paracaspases. Functional analysis of protein–protein interactions, NF-κB signaling, and CYLD cleavage for selected invertebrate type 1 paracaspase and Bcl10 homologs supports this scenario and indicates an ancient origin of the CARD–CC/Bcl10/paracaspase signaling complex. By contrast, many of the known MALT1-associated activities evolved fairly recently, indicating that unknown functions are at the basis of the protein conservation. As a proof-of-concept, we provide initial evidence for a CBM- and NF-κB-independent neuronal function of the Caenorhabditis elegans type 1 paracaspase malt-1. In conclusion, this study shows how evolutionary insights may point at alternative functions of MALT1.

  14. HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex

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    He-Ting Mao

    2016-05-01

    Full Text Available During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation.

  15. Hypothalamic roles of mTOR complex I: Integration of nutrient and hormone signals to regulate energy homeostasis

    Science.gov (United States)

    Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight...

  16. Conservation of Functional Sites on Interleukin-6 and Implications for Evolution of Signaling Complex Assembly and Therapeutic Intervention

    Czech Academy of Sciences Publication Activity Database

    Veverka, Václav; Baker, T.; Redpath, N. T.; Carrington, B.; Muskett, F. W.; Taylor, R. J.; Lawson, A. D. G.; Henry, A. J.; Carr, M. D.

    2012-01-01

    Roč. 287, č. 47 (2012), s. 40043-40050 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z40550506 Keywords : interleukin-6 * cell signalling * NMR Subject RIV: CE - Biochemistry Impact factor: 4.651, year: 2012

  17. High frequency seismic signal generated by landslides on complex topographies: from point source to spatially distributed sources

    Science.gov (United States)

    Mangeney, A.; Kuehnert, J.; Capdeville, Y.; Durand, V.; Stutzmann, E.; Kone, E. H.; Sethi, S.

    2017-12-01

    During their flow along the topography, landslides generate seismic waves in a wide frequency range. These so called landquakes can be recorded at very large distances (a few hundreds of km for large landslides). The recorded signals depend on the landslide seismic source and the seismic wave propagation. If the wave propagation is well understood, the seismic signals can be inverted for the seismic source and thus can be used to get information on the landslide properties and dynamics. Analysis and modeling of long period seismic signals (10-150s) have helped in this way to discriminate between different landslide scenarios and to constrain rheological parameters (e.g. Favreau et al., 2010). This was possible as topography poorly affects wave propagation at these long periods and the landslide seismic source can be approximated as a point source. In the near-field and at higher frequencies (> 1 Hz) the spatial extent of the source has to be taken into account and the influence of the topography on the recorded seismic signal should be quantified in order to extract information on the landslide properties and dynamics. The characteristic signature of distributed sources and varying topographies is studied as a function of frequency and recording distance.The time dependent spatial distribution of the forces applied to the ground by the landslide are obtained using granular flow numerical modeling on 3D topography. The generated seismic waves are simulated using the spectral element method. The simulated seismic signal is compared to observed seismic data from rockfalls at the Dolomieu Crater of Piton de la Fournaise (La Réunion).Favreau, P., Mangeney, A., Lucas, A., Crosta, G., and Bouchut, F. (2010). Numerical modeling of landquakes. Geophysical Research Letters, 37(15):1-5.

  18. The late endosomal HOPS complex anchors active G-protein signaling essential for pathogenesis in magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Ravikrishna Ramanujam

    Full Text Available In Magnaporthe oryzae, the causal ascomycete of the devastating rice blast disease, the conidial germ tube tip must sense and respond to a wide array of requisite cues from the host in order to switch from polarized to isotropic growth, ultimately forming the dome-shaped infection cell known as the appressorium. Although the role for G-protein mediated Cyclic AMP signaling in appressorium formation was first identified almost two decades ago, little is known about the spatio-temporal dynamics of the cascade and how the signal is transmitted through the intracellular network during cell growth and morphogenesis. In this study, we demonstrate that the late endosomal compartments, comprising of a PI3P-rich (Phosphatidylinositol 3-phosphate highly dynamic tubulo-vesicular network, scaffold active MagA/GαS, Rgs1 (a GAP for MagA, Adenylate cyclase and Pth11 (a non-canonical GPCR in the likely absence of AKAP-like anchors during early pathogenic development in M. oryzae. Loss of HOPS component Vps39 and consequently the late endosomal function caused a disruption of adenylate cyclase localization, cAMP signaling and appressorium formation. Remarkably, exogenous cAMP rescued the appressorium formation defects associated with VPS39 deletion in M. oryzae. We propose that sequestration of key G-protein signaling components on dynamic late endosomes and/or endolysosomes, provides an effective molecular means to compartmentalize and control the spatio-temporal activation and rapid downregulation (likely via vacuolar degradation of cAMP signaling amidst changing cellular geometry during pathogenic development in M. oryzae.

  19. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    Science.gov (United States)

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

  20. DDX3 directly regulates TRAF3 ubiquitination and acts as a scaffold to co-ordinate assembly of signalling complexes downstream from MAVS.

    Science.gov (United States)

    Gu, Lili; Fullam, Anthony; McCormack, Niamh; Höhn, Yvette; Schröder, Martina

    2017-02-15

    The human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon (IFN) induction downstream from antiviral pattern recognition receptors. It binds to TANK-binding kinase 1 and IκB-kinase-ε (IKKε), the two key kinases mediating activation of IFN regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream from RIG-I and then links the activated kinase to IRF3. In the present study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TNF receptor-associated factor 3 (TRAF3) mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination. Interestingly, we observed two waves of K63-linked TRAF3 ubiquitination following RIG-I activation by Sendai virus (SeV) infection, both of which were suppressed by DDX3 knockdown. We also investigated the spatiotemporal formation of endogenous downstream signalling complexes containing the mitochondrial antiviral signalling (MAVS) adaptor, DDX3, IκB-kinase-ε (IKKε), TRAF3 and IRF3. DDX3 was recruited to MAVS early after SeV infection, suggesting that it might mediate subsequent recruitment of other molecules. Indeed, knockdown of DDX3 prevented the formation of TRAF3-MAVS and TRAF3-IKKε complexes. Based on our data, we propose that early TRAF3 ubiquitination is required for the formation of a stable MAVS-TRAF3 complex, while the second wave of TRAF3 ubiquitination mediates IRF3 recruitment and activation. Our study characterises DDX3 as a multifunctional adaptor molecule that co-ordinates assembly of different TRAF3, IKKε and IRF3-containing signalling complexes downstream from MAVS. Additionally, it provides novel insights into the role of TRAF3 in RIG-I signalling. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. Sensitive and fast detection of fructose in complex media via symmetry breaking and signal amplification using surface-enhanced Raman spectroscopy.

    Science.gov (United States)

    Sun, Fang; Bai, Tao; Zhang, Lei; Ella-Menye, Jean-Rene; Liu, Sijun; Nowinski, Ann K; Jiang, Shaoyi; Yu, Qiuming

    2014-03-04

    A new strategy is proposed to sensitively and rapidly detect analytes with weak Raman signals in complex media using surface-enhanced Raman spectroscopy (SERS) via detecting the SERS signal changes of the immobilized probe molecules on SERS-active substrates upon binding of the analytes. In this work, 4-mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-three-dimensional plasmonic nanostructure array (Q3D-PNA) SERS substrate to detect fructose. The molecule of 4-MPBA possesses three key functions: molecule recognition and reversible binding of the analyte via the boronic acid group, amplification of SERS signals by the phenyl group and thus shielding of the background noise of complex media, and immobilization on the surface of SERS-active substrates via the thiol group. Most importantly, the symmetry breaking of the 4-MPBA molecule upon fructose binding leads to the change of area ratio between totally symmetric 8a ring mode and nontotally symmetric 8b ring mode, which enables the detection. The detection curves were obtained in phosphate-buffered saline (PBS) and in undiluted artificial urine at clinically relevant concentrations, and the limit of detection of 0.05 mM was achieved.

  2. The ShcA SH2 domain engages a 14-3-3/PI3'K signaling complex and promotes breast cancer cell survival.

    Science.gov (United States)

    Ursini-Siegel, J; Hardy, W R; Zheng, Y; Ling, C; Zuo, D; Zhang, C; Podmore, L; Pawson, T; Muller, W J

    2012-11-29

    The ShcA adapter protein transmits activating signals downstream of receptor and cytoplasmic tyrosine kinases through the establishment of phosphotyrosine-dependent complexes. In this regard, ShcA possesses both a phosphotyrosine-binding domain (PTB) and Src homology 2 domain (SH2), which bind phosphotyrosine residues in a sequence-specific manner. Although the majority of receptor tyrosine kinases expressed in breast cancer cells bind the PTB domain, very little is known regarding the biological importance of SH2-driven ShcA signaling during mammary tumorigenesis. To address this, we employed transgenic mice expressing a mutant ShcA allele harboring a non-functional SH2 domain (ShcR397K) under the transcriptional control of the endogenous ShcA promoter. Using transplantation approaches, we demonstrate that SH2-dependent ShcA signaling within the mammary epithelial compartment is essential for breast tumor outgrowth, survival and the development of lung metastases. We further show that the ShcA SH2 domain activates the AKT pathway, potentially through a novel SH2-mediated complex between ShcA, 14-3-3ζ and the p85 regulatory subunit of phosphatidylinositol 3 (PI3') kinase. This study is the first to demonstrate that the SH2 domain of ShcA is critical for tumor survival during mammary tumorigenesis.

  3. Distinctive EPR signals provide an understanding of the affinity of bis-(3-hydroxy-4-pyridinonato) copper(II) complexes for hydrophobic environments.

    Science.gov (United States)

    Rangel, Maria; Leite, Andreia; Silva, André M N; Moniz, Tânia; Nunes, Ana; Amorim, M João; Queirós, Carla; Cunha-Silva, Luís; Gameiro, Paula; Burgess, John

    2014-07-07

    In this work we report the synthesis and characterization of a set of 3-hydroxy-4-pyridinone copper(ii) complexes with variable lipophilicity. EPR spectroscopy was used to characterize the structure of copper(ii) complexes in solution, and as a tool to gain insight into solvent interactions. EPR spectra of solutions of the [CuL2] complexes recorded in different solvents reveal the presence of two copper species whose ratio depends on the nature of the solvent. Investigation of EPR spectra in the pure solvents methanol, dimethylsulfoxide, dichloromethane and their 50% (v/v) mixtures with toluene allowed the characterization of two types of copper signals (gzz = 2.30 and gzz = 2.26) whose spin-Hamiltonian parameters are consistent with solvated and non-solvated square-planar copper(ii) complexes. Regarding the potential biological application of ligands and complexes and to get insight into the partition properties in water-membrane interfaces, EPR spectra were also obtained in water-saturated octanol, an aqueous solution buffered at pH = 7.4 and liposome suspensions, for three compounds representative of different hydro-lipophilic balances. Analysis of the EPR spectra obtained in liposomes allowed establishment of the location of the complexes in the water and lipid phases. In view of the results of this work we put forward the use of EPR spectroscopy to assess the affinity of copper(ii) complexes for a hydrophobic environment and also to obtain indirect information about the lipophilicity of the ligands and similar EPR silent complexes.

  4. [Effects of Biejiajian Pills on Wnt signal pathway signal molecules β-catenin/TCF4 complex activities and downstream proteins cyclin D1 and MMP-2 in hepatocellular carcinoma cells].

    Science.gov (United States)

    Wen, Bin; Sun, Haitao; He, Songqi; Cheng, Yang; Jia, Wenyan; Fan, Eryan; Pang, Jie

    2014-12-01

    To study the effect of Biejiajian Pills on Wnt signal pathway and the mechanisms underlying its action to suppress the invasiveness of hepatocellular carcinoma. HepG2 cells cultured in the serum of rats fed with Biejiajian Pills for 48 h were examined for β-catenin expression using immunofluorescence, β-catenin/TCF4 complex activity with luciferase, and expressions of the downstream proteins cyclin D1 and MMP-2 using qRT-PCR. Biejiajian Pills-treated sera significantly reduced the expressions of cytoplasmic and nuclear β-catenin protein, cyclin D1 and MMP-2 proteins and lowered the activities of β-catenin/TCF4 complex. Biejiajian Pills may serve as a potential anti-tumor agent, whose effect might be mediated by inhibiting the Wnt/β-catenin pathway.

  5. R7-binding protein targets the G protein β5/R7-regulator of G protein signaling complex to lipid rafts in neuronal cells and brain

    Directory of Open Access Journals (Sweden)

    Zhang Jian-Hua

    2007-09-01

    Full Text Available Abstract Background Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins, composed of Gα, Gβ, and Gγ subunits, are positioned at the inner face of the plasma membrane and relay signals from activated G protein-coupled cell surface receptors to various signaling pathways. Gβ5 is the most structurally divergent Gβ isoform and forms tight heterodimers with regulator of G protein signalling (RGS proteins of the R7 subfamily (R7-RGS. The subcellular localization of Gβ 5/R7-RGS protein complexes is regulated by the palmitoylation status of the associated R7-binding protein (R7BP, a recently discovered SNARE-like protein. We investigate here whether R7BP controls the targeting of Gβ5/R7-RGS complexes to lipid rafts, cholesterol-rich membrane microdomains where conventional heterotrimeric G proteins and some effector proteins are concentrated in neurons and brain. Results We show that endogenous Gβ5/R7-RGS/R7BP protein complexes are present in native neuron-like PC12 cells and that a fraction is targeted to low-density, detergent-resistant membrane lipid rafts. The buoyant density of endogenous raft-associated Gβ5/R7-RGS protein complexes in PC12 cells was similar to that of lipid rafts containing the palmitoylated marker proteins PSD-95 and LAT, but distinct from that of the membrane microdomain where flotillin was localized. Overexpression of wild-type R7BP, but not its palmitoylation-deficient mutant, greatly enriched the fraction of endogenous Gβ5/R7-RGS protein complexes in the lipid rafts. In HEK-293 cells the palmitoylation status of R7BP also regulated the lipid raft targeting of co-expressed Gβ5/R7-RGS/R7BP proteins. A fraction of endogenous Gβ5/R7-RGS/R7BP complexes was also present in lipid rafts in mouse brain. Conclusion A fraction of Gβ5/R7-RGS/R7BP protein complexes is targeted to low-density, detergent-resistant membrane lipid rafts in PC12 cells and brain. In cultured cells, the palmitoylation status of

  6. Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.

    Directory of Open Access Journals (Sweden)

    Wyatt B Potter

    Full Text Available Tuberous sclerosis complex (TSC is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/- CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/- hippocampal slices. We also report that adult TSC2(+/- mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.

  7. The bHLH factors Dpn and members of the E(spl complex mediate the function of Notch signalling regulating cell proliferation during wing disc development

    Directory of Open Access Journals (Sweden)

    Beatriz P. San Juan

    2012-05-01

    The Notch signalling pathway plays an essential role in the intricate control of cell proliferation and pattern formation in many organs during animal development. In addition, mutations in most members of this pathway are well characterized and frequently lead to tumour formation. The Drosophila imaginal wing discs have provided a suitable model system for the genetic and molecular analysis of the different pathway functions. During disc development, Notch signalling at the presumptive wing margin is necessary for the restricted activation of genes required for pattern formation control and disc proliferation. Interestingly, in different cellular contexts within the wing disc, Notch can either promote cell proliferation or can block the G1-S transition by negatively regulating the expression of dmyc and bantam micro RNA. The target genes of Notch signalling that are required for these functions have not been identified. Here, we show that the Hes vertebrate homolog, deadpan (dpn, and the Enhancer-of-split complex (E(splC genes act redundantly and cooperatively to mediate the Notch signalling function regulating cell proliferation during wing disc development.

  8. Feasibility study in the application of optical signal analysis to non-destructive testing of complex structures

    Science.gov (United States)

    Baker, B.; Brown, H.

    1974-01-01

    Advantages of the large time bandwidth product of optical processing are presented. Experiments were performed to study the feasibility of the use of optical spectral analysis for detection of flaws in structural elements excited by random noise. Photographic and electronic methods of comparison of complex spectra were developed. Limitations were explored, and suggestions for further work are offered.

  9. The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling

    Science.gov (United States)

    Barrington, Chloe L.; Katsanis, Nicholas

    2017-01-01

    The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS) complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh) dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure. PMID:28291807

  10. The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    Sarah C Goetz

    Full Text Available The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure.

  11. 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.

  12. NAFASS: Fluctuation spectroscopy and the Prony spectrum for description of multi-frequency signals in complex systems

    Science.gov (United States)

    Nigmatullin, R. R.; Gubaidullin, I. A.

    2018-03-01

    In this paper, we essentially modernize the NAFASS (Non-orthogonal Amplitude Frequency Analysis of the Smoothed Signals) approach suggested earlier. Actually, we solved two important problems: (a) new and effective algorithm was proposed and (b) we proved that the segment of the Prony spectrum could be used as the fitting function for description of the desired frequency spectrum. These two basic elements open an alternative way for creation of the fluctuation spectroscopy when the segment of the Fourier series can fit any random signal with trend but the dispersion spectrum of the Fourier series ω0 · k(ω0 ≡ 2 π / T) ⇒Ωk(k = 0 , 1 , 2 , . . . , K - 1) is replaced by the specific dispersion law Ωk calculated with the help of original algorithm described below. It implies that any finite signal will have a compact amplitude-frequency response (AFR), where the number of the modes is much less in comparison with the number of data points (K economic data and compare 30-years world prices for meat (beef, chicken, lamb and pork) entering as the basic components to every-day food consumption. These data were taken from the official site http://www.indexmundi.com/commodities/. We fitted these random functions with the high accuracy and calculated the desired ;amplitude-frequency; response for these random price fluctuations. The calculated distribution of the amplitudes (Ack, Ask) and frequency spectrum Ωk (k = 0, 1,…, K-1) allows one to compress initial data (K (number of modes) << N (number of data points), N/K ≅ 20-40) and receive an additional information for their comparison with each other. As the second example, we considered the transcendental/irrational numbers description in the frame of the proposed NAFASS approach, as well. This possibility was demonstrated on the quantitative description of the transcendental number π = 3.1415926535897932…, containing initially 6ṡ104 digits. The results obtained for the second type of data can be useful for

  13. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    Science.gov (United States)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  14. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    International Nuclear Information System (INIS)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-01-01

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface

  15. High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling.

    Science.gov (United States)

    Burns, Michael C; Howes, Jennifer E; Sun, Qi; Little, Andrew J; Camper, DeMarco V; Abbott, Jason R; Phan, Jason; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

    2018-05-01

    K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Synergistic effect of signaling from receptors of soluble platelet agonists and outside-in signaling in formation of a stable fibrinogen-integrin αIIbβ3-actin cytoskeleton complex.

    Science.gov (United States)

    Budnik, Ivan; Shenkman, Boris; Savion, Naphtali

    2015-01-01

    Thrombus formation in the injured vessel wall is a highly complex process involving various blood-born components that go through specific temporal and spatial changes as observed by intravital videomicroscopy. Platelets bind transiently to the developing thrombus and may either become stably incorporated into or disengage from the thrombus. The aim of the present study was to reveal the processes involved in the formation of a stable thrombus. Platelet-rich plasma and washed platelets were studied by the aggregometer. The aggregate stability was challenged by eptifibatide. Platelet Triton-insoluble fraction was prepared and the actin and αIIb content in the cytoskeleton was analyzed by western blot. Maximal actin polymerization is achieved 1min after platelet activation while maximal αIIbβ3-actin cytoskeleton association requires 5 to 10min of activation and fibrinogen-mediated platelet-to-platelet bridging. Thus, actin polymerization is dependent on platelet activation and requires neither αIIbβ3 integrin occupation nor platelet aggregation. Formation of a stable aggregate requires platelet activation for more than 1min, complete increase in actin cytoskeleton fraction and partial association of αIIbβ3 with the actin cytoskeleton. However, direct αIIbβ3 activation is not sufficient for cytoskeleton complex formation. Thus, stable αIIbβ3-fibrinogen interaction, representing stable aggregate, is achieved after more than 1min agonist activation, involving inside-out and outside-in signaling but not after direct integrin activation, involving only outside-in signaling. Formation of a stable fibrinogen-αIIbβ3-actin cytoskeleton complex is the result of the combined effect of platelet stimulation by soluble agonists, activation of αIIbβ3, fibrinogen binding and platelet-to-platelet bridging. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. PI3K-AKT-mTOR-Signaling and beyond: the Complex Network in Gastroenteropancreatic Neuroendocrine Neoplasms

    Science.gov (United States)

    Briest, Franziska; Grabowski, Patricia

    2014-01-01

    Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due to the lack of a broad mechanistic knowledge, an insufficient classification of specific diagnostic sub-groups, and predictive markers. GEP-NEN tumors evade early diagnosis because of slow asymptomatic growth behavior and are frequently not detected until metastasized. How signaling networks contribute to tumor progression and how these networks interact remains unclear in large parts. In this review we summarize the knowledge on the growth factor responsive non-angiogenetic pathways in sporadic GEP-NENs, highlight promising mechanistic research approaches, and describe important therapy targets. PMID:24578720

  18. ER stress stimulates production of the key antimicrobial peptide, cathelicidin, by forming a previously unidentified intracellular S1P signaling complex.

    Science.gov (United States)

    Park, Kyungho; Ikushiro, Hiroko; Seo, Ho Seong; Shin, Kyong-Oh; Kim, Young Il; Kim, Jong Youl; Lee, Yong-Moon; Yano, Takato; Holleran, Walter M; Elias, Peter; Uchida, Yoshikazu

    2016-03-08

    We recently identified a previously unidentified sphingosine-1-phosphate (S1P) signaling mechanism that stimulates production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), in mammalian cells exposed to external perturbations, such as UVB irradiation and other oxidative stressors that provoke subapoptotic levels of endoplasmic reticulum (ER) stress, independent of the well-known vitamin D receptor-dependent mechanism. ER stress increases cellular ceramide and one of its distal metabolites, S1P, which activates NF-κB followed by C/EBPα activation, leading to CAMP production, but in a S1P receptor-independent fashion. We now show that S1P activates NF-κB through formation of a previously unidentified signaling complex, consisting of S1P, TRAF2, and RIP1 that further associates with three stress-responsive proteins; i.e., heat shock proteins (GRP94 and HSP90α) and IRE1α. S1P specifically interacts with the N-terminal domain of heat shock proteins. Because this ER stress-initiated mechanism is operative in both epithelial cells and macrophages, it appears to be a universal, highly conserved response, broadly protective against diverse external perturbations that lead to increased ER stress. Finally, these studies further illuminate how ER stress and S1P orchestrate critical stress-specific signals that regulate production of one protective response by stimulating production of the key innate immune element, CAMP.

  19. Nuclear pore complex-mediated modulation of TCR signaling is required for naïve CD4+ T cell homeostasis.

    Science.gov (United States)

    Borlido, Joana; Sakuma, Stephen; Raices, Marcela; Carrette, Florent; Tinoco, Roberto; Bradley, Linda M; D'Angelo, Maximiliano A

    2018-05-07

    Nuclear pore complexes (NPCs) are channels connecting the nucleus with the cytoplasm. We report that loss of the tissue-specific NPC component Nup210 causes a severe deficit of naïve CD4 + T cells. Nup210-deficient CD4 + T lymphocytes develop normally but fail to survive in the periphery. The decreased survival results from both an impaired ability to transmit tonic T cell receptor (TCR) signals and increased levels of Fas, which sensitize Nup210 -/- naïve CD4 + T cells to Fas-mediated cell death. Mechanistically, Nup210 regulates these processes by modulating the expression of Cav2 (encoding Caveolin-2) and Jun at the nuclear periphery. Whereas the TCR-dependent and CD4 + T cell-specific upregulation of Cav2 is critical for proximal TCR signaling, cJun expression is required for STAT3-dependent repression of Fas. Our results uncover an unexpected role for Nup210 as a cell-intrinsic regulator of TCR signaling and T cell homeostasis and expose NPCs as key players in the adaptive immune system.

