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Sample records for calcium signaling controls

  1. Connexins regulate calcium signaling by controlling ATP release

    OpenAIRE

    Cotrina, Maria Luisa; Lin, Jane H.-C.; Alves-Rodrigues, Alexandra; Liu, Shujun; Li, Jiang; Azmi-Ghadimi, Hooman; Kang, Jian; Naus, Christian C.G.; Nedergaard, Maiken

    1998-01-01

    Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca2+ mobilization and was inhibited by Cl− channel blockers. Calcium wave propagation also was reduced by purinergic receptor antag...

  2. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

    This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Geneviève Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Université Libre de Bruxelles;Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbrück Center for Molecular Medicine, Berlin;Vivien Kirk is an Associate Professor in the Depar...

  3. Calcium signaling in physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    He-ping CHENG; Sheng WEI; Li-ping WEI; Alexei VERKHRATSKY

    2006-01-01

    Calcium ions are the most ubiquitous and pluripotent cellular signaling molecules that control a wide variety of cellular processes.The calcium signaling system is represented by a relatively limited number of highly conserved transporters and channels,which execute Ca2+ movements across biological membranes and by many thousands of Ca2+-sensitive effectors.Molecular cascades,responsible for the generation of calcium signals,are tightly controlled by Ca2+ ions themselves and by genetic factors,which tune the expression of different Ca2+-handling molecules according to adaptational requirements.Ca2+ ions determine normal physiological reactions and the development of many pathological processes.

  4. Calcium signals and calcium channels in osteoblastic cells

    Science.gov (United States)

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

    1998-01-01

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

  5. The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction

    OpenAIRE

    Mackenzie, L; Roderick, H Llewelyn; Berridge, MJ; Conway, SJ; Bootman, MD

    2004-01-01

    We examined the regulation of calcium signalling in atrial cardiomyocytes during excitation-contraction coupling, and how changes in the distribution of calcium impacts on contractility. Under control conditions, calcium transients originated in subsarcolemmal locations and showed local regeneration through activation of calcium-induced calcium release from ryanodine receptors. Despite functional ryanodine receptors being expressed at regular (~2 μm) intervals throughout atrial myocytes, the ...

  6. CCN3 and calcium signaling

    Directory of Open Access Journals (Sweden)

    Li Chang Long

    2003-08-01

    Full Text Available Abstract The CCN family of genes consists presently of six members in human (CCN1-6 also known as Cyr61 (Cystein rich 61, CTGF (Connective Tissue Growth Factor, NOV (Nephroblastoma Overexpressed gene, WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins. Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions. In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.

  7. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others

  8. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s...... affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be...

  9. Interorganellar Membrane Microdomains: Dynamic Platforms in the Control of Calcium Signaling and Apoptosis

    Directory of Open Access Journals (Sweden)

    Alessandra d'Azzo

    2013-08-01

    Full Text Available The dynamic interplay among intracellular organelles occurs at specific membrane tethering sites, where two organellar membranes come in close apposition but do not fuse. Such membrane microdomains allow for rapid and efficient interorganelle communication that contributes to the maintenance of cell physiology. Pathological conditions that interfere with the proper composition, number, and physical vicinity of the apposing membranes initiate a cascade of events resulting in cell death. Membrane contact sites have now been identified that tether the extensive network of the endoplasmic reticulum (ER membranes with the mitochondria, the plasma membrane (PM, the Golgi and the endosomes/lysosomes. Thus far, the most extensively studied are the MAMs, or mitochondria associated ER membranes, and the ER-PM junctions that share functional properties and crosstalk to one another. Specific molecular components that define these microdomains have been shown to promote the interaction in trans between these intracellular compartments and the transfer or exchange of Ca2+ ions, lipids, and metabolic signaling molecules that determine the fate of the cell.

  10. Stochastic models of intracellular calcium signals

    International Nuclear Information System (INIS)

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed

  11. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

    Rüdiger, Sten, E-mail: sten.ruediger@physik.hu-berlin.de

    2014-01-10

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  12. Glial calcium signaling in physiology and pathophysioilogy

    Institute of Scientific and Technical Information of China (English)

    Alexei VERKHRASKY

    2006-01-01

    Neuronal-glial circuits underlie integrative processes in the nervous system.Function of glial syncytium is,to a very large extent,regulated by the intracellular calcium signaling system.Glial calcium signals are triggered by activation of multiple receptors,expressed in glial membrane,which regulate both Ca2+ entry and Ca2+ release from the endoplasmic reticulum.The endoplasmic reticulum also endows glial cells with intracellular excitable media,which is able to produce and maintain long-ranging signaling in a form of propagating Ca2+ waves.In pathological conditions,calcium signals regulate glial response to injury,which might have both protective and detrimental effects on the nervous tissue.

  13. STIM1 is a Calcium Sensor Specialized for Digital Signaling

    OpenAIRE

    Bird, Gary S.; Hwang, Sung-Yong; Smyth, Jeremy T.; Fukushima, Miwako; Boyles, Rebecca R.; Putney, James W.

    2009-01-01

    When cells are activated by calcium-mobilizing agonists at low, physiological concentrations, the resulting calcium signals generally take the form of repetitive regenerative discharges of stored calcium, termed calcium oscillations [1]. These intracellular calcium oscillations have long fascinated biologists as representing a mode of digitized intracellular signaling. Recent work has highlighted the role of calcium influx as an essential component of calcium oscillations [2]. This influx occ...

  14. Astrocyte calcium signaling: the third wave.

    Science.gov (United States)

    Bazargani, Narges; Attwell, David

    2016-01-27

    The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function. PMID:26814587

  15. Calcium Signals from the Vacuole

    Directory of Open Access Journals (Sweden)

    Gerald Schönknecht

    2013-10-01

    Full Text Available The vacuole is by far the largest intracellular Ca2+ store in most plant cells. Here, the current knowledge about the molecular mechanisms of vacuolar Ca2+ release and Ca2+ uptake is summarized, and how different vacuolar Ca2+ channels and Ca2+ pumps may contribute to Ca2+ signaling in plant cells is discussed. To provide a phylogenetic perspective, the distribution of potential vacuolar Ca2+ transporters is compared for different clades of photosynthetic eukaryotes. There are several candidates for vacuolar Ca2+ channels that could elicit cytosolic [Ca2+] transients. Typical second messengers, such as InsP3 and cADPR, seem to trigger vacuolar Ca2+ release, but the molecular mechanism of this Ca2+ release still awaits elucidation. Some vacuolar Ca2+ channels have been identified on a molecular level, the voltage-dependent SV/TPC1 channel, and recently two cyclic-nucleotide-gated cation channels. However, their function in Ca2+ signaling still has to be demonstrated. Ca2+ pumps in addition to establishing long-term Ca2+ homeostasis can shape cytosolic [Ca2+] transients by limiting their amplitude and duration, and may thus affect Ca2+ signaling.

  16. Sodium/Calcium Exchangers Selectively Regulate Calcium Signaling in Mouse Taste Receptor Cells

    OpenAIRE

    Szebenyi, Steven A.; Laskowski, Agnieszka I.; Medler, Kathryn F.

    2010-01-01

    Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium release from intracellular stores while other stimuli depolarize taste cells to cause calcium influx through voltage-gated calcium channels (VGCCs). While the signaling mechanisms that initiate calcium signals have been described in taste cells, the calcium clearance mechanisms (CCMs) that contrib...

  17. Calcium signaling: A tale for all seasons

    OpenAIRE

    Carafoli, Ernesto

    2002-01-01

    An experiment performed in London nearly 120 years ago, which by today's standards would be considered unacceptably sloppy, marked the beginning of the calcium (Ca2+) signaling saga. Sidney Ringer [Ringer, S. (1883) J. Physiol. 4, 29–43] was studying the contraction of isolated rat hearts. In earlier experiments, Ringer had suspended them in a saline medium for which he admitted to having used London tap water, which is hard: The hearts contracted beautifully. When he proceeded to replace the...

  18. Coupling Effect of Ion Channel Clusters on Calcium Signalling

    International Nuclear Information System (INIS)

    Based on a modified intracellular Ca2+ model involving diffusive coupling of two calcium ion channel clusters, the effects of coupling on calcium signalling are numerically investigated. The simulation results indicate that the diffusive coupling of clusters together with internal noise determine the calcium dynamics of single cluster, and for either homogeneous or heterogeneous coupled clusters, the synchronization of clusters, which is important to calcium signalling, is enhanced by the coupling effect

  19. Coupling Effect of Ion Channel Clusters on Calcium Signalling

    Institute of Scientific and Technical Information of China (English)

    TANG Jun; JIA Ya; YI Ming; MA Jun; YU Guang

    2008-01-01

    @@ Based on a modified intracellular Ca2+ model involving diffusive coupling of two calcium ion channel clusters,the effects of coupling on calcium signalling are numerically investigated.The simulation results indicate that the diffusive coupling of clusters together with internal noise determine the calcium dynamics of single cluster,and for either homogeneous or heterogeneous coupled clusters,the synchronization of clusters,which is important to calcium signalling,is enhanced by the coupling effect.

  20. Calcium-Mediated Abiotic Stress Signaling in Roots.

    Science.gov (United States)

    Wilkins, Katie A; Matthus, Elsa; Swarbreck, Stéphanie M; Davies, Julia M

    2016-01-01

    Roots are subjected to a range of abiotic stresses as they forage for water and nutrients. Cytosolic free calcium is a common second messenger in the signaling of abiotic stress. In addition, roots take up calcium both as a nutrient and to stimulate exocytosis in growth. For calcium to fulfill its multiple roles must require strict spatio-temporal regulation of its uptake and efflux across the plasma membrane, its buffering in the cytosol and its sequestration or release from internal stores. This prompts the question of how specificity of signaling output can be achieved against the background of calcium's other uses. Threats to agriculture such as salinity, water availability and hypoxia are signaled through calcium. Nutrient deficiency is also emerging as a stress that is signaled through cytosolic free calcium, with progress in potassium, nitrate and boron deficiency signaling now being made. Heavy metals have the capacity to trigger or modulate root calcium signaling depending on their dose and their capacity to catalyze production of hydroxyl radicals. Mechanical stress and cold stress can both trigger an increase in root cytosolic free calcium, with the possibility of membrane deformation playing a part in initiating the calcium signal. This review addresses progress in identifying the calcium transporting proteins (particularly channels such as annexins and cyclic nucleotide-gated channels) that effect stress-induced calcium increases in roots and explores links to reactive oxygen species, lipid signaling, and the unfolded protein response. PMID:27621742

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

    Science.gov (United States)

    Baba, Yoshihiro; Kurosaki, Tomohiro

    2016-01-01

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

  2. Regulation of PKC mediated signaling by calcium during visceral leishmaniasis.

    Science.gov (United States)

    Roy, Nivedita; Chakraborty, Supriya; Paul Chowdhury, Bidisha; Banerjee, Sayantan; Halder, Kuntal; Majumder, Saikat; Majumdar, Subrata; Sen, Parimal C

    2014-01-01

    Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis. PMID:25329062

  3. Regulation of PKC mediated signaling by calcium during visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Nivedita Roy

    Full Text Available Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA and Sarco/endoplasmic reticulum calcium ATPase (SERCA which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis.

  4. Calcium microdomains near R-type calcium channels control the induction of presynaptic LTP at parallel fiber to Purkinje cell synapses

    OpenAIRE

    Myoga, Michael H.; Regehr, Wade G.

    2011-01-01

    R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium-calmodulin sensitive potassium channel that in turn regulates postsynaptic hippocampal LTP. Here we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated ...

  5. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    Losiana Nayak; Rajat K De

    2007-08-01

    Signalling pathways are complex biochemical networks responsible for reg ulation of numerous cellular functions. These networks function by serial and successive interactions among a large number of vital biomolecules and chemical compounds. For deciphering and analysing the underlying mechanism of such networks, a modularized study is quite helpful. Here we propose an algorithm for modularization of calcium signalling pathway of H. sapiens. The idea that ``a node whose function is dependant on maximum number of other nodes tends to be the center of a sub network” is used to divide a large signalling network into smaller sub networks. Inclusion of node(s) into sub networks(s) is dependant on the outdegree of the node(s). Here outdegree of a node refers to the number of re lations of the considered node lying outside the constructed sub network. Node(s) having more than c relations lying outside the expanding subnetwork have to be excluded from it. Here is a specified variable based on user preference, which is finally fixed during adjustments of created subnetworks, so that certain biological significance can be conferred on them.

  6. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Audrey E. McCalley

    2014-06-01

    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  7. Calcium signaling in cognition and aging-dependent cognitive decline.

    Science.gov (United States)

    Oliveira, Ana M M; Bading, Hilmar

    2011-01-01

    Calcium-dependent signals are key triggers of the molecular mechanisms underlying learning and memory and dysregulation of calcium homeostasis in the aging brain has been proposed to underlie aging-dependent cognitive decline. Mechanisms triggered by calcium in neurons include activity-dependent activation of transcription responsible for the synthesis of molecules underlying the long-term changes of neuronal function. Effectors of calcium signaling with a primordial role in transcription regulation are calcium signal-regulated transcription factors. In this review, we summarize the current knowledge of the contribution of key calcium signal-regulated transcription factors, namely CREB, NFAT, and DREAM, to memory formation. We further describe evidence for dysregulation of the activity of these factors during aging. PMID:21698696

  8. Emanuel Strehler’s work on calcium pumps and calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Emanuel; E; Strehler

    2011-01-01

    Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders including heart disease, Alzheimer’s disease and stroke. Ca 2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca 2+ homeostasis in the cell, as well as on the mechanisms of localized Ca 2+ signaling. A longterm focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca 2+ levels, but also to local Ca 2+ signaling and vectorial Ca 2+ transport. A second major research arearevolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.