  20. A multi-step method with signal quality assessment and fine-tuning procedure to locate maternal and fetal QRS complexes from abdominal ECG recordings

    International Nuclear Information System (INIS)

    Liu, Chengyu; Li, Peng; Zhao, Lina; Di Maria, Costanzo; Zhang, Henggui; Chen, Zhiqing

    2014-01-01

    Non-invasive monitoring of fetal electrocardiogram (fECG) plays an important role in detecting and diagnosing fetal diseases. This study aimed to develop a multi-step method for locating both maternal and fetal QRS complexes from abdominal ECG (aECG) recordings. The proposed method included four major steps: abdominal ECG pre-processing, maternal QRS complex locating, maternal ECG cancellation and fetal QRS complex locating. Signal quality assessment (SQA) and fine-tuning for maternal ECG (FTM) were implemented in the first and third steps, respectively. The method was then evaluated using 75 non-invasive 4-channel aECG recordings provided by the PhysioNet/Computing in Cardiology Challenge 2013. The F 1 measure, which is a new index introduced by Behar et al (2013 Proc. Comput. Cardiol. 40 297–300), was used to assess the locating accuracy. The other two indices, mean squared error of heart rate (MSE H R) between the fetal HR signals estimated from the reference and our method (MSE H R in bpm 2 ) and root mean squared difference between the corresponding fetal RR intervals (MSE R R in ms) were also used to assess the locating accuracy. Overall, for the maternal QRS complex, the F 1 measure was 98.4% from the method without the implementation of SQA, and it was improved to 99.8% with SQA. For the fetal QRS complex, the F 1 measure, MSE H R and MSE R R were 84.9%, 185.6 bpm 2 and 19.4 ms for the method without both SQA and FTM procedures. They were improved to 93.9%, 47.5 bpm 2 and 7.6 ms with both SQA and FTM procedures. These improvements were observed from each individual subject. It can be concluded that implementing both SQA and FTM procedures could achieve better performance for locating both maternal and fetal QRS complexes. (paper)

  1. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures

    Science.gov (United States)

    Knierim, Ellen; Hirata, Hiromi; Wolf, Nicole I.; Morales-Gonzalez, Susanne; Schottmann, Gudrun; Tanaka, Yu; Rudnik-Schöneborn, Sabine; Orgeur, Mickael; Zerres, Klaus; Vogt, Stefanie; van Riesen, Anne; Gill, Esther; Seifert, Franziska; Zwirner, Angelika; Kirschner, Janbernd; Goebel, Hans Hilmar; Hübner, Christoph; Stricker, Sigmar; Meierhofer, David; Stenzel, Werner; Schuelke, Markus

    2016-01-01

    Transcriptional signal cointegrators associate with transcription factors or nuclear receptors and coregulate tissue-specific gene transcription. We report on recessive loss-of-function mutations in two genes (TRIP4 and ASCC1) that encode subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex. We used autozygosity mapping and whole-exome sequencing to search for pathogenic mutations in four families. Affected individuals presented with prenatal-onset spinal muscular atrophy (SMA), multiple congenital contractures (arthrogryposis multiplex congenita), respiratory distress, and congenital bone fractures. We identified homozygous and compound-heterozygous nonsense and frameshift TRIP4 and ASCC1 mutations that led to a truncation or the entire absence of the respective proteins and cosegregated with the disease phenotype. Trip4 and Ascc1 have identical expression patterns in 17.5-day-old mouse embryos with high expression levels in the spinal cord, brain, paraspinal ganglia, thyroid, and submandibular glands. Antisense morpholino-mediated knockdown of either trip4 or ascc1 in zebrafish disrupted the highly patterned and coordinated process of α-motoneuron outgrowth and formation of myotomes and neuromuscular junctions and led to a swimming defect in the larvae. Immunoprecipitation of the ASC-1 complex consistently copurified cysteine and glycine rich protein 1 (CSRP1), a transcriptional cofactor, which is known to be involved in spinal cord regeneration upon injury in adult zebrafish. ASCC1 mutant fibroblasts downregulated genes associated with neurogenesis, neuronal migration, and pathfinding (SERPINF1, DAB1, SEMA3D, SEMA3A), as well as with bone development (TNFRSF11B, RASSF2, STC1). Our findings indicate that the dysfunction of a transcriptional coactivator complex can result in a clinical syndrome affecting the neuromuscular system. PMID:26924529

  2. A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2.

    Science.gov (United States)

    Rodgers, K K; Villey, I J; Ptaszek, L; Corbett, E; Schatz, D G; Coleman, J E

    1999-07-15

    RAG1 and RAG2 are the two lymphoid-specific proteins required for the cleavage of DNA sequences known as the recombination signal sequences (RSSs) flanking V, D or J regions of the antigen-binding genes. Previous studies have shown that RAG1 alone is capable of binding to the RSS, whereas RAG2 only binds as a RAG1/RAG2 complex. We have expressed recombinant core RAG1 (amino acids 384-1008) in Escherichia coli and demonstrated catalytic activity when combined with RAG2. This protein was then used to determine its oligomeric forms and the dissociation constant of binding to the RSS. Electrophoretic mobility shift assays show that up to three oligomeric complexes of core RAG1 form with a single RSS. Core RAG1 was found to exist as a dimer both when free in solution and as the minimal species bound to the RSS. Competition assays show that RAG1 recognizes both the conserved nonamer and heptamer sequences of the RSS. Zinc analysis shows the core to contain two zinc ions. The purified RAG1 protein overexpressed in E.coli exhibited the expected cleavage activity when combined with RAG2 purified from transfected 293T cells. The high mobility group protein HMG2 is stably incorporated into the recombinant RAG1/RSS complex and can increase the affinity of RAG1 for the RSS in the absence of RAG2.

  3. The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression.

    Science.gov (United States)

    Silva, Nicola; Ferrandiz, Nuria; Barroso, Consuelo; Tognetti, Silvia; Lightfoot, James; Telecan, Oana; Encheva, Vesela; Faull, Peter; Hanni, Simon; Furger, Andre; Snijders, Ambrosius P; Speck, Christian; Martinez-Perez, Enrique

    2014-11-24

    Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, and poorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Induction of biogenic magnetization and redox control by a component of the target of rapamycin complex 1 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Keiji Nishida

    Full Text Available Most organisms are simply diamagnetic, while magnetotactic bacteria and migratory animals are among organisms that exploit magnetism. Biogenic magnetization not only is of fundamental interest, but also has industrial potential. However, the key factor(s that enable biogenic magnetization in coordination with other cellular functions and metabolism remain unknown. To address the requirements for induction and the application of synthetic bio-magnetism, we explored the creation of magnetism in a simple model organism. Cell magnetization was first observed by attraction towards a magnet when normally diamagnetic yeast Saccharomyces cerevisiae were grown with ferric citrate. The magnetization was further enhanced by genetic modification of iron homeostasis and introduction of ferritin. The acquired magnetizable properties enabled the cells to be attracted to a magnet, and be trapped by a magnetic column. Superconducting quantum interference device (SQUID magnetometry confirmed and quantitatively characterized the acquired paramagnetism. Electron microscopy and energy-dispersive X-ray spectroscopy showed electron-dense iron-containing aggregates within the magnetized cells. Magnetization-based screening of gene knockouts identified Tco89p, a component of TORC1 (Target of rapamycin complex 1, as important for magnetization; loss of TCO89 and treatment with rapamycin reduced magnetization in a TCO89-dependent manner. The TCO89 expression level positively correlated with magnetization, enabling inducible magnetization. Several carbon metabolism genes were also shown to affect magnetization. Redox mediators indicated that TCO89 alters the intracellular redox to an oxidized state in a dose-dependent manner. Taken together, we demonstrated that synthetic induction of magnetization is possible and that the key factors are local redox control through carbon metabolism and iron supply.

  5. Detection of gear cracks in a complex gearbox of wind turbines using supervised bounded component analysis of vibration signals collected from multi-channel sensors

    Science.gov (United States)

    Li, Zhixiong; Yan, Xinping; Wang, Xuping; Peng, Zhongxiao

    2016-06-01

    In the complex gear transmission systems, in wind turbines a crack is one of the most common failure modes and can be fatal to the wind turbine power systems. A single sensor may suffer with issues relating to its installation position and direction, resulting in the collection of weak dynamic responses of the cracked gear. A multi-channel sensor system is hence applied in the signal acquisition and the blind source separation (BSS) technologies are employed to optimally process the information collected from multiple sensors. However, literature review finds that most of the BSS based fault detectors did not address the dependence/correlation between different moving components in the gear systems; particularly, the popular used independent component analysis (ICA) assumes mutual independence of different vibration sources. The fault detection performance may be significantly influenced by the dependence/correlation between vibration sources. In order to address this issue, this paper presents a new method based on the supervised order tracking bounded component analysis (SOTBCA) for gear crack detection in wind turbines. The bounded component analysis (BCA) is a state of art technology for dependent source separation and is applied limitedly to communication signals. To make it applicable for vibration analysis, in this work, the order tracking has been appropriately incorporated into the BCA framework to eliminate the noise and disturbance signal components. Then an autoregressive (AR) model built with prior knowledge about the crack fault is employed to supervise the reconstruction of the crack vibration source signature. The SOTBCA only outputs one source signal that has the closest distance with the AR model. Owing to the dependence tolerance ability of the BCA framework, interfering vibration sources that are dependent/correlated with the crack vibration source could be recognized by the SOTBCA, and hence, only useful fault information could be preserved in

  6. Electrogenerated chemiluminescence biosensing for the detection of prostate PC-3 cancer cells incorporating antibody as capture probe and ruthenium complex-labelled wheat germ agglutinin as signal probe

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Haiying [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062 (China); Department of Chemistry, Yuncheng University, Yuncheng 044300 (China); Li, Zhejian; Shan, Meng; Li, Congcong; Qi, Honglan; Gao, Qiang [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062 (China); Wang, Jinyi [College of Science and College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Zhang, Chengxiao, E-mail: cxzhang@snnu.edu.cn [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062 (China)

    2015-03-10

    Highlights: • A novel biosensor was developed for the detection of prostate cancer cells. • The selectivity of the biosensor was improved using antibody as capture probe. • The biosensor showed the low extremely detection limit of 2.6 × 10{sup 2} cells mL{sup −1}. • The ruthenium complex-labelled WGA can be transported in the cell vesicles. - Abstract: A highly selective and sensitive electrogenerated chemiluminescence (ECL) biosensor for the detection of prostate PC-3 cancer cells was designed using a prostate specific antibody as a capture probe and ruthenium complex-labelled wheat germ agglutinin as a signal probe. The ECL biosensor was fabricated by covalently immobilising the capture probe on a graphene oxide-coated glassy carbon electrode. Target PC-3 cells were selectively captured on the surface of the biosensor, and then, the signal probe was bound with the captured PC-3 cells to form a sandwich. In the presence of tripropylamine, the ECL intensity of the sandwich biosensor was logarithmically directly proportion to the concentration of PC-3 cells over a range from 7.0 × 10{sup 2} to 3.0 × 10{sup 4} cells mL{sup −1}, with a detection limit of 2.6 × 10{sup 2} cells mL{sup −1}. The ECL biosensor was also applied to detect prostate specific antigen with a detection limit of 0.1 ng mL{sup −1}. The high selectivity of the biosensor was demonstrated in comparison with that of a lectin-based biosensor. The strategy developed in this study may be a promising approach and could be extended to the design of ECL biosensors for highly sensitive and selective detection of other cancer-related cells or cancer biomarkers using different probes.

  7. Electrogenerated chemiluminescence biosensing for the detection of prostate PC-3 cancer cells incorporating antibody as capture probe and ruthenium complex-labelled wheat germ agglutinin as signal probe

    International Nuclear Information System (INIS)

    Yang, Haiying; Li, Zhejian; Shan, Meng; Li, Congcong; Qi, Honglan; Gao, Qiang; Wang, Jinyi; Zhang, Chengxiao

    2015-01-01

    Highlights: • A novel biosensor was developed for the detection of prostate cancer cells. • The selectivity of the biosensor was improved using antibody as capture probe. • The biosensor showed the low extremely detection limit of 2.6 × 10 2 cells mL −1 . • The ruthenium complex-labelled WGA can be transported in the cell vesicles. - Abstract: A highly selective and sensitive electrogenerated chemiluminescence (ECL) biosensor for the detection of prostate PC-3 cancer cells was designed using a prostate specific antibody as a capture probe and ruthenium complex-labelled wheat germ agglutinin as a signal probe. The ECL biosensor was fabricated by covalently immobilising the capture probe on a graphene oxide-coated glassy carbon electrode. Target PC-3 cells were selectively captured on the surface of the biosensor, and then, the signal probe was bound with the captured PC-3 cells to form a sandwich. In the presence of tripropylamine, the ECL intensity of the sandwich biosensor was logarithmically directly proportion to the concentration of PC-3 cells over a range from 7.0 × 10 2 to 3.0 × 10 4 cells mL −1 , with a detection limit of 2.6 × 10 2 cells mL −1 . The ECL biosensor was also applied to detect prostate specific antigen with a detection limit of 0.1 ng mL −1 . The high selectivity of the biosensor was demonstrated in comparison with that of a lectin-based biosensor. The strategy developed in this study may be a promising approach and could be extended to the design of ECL biosensors for highly sensitive and selective detection of other cancer-related cells or cancer biomarkers using different probes

  8. Presence of proNGF-Sortilin Signaling Complex in Nigral Dopamine Neurons and Its Variation in Relation to Aging, Lactacystin and 6-OHDA Insults

    Directory of Open Access Journals (Sweden)

    Ken Kam-Lin Yung

    2013-07-01

    Full Text Available Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA rat models of Parkinson’s disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson’s disease; the underlying mechanism and key signaling pathways involved warrant further investigation.

  9. A complex molecular interplay of auxin and ethylene signaling pathways is involved in Arabidopsis growth promotion by Burkholderia phytofirmans PsJN

    Directory of Open Access Journals (Sweden)

    María Josefina Poupin

    2016-04-01

    Full Text Available Modulation of phytohormones homeostasis is one of the proposed mechanisms to explain plant growth promotion induced by beneficial rhizobacteria (PGPR. However, there is still limited knowledge about the molecular signals and pathways underlying these beneficial interactions. Even less is known concerning the interplay between phytohormones in plants inoculated with PGPR. Auxin and ethylene are crucial hormones in the control of plant growth and development, and recent studies report an important and complex crosstalk between them in the regulation of different plant developmental processes. The objective of this work was to study the role of both hormones in the growth promotion of Arabidopsis thaliana plants induced by the well-known PGPR Burkholderia phytofirmans PsJN. For this, the spatiotemporal expression patterns of several genes related to auxin biosynthesis, perception and response and ethylene biosynthesis were studied, finding that most of these genes showed specific transcriptional regulations after inoculation in roots and shoots. PsJN-growth promotion was not observed in Arabidopsis mutants with an impaired ethylene (ein2-1 or auxin (axr1-5 signaling. Even, PsJN did not promote growth in an ethylene overproducer (eto2, indicating that a fine regulation of both hormones signaling and homeostasis is necessary to induce growth of the aerial and root tissues. Auxin polar transport is also involved in growth promotion, since PsJN did not promote primary root growth in the pin2 mutant or under chemical inhibition of transport in wild type plants. Finally, a key role for ethylene biosynthesis was found in the PsJN-mediated increase in root hair number. These results not only give new insights of PGPR regulation of plant growth but also are also useful to understand key aspects of Arabidopsis growth control.

  10. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2......) dependent to demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells...... resulted in the upregulated expression of MHC II and of CD54 and B7, respectively, analogous to the effect of fixed activated Th1 cells. B7 expression was further enhanced by co-cross-linking CD54 and MHC II. Cross-linking of CD40 achieved comparable effects. Strikingly, cross-linking ligation of CD54...

  11. Kobuvirus VP3 protein restricts the IFN-β-triggered signaling pathway by inhibiting STAT2-IRF9 and STAT2-STAT2 complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Qianqian; Lan, Xi; Wang, Chen [State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046 (China); Ren, Yujie; Yue, Ningning [College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wang, Junyong [State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046 (China); Zhong, Bo [College of Life Sciences, Wuhan University, Wuhan 430072 (China); Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhu, Qiyun, E-mail: zhuqiyun@caas.cn [State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046 (China)

    2017-07-15

    Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-β-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-β downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9. Taken together, these data reveal a new mechanism for immune evasion of PKV. - Highlights: •PKV VP3 inhibits the IFN-β-triggered signaling pathway. •VP3 associates with STAT2 and IRF9. •VP3 blocks the STAT2-IRF9 nuclear translocation. •VP3 utilizes a novel strategy for innate immune evasion.

  12. Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

    Science.gov (United States)

    Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

    2014-01-01

    The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

  13. Axon Regeneration Is Regulated by Ets-C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Chun Li

    2015-10-01

    Full Text Available The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. In Caenorhabditis elegans, the JNK and p38 MAPK pathways are important for axon regeneration. Axonal injury induces expression of the svh-2 gene encoding a receptor tyrosine kinase, stimulation of which by the SVH-1 growth factor leads to activation of the JNK pathway. Here, we identify ETS-4 and CEBP-1, related to mammalian Ets and C/EBP, respectively, as transcriptional activators of svh-2 expression following axon injury. ETS-4 and CEBP-1 function downstream of the cAMP and Ca2+-p38 MAPK pathways, respectively. We show that PKA-dependent phosphorylation of ETS-4 promotes its complex formation with CEBP-1. Furthermore, activation of both cAMP and Ca2+ signaling is required for activation of svh-2 expression. Thus, the cAMP/Ca2+ signaling pathways cooperatively activate the JNK pathway, which then promotes axon regeneration.

  14. mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells.

    Science.gov (United States)

    Ito, Daisuke; Nojima, Satoshi; Nishide, Masayuki; Okuno, Tatsusada; Takamatsu, Hyota; Kang, Sujin; Kimura, Tetsuya; Yoshida, Yuji; Morimoto, Keiko; Maeda, Yohei; Hosokawa, Takashi; Toyofuku, Toshihiko; Ohshima, Jun; Kamimura, Daisuke; Yamamoto, Masahiro; Murakami, Masaaki; Morii, Eiichi; Rakugi, Hiromi; Isaka, Yoshitaka; Kumanogoh, Atsushi

    2015-08-01

    Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4(+) T cell responses, the involvement of mTOR in CD8(+) T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8(+) T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A(-/-) CD8(+) T cells exhibited impairments in production of IFN-γ and TNF-α and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8(+) T cell responses were significantly impaired in SEMA4A(-/-) mice. Furthermore, SEMA4A(-/-) CD8(+) T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8(+) T cells. IFN-γ production and mTORC1 activity in SEMA4A(-/-) CD8(+) T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8(+) T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8(+) T cells, but also reveal a novel link between a semaphorin and mTOR signaling. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Polycomb Repressive Complex 2 Enacts Wnt Signaling in Intestinal Homeostasis and Contributes to the Instigation of Stemness in Diseases Entailing Epithelial Hyperplasia or Neoplasia.

    Science.gov (United States)

    Oittinen, Mikko; Popp, Alina; Kurppa, Kalle; Lindfors, Katri; Mäki, Markku; Kaikkonen, Minna U; Viiri, Keijo

    2017-02-01

    Canonical Wnt/β-catenin signaling regulates the homeostasis of intestinal epithelium by controlling the balance between intestinal stem cell self-renewal and differentiation but epigenetic mechanisms enacting the process are not known. We hypothesized that epigenetic regulator, Polycomb Repressive Complex-2 (PRC2), is involved in Wnt-mediated epithelial homeostasis on the crypt-villus axis and aberrancies therein are implicated both in celiac disease and in intestinal malignancies. We found that PRC2 establishes repressive crypt and villus specific trimethylation of histone H3 lysine 27 (H3K27me3) signature on genes responsible for, for example, nutrient transport and cell killing in crypts and, for example, proliferation and differentiation in mature villi, suggesting that PRC2 facilitates the Wnt-governed intestinal homeostasis. When celiac patients are on gluten-containing diet PRC2 is out-of-bounds active and consequently its target genes were found affected in intestinal epithelium. Significant set of effective intestinal PRC2 targets are also differentially expressed in colorectal adenoma and carcinomas. Our results suggest that PRC2 gives rise and maintains polar crypt and villus specific H3K27me3 signatures. As H3K27me3 is a mark enriched in developmentally important genes, identified intestinal PRC2 targets are possibly imperative drivers for enterocyte differentiation and intestinal stem cell maintenance downstream to Wnt-signaling. Our work also elucidates the mechanism sustaining the crypt hyperplasia in celiac disease and suggest that PRC2-dependent fostering of epithelial stemness is a common attribute in intestinal diseases in which epithelial hyperplasia or neoplasia prevails. Finally, this work demonstrates that in intestine PRC2 represses genes having both pro-stemness and pro-differentiation functions, fact need to be considered when designing epigenetic therapies including PRC2 as a drug target. Stem Cells 2017;35:445-457. © 2016 Alpha

  16. Temporal Patterns in Sheep Fetal Heart Rate Variability Correlate to Systemic Cytokine Inflammatory Response: A Methodological Exploration of Monitoring Potential Using Complex Signals Bioinformatics.

    Directory of Open Access Journals (Sweden)

    Christophe L Herry

    Full Text Available Fetal inflammation is associated with increased risk for postnatal organ injuries. No means of early detection exist. We hypothesized that systemic fetal inflammation leads to distinct alterations of fetal heart rate variability (fHRV. We tested this hypothesis deploying a novel series of approaches from complex signals bioinformatics. In chronically instrumented near-term fetal sheep, we induced an inflammatory response with lipopolysaccharide (LPS injected intravenously (n = 10 observing it over 54 hours; seven additional fetuses served as controls. Fifty-one fHRV measures were determined continuously every 5 minutes using Continuous Individualized Multi-organ Variability Analysis (CIMVA. CIMVA creates an fHRV measures matrix across five signal-analytical domains, thus describing complementary properties of fHRV. We implemented, validated and tested methodology to obtain a subset of CIMVA fHRV measures that matched best the temporal profile of the inflammatory cytokine IL-6. In the LPS group, IL-6 peaked at 3 hours. For the LPS, but not control group, a sharp increase in standardized difference in variability with respect to baseline levels was observed between 3 h and 6 h abating to baseline levels, thus tracking closely the IL-6 inflammatory profile. We derived fHRV inflammatory index (FII consisting of 15 fHRV measures reflecting the fetal inflammatory response with prediction accuracy of 90%. Hierarchical clustering validated the selection of 14 out of 15 fHRV measures comprising FII. We developed methodology to identify a distinctive subset of fHRV measures that tracks inflammation over time. The broader potential of this bioinformatics approach is discussed to detect physiological responses encoded in HRV measures.

  17. Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

    Science.gov (United States)

    Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

    2011-01-01

    Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

  18. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

    Science.gov (United States)

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

    2014-01-03

    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Changes in signal transducer and activator of transcription 3 (STAT3) dynamics induced by complexation with pharmacological inhibitors of Src homology 2 (SH2) domain dimerization.

    Science.gov (United States)

    Resetca, Diana; Haftchenary, Sina; Gunning, Patrick T; Wilson, Derek J

    2014-11-21

    The activity of the transcription factor signal transducer and activator of transcription 3 (STAT3) is dysregulated in a number of hematological and solid malignancies. Development of pharmacological STAT3 Src homology 2 (SH2) domain interaction inhibitors holds great promise for cancer therapy, and a novel class of salicylic acid-based STAT3 dimerization inhibitors that includes orally bioavailable drug candidates has been recently developed. The compounds SF-1-066 and BP-1-102 are predicted to bind to the STAT3 SH2 domain. However, given the highly unstructured and dynamic nature of the SH2 domain, experimental confirmation of this prediction was elusive. We have interrogated the protein-ligand interaction of STAT3 with these small molecule inhibitors by means of time-resolved electrospray ionization hydrogen-deuterium exchange mass spectrometry. Analysis of site-specific evolution of deuterium uptake induced by the complexation of STAT3 with SF-1-066 or BP-1-102 under physiological conditions enabled the mapping of the in silico predicted inhibitor binding site to the STAT3 SH2 domain. The binding of both inhibitors to the SH2 domain resulted in significant local decreases in dynamics, consistent with solvent exclusion at the inhibitor binding site and increased rigidity of the inhibitor-complexed SH2 domain. Interestingly, inhibitor binding induced hot spots of allosteric perturbations outside of the SH2 domain, manifesting mainly as increased deuterium uptake, in regions of STAT3 important for DNA binding and nuclear localization. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. SKR-1, a homolog of Skp1 and a member of the SCFSEL-10 complex, regulates sex-determination and LIN-12/Notch signaling in C. elegans

    Science.gov (United States)

    Killian, Darrell J.; Harvey, Elizabeth; Johnson, Peter; Otori, Muneyoshi; Mitani, Shohei; Xue, Ding

    2008-01-01

    Sex-determination in C. elegans requires regulation of gene transcription and protein activity and stability. sel-10 encodes a WD40-repeat-containing F-box protein that likely mediates the ubiquitin-mediated degradation of important sex-determination factors. Loss of sel-10 results in a mild masculinization of hermaphrodites, whereas dominant alleles of sel-10, such as sel-10(n1074), cause a more severe masculinization, including a reversal of the life versus death decision in sex-specific neurons. To investigate about how sel-10 regulates sex-determination, we conducted a sel-10(n1074) suppressor screen and isolated a weak loss-of-function allele of skr-1, one of 21 Skp1-related genes in C. elegans. Skp1, Cullin, and F-box proteins, such as SEL-10, are components of the SCF E3 ubiquitin ligase complex. We present genetic evidence that the sel-10(n1074) masculinization phenotype is dependent upon skr-1 and cul-1 activity. Furthermore, we show that the SKR-1(M140I) weak loss-of-function mutation interferes with SKR-1/SEL-10 binding. Unexpectedly, we found that the G567E substitution in SEL-10 caused by the n1074 allele impairs the binding of SEL-10 to SKR-1 and the dimerization of SEL-10, which may be important for SEL-10 function. Our results suggest that SKR-1, CUL-1 and SEL-10 constitute an SCF E3 ligase complex that plays an important role in modulating sex-determination and LIN-12/Notch signaling in C. elegans. PMID:18718460

  1. Coordinate Activation of Redox-Dependent ASK1/TGF-β Signaling by a Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and Lipid Metabolism in Mice.

    Science.gov (United States)

    Seong, Hyun-A; Manoharan, Ravi; Ha, Hyunjung

    2016-03-10

    To explore the molecular connections between redox-dependent apoptosis signal-regulating kinase 1 (ASK1) and transforming growth factor-β (TGF-β) signaling pathways and to examine the physiological processes in which coordinated regulation of these two signaling pathways plays a critical role. We provide evidence that the ASK1 and TGF-β signaling pathways are interconnected by a multiprotein complex harboring murine protein serine-threonine kinase 38 (MPK38), ASK1, Sma- and Mad-related proteins (SMADs), zinc-finger-like protein 9 (ZPR9), and thioredoxin (TRX) and demonstrate that the activation of either ASK1 or TGF-β activity is sufficient to activate both the redox-dependent ASK1 and TGF-β signaling pathways. Physiologically, the restoration of the downregulated activation levels of ASK1 and TGF-β signaling in genetically and diet-induced obese mice by adenoviral delivery of SMAD3 or ZPR9 results in the amelioration of adiposity, hyperglycemia, hyperlipidemia, and impaired ketogenesis. Our data suggest that the multiprotein complex linking ASK1 and TGF-β signaling pathways may be a potential target for redox-mediated metabolic complications.

  2. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1.

    Science.gov (United States)

    Esser, Karlheinz; Tursun, Baris; Ingenhoven, Martin; Michaelis, Georg; Pratje, Elke

    2002-11-08

    The yeast protein cytochrome c peroxidase (Ccp1) is nuclearly encoded and imported into the mitochondrial intermembrane space, where it is involved in degradation of reactive oxygen species. It is known, that Ccp1 is synthesised as a precursor with a N-terminal pre-sequence, that is proteolytically removed during transport of the protein. Here we present evidence for a new processing pathway, involving novel signal peptidase activities. The mAAA protease subunits Yta10 (Afg3) and Yta12 (Rca1) were identified both to be essential for the first processing step. In addition, the Pcp1 (Ygr101w) gene product was found to be required for the second processing step, yielding the mature Ccp1 protein. The newly identified Pcp1 protein belongs to the rhomboid-GlpG superfamily of putative intramembrane peptidases. Inactivation of the protease motifs in mAAA and Pcp1 blocks the respective steps of proteolysis. A model of coupled Ccp1 transport and N-terminal processing by the mAAA complex and Pcp1 is discussed. Similar processing mechanisms may exist, because the mAAA subunits and the newly identified Pcp1 protein belong to ubiquitous protein families.

  3. Efficient and accurate simulations of two-dimensional electronic photon-echo signals: Illustration for a simple model of the Fenna-Matthews-Olson complex

    International Nuclear Information System (INIS)

    Sharp, Leah Z.; Egorova, Dassia; Domcke, Wolfgang

    2010-01-01

    Two-dimensional (2D) photon-echo spectra of a single subunit of the Fenna-Matthews-Olson (FMO) bacteriochlorophyll trimer of Chlorobium tepidum are simulated, employing the equation-of-motion phase-matching approach (EOM-PMA). We consider a slightly extended version of the previously proposed Frenkel exciton model, which explicitly accounts for exciton coherences in the secular approximation. The study is motivated by a recent experiment reporting long-lived coherent oscillations in 2D transients [Engel et al., Nature 446, 782 (2007)] and aims primarily at accurate simulations of the spectroscopic signals, with the focus on oscillations of 2D peak intensities with population time. The EOM-PMA accurately accounts for finite pulse durations as well as pulse-overlap effects and does not invoke approximations apart from the weak-field limit for a given material system. The population relaxation parameters of the exciton model are taken from the literature. The effects of various dephasing mechanisms on coherence lifetimes are thoroughly studied. It is found that the experimentally detected multiple frequencies in peak oscillations cannot be reproduced by the employed FMO model, which calls for the development of a more sophisticated exciton model of the FMO complex.

  4. The complex becomes more complex: protein-protein interactions of SnRK1 with DUF581 family proteins provide a framework for cell- and stimulus type-specific SnRK1 signaling in plants

    Directory of Open Access Journals (Sweden)

    Madlen eNietzsche

    2014-02-01

    Full Text Available In plants, SNF1-related kinase (SnRK1 responds to the availability of carbohydrates as well as to environmental stresses by down-regulating ATP consuming biosynthetic processes, while stimulating energy-generating catabolic reactions through gene expression and post-transcriptional regulation. The functional SnRK1 complex is a heterotrimer where the catalytic alpha subunit associates with a regulatory beta subunit and an activating gamma subunit. Several different metabolites as well as the hormone abscisic acid (ABA have been shown to modulate SnRK1 activity in a cell- and stimulus-type specific manner. It has been proposed that tissue- or stimulus-specific expression of adapter proteins mediating SnRK1 regulation can at least partly explain the differences observed in SnRK1 signaling. By using yeast two-hybrid and in planta bi-molecular fluorescence complementation assays we were able to demonstrate that proteins containing the domain of unknown function (DUF 581 could interact with both isoforms of the SnRK1 alpha subunit (AKIN10/11 of Arabidopsis. A structure/function analysis suggests that the DUF581 is a generic SnRK1 interaction module and co-expression with DUF581 proteins in plant cells leads to reallocation of the kinase to specific regions within the nucleus. Yeast two-hybrid analyses suggest that SnRK1 and DUF581 proteins can share common interaction partners inside the nucleus. The analysis of available microarray data implies that expression of the 19 members of the DUF581 encoding gene family in Arabidopsis is differentially regulated by hormones and environmental cues, indicating specialized functions of individual family members. We hypothesize that DUF581 proteins could act as mediators conferring tissue- and stimulus-type specific differences in SnRK1 regulation.

  5. Rheb Protein Binds CAD (Carbamoyl-phosphate Synthetase 2, Aspartate Transcarbamoylase, and Dihydroorotase) Protein in a GTP- and Effector Domain-dependent Manner and Influences Its Cellular Localization and Carbamoyl-phosphate Synthetase (CPSase) Activity*

    Science.gov (United States)

    Sato, Tatsuhiro; Akasu, Hitomi; Shimono, Wataru; Matsu, Chisa; Fujiwara, Yuki; Shibagaki, Yoshio; Heard, Jeffrey J.; Tamanoi, Fuyuhiko; Hattori, Seisuke

    2015-01-01

    Rheb small GTPases, which consist of Rheb1 and Rheb2 (also known as RhebL1) in mammalian cells, are unique members of the Ras superfamily and play central roles in regulating protein synthesis and cell growth by activating mTOR. To gain further insight into the function of Rheb, we carried out a search for Rheb-binding proteins and found that Rheb binds to CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase), a multifunctional enzyme required for the de novo synthesis of pyrimidine nucleotides. CAD binding is more pronounced with Rheb2 than with Rheb1. Rheb binds CAD in a GTP- and effector domain-dependent manner. The region of CAD where Rheb binds is located at the C-terminal region of the carbamoyl-phosphate synthetase domain and not in the dihydroorotase and aspartate transcarbamoylase domains. Rheb stimulated carbamoyl-phosphate synthetase activity of CAD in vitro. In addition, an elevated level of intracellular UTP pyrimidine nucleotide was observed in Tsc2-deficient cells, which was attenuated by knocking down of Rheb. Immunostaining analysis showed that expression of Rheb leads to increased accumulation of CAD on lysosomes. Both a farnesyltransferase inhibitor that blocks membrane association of Rheb and knockdown of Rheb mislocalized CAD. These results establish CAD as a downstream effector of Rheb and suggest a possible role of Rheb in regulating de novo pyrimidine nucleotide synthesis. PMID:25422319

  6. Rheb protein binds CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase) protein in a GTP- and effector domain-dependent manner and influences its cellular localization and carbamoyl-phosphate synthetase (CPSase) activity.

    Science.gov (United States)

    Sato, Tatsuhiro; Akasu, Hitomi; Shimono, Wataru; Matsu, Chisa; Fujiwara, Yuki; Shibagaki, Yoshio; Heard, Jeffrey J; Tamanoi, Fuyuhiko; Hattori, Seisuke

    2015-01-09

    Rheb small GTPases, which consist of Rheb1 and Rheb2 (also known as RhebL1) in mammalian cells, are unique members of the Ras superfamily and play central roles in regulating protein synthesis and cell growth by activating mTOR. To gain further insight into the function of Rheb, we carried out a search for Rheb-binding proteins and found that Rheb binds to CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase), a multifunctional enzyme required for the de novo synthesis of pyrimidine nucleotides. CAD binding is more pronounced with Rheb2 than with Rheb1. Rheb binds CAD in a GTP- and effector domain-dependent manner. The region of CAD where Rheb binds is located at the C-terminal region of the carbamoyl-phosphate synthetase domain and not in the dihydroorotase and aspartate transcarbamoylase domains. Rheb stimulated carbamoyl-phosphate synthetase activity of CAD in vitro. In addition, an elevated level of intracellular UTP pyrimidine nucleotide was observed in Tsc2-deficient cells, which was attenuated by knocking down of Rheb. Immunostaining analysis showed that expression of Rheb leads to increased accumulation of CAD on lysosomes. Both a farnesyltransferase inhibitor that blocks membrane association of Rheb and knockdown of Rheb mislocalized CAD. These results establish CAD as a downstream effector of Rheb and suggest a possible role of Rheb in regulating de novo pyrimidine nucleotide synthesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. 9.4 COMPLEX SYSTEM THEORY AND THE TRANSDIAGNOSTIC USE OF EARLY WARNING SIGNALS TO FORESEE THE TYPE OF FUTURE TRANSITIONS IN SYMPTOMS

    Science.gov (United States)

    Wichers, Marieke; Schreuder, Marieke; Hartman, Catharina; Wigman, Hanneke

    2018-01-01

    Abstract Background Recently, we showed that assumptions from complex system theory seem applicable in the field of psychiatry. This means that indicators of critical slowing down in the system signal the risk for a critical transition in the near future. In the current study we wanted to explore whether the principle of critical slowing down may also be informative to anticipate on the type of symptoms that individuals are most likely to develop. This is relevant as it may lead to personalized prediction of risk of whether adolescents with mixed complaints are most likely to develop either depression, anxiety, somatic or psychotic symptoms in the near future. For example, we hypothesized that critical slowing down in feeling ‘suspicious’ more strongly indicates risk for a future transition to psychotic symptoms, while critical slowing down in feeling ‘down’ more strongly indicates risk for a transition to depressive symptoms. Methods We examined this in a population of adolescents (most between 15 and 18 years) as adolescents are an at-risk group for the development of psychopathology. At baseline experience sampling was performed for 6 days, 10 measurements a day. Affect items were used to assess autocorrelation as an indicator of ‘critical slowing down’ of the system. At baseline and follow-up SCL-90 questionnaires were administered. In total, 147 adolescents participated both in baseline and follow-up measures and showed increases in at least one of the defined symptom dimensions. We examined whether autocorrelation was positively associated with the size of symptom transition and whether different type of transitions (in depression, anxiety etc.) were differentially predicted by autocorrelations in specific affect states. Results The analyses were done very recently, and findings have not been presented before. We found both shared and specific indicators of risk in the development for transition to various symptom dimensions. First

  8. FSHR and LHR Expression and Signaling as Well as Maturation and Apoptosis of Cumulus-Oocyte Complexes Following Treatment with FSH Receptor Binding Inhibitor in Sheep

    Directory of Open Access Journals (Sweden)

    Suocheng Wei

    2017-09-01

    Full Text Available Background/Aims: Currently, it remains unknown whether FSH receptor binding inhibitor (FRBI influences follicular development and reproduction functions in humans and animals. The present study aimed to investigate FRBI effects on in vitro maturation (IVM and apoptosis of cumulus-oocyte complexes (COCs of sheep, to determine the effect of FRBI on mRNA and protein levels of FSHR and LHR in COCs, and to elucidate the signal pathway of FRBI effects. Methods: COCs were in vitro cultured for 24h in the IVM media supplemented with varying concentrations of FRBI (0, 10, 20, 30 and 40µg/mL and FSH (10IU/mL. The harvested COCs were observed under an inverted microscope and maturation rates of COCs were determined. Real time RT-PCR and Western blotting were utilized to detect mRNA and protein levels of FSHR and LHR. The concentrations of FSH, LH and caspase-3 were determined using especial ELISA kits for sheep, respectively. Results: Maturation rates of COCs decreased gradually as FRBI concentrations increased from 0 to 40µg/mL, reaching a bottom value of 23.76% of the FRBI-4 group. The maximal apoptosis rate was detected in the FRBI-4 group. IP3 contents of FRBI-3 and FRBI-4 groups were reduced as compared to control group (CG and FSH groups (P<0.05. Levels of FSHR protein of FRBI-3 and FRBI-4 groups as well as LHR protein of FRBI-4 group were significantly less than that of CG and FSH group. FSH contents of four FRBI treatment groups were gradually decreased along with the supplementation doses of FRBI. Caspase-3 contents of FRBI groups were reduced with a maximum reduction of the FRBI-2 group. Conclusion: Our results revealed supplement of FRBI into IVM media could dose-dependently decrease the maturation rate and increase apoptosis rate of sheep COCs. A lower dose of FRBI treatment slightly promoted IP3 production, but a higher dose of FRBI reduced IP3 production. FRBI suppressed the mRNA and protein expression levels of FSHR and LHR in sheep COCs

  9. The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains.

    Science.gov (United States)

    Han, Sangyeul; Kim, Sun; Bahl, Samira; Li, Lin; Burande, Clara F; Smith, Nicole; James, Marianne; Beauchamp, Roberta L; Bhide, Pradeep; DiAntonio, Aaron; Ramesh, Vijaya

    2012-08-31

    Pam and its homologs (the PHR protein family) are large E3 ubiquitin ligases that function to regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans. Phr1-deficient mouse models (Phr1(Δ8,9) and Phr1(Magellan), with deletions in the N-terminal putative guanine exchange factor region and the C-terminal ubiquitin ligase region, respectively) exhibit axon guidance/outgrowth defects and striking defects of major axon tracts in the CNS. Our earlier studies identified Pam to be associated with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Here, we examine the potential involvement of the TSC/mTOR complex 1(mTORC1) signaling pathway in Phr1-deficient mouse models. We observed attenuation of mTORC1 signaling in the brains of both Phr1(Δ8,9) and Phr1(Magellan) mouse models. Our results establish that Pam regulates TSC/mTOR signaling in vitro and in vivo through two distinct domains. To further address whether Pam regulates mTORC1 through two functionally independent domains, we undertook heterozygous mutant crossing between Phr1(Δ8,9) and Phr1(Magellan) mice to generate a compound heterozygous model to determine whether these two domains can complement each other. mTORC1 signaling was not attenuated in the brains of double mutants (Phr1(Δ8,9/Mag)), confirming that Pam displays dual regulation of the mTORC1 pathway through two functional domains. Our results also suggest that although dysregulation of mTORC1 signaling may be responsible for the corpus callosum defects, other neurodevelopmental defects observed with Phr1 deficiency are independent of mTORC1 signaling. The ubiquitin ligase complex containing Pam-Fbxo45 likely targets additional synaptic and axonal proteins, which may explain the overlapping neurodevelopmental defects observed in Phr1 and Fbxo45 deficiency.

  10. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

  11. Second-hand signals

    DEFF Research Database (Denmark)

    Bergenholtz, Carsten

    2014-01-01

    Studies of signaling theory have traditionally focused on the dyadic link between the sender and receiver of the signal. Within a science‐based perspective this framing has led scholars to investigate how patents and publications of firms function as signals. I explore another important type...... used by various agents in their search for and assessment of products and firms. I conclude by arguing how this second‐hand nature of signals goes beyond a simple dyadic focus on senders and receivers of signals, and thus elucidates the more complex interrelations of the various types of agents...

  12. Time–frequency analysis of nonstationary complex magneto-hydro-dynamics in fusion plasma signals using the Choi–Williams distribution

    International Nuclear Information System (INIS)

    Xu, L.Q.; Hu, L.Q.; Chen, K.Y.; Li, E.Z.

    2013-01-01

    Highlights: • Choi–Williams distribution yields excellent time–frequency resolution for discrete signal. • CWD method provides clear time–frequency pictures of EAST and HT-7 fast MHD events. • CWD method has advantages to wavelets transform scalogram and the short-time Fourier transform spectrogram. • We discuss about how to choose the windows and free parameter of CWD method. -- Abstract: The Choi–Williams distribution is applied to the time–frequency analysis of signals describing rapid magneto-hydro-dynamic (MHD) modes and events in tokamak plasmas. A comparison is made with Soft X-ray (SXR) signals as well as Mirnov signal that shows the advantages of the Choi–Williams distribution over both continuous wavelets transform scalogram and the short-time Fourier transform spectrogram. Examples of MHD activities in HT-7 and EAST tokamak are shown, namely the onset of coupling tearing modes, high frequency precursors of sawtooth, and low frequency MHD instabilities in edge localized mode (ELM) free in H mode discharge

  13. Diverse in- and output polarities and high complexity of local synaptic and nonsynaptic signalling within a chemically defined class of peptidergic Drosophila neurons

    Science.gov (United States)

    Peptidergic neurons are not easily integrated into current connectomics concepts, since their peptide messages can be distributed via non-synaptic paracrine signaling or even via volume transmission. Moreover, and especially in insects, the polarity of peptidergic interneurons in terms of in- and o...

  14. Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5)·extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1.

    Science.gov (United States)

    Mazalouskas, Matthew D; Godoy-Ruiz, Raquel; Weber, David J; Zimmer, Danna B; Honkanen, Richard E; Wadzinski, Brian E

    2014-02-14

    Serine/threonine protein phosphatase 5 (PP5, PPP5C) is known to interact with the chaperonin heat shock protein 90 (HSP90) and is involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, such as cell growth, differentiation, proliferation, motility, and apoptosis. Here, we identify PP5 in stable complexes with extracellular signal-regulated kinases (ERKs). Studies using mutant proteins reveal that the formation of PP5·ERK1 and PP5·ERK2 complexes partially depends on HSP90 binding to PP5 but does not require PP5 or ERK1/2 activity. However, PP5 and ERK activity regulates the phosphorylation state of Raf1 kinase, an upstream activator of ERK signaling. Whereas expression of constitutively active Rac1 promotes the assembly of PP5·ERK1/2 complexes, acute activation of ERK1/2 fails to influence the phosphatase-kinase interaction. Introduction of oncogenic HRas (HRas(V12)) has no effect on PP5-ERK1 binding but selectively decreases the interaction of PP5 with ERK2, in a manner that is independent of PP5 and MAPK/ERK kinase (MEK) activity, yet paradoxically requires ERK2 activity. Additional studies conducted with oncogenic variants of KRas4B reveal that KRas(L61), but not KRas(V12), also decreases the PP5-ERK2 interaction. The expression of wild type HRas or KRas proteins fails to reduce PP5-ERK2 binding, indicating that the effect is specific to HRas(V12) and KRas(L61) gain-of-function mutations. These findings reveal a novel, differential responsiveness of PP5-ERK1 and PP5-ERK2 interactions to select oncogenic Ras variants and also support a role for PP5·ERK complexes in regulating the feedback phosphorylation of PP5-associated Raf1.

  15. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  16. Spatial Navigation in Complex and Radial Mazes in APP23 Animals and Neurotrophin Signaling as a Biological Marker of Early Impairment

    Science.gov (United States)

    Hellweg, Rainer; Huber, Roman; Kuhl, Alexander; Riepe, Matthias W.; Lohmann, Peter

    2006-01-01

    Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease(AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse…

  17. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  18. Conflict and inhibition differentially affect the N200/P300 complex in a combined go/nogo and stop-signal task.

    Science.gov (United States)

    Enriquez-Geppert, Stefanie; Konrad, Carsten; Pantev, Christo; Huster, René J

    2010-06-01

    Conflict and inhibition are considered to exert strong influences on the neurophysiological N200 and P300 brain responses as evoked in go/nogo and stop-signal tasks. In order to separate their underlying neural and functional mechanisms, the current experiment manipulated both conflict and inhibition. To do so, the go/nogo and stop-signal tasks were merged into one paradigm. Conflict was manipulated by varying go-trial frequencies across blocks (75% vs. 25%). Motor inhibition was manipulated by using go, nogo and stop trials each representing a different load of inhibition. Event-related potentials (ERPs) as well as current density reconstructions (CDRs) of fifteen healthy participants were analyzed. Overall, infrequent trials evoked significantly more pronounced N200s than frequent trials. The P300 predominantly revealed significant variations between trial types (go, nogo, stop). Estimated source activations of the MCC and the IFC supported the ERP results; N200-related effects were revealed in both regions, whereas the condition-specific variations of the P300 were only observed in the IFC. The results indicate that the N200 primarily reflects conflict-related effects whereas the P300 predominantly represents motor inhibition. Copyright 2010 Elsevier Inc. All rights reserved.

  19. HIF-inducible miR-191 promotes migration in breast cancer through complex regulation of TGFβ-signaling in hypoxic microenvironment.

    Science.gov (United States)

    Nagpal, Neha; Ahmad, Hafiz M.; Chameettachal, Shibu; Sundar, Durai; Ghosh, Sourabh; Kulshreshtha, Ritu

    2015-01-01

    The molecular mechanisms of hypoxia induced breast cell migration remain incompletely understood. Our results show that hypoxia through hypoxia-inducible factor (HIF) brings about a time-dependent increase in the level of an oncogenic microRNA, miR-191 in various breast cancer cell lines. miR-191 enhances breast cancer aggressiveness by promoting cell proliferation, migration and survival under hypoxia. We further established that miR-191 is a critical regulator of transforming growth factor beta (TGFβ)-signaling and promotes cell migration by inducing TGFβ2 expression under hypoxia through direct binding and indirectly by regulating levels of a RNA binding protein, human antigen R (HuR). The levels of several TGFβ pathway genes (like VEGFA, SMAD3, CTGF and BMP4) were found to be higher in miR-191 overexpressing cells. Lastly, anti-miR-191 treatment given to breast tumor spheroids led to drastic reduction in spheroid tumor volume. This stands as a first report of identification of a microRNA mediator that links hypoxia and the TGFβ signaling pathways, both of which are involved in regulation of breast cancer metastasis. Together, our results show a critical role of miR-191 in hypoxia-induced cancer progression and suggest that miR-191 inhibition may offer a novel therapy for hypoxic breast tumors. PMID:25867965

  20. A chemical approach for site-specific identification of NMR signals from protein side-chain NH{sub 3}{sup +} groups forming intermolecular ion pairs in protein–nucleic acid complexes

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Kurtis M. [University of Texas Health Science Center at Houston, Department of NanoMedicine and Biomedical Engineering and Institute of Molecular Medicine (United States); Nguyen, Dan; Esadze, Alexandre; Zandrashvili, Levani [University of Texas Medical Branch, Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics (United States); Gorenstein, David G. [University of Texas Health Science Center at Houston, Department of NanoMedicine and Biomedical Engineering and Institute of Molecular Medicine (United States); Iwahara, Junji, E-mail: juiwahar@utmb.edu, E-mail: j.iwahara@utmb.edu [University of Texas Medical Branch, Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics (United States)

    2015-05-15

    Protein–nucleic acid interactions involve intermolecular ion pairs of protein side-chain and DNA or RNA phosphate groups. Using three protein–DNA complexes, we demonstrate that site-specific oxygen-to-sulfur substitution in phosphate groups allows for identification of NMR signals from the protein side-chain NH{sub 3}{sup +} groups forming the intermolecular ion pairs. A characteristic change in their {sup 1}H and {sup 15}N resonances upon this modification (i.e., substitution of phosphate to phosphorodithioate) can represent a signature of an intermolecular ion pair. Hydrogen-bond scalar coupling between protein side-chain {sup 15}N and DNA phosphorodithiaote {sup 31}P nuclei provides direct confirmation of the intermolecular ion pair. The same approach is likely applicable to protein–RNA complexes as well.

  1. A chemical approach for site-specific identification of NMR signals from protein side-chain NH3+ groups forming intermolecular ion pairs in protein–nucleic acid complexes

    International Nuclear Information System (INIS)

    Anderson, Kurtis M.; Nguyen, Dan; Esadze, Alexandre; Zandrashvili, Levani; Gorenstein, David G.; Iwahara, Junji

    2015-01-01

    Protein–nucleic acid interactions involve intermolecular ion pairs of protein side-chain and DNA or RNA phosphate groups. Using three protein–DNA complexes, we demonstrate that site-specific oxygen-to-sulfur substitution in phosphate groups allows for identification of NMR signals from the protein side-chain NH 3 + groups forming the intermolecular ion pairs. A characteristic change in their 1 H and 15 N resonances upon this modification (i.e., substitution of phosphate to phosphorodithioate) can represent a signature of an intermolecular ion pair. Hydrogen-bond scalar coupling between protein side-chain 15 N and DNA phosphorodithiaote 31 P nuclei provides direct confirmation of the intermolecular ion pair. The same approach is likely applicable to protein–RNA complexes as well

  2. HAB1–SWI3B Interaction Reveals a Link between Abscisic Acid Signaling and Putative SWI/SNF Chromatin-Remodeling Complexes in Arabidopsis[C][W

    Science.gov (United States)

    Saez, Angela; Rodrigues, Americo; Santiago, Julia; Rubio, Silvia; Rodriguez, Pedro L.

    2008-01-01

    Abscisic acid (ABA) has an important role for plant growth, development, and stress adaptation. HYPERSENSITIVE TO ABA1 (HAB1) is a protein phosphatase type 2C that plays a key role as a negative regulator of ABA signaling; however, the molecular details of HAB1 action in this process are not known. A two-hybrid screen revealed that SWI3B, an Arabidopsis thaliana homolog of the yeast SWI3 subunit of SWI/SNF chromatin-remodeling complexes, is a prevalent interacting partner of HAB1. The interaction mapped to the N-terminal half of SWI3B and required an intact protein phosphatase catalytic domain. Bimolecular fluorescence complementation and coimmunoprecipitation assays confirmed the interaction of HAB1 and SWI3B in the nucleus of plant cells. swi3b mutants showed a reduced sensitivity to ABA-mediated inhibition of seed germination and growth and reduced expression of the ABA-responsive genes RAB18 and RD29B. Chromatin immunoprecipitation experiments showed that the presence of HAB1 in the vicinity of RD29B and RAB18 promoters was abolished by ABA, which suggests a direct involvement of HAB1 in the regulation of ABA-induced transcription. Additionally, our results uncover SWI3B as a novel positive regulator of ABA signaling and suggest that HAB1 modulates ABA response through the regulation of a putative SWI/SNF chromatin-remodeling complex. PMID:19033529

  3. Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells.