  9. The calcium-signaling toolkit: Updates needed.

    Science.gov (United States)

    Dubois, Charlotte; Prevarskaya, Natalia; Vanden Abeele, Fabien

    2016-06-01

    Here, we review the role of Ca(2+) in apoptosis, namely that ER Ca(2+) depletion or a sustained elevation of cytosolic or mitochondrial Ca(2+) concentration are sufficient to trigger apoptosis. These concepts have emerged by the use of ER stressor agents that decrease the ER Ca(2+) pool by inhibiting SERCA pumps. However, aside from their well-known actions on Ca(2+) homeostasis disruption leading to apoptosis, new evidence show that some ER Ca(2+) modulators have significant implications in other Ca(2+)-mediated or Ca(2+)-independent pathways determining cell fate suggesting a more complex regulation of apoptosis by intracellular Ca(2+). Here, we discuss the crucial interplay between Ca(2+) mediated apoptosis, the Unfold Protein Response and autophagy determining cell fate, and the molecular compounds that have been used to depict these pathways. This review of the literature clearly shows the need for new inhibitors that do not interfere concomitantly with autophagy and Ca(2+) signaling. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26658643

  10. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2005-01-01

    biological effects in bone. Intercellular calcium waves are increases in intracellular calcium concentration in single cells, subsequently propagating to adjacent cells, and can be a possible mechanism for the coupling of bone formation to bone resorption. The aim of the present studies was to investigate...... whether bone cells are capable of communicating via intercellular calcium signals, and determine by which mechanisms the cells propagate the signals. First, we found that osteoblastic cells can propagate intercellular calcium transients upon mechanical stimulation, and that there are two principally...... different mechanisms for this propagation. One mechanism involves the secretion of a nucleotide, possibly ATP, acting in an autocrine action to purinergic P2Y2 receptors on the neighboring cells, leading to intracellular IP3 generation and subsequent release of calcium from intracellular stores. The other...

  11. Relating a calcium indicator signal to the unperturbed calcium concentration time-course

    Directory of Open Access Journals (Sweden)

    Abarbanel Henry DI

    2007-02-01

    Full Text Available Abstract Background Optical indicators of cytosolic calcium levels have become important experimental tools in systems and cellular neuroscience. Indicators are known to interfere with intracellular calcium levels by acting as additional buffers, and this may strongly alter the time-course of various dynamical variables to be measured. Results By investigating the underlying reaction kinetics, we show that in some ranges of kinetic parameters one can explicitly link the time dependent indicator signal to the time-course of the calcium influx, and thus, to the unperturbed calcium level had there been no indicator in the cell.

  12. Involvement of aberrant calcium signalling in herpetic neuralgia.

    Science.gov (United States)

    Warwick, Rebekah A; Hanani, Menachem

    2016-03-01

    Alpha-herpesviruses, herpes simplex viruses (HSV) and varicella zoster virus (VZV), are pathogens of the peripheral nervous system. After primary infection, these viruses establish latency within sensory ganglia, while retaining the ability to reactivate. Reactivation of VZV results in herpes zoster, a condition characterized by skin lesions that leads to post-herpetic neuralgia. Recurrent reactivations of HSV, which cause mucocutaneous lesions, may also result in neuralgia. During reactivation of alpha-herpesviruses, satellite glial cells (SGCs), which surround neurons in sensory ganglia, become infected with the replicating virus. SGCs are known to contribute to neuropathic pain in a variety of animal pain models. Here we investigated how infection of short-term cultures of mouse trigeminal ganglia with HSV-1 affects communication between SGCs and neurons, and how this altered communication may increase neuronal excitability, thus contributing to herpetic neuralgia. Mechanical stimulation of single neurons or SGCs resulted in intercellular calcium waves, which were larger in cultures infected with HSV-1. Two differences were observed between control and HSV-1 infected cultures that could account for this augmentation. Firstly, HSV-1 infection induced cell fusion among SGCs and neurons, which would facilitate the spread of calcium signals over farther distances. Secondly, using calcium imaging and intracellular electrical recordings, we found that neurons in the HSV-1 infected cultures exhibited augmented influx of calcium upon depolarization. These virally induced changes may not only cause more neurons in the sensory ganglia to fire action potentials, but may also increase neurotransmitter release at the presynaptic terminals in the spinal cord. They are therefore likely to be contributing factors to herpetic neuralgia. PMID:26684187

  13. Enhanced Synchronization of Intercellular Calcium Oscillations by Noise Contaminated Signals

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ji-Qian; CHEN Han-Shuang; WANG Mao-Sheng

    2008-01-01

    We consider the dynamics of locally coupled calcium oscillation systems, each cell is subjected to extracel-lular contaminated signal, which contains common sub-threshold signal and independent Gaussian noise. It is found that intermediate noise can enhance synchronized oscillations of calcium ions, where the frequency of noise-induced oscilla-tions is matched with the one of sub-threshold external signal. We show that synchronization is enhanced as a result of the entrainment of external signal Furthermore, the effect of coupling strength is considered. We find above-mentioned phenomenon exists only when coupling strength is very small Our findings may exhibit that noise can enhance the detection of feeble external signal through the mechanism of synchronization of intercellular calcium ions.

  14. Multilevel complexity of calcium signaling:Modeling angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Luca; Munaron; Marco; Scianna

    2012-01-01

    Intracellular calcium signaling is a universal,evolutionary conserved and versatile regulator of cell biochemistry.The complexity of calcium signaling and related cell machinery can be investigated by the use of experimental strategies,as well as by computational approaches.Vascular endothelium is a fascinating model to study the specific properties and roles of calcium signals at multiple biological levels.During the past 20 years,live cell imaging,patch clamp and other techniques have allowed us to detect and interfere with calcium signaling in endothelial cells(ECs),providing a huge amount of information on the regulation of vascularization(angiogenesis) in normal and tumoral tissues.These data range from the spatiotemporal dynamics of calcium within different cell microcompartments to those in entire multicellular and organized EC networks.Beside experimental strategies,in silico endothelial models,specifically designed for simulating calcium signaling,are contributing to our knowledge of vascular physiol-ogy and pathology.They help to investigate and predict the quantitative features of proangiogenic events moving through subcellular,cellular and supracellular levels.This review focuses on some recent developments of computational approaches for proangiogenic endothelial calcium signaling.In particular,we discuss the creation of hybrid simulation environments,which combine and integrate discrete Cellular Potts Models.They are able to capture the phenomenological mechanisms of cell morphological reorganization,migration,and intercellular adhesion,with single-cell spatiotemporal models,based on reaction-diffusion equations that describe the agonist-induced intracellular calcium events.

  15. Multimodal encoding in a simplified model of intracellular calcium signaling

    OpenAIRE

    De Pitta`, Maurizio; Volman, Vladislav; Levine, Herbert; Ben-Jacob, Eshel

    2009-01-01

    Many cells use calcium signalling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca2+ signalling, much effort has been devoted to understand the functional role of Ca2+ responses and to decipher how their complex dynamics is regulated by the biochemical network of Ca2+-related signal transduction pathways. Experimental observations show that Ca2+ signals in response t...

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

    Science.gov (United States)

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

    2014-01-01

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

  17. Calcium signaling in UV-induced damage

    Science.gov (United States)

    Sun, Dan; Zhang, Su-juan; Li, Yuan-yuan; Qu, Ying; Ren, Zhao-Yu

    2007-05-01

    Hepa1-6 cells were irradiated with UV and incubated for varying periods of time. [Ca 2+] i (intracellular calcium concentration) of UV-irradiated cell was measured by ratio fluorescence imaging system. The comet assay was used to determine DNA damage. During the UVB-irradiation, [Ca 2+] i had an ascending tendency from 0.88 J/m2 to 92.4J/m2. Comet assay instant test indicated that when the irradiation dosage was above 0.88J/m2, DNA damage was observed. Even after approximate 2 h of incubation, DNA damage was still not detected by 0.88J/m2 of UVB irradiation. During UVA-irradiation, the elevation of [Ca 2+] i was not dose-dependent in a range of 1200 J/m2-6000J/m2 and DNA damage was not observed by comet assay. These results suggested that several intracellular UV receptors might induce [Ca 2+] i rising by absorption of the UV energy. Just [Ca 2+] i rising can't induce DNA damage certainly, it is very likely that the breakdown of calcium steady state induces DNA damage.u

  18. New concepts in calcium-sensing receptor pharmacology and signalling

    OpenAIRE

    Ward, Donald T.; Riccardi, Daniela

    2012-01-01

    The calcium-sensing receptor (CaR) is the key controller of extracellular calcium (Ca2+o) homeostasis via its regulation of parathyroid hormone (PTH) secretion and renal Ca2+ reabsorption. The CaR-selective calcimimetic drug Cinacalcet stimulates the CaR to suppress PTH secretion in chronic kidney disease and represents the world's first clinically available receptor positive allosteric modulator (PAM). Negative CaR allosteric modulators (NAMs), known as calcilytics, can increase PTH secretio...

  19. Calcium signaling and T-type calcium channels in cancer cell cycling

    Institute of Scientific and Technical Information of China (English)

    James T Taylor; Xiang-Bin Zeng; Jonathan E Pottle; Kevin Lee; Alun R Wang; Stephenie G Yi; Jennifer A S Scruggs; Suresh S Sikka; Ming Li

    2008-01-01

    Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells,free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear;however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers.

  20. Calcium signaling in the cochlea – Molecular mechanisms and physiopathological implications

    Directory of Open Access Journals (Sweden)

    Ceriani Federico

    2012-07-01

    Full Text Available Abstract Calcium ions (Ca2+ regulate numerous and diverse aspects of cochlear and vestibular physiology. This review focuses on the Ca2+ control of mechanotransduction and synaptic transmission in sensory hair cells, as well as on Ca2+ signalling in non-sensory cells of the developing cochlea.

  1. Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels.

    Science.gov (United States)

    Zemkova, Hana; Tomić, Melanija; Kucka, Marek; Aguilera, Greti; Stojilkovic, Stanko S

    2016-04-01

    Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage-insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling. PMID:26901094

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

    OpenAIRE

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

    2009-01-01

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

  3. T-type calcium channel: a privileged gate for calcium entry and control of adrenal steroidogenesis

    Directory of Open Access Journals (Sweden)

    Michel Florian Rossier

    2016-05-01

    Full Text Available Intracellular calcium plays a crucial role in modulating a variety of functions such as muscle contraction, hormone secretion, gene expression or cell growth. Calcium signaling has been however shown to be more complex than initially thought. Indeed, it is confined within cell microdomains and different calcium channels are associated with different functions, as shown by various channelopathies.Sporadic mutations on voltage-operated L-type calcium channels in adrenal glomerulosa cells have been shown recently to be the second most prevalent genetic abnormalities present in human aldosterone-producing adenoma. The observed modification of the threshold of activation of the mutated channels not only provides an explanation for this gain of function but reminds us on the importance of maintaining adequate electrophysiological characteristics to make channels able to exert specific cellular functions. Indeed, the contribution to steroid production of the various calcium channels expressed in adrenocortical cells is not equal and the reason has been investigated for a long time. Given the very negative resting potential of these cells, and the small membrane depolarization induced by their physiological agonists, low threshold T-type calcium channels are particularly well suited for responding under these conditions and conveying calcium into the cell, at the right place for controlling steroidogenesis. In contrast, high threshold L-type channels are normally activated by much stronger cell depolarizations. The fact that dihydropyridine calcium antagonists, specific for L-type channels, are poorly efficient for reducing aldosterone secretion either in vivo or in vitro, strongly supports the view that these two types of channels differently affect steroid biosynthesis.Whether a similar analysis is transposable to fasciculata cells and cortisol secretion is one of the questions addressed in the present review. No similar mutations on L-type or T

  4. Cytosolic organelles shape calcium signals and exo-endocytotic responses of chromaffin cells.

    Science.gov (United States)

    García, Antonio G; Padín, Fernando; Fernández-Morales, José C; Maroto, Marcos; García-Sancho, Javier

    2012-01-01

    The concept of stimulus-secretion coupling was born from experiments performed in chromaffin cells 50 years ago. Stimulation of these cells with acetylcholine enhances calcium (Ca(2+)) entry and this generates a transient elevation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) that triggers the exocytotic release of catecholamines. The control of the [Ca(2+)](c) signal is complex and depends on various classes of plasmalemmal calcium channels, cytosolic calcium buffers, the uptake and release of Ca(2+) from cytoplasmic organelles, such as the endoplasmic reticulum, mitochondria, chromaffin vesicles and the nucleus, and Ca(2+) extrusion mechanisms, such as the plasma membrane Ca(2+)-stimulated ATPase, and the Na(+)/Ca(2+) exchanger. Computation of the rates of Ca(2+) fluxes between the different cell compartments support the proposal that the chromaffin cell has developed functional calcium tetrads formed by calcium channels, cytosolic calcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca(2+) transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytotic responses. The different patterns of catecholamine secretion in response to stress may thus depend on such local [Ca(2+)](c) transients occurring at different cell compartments, and generated by redistribution and release of Ca(2+) by cytoplasmic organelles. In this manner, the calcium tetrads serve to couple the variable energy demands due to exo-endocytotic activities with energy production and protein synthesis. PMID:22209033

  5. Calcium and cell death signaling in neurodegeneration and aging

    Directory of Open Access Journals (Sweden)

    Soraya Smaili

    2009-09-01

    Full Text Available Transient increase in cytosolic (Cac2+ and mitochondrial Ca2+ (Ca m2+ are essential elements in the control of many physiological processes. However, sustained increases in Ca c2+ and Ca m2+ may contribute to oxidative stress and cell death. Several events are related to the increase in Ca m2+, including regulation and activation of a number of Ca2+ dependent enzymes, such as phospholipases, proteases and nucleases. Mitochondria and endoplasmic reticulum (ER play pivotal roles in the maintenance of intracellular Ca2+ homeostasis and regulation of cell death. Several lines of evidence have shown that, in the presence of some apoptotic stimuli, the activation of mitochondrial processes maylead to the release of cytochrome c followed by the activation of caspases, nuclear fragmentation and apoptotic cell death. The aim of this review was to show how changes in calcium signaling can be related to the apoptotic cell death induction. Calcium homeostasis was also shown to be an important mechanism involved in neurodegenerative and aging processes.Aumentos transientes no cálcio citosólico (Ca c2+ e mitocondrial (Ca m2+ são elementos essenciais no controle de muitos processos fisiológicos. No entanto, aumentos sustentados do Ca c2+ e do Ca m2+ podem contribuir para o estresse oxidativo ea morte celular. Muitos eventos estão relacionados ao aumentono Ca c2+, incluindo a regulação e ativação de várias enzimas dependentes de Ca2+ como as fosfolipases, proteases e nucleases. A mitocôndria e o retículo endoplasmático têm um papel central na manutenção da homeostase intracellular de Ca c2+ e na regulação da morte celular. Várias evidências mostraram que, na presença de certos estímulos apoptóticos, a ativação dos processos mitocondriais pode promover a liberação de citocromo c, seguida da ativação de caspases, fragmentação nuclear e morte celular por apoptose. O objetivo desta revisão é mostrar como aumentos na sinalização de

  6. Interaction between Calcium and Actin in Guard Cell and Pollen Signaling Networks

    Directory of Open Access Journals (Sweden)

    Dong-Hua Chen

    2013-10-01

    Full Text Available Calcium (Ca2+ plays important roles in plant growth, development, and signal transduction. It is a vital nutrient for plant physical design, such as cell wall and membrane, and also serves as a counter-cation for biochemical, inorganic, and organic anions, and more particularly, its concentration change in cytosol is a ubiquitous second messenger in plant physiological signaling in responses to developmental and environmental stimuli. Actin cytoskeleton is well known for its importance in cellular architecture maintenance and its significance in cytoplasmic streaming and cell division. In plant cell system, the actin dynamics is a process of polymerization and de-polymerization of globular actin and filamentous actin and that acts as an active regulator for calcium signaling by controlling calcium evoked physiological responses. The elucidation of the interaction between calcium and actin dynamics will be helpful for further investigation of plant cell signaling networks at molecular level. This review mainly focuses on the recent advances in understanding the interaction between the two aforementioned signaling components in two well-established model systems of plant, guard cell, and pollen.