    Science.gov (United States)

    Lin, Meng-Liang; Lu, Yao-Cheng; Chen, Hung-Yi; Lee, Chuan-Chun; Chung, Jing-Gung; Chen, Shih-Shun

    2014-05-01

    Stromal cell-derived factor-1α (SDF-1α) is a ligand for C-X-C chemokine receptor type 4 (CXCR4), which contributes to the metastasis of cancer cells by promoting cell migration. Here, we show that the SDF-1α/CXCR4 axis can significantly increase invasion of esophageal carcinoma (EC) cells. We accomplished this by examining the effects of CXCR4 knockdown as well as treatment with a CXCR4-neutralizing antibody and the CXCR4-specific inhibitor AMD3100. Curcumin suppressed SDF-1α-induced cell invasion and matrix metalloproteinase-2 (MMP-2) promoter activity, cell surface localization of CXCR4 at lipid rafts, and lipid raft-associated ras-related C3 botulinum toxin substrate 1 (Rac1)/phosphatidylinositol 3-kinase (PI3K) p85α/Akt signaling. Curcumin inhibited SDF-1α-induced cell invasion by suppressing the Rac1-PI3K signaling complex at lipid rafts but did not abrogate lipid raft formation. We further demonstrate that the attenuation of lipid raft-associated Rac1 activity by curcumin was critical for the inhibition of SDF-1α-induced PI3K/Akt/NF-κB activation, cell surface localization of CXCR4 at lipid rafts, MMP-2 promoter activity, and cell invasion. Collectively, our results indicate that curcumin inhibits SDF-1α-induced EC cell invasion by suppressing the formation of the lipid raft-associated Rac1-PI3K-Akt signaling complex, the localization of CXCR4 with lipid rafts at the cell surface, and MMP-2 promoter activity, likely through the inhibition of Rac1 activity. © 2012 Wiley Periodicals, Inc.

  4. Capturing the photo-signaling state of a photoreceptor in a steady-state fashion by binding a transition metal complex.

    Science.gov (United States)

    Yu, Pengyun; Song, Lei; Qin, Jun; Wang, Jianping

    2017-11-01

    Binding a small molecule to proteins causes conformational changes, but often to a limited extent. Here, we demonstrate that the interaction of a CO-releasing molecule (CORM3) with a photoreceptor photoactive yellow protein (PYP) drives large structural changes in the latter. The interaction of CORM3 and a mutant of PYP, Met100Ala, not only trigger the isomerization of its chromophore, p-coumaric acid, from its anionic trans configuration to a protonated cis configuration, but also increases the content of β-sheet at the cost of α-helix and random coil in the secondary structure of the protein. The CORM3 derived Met100Ala is found to highly resemble the signaling state, which is one of the key photo-intermediates of this photoactive protein, in both protein local conformation and chromophore configuration. The organometallic reagents hold promise as protein engineering tools. This work highlights a novel approach to structurally accessing short lived intermediates of proteins in a steady-state fashion. © 2017 The Protein Society.

  5. Structural modelling and molecular dynamics of a multi-stress responsive WRKY TF-DNA complex towards elucidating its role in stress signalling mechanisms in chickpea.

    Science.gov (United States)

    Konda, Aravind Kumar; Farmer, Rohit; Soren, Khela Ram; P S, Shanmugavadivel; Setti, Aravind

    2017-07-28

    Chickpea is a premier food legume crop with high nutritional quality and attains prime importance in the current era of 795 million people being undernourished worldwide. Chickpea production encounters setbacks due to various stresses and understanding the role of key transcription factors (TFs) involved in multiple stresses becomes inevitable. We have recently identified a multi-stress responsive WRKY TF in chickpea. The present study was conducted to predict the structure of WRKY TF to identify the DNA-interacting residues and decipher DNA-protein interactions. Comparative modelling approach produced 3D model of the WRKY TF with good stereochemistry, local/global quality and further revealed W19, R20, K21, and Y22 motifs within a vicinity of 5 Å to the DNA amongst R18, G23, Q24, K25, Y36, Y37, R38 and K47 and these positions were equivalent to the 2LEX WRKY domain of Arabidopsis. Molecular simulations analysis of reference protein -PDB ID 2LEX, along with Car-WRKY TF modelled structure with the DNA coordinates derived from PDB ID 2LEX and docked using HADDOCK were executed. Root Mean Square (RMS) Deviation and RMS Fluctuation values yielded consistently stable trajectories over 50 ns simulation. Strengthening the obtained results, neither radius of gyration, distance and total energy showed any signs of DNA-WRKY complex falling apart nor any significant dissociation event over 50 ns run. Therefore, the study provides first insights into the structural properties of multi-stress responsive WRKY TF-DNA complex in chickpea, enabling genome wide identification of TF binding sites and thereby deciphers their gene regulatory networks.

  6. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Xie, Dan; Yu, Shi-Cang; Yang, Xiao-Jun; He, Li-Ru; Yang, Jing; Ping, Yi-Fang; Wang, Bin; Yang, Lang; Xu, Sen-Lin; Cui, Wei; Wang, Qing-Liang; Fu, Wen-Juan; Liu, Qing; Qian, Cheng; Cui, You-Hong; Rich, Jeremy N; Kung, Hsiang-Fu; Zhang, Xia; Bian, Xiu-Wu

    2013-05-15

    Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade. POU5F1 could form a novel complex with β-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathologic specimens excised from 200 patients with lung adenocarcinoma, we found that colocalization of highly expressed IGF-IR with β-catenin and POU5F1 predicted poor prognosis. Taken together, we show that IGF-IR-mediated POU5F1 expression to form a complex with β-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-IR, β-catenin, and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma. ©2013 AACR.

  7. Method of signal analysis

    International Nuclear Information System (INIS)

    Berthomier, Charles

    1975-01-01

    A method capable of handling the amplitude and the frequency time laws of a certain kind of geophysical signals is described here. This method is based upon the analytical signal idea of Gabor and Ville, which is constructed either in the time domain by adding an imaginary part to the real signal (in-quadrature signal), or in the frequency domain by suppressing negative frequency components. The instantaneous frequency of the initial signal is then defined as the time derivative of the phase of the analytical signal, and his amplitude, or envelope, as the modulus of this complex signal. The method is applied to three types of magnetospheric signals: chorus, whistlers and pearls. The results obtained by analog and numerical calculations are compared to results obtained by classical systems using filters, i.e. based upon a different definition of the concept of frequency. The precision with which the frequency-time laws are determined leads then to the examination of the principle of the method and to a definition of instantaneous power density spectrum attached to the signal, and to the first consequences of this definition. In this way, a two-dimensional representation of the signal is introduced which is less deformed by the analysis system properties than the usual representation, and which moreover has the advantage of being obtainable practically in real time [fr

  8. Effect of low dose of gamma radiation on the induction and signalling of complex damages of DNA in the mammals cells

    International Nuclear Information System (INIS)

    Boucher, D.

    2006-09-01

    The work presented in the frame of this thesis are in line with the studies on the radioinduced damages of DNA in order to better understand their genotoxic effects and the associated risks. The different radioinduced damages of DNA are given, the complex damages, double strand-break and multiple damages are particularly detailed as well as their methods of detection. Are presented the systems implemented in the cell in order to point the radioinduced damages and to implement the repair systems of these lesions. Then, are presented the knowledge on the effects of low doses and low dose rates. The whole of this work has for objective to highlight the mechanisms by which the reduction of dose rate allows an increase of cell survival. By a better knowledge of the system implemented in response to a low dose rate irradiation, it is possible to valid or not the linear without threshold model of low doses effects and consequently to better understand the eventual risks of cancer linked to exposures of low doses of ionizing radiation. (N.C.)

  9. In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway.

    Science.gov (United States)

    Pantovic, Aleksandar; Bosnjak, Mihajlo; Arsikin, Katarina; Kosic, Milica; Mandic, Milos; Ristic, Biljana; Tosic, Jelena; Grujicic, Danica; Isakovic, Aleksandra; Micic, Nikola; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2017-02-01

    We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G 2 M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-β-signaling pathways regulates the innate inflammatory response.

    Science.gov (United States)

    Wang, Huizhi; Brown, Jonathan; Gu, Zhen; Garcia, Carlos A; Liang, Ruqiang; Alard, Pascale; Beurel, Eléonore; Jope, Richard S; Greenway, Terrance; Martin, Michael

    2011-05-01

    The PI3K pathway and its regulation of mammalian target of rapamycin complex 1 (mTORC1) and glycogen synthase kinase 3 (GSK3) play pivotal roles in controlling inflammation. In this article, we show that mTORC1 and GSK3-β converge and that the capacity of mTORC1 to affect the inflammatory response is due to the inactivation of GSK3-β. Inhibition of mTORC1 attenuated GSK3 phosphorylation and increased its kinase activity. Immunoprecipitation and in vitro kinase assays demonstrated that GSK3-β associated with a downstream target of mTORC1, p85S6K, and phosphorylated GSK3-β. Inhibition of S6K1 abrogated the phosphorylation of GSK3-β while increasing and decreasing the levels of IL-12 and IL-10, respectively, in LPS-stimulated monocytes. In contrast, the direct inhibition of GSK3 attenuated the capacity of S6K1 inhibition to influence the levels of IL-10 and IL-12 produced by LPS-stimulated cells. At the transcriptional level, mTORC1 inhibition reduced the DNA binding of CREB and this effect was reversed by GSK3 inhibition. As a result, mTORC1 inhibition increased the levels of NF-κB p65 associated with CREB-binding protein. Inhibition of NF-κB p65 attenuated rapamycin's ability to influence the levels of pro- or anti-inflammatory cytokine production in monocytes stimulated with LPS. These studies identify the molecular mechanism by which mTORC1 affects GSK3 and show that mTORC1 inhibition regulates pro- and anti-inflammatory cytokine production via its capacity to inactivate GSK3.

  11. Convergence of the Mammalian Target of Rapamycin Complex 1- and Glycogen Synthase Kinase 3-β–Signaling Pathways Regulates the Innate Inflammatory Response

    Science.gov (United States)

    Wang, Huizhi; Brown, Jonathan; Gu, Zhen; Garcia, Carlos A.; Liang, Ruqiang; Alard, Pascale; Beurel, Eléonore; Jope, Richard S.; Greenway, Terrance; Martin, Michael

    2011-01-01

    The PI3K pathway and its regulation of mammalian target of rapamycin complex 1 (mTORC1) and glycogen synthase kinase 3 (GSK3) play pivotal roles in controlling inflammation. In this article, we show that mTORC1 and GSK3-β converge and that the capacity of mTORC1 to affect the inflammatory response is due to the inactivation of GSK3-β. Inhibition of mTORC1 attenuated GSK3 phosphorylation and increased its kinase activity. Immunoprecipitation and in vitro kinase assays demonstrated that GSK3-β associated with a downstream target of mTORC1, p85S6K, and phosphorylated GSK3-β. Inhibition of S6K1 abrogated the phosphorylation of GSK3-β while increasing and decreasing the levels of IL-12 and IL-10, respectively, in LPS-stimulated monocytes. In contrast, the direct inhibition of GSK3 attenuated the capacity of S6K1 inhibition to influence the levels of IL-10 and IL-12 produced by LPS-stimulated cells. At the transcriptional level, mTORC1 inhibition reduced the DNA binding of CREB and this effect was reversed by GSK3 inhibition. As a result, mTORC1 inhibition increased the levels of NF-κB p65 associated with CREB-binding protein. Inhibition of NF-κB p65 attenuated rapamycin’s ability to influence the levels of pro- or anti-inflammatory cytokine production in monocytes stimulated with LPS. These studies identify the molecular mechanism by which mTORC1 affects GSK3 and show that mTORC1 inhibition regulates pro- and anti-inflammatory cytokine production via its capacity to inactivate GSK3. PMID:21422248

  12. ATP signals

    DEFF Research Database (Denmark)

    Novak, Ivana

    2016-01-01

    The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas......The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas...

  13. Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels.

    Directory of Open Access Journals (Sweden)

    Alexander V Maltsev

    2017-08-01

    Full Text Available Intracellular Local Ca releases (LCRs from sarcoplasmic reticulum (SR regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s. Background Ca (in locations lacking LCRs quickly decays to resting Ca levels (<100 nM at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates.

  14. Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Liao, Hsien-Ching; Chen, Mei-Yu

    2012-02-24

    The conserved Ser/Thr kinase target of rapamycin (TOR) serves as a central regulator in controlling cell growth-related functions. There exist two distinct TOR complexes, TORC1 and TORC2, each coupling to specific downstream effectors and signaling pathways. In Saccharomyces cerevisiae, TORC2 is involved in regulating actin organization and maintaining cell wall integrity. Ypk2 (yeast protein kinase 2), a member of the cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase family, is a TORC2 substrate known to participate in actin and cell wall regulation. Employing avo3(ts) mutants with defects in TORC2 functions that are suppressible by active Ypk2, we investigated the molecular interactions involved in mediating TORC2 signaling to Ypk2. GST pulldown assays in yeast lysates demonstrated physical interactions between Ypk2 and components of TORC2. In vitro binding assays revealed that Avo1 directly binds to Ypk2. In avo3(ts) mutants, the TORC2-Ypk2 interaction was reduced and could be restored by AVO1 overexpression, highlighting the important role of Avo1 in coupling TORC2 to Ypk2. The interaction was mapped to an internal region (amino acids 600-840) of Avo1 and a C-terminal region of Ypk2. Ypk2(334-677), a truncated form of Ypk2 containing the Avo1-interacting region, was able to interfere with Avo1-Ypk2 interaction in vitro. Overexpressing Ypk2(334-677) in yeast cells resulted in a perturbation of TORC2 functions, causing defective cell wall integrity, aberrant actin organization, and diminished TORC2-dependent Ypk2 phosphorylation evidenced by the loss of an electrophoretic mobility shift. Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway.

  15. A new signal-on method for the detection of protein based on binding-induced strategy and photoinduced electron transfer between Ag nanoclusters and split G-quadruplex-hemin complexes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kai, E-mail: zhangkai@jsinm.org; Wang, Ke; Zhu, Xue; Xie, Minhao

    2015-08-05

    Proteins play important roles in biological and cellular processes. The levels of proteins can be useful biomarkers for cellular events or disease diagnosis, thus the method for sensitive and selective detection of proteins is imperative to proteins express, study, and clinical diagnosis. Herein, we report a “signal-on” platform for the assay of protein based on binding-induced strategy and photoinduced electron transfer between Ag nanoclusters and split G-quadruplex-hemin complexes. By using biotin as the affinity ligand, this simple protocol could sensitively detect streptavidin with a detection limit down to 10 pM. With the use of an antibody as the affinity ligand, a method for homogeneous fluorescence detection of Prostate Specific Antigen (PSA) was also proposed with a detection limit of 10 pM. The one-step and wash-free assay showed good selectivity. Its high sensitivity, acceptable accuracy, and satisfactory versatility of analytes led to various applications in bioanalysis. - Highlights: • AgNCs have great potential for application in biomedicine. • Binding of two affinity ligands can result in binding-induced DNA assemblies. • PET can be happened between DNA/AgNCs and G-quadruplex/hemin complexes. • A platform for the detection of proteins was proposed by using PET and binding-induced strategy.

  16. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Signals and systems for dummies

    CERN Document Server

    Wickert, Mark

    2013-01-01

    Getting mixed signals in your signals and systems course? The concepts covered in a typical signals and systems course are often considered by engineering students to be some of the most difficult to master. Thankfully, Signals & Systems For Dummies is your intuitive guide to this tricky course, walking you step-by-step through some of the more complex theories and mathematical formulas in a way that is easy to understand. From Laplace Transforms to Fourier Analyses, Signals & Systems For Dummies explains in plain English the difficult concepts that can trip you up

  18. Detection of signals in noise

    CERN Document Server

    Whalen, Anthony D; Declaris, Nicholas

    1971-01-01

    Detection of Signals in Noise serves as an introduction to the principles and applications of the statistical theory of signal detection. The book discusses probability and random processes; narrowband signals, their complex representation, and their properties described with the aid of the Hilbert transform; and Gaussian-derived processes. The text also describes the application of hypothesis testing for the detection of signals and the fundamentals required for statistical detection of signals in noise. Problem exercises, references, and a supplementary bibliography are included after each c

  19. Multiscale Signal Analysis and Modeling

    CERN Document Server

    Zayed, Ahmed

    2013-01-01

    Multiscale Signal Analysis and Modeling presents recent advances in multiscale analysis and modeling using wavelets and other systems. This book also presents applications in digital signal processing using sampling theory and techniques from various function spaces, filter design, feature extraction and classification, signal and image representation/transmission, coding, nonparametric statistical signal processing, and statistical learning theory. This book also: Discusses recently developed signal modeling techniques, such as the multiscale method for complex time series modeling, multiscale positive density estimations, Bayesian Shrinkage Strategies, and algorithms for data adaptive statistics Introduces new sampling algorithms for multidimensional signal processing Provides comprehensive coverage of wavelets with presentations on waveform design and modeling, wavelet analysis of ECG signals and wavelet filters Reviews features extraction and classification algorithms for multiscale signal and image proce...

  20. Change of the high-latitude ionosphere during heating by a powerful short radio wave of the EISCAT/Heating complex according to signals of the GLONASS satellite and the incoherent scattering radar

    Directory of Open Access Journals (Sweden)

    Tereshchenko E. D.

    2018-03-01

    Full Text Available Results of observations of variations of temperature, electron concentration and total electron content of the high-latitude region of the ionosphere during its modification by powerful short radio waves of the heating complex EISCAT/Heating (Tromsø, Norway according to signals of the GLONASS satellites and the incoherent scattering UHF EISCAT radar (Tromsø, Norway have been provided. The geometry of passes of the GLONASS and GPS satellites for operating conditions of the heating complex in Tromsø has been considered. It has been shown that during the experiments on the EISCAT/Heating complex for the study of the modified structure of the high-latitude ionosphere it is more convenient to use the GLONASS satellites. Parameters of orbits of these satellites allow researching changes of total electron content in the direction along the geomagnetic field line at the place of observation. It has been shown that during heating of the ionosphere by powerful short radio waves its structure is becoming an irregular one. Operation of the heating complex in the mode "switched on – switched off" has caused appearance of wavy variations of total electron content with the periods close to the heating period. The main features of behavior of the total electron content in the case of the continuous heating of the ionosphere in the direction of the magnetic zenith according to the GLONASS satellite are: reduction of total electron content in the central zone of the antenna diagram, i. e. in the direction of the magnetic zenith, and presence of the increased values of total electron content at the edges of the heating zone. According to the incoherent scattering radar the heating of the ionosphere by the powerful short radio wave has created the region of the increased electron temperature and electron concentration along the direction of the magnetic zenith. The behavior of total electron content according to the GLONASS satellite and the radar of

  1. Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt.

    Science.gov (United States)

    Zhang, Q-G; Han, D; Xu, J; Lv, Q; Wang, R; Yin, X-H; Xu, T-L; Zhang, G-Y

    2006-12-01

    Activation of Akt/protein kinase B has been recently reported to play an important role in ischemic tolerance. We here demonstrate that the decreased protein expression and phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co-immunoprecipitation analysis reveals that Akt physically interacts with Rac1, a small Rho family GTPase required for mixed lineage kinase 3 (MLK3) autophosphorylation, and both this interaction and Rac1-Ser-71 phosphorylation induced by Akt are promoted in preconditioned rats. In addition, we show that Akt activation results in the disassembly of the plenty of SH3s (POSH)-MLK3-Rac1 signaling complex and down-regulation of the activation of MLK3/c-Jun N-terminal kinase (JNK) pathway. Akt activation results in decreased serine phosphorylation of 14-3-3, a cytoplasmic anchor of Bax, and prevents ischemia-induced mitochondrial translocation of Bax, release of cytochrome c, and activation of caspase-3. The expression of Fas ligand is also decreased in the CA1 region. Akt activation protects against apoptotic neuronal death as shown in TUNEL staining following IPC. Intracerebral infusion of LY294002 before IPC reverses the increase in Akt phosphorylation and the decrease in JNK signaling activation, as well as the neuroprotective action of IPC. Our results suggest that activation of pro-apoptotic MLK3/JNK3 cascade can be suppressed through activating anti-apoptotic phosphoinositide 3-kinase/Akt pathway induced by a sublethal ischemic insult, which provides a functional link between Akt and the JNK family of stress-activated kinases in ischemic tolerance.

  2. Signal detection

    International Nuclear Information System (INIS)

    Tholomier, M.

    1985-01-01

    In a scanning electron microscope, whatever is the measured signal, the same set is found: incident beam, sample, signal detection, signal amplification. The resulting signal is used to control the spot luminosity with the observer cathodoscope. This is synchronized with the beam scanning on the sample; on the cathodoscope, the image in secondary electrons, backscattered electrons,... of the sample surface is reconstituted. The best compromise must be found between a register time low enough to remove eventual variations (under the incident beam) of the nature of the observed phenomenon, and a good spatial resolution of the image and a signal-to-noise ratio high enough. The noise is one of the basic limitations of the scanning electron microscope performance. The whose measurement line must be optimized to reduce it [fr

  3. G Protein-coupled Receptors and Resistance to Inhibitors of Cholinesterase-8A (Ric-8A) Both Regulate the Regulator of G Protein Signaling 14 (RGS14)·Gαi1 Complex in Live Cells*

    OpenAIRE

    Vellano, Christopher P.; Maher, Ellen M.; Hepler, John R.; Blumer, Joe B.

    2011-01-01

    Background: Regulator of G protein signaling 14 (RGS14) is a G protein regulatory (GPR) protein that participates in unconventional G protein signaling independent of G protein-coupled receptors (GPCRs).

  4. Redox signaling in plants.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham

    2013-06-01

    Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment.

  5. Signal Processing

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Signal processing techniques, extensively used nowadays to maximize the performance of audio and video equipment, have been a key part in the design of hardware and software for high energy physics detectors since pioneering applications in the UA1 experiment at CERN in 1979

  6. Multimodal signalling in estrildid finches

    DEFF Research Database (Denmark)

    Gomes, A. C. R.; Funghi, C.; Soma, M.

    2017-01-01

    Sexual traits (e.g. visual ornaments, acoustic signals, courtship behaviour) are often displayed together as multimodal signals. Some hypotheses predict joint evolution of different sexual signals (e.g. to increase the efficiency of communication) or that different signals trade off with each other...... (e.g. due to limited resources). Alternatively, multiple signals may evolve independently for different functions, or to communicate different information (multiple message hypothesis). We evaluated these hypotheses with a comparative study in the family Estrildidae, one of the largest songbird...... compromise, but generally courtship dance also evolved independently from other signals. Instead of correlated evolution, we found that song, dance and colour are each related to different socio-ecological traits. Song complexity evolved together with ecological generalism, song performance with investment...

  7. Non-Smad signaling pathways.

    Science.gov (United States)

    Mu, Yabing; Gudey, Shyam Kumar; Landström, Maréne

    2012-01-01

    Transforming growth factor-beta (TGFβ) is a key regulator of cell fate during embryogenesis and has also emerged as a potent driver of the epithelial-mesenchymal transition during tumor progression. TGFβ signals are transduced by transmembrane type I and type II serine/threonine kinase receptors (TβRI and TβRII, respectively). The activated TβR complex phosphorylates Smad2 and Smad3, converting them into transcriptional regulators that complex with Smad4. TGFβ also uses non-Smad signaling pathways such as the p38 and Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways to convey its signals. Ubiquitin ligase tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6) and TGFβ-associated kinase 1 (TAK1) have recently been shown to be crucial for the activation of the p38 and JNK MAPK pathways. Other TGFβ-induced non-Smad signaling pathways include the phosphoinositide 3-kinase-Akt-mTOR pathway, the small GTPases Rho, Rac, and Cdc42, and the Ras-Erk-MAPK pathway. Signals induced by TGFβ are tightly regulated and specified by post-translational modifications of the signaling components, since they dictate the subcellular localization, activity, and duration of the signal. In this review, we discuss recent findings in the field of TGFβ-induced responses by non-Smad signaling pathways.

  8. Integrin Signalling

    OpenAIRE

    Schelfaut, Roselien

    2005-01-01

    Integrins are receptors presented on most cells. By binding ligand they can generate signalling pathways inside the cell. Those pathways are a linkage to proteins in the cytosol. It is known that tumor cells can survive and proliferate in the absence of a solid support while normal cells need to be bound to ligand. To understand why tumour cells act that way, we first have to know how ligand-binding to integrins affect the cell. This research field includes studies on activation of proteins b...

  9. Lymphocyte signaling: beyond knockouts.

    Science.gov (United States)

    Saveliev, Alexander; Tybulewicz, Victor L J

    2009-04-01

    The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Although this gene 'knockout' approach is often informative, in many cases, the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data.

  10. The Evolution of Covert Signaling.

    Science.gov (United States)

    Smaldino, Paul E; Flamson, Thomas J; McElreath, Richard

    2018-03-20

    Human sociality depends upon the benefits of mutual aid and extensive communication. However, diverse norms and preferences complicate mutual aid, and ambiguity in meaning hinders communication. Here we demonstrate that these two problems can work together to enhance cooperation through the strategic use of deliberately ambiguous signals: covert signaling. Covert signaling is the transmission of information that is accurately received by its intended audience but obscured when perceived by others. Such signals may allow coordination and enhanced cooperation while also avoiding the alienation or hostile reactions of individuals with different preferences. Although the empirical literature has identified potential mechanisms of covert signaling, such as encryption in humor, there is to date no formal theory of its dynamics. We introduce a novel mathematical model to assess when a covert signaling strategy will evolve, as well as how receiver attitudes coevolve with covert signals. Covert signaling plausibly serves an important function in facilitating within-group cooperative assortment by allowing individuals to pair up with similar group members when possible and to get along with dissimilar ones when necessary. This mechanism has broad implications for theories of signaling and cooperation, humor, social identity, political psychology, and the evolution of human cultural complexity.

  11. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  12. Complex chemistry

    International Nuclear Information System (INIS)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-01

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  13. Dynamic complexity: plant receptor complexes at the plasma membrane.

    Science.gov (United States)

    Burkart, Rebecca C; Stahl, Yvonne

    2017-12-01

    Plant receptor complexes at the cell surface perceive many different external and internal signalling molecules and relay these signals into the cell to regulate development, growth and immunity. Recent progress in the analyses of receptor complexes using different live cell imaging approaches have shown that receptor complex formation and composition are dynamic and take place at specific microdomains at the plasma membrane. In this review we focus on three prominent examples of Arabidopsis thaliana receptor complexes and how their dynamic spatio-temporal distribution at the PM has been studied recently. We will elaborate on the newly emerging concept of plasma membrane microdomains as potential hubs for specific receptor complex assembly and signalling outputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Regulator of G protein signaling 2 (RGS2 and RGS4 form distinct G protein-dependent complexes with protease activated-receptor 1 (PAR1 in live cells.

    Directory of Open Access Journals (Sweden)

    Sungho Ghil

    Full Text Available Protease-activated receptor 1 (PAR1 is a G-protein coupled receptor (GPCR that is activated by natural proteases to regulate many physiological actions. We previously reported that PAR1 couples to Gi, Gq and G12 to activate linked signaling pathways. Regulators of G protein signaling (RGS proteins serve as GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins interact directly with certain GPCRs to modulate their signals, though cellular mechanisms dictating selective RGS/GPCR coupling are poorly understood. Here, using bioluminescence resonance energy transfer (BRET, we tested whether RGS2 and RGS4 bind to PAR1 in live COS-7 cells to regulate PAR1/Gα-mediated signaling. We report that PAR1 selectively interacts with either RGS2 or RGS4 in a G protein-dependent manner. Very little BRET activity is observed between PAR1-Venus (PAR1-Ven and either RGS2-Luciferase (RGS2-Luc or RGS4-Luc in the absence of Gα. However, in the presence of specific Gα subunits, BRET activity was markedly enhanced between PAR1-RGS2 by Gαq/11, and PAR1-RGS4 by Gαo, but not by other Gα subunits. Gαq/11-YFP/RGS2-Luc BRET activity is promoted by PAR1 and is markedly enhanced by agonist (TFLLR stimulation. However, PAR1-Ven/RGS-Luc BRET activity was blocked by a PAR1 mutant (R205A that eliminates PAR1-Gq/11 coupling. The purified intracellular third loop of PAR1 binds directly to purified His-RGS2 or His-RGS4. In cells, RGS2 and RGS4 inhibited PAR1/Gα-mediated calcium and MAPK/ERK signaling, respectively, but not RhoA signaling. Our findings indicate that RGS2 and RGS4 interact directly with PAR1 in Gα-dependent manner to modulate PAR1/Gα-mediated signaling, and highlight a cellular mechanism for selective GPCR/G protein/RGS coupling.

  15. Signaling equilibria in sensorimotor interactions.

    Science.gov (United States)

    Leibfried, Felix; Grau-Moya, Jordi; Braun, Daniel A

    2015-08-01

    Although complex forms of communication like human language are often assumed to have evolved out of more simple forms of sensorimotor signaling, less attention has been devoted to investigate the latter. Here, we study communicative sensorimotor behavior of humans in a two-person joint motor task where each player controls one dimension of a planar motion. We designed this joint task as a game where one player (the sender) possesses private information about a hidden target the other player (the receiver) wants to know about, and where the sender's actions are costly signals that influence the receiver's control strategy. We developed a game-theoretic model within the framework of signaling games to investigate whether subjects' behavior could be adequately described by the corresponding equilibrium solutions. The model predicts both separating and pooling equilibria, in which signaling does and does not occur respectively. We observed both kinds of equilibria in subjects and found that, in line with model predictions, the propensity of signaling decreased with increasing signaling costs and decreasing uncertainty on the part of the receiver. Our study demonstrates that signaling games, which have previously been applied to economic decision-making and animal communication, provide a framework for human signaling behavior arising during sensorimotor interactions in continuous and dynamic environments. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Eliminating ambiguity in digital signals

    Science.gov (United States)

    Weber, W. J., III

    1979-01-01

    Multiamplitude minimum shift keying (mamsk) transmission system, method of differential encoding overcomes problem of ambiguity associated with advanced digital-transmission techniques with little or no penalty in transmission rate, error rate, or system complexity. Principle of method states, if signal points are properly encoded and decoded, bits are detected correctly, regardless of phase ambiguities.

  17. Tyrosine Phosphorylation in Brassinosteroid Signaling

    Science.gov (United States)

    Brassinosteroids (BRs) regulate plant growth and development through a complex signal transduction pathway involving BRASSINOSTEROID INSENSITIVE 1 (BRI1), which is the BR receptor, and its co-receptor BRI1-ASSOCIATED KINASE 1 (BAK1). Both proteins are classified as Ser/Thr protein kinases. Recently,...

  18. Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy.

    Science.gov (United States)

    Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K

    2002-11-15

    Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.

  19. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia

    2017-11-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  20. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia; Pluta, Dustin; Shen, Tong; Chen, Chuansheng; Xue, Gui; Ombao, Hernando

    2017-01-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible

  1. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  2. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  3. Photoacoustic signal amplification through plasmonic nanoparticle aggregation

    OpenAIRE

    Bayer, Carolyn L.; Nam, Seung Yun; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-01-01

    Photoacoustic imaging, using targeted plasmonic metallic nanoparticles, is a promising noninvasive molecular imaging method. Analysis of the photoacoustic signal generated by plasmonic metallic nanoparticles is complex because of the dependence upon physical properties of both the nanoparticle and the surrounding environment. We studied the effect of the aggregation of gold nanoparticles on the photoacoustic signal amplitude. We found that the photoacoustic signal from aggregated silica-coate...

  4. Power Spectrum Estimation of Randomly Sampled Signals

    DEFF Research Database (Denmark)

    Velte, Clara M.; Buchhave, Preben; K. George, William

    2014-01-01

    proportional to velocity magnitude that consist of well-defined frequency content, which makes bias easy to spot. The idea is that if the algorithms are not able to produce correct statistics from this simple signal, then they will certainly not be able to function well for a more complex measured LDA signal...

  5. CD147-CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Fei, Fei; Li, Xiaofei; Xu, Li; Li, Deyang; Zhang, Zhipei; Guo, Xu; Yang, Hushan; Chen, Zhinan; Xing, Jinliang

    2014-12-01

    It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated. The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation. Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147-/CD98hc-, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc. Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.

  6. A Cryo Complex Control

    CERN Document Server

    Alferov, V; Fedorchenko, V; Ivanova, N; Kholkin, A; Klimov, S; Krendelev, V; Kuznetsov, S; Lukyantsev, A; Lutchev, A; Milutkin, V; Sytin, A N; Vasilev, D

    2004-01-01

    A Cryogenic complex is being constructed to provide by liquid helium and nitrogen the RF-separator of kaons. About 500 parameters including temperature (1,8…300)K, liquid helium/nitrogen level, vacuum, 300 digital signals have to be measured, 70 commands generated, 20 closed loops activated. The paper describes controls electronics which includes home made I8051 compatible controllers connected by the CAN field bus to a bus controller and interface electronic modules for: - temperature measurements; - liquid Ni and He level measurements; - vacuum pumps current measurements; - analog and digital signals measurements and generations. The modules are tested together with signal imitators within a vertical slice of the Control System based on EPICS tools.

  7. Multivariate Analysis for the Processing of Signals

    Directory of Open Access Journals (Sweden)

    Beattie J.R.

    2014-01-01

    Full Text Available Real-world experiments are becoming increasingly more complex, needing techniques capable of tracking this complexity. Signal based measurements are often used to capture this complexity, where a signal is a record of a sample’s response to a parameter (e.g. time, displacement, voltage, wavelength that is varied over a range of values. In signals the responses at each value of the varied parameter are related to each other, depending on the composition or state sample being measured. Since signals contain multiple information points, they have rich information content but are generally complex to comprehend. Multivariate Analysis (MA has profoundly transformed their analysis by allowing gross simplification of the tangled web of variation. In addition MA has also provided the advantage of being much more robust to the influence of noise than univariate methods of analysis. In recent years, there has been a growing awareness that the nature of the multivariate methods allows exploitation of its benefits for purposes other than data analysis, such as pre-processing of signals with the aim of eliminating irrelevant variations prior to analysis of the signal of interest. It has been shown that exploiting multivariate data reduction in an appropriate way can allow high fidelity denoising (removal of irreproducible non-signals, consistent and reproducible noise-insensitive correction of baseline distortions (removal of reproducible non-signals, accurate elimination of interfering signals (removal of reproducible but unwanted signals and the standardisation of signal amplitude fluctuations. At present, the field is relatively small but the possibilities for much wider application are considerable. Where signal properties are suitable for MA (such as the signal being stationary along the x-axis, these signal based corrections have the potential to be highly reproducible, and highly adaptable and are applicable in situations where the data is noisy or

  8. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  9. Purinergic signalling and diabetes

    DEFF Research Database (Denmark)

    Burnstock, Geoffrey; Novak, Ivana

    2013-01-01

    , and common and divergent roles of receptors for nucleotides and nucleosides in different organ systems will be given. This integrated picture will aid our understanding of the challenges of the potential and currently used drugs targeted to specific organ/cells or disorders associated with diabetes.......The pancreas is an organ with a central role in nutrient breakdown, nutrient sensing and release of hormones regulating whole body nutrient homeostasis. In diabetes mellitus, the balance is broken-cells can be starving in the midst of plenty. There are indications that the incidence of diabetes...... type 1 and 2, and possibly pancreatogenic diabetes, is rising globally. Events leading to insulin secretion and action are complex, but there is emerging evidence that intracellular nucleotides and nucleotides are not only important as intracellular energy molecules but also as extracellular signalling...

  10. Pathophysiology of Glucocorticoid Signaling.

    Science.gov (United States)

    Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

    2018-06-01

    Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Insulin Signaling and Heart Failure

    Science.gov (United States)

    Riehle, Christian; Abel, E. Dale

    2016-01-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  12. Wnt signaling: Ig-norrin the dogma.

    Science.gov (United States)

    Clevers, Hans

    2004-06-08

    Secreted Wnt proteins trigger the intracellular Wnt signaling cascade upon engagement of dedicated Frizzled-Lrp receptor complexes. Unexpectedly, a non-Wnt ligand for this receptor complex has now been discovered. This novel ligand, Norrin, is mutated in the hereditary ocular Norrie syndrome. Copyright 2004 Elsevier Ltd.

  13. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

  14. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  15. Spectral Correlation of Multicarrier Modulated Signals and Its Application for Signal Detection

    Directory of Open Access Journals (Sweden)

    Zhang Haijian

    2010-01-01

    Full Text Available Spectral correlation theory for cyclostationary time-series signals has been studied for decades. Explicit formulas of spectral correlation function for various types of analog-modulated and digital-modulated signals are already derived. In this paper, we investigate and exploit the cyclostationarity characteristics for two kinds of multicarrier modulated (MCM signals: conventional OFDM and filter bank based multicarrier (FBMC signals. The spectral correlation characterization of MCM signal can be described by a special linear periodic time-variant (LPTV system. Using this LPTV description, we have derived the explicit theoretical formulas of nonconjugate and conjugate cyclic autocorrelation function (CAF and spectral correlation function (SCF for OFDM and FBMC signals. According to theoretical spectral analysis, Cyclostationary Signatures (CS are artificially embedded into MCM signal and a low-complexity signature detector is, therefore, presented for detecting MCM signal. Theoretical analysis and simulation results demonstrate the efficiency and robustness of this CS detector compared to traditionary energy detector.

  16. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    and into French. The complexity of the undertaking proved to be a central element in the students' learning, as the collaboration closely resembles the complexity of international documentation workplaces of language service providers. © Association of Teachers of Technical Writing.......This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dutch...

  17. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  18. Design of a Low-Power, Small-Area AEC-Q100-Compliant SENT Transmitter in Signal Conditioning IC for Automotive Pressure and Temperature Complex Sensors in 180 Nm CMOS Technology

    Science.gov (United States)

    Rikhan, Behnam Samadpoor; Kim, Dong-Gyu; Lee, Dong-Soo; Rehman, Muhammad Riaz Ur; Abbasizadeh, Hamed; Asif, Muhammad; Lee, Minjae; Yang, Youngoo; Lee, Kang-Yoon

    2018-01-01

    In this paper, a low-power and small-area Single Edge Nibble Transmission (SENT) transmitter design is proposed for automotive pressure and temperature complex sensor applications. To reduce the cost and size of the hardware, the pressure and temperature information is processed with a single integrated circuit (IC) and transmitted at the same time to the electronic control unit (ECU) through SENT. Due to its digital nature, it is immune to noise, has reduced sensitivity to electromagnetic interference (EMI), and generates low EMI. It requires only one PAD for its connectivity with ECU, and thus reduces the pin requirements, simplifies the connectivity, and minimizes the printed circuit board (PCB) complexity. The design is fully synthesizable, and independent of technology. The finite state machine-based approach is employed for area efficient implementation, and to translate the proposed architecture into hardware. The IC is fabricated in 1P6M 180 nm CMOS process with an area of (116 μm × 116 μm) and 4.314 K gates. The current consumption is 50 μA from a 1.8 V supply with a total 90 μW power. For compliance with AEC-Q100 for automotive reliability, a reverse and over voltage protection circuit is also implemented with human body model (HBM) electro-static discharge (ESD) of +6 kV, reverse voltage of −16 V to 0 V, over voltage of 8.2 V to 16 V, and fabricated area of 330 μm × 680 μm. The extensive testing, measurement, and simulation results prove that the design is fully compliant with SAE J2716 standard. PMID:29757996

  19. Softball Complex

    Science.gov (United States)

    Ellis, Jim

    1977-01-01

    The Parks and Recreation Department of Montgomery, Alabama, has developed a five-field softball complex as part of a growing community park with facilities for camping, golf, aquatics, tennis, and picnicking. (MJB)

  20. Lecithin Complex

    African Journals Online (AJOL)

    1Department of Food Science and Engineering, Xinyang College of Agriculture and ... Results: The UV and IR spectra of the complex showed an additive effect of polydatin-lecithin, in which .... Monochromatic Cu Ka radiation (wavelength =.

  1. Retroactive signaling in short signaling pathways.

    Directory of Open Access Journals (Sweden)

    Jacques-Alexandre Sepulchre

    Full Text Available In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles.

  2. Calcium Signaling in Taste Cells

    Science.gov (United States)

    Medler, Kathryn F.

    2014-01-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. PMID:25450977

  3. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  4. Subgroup complexes

    CERN Document Server

    Smith, Stephen D

    2011-01-01

    This book is intended as an overview of a research area that combines geometries for groups (such as Tits buildings and generalizations), topological aspects of simplicial complexes from p-subgroups of a group (in the spirit of Brown, Quillen, and Webb), and combinatorics of partially ordered sets. The material is intended to serve as an advanced graduate-level text and partly as a general reference on the research area. The treatment offers optional tracks for the reader interested in buildings, geometries for sporadic simple groups, and G-equivariant equivalences and homology for subgroup complexes.

  5. Complex manifolds

    CERN Document Server

    Morrow, James

    2006-01-01

    This book, a revision and organization of lectures given by Kodaira at Stanford University in 1965-66, is an excellent, well-written introduction to the study of abstract complex (analytic) manifolds-a subject that began in the late 1940's and early 1950's. It is largely self-contained, except for some standard results about elliptic partial differential equations, for which complete references are given. -D. C. Spencer, MathSciNet The book under review is the faithful reprint of the original edition of one of the most influential textbooks in modern complex analysis and geometry. The classic

  6. Complex Networks

    CERN Document Server

    Evsukoff, Alexandre; González, Marta

    2013-01-01

    In the last decade we have seen the emergence of a new inter-disciplinary field focusing on the understanding of networks which are dynamic, large, open, and have a structure sometimes called random-biased. The field of Complex Networks is helping us better understand many complex phenomena such as the spread of  deseases, protein interactions, social relationships, to name but a few. Studies in Complex Networks are gaining attention due to some major scientific breakthroughs proposed by network scientists helping us understand and model interactions contained in large datasets. In fact, if we could point to one event leading to the widespread use of complex network analysis is the availability of online databases. Theories of Random Graphs from Erdös and Rényi from the late 1950s led us to believe that most networks had random characteristics. The work on large online datasets told us otherwise. Starting with the work of Barabási and Albert as well as Watts and Strogatz in the late 1990s, we now know th...

  7. Psychophysics of Complex Auditory and Speech Stimuli

    National Research Council Canada - National Science Library

    Pastore, Richard

    1996-01-01

    The supported research provides a careful examination of the many different interrelated factors, processes, and constructs important to the perception by humans of complex acoustic signals, including speech and music...

  8. Signal sciences workshop proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Candy, J.V.

    1997-05-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing.

  9. Signal sciences workshop. Proceedings

    International Nuclear Information System (INIS)

    Candy, J.V.

    1997-01-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing

  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. Biophysical Aspects of Transmembrane Signaling

    CERN Document Server

    Damjanovich, Sandor

    2005-01-01

    Transmembrane signaling is one of the most significant cell biological events in the life and death of cells in general and lymphocytes in particular. Until recently biochemists and biophysicists were not accustomed to thinking of these processes from the side of a high number of complex biochemical events and an equally high number of physical changes at molecular and cellular levels at the same time. Both types of researchers were convinced that their findings are the most decisive, having higher importance than the findings of the other scientist population. Both casts were wrong. Life, even at cellular level, has a number of interacting physical and biochemical mechanisms, which finally build up the creation of an "excited" cell that will respond to particular signals from the outer or inner world. This book handles both aspects of the signalling events, and in some cases tries to unify our concepts and help understand the signals that govern the life and death of our cells. Not only the understanding, bu...

  12. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  13. ECG signal processing

    NARCIS (Netherlands)

    2009-01-01

    A system extracts an ECG signal from a composite signal (308) representing an electric measurement of a living subject. Identification means (304) identify a plurality of temporal segments (309) of the composite signal corresponding to a plurality of predetermined segments (202,204,206) of an ECG

  14. Knee joint vibroarthrographic signal processing and analysis

    CERN Document Server

    Wu, Yunfeng

    2015-01-01

    This book presents the cutting-edge technologies of knee joint vibroarthrographic signal analysis for the screening and detection of knee joint injuries. It describes a number of effective computer-aided methods for analysis of the nonlinear and nonstationary biomedical signals generated by complex physiological mechanics. This book also introduces several popular machine learning and pattern recognition algorithms for biomedical signal classifications. The book is well-suited for all researchers looking to better understand knee joint biomechanics and the advanced technology for vibration arthrometry. Dr. Yunfeng Wu is an Associate Professor at the School of Information Science and Technology, Xiamen University, Xiamen, Fujian, China.

  15. Optimal Signal Quality Index for Photoplethysmogram Signals

    Directory of Open Access Journals (Sweden)

    Mohamed Elgendi

    2016-09-01

    Full Text Available A photoplethysmogram (PPG is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

  16. Optimal Signal Quality Index for Photoplethysmogram Signals.

    Science.gov (United States)

    Elgendi, Mohamed

    2016-09-22

    A photoplethysmogram (PPG) is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI) is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each) and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

  17. ROS and ROS-Mediated Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Jixiang Zhang

    2016-01-01

    Full Text Available It has long been recognized that an increase of reactive oxygen species (ROS can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary. In this review paper, we particularly focus on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins (NF-κB, MAPKs, Keap1-Nrf2-ARE, and PI3K-Akt, ion channels and transporters (Ca2+ and mPTP, and modifying protein kinase and Ubiquitination/Proteasome System.

  18. Signals and systems laboratory with Matlab

    CERN Document Server

    Palamides, Alex

    2010-01-01

    Introduction to MATLAB®Working EnvironmentGetting StartedMemory ManagementVectorsMatricesPlotting with MATLABComplex NumbersM-FilesInput-Output CommandsFile ManagementLogical-Relational OperatorsControl FlowSymbolic VariablesPolynomials(Pseudo)Random NumbersSignalsCategorization by the Variable TypeBasic Continuous-Time SignalsDiscrete-Time SignalsProperties of SignalsTransformations of the Time Variable for Continuous-Time SignalsTransformations of the Time Variable for Discrete-Time SignalsSystemsSystems ClassificationProperties of SystemsTime Domain System AnalysisImpulse ResponseContinuous Time Convolution Convolution PropertiesInterconnections of SystemsStabilityDiscrete-Time ConvolutionSystems Described by Difference EquationsFiltersStability Criterion for Discrete-Time SystemsSystems Described by Differential EquationsStep Response of a SystemFourier SeriesOrthogonality of Complex Exponential SignalsComplex Exponential Fourier SeriesTrigonometric Fourier SeriesFourier Series in the Cosine with Phase F...

  19. Regulator of G-protein signaling - 5 (RGS5 is a novel repressor of hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    William M Mahoney

    Full Text Available Hedgehog (Hh signaling plays fundamental roles in morphogenesis, tissue repair, and human disease. Initiation of Hh signaling is controlled by the interaction of two multipass membrane proteins, patched (Ptc and smoothened (Smo. Recent studies identify Smo as a G-protein coupled receptor (GPCR-like protein that signals through large G-protein complexes which contain the Gαi subunit. We hypothesize Regulator of G-Protein Signaling (RGS proteins, and specifically RGS5, are endogenous repressors of Hh signaling via their ability to act as GTPase activating proteins (GAPs for GTP-bound Gαi, downstream of Smo. In support of this hypothesis, we demonstrate that RGS5 over-expression inhibits sonic hedgehog (Shh-mediated signaling and osteogenesis in C3H10T1/2 cells. Conversely, signaling is potentiated by siRNA-mediated knock-down of RGS5 expression, but not RGS4 expression. Furthermore, using immuohistochemical analysis and co-immunoprecipitation (Co-IP, we demonstrate that RGS5 is present with Smo in primary cilia. This organelle is required for canonical Hh signaling in mammalian cells, and RGS5 is found in a physical complex with Smo in these cells. We therefore conclude that RGS5 is an endogenous regulator of Hh-mediated signaling and that RGS proteins are potential targets for novel therapeutics in Hh-mediated diseases.

  20. Cyclometallated ruthenium(II) carbonyl complexes with 1 ...

    Indian Academy of Sciences (India)

    The characterization of the complexes having the ... Electronic spectra of the complexes display multiple strong absorptions in the ... Microanalyses (CHN) were performed by using a ..... proton.47,49 Absence of this signal in the spectra of.

  1. Small signal microwave amplifier design

    CERN Document Server

    Grosch, Theodore

    2000-01-01

    This book explains techniques and examples for designing stable amplifiers for high-frequency applications in which the signal is small and the amplifier circuit is linear. An in-depth discussion of linear network theory provides the foundation needed to develop actual designs. Examples throughout the book will show you how to apply the knowledge gained in each chapter leading to the complex design of low noise amplifiers. Many exercises at the end of each chapter will help students to practice their skills. The solutions to these design problems are available in an accompanying solutions book

  2. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  3. 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

  4. Complex dynamics

    CERN Document Server

    Carleson, Lennart

    1993-01-01

    Complex dynamics is today very much a focus of interest. Though several fine expository articles were available, by P. Blanchard and by M. Yu. Lyubich in particular, until recently there was no single source where students could find the material with proofs. For anyone in our position, gathering and organizing the material required a great deal of work going through preprints and papers and in some cases even finding a proof. We hope that the results of our efforts will be of help to others who plan to learn about complex dynamics and perhaps even lecture. Meanwhile books in the field a. re beginning to appear. The Stony Brook course notes of J. Milnor were particularly welcome and useful. Still we hope that our special emphasis on the analytic side will satisfy a need. This book is a revised and expanded version of notes based on lectures of the first author at UCLA over several \\Vinter Quarters, particularly 1986 and 1990. We owe Chris Bishop a great deal of gratitude for supervising the production of cour...

  5. Measurand transient signal suppressor

    Science.gov (United States)

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    A transient signal suppressor for use in a controls system which is adapted to respond to a change in a physical parameter whenever it crosses a predetermined threshold value in a selected direction of increasing or decreasing values with respect to the threshold value and is sustained for a selected discrete time interval is presented. The suppressor includes a sensor transducer for sensing the physical parameter and generating an electrical input signal whenever the sensed physical parameter crosses the threshold level in the selected direction. A manually operated switch is provided for adapting the suppressor to produce an output drive signal whenever the physical parameter crosses the threshold value in the selected direction of increasing or decreasing values. A time delay circuit is selectively adjustable for suppressing the transducer input signal for a preselected one of a plurality of available discrete suppression time and producing an output signal only if the input signal is sustained for a time greater than the selected suppression time. An electronic gate is coupled to receive the transducer input signal and the timer output signal and produce an output drive signal for energizing a control relay whenever the transducer input is a non-transient signal which is sustained beyond the selected time interval.