  7. The Medicago truncatula DMI1 protein modulates cytosolic calcium signaling

    DEFF Research Database (Denmark)

    Peiter, Edgar; Sun, Jongho; Heckmann, Anne Birgitte Lau;

    2007-01-01

    Methanobacterium thermoautotrophicum potassium channel (MthK). The cytosolic C terminus of DMI1 contains a RCK (regulator of the conductance of K+) domain that in MthK acts as a calcium-regulated gating ring controlling the activity of the channel. Here we show that a dmi1 mutant lacking the entire C terminus acts...

  8. Human osteoblastic cells propagate intercellular calcium signals by two different mechanisms

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Henriksen, Z; Brot, C;

    2000-01-01

    . After the fast intercellular calcium waves were blocked, we observed slower calcium waves that were dependent on gap junctional communication and influx of extracellular calcium. These results show that human osteoblastic cells can propagate calcium signals from cell to cell by two markedly different...... cells: autocrine activation of P2 (purinergic) receptors leading to release of intracellular calcium stores, and gap junction-mediated communication resulting in influx of extracellular calcium. In the current work we asked whether human osteoblastic cells (HOB) were capable of mechanically induced...... intercellular calcium signaling, and if so, by which mechanisms. Upon mechanical stimulation, human osteoblasts propagated fast intercellular calcium waves, which required activation of P2 receptors and release of intracellular calcium stores but did not require calcium influx or gap junctional communication...

  9. Store-operated calcium channels and pro-inflammatory signals

    Institute of Scientific and Technical Information of China (English)

    Wei-chiao CHANG

    2006-01-01

    In non-excitable cells such as T lymphocytes,hepatocytes,mast cells,endothelia and epithelia,the major pathway for calcium(Ca2+)entry is through store-operated Ca2+ channels in the plasma membrane.These channels are activated by the emptying of intracellular Ca2+ stores,however,neither the gating mechanism nor the downstream targets of these channels has been clear established.Here,I review some of the proposed gating mechanisms of store-operated Ca2+ channels and the functional implications in regulating pro-inflammatory signals.

  10. Cross-talk between calcium and reactive oxygen species signaling

    Institute of Scientific and Technical Information of China (English)

    Yuan YAN; Chao-liang WEI; Wan-rui ZHANG; He-ping CHENG; Jie LIU

    2006-01-01

    Calcium(Ca2+) and reactive oxygen species(ROS)constitute the most important intracellular signaling molecules participating in the regulation and integration of diverse cellular functions.Here we briefly review cross-talk between the two prominent signaling systems that finely tune the homeostasis and integrate functionality of Ca2+ and ROS in different types of cells.Ca2+ modulates ROS homeostasis by regulating ROS generation and annihilation mechanisms in both the mitochondria and the cytosol.Reciprocal redox regulation of Ca2+ homeostasis occurs in different physiological and pathological processes,by modulating components of the Ca2+ signaling toolkit and altering characteristics of local and global Ca2+ signals.Functionally,interactions between Ca2+ and ROS signaling systems can be both stimulatory and inhibitory,depending on the type of target proteins,the ROS species,the dose,duration of exposure,and the cell contexts.Such extensive and complex cross-talk might enhance signaling coordination and integration,whereas abnormalities in either system might propagate into the other system and undermine the stability of both systems.

  11. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    Directory of Open Access Journals (Sweden)

    János Brunner

    2014-03-01

    resulted in faster repolarization and increased AP related calcium signals relative to the control (i. e. in the absence of the extra conductance at the same membrane potential. In conclusion, our results revealed that activation of potassium currents can profoundly enhance dendritic bAP-evoked calcium signals in GC dendrites, thus providing a previously unknown state-dependent modulatory mechanism in dendritic signalization.

  12. The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease.

    Science.gov (United States)

    Berridge, Michael J

    2016-10-01

    Many cellular functions are regulated by calcium (Ca(2+)) signals that are generated by different signaling pathways. One of these is the inositol 1,4,5-trisphosphate/calcium (InsP3/Ca(2+)) signaling pathway that operates through either primary or modulatory mechanisms. In its primary role, it generates the Ca(2+) that acts directly to control processes such as metabolism, secretion, fertilization, proliferation, and smooth muscle contraction. Its modulatory role occurs in excitable cells where it modulates the primary Ca(2+) signal generated by the entry of Ca(2+) through voltage-operated channels that releases Ca(2+) from ryanodine receptors (RYRs) on the internal stores. In carrying out this modulatory role, the InsP3/Ca(2+) signaling pathway induces subtle changes in the generation and function of the voltage-dependent primary Ca(2+) signal. Changes in the nature of both the primary and modulatory roles of InsP3/Ca(2+) signaling are a contributory factor responsible for the onset of a large number human diseases. PMID:27512009

  13. 14-3-3 Proteins Buffer Intracellular Calcium Sensing Receptors to Constrain Signaling.

    Directory of Open Access Journals (Sweden)

    Michael P Grant

    Full Text Available Calcium sensing receptors (CaSR interact with 14-3-3 binding proteins at a carboxyl terminal arginine-rich motif. Mutations identified in patients with familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia, pancreatitis or idiopathic epilepsy support the functional importance of this motif. We combined total internal reflection fluorescence microscopy and biochemical approaches to determine the mechanism of 14-3-3 protein regulation of CaSR signaling. Loss of 14-3-3 binding caused increased basal CaSR signaling and plasma membrane levels, and a significantly larger signaling-evoked increase in plasma membrane receptors. Block of core glycosylation with tunicamycin demonstrated that changes in plasma membrane CaSR levels were due to differences in exocytic rate. Western blotting to quantify time-dependent changes in maturation of expressed wt CaSR and a 14-3-3 protein binding-defective mutant demonstrated that signaling increases synthesis to maintain constant levels of the immaturely and maturely glycosylated forms. CaSR thus operates by a feed-forward mechanism, whereby signaling not only induces anterograde trafficking of nascent receptors but also increases biosynthesis to maintain steady state levels of net cellular CaSR. Overall, these studies suggest that 14-3-3 binding at the carboxyl terminus provides an important buffering mechanism to increase the intracellular pool of CaSR available for signaling-evoked trafficking, but attenuates trafficking to control the dynamic range of responses to extracellular calcium.

  14. Neuronal calcium signaling, mitochondrial dysfunction and Alzheimer’s disease

    Science.gov (United States)

    Supnet, Charlene; Bezprozvanny, Ilya

    2016-01-01

    Alzheimer disease (AD) is the most common neurodegenerative disorder that affects millions of ageing people worldwide. AD is characterized by extensive synaptic and neuronal loss which lead to impaired memory and cognitive decline. The cause of pathology in AD is not completely understood and no effective therapy so far has been developed. The accumulation of toxic amyloid-beta 42 (Aβ42) peptide oligomers and aggregates in AD brain has been proposed to be primarily responsible for the pathology of the disease, an idea dubbed ‘amyloid hypothesis’ of AD etiology. In addition to increase in Aβ42 levels, disturbances in neuronal calcium (Ca2+) signaling and alterations in expression levels of Ca2+ signaling proteins have been observed in animal models of familial AD and in studies of postmortem brain samples from sporadic AD patients. Based on these evidence ‘Ca2+ hypothesis of AD’ has been proposed. In particular, familal AD has been linked with enhanced Ca2+ release from the endoplasmic reticulum (ER) and elevated cytosolic Ca2+ levels. The augmented cytosolic Ca2+ levels can trigger signaling cascades that affect synaptic stability and function and can be detrimental to neuronal health, such as Ca2+-dependent phosphatase calcineurin and Ca2+-dependent proteases calpains. Here we review the latest results supporting ‘Ca2+ hypothesis’ of AD pathogenesis. We further argue that over long period of time supranormal cytosolic Ca2+ signaling can impaire mitochondrial function in AD neurons. We conclude that inhibitors and stablizers of neuronal Ca2+ signaling and mitochondrial function may have a therapeutic potential for treatment of AD. We discuss latest and planned AD therapeutic trials of agents targeting Ca2+ channels and mitochodria. PMID:20413848

  15. Calcium and protein phosphorylation in the transduction of gravity signal in corn roots

    Science.gov (United States)

    Friedmann, M.; Poovaiah, B. W.

    1991-01-01

    The involvement of calcium and protein phosphorylation in the transduction of gravity signal was studied using corn roots of a light-insensitive variety (Zea mays L., cv. Patriot). The gravitropic response was calcium-dependent. Horizontal placement of roots preloaded with 32P for three minutes resulted in changes in protein phosphorylation of polypeptides of 32 and 35 kD. Calcium depletion resulted in decreased phosphorylation of these phosphoproteins and replenishment of calcium restored the phosphorylation.

  16. Constant change: dynamic regulation of membrane transport by calcium signalling networks keeps plants in tune with their environment.

    Science.gov (United States)

    Kleist, Thomas J; Luan, Sheng

    2016-03-01

    Despite substantial variation and irregularities in their environment, plants must conform to spatiotemporal demands on the molecular composition of their cytosol. Cell membranes are the major interface between organisms and their environment and the basis for controlling the contents and intracellular organization of the cell. Membrane transport proteins (MTPs) govern the flow of molecules across membranes, and their activities are closely monitored and regulated by cell signalling networks. By continuously adjusting MTP activities, plants can mitigate the effects of environmental perturbations, but effective implementation of this strategy is reliant on precise coordination among transport systems that reside in distinct cell types and membranes. Here, we examine the role of calcium signalling in the coordination of membrane transport, with an emphasis on potassium transport. Potassium is an exceptionally abundant and mobile ion in plants, and plant potassium transport has been intensively studied for decades. Classic and recent studies have underscored the importance of calcium in plant environmental responses and membrane transport regulation. In reviewing recent advances in our understanding of the coding and decoding of calcium signals, we highlight established and emerging roles of calcium signalling in coordinating membrane transport among multiple subcellular locations and distinct transport systems in plants, drawing examples from the CBL-CIPK signalling network. By synthesizing classical studies and recent findings, we aim to provide timely insights on the role of calcium signalling networks in the modulation of membrane transport and its importance in plant environmental responses. PMID:26139029

  17. Calcium and ATP control multiple vital functions

    Science.gov (United States)

    Verkhratsky, Alexei

    2016-01-01

    Life on Planet Earth, as we know it, revolves around adenosine triphosphate (ATP) as a universal energy storing molecule. The metabolism of ATP requires a low cytosolic Ca2+ concentration, and hence tethers these two molecules together. The exceedingly low cytosolic Ca2+ concentration (which in all life forms is kept around 50–100 nM) forms the basis for a universal intracellular signalling system in which Ca2+ acts as a second messenger. Maintenance of transmembrane Ca2+ gradients, in turn, requires ATP-dependent Ca2+ transport, thus further emphasizing the inseparable links between these two substances. Ca2+ signalling controls the most fundamental processes in the living organism, from heartbeat and neurotransmission to cell energetics and secretion. The versatility and plasticity of Ca2+ signalling relies on cell specific Ca2+ signalling toolkits, remodelling of which underlies adaptive cellular responses. Alterations of these Ca2+ signalling toolkits lead to aberrant Ca2+ signalling which is fundamental for the pathophysiology of numerous diseases from acute pancreatitis to neurodegeneration. This paper introduces a theme issue on this topic, which arose from a Royal Society Theo Murphy scientific meeting held in March 2016. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377728

  18. Calcium and ATP control multiple vital functions.

    Science.gov (United States)

    Petersen, Ole H; Verkhratsky, Alexei

    2016-08-01

    Life on Planet Earth, as we know it, revolves around adenosine triphosphate (ATP) as a universal energy storing molecule. The metabolism of ATP requires a low cytosolic Ca(2+) concentration, and hence tethers these two molecules together. The exceedingly low cytosolic Ca(2+) concentration (which in all life forms is kept around 50-100 nM) forms the basis for a universal intracellular signalling system in which Ca(2+) acts as a second messenger. Maintenance of transmembrane Ca(2+) gradients, in turn, requires ATP-dependent Ca(2+) transport, thus further emphasizing the inseparable links between these two substances. Ca(2+) signalling controls the most fundamental processes in the living organism, from heartbeat and neurotransmission to cell energetics and secretion. The versatility and plasticity of Ca(2+) signalling relies on cell specific Ca(2+) signalling toolkits, remodelling of which underlies adaptive cellular responses. Alterations of these Ca(2+) signalling toolkits lead to aberrant Ca(2+) signalling which is fundamental for the pathophysiology of numerous diseases from acute pancreatitis to neurodegeneration. This paper introduces a theme issue on this topic, which arose from a Royal Society Theo Murphy scientific meeting held in March 2016.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377728

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

    Directory of Open Access Journals (Sweden)

    Fernando Siso-Nadal

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

  20. Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo.