  6. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  7. Neural correlates of quality perception for complex speech signals

    CERN Document Server

    Antons, Jan-Niklas

    2015-01-01

    This book interconnects two essential disciplines to study the perception of speech: Neuroscience and Quality of Experience, which to date have rarely been used together for the purposes of research on speech quality perception. In five key experiments, the book demonstrates the application of standard clinical methods in neurophysiology on the one hand, and of methods used in fields of research concerned with speech quality perception on the other. Using this combination, the book shows that speech stimuli with different lengths and different quality impairments are accompanied by physiological reactions related to quality variations, e.g., a positive peak in an event-related potential. Furthermore, it demonstrates that – in most cases – quality impairment intensity has an impact on the intensity of physiological reactions.

  8. Wnt signaling in cancer

    Science.gov (United States)

    Zhan, T; Rindtorff, N; Boutros, M

    2017-01-01

    Wnt signaling is one of the key cascades regulating development and stemness, and has also been tightly associated with cancer. The role of Wnt signaling in carcinogenesis has most prominently been described for colorectal cancer, but aberrant Wnt signaling is observed in many more cancer entities. Here, we review current insights into novel components of Wnt pathways and describe their impact on cancer development. Furthermore, we highlight expanding functions of Wnt signaling for both solid and liquid tumors. We also describe current findings how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control. Finally, we provide an overview of current strategies to antagonize Wnt signaling in cancer and challenges that are associated with such approaches. PMID:27617575

  9. Mathematical modelling of SERK mediated BR signalling

    NARCIS (Netherlands)

    Esse, van G.W.

    2013-01-01

    Being sessile by nature plants are continuously challenged by biotic and abiotic stress factors. At the cellular level, different stimuli are perceived and translated to the desired response. In order to achieve this, signal transduction cascades have to be interlinked. Complex networks

  10. Targeting and localized signalling by small GTPases

    NARCIS (Netherlands)

    ten Klooster, Jean Paul; Hordijk, Peter L.

    2007-01-01

    Polarized cellular responses, for example, cell migration, require the co-ordinated assembly of signalling complexes at a particular subcellular location, such as the leading edge of cells. Small GTPases of the Ras superfamily play central roles in many (polarized) responses to growth factors,

  11. Traffic signal synchronization.

    Science.gov (United States)

    Huang, Ding-wei; Huang, Wei-neng

    2003-05-01

    The benefits of traffic signal synchronization are examined within the cellular automata approach. The microsimulations of traffic flow are obtained with different settings of signal period T and time delay delta. Both numerical results and analytical approximations are presented. For undersaturated traffic, the green-light wave solutions can be realized. For saturated traffic, the correlation among the traffic signals has no effect on the throughput. For oversaturated traffic, the benefits of synchronization are manifest only when stochastic noise is suppressed.

  12. Cytoskeleton in Mast Cell Signaling

    Science.gov (United States)

    Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

    2012-01-01

    Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling. PMID:22654883

  13. Complex diffusion process for noise reduction

    DEFF Research Database (Denmark)

    Nadernejad, Ehsan; Barari, A.

    2014-01-01

    equations (PDEs) in image restoration and de-noising prompted many researchers to search for an improvement in the technique. In this paper, a new method is presented for signal de-noising, based on PDEs and Schrodinger equations, named as complex diffusion process (CDP). This method assumes that variations...... for signal de-noising. To evaluate the performance of the proposed method, a number of experiments have been performed using Sinusoid, multi-component and FM signals cluttered with noise. The results indicate that the proposed method outperforms the approaches for signal de-noising known in prior art....

  14. Digital signal processing the Tevatron BPM signals

    International Nuclear Information System (INIS)

    Cancelo, G.; James, E.; Wolbers, S.

    2005-01-01

    The Beam Position Monitor (TeV BPM) readout system at Fermilab's Tevatron has been updated and is currently being commissioned. The new BPMs use new analog and digital hardware to achieve better beam position measurement resolution. The new system reads signals from both ends of the existing directional stripline pickups to provide simultaneous proton and antiproton measurements. The signals provided by the two ends of the BPM pickups are processed by analog band-pass filters and sampled by 14-bit ADCs at 74.3MHz. A crucial part of this work has been the design of digital filters that process the signal. This paper describes the digital processing and estimation techniques used to optimize the beam position measurement. The BPM electronics must operate in narrow-band and wide-band modes to enable measurements of closed-orbit and turn-by-turn positions. The filtering and timing conditions of the signals are tuned accordingly for the operational modes. The analysis and the optimized result for each mode are presented

  15. Nichtkontinuierliche (zeitdiskrete) Signale

    Science.gov (United States)

    Plaßmann, Wilfried

    Zeitdiskrete Signale werden häufig aus zeitkontinuierlichen Signalen durch Abtastung erzeugt. Dass beide Signale gleichwertig sind, zeigt das Abtasttheorem (Kap. 116) von Shannon, sofern die Bedingung nach (116.2), f_{ab}≈(2{,}2 {\\ldots} 4)\\cdot fg) eingehalten wird. Digitale Signale haben Vorteile: Einfache Speicherung, Weiterverarbeitung in Rechnern, wenig störanfällige Übertragung. Für die Bearbeitung dieser Signale dienen die im Kapitel dargestellten Hilfsmittel: Diskrete Fouriertransformation; Schnelle Fouriertransformation; z-Transformation: Darstellung, Sätze zur z-Transformation, Korrespondenzen zu Zeitfunktionen, Beispiele.

  16. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  17. Radiation signal processing system

    International Nuclear Information System (INIS)

    Bennett, M.; Knoll, G.; Strange, D.

    1980-01-01

    An improved signal processing system for radiation imaging apparatus comprises: a radiation transducer producing transducer signals proportional to apparent spatial coordinates of detected radiation events; means for storing true spatial coordinates corresponding to a plurality of predetermined apparent spatial coordinates relative to selected detected radiation events said means for storing responsive to said transducer signal and producing an output signal representative of said true spatial coordinates; and means for interpolating the true spatial coordinates of the detected radiation events located intermediate the stored true spatial coordinates, said means for interpolating communicating with said means for storing

  18. Digital signal processing

    CERN Document Server

    O'Shea, Peter; Hussain, Zahir M

    2011-01-01

    In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel

  19. Bile Acid Metabolism and Signaling

    Science.gov (United States)

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  20. Wnt signaling in triple-negative breast cancer

    Science.gov (United States)

    Pohl, SÖ-G; Brook, N; Agostino, M; Arfuso, F; Kumar, A P; Dharmarajan, A

    2017-01-01

    Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease. PMID:28368389

  1. Proceedings of the IEEE Machine Learning for Signal Processing XVII

    DEFF Research Database (Denmark)

    The seventeenth of a series of workshops sponsored by the IEEE Signal Processing Society and organized by the Machine Learning for Signal Processing Technical Committee (MLSP-TC). The field of machine learning has matured considerably in both methodology and real-world application domains and has...... become particularly important for solution of problems in signal processing. As reflected in this collection, machine learning for signal processing combines many ideas from adaptive signal/image processing, learning theory and models, and statistics in order to solve complex real-world signal processing......, and two papers from the winners of the Data Analysis Competition. The program included papers in the following areas: genomic signal processing, pattern recognition and classification, image and video processing, blind signal processing, models, learning algorithms, and applications of machine learning...

  2. Dynamic decomposition of spatiotemporal neural signals.

    Directory of Open Access Journals (Sweden)

    Luca Ambrogioni

    2017-05-01

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

  3. Recent advances in understanding neurotrophin signaling.

    Science.gov (United States)

    Bothwell, Mark

    2016-01-01

    The nerve growth factor family of growth factors, collectively known as neurotrophins, are evolutionarily ancient regulators with an enormous range of biological functions. Reflecting this long history and functional diversity, mechanisms for cellular responses to neurotrophins are exceptionally complex. Neurotrophins signal through p75 (NTR), a member of the TNF receptor superfamily member, and through receptor tyrosine kinases (TrkA, TrkB, TrkC), often with opposite functional outcomes. The two classes of receptors are activated preferentially by proneurotrophins and mature processed neurotrophins, respectively. However, both receptor classes also possess neurotrophin-independent signaling functions. Signaling functions of p75 (NTR) and Trk receptors are each influenced by the other class of receptors. This review focuses on the mechanisms responsible for the functional interplay between the two neurotrophin receptor signaling systems.

  4. Glucocorticoid receptor signaling in health and disease

    Science.gov (United States)

    Kadmiel, Mahita; Cidlowski, John A.

    2013-01-01

    Glucocorticoids are steroid hormones regulated in a circadian and stres-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the last few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor, a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we will provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body. PMID:23953592

  5. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX......)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers....... Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon...

  6. Intracellular calcium homeostasis and signaling.

    Science.gov (United States)

    Brini, Marisa; Calì, Tito; Ottolini, Denis; Carafoli, Ernesto

    2013-01-01

    Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.

  7. Drought Signaling in Plants

    Indian Academy of Sciences (India)

    depending upon the source and nature of signaling: (i) hormone signal, (ii) .... plants to regulate the rate of transpiration through minor structural .... cell has to keep spending energy (in the form of A TP) to maintain a .... enzymes and proteins in the regulation of cellular metabolism can be determined by either inactivating.

  8. Ubiquitination in apoptosis signaling

    NARCIS (Netherlands)

    van de Kooij, L.W.

    2014-01-01

    The work described in this thesis focuses on ubiquitination and protein degradation, with an emphasis on how these processes regulate apoptosis signaling. More specifically, our aims were: 1. To increase the understanding of ubiquitin-mediated regulation of apoptosis signaling. 2. To identify the E3

  9. Multiresolution signal decomposition schemes

    NARCIS (Netherlands)

    J. Goutsias (John); H.J.A.M. Heijmans (Henk)

    1998-01-01

    textabstract[PNA-R9810] Interest in multiresolution techniques for signal processing and analysis is increasing steadily. An important instance of such a technique is the so-called pyramid decomposition scheme. This report proposes a general axiomatic pyramid decomposition scheme for signal analysis

  10. SignalR blueprints

    CERN Document Server

    Ingebrigtsen, Einar

    2015-01-01

    This book is designed for software developers, primarily those with knowledge of C#, .NET, and JavaScript. Good knowledge and understanding of SignalR is assumed to allow efficient programming of core elements and applications in SignalR.

  11. Optimal fault signal estimation

    NARCIS (Netherlands)

    Stoorvogel, Antonie Arij; Niemann, H.H.; Saberi, A.; Sannuti, P.

    2002-01-01

    We consider here both fault identification and fault signal estimation. Regarding fault identification, we seek either exact or almost fault identification. On the other hand, regarding fault signal estimation, we seek either $H_2$ optimal, $H_2$ suboptimal or Hinfinity suboptimal estimation. By

  12. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  13. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  14. Supervised Learning with Complex-valued Neural Networks

    CERN Document Server

    Suresh, Sundaram; Savitha, Ramasamy

    2013-01-01

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

  15. Bioelectric Signal Measuring System

    Science.gov (United States)

    Guadarrama-Santana, A.; Pólo-Parada, L.; García-Valenzuela, A.

    2015-01-01

    We describe a low noise measuring system based on interdigitated electrodes for sensing bioelectrical signals. The system registers differential voltage measurements in order of microvolts. The base noise during measurements was in nanovolts and thus, the sensing signals presented a very good signal to noise ratio. An excitation voltage of 1Vrms with 10 KHz frequency was applied to an interdigitated capacitive sensor without a material under test and to a mirror device simultaneously. The output signals of both devices was then subtracted in order to obtain an initial reference value near cero volts and reduce parasitic capacitances due to the electronics, wiring and system hardware as well. The response of the measuring system was characterized by monitoring temporal bioelectrical signals in real time of biological materials such as embryo chicken heart cells and bovine suprarenal gland cells.

  16. Acoustic Signals and Systems

    DEFF Research Database (Denmark)

    2008-01-01

    The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook...... will present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...... from different areas, will find the self-contained chapters accessible and will be interested in the similarities and differences between the approaches and techniques used in different areas of acoustics....

  17. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  18. Adaptive signal processor

    Energy Technology Data Exchange (ETDEWEB)

    Walz, H.V.

    1980-07-01

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 ..mu..sec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed.

  19. Adaptive signal processor

    International Nuclear Information System (INIS)

    Walz, H.V.

    1980-07-01

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 μsec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed

  20. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

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

  1. Social knowledge and signals in primates.

    Science.gov (United States)

    Bergman, Thore J; Sheehan, Michael J

    2013-07-01

    Primates are notable for having a rich and detailed understanding of their social environment and there has been great interest in the evolution and function of social knowledge in primates. Indeed, primates have been shown to have impressive understandings of not only other group members but also the complex relationships among them. To be useful, however, social knowledge requires memories from previous encounters and observations about individual traits that are stable. Here, we argue that social systems or traits that make social knowledge more costly or less accurate will favor signals that either supplement or replace social knowledge. Thus, the relationship between signals and social knowledge can be complementary or antagonistic depending on the type of signal. Our goal in this review is to elucidate the relationships between signals and social knowledge in primates. We categorize signals into three types, each with different relationships to social knowledge. (1) Identity signals directly facilitate social knowledge, (2) current-state signals supplement information gained through social knowledge, and (3) badges of status replace social knowledge. Primates rely extensively on identity information, but it remains to be determined to what extent this is based on receiver perception of individual variation or senders using identity signals. Primates frequently utilize current-state signals including signals of intent to augment their interactions with familiar individuals. Badges of status are rare in primates, and the cases where they are used point to a functional and evolutionary trade-off between badges of status and social knowledge. However, the nature of this relationship needs further exploration. © 2012 Wiley Periodicals, Inc.

  2. Weak signal detection: A discrete window of opportunity for ...

    African Journals Online (AJOL)

    weak signal detection' as a potential opportunity to fill this void. Method: Combining futures and complexity theory, we reflect on two pilot case studies that involved the Archetype Extraction technique and the SenseMakerw CollectorTM tool.

  3. Functionalized active-nucleus complex sensor

    Science.gov (United States)

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  4. GEFs: Dual regulation of Rac1 signaling.

    Science.gov (United States)

    Marei, Hadir; Malliri, Angeliki

    2017-04-03

    GEFs play a critical role in regulating Rac1 signaling. They serve as signaling nodes converting upstream signals into downstream Rac1-driven cellular responses. Through associating with membrane-bound Rac1, GEFs facilitate the exchange of GDP for GTP, thereby activating Rac1. As a result, Rac1 undergoes conformational changes that mediate its interaction with downstream effectors, linking Rac1 to a multitude of physiological and pathological processes. Interestingly, there are at least 20 GEFs involved in Rac1 activation, suggesting a more complex role of GEFs in regulating Rac1 signaling apart from promoting the exchange of GDP for GTP. Indeed, accumulating evidence implicates GEFs in directing the specificity of Rac1-driven signaling cascades, although the underlying mechanisms were poorly defined. Recently, through conducting a comparative study, we highlighted the role of 2 Rac-specific GEFs, Tiam1 and P-Rex1, in dictating the biological outcome downstream of Rac1. Importantly, further proteomic analysis uncovered a GEF activity-independent function for both GEFs in modulating the Rac1 interactome, which results in the stimulation of GEF-specific signaling cascades. Here, we provide an overview of our recent findings and discuss the role of GEFs as master regulators of Rac1 signaling with a particular focus on GEF-mediated modulation of cell migration following Rac1 activation.

  5. The function of endocytosis in Wnt signaling.

    Science.gov (United States)

    Brunt, Lucy; Scholpp, Steffen

    2018-03-01

    Wnt growth factors regulate one of the most important signaling networks during development, tissue homeostasis and disease. Despite the biological importance of Wnt signaling, the mechanism of endocytosis during this process is ill described. Wnt molecules can act as paracrine signals, which are secreted from the producing cells and transported through neighboring tissue to activate signaling in target cells. Endocytosis of the ligand is important at several stages of action: One central function of endocytic trafficking in the Wnt pathway occurs in the source cell. Furthermore, the β-catenin-dependent Wnt ligands require endocytosis for signal activation and to regulate gene transcription in the responding cells. Alternatively, Wnt/β-catenin-independent signaling regulates endocytosis of cell adherence plaques to control cell migration. In this comparative review, we elucidate these three fundamental interconnected functions, which together regulate cellular fate and cellular behavior. Based on established hypotheses and recent findings, we develop a revised picture for the complex function of endocytosis in the Wnt signaling network.

  6. Macroevolution of perfume signalling in orchid bees.

    Science.gov (United States)

    Weber, Marjorie G; Mitko, Lukasz; Eltz, Thomas; Ramírez, Santiago R

    2016-11-01

    Theory predicts that both stabilising selection and diversifying selection jointly contribute to the evolution of sexual signalling traits by (1) maintaining the integrity of communication signals within species and (2) promoting the diversification of traits among lineages. However, for many important signalling traits, little is known about whether these dynamics translate into predictable macroevolutionary signatures. Here, we test for macroevolutionary patterns consistent with sexual signalling theory in the perfume signals of neotropical orchid bees, a group well studied for their chemical sexual communication. Our results revealed both high species-specificity and elevated rates of evolution in perfume signals compared to nonsignalling traits. Perfume complexity was correlated with the number of congeners in a species' range, suggesting that perfume evolution may be tied to the remarkably high number of orchid bee species coexisting together in some neotropical communities. Finally, sister-pair comparisons were consistent with both rapid divergence at speciation and character displacement upon secondary contact. Together, our results provide new insight into the macroevolution of sexual signalling in insects. © 2016 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  7. Oversampling ad converters with improved signal transfer functions

    CERN Document Server

    Pandita, Bupesh

    2011-01-01

    This book describes techniques for designing complex, discrete-time I""IGBP ADCs with signal-transfer functions that significantly filter interfering signals. The book provides an understanding of theory, issues, and implementation of discrete complex I""IGBP ADCs. The concepts developed in each chapter are further explained by applying them to a target application of I""IGBP ADCs in DTV receivers.

  8. High-speed optical signal processing using time lenses

    DEFF Research Database (Denmark)

    Galili, Michael; Hu, Hao; Guan, Pengyu

    2015-01-01

    This paper will discuss time lenses and their broad range of applications. A number of recent demonstrations of complex high-speed optical signal processing using time lenses will be outlined with focus on the operating principle.......This paper will discuss time lenses and their broad range of applications. A number of recent demonstrations of complex high-speed optical signal processing using time lenses will be outlined with focus on the operating principle....

  9. Orexin/Hypocretin Signaling.

    Science.gov (United States)

    Kukkonen, Jyrki P

    Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX 1 and OX 2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling. The general picture suggests an inherently high degree of diversity in orexin receptor signaling.In the current chapter, I present orexin signaling on the cellular and molecular levels. Discussion of the connection to (potential) physiological orexin responses is only brief since these are in focus of other chapters in this book. The same goes for the post-synaptic signaling mechanisms, which are dealt with in Burdakov: Postsynaptic actions of orexin. The current chapter is organized according to the tissue type, starting from the central nervous system. Finally, receptor signaling pathways are discussed across tissues, cell types, and even species.

  10. Social Signals, their function, and automatic analysis: A survey

    NARCIS (Netherlands)

    Vinciarelli, Alessandro; Pantic, Maja; Bourlard, Hervé; Pentland, Alex

    2008-01-01

    Social Signal Processing (SSP) aims at the analysis of social behaviour in both Human-Human and Human-Computer interactions. SSP revolves around automatic sensing and interpretation of social signals, complex aggregates of nonverbal behaviours through which individuals express their attitudes

  11. receive signal strength prediction in the gsm band using wavelet

    African Journals Online (AJOL)

    user

    strength was measured on a Mobile Equipment (ME). One-dimensional ... used to predict the fading phenomenon of the GSM receive signal strength measured. Wavelet ... radio wavelength. The prediction is ... realized by reusing frequency in a dense or complex .... NETWORK SIGNAL PRO software, down loaded from.

  12. Hedgehog signaling in development and homeostasis of the gastrointestinal tract

    NARCIS (Netherlands)

    van den Brink, Gijs R.

    2007-01-01

    The Hedgehog family of secreted morphogenetic proteins acts through a complex evolutionary conserved signaling pathway to regulate patterning events during development and in the adult organism. In this review I discuss the role of Hedgehog signaling in the development, postnatal maintenance, and

  13. Measuring Workload Weak Resilience Signals at a Rail Control Post

    NARCIS (Netherlands)

    Siegel, A.W.; Schraagen, J.M.C.

    2014-01-01

    OCCUPATIONAL APPLICATIONS This article describes an observational study at a rail control post to measure workload weak resilience signals. A weak resilience signal indicates a possible degradation of a system's resilience, which is defined as the ability of a complex socio-technical system to cope

  14. Quaternion Fourier transforms for signal and image processing

    CERN Document Server

    Ell, Todd A; Sangwine, Stephen J

    2014-01-01

    Based on updates to signal and image processing technology made in the last two decades, this text examines the most recent research results pertaining to Quaternion Fourier Transforms. QFT is a central component of processing color images and complex valued signals. The book's attention to mathematical concepts, imaging applications, and Matlab compatibility render it an irreplaceable resource for students, scientists, researchers, and engineers.

  15. Signal flow analysis

    CERN Document Server

    Abrahams, J R; Hiller, N

    1965-01-01

    Signal Flow Analysis provides information pertinent to the fundamental aspects of signal flow analysis. This book discusses the basic theory of signal flow graphs and shows their relation to the usual algebraic equations.Organized into seven chapters, this book begins with an overview of properties of a flow graph. This text then demonstrates how flow graphs can be applied to a wide range of electrical circuits that do not involve amplification. Other chapters deal with the parameters as well as circuit applications of transistors. This book discusses as well the variety of circuits using ther

  16. Basolateral BMP signaling in polarized epithelial cells.

    Directory of Open Access Journals (Sweden)

    Masao Saitoh

    Full Text Available Bone morphogenetic proteins (BMPs regulate various biological processes, mostly mediated by cells of mesenchymal origin. However, the roles of BMPs in epithelial cells are poorly understood. Here, we demonstrate that, in polarized epithelial cells, BMP signals are transmitted from BMP receptor complexes exclusively localized at the basolateral surface of the cell membrane. In addition, basolateral stimulation with BMP increased expression of components of tight junctions and enhanced the transepithelial resistance (TER, counteracting reduction of TER by treatment with TGF-β or an anti-tumor drug. We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors.

  17. Underwater Acoustic Signal Processing

    National Research Council Canada - National Science Library

    Culver, Richard L; Sibul, Leon H; Bradley, David L

    2007-01-01

    .... The research is directed toward passive sonar detection and classification, continuous wave (CW) and broadband signals, shallow water operation, both platform-mounted and distributed systems, and frequencies below 1 kHz...

  18. Signals and systems

    CERN Document Server

    Rao, K Deergha

    2018-01-01

    This textbook covers the fundamental theories of signals and systems analysis, while incorporating recent developments from integrated circuits technology into its examples. Starting with basic definitions in signal theory, the text explains the properties of continuous-time and discrete-time systems and their representation by differential equations and state space. From those tools, explanations for the processes of Fourier analysis, the Laplace transform, and the z-Transform provide new ways of experimenting with different kinds of time systems. The text also covers the separate classes of analog filters and their uses in signal processing applications. Intended for undergraduate electrical engineering students, chapter sections include exercise for review and practice for the systems concepts of each chapter. Along with exercises, the text includes MATLAB-based examples to allow readers to experiment with signals and systems code on their own. An online repository of the MATLAB code from this textbook can...

  19. Topological signal processing

    CERN Document Server

    Robinson, Michael

    2014-01-01

    Signal processing is the discipline of extracting information from collections of measurements. To be effective, the measurements must be organized and then filtered, detected, or transformed to expose the desired information.  Distortions caused by uncertainty, noise, and clutter degrade the performance of practical signal processing systems. In aggressively uncertain situations, the full truth about an underlying signal cannot be known.  This book develops the theory and practice of signal processing systems for these situations that extract useful, qualitative information using the mathematics of topology -- the study of spaces under continuous transformations.  Since the collection of continuous transformations is large and varied, tools which are topologically-motivated are automatically insensitive to substantial distortion. The target audience comprises practitioners as well as researchers, but the book may also be beneficial for graduate students.

  20. Acoustic MIMO signal processing

    CERN Document Server

    Huang, Yiteng; Chen, Jingdong

    2006-01-01

    A timely and important book addressing a variety of acoustic signal processing problems under multiple-input multiple-output (MIMO) scenarios. It uniquely investigates these problems within a unified framework offering a novel and penetrating analysis.

  1. Ultrahigh bandwidth signal processing

    DEFF Research Database (Denmark)

    Oxenløwe, Leif Katsuo

    2016-01-01

    Optical time lenses have proven to be very versatile for advanced optical signal processing. Based on a controlled interplay between dispersion and phase-modulation by e.g. four-wave mixing, the processing is phase-preserving, an hence useful for all types of data signals including coherent multi......-level modulation founats. This has enabled processing of phase-modulated spectrally efficient data signals, such as orthogonal frequency division multiplexed (OFDM) signa In that case, a spectral telescope system was used, using two time lenses with different focal lengths (chirp rates), yielding a spectral...... regeneratio These operations require a broad bandwidth nonlinear platform, and novel photonic integrated nonlinear platform like aluminum gallium arsenide nano-waveguides used for 1.28 Tbaud optical signal processing will be described....

  2. Traffic Signal Cycle Lengths

    Data.gov (United States)

    Town of Chapel Hill, North Carolina — Traffic signal location list for the town of Chapel Hill. This data set includes light cycle information as well as as intersection information.The Town of Chapel...

  3. Foundations of signal processing

    CERN Document Server

    Vetterli, Martin; Goyal, Vivek K

    2014-01-01

    This comprehensive and engaging textbook introduces the basic principles and techniques of signal processing, from the fundamental ideas of signals and systems theory to real-world applications. Students are introduced to the powerful foundations of modern signal processing, including the basic geometry of Hilbert space, the mathematics of Fourier transforms, and essentials of sampling, interpolation, approximation and compression. The authors discuss real-world issues and hurdles to using these tools, and ways of adapting them to overcome problems of finiteness and localisation, the limitations of uncertainty and computational costs. Standard engineering notation is used throughout, making mathematical examples easy for students to follow, understand and apply. It includes over 150 homework problems and over 180 worked examples, specifically designed to test and expand students' understanding of the fundamentals of signal processing, and is accompanied by extensive online materials designed to aid learning, ...

  4. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

    Directory of Open Access Journals (Sweden)

    John Paul SanGiovanni

    Full Text Available Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs and use of peroxisome proliferator activator receptor (PPAR-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG co-activator 1 alpha (PPARGC1A, a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR transcription complex, may influence neovascularization (NV in age-related macular degeneration (AMD.We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A.A DNA coding variant (rs3736265 and a 3'UTR-resident regulatory variant (rs3774923 in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs. SNP-SNP interactions existed for NV AMD (P<0.005 with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559. PPARGC1A influences activation of the AMD-associated complement component 3 (C3 promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003 of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033, a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678 showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003. C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice

  5. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

    Science.gov (United States)

    SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M; Stahl, Andreas; Clemons, Traci E; Chew, Emily Y; Smith, Lois E H

    2013-01-01

    Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (Pcomplement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice - these animals also showed 70% reduction in retinal NV (P

  6. Source of seismic signals

    Energy Technology Data Exchange (ETDEWEB)

    Frankovskii, B.A.; Khor' yakov, K.A.

    1980-08-30

    Patented is a source of seismic signals consisting of a shock generator with a basic low-voltage and auxillary high-voltage stator coils, a capacitive transformer and control switches. To increase the amplitude of signal excitation a condensor battery and auxillary commutator are introduced into the device, which are connected in parallel and serially into the circuit of the main low-voltage stator coil.

  7. Transient-Switch-Signal Suppressor

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1995-01-01

    Circuit delays transmission of switch-opening or switch-closing signal until after preset suppression time. Used to prevent transmission of undesired momentary switch signal. Basic mode of operation simple. Beginning of switch signal initiates timing sequence. If switch signal persists after preset suppression time, circuit transmits switch signal to external circuitry. If switch signal no longer present after suppression time, switch signal deemed transient, and circuit does not pass signal on to external circuitry, as though no transient switch signal. Suppression time preset at value large enough to allow for damping of underlying pressure wave or other mechanical transient.

  8. Fundamentals of adaptive signal processing

    CERN Document Server

    Uncini, Aurelio

    2015-01-01

    This book is an accessible guide to adaptive signal processing methods that equips the reader with advanced theoretical and practical tools for the study and development of circuit structures and provides robust algorithms relevant to a wide variety of application scenarios. Examples include multimodal and multimedia communications, the biological and biomedical fields, economic models, environmental sciences, acoustics, telecommunications, remote sensing, monitoring, and, in general, the modeling and prediction of complex physical phenomena. The reader will learn not only how to design and implement the algorithms but also how to evaluate their performance for specific applications utilizing the tools provided. While using a simple mathematical language, the employed approach is very rigorous. The text will be of value both for research purposes and for courses of study.

  9. Digital Signal Processing applied to Physical Signals

    CERN Document Server

    Alberto, Diego; Musa, L

    2011-01-01

    It is well known that many of the scientific and technological discoveries of the XXI century will depend on the capability of processing and understanding a huge quantity of data. With the advent of the digital era, a fully digital and automated treatment can be designed and performed. From data mining to data compression, from signal elaboration to noise reduction, a processing is essential to manage and enhance features of interest after every data acquisition (DAQ) session. In the near future, science will go towards interdisciplinary research. In this work there will be given an example of the application of signal processing to different fields of Physics from nuclear particle detectors to biomedical examinations. In Chapter 1 a brief description of the collaborations that allowed this thesis is given, together with a list of the publications co-produced by the author in these three years. The most important notations, definitions and acronyms used in the work are also provided. In Chapter 2, the last r...

  10. Can complexity decrease in congestive heart failure?

    Science.gov (United States)

    Mukherjee, Sayan; Palit, Sanjay Kumar; Banerjee, Santo; Ariffin, M. R. K.; Rondoni, Lamberto; Bhattacharya, D. K.

    2015-12-01

    The complexity of a signal can be measured by the Recurrence period density entropy (RPDE) from the reconstructed phase space. We have chosen a window based RPDE method for the classification of signals, as RPDE is an average entropic measure of the whole phase space. We have observed the changes in the complexity in cardiac signals of normal healthy person (NHP) and congestive heart failure patients (CHFP). The results show that the cardiac dynamics of a healthy subject is more complex and random compare to the same for a heart failure patient, whose dynamics is more deterministic. We have constructed a general threshold to distinguish the border line between a healthy and a congestive heart failure dynamics. The results may be useful for wide range for physiological and biomedical analysis.

  11. Spectroscopy of plutonium-organic complexes

    International Nuclear Information System (INIS)

    Richmann, M.K.; Reed, D.T.

    1995-01-01

    Information on the spectroscopy of plutonium-organic complexes is needed to help establish the speciation of these complexes under environmentally relevant conditions. Laser photoacoustic spectroscopy (LPAS) and absorption spectrometry were used to characterize the Pu(IV)-citrate and Pu(IV)-nitrilotriacetic acid (NTA) complexes at concentrations of 10 -3 --10 -7 M in aqueous solution. Good agreement was observed between the band shape of the LPAS and absorption spectra for the Pu(IV)-NTA complex. Agreement for the Pu(IV)-citrate complex was not quite as good. In both cases, a linear dependence of the LPAS signal on laser power and total concentration of the complexes was noted. This work is part of an ongoing research effort to study key subsurface interactions of plutonium-organic complexes

  12. Classical correlations, Bell inequalities, and communication complexity

    Energy Technology Data Exchange (ETDEWEB)

    Wilms, Johannes; Alber, Gernot [Institut fuer Angewandte Physik, Technische Universitaet Darmstadt, D-64289 Darmstadt (Germany); Percival, Ian C. [Department of Physics, Univ. of London (United Kingdom)

    2007-07-01

    A computer program is presented which is capable of exploring generalizations of Bell-type inequalities for arbitrary numbers of classical inputs and outputs. Thereby, polytopes can be described which represent classical local realistic theories, classical theories without signaling, or classical theories with explicit signaling. These latter polytopes may also be of interest for exploring basic problems of communication complexity. As a first application the influence of non-perfect detectors is discussed in simple Bell experiments.

  13. Feature selection and classifier parameters estimation for EEG signals peak detection using particle swarm optimization.

    Science.gov (United States)

    Adam, Asrul; Shapiai, Mohd Ibrahim; Tumari, Mohd Zaidi Mohd; Mohamad, Mohd Saberi; Mubin, Marizan

    2014-01-01

    Electroencephalogram (EEG) signal peak detection is widely used in clinical applications. The peak point can be detected using several approaches, including time, frequency, time-frequency, and nonlinear domains depending on various peak features from several models. However, there is no study that provides the importance of every peak feature in contributing to a good and generalized model. In this study, feature selection and classifier parameters estimation based on particle swarm optimization (PSO) are proposed as a framework for peak detection on EEG signals in time domain analysis. Two versions of PSO are used in the study: (1) standard PSO and (2) random asynchronous particle swarm optimization (RA-PSO). The proposed framework tries to find the best combination of all the available features that offers good peak detection and a high classification rate from the results in the conducted experiments. The evaluation results indicate that the accuracy of the peak detection can be improved up to 99.90% and 98.59% for training and testing, respectively, as compared to the framework without feature selection adaptation. Additionally, the proposed framework based on RA-PSO offers a better and reliable classification rate as compared to standard PSO as it produces low variance model.

  14. Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment.

    Science.gov (United States)

    Filomeni, Giuseppe; Cardaci, Simone; Da Costa Ferreira, Ana Maria; Rotilio, Giuseppe; Ciriolo, Maria Rosa

    2011-08-01

    We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N']copper(II), named [Cu(isaepy)(2)], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38(MAPK) (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38(MAPK) and p53. Similarly, reverse genetics of p38(MAPK) yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38(MAPK)/p53. Fuel supplies counteracted [Cu(isaepy)(2)]-induced apoptosis and AMPK/p38(MAPK)/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)(2)] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38(MAPK)/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)(2)] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)(2)] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment. © The Authors Journal compilation © 2011 Biochemical Society

  15. Cellular signalling properties in microcircuits

    DEFF Research Database (Denmark)

    Toledo-Rodriguez, Maria; El Manira, Abdeljabbar; Wallén, Peter

    2005-01-01

    Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties...

  16. VLSI signal processing technology

    CERN Document Server

    Swartzlander, Earl

    1994-01-01

    This book is the first in a set of forthcoming books focussed on state-of-the-art development in the VLSI Signal Processing area. It is a response to the tremendous research activities taking place in that field. These activities have been driven by two factors: the dramatic increase in demand for high speed signal processing, especially in consumer elec­ tronics, and the evolving microelectronic technologies. The available technology has always been one of the main factors in determining al­ gorithms, architectures, and design strategies to be followed. With every new technology, signal processing systems go through many changes in concepts, design methods, and implementation. The goal of this book is to introduce the reader to the main features of VLSI Signal Processing and the ongoing developments in this area. The focus of this book is on: • Current developments in Digital Signal Processing (DSP) pro­ cessors and architectures - several examples and case studies of existing DSP chips are discussed in...

  17. Adaptive Evolution of Signaling Partners

    Science.gov (United States)

    Urano, Daisuke; Dong, Taoran; Bennetzen, Jeffrey L.; Jones, Alan M.

    2015-01-01

    Proteins that interact coevolve their structures. When mutation disrupts the interaction, compensation by the partner occurs to restore interaction otherwise counterselection occurs. We show in this study how a destabilizing mutation in one protein is compensated by a stabilizing mutation in its protein partner and their coevolving path. The pathway in this case and likely a general principle of coevolution is that the compensatory change must tolerate both the original and derived structures with equivalence in function and activity. Evolution of the structure of signaling elements in a network is constrained by specific protein pair interactions, by requisite conformational changes, and by catalytic activity. The heterotrimeric G protein-coupled signaling is a paragon of this protein interaction/function complexity and our deep understanding of this pathway in diverse organisms lends itself to evolutionary study. Regulators of G protein Signaling (RGS) proteins accelerate the intrinsic GTP hydrolysis rate of the Gα subunit of the heterotrimeric G protein complex. An important RGS-contact site is a hydroxyl-bearing residue on the switch I region of Gα subunits in animals and most plants, such as Arabidopsis. The exception is the grasses (e.g., rice, maize, sugarcane, millets); these plants have Gα subunits that replaced the critical hydroxyl-bearing threonine with a destabilizing asparagine shown to disrupt interaction between Arabidopsis RGS protein (AtRGS1) and the grass Gα subunit. With one known exception (Setaria italica), grasses do not encode RGS genes. One parsimonious deduction is that the RGS gene was lost in the ancestor to the grasses and then recently acquired horizontally in the lineage S. italica from a nongrass monocot. Like all investigated grasses, S. italica has the Gα subunit with the destabilizing asparagine residue in the protein interface but, unlike other known grass genomes, still encodes an expressed RGS gene, SiRGS1. SiRGS1

  18. Anchoring Proteins as Regulators of Signaling Pathways

    Science.gov (United States)

    Perino, Alessia; Ghigo, Alessandra; Scott, John D.; Hirsch, Emilio

    2012-01-01

    Spatial and temporal organization of signal transduction is coordinated through the segregation of signaling enzymes in selected cellular compartments. This highly evolved regulatory mechanism ensures the activation of selected enzymes only in the vicinity of their target proteins. In this context, cAMP-responsive triggering of protein kinase A is modulated by a family of scaffold proteins referred to as A-kinase anchoring proteins. A-kinase anchoring proteins form the core of multiprotein complexes and enable simultaneous but segregated cAMP signaling events to occur in defined cellular compartments. In this review we will focus on the description of A-kinase anchoring protein function in the regulation of cardiac physiopathology. PMID:22859670

  19. Lipid rafts and B cell signaling.

    Science.gov (United States)

    Gupta, Neetu; DeFranco, Anthony L

    2007-10-01

    B cells comprise an essential component of the humoral immune system. They are equipped with the unique ability to synthesize and secrete pathogen-neutralizing antibodies, and share with professional antigen presenting cells the ability to internalize foreign antigens, and process them for presentation to helper T cells. Recent evidence indicates that specialized cholesterol- and glycosphingolipid-rich microdomains in the plasma membrane commonly referred to as lipid rafts, serve to compartmentalize key signaling molecules during the different stages of B cell activation including B cell antigen receptor (BCR)-initiated signal transduction, endocytosis of BCR-antigen complexes, loading of antigenic peptides onto MHC class II molecules, MHC-II associated antigen presentation to helper T cells, and receipt of helper signals via the CD40 receptor. Here we review the recent literature arguing for a role of lipid rafts in the spatial organization of B cell function.

  20. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this 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...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  1. Signals and transforms in linear systems analysis

    CERN Document Server

    Wasylkiwskyj, Wasyl

    2013-01-01

    Signals and Transforms in Linear Systems Analysis covers the subject of signals and transforms, particularly in the context of linear systems theory. Chapter 2 provides the theoretical background for the remainder of the text. Chapter 3 treats Fourier series and integrals. Particular attention is paid to convergence properties at step discontinuities. This includes the Gibbs phenomenon and its amelioration via the Fejer summation techniques. Special topics include modulation and analytic signal representation, Fourier transforms and analytic function theory, time-frequency analysis and frequency dispersion. Fundamentals of linear system theory for LTI analogue systems, with a brief account of time-varying systems, are covered in Chapter 4 . Discrete systems are covered in Chapters 6 and 7.  The Laplace transform treatment in Chapter 5 relies heavily on analytic function theory as does Chapter 8 on Z -transforms. The necessary background on complex variables is provided in Appendix A. This book is intended to...

  2. Pattern theory the stochastic analysis of real-world signals

    CERN Document Server

    Mumford, David

    2010-01-01

    Pattern theory is a distinctive approach to the analysis of all forms of real-world signals. At its core is the design of a large variety of probabilistic models whose samples reproduce the look and feel of the real signals, their patterns, and their variability. Bayesian statistical inference then allows you to apply these models in the analysis of new signals. This book treats the mathematical tools, the models themselves, and the computational algorithms for applying statistics to analyze six representative classes of signals of increasing complexity. The book covers patterns in text, sound

  3. Signal integrity characterization techniques

    CERN Document Server

    Bogatin, Eric

    2009-01-01

    "Signal Integrity Characterization Techniques" addresses the gap between traditional digital and microwave curricula all while focusing on a practical and intuitive understanding of signal integrity effects within the data transmission channel. High-speed interconnects such as connectors, PCBs, cables, IC packages, and backplanes are critical elements of differential channels that must be designed using today's most powerful analysis and characterization tools.Both measurements and simulation must be done on the device under test, and both activities must yield data that correlates with each other. Most of this book focuses on real-world applications of signal integrity measurements - from backplane for design challenges to error correction techniques to jitter measurement technologies. The authors' approach wisely addresses some of these new high-speed technologies, and it also provides valuable insight into its future direction and will teach the reader valuable lessons on the industry.

  4. Quantum signaling game

    International Nuclear Information System (INIS)

    Frackiewicz, Piotr

    2014-01-01

    We present a quantum approach to a signaling game; a special kind of extensive game of incomplete information. Our model is based on quantum schemes for games in strategic form where players perform unitary operators on their own qubits of some fixed initial state and the payoff function is given by a measurement on the resulting final state. We show that the quantum game induced by our scheme coincides with a signaling game as a special case and outputs nonclassical results in general. As an example, we consider a quantum extension of the signaling game in which the chance move is a three-parameter unitary operator whereas the players' actions are equivalent to classical ones. In this case, we study the game in terms of Nash equilibria and refine the pure Nash equilibria adapting to the quantum game the notion of a weak perfect Bayesian equilibrium. (paper)

  5. Hedgehog Signalling in the Embryonic Mouse Thymus

    Directory of Open Access Journals (Sweden)

    Alessandro Barbarulo

    2016-07-01

    Full Text Available T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation.

  6. Signals, processes, and systems an interactive multimedia introduction to signal processing

    CERN Document Server

    Karrenberg, Ulrich

    2013-01-01

    This is a very new concept for learning Signal Processing, not only from the physically-based scientific fundamentals, but also from the didactic perspective, based on modern results of brain research. The textbook together with the DVD form a learning system that provides investigative studies and enables the reader to interactively visualize even complex processes. The unique didactic concept is built on visualizing signals and processes on the one hand, and on graphical programming of signal processing systems on the other. The concept has been designed especially for microelectronics, computer technology and communication. The book allows to develop, modify, and optimize useful applications using DasyLab - a professional and globally supported software for metrology and control engineering. With the 3rd edition, the software is also suitable for 64 bit systems running on Windows 7. Real signals can be acquired, processed and played on the sound card of your computer. The book provides more than 200 pre-pr...

  7. PKD signaling and pancreatitis

    Science.gov (United States)

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  8. Signal processing in microdosimetry

    International Nuclear Information System (INIS)

    Arbel, A.

    1984-01-01

    Signals occurring in microdosimetric measurements cover a dynamic range of 100 dB at a counting rate which normally stays below 10 4 but could increase significantly in case of an accident. The need for high resolution at low energies, non-linear signal processing to accommodate the specified dynamic range, easy calibration and thermal stability are conflicting requirements which pose formidable design problems. These problems are reviewed, and a practical approach to their solution is given employing a single processing channel. (author)

  9. Understanding signal integrity

    CERN Document Server

    Thierauf, Stephen C

    2010-01-01

    This unique book provides you with practical guidance on understanding and interpreting signal integrity (SI) performance to help you with your challenging circuit board design projects. You find high-level discussions of important SI concepts presented in a clear and easily accessible format, including question and answer sections and bulleted lists.This valuable resource features rules of thumb and simple equations to help you make estimates of critical signal integrity parameters without using circuit simulators of CAD (computer-aided design). The book is supported with over 120 illustratio

  10. Electronic signal conditioning

    CERN Document Server

    NEWBY, BRUCE

    1994-01-01

    At technician level, brief references to signal conditioning crop up in a fragmented way in various textbooks, but there has been no single textbook, until now!More advanced texts do exist but they are more mathematical and presuppose a higher level of understanding of electronics and statistics. Electronic Signal Conditioning is designed for HNC/D students and City & Guilds Electronics Servicing 2240 Parts 2 & 3. It will also be useful for BTEC National, Advanced GNVQ, A-level electronics and introductory courses at degree level.

  11. TOR signalling in plants.

    Science.gov (United States)

    Rexin, Daniel; Meyer, Christian; Robaglia, Christophe; Veit, Bruce

    2015-08-15

    Although the eukaryotic TOR (target of rapamycin) kinase signalling pathway has emerged as a key player for integrating nutrient-, energy- and stress-related cues with growth and metabolic outputs, relatively little is known of how this ancient regulatory mechanism has been adapted in higher plants. Drawing comparisons with the substantial knowledge base around TOR kinase signalling in fungal and animal systems, functional aspects of this pathway in plants are reviewed. Both conserved and divergent elements are discussed in relation to unique aspects associated with an autotrophic mode of nutrition and adaptive strategies for multicellular development exhibited by plants. © 2015 Authors; published by Portland Press Limited.

  12. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  13. RF measurements I: signal receiving techniques

    CERN Document Server

    Caspers, F

    2011-01-01

    For the characterization of components, systems and signals in the RF and microwave range, several dedicated instruments are in use. In this paper the fundamentals of the RF-signal sampling technique, which has found widespread applications in 'digital' oscilloscopes and sampling scopes, are discussed. The key element in these front-ends is the Schottky diode which can be used either as an RF mixer or as a single sampler. The spectrum analyser has become an absolutely indispensable tool for RF signal analysis. Here the front-end is the RF mixer as the RF section of modern spectrum analysers has a rather complex architecture. The reasons for this complexity and certain working principles as well as limitations are discussed. In addition, an overview of the development of scalar and vector signal analysers is given. For the determination of the noise temperature of a one-port and the noise figure of a two-port, basic concepts and relations are shown. A brief discussion of commonly used noise measurement techniq...

  14. Linear ubiquitination signals in adaptive immune responses.

    Science.gov (United States)

    Ikeda, Fumiyo

    2015-07-01

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

  15. TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling.

    Science.gov (United States)

    Zhong, Jun; Sharma, Jyoti; Raju, Rajesh; Palapetta, Shyam Mohan; Prasad, T S Keshava; Huang, Tai-Chung; Yoda, Akinori; Tyner, Jeffrey W; van Bodegom, Diederik; Weinstock, David M; Ziegler, Steven F; Pandey, Akhilesh

    2014-01-01

    Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a critical role in the regulation of immune responses and in the differentiation of hematopoietic cells. TSLP signals through a heterodimeric receptor complex consisting of an interleukin-7 receptor α chain and a unique TSLP receptor (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway. Aberrant TSLP/TSLPR signaling has been associated with a variety of human diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic leukemia. A centralized resource of the TSLP signaling pathway cataloging signaling events is not yet available. In this study, we present a literature-annotated resource of reactions in the TSLP signaling pathway. This pathway map is publicly available through NetPath (http://www.netpath.org/), an open access signal transduction pathway resource developed previously by our group. This map includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR signaling pathway. We expect that the TSLP signaling pathway map will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated TSLP/TSLPR signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_24.

  16. The Complex Cepstrum - Revisited

    Science.gov (United States)

    Kemerait, R. C., Sr.

    2016-12-01

    Since this paper comes at the twilight of my career, it is appropriate to share my views on a subject very dear to my heart and to my long career. In 2004 "From Frequency to Quefrency: A History of the Cepstrum" was published in the IEEE Signal Processing magazine. There is no question that the authors, Alan V. Oppenheim and Ronald W. Schafer, were pioneers in this area of research, and this publication documents their involvement quite nicely. In parallel research also performed in the 1960's, Childers, et. al., renamed the original "Cepstrum" to the "Power Cepstrum" to avoid confusion with the principal topic of their research, that being the "Complex Cepstrum." The term "Power Cepstrum" has become widely used in the literature since that time. The Childers team, including Dr. Kemerait, published a summary of their work, as of that date, in the IEEE Proceedings of October 1977, and titled the article "The Cepstrum: A Guide to Processing." In the subsequent 40 years, Dr. Kemerait has continued to research cepstral techniques applied to many diverse problems; however, his primary research has been on estimating the depth of underground and underwater events. He has also applied these techniques to biomedical data: EEG, EKG, and Visua-evoked responses as well as on hydroacoustic data ; thereby, determining the "bubble pulse frequency", and the depths of the explosion and the ocean depth at the explosion point. He has also used cepstral techniques in the processing of ground penetrating radar, speech, machine diagnostics, and, throughout these years, seismic data. This paper emphasizes his recent improvements in processing primarily seismic and infrasound data associated with nuclear treaty monitoring. The emphasis is mainly on the recent improvements and the automation of the Complex Cepstrum process.

  17. Randomness control of vehicular motion through a sequence of traffic signals at irregular intervals

    International Nuclear Information System (INIS)

    Nagatani, Takashi

    2010-01-01

    We study the regularization of irregular motion of a vehicle moving through the sequence of traffic signals with a disordered configuration. Each traffic signal is controlled by both cycle time and phase shift. The cycle time is the same for all signals, while the phase shift varies from signal to signal by synchronizing with intervals between a signal and the next signal. The nonlinear dynamic model of the vehicular motion is presented by the stochastic nonlinear map. The vehicle exhibits the very complex behavior with varying both cycle time and strength of irregular intervals. The irregular motion induced by the disordered configuration is regularized by adjusting the phase shift within the regularization regions.

  18. Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish

    Science.gov (United States)

    Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.

    2016-01-01

    The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

  19. Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

    KAUST Repository

    Kim, Tae-Houn

    2010-05-04

    Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms.

  20. Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

    KAUST Repository

    Kim, Tae-Houn; Bö hmer, Maik; Hu, Honghong; Nishimura, Noriyuki; Schroeder, Julian I.

    2010-01-01

    Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms.

  1. SCAR/WAVE: A complex issue.

    Science.gov (United States)

    Davidson, Andrew J; Insall, Robert H

    2013-11-01

    The SCAR/WAVE complex drives the actin polymerisation that underlies protrusion of the front of the cell and thus drives migration. However, it is not understood how the activity of SCAR/WAVE is regulated to generate the infinite range of cellular shape changes observed during cell motility. What are the relative roles of the subunits of the SCAR/WAVE complex? What signaling molecules do they interact with? And how does the complex integrate all this information in order to control the temporal and spatial polymerisation of actin during protrusion formation? Unfortunately, the interdependence of SCAR complex members has made genetic dissection hard. In our recent paper,(1) we describe stabilization of the Dictyostelium SCAR complex by a small fragment of Abi. Here we summarize the main findings and discuss how this approach can help reveal the inner workings of this impenetrable complex.