    Science.gov (United States)

    Boerman, Erika M; Everhart, Jesse E; Segal, Steven S

    2016-05-01

    Aging is associated with vascular dysfunction that impairs tissue perfusion, physical activity, and the quality of life. Calcium signaling in endothelial cells (ECs) is integral to vasomotor control, exemplified by localized Ca(2+) signals within EC projections through holes in the internal elastic lamina (IEL). Within these microdomains, endothelium-derived hyperpolarization is integral to smooth muscle cell (SMC) relaxation via coupling through myoendothelial gap junctions. However, the effects of aging on local EC Ca(2+) signals (and thereby signaling between ECs and SMCs) remain unclear, and these events have not been investigated in vivo. Furthermore, it is unknown whether aging affects either the number or the size of IEL holes. In the present study, we tested the hypothesis that local EC Ca(2+) signaling is impaired with advanced age along with a reduction in IEL holes. In anesthetized mice expressing a Ca(2+)-sensitive fluorescent protein (GCaMP2) selectively in ECs, our findings illustrate that for mesenteric arteries controlling splanchnic blood flow the frequency of spontaneous local Ca(2+) signals in ECs was reduced by ∼85% in old (24-26 mo) vs. young (3-6 mo) animals. At the same time, the number (and total area) of holes per square millimeter of IEL was reduced by ∼40%. We suggest that diminished signaling between ECs and SMCs contributes to dysfunction of resistance arteries with advanced age.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-impairs-endothelial-ca2-signaling/. PMID:26945073

  1. EXERCISE ENHANCING CALCIUM ABSORPTION MECHANISM

    OpenAIRE

    Muliani

    2013-01-01

    Calcium has important role in many biological processes therefore calcium homeostasis should be maintained. Imbalance in calcium homeostasis would affects the bone metabolism, neuromuscular function, blood coagulation, cell proliferation and signal transduction. Homeostasis of calcium is maintained by three major organs: gastrointestinal tract, bone and kidney. Intestinal calcium absorption is the sole mechanism to supply calcium to the body. Calcium absorption controlled by calcitropic hormo...

  2. Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

    Institute of Scientific and Technical Information of China (English)

    Jian-xin SHEN; Jerrel L YAKEL

    2009-01-01

    Based on the composition of the five subunits forming functional neuronal nicotinic acetylcholine receptors (nAChRs), they are grouped into either heteromeric (comprising both α and β subunits) or homomeric (comprising only α subunits) recep-tors. The nAChRs are known to be differentially permeable to calcium ions, with the α7 nAChR subtype having one of the highest permeabilities to calcium. Calcium influx through nAChRs, particularly through the α-bungarotoxin-sensitive α7-containing nAChRs, is a very efficient way to raise cytoplasmic calcium levels. The activation of nAChRs can mediate three types of cytoplasmic calcium signals: (1) direct calcium influx through the nAChRs, (2) indirect calcium influx through voltage-dependent calcium channels (VDCCs) which are activated by the nAChR-mediated depolarization, and (3) calcium-induced calcium release (CICR) (triggered by the first two sources) from the endoplasmic reticulum (ER) through the ryanodine receptors and inositol (1,4,5)-triphosphate receptors (IP3Rs). Downstream signaling events mediated by nAChR-mediated calcium responses can be grouped into instantaneous effects (such as neurotransmitter release, which can occur in milliseconds after nAChR activation), short-term effects (such as the recovery of nAChR desensitization through cellular signaling cascades), and long-term effects (such as neuroprotection via gene expression). In addition, nAChR activity can be regulated by cytoplasmic calcium levels, suggesting a complex reciprocal relationship. Further advances in imaging techniques, animal models, and more potent and subtype-selective ligands for neuronal nAChRs would help in understand-ing the neuronal nAChR-mediated calcium signaling, and lead to the development of improved therapeutic treatments.

  3. Calcium signaling orchestrates glioblastoma development: Facts and conjunctures.

    Science.gov (United States)

    Leclerc, Catherine; Haeich, Jacques; Aulestia, Francisco J; Kilhoffer, Marie-Claude; Miller, Andrew L; Néant, Isabelle; Webb, Sarah E; Schaeffer, Etienne; Junier, Marie-Pierre; Chneiweiss, Hervé; Moreau, Marc

    2016-06-01

    While it is a relatively rare disease, glioblastoma multiform (GBM) is one of the more deadly adult cancers. Following current interventions, the tumor is never eliminated whatever the treatment performed; whether it is radiotherapy, chemotherapy, or surgery. One hypothesis to explain this poor outcome is the "cancer stem cell" hypothesis. This concept proposes that a minority of cells within the tumor mass share many of the properties of adult neural stem cells and it is these that are responsible for the growth of the tumor and its resistance to existing therapies. Accumulating evidence suggests that Ca(2+) might also be an important positive regulator of tumorigenesis in GBM, in processes involving quiescence, maintenance, proliferation, or migration. Glioblastoma tumors are generally thought to develop by co-opting pathways that are involved in the formation of an organ. We propose that the cells initiating the tumor, and subsequently the cells of the tumor mass, must hijack the different checkpoints that evolution has selected in order to prevent the pathological development of an organ. In this article, two main points are discussed. (i) The first is the establishment of a so-called "cellular society," which is required to create a favorable microenvironment. (ii) The second is that GBM can be considered to be an organism, which fights to survive and develop. Since GBM evolves in a limited space, its only chance of development is to overcome the evolutionary checkpoints. For example, the deregulation of the normal Ca(2+) signaling elements contributes to the progression of the disease. Thus, by manipulating the Ca(2+) signaling, the GBM cells might not be killed, but might be reprogrammed toward a new fate that is either easy to cure or that has no aberrant functioning. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26826650

  4. Differential modulation of ATP-induced calcium signalling by A1 and A2 adenosine receptors in cultured cortical astrocytes

    OpenAIRE

    Alloisio, Susanna; Cugnoli, Carlo; Ferroni, Stefano; Nobile, Mario

    2004-01-01

    Despite the accumulating evidence that under various pathological conditions the extracellular elevation of adenine-based nucleotides and nucleosides plays a key role in the control of astroglial reactivity, how these signalling molecules interact in the regulation of astrocyte function is still largely elusive.The action of the nucleoside adenosine in the modulation of the intracellular calcium signalling ([Ca2+]i) elicited by adenosine 5′-triphosphate (ATP)-induced activation of P2 purinoce...

  5. Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Li

    2013-01-01

    Full Text Available Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP cation channel superfamily are candidate calcium influx channels. NFκB activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1 in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in [Ca2+]i in HuH-7 cells. The increase in [Ca2+]i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca2+]i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NFκB activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NFκB activation was dependent on the calcium gradient and TRPV1. The rapid NFκB activation by S-[6]-gingerol was associated with an increase in mRNA levels of NFκB-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins.

  6. Signal processing by T-type calcium channel interactions in the cerebellum

    Science.gov (United States)

    Engbers, Jordan D. T.; Anderson, Dustin; Zamponi, Gerald W.; Turner, Ray W.

    2013-01-01

    T-type calcium channels of the Cav3 family are unique among voltage-gated calcium channels due to their low activation voltage, rapid inactivation, and small single channel conductance. These special properties allow Cav3 calcium channels to regulate neuronal processing in the subthreshold voltage range. Here, we review two different subthreshold ion channel interactions involving Cav3 channels and explore the ability of these interactions to expand the functional roles of Cav3 channels. In cerebellar Purkinje cells, Cav3 and intermediate conductance calcium-activated potassium (IKCa) channels form a novel complex which creates a low voltage-activated, transient outward current capable of suppressing temporal summation of excitatory postsynaptic potentials (EPSPs). In large diameter neurons of the deep cerebellar nuclei, Cav3-mediated calcium current (IT) and hyperpolarization-activated cation current (IH) are activated during trains of inhibitory postsynaptic potentials. These currents have distinct, and yet synergistic, roles in the subthreshold domain with IT generating a rebound burst and IH controlling first spike latency and rebound spike precision. However, by shortening the membrane time constant the membrane returns towards resting value at a faster rate, allowing IH to increase the efficacy of IT and increase the range of burst frequencies that can be generated. The net effect of Cav3 channels thus depends on the channels with which they are paired. When expressed in a complex with a KCa channel, Cav3 channels reduce excitability when processing excitatory inputs. If functionally coupled with an HCN channel, the depolarizing effect of Cav3 channels is accentuated, allowing for efficient inversion of inhibitory inputs to generate a rebound burst output. Therefore, signal processing relies not only on the activity of individual subtypes of channels but also on complex interactions between ion channels whether based on a physical complex or by indirect

  7. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    Science.gov (United States)

    Jorgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne; Civitelli, Roberto; Sorensen, Ole Helmer; Steinberg, Thomas H.

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium.

  8. Structure of Signaling Enzyme Reveals How Calcium Turns It On

    OpenAIRE

    Rellos, Peter; Pike, Ashley C. W.; Niesen, Frank H.; Salah, Eidarus; Lee, Wen Hwa; von Delft, Frank; Knapp, Stefan

    2010-01-01

    Long-term potentiation (LTP), a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM)-dependent kinase II (CaMKII). CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe th...

  9. A history of stress alters drought calcium signalling pathways in Arabidopsis.

    Science.gov (United States)

    Knight, H; Brandt, S; Knight, M R

    1998-12-01

    Environmental stresses commonly encountered by plants lead to rapid transient elevations in cytosolic free calcium concentration ([Ca2+]cyt) (Bush, 1995; Knight et al., 1991). These cellular calcium (Ca2+) signals lead ultimately to the increased expression of stress-responsive genes, including those encoding proteins of protective function (Knight et al., 1996; Knight et al., 1997). The kinetics and magnitude of the Ca2+ signal, or 'calcium signature', differ between different stimuli and are thought to contribute to the specificity of the end response (Dolmetsch et al., 1997; McAinsh and Hetherington, 1998). We measured [Ca2+]cyt changes during treatment with mannitol (to mimic drought stress) in whole intact seedlings of Arabidopsis thaliana. The responses of plants which were previously exposed to osmotic and oxidative stresses were compared to those of control plants. We show here that osmotic stress-induced Ca2+ responses can be markedly altered by previous encounters with either osmotic or oxidative stress. The nature of the alterations in Ca2+ response depends on the identity and severity of the previous stress: oxidative stress pre-treatment reduced the mannitol-induced [Ca2+]cyt response whereas osmotic stress pretreatment increased the [Ca2+]cyt response. Therefore, our data show that different combinations of environmental stress can produce novel Ca2+ signal outputs. These alterations are accompanied by corresponding changes in the patterns of osmotic stress-induced gene expression and, in the case of osmotic stress pre-treatment, the acquisition of stress-tolerance. This suggests that altered Ca2+ responses encode a 'memory' of previous stress encounters and thus may perhaps be involved in acclimation to environmental stresses. PMID:10069075

  10. Sensory-Driven Enhancement of Calcium Signals in Individual Purkinje Cell Dendrites of Awake Mice

    Directory of Open Access Journals (Sweden)

    Farzaneh Najafi

    2014-03-01

    Full Text Available Climbing fibers (CFs are thought to contribute to cerebellar plasticity and learning by triggering a large influx of dendritic calcium in the postsynaptic Purkinje cell (PC to signal the occurrence of an unexpected sensory event. However, CFs fire about once per second whether or not an event occurs, raising the question of how sensory-driven signals might be distinguished from a background of ongoing spontaneous activity. Here, we report that in PC dendrites of awake mice, CF-triggered calcium signals are enhanced when the trigger is a sensory event. In addition, we show that a large fraction of the total enhancement in each PC dendrite can be accounted for by an additional boost of calcium provided by sensory activation of a non-CF input. We suggest that sensory stimulation may modulate dendritic voltage and calcium concentration in PCs to increase the strength of plasticity signals during cerebellar learning.

  11. Role of Calcium Signaling in the Transcriptional Regulation of the Apicoplast Genome of Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Sabna Cheemadan

    2014-01-01

    Full Text Available Calcium is a universal second messenger that plays an important role in regulatory processes in eukaryotic cells. To understand calcium-dependent signaling in malaria parasites, we analyzed transcriptional responses of Plasmodium falciparum to two calcium ionophores (A23187 and ionomycin that cause redistribution of intracellular calcium within the cytoplasm. While ionomycin induced a specific transcriptional response defined by up- or downregulation of a narrow set of genes, A23187 caused a developmental arrest in the schizont stage. In addition, we observed a dramatic decrease of mRNA levels of the transcripts encoded by the apicoplast genome during the exposure of P. falciparum to both calcium ionophores. Neither of the ionophores caused any disruptions to the DNA replication or the overall apicoplast morphology. This suggests that the mRNA downregulation reflects direct inhibition of the apicoplast gene transcription. Next, we identify a nuclear encoded protein with a calcium binding domain (EF-hand that is localized to the apicoplast. Overexpression of this protein (termed PfACBP1 in P. falciparum cells mediates an increased resistance to the ionophores which suggests its role in calcium-dependent signaling within the apicoplast. Our data indicate that the P. falciparum apicoplast requires calcium-dependent signaling that involves a novel protein PfACBP1.

  12. Characterization of calcium signals provoked by lysophosphatidylinositol in human microvascular endothelial cells.

    Science.gov (United States)

    Al Suleimani, Y M; Hiley, C R

    2016-01-01

    The lipid molecule, lysophosphatidylinositol (LPI), is hypothesised to form part of a novel lipid signalling system that involves the G protein-coupled receptor GPR55 and distinct intracellular signalling cascades in endothelial cells. This work aimed to study the possible mechanisms involved in LPI-evoked cytosolic Ca(2+) mobilization in human brain microvascular endothelial cells. Changes in intracellular Ca(2+) concentrations were measured using cell population Ca(2+) assay. LPI evoked biphasic elevation of intracellular calcium concentration, a rapid phase and a sustained phase. The rapid phase was attenuated by the inhibitor of PLC (U 73122), inhibitor of IP(3) receptors, 2-APB and the depletor of endoplasmic reticulum Ca(2+) store, thapsigargin. The sustained phase, on the other hand, was enhanced by U 73122 and abolished by the RhoA kinase inhibitor, Y-27632. In conclusion, the Ca(2+) signal evoked by LPI is characterised by a rapid phase of Ca(2+) release from the endoplasmic reticulum, and requires activation of the PLC-IP(3) signalling pathway. The sustained phase mainly depends on RhoA kinase activation. LPI acts as novel lipid signalling molecule in endothelial cells, and elevation of cytosolic Ca(2+) triggered by it may present an important intracellular message required in gene expression and controlling of vascular tone. PMID:26596318

  13. Neuronal calcium sparks and intracellular calcium “noise”

    OpenAIRE

    Melamed-Book, Naomi; Kachalsky, Sylvia G.; Kaiserman, Igor; Rahamimoff, Rami

    1999-01-01

    Intracellular calcium ions are involved in many forms of cellular function. To accommodate so many control functions, a complex spatiotemporal organization of calcium signaling has developed. In both excitable and nonexcitable cells, calcium signaling was found to fluctuate. Sudden localized increases in the intracellular calcium concentration—or calcium sparks—were found in heart, striated and smooth muscle, Xenopus Laevis oocytes, and HeLa and P12 cells. In the nervous system, intracellular...

  14. MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes

    Science.gov (United States)

    Wu, Junnan; Zheng, Chunxia; Wang, Xiao; Yun, Shifeng; Zhao, Yue; Liu, Lin; Lu, Yuqiu; Ye, Yuting; Zhu, Xiaodong; Zhang, Changming; Shi, Shaolin; Liu, Zhihong

    2015-01-01

    Calcium/calcineurin signaling is critical for normal cellular physiology. Abnormalities in this pathway cause many diseases, including podocytopathy; therefore, understanding the mechanisms that underlie the regulation of calcium/calcineurin signaling is essential. Here, we showed that critical components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s). We found that these 5 genes are highly expressed as mRNA, but the level of the proteins is low in normal podocytes. Conversely, protein levels were markedly elevated in podocytes from rats treated with puromycin aminonucleoside (PAN) and from patients with focal segmental glomerulosclerosis (FSGS). In both FSGS patients and PAN-treated rats, miR-30s were downregulated in podocytes. In cultured podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and calcineurin activity. Moreover, NFATC3 nuclear translocation, synaptopodin degradation, integrin β3 (ITGB3) activation, and actin fiber loss, which are downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but blocked by the calcineurin inhibitor FK506. Podocyte-specific expression of the miR-30 sponge in mice increased calcium/calcineurin pathway component protein expression and calcineurin activity. The mice developed podocyte foot process effacement and proteinuria, which were prevented by FK506. miR-30s also regulated calcium/calcineurin signaling in cardiomyocytes. Together, our results identify miR-30s as essential regulators of calcium/calcineurin signaling. PMID:26436650

  15. Nuclear proton dynamics and interactions with calcium signaling.

    Science.gov (United States)

    Hulikova, Alzbeta; Swietach, Pawel

    2016-07-01

    Biochemical signals acting on the nucleus can regulate gene expression. Despite the inherent affinity of nucleic acids and nuclear proteins (e.g. transcription factors) for protons, little is known about the mechanisms that regulate nuclear pH (pHnuc), and how these could be exploited to control gene expression. Here, we show that pHnuc dynamics can be imaged using the DNA-binding dye Hoechst 33342. Nuclear pores allow the passage of medium-sized molecules (calcein), but protons must first bind to mobile buffers in order to gain access to the nucleoplasm. Fixed buffering residing in the nucleus of permeabilized cells was estimated to be very weak on the basis of the large amplitude of pHnuc transients evoked by photolytic H(+)-uncaging or exposure to weak acids/bases. Consequently, the majority of nuclear pH buffering is sourced from the cytoplasm in the form of mobile buffers. Effective proton diffusion was faster in nucleoplasm than in cytoplasm, in agreement with the higher mobile-to-fixed buffering ratio in the nucleus. Cardiac myocyte pHnuc changed in response to maneuvers that alter nuclear Ca(2+) signals. Blocking Ca(2+) release from inositol-1,4,5-trisphosphate receptors stably alkalinized the nucleus. This Ca(2+)-pH interaction may arise from competitive binding to common chemical moieties. Competitive binding to mobile buffers may couple the efflux of Ca(2+)via nuclear pores with a counterflux of protons. This would generate a stable pH gradient between cytoplasm and nucleus that is sensitive to the state of nuclear Ca(2+) signaling. The unusual behavior of protons in the nucleus provides new mechanisms for regulating cardiac nuclear biology. PMID:26183898

  16. Calcium-phosphate-osteopontin particles for caries control

    DEFF Research Database (Denmark)

    Schlafer, Sebastian; Birkedal, Henrik; Olsen, Jakob;

    2016-01-01

    Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co-precipitation ......Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co......, and the pH always remained above 5.5. Hence, calcium-phosphate-osteopontin particles show potential for applications in caries control....

  17. Diffusion Modeling of ATP Signaling Suggests a Partially Regenerative Mechanism Underlies Astrocyte Intercellular Calcium Waves

    OpenAIRE

    MacDonald, Christopher L.; Yu, Diana; Buibas, Marius; Silva, Gabriel A.

    2008-01-01

    Network signaling through astrocyte syncytiums putatively contribute to the regulation of a number of both physiological and pathophysiological processes in the mammalian central nervous system. As such, an understanding of the underlying mechanisms is critical to determining any roles played by signaling through astrocyte networks. Astrocyte signaling is primarily mediated by the propagation of intercellular calcium waves (ICW) in the sense that paracrine signaling results in measurable intr...

  18. Characteristics of calcium signaling in astrocytes induced by photostimulation with femtosecond laser

    Science.gov (United States)

    Zhao, Yuan; Zhang, Yuan; Zhou, Wei; Liu, Xiuli; Zeng, Shaoqun; Luo, Qingming

    2010-05-01

    Astrocytes have been identified to actively contribute to brain functions through Ca2+ signaling, serving as a bridge to communicate with neurons and other brain cells. However, conventional stimulation techniques are hard to apply to delicate investigations on astrocytes. Our group previously reported photostimulation with a femtosecond laser to evoke astrocytic calcium (Ca2+) waves, providing a noninvasive and efficient approach with highly precise targeting. In this work, detailed characteristics of astrocytic Ca2+ signaling induced by photostimulation are presented. In a purified astrocytic culture, after the illumination of a femtosecond laser onto one cell, a Ca2+ wave throughout the network with reduced speed is induced, and intracellular Ca2+ oscillations are observed. The intercellular propagation is pharmacologically confirmed to be mainly mediated by ATP through P2Y receptors. Different patterns of Ca2+ elevations with increased amplitude in the stimulated astrocyte are discovered by varying the femtosecond laser power, which is correspondingly followed by broader intercellular waves. These indicate that the strength of photogenerated Ca2+ signaling in astrocytes has a positive relationship with the stimulating laser power. Therefore, distinct Ca2+ signaling is feasibly available for specific studies on astrocytes by employing precisely controlled photostimulation.

  19. Visualization of Plasticity in Fear-Evoked Calcium Signals in Midbrain Dopamine Neurons

    Science.gov (United States)

    Gore, Bryan B.; Soden, Marta E.; Zweifel, Larry S.

    2014-01-01

    Dopamine is broadly implicated in fear-related processes, yet we know very little about signaling dynamics in these neurons during active fear conditioning. We describe the direct imaging of calcium signals of dopamine neurons during Pavlovian fear conditioning using fiber-optic confocal microscopy coupled with the genetically encoded calcium…

  20. Dynamic visualization of calcium-dependent signaling in cellular microdomains.

    Science.gov (United States)

    Mehta, Sohum; Zhang, Jin

    2015-10-01

    Cells rely on the coordinated action of diverse signaling molecules to sense, interpret, and respond to their highly dynamic external environment. To ensure the specific and robust flow of information, signaling molecules are often spatially organized to form distinct signaling compartments, and our understanding of the molecular mechanisms that guide intracellular signaling hinges on the ability to directly probe signaling events within these cellular microdomains. Ca(2+) signaling in particular owes much of its functional versatility to this type of exquisite spatial regulation. As discussed below, a number of methods have been developed to investigate the mechanistic and functional implications of microdomains of Ca(2+) signaling, ranging from the application of Ca(2+) buffers to the direct and targeted visualization of Ca(2+) signaling microdomains using genetically encoded fluorescent reporters. PMID:25703691

  1. Calcium as a branching signal in Neurospora crassa.

    OpenAIRE

    Reissig, J L; Kinney, S G

    1983-01-01

    The divalent cation ionophore A23187 was found to induce apical branching in Neurospora crassa. Optimal effects were obtained by treatment with 0.1 mM ionophore for 30 min. Branching first became manifest during or shortly after treatment; successive rounds of branching could be observed at later times. Calcium starvation of the mycelium markedly reduced its subsequent response to the ionophore, whereas starvation for other divalent cations had no detectable effect. The branching response was...

  2. Diffusion modeling of ATP signaling suggests a partially regenerative mechanism underlies astrocyte intercellular calcium waves

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available Network signaling through astrocyte syncytiums putatively contribute to the regulation of a number of both physiological and pathophysiological processes in the mammalian central nervous system. As such, an understanding of the underlying mechanisms is critical to determining any roles played by signaling through astrocyte networks. Astrocyte signaling is primarily mediated by the propagation of intercellular calcium waves in the sense that paracrine signaling results in measurable intracellular calcium transients. Although the molecular mechanisms are relatively well known, there is conflicting data regarding the mechanism by which the signal propagates through the network. Experimentally there is evidence for both a point source signaling model in which adenosine triphosphate (ATP is released by an initially activated astrocyte only, and a regenerative signaling model in which downstream astrocytes release ATP. We modeled both conditions as a simple lumped parameter phenomenological diffusion model and show that the only possible mechanism that can accurately reproduce experimentally measured results is a dual signaling mechanism that incorporates elements of both proposed signaling models. Specifically, we were able to accurately simulate experimentally measured in vitro intercellular calcium wave dynamics by assuming a point source signaling model with a downstream regenerative component. These results suggest that seemingly conflicting data in the literature are actually complimentary, and represents a highly efficient and robustly engineered signaling mechanism.

  3. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic

    2013-05-01

    Full Text Available The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

  4. Calcium-phosphate-osteopontin particles for caries control

    DEFF Research Database (Denmark)

    Schlafer, Sebastian

    Oftentimes caries lesions develop in protected sites that are difficult to access by self-performed mechanical tooth cleaning. At present, there is a growing interest in chemical adjuncts to mechanical procedures of oral hygiene that aim at biofilm control rather than biofilm eradication. Calcium...... drops to 6 or below and release buffering phosphate ions that stabilize biofilm pH above the critical level for enamel dissolution. With that twofold approach, calcium-phosphate-osteopontin particles may make a relevant contribution to clinical caries control....

  5. Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow

    CERN Document Server

    Buibas, Marius; Nizar, Krystal; Silva, Gabriel A

    2009-01-01

    An optical flow gradient algorithm was applied to spontaneously forming networks of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e. a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling patterns. We begin by briefly reviewing the mathematics of the optical flow algorithm, describe how to solve for the displacement vectors, and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the ...

  6. Consumption of calcium-fortified cereal bars to improve dietary calcium intake of healthy women: randomized controlled feasibility study.

    Directory of Open Access Journals (Sweden)

    Jennifer T Lee

    Full Text Available Calcium is an important structural component of the skeletal system. Although an adequate intake of calcium helps to maintain bone health and reduce the risk of osteoporosis, many women do not meet recommended daily intakes of calcium. Previous interventions studies designed to increase dietary intake of women have utilized primarily dairy sources of calcium or supplements. However, lactose intolerance, milk protein allergies, or food preferences may lead many women to exclude important dairy sources of dietary calcium. Therefore, we undertook a 9 week randomized crossover design trial to examine the potential benefit of including a non-dairy source of calcium in the diet of women. Following a 3 week run-in baseline period, 35 healthy women > 18 years were randomized by crossover design into either Group I or Group II. Group I added 2 calcium-fortified cereal bars daily (total of 400 mg calcium/day (intervention to their usual diet and Group II continued their usual diet (control. At the end of 3 weeks, diets were switched for another 3 weeks. Intakes of calcium and energy were estimated from 3-day diet and supplemental diaries. Wilcoxon signed-rank tests were used for within group comparisons and Mann Whitney U tests were used for between group comparisons of calcium and energy intake. Dietary calcium was significantly higher during intervention (1071 mg/d when participants consumed 2 calcium-fortified cereal bars daily than during the baseline (720 mg/d, P <0.0001 or control diets (775 mg/d, P = 0.0001 periods. Furthermore, the addition of 2 calcium-fortified cereal bars daily for the 3 week intervention did not significantly increase total energy intake or result in weight gain. In conclusion, consumption of calcium-fortified cereal bars significantly increased calcium intake of women. Further research examining the potential ability of fortified cereal bars to help maintain and improve bone health of women is warranted.ClinicalTrials.gov NCT

  7. Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi.

    Science.gov (United States)

    Rispail, Nicolas; Soanes, Darren M; Ant, Cemile; Czajkowski, Robert; Grünler, Anke; Huguet, Romain; Perez-Nadales, Elena; Poli, Anna; Sartorel, Elodie; Valiante, Vito; Yang, Meng; Beffa, Roland; Brakhage, Axel A; Gow, Neil A R; Kahmann, Regine; Lebrun, Marc-Henri; Lenasi, Helena; Perez-Martin, José; Talbot, Nicholas J; Wendland, Jürgen; Di Pietro, Antonio

    2009-04-01

    Mitogen-activated protein kinase (MAPK) cascades and the calcium-calcineurin pathway control fundamental aspects of fungal growth, development and reproduction. Core elements of these signalling pathways are required for virulence in a wide array of fungal pathogens of plants and mammals. In this review, we have used the available genome databases to explore the structural conservation of three MAPK cascades and the calcium-calcineurin pathway in ten different fungal species, including model organisms, plant pathogens and human pathogens. While most known pathway components from the model yeast Saccharomyces cerevisiae appear to be widely conserved among taxonomically and biologically diverse fungi, some of them were found to be restricted to the Saccharomycotina. The presence of multiple paralogues in certain species such as the zygomycete Rhizopus oryzae and the incorporation of new functional domains that are lacking in S. cerevisiae signalling proteins, most likely reflect functional diversification or adaptation as filamentous fungi have evolved to occupy distinct ecological niches. PMID:19570501

  8. Disruption of Vitamin D and Calcium Signaling in Keratinocytes Predisposes to Skin Cancer

    Science.gov (United States)

    Bikle, Daniel D.; Jiang, Yan; Nguyen, Thai; Oda, Yuko; Tu, Chia-ling

    2016-01-01

    1,25 dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, and calcium regulate epidermal differentiation. 1,25(OH)2D exerts its effects through the vitamin D receptor (VDR), a transcription factor in the nuclear hormone receptor family, whereas calcium acts through the calcium sensing receptor (Casr), a membrane bound member of the G protein coupled receptor family. We have developed mouse models in which the Vdr and Casr have been deleted in the epidermis (epidVdr−∕− and epidCasr−∕−). Both genotypes show abnormalities in calcium induced epidermal differentiation in vivo and in vitro, associated with altered hedgehog (HH) and β–catenin signaling that when abnormally expressed lead to basal cell carcinomas (BCC) and trichofolliculomas, respectively. The Vdr−∕− mice are susceptible to tumor formation following UVB or chemical carcinogen exposure. More recently we found that the keratinocytes from these mice over express long non-coding RNA (lncRNA) oncogenes such as H19 and under express lncRNA tumor suppressors such as lincRNA-21. Spontaneous tumors have not been observed in either the epidVdr−∕− or epidCasr−∕−. But in mice with epidermal specific deletion of both Vdr and Casr (epidVdr−∕−/epidCasr−∕− [DKO]) tumor formation occurs spontaneously when the DKO mice are placed on a low calcium diet. These results demonstrate important interactions between vitamin D and calcium signaling through their respective receptors that lead to cancer when these signals are disrupted. The roles of the β–catenin, hedgehog, and lncRNA pathways in predisposing the epidermis to tumor formation when vitamin D and calcium signaling are disrupted will be discussed. PMID:27462278

  9. Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

    Institute of Scientific and Technical Information of China (English)

    Mary; Louisa; Holton; Michael; Emerson; Ludwig; Neyses; Angel; L; Armesilla

    2010-01-01

    Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.