  2. Adaptive Beamforming Based on Complex Quaternion Processes

    Directory of Open Access Journals (Sweden)

    Jian-wu Tao

    2014-01-01

    Full Text Available Motivated by the benefits of array signal processing in quaternion domain, we investigate the problem of adaptive beamforming based on complex quaternion processes in this paper. First, a complex quaternion least-mean squares (CQLMS algorithm is proposed and its performance is analyzed. The CQLMS algorithm is suitable for adaptive beamforming of vector-sensor array. The weight vector update of CQLMS algorithm is derived based on the complex gradient, leading to lower computational complexity. Because the complex quaternion can exhibit the orthogonal structure of an electromagnetic vector-sensor in a natural way, a complex quaternion model in time domain is provided for a 3-component vector-sensor array. And the normalized adaptive beamformer using CQLMS is presented. Finally, simulation results are given to validate the performance of the proposed adaptive beamformer.

  3. Television picture signal processing

    NARCIS (Netherlands)

    1998-01-01

    Field or frame memories are often used in television receivers for video signal processing functions, such as noise reduction and/or flicker reduction. Television receivers also have graphic features such as teletext, menu-driven control systems, multilingual subtitling, an electronic TV-Guide, etc.

  4. Signals: Applying Academic Analytics

    Science.gov (United States)

    Arnold, Kimberly E.

    2010-01-01

    Academic analytics helps address the public's desire for institutional accountability with regard to student success, given the widespread concern over the cost of higher education and the difficult economic and budgetary conditions prevailing worldwide. Purdue University's Signals project applies the principles of analytics widely used in…

  5. Communication Signals in Lizards.

    Science.gov (United States)

    Carpenter, Charles C.

    1983-01-01

    Discusses mechanisms and functional intent of visual communication signals in iguanid/agamid lizards. Demonstrated that lizards communicate with each other by using pushups and head nods and that each species does this in its own way, conveying different types of information. (JN)

  6. Modeling binaural signal detection

    NARCIS (Netherlands)

    Breebaart, D.J.

    2001-01-01

    With the advent of multimedia technology and powerful signal processing systems, audio processing and reproduction has gained renewed interest. Examples of products that have been developed are audio coding algorithms to efficiently store and transmit music and speech, or audio reproduction systems

  7. Quantum cloning and signaling

    International Nuclear Information System (INIS)

    Simon, C.; Weihs, G.; Zeilinger, A.

    1999-01-01

    We discuss the close connections between cloning of quantum states and superluminal signaling. We present an optimal universal cloning machine based on stimulated emission recently proposed by the authors. As an instructive example, we show how a scheme for superluminal communication based on this cloning machine fails. (Authors)

  8. "Utilizing" signal detection theory.

    Science.gov (United States)

    Lynn, Spencer K; Barrett, Lisa Feldman

    2014-09-01

    What do inferring what a person is thinking or feeling, judging a defendant's guilt, and navigating a dimly lit room have in common? They involve perceptual uncertainty (e.g., a scowling face might indicate anger or concentration, for which different responses are appropriate) and behavioral risk (e.g., a cost to making the wrong response). Signal detection theory describes these types of decisions. In this tutorial, we show how incorporating the economic concept of utility allows signal detection theory to serve as a model of optimal decision making, going beyond its common use as an analytic method. This utility approach to signal detection theory clarifies otherwise enigmatic influences of perceptual uncertainty on measures of decision-making performance (accuracy and optimality) and on behavior (an inverse relationship between bias magnitude and sensitivity optimizes utility). A "utilized" signal detection theory offers the possibility of expanding the phenomena that can be understood within a decision-making framework. © The Author(s) 2014.

  9. Mechanisms of Wnt signaling and control.

    Science.gov (United States)

    Grainger, Stephanie; Willert, Karl

    2018-03-30

    The Wnt signaling pathway is a highly conserved system that regulates complex biological processes across all metazoan species. At the cellular level, secreted Wnt proteins serve to break symmetry and provide cells with positional information that is critical to the patterning of the entire body plan. At the organismal level, Wnt signals are employed to orchestrate fundamental developmental processes, including the specification of the anterior-posterior body axis, induction of the primitive streak and ensuing gastrulation movements, and the generation of cell and tissue diversity. Wnt functions extend into adulthood where they regulate stem cell behavior, tissue homeostasis, and damage repair. Disruption of Wnt signaling activity during embryonic development or in adults results in a spectrum of abnormalities and diseases, including cancer. The molecular mechanisms that underlie the myriad of Wnt-regulated biological effects have been the subject of intense research for over three decades. This review is intended to summarize our current understanding of how Wnt signals are generated and interpreted. This article is categorized under: Biological Mechanisms > Cell Signaling Developmental Biology > Stem Cell Biology and Regeneration. © 2018 Wiley Periodicals, Inc.

  10. Maynard Smith: amplifying the reasons for signal reliability.

    Science.gov (United States)

    Harper, D G C

    2006-03-21

    One of the many questions to which John Maynard Smith contributed was that of why most animal signals are reliable. He initially rejected the "handicap" argument but gradually accepted it, a process I briefly describe. This episode illustrated his preference for mathematical models over verbal ones, and the generosity with which he could change his mind. Even after accepting that some signals are reliable because of their strategic costs, he argued for a pluralistic approach to signal reliability. Signal complexity was a developing interest when he died. Signals usually involve several components, some of which appear to amplify other signal components. The terms "amplifier" and "index" require more thought to reduce the scope for semantic confusion. I conclude by describing Maynard Smith's fascination with peacocks Pavo cristatus.

  11. Sinusoidal Representation of Acoustic Signals

    Science.gov (United States)

    Honda, Masaaki

    Sinusoidal representation of acoustic signals has been an important tool in speech and music processing like signal analysis, synthesis and time scale or pitch modifications. It can be applicable to arbitrary signals, which is an important advantage over other signal representations like physical modeling of acoustic signals. In sinusoidal representation, acoustic signals are composed as sums of sinusoid (sine wave) with different amplitudes, frequencies and phases, which is based on the timedependent short-time Fourier transform (STFT). This article describes the principles of acoustic signal analysis/synthesis based on a sinusoid representation with focus on sine waves with rapidly varying frequency.

  12. Fetal QRS extraction from abdominal recordings via model-based signal processing and intelligent signal merging

    International Nuclear Information System (INIS)

    Haghpanahi, Masoumeh; Borkholder, David A

    2014-01-01

    Noninvasive fetal ECG (fECG) monitoring has potential applications in diagnosing congenital heart diseases in a timely manner and assisting clinicians to make more appropriate decisions during labor. However, despite advances in signal processing and machine learning techniques, the analysis of fECG signals has still remained in its preliminary stages. In this work, we describe an algorithm to automatically locate QRS complexes in noninvasive fECG signals obtained from a set of four electrodes placed on the mother’s abdomen. The algorithm is based on an iterative decomposition of the maternal and fetal subspaces and filtering of the maternal ECG (mECG) components from the fECG recordings. Once the maternal components are removed, a novel merging technique is applied to merge the signals and detect the fetal QRS (fQRS) complexes. The algorithm was trained and tested on the fECG datasets provided by the PhysioNet/CinC challenge 2013. The final results indicate that the algorithm is able to detect fetal peaks for a variety of signals with different morphologies and strength levels encountered in clinical practice. (paper)

  13. The newest digital signal processing

    International Nuclear Information System (INIS)

    Lee, Chae Uk

    2002-08-01

    This book deal with the newest digital signal processing, which contains introduction on conception of digital signal processing, constitution and purpose, signal and system such as signal, continuos signal, discrete signal and discrete system, I/O expression on impress response, convolution, mutual connection of system and frequency character,z transform of definition, range, application of z transform and relationship with laplace transform, Discrete fourier, Fast fourier transform on IDFT algorithm and FFT application, foundation of digital filter of notion, expression, types, frequency characteristic of digital filter and design order of filter, Design order of filter, Design of FIR digital filter, Design of IIR digital filter, Adaptive signal processing, Audio signal processing, video signal processing and application of digital signal processing.

  14. Variable reflectivity signal mirrors and signal response measurements

    International Nuclear Information System (INIS)

    Vine, Glenn de; Shaddock, Daniel A; McClelland, David E

    2002-01-01

    Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations

  15. Variable reflectivity signal mirrors and signal response measurements

    CERN Document Server

    Vine, G D; McClelland, D E

    2002-01-01

    Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations.

  16. Directional dual-tree rational-dilation complex wavelet transform.

    Science.gov (United States)

    Serbes, Gorkem; Gulcur, Halil Ozcan; Aydin, Nizamettin

    2014-01-01

    Dyadic discrete wavelet transform (DWT) has been used successfully in processing signals having non-oscillatory transient behaviour. However, due to the low Q-factor property of their wavelet atoms, the dyadic DWT is less effective in processing oscillatory signals such as embolic signals (ESs). ESs are extracted from quadrature Doppler signals, which are the output of Doppler ultrasound systems. In order to process ESs, firstly, a pre-processing operation known as phase filtering for obtaining directional signals from quadrature Doppler signals must be employed. Only then, wavelet based methods can be applied to these directional signals for further analysis. In this study, a directional dual-tree rational-dilation complex wavelet transform, which can be applied directly to quadrature signals and has the ability of extracting directional information during analysis, is introduced.

  17. ASIC For Complex Fixed-Point Arithmetic

    Science.gov (United States)

    Petilli, Stephen G.; Grimm, Michael J.; Olson, Erlend M.

    1995-01-01

    Application-specific integrated circuit (ASIC) performs 24-bit, fixed-point arithmetic operations on arrays of complex-valued input data. High-performance, wide-band arithmetic logic unit (ALU) designed for use in computing fast Fourier transforms (FFTs) and for performing ditigal filtering functions. Other applications include general computations involved in analysis of spectra and digital signal processing.

  18. Complex-Valued Neural Networks

    CERN Document Server

    Hirose, Akira

    2012-01-01

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

  19. Complex analysis and geometry

    CERN Document Server

    Silva, Alessandro

    1993-01-01

    The papers in this wide-ranging collection report on the results of investigations from a number of linked disciplines, including complex algebraic geometry, complex analytic geometry of manifolds and spaces, and complex differential geometry.

  20. Complex Systems: An Introduction

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 9. Complex Systems: An Introduction - Anthropic Principle, Terrestrial Complexity, Complex Materials. V K Wadhawan. General Article Volume 14 Issue 9 September 2009 pp 894-906 ...

  1. Sphingosine signaling and atherogenesis

    DEFF Research Database (Denmark)

    Xu, Cang-bao; Hansen-Schwartz, Jacob; Edvinsson, Lars

    2004-01-01

    Sphingosine-1-phosphate (S1P) has diverse biological functions acting inside cells as a second messenger to regulate cell proliferation and survival, and extracellularly, as a ligand for a group of G protein-coupled receptors (GPCRs) named the endothelial differentiation gene (EDG) family. Five...... closely related GPCRs of EDG family (EDG1, EDG3, EDG5, EDG6, and EDG8) have recently been identified as high-affinity S1P receptors. These receptors are coupled via Gi, Gq, G12/13, and Rho. The signaling pathways are linked to vascular cell migration, proliferation, apoptosis, intracellular Ca2......+ mobilization, and expression of adhesion molecules. The formation of an atherosclerotic lesion occurs through activation of cellular events that include monocyte adhesion to the endothelium and vascular smooth muscle cell (VSMC) migration and proliferation. Thus, S1P signaling may play an important role...

  2. NMR signal transducer

    International Nuclear Information System (INIS)

    Kucheryaev, A.G.; Oliferchuk, N.L.

    1975-01-01

    A signal transducer of nuclear magnetic resonance for simultaneously measuring frequency and intensitivity of two various isotope signals, which are in one specimen is described. The transducer represents radiofrequency circuit with two resonance frequences, which is common for two autodyne generators. To decrease measuring time and to increase recording diagram stability the radiofrequency circuit has LC netork, in the inductivity of which investigated specimen is located; a circuit variable capacity is connected in parallel with one of the autodyne generators. Besides the radiofrequency circuit has an inductance coil in series with a standard specimen inside as well as a variable capacitor connected in parallel with the second autodyne generator. An amplitude of oscillation of each resonance frequency is controlled and adjusted separately. The transducer described can be used for the measurement of a nuclei concentration, isotope concentration and for the spin determination

  3. Noise reduction with complex bilateral filter.

    Science.gov (United States)

    Matsumoto, Mitsuharu

    2017-12-01

    This study introduces a noise reduction technique that uses a complex bilateral filter. A bilateral filter is a nonlinear filter originally developed for images that can reduce noise while preserving edge information. It is an attractive filter and has been used in many applications in image processing. When it is applied to an acoustical signal, small-amplitude noise is reduced while the speech signal is preserved. However, a bilateral filter cannot handle noise with relatively large amplitudes owing to its innate characteristics. In this study, the noisy signal is transformed into the time-frequency domain and the filter is improved to handle complex spectra. The high-amplitude noise is reduced in the time-frequency domain via the proposed filter. The features and the potential of the proposed filter are also confirmed through experiments.

  4. Cell Signaling and Neurotoxicity: 3H-Arachidonic acid release (Phospholipase A2) in cerebellar granule neurons

    Science.gov (United States)

    Cell signaling is a complex process which controls basic cellular activities and coordinates actions to maintain normal cellular homeostasis. Alterations in signaling processes have been associated with neurological diseases such as Alzheimer's and cerebellar ataxia, as well as, ...

  5. Biomedical signal analysis

    CERN Document Server

    Rangayyan, Rangaraj M

    2015-01-01

    The book will help assist a reader in the development of techniques for analysis of biomedical signals and computer aided diagnoses with a pedagogical examination of basic and advanced topics accompanied by over 350 figures and illustrations. Wide range of filtering techniques presented to address various applications. 800 mathematical expressions and equations. Practical questions, problems and laboratory exercises. Includes fractals and chaos theory with biomedical applications.

  6. Protein scaffolds and higher-order complexes in synthetic biology

    NARCIS (Netherlands)

    den Hamer, A.; Rosier, B.J.H.M.; Brunsveld, L.; de Greef, T.F.A.; Ryadnov, M.; Brunsveld, L.; Suga, H.

    2017-01-01

    Interactions between proteins control molecular functions such as signalling or metabolic activity. Assembly of proteins via scaffold proteins or in higher-order complexes is a key regulatory mechanism. Understanding and functionally applying this concept requires the construction, study, and

  7. On-Line QRS Complex Detection Using Wavelet Filtering

    National Research Council Canada - National Science Library

    Szilagyi, L

    2001-01-01

    ...: first a wavelet transform filtering is applied to the signal, then QRS complex localization is performed using a maximum detection and peak classification algorithm The algorithm has been tested...

  8. Calcium signaling in liver.

    Science.gov (United States)

    Gaspers, Lawrence D; Thomas, Andrew P

    2005-01-01

    In hepatocytes, hormones linked to the formation of the second messenger inositol 1,4,5-trisphosphate (InsP3) evoke transient increases or spikes in cytosolic free calcium ([Ca2+]i), that increase in frequency with the agonist concentration. These oscillatory Ca2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca2+-sensitive metabolic processes. We have utilized both confocal and wide field fluorescence microscopy techniques to study the InsP3-dependent signaling pathway at the cellular and subcellular levels in the intact perfused liver. Typically InsP3-dependent [Ca2+]i spikes manifest as Ca2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca2+]i increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca2+ provides a means to coordinate the function of metabolic zones of the lobule and thus, liver function. In this article, we describe the characteristics of agonist-evoked [Ca2+]i signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ.

  9. A deep learning approach for fetal QRS complex detection.

    Science.gov (United States)

    Zhong, Wei; Liao, Lijuan; Guo, Xuemei; Wang, Guoli

    2018-04-20

    Non-invasive foetal electrocardiography (NI-FECG) has the potential to provide more additional clinical information for detecting and diagnosing fetal diseases. We propose and demonstrate a deep learning approach for fetal QRS complex detection from raw NI-FECG signals by using a convolutional neural network (CNN) model. The main objective is to investigate whether reliable fetal QRS complex detection performance can still be obtained from features of single-channel NI-FECG signals, without canceling maternal ECG (MECG) signals. A deep learning method is proposed for recognizing fetal QRS complexes. Firstly, we collect data from set-a of the PhysioNet/computing in Cardiology Challenge database. The sample entropy method is used for signal quality assessment. Part of the bad quality signals is excluded in the further analysis. Secondly, in the proposed method, the features of raw NI-FECG signals are normalized before they are fed to a CNN classifier to perform fetal QRS complex detection. We use precision, recall, F-measure and accuracy as the evaluation metrics to assess the performance of fetal QRS complex detection. The proposed deep learning method can achieve relatively high precision (75.33%), recall (80.54%), and F-measure scores (77.85%) compared with three other well-known pattern classification methods, namely KNN, naive Bayes and SVM. the proposed deep learning method can attain reliable fetal QRS complex detection performance from the raw NI-FECG signals without canceling MECG signals. In addition, the influence of different activation functions and signal quality assessment on classification performance are evaluated, and results show that Relu outperforms the Sigmoid and Tanh on this particular task, and better classification performance is obtained with the signal quality assessment step in this study.

  10. Updating signal typing in voice: addition of type 4 signals.

    Science.gov (United States)

    Sprecher, Alicia; Olszewski, Aleksandra; Jiang, Jack J; Zhang, Yu

    2010-06-01

    The addition of a fourth type of voice to Titze's voice classification scheme is proposed. This fourth voice type is characterized by primarily stochastic noise behavior and is therefore unsuitable for both perturbation and correlation dimension analysis. Forty voice samples were classified into the proposed four types using narrowband spectrograms. Acoustic, perceptual, and correlation dimension analyses were completed for all voice samples. Perturbation measures tended to increase with voice type. Based on reliability cutoffs, the type 1 and type 2 voices were considered suitable for perturbation analysis. Measures of unreliability were higher for type 3 and 4 voices. Correlation dimension analyses increased significantly with signal type as indicated by a one-way analysis of variance. Notably, correlation dimension analysis could not quantify the type 4 voices. The proposed fourth voice type represents a subset of voices dominated by noise behavior. Current measures capable of evaluating type 4 voices provide only qualitative data (spectrograms, perceptual analysis, and an infinite correlation dimension). Type 4 voices are highly complex and the development of objective measures capable of analyzing these voices remains a topic of future investigation.

  11. Generation and coherent detection of QPSK signal using a novel method of digital signal processing

    Science.gov (United States)

    Zhao, Yuan; Hu, Bingliang; He, Zhen-An; Xie, Wenjia; Gao, Xiaohui

    2018-02-01

    We demonstrate an optical quadrature phase-shift keying (QPSK) signal transmitter and an optical receiver for demodulating optical QPSK signal with homodyne detection and digital signal processing (DSP). DSP on the homodyne detection scheme is employed without locking the phase of the local oscillator (LO). In this paper, we present an extracting one-dimensional array of down-sampling method for reducing unwanted samples of constellation diagram measurement. Such a novel scheme embodies the following major advantages over the other conventional optical QPSK signal detection methods. First, this homodyne detection scheme does not need strict requirement on LO in comparison with linear optical sampling, such as having a flat spectral density and phase over the spectral support of the source under test. Second, the LabVIEW software is directly used for recovering the QPSK signal constellation without employing complex DSP circuit. Third, this scheme is applicable to multilevel modulation formats such as M-ary PSK and quadrature amplitude modulation (QAM) or higher speed signals by making minor changes.

  12. Nonlinear Silicon Photonic Signal Processing Devices for Future Optical Networks

    Directory of Open Access Journals (Sweden)

    Cosimo Lacava

    2017-01-01

    Full Text Available In this paper, we present a review on silicon-based nonlinear devices for all optical nonlinear processing of complex telecommunication signals. We discuss some recent developments achieved by our research group, through extensive collaborations with academic partners across Europe, on optical signal processing using silicon-germanium and amorphous silicon based waveguides as well as novel materials such as silicon rich silicon nitride and tantalum pentoxide. We review the performance of four wave mixing wavelength conversion applied on complex signals such as Differential Phase Shift Keying (DPSK, Quadrature Phase Shift Keying (QPSK, 16-Quadrature Amplitude Modulation (QAM and 64-QAM that dramatically enhance the telecom signal spectral efficiency, paving the way to next generation terabit all-optical networks.

  13. Biomedical signal and image processing

    CERN Document Server

    Najarian, Kayvan

    2012-01-01

    INTRODUCTION TO DIGITAL SIGNAL AND IMAGE PROCESSINGSignals and Biomedical Signal ProcessingIntroduction and OverviewWhat is a ""Signal""?Analog, Discrete, and Digital SignalsProcessing and Transformation of SignalsSignal Processing for Feature ExtractionSome Characteristics of Digital ImagesSummaryProblemsFourier TransformIntroduction and OverviewOne-Dimensional Continuous Fourier TransformSampling and NYQUIST RateOne-Dimensional Discrete Fourier TransformTwo-Dimensional Discrete Fourier TransformFilter DesignSummaryProblemsImage Filtering, Enhancement, and RestorationIntroduction and Overview

  14. Signal multiplexing scheme for LINAC

    International Nuclear Information System (INIS)

    Sujo, C.I.; Mohan, Shyam; Joshi, Gopal; Singh, S.K.; Karande, Jitendra

    2004-01-01

    For the proper operation of the LINAC some signals, RF (radio frequency) as well as LF (low frequency) have to be available at the Master Control Station (MCS). These signals are needed to control, calibrate and characterize the RF fields in the resonators. This can be achieved by proper multiplexing of various signals locally and then routing the selected signals to the MCS. A multiplexing scheme has been designed and implemented, which will allow the signals from the selected cavity to the MCS. High isolation between channels and low insertion loss for a given signal are important issues while selecting the multiplexing scheme. (author)

  15. Modeling High-Dimensional Multichannel Brain Signals

    KAUST Repository

    Hu, Lechuan

    2017-12-12

    Our goal is to model and measure functional and effective (directional) connectivity in multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The difficulties from analyzing these data mainly come from two aspects: first, there are major statistical and computational challenges for modeling and analyzing high-dimensional multichannel brain signals; second, there is no set of universally agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with potentially high lag order so that complex lead-lag temporal dynamics between the channels can be captured. Estimates of the VAR model will be obtained by our proposed hybrid LASSLE (LASSO + LSE) method which combines regularization (to control for sparsity) and least squares estimation (to improve bias and mean-squared error). Then we employ some measures of connectivity but put an emphasis on partial directed coherence (PDC) which can capture the directional connectivity between channels. PDC is a frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative to all possible receivers in the network. The proposed modeling approach provided key insights into potential functional relationships among simultaneously recorded sites during performance of a complex memory task. Specifically, this novel method was successful in quantifying patterns of effective connectivity across electrode locations, and in capturing how these patterns varied across trial epochs and trial types.

  16. Domain dependent associations between cognitive functioning and regular voluntary exercise behavior

    NARCIS (Netherlands)

    Swagerman, Suzanne C; de Geus, Eco J C; Koenis, Marinka M G; Hulshoff Pol, Hilleke E; Boomsma, Dorret I; Kan, Kees-Jan

    Regular exercise has often been suggested to have beneficial effects on cognition, but empirical findings are mixed because of heterogeneity in sample composition (age and sex); the cognitive domain being investigated; the definition and reliability of exercise behavior measures; and study design

  17. Domain dependent associations between cognitive functioning and regular voluntary exercise behavior

    NARCIS (Netherlands)

    Swagerman, S.C.; de Geus, E.J.C.; Koenis, M.M.G.; Hulshoff Pol, H.E.; Boomsma, D.I.; Kan, K.J.

    2015-01-01

    Regular exercise has often been suggested to have beneficial effects on cognition, but empirical findings are mixed because of heterogeneity in sample composition (age and sex); the cognitive domain being investigated; the definition and reliability of exercise behavior measures; and study design

  18. Deficiency in chromosome congression by the inhibition of Plk1 polo box domain-dependent recognition.

    Science.gov (United States)

    Watanabe, Nobumoto; Sekine, Tomomi; Takagi, Masatoshi; Iwasaki, Jun-ichi; Imamoto, Naoko; Kawasaki, Hisashi; Osada, Hiroyuki

    2009-01-23

    Polo-like kinase 1 (Plk1) is one of the key regulators of mitotic cell division. In addition to an N-terminal protein kinase catalytic domain, Plk1 possesses a phosphopeptide binding domain named polo box domain (PBD) at its C terminus. PBD is postulated to be essential for Plk1 localization and substrate targeting. Here, we developed a high-throughput screening system to identify inhibitors of PBD-dependent binding and screened a chemical library. We isolated a benzotropolone-containing natural compound derived from nutgalls (purpurogallin (PPG)) that inhibited PBD-dependent binding in vitro and in vivo. PPG not only delayed the onset of mitosis but also prolonged the progression of mitosis in HeLa cells. Although apparently normal bipolar spindles were formed even in the presence of PPG, the perturbation of chromosome alignment at metaphase plates activated the spindle assembly checkpoint pathway. These results demonstrate the predominant role of PBD-dependent binding on smooth chromosome congression at metaphase.

  19. Dissection of the insulin signaling pathway via quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Krüger, Marcus; Kratchmarova, Irina; Blagoev, Blagoy

    2008-01-01

    spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC......The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full...

  20. A Mixed-Signal Embedded Platform for Automotive Sensor Conditioning

    OpenAIRE

    Emilio Volpi; Luca Fanucci; Adolfo Giambastiani; Alessandro Rocchi; Francesco D'Ascoli; Marco Tonarelli; Massimiliano Melani; Corrado Marino

    2010-01-01

    Abstract A mixed-signal embedded system called Intelligent Sensor InterFace (ISIF) suited to fast identify, trim, and verify an architecture to interface a given sensor is presented. This system has been developed according to a platform-based design approach, a methodology that has proved to be efficient for building complex mixed-signal embedded systems with short time-to-market. Such platform consists in a wide set of optimized high-performance analog, digital, and software intellectual pr...