  10. Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors

    DEFF Research Database (Denmark)

    Rossol, Manuela; Pierer, Matthias; Raulien, Nora; Quandt, Dagmar; Meusch, Undine; Rothe, Kathrin; Schubert, Kristin; Schöneberg, Torsten; Schaefer, Michael; Krügel, Ute; Smajilovic, Sanela; Bräuner-Osborne, Hans; Baerwald, Christoph; Wagner, Ulf

    2012-01-01

    calcium activates the NLRP3 inflammasome via stimulation of G protein-coupled calcium sensing receptors. Activation is mediated by signalling through the calcium-sensing receptor and GPRC6A via the phosphatidyl inositol/Ca(2+) pathway. The resulting increase in the intracellular calcium concentration...... this effect was inhibited in GPRC6A(-/-) mice. Our results demonstrate that G-protein-coupled receptors can activate the inflammasome, and indicate that increased extracellular calcium has a role as a danger signal and amplifier of inflammation....

  11. Plasmonic activation of gold nanorods for remote stimulation of calcium signaling and protein expression in HEK 293T cells.

    Science.gov (United States)

    Sanchez-Rodriguez, Sandra P; Sauer, Jeremy P; Stanley, Sarah A; Qian, Xi; Gottesdiener, Andrew; Friedman, Jeffrey M; Dordick, Jonathan S

    2016-10-01

    Remote activation of specific cells of a heterogeneous population can provide a useful research tool for clinical and therapeutic applications. Here, we demonstrate that photostimulation of gold nanorods (AuNRs) using a tunable near-infrared (NIR) laser at specific longitudinal surface plasmon resonance wavelengths can induce the selective and temporal internalization of calcium in HEK 293T cells. Biotin-PEG-Au nanorods coated with streptavidin Alexa Fluor-633 and biotinylated anti-His antibodies were used to decorate cells genetically modified with His-tagged TRPV1 temperature-sensitive ion channel and AuNRs conjugated to biotinylated RGD peptide were used to decorate integrins in unmodified cells. Plasmonic activation can be stimulated at weak laser power (0.7-4.0 W/cm(2) ) without causing cell damage. Selective activation of TRPV1 channels could be controlled by laser power between 1.0 and 1.5 W/cm(2) . Integrin targeting robustly stimulated calcium signaling due to a dense cellular distribution of nanoparticles. Such an approach represents a functional tool for combinatorial activation of cell signaling in heterogeneous cell populations. Our results suggest that it is possible to induce cell activation via NIR-induced gold nanorod heating through the selective targeting of membrane proteins in unmodified cells to produce calcium signaling and downstream expression of specific genes with significant relevance for both in vitro and therapeutic applications. Biotechnol. Bioeng. 2016;113: 2228-2240. © 2016 Wiley Periodicals, Inc. PMID:27563853

  12. Angiotensin II activates different calcium signaling pathways in adipocytes.

    Science.gov (United States)

    Dolgacheva, Lyudmila P; Turovskaya, Maria V; Dynnik, Vladimir V; Zinchenko, Valery P; Goncharov, Nikolay V; Davletov, Bazbek; Turovsky, Egor A

    2016-03-01

    Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (АТ1 and АТ2). The current work was carried out with the primary white adipocytes culture, and Са(2+) signaling pathways activated by Ang II were investigated using fluorescent microscopy. Са(2+)-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Са(2+)-oscillations and transient responses by activating АТ1 and АТ2 receptors and involving branched signaling cascades:In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2diabetes. PMID:26850364

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

  15. Effects of tetracaine on charge movements and calcium signals in frog skeletal muscle fibers

    OpenAIRE

    Vergara, Julio; Caputo, Carlo

    1983-01-01

    Intramembrane charge movements in skeletal muscle fibers contain a tetracaine-sensitive component that can be isolated by the use of this drug. The time course and voltage dependence of this component, studied in relation to antipyrylazo III absorbance signals, suggest its direct involvement in the calcium release process in muscle.

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

    OpenAIRE

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

    2013-01-01

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

  17. Precipitation of calcium carbonate and calcium phosphate under diffusion controlled mixing

    Energy Technology Data Exchange (ETDEWEB)

    Tsigabu Gebrehiwet; James R. Henriksen; Luanjing Guo; Don T. Fox; Hai Huang; Lee Tu; Yoshiko Fujita; Robert W. Smith; George Redden

    2014-07-01

    Multi-component mineral precipitation in porous, subsurface environments is challenging to simulate or engineer when in situ reactant mixing is controlled by diffusion. In contrast to well-mixed systems, the conditions that favor mineral precipitation in porous media are distributed along chemical gradients, which evolve spatially due to concurrent mineral precipitation and modification of solute transport in the media. The resulting physical and chemical characteristics of a mixing/precipitation zone are a consequence of coupling between transport and chemical processes, and the distinctive properties of individual chemical systems. We examined the spatial distribution of precipitates formed in “double diffusion” columns for two chemical systems, calcium carbonate and calcium phosphate. Polyacrylamide hydrogel was used as a low permeability, high porosity medium to maximize diffusive mixing and minimize pressure- and density-driven flow between reactant solutions. In the calcium phosphate system, multiple, visually dense and narrow bands of precipitates were observed that were reminiscent of previously reported Liesegang patterns. In the calcium carbonate system, wider precipitation zones characterized by more sparse distributions of precipitates and a more open channel structure were observed. In both cases, formation of precipitates inhibited, but did not necessarily eliminate, continued transport and mixing of the reactants. A reactive transport model with fully implicit coupling between diffusion, chemical speciation and precipitation kinetics, but where explicit details of nucleation processes were neglected, was able to qualitatively simulate properties of the precipitation zones. The results help to illustrate how changes in the physical properties of a precipitation zone depend on coupling between diffusion-controlled reactant mixing and chemistry-specific details of precipitation kinetics.

  18. Mercury Control with Calcium-Based Sorbents and Oxidizing Agents

    Energy Technology Data Exchange (ETDEWEB)

    Thomas K. Gale

    2005-07-01

    This Final Report contains the test descriptions, results, analysis, correlations, theoretical descriptions, and model derivations produced from many different investigations performed on a project funded by the U.S. Department of Energy, to investigate calcium-based sorbents and injection of oxidizing agents for the removal of mercury. Among the technologies were (a) calcium-based sorbents in general, (b) oxidant-additive sorbents developed originally at the EPA, and (c) optimized calcium/carbon synergism for mercury-removal enhancement. In addition, (d) sodium-tetrasulfide injection was found to effectively capture both forms of mercury across baghouses and ESPs, and has since been demonstrated at a slipstream treating PRB coal. It has been shown that sodium-tetrasulfide had little impact on the foam index of PRB flyash, which may indicate that sodium-tetrasulfide injection could be used at power plants without affecting flyash sales. Another technology, (e) coal blending, was shown to be an effective means of increasing mercury removal, by optimizing the concentration of calcium and carbon in the flyash. In addition to the investigation and validation of multiple mercury-control technologies (a through e above), important fundamental mechanism governing mercury kinetics in flue gas were elucidated. For example, it was shown, for the range of chlorine and unburned-carbon (UBC) concentrations in coal-fired utilities, that chlorine has much less effect on mercury oxidation and removal than UBC in the flyash. Unburned carbon enhances mercury oxidation in the flue gas by reacting with HCl to form chlorinated-carbon sites, which then react with elemental mercury to form mercuric chloride, which subsequently desorbs back into the flue gas. Calcium was found to enhance mercury removal by stabilizing the oxidized mercury formed on carbon surfaces. Finally, a model was developed to describe these mercury adsorption, desorption, oxidation, and removal mechanisms, including

  19. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

    Energy Technology Data Exchange (ETDEWEB)

    Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France); Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l' Exercice en conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171 Aubière cedex (France); Fabre, O.; Bordenave, S. [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France); Hillaire-Buys, D. [CHRU Montpellier, 34295 Montpellier (France); Raynaud De Mauverger, E.; Lacampagne, A.; Mercier, J. [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France)

    2012-03-01

    The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complex I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.

  20. RNA-induced silencing attenuates G protein-mediated calcium signals.

    Science.gov (United States)

    Philip, Finly; Sahu, Shriya; Golebiewska, Urszula; Scarlata, Suzanne

    2016-05-01

    Phospholipase Cβ (PLCβ) is activated by G protein subunits in response to environmental stimuli to increase intracellular calcium. In cells, a significant portion of PLCβ is cytosolic, where it binds a protein complex required for efficient RNA-induced silencing called C3PO (component 3 promoter of RISC). Binding between C3PO and PLCβ raises the possibility that RNA silencing activity can affect the ability of PLCβ to mediate calcium signals. By use of human and rat neuronal cell lines (SK-N-SH and PC12), we show that overexpression of one of the main components of C3PO diminishes Ca(2+) release in response to Gαq/PLCβ stimulation by 30 to 40%. In untransfected SK-N-SH or PC12 cells, the introduction of siRNA(GAPDH) [small interfering RNA(glyceraldehyde 3-phosphate dehydrogenase)] reduces PLCβ-mediated calcium signals by ∼30%, but addition of siRNA(Hsp90) (heat shock protein 90) had little effect. Fluorescence imaging studies suggest an increase in PLCβ-C3PO association in cells treated with siRNA(GAPDH) but not siRNA(Hsp90). Taken together, our studies raise the possibility that Ca(2+) responses to extracellular stimuli can be modulated by components of the RNA silencing machinery.-Philip, F., Sahu, S., Golebiewska, U., Scarlata, S. RNA-induced silencing attenuates G protein-mediated calcium signals. PMID:26862135

  1. Characterization of NAADP-mediated calcium signaling in human spermatozoa

    International Nuclear Information System (INIS)

    Highlights: •Human sperm cells synthesize NAADP. •NAADP-AM mediates [Ca2+]i increases in human sperm in the absence of [Ca2+]o. •Human sperm have two acidic compartments located in the head and midpiece. -- Abstract: Ca2+ signaling in spermatozoa plays a crucial role during processes such as capacitation and release of the acrosome, but the underlying molecular mechanisms still remain unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-releasing second messenger in a variety of cellular processes. The presence of a NAADP synthesizing enzyme in sea urchin sperm has been previously reported, suggesting a possible role of NAADP in sperm Ca2+ signaling. In this work we used in vitro enzyme assays to show the presence of a novel NAADP synthesizing enzyme in human sperm, and to characterize its sensitivity to Ca2+ and pH. Ca2+ fluorescence imaging studies demonstrated that the permeable form of NAADP (NAADP-AM) induces intracellular [Ca2+] increases in human sperm even in the absence of extracellular Ca2+. Using LysoTracker®, a fluorescent probe that selectively accumulates in acidic compartments, we identified two such stores in human sperm cells. Their acidic nature was further confirmed by the reduction in staining intensity observed upon inhibition of the endo-lysosomal proton pump with Bafilomycin, or after lysosomal bursting with glycyl-L-phenylalanine-2-naphthylamide. The selective fluorescent NAADP analog, Ned-19, stained the same subcellular regions as LysoTracker®, suggesting that these stores are the targets of NAADP action

  2. Characterization of NAADP-mediated calcium signaling in human spermatozoa

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Tusie, A.A. [Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos (Mexico); Vasudevan, S.R.; Churchill, G.C. [Department of Pharmacology, University of Oxford, Oxford OX1 3QT, England (United Kingdom); Nishigaki, T. [Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos (Mexico); Treviño, C.L., E-mail: ctrevino@ibt.unam.mx [Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos (Mexico)

    2014-01-10

    Highlights: •Human sperm cells synthesize NAADP. •NAADP-AM mediates [Ca{sup 2+}]{sub i} increases in human sperm in the absence of [Ca{sup 2+}]{sub o}. •Human sperm have two acidic compartments located in the head and midpiece. -- Abstract: Ca{sup 2+} signaling in spermatozoa plays a crucial role during processes such as capacitation and release of the acrosome, but the underlying molecular mechanisms still remain unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca{sup 2+}-releasing second messenger in a variety of cellular processes. The presence of a NAADP synthesizing enzyme in sea urchin sperm has been previously reported, suggesting a possible role of NAADP in sperm Ca{sup 2+} signaling. In this work we used in vitro enzyme assays to show the presence of a novel NAADP synthesizing enzyme in human sperm, and to characterize its sensitivity to Ca{sup 2+} and pH. Ca{sup 2+} fluorescence imaging studies demonstrated that the permeable form of NAADP (NAADP-AM) induces intracellular [Ca{sup 2+}] increases in human sperm even in the absence of extracellular Ca{sup 2+}. Using LysoTracker®, a fluorescent probe that selectively accumulates in acidic compartments, we identified two such stores in human sperm cells. Their acidic nature was further confirmed by the reduction in staining intensity observed upon inhibition of the endo-lysosomal proton pump with Bafilomycin, or after lysosomal bursting with glycyl-L-phenylalanine-2-naphthylamide. The selective fluorescent NAADP analog, Ned-19, stained the same subcellular regions as LysoTracker®, suggesting that these stores are the targets of NAADP action.

  3. Calcium Oscillations

    OpenAIRE

    Dupont, Geneviève; Combettes, Laurent; Bird, Gary S.; Putney, James W.

    2011-01-01

    Calcium signaling results from a complex interplay between activation and inactivation of intracellular and extracellular calcium permeable channels. This complexity is obvious from the pattern of calcium signals observed with modest, physiological concentrations of calcium-mobilizing agonists, which typically present as sequential regenerative discharges of stored calcium, a process referred to as calcium oscillations. In this review, we discuss recent advances in understanding the underlyin...

  4. Effect of TGFβ on calcium signaling in megakaryocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jing [Department of Physiology I, University of Tübingen, Tübingen (Germany); Schmid, Evi [Department of Physiology I, University of Tübingen, Tübingen (Germany); Department of Pediatric Surgery and Pediatric Urology, University Children' s Hospital Tübingen, Tübingen (Germany); Almilaji, Ahmad; Shumilina, Ekaterina [Department of Physiology I, University of Tübingen, Tübingen (Germany); Borst, Oliver [Department of Physiology I, University of Tübingen, Tübingen (Germany); Department of Cardiology & Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Laufer, Stefan [Department of Pharmacy, University of Tübingen, Tübingen (Germany); Gawaz, Meinrad [Department of Cardiology & Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology I, University of Tübingen, Tübingen (Germany)

    2015-05-22

    TGFβ is a powerful regulator of megakaryocyte maturation and platelet formation. As previously shown for other cell types, TGFβ may up-regulate the expression of the serum & glucocorticoid inducible kinase SGK1, an effect requiring p38 kinase. SGK1 has in turn recently been shown to participate in the regulation of cytosolic Ca{sup 2+} activity ([Ca{sup 2+}]{sub i}) in megakaryocytes and platelets. SGK1 phosphorylates the IκB kinase (IKKα/β), which in turn phosphorylates the inhibitor protein IκBα resulting in nuclear translocation of nuclear factor NFκB. Genes up-regulated by NFκB include Orai1, the pore forming ion channel subunit accomplishing store operated Ca{sup 2+} entry (SOCE). The present study explored whether TGFβ influences Ca{sup 2+} signaling in megakaryocytes. [Ca{sup 2+}]{sub i} was determined by Fura-2 fluorescence and SOCE from the increase of [Ca{sup 2+}]{sub i} following re-addition of extracellular Ca{sup 2+} after store depletion by removal of extracellular Ca{sup 2+} and inhibition of the sarcoendoplasmatic Ca{sup 2+} ATPase (SERCA) with thapsigargin (1 μM). As a result, TGFβ (60 ng, 24 h) increased SOCE, an effect significantly blunted by p38 kinase inhibitor Skepinone-L (1 μM), SGK1 inhibitor EMD638683 (50 μM) and NFκB inhibitor wogonin (100 μM). In conclusion, TGFβ is a powerful regulator of store operated Ca{sup 2+} entry into megakaryocytes, an effect mediated by a signaling cascade involving p38 kinase, SGK1 and NFκB. - Highlights: • TGFβ up-regulates store operated Ca{sup 2+} entry (SOCE) in megakaryocytes. • The effect of TGFβ on SOCE is blunted by p38 kinase inhibitor Skepinone-L. • The effect of TGFβ on SOCE is virtually abrogated by SGK1 inhibitor EMD638683. • The effect of TGFβ on SOCE is almost abolished by NFκB inhibitor wogonin. • The effect of TGFβ is expected to enhance sensitivity of platelets to activation.

  5. Effect of TGFβ on calcium signaling in megakaryocytes

    International Nuclear Information System (INIS)

    TGFβ is a powerful regulator of megakaryocyte maturation and platelet formation. As previously shown for other cell types, TGFβ may up-regulate the expression of the serum & glucocorticoid inducible kinase SGK1, an effect requiring p38 kinase. SGK1 has in turn recently been shown to participate in the regulation of cytosolic Ca2+ activity ([Ca2+]i) in megakaryocytes and platelets. SGK1 phosphorylates the IκB kinase (IKKα/β), which in turn phosphorylates the inhibitor protein IκBα resulting in nuclear translocation of nuclear factor NFκB. Genes up-regulated by NFκB include Orai1, the pore forming ion channel subunit accomplishing store operated Ca2+ entry (SOCE). The present study explored whether TGFβ influences Ca2+ signaling in megakaryocytes. [Ca2+]i was determined by Fura-2 fluorescence and SOCE from the increase of [Ca2+]i following re-addition of extracellular Ca2+ after store depletion by removal of extracellular Ca2+ and inhibition of the sarcoendoplasmatic Ca2+ ATPase (SERCA) with thapsigargin (1 μM). As a result, TGFβ (60 ng, 24 h) increased SOCE, an effect significantly blunted by p38 kinase inhibitor Skepinone-L (1 μM), SGK1 inhibitor EMD638683 (50 μM) and NFκB inhibitor wogonin (100 μM). In conclusion, TGFβ is a powerful regulator of store operated Ca2+ entry into megakaryocytes, an effect mediated by a signaling cascade involving p38 kinase, SGK1 and NFκB. - Highlights: • TGFβ up-regulates store operated Ca2+ entry (SOCE) in megakaryocytes. • The effect of TGFβ on SOCE is blunted by p38 kinase inhibitor Skepinone-L. • The effect of TGFβ on SOCE is virtually abrogated by SGK1 inhibitor EMD638683. • The effect of TGFβ on SOCE is almost abolished by NFκB inhibitor wogonin. • The effect of TGFβ is expected to enhance sensitivity of platelets to activation

  6. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R; Henriksen, Zanne; Sørensen, Ole;

    2002-01-01

    Signaling between osteoblasts and osteoclasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified...... mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. Intercellular calcium responses in osteoclasts required P2 receptor activation but not gap junctional communication. Pharmacological studies and reverse transcriptase-PCR amplification demonstrated...... that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium...

  7. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling

    Directory of Open Access Journals (Sweden)

    Chowdhury Parimal

    2013-01-01

    Full Text Available Abstract Background Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure. Methods Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3 receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process. Results Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3 receptor blockers. Conclusions The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… The results implicate the role of nicotine in the mobilization of both intra- and extracellular calcium in the regulation of stimulus-secretory response of enzyme secretion in this cell system. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

  8. A model of calcium signaling and degranulation dynamics induced by laser irradiation in mast cells

    Institute of Scientific and Technical Information of China (English)

    SHI XiaoMin; ZHENG YuFan; LIU ZengRong; YANG WenZhong

    2008-01-01

    Recent experiments show that calcium signaling and degranulation dynamics induced by low power laser irradiation in mast cells must rely on extracellular Ca2+ influx. An analytical expression of Ca2+ flux through TRPV4 cation channel in response to interaction of laser photon energy and extracellular Ca2+ is deduced, and a model characterizing dynamics of calcium signaling and degranulation activated by laser irradiation in mast cells is established. The model indicates that the characteristics of calcium signaling and degranulation dynamics are determined by interaction between laser photon energy and Ca2+ influx. Extracellular Ca2+ concentration is so high that even small photon energy can activate mast cells, thus avoiding the possible injury caused by laser irradiation with shorter wavelengths. The model predicts that there exists a narrow parameter domain of photon energy and extracellular Ca2+ concentration of which results in cytosolic Ca2+ limit cycle oscillations, and shows that PKC activity is in direct proportion to the frequency of Ca2+ oscillations. With the model it is found that sustained and stable maximum plateau of cytosolic Ca2+ concentration can get optimal degranulation rate. Furthermore, the idea of introducing the realistic physical energy into model is applicable to modeling other physical signal transduction systems.

  9. Consumption of Calcium-Fortified Cereal Bars to Improve Dietary Calcium Intake of Healthy Women: Randomized Controlled Feasibility Study

    Science.gov (United States)

    Lee, Jennifer T.; Moore, Carolyn E.; Radcliffe, John D.

    2015-01-01

    Calcium is an important structural component of the skeletal system. Although an adequate intake of calcium helps to maintain bone health and reduce the risk of osteoporosis, many women do not meet recommended daily intakes of calcium. Previous interventions studies designed to increase dietary intake of women have utilized primarily dairy sources of calcium or supplements. However, lactose intolerance, milk protein allergies, or food preferences may lead many women to exclude important dairy sources of dietary calcium. Therefore, we undertook a 9 week randomized crossover design trial to examine the potential benefit of including a non-dairy source of calcium in the diet of women. Following a 3 week run-in baseline period, 35 healthy women > 18 years were randomized by crossover design into either Group I or Group II. Group I added 2 calcium-fortified cereal bars daily (total of 400 mg calcium/day) (intervention) to their usual diet and Group II continued their usual diet (control). At the end of 3 weeks, diets were switched for another 3 weeks. Intakes of calcium and energy were estimated from 3-day diet and supplemental diaries. Wilcoxon signed-rank tests were used for within group comparisons and Mann Whitney U tests were used for between group comparisons of calcium and energy intake. Dietary calcium was significantly higher during intervention (1071 mg/d) when participants consumed 2 calcium-fortified cereal bars daily than during the baseline (720 mg/d, P <0.0001) or control diets (775 mg/d, P = 0.0001) periods. Furthermore, the addition of 2 calcium-fortified cereal bars daily for the 3 week intervention did not significantly increase total energy intake or result in weight gain. In conclusion, consumption of calcium-fortified cereal bars significantly increased calcium intake of women. Further research examining the potential ability of fortified cereal bars to help maintain and improve bone health of women is warranted. Trial Registration Clinical

  10. ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct

    DEFF Research Database (Denmark)

    Svenningsen, Per; Burford, James L; Peti-Peterdi, János

    2013-01-01

    ATP in the renal tubular fluid is an important regulator of salt and water reabsorption via purinergic calcium signaling that involves the P2Y2 receptor, ENaC, and AQP2. Recently, we have shown that connexin (Cx) 30 hemichannels are localized to the non-junctional apical membrane of cells in the...... distal nephron-collecting duct (CD) and release ATP into the tubular fluid upon mechanical stimuli, leading to reduced salt and water reabsorption. Cx30(-/-) mice show salt-dependent elevations in BP and impaired pressure-natriuresis. Thus, we hypothesized that increased tubular flow rate leads to Cx30...... suramin. Taken together, these data confirm that mechanosensitive Cx30 hemichannels mediate tubular ATP release and purinergic calcium signaling in the CD which mechanism plays an important role in the regulation of CD salt and water reabsorption....

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

    Science.gov (United States)

    Kazantsev, V. B.

    2009-01-01

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

  12. The role of calcium in hypoxia-induced signal transduction and gene expression.

    Science.gov (United States)

    Seta, Karen A; Yuan, Yong; Spicer, Zachary; Lu, Gang; Bedard, James; Ferguson, Tsuneo K; Pathrose, Peterson; Cole-Strauss, Allyson; Kaufhold, Alexa; Millhorn, David E

    2004-01-01

    Mammalian cells require a constant supply of oxygen in order to maintain adequate energy production, which is essential for maintaining normal function and for ensuring cell survival. Sustained hypoxia can result in cell death. Sophisticated mechanisms have therefore evolved which allow cells to respond and adapt to hypoxia. Specialized oxygen-sensing cells have the ability to detect changes in oxygen tension and transduce this signal into organ system functions that enhance the delivery of oxygen to tissue in a wide variety of different organisms. An increase in intracellular calcium levels is a primary response of many cell types to hypoxia/ischemia. The response to hypoxia is complex and involves the regulation of multiple signaling pathways and coordinated expression of perhaps hundreds of genes. This review discusses the role of calcium in hypoxia-induced regulation of signal transduction pathways and gene expression. An understanding of the molecular events initiated by changes in intracellular calcium will lead to the development of therapeutic approaches toward the treatment of hypoxic/ischemic diseases and tumors. PMID:15261489

  13. The APP670/671 mutation alters calcium signaling and response to hyperosmotic stress in rat primary hippocampal neurons

    DEFF Research Database (Denmark)

    Kloskowska, Ewa; Bruton, Joseph D; Winblad, Bengt; Benedikz, Eirikur

    2008-01-01

    Altered calcium homeostasis is implicated in the pathogenesis of Alzheimer's disease and much effort has been put into understanding the association between the autosomal dominant gene mutations causative of this devastating disease and perturbed calcium signaling. We have focused our attention o...

  14. Localized Calcium Signals along the Cleavage Furrow of the Xenopus Egg Are Not Involved in Cytokinesis

    OpenAIRE

    Noguchi, Tatsuhiko; Mabuchi, Issei

    2002-01-01

    It has been proposed that a localized calcium (Ca) signal at the growing end of the cleavage furrow triggers cleavage furrow formation in large eggs. We have examined the possible role of a Ca signal in cleavage furrow formation in the Xenopus laevis egg during the first cleavage. We were able to detect two kinds of Ca waves along the cleavage furrow. However, the Ca waves appeared after cleavage furrow formation in late stages of the first cleavage. In addition, cleavage was not affected by ...

  15. Calcium-phosphate-osteopontin particles for caries control.

    Science.gov (United States)

    Schlafer, Sebastian; Birkedal, Henrik; Olsen, Jakob; Skovgaard, Jonas; Sutherland, Duncan S; Wejse, Peter L; Nyvad, Bente; Meyer, Rikke L

    2016-01-01

    Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co-precipitation and designed to bind to bacteria in biofilms, impede biofilm build-up without killing the microflora, and release phosphate ions to buffer bacterial acid production if the pH decreases below 6. Analysis of biofilm formation and pH in a five-species biofilm model for dental caries showed that treatment with particles or pure osteopontin led to less biofilm formation compared to untreated controls or biofilms treated with osteopontin-free particles. The anti-biofilm effect can thus be ascribed to osteopontin. The particles also led to a slower acidification of the biofilm after exposure to glucose, and the pH always remained above 5.5. Hence, calcium-phosphate-osteopontin particles show potential for applications in caries control. PMID:26923119

  16. The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

    Science.gov (United States)

    Pickard, B. G.; Ding, J. P.

    1993-01-01

    Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

  17. Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx

    DEFF Research Database (Denmark)

    Lei, Ying; Cao, Yongxiao; Zhang, Yaping;

    2011-01-01

    airway smooth muscle cells by using an organ culture model and a set of selective pharmacological inhibitors for mitogen-activated protein kinase (MAPK) and calcium signal pathways. Western-blot, immunohistochemistry, myograph and a selective TP receptor agonist U46619 were used for examining TP receptor...... signal proteins and function. Organ culture of rat bronchial segments for up to 48 h induces a time-dependently increased airway contractile response to U46619. This indicates that organ culture increases TP receptor signaling in the airway smooth muscle cells. The enhanced bronchial contraction was...... attenuated by the inhibition of c-Jun N-terminal kinase (JNK) MAPK activity, chelation of extracellular calcium and calcium channel blocker nifedipine, suggesting that JNK MAPK activity and elevated intracellular calcium level are required for the TP receptor signaling. In conclusion, airway smooth muscle...

  18. Shuffling the cards in signal transduction: Calcium, arachidonic acid and mechanosensitivity

    Institute of Scientific and Technical Information of China (English)

    Luca; Munaron

    2011-01-01

    Cell signaling is a very complex network of biochemical reactions triggered by a huge number of stimuli coming from the external medium. The function of any single signaling component depends not only on its own structure but also on its connections with other biomolecules. During prokaryotic-eukaryotic transition, the rearrangement of cell organization in terms of diffusional compartmentalization exerts a deep change in cell signaling functional potentiality. In this review I briefly introduce an intriguing ancient relationship between pathways involved in cell responses to chemical agonists (growth factors, nutrients, hormones) as well as to mechanical forces (stretch, osmotic changes). Some biomolecules (ion channels and enzymes) act as "hubs", thanks to their ability to be directly or indirectly chemically/mechanically co-regulated. In particular calcium signaling machinery and arachidonic acid metabolism are very ancient networks, already present before eukaryotic appearance. A number of molecular "hubs", including phospholipase A2 and some calcium channels, appear tightly interconnected in a cross regulation leading to the cellular response to chemical and mechanical stimulations.

  19. The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Schaal, Courtney [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States); Padmanabhan, Jaya [Department of Molecular Medicine and USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, FL 33612 (United States); Chellappan, Srikumar, E-mail: Srikumar.Chellappan@moffitt.org [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States)

    2015-07-31

    Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer.

  20. Role of calcium signaling in down-regulation of aggrecan induced by cyclic tensile strain in annulus fibrosus cells

    Institute of Scientific and Technical Information of China (English)

    GUO Zhi-liang; ZHOU Yue; LI Hua-zhuang; CAO Guo-yong; TENG Hai-jun

    2006-01-01

    Objective:To study the role of intracellular calcium signal pathway in the down-regulation of aggrecan induced by cyclic tensile strain in the annulus fibrosus cells. Methods :The expression of aggrecan mRNA and core protein were respectively detected with RT-PCR and western blot after the channels transmitting calcium ions were blocked with EGTA, gadolinium and verapamil. Results:EGTA, gadolinium and verapamil partially prevented the effects of cyclic tensile strain on the expression of aggrecan in annulus fibrosus cells. Conclusion:The calcium signaling is involved in the down-regulation of proteoglycan resulting from cyclic tensile strain in the annulus fibrosus cells.

  1. Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling

    OpenAIRE

    Kornélia Szebényi; András Füredi; Orsolya Kolacsek; Enikő Pergel; Zsuzsanna Bősze; Balázs Bender; Péter Vajdovich; József Tóvári; László Homolya; Gergely Szakács; László Héja; Ágnes Enyedi; Balázs Sarkadi; Ágota Apáti; Orbán, Tamás I.

    2015-01-01

    In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, an...

  2. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Directory of Open Access Journals (Sweden)

    Wagner Shin Nishitani

    Full Text Available A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7 expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  3. Macroscopic consequences of calcium signaling in microdomains: A first passage time approach

    CERN Document Server

    Rovetti, Robert; Garfinkel, Alan; Shiferaw, Yohannes

    2007-01-01

    Calcium (Ca) plays an important role in regulating various cellular processes. In a variety of cell types, Ca signaling occurs within microdomains where channels deliver localized pulses of Ca which activate a nearby collection of Ca-sensitive receptors. The small number of channels involved ensures that the signaling process is stochastic. The aggregate response of several thousand of these microdomains yields a whole-cell response which dictates the cell behavior. Here, we study analytically the statistical properties of a population of these microdomains in response to a trigger signal. We apply these results to understand the relationship between Ca influx and Ca release in cardiac cells. In this context, we use a first passage time approach to show analytically how Ca release in the whole cell depends on the single channel kinetics of Ca channels and the properties of microdomains. Using these results, we explain the underlying mechanism for the graded relationship between Ca influx and Ca release in car...

  4. 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.

  5. Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease

    Science.gov (United States)

    Guauque-Olarte, Sandra; Messika-Zeitoun, David; Droit, Arnaud; Lamontagne, Maxime; Tremblay-Marchand, Joël; Lavoie-Charland, Emilie; Gaudreault, Nathalie; Arsenault, Benoit J.; Dubé, Marie-Pierre; Tardif, Jean-Claude; Body, Simon C.; Seidman, Jonathan G.; Boileau, Catherine; Mathieu, Patrick; Pibarot, Philippe; Bossé, Yohan

    2016-01-01

    Background Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. Methods and Results A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had Pmeta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33×10−5). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. Conclusions This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway. PMID:26553695

  6. Role of endoplasmic reticulum calcium signaling in the pathogenesis of Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Elena ePopugaeva

    2013-09-01

    Full Text Available Alzheimer disease (AD is a major threat of XXI century that is responsible for the majority of dementia in the elderly. Development of effective AD-preventing therapies are the top priority tasks for neuroscience research. Amyloid hypothesis of AD is a dominant idea in the field, but so far all amyloid-targeting therapies have failed in clinical trials. In addition to amyloid accumulation, there are consistent reports of abnormal calcium signaling in AD neurons. AD neurons exhibit enhanced intracellular calcium (Ca2+ liberation from the endoplasmic reticulum (ER and reduced store-operated Ca2+ entry (SOC. These changes occur primarily as a result of ER Ca2+ overload. We argue that normalization of intracellular Ca2+ homeostasis could be a strategy for development of effective disease-modifying therapies. The current review summarizes recent data about changes in ER Ca2+ signaling in AD. Ca2+ channels that are discussed in the current review include: inositol trisphosphate receptors (InsP3R, ryanodine receptors (RyanR, presenilins as ER Ca2+ leak channels and neuronal SOC channels. We discuss how function of these channels is altered in AD and how important are resulting Ca2+ signaling changes for AD pathogenesis.

  7. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne;

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in...... extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx......43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium....

  8. Intracellular calcium signals display an avalanche-like behavior over multiple lengthscales.

    Science.gov (United States)

    Lopez, Lucía; Piegari, Estefanía; Sigaut, Lorena; Ponce Dawson, Silvina

    2012-01-01

    Many natural phenomena display "self-organized criticality" (SOC), (Bak et al., 1987). This refers to spatially extended systems for which patterns of activity characterized by different lengthscales can occur with a probability density that follows a power law with pattern size. Differently from power laws at phase transitions, systems displaying SOC do not need the tuning of an external parameter. Here we analyze intracellular calcium (Ca(2+)) signals, a key component of the signaling toolkit of almost any cell type. Ca(2+) signals can either be spatially restricted (local) or propagate throughout the cell (global). Different models have suggested that the transition from local to global signals is similar to that of directed percolation. Directed percolation has been associated, in turn, to the appearance of SOC. In this paper we discuss these issues within the framework of simple models of Ca(2+) signal propagation. We also analyze the size distribution of local signals ("puffs") observed in immature Xenopus Laevis oocytes. The puff amplitude distribution obtained from observed local signals is not Gaussian with a noticeable fraction of large size events. The experimental distribution of puff areas in the spatio-temporal record of the image has a long tail that is approximately log-normal. The distribution can also be fitted with a power law relationship albeit with a smaller goodness of fit. The power law behavior is encountered within a simple model that includes some coupling among individual signals for a wide range of parameter values. An analysis of the model shows that a global elevation of the Ca(2+) concentration plays a major role in determining whether the puff size distribution is long-tailed or not. This suggests that Ca(2+)-clearing from the cytosol is key to determine whether IP(3)-mediated Ca(2+) signals can display a SOC-like behavior or not. PMID:22969730

  9. Intracellular calcium signals display an avalanche-like behavior over multiple lengthscales.

    Directory of Open Access Journals (Sweden)

    LucíaLopez

    2012-09-01

    Full Text Available Many natural phenomena display "self-organized criticality'' (SOC. This refers to spatially extended systems for which patterns of activity characterized by different lengthscales can occur with a probability density that follows a power law with pattern size. Differently from power laws at phase transitions, systems displaying SOC do not need the tuning of an external parameter. Here we analyze intracellular calcium Ca2+ signals, a key component of the signaling toolkit of almost any cell type. Ca2+ signals can either be spatially restricted (local or propagate throughout the cell (global. Different models have suggested that the transition from local to global signals is similar to that of directed percolation. Directed percolation has been associated, in turn, to the appearance of self-organized criticality. In this paper we discuss these issues within the framework of simple models of Ca2+ signal propagation. We also analyze the size distribution of local signals ("puffs'' observed in immature Xenopus Laevis oocytes. The puff amplitude distribution obtained from observed local signals is not Gaussian with a noticeable fraction of large size events. The experimental distribution of puff areas in the spatio-temporal record of the image has a long tail that is approximately log-normal. The distribution can also be fitted with a power law relationship albeit with a smaller goodness of fit. The power law behavior is encountered within a simple model that includes some coupling among individual signals for a wide range of parameter values. An analysis of the model shows that a global elevation of the Ca2+ concentration plays a major role in determining whether the puff size distribution is long-tailed or not. This suggests that Ca2+-clearing from the cytosol is key to determine whether IP3-mediated Ca2+ signals can display a SOC-like behavior or not.

  10. Dietary calcium intake and the risk of colorectal cancer: a case control study

    OpenAIRE

    Han, Changwoo; Shin, Aesun; Lee, Jeonghee; Lee, Jeeyoo; Park, Ji Won; Oh, Jae Hwan; Kim, Jeongseon

    2015-01-01

    Background High intake of dietary calcium has been thought to be a protective factor against colorectal cancer. To explore the dose-response relationship in the associations between dietary calcium intake and colorectal cancer risk by cancer location, we conducted a case-control study among Korean population, whose dietary calcium intake levels are relatively low. Methods The colorectal cancer cases and controls were recruited from the National Cancer Center in Korea between August 2010 and A...

  11. Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation.

    Science.gov (United States)

    Boehmerle, Wolfgang; Zhang, Kun; Sivula, Michael; Heidrich, Felix M; Lee, Yashang; Jordt, Sven-Eric; Ehrlich, Barbara E

    2007-06-26

    Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP(3))-mediated Ca(2+) signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP(3) receptor (InsP(3)R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca(2+) signaling. When NCS-1 protein levels recovered, so did InsP(3)-mediated Ca(2+) signaling. Inhibition of the Ca(2+)-activated protease mu-calpain prevented alterations in phosphoinositide-mediated Ca(2+) signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by mu-calpain in vitro and that mu-calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates mu-calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP(3)mediated Ca(2+) signaling. These findings provide a previously undescribed approach to understanding and treating Taxol-induced peripheral neuropathy. PMID:17581879

  12. Net analyte signal based statistical quality control

    NARCIS (Netherlands)

    Skibsted, E.T.S.; Boelens, H.F.M.; Westerhuis, J.A.; Smilde, A.K.; Broad, N.W.; Rees, D.R.; Witte, D.T.

    2005-01-01

    Net analyte signal statistical quality control (NAS-SQC) is a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is sep

  13. Stroma cell-derived factor-1α signaling enhances calcium transients and beating frequency in rat neonatal cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Ielham Hadad

    Full Text Available Stroma cell-derived factor-1α (SDF-1α is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1α induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1α signaling might have direct effects on calcium transients and beating frequency.Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1α in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IP3R blocker, but not with a ryanodine receptor (RyR antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IP3R blocker. Treatment with forskolin or SDF-1α increased cardiomyocyte beating frequency and their effects were additive. In vivo, treatment with SDF-1α increased left ventricular dP/dtmax.These results suggest that in rat neonatal cardiomyocytes, the SDF-1α/CXCR4 signaling increases calcium transients in an IP3-gated fashion leading to a positive chronotropic and inotropic effect.

  14. Control of calcium carbonate precipitation in anaerobic reactors.

    OpenAIRE

    Langerak, van, B.

    1998-01-01

    Anaerobic treatment of waste waters with a high calcium content may lead to excessive precipitation of calcium carbonate. So far, no proper methods were available to predict or reduce the extent of precipitation in an anaerobic treatment system. Moreover, it also was not clear to what extent precipitation in an anaerobic reactor can be tolerated because adequate knowledge on the structure and quality of methanogenic sludges with high calcium carbonate content was lacking. In this thesis, the ...

  15. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion

    OpenAIRE

    Wagner Shin Nishitani; Adriano Mesquita Alencar; Yingxiao Wang

    2015-01-01

    A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs) in terms of calcium signaling. The intracellular calcium i...

  16. Scotopic Visual Signaling in the Mouse Retina Is Modulated by High-Affinity Plasma Membrane Calcium Extrusion

    OpenAIRE

    Duncan, Jacque L.; Yang, Haidong; Doan, Thuy; Silverstein, Robert S.; Murphy, Gabe J.; Nune, George; Liu, Xiaorong; Copenhagen, David; Tempel, Bruce L; Rieke, Fred; KRIŽAJ, DAVID

    2006-01-01

    Transmission of visual signals at the first retinal synapse is associated with changes in calcium concentration in photoreceptors and bipolar cells. We investigated how loss of plasma membrane Ca2+ ATPase isoform 2 (PMCA2), the calcium transporter isoform with the highest affinity for Ca2+/calmodulin, affects transmission of rod- and cone-mediated responses. PMCA2 expression in the neuroblast layer was observed soon after birth; in the adult, PMCA2 was expressed in inner segments and synaptic...

  17. Simple Signal Source based Micro Controller

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Using micro controller, DAC and Multi-periods syn-thesis, we can buildup a very simple signal source with precisefrequency, amplitude and waveform. Wave parameters can beprogrammed in advance. The circuit can satisfy some special re-quirements.

  18. Comparative Detection of Calcium Fluctuations in Single Female Sex Cells of Tobacco to Distinguish Calcium Signals Triggered by in vitro Fertilization

    Institute of Scientific and Technical Information of China (English)

    Xiong-Bo Peng; Meng-Xiang Sun; Hong-Yuan Yang

    2009-01-01

    Double fertilization is a key process of sexual reproduction in higher plants. The role of calcium In the activation of female sex cells through fertilization has recently received a great deal of attention. The establishment of a Ca-imaging technique for living, single, female sex cells is a difficult but necessary prerequisite for evaluating the role of Ca in the transduction of external stimuli, including the fusion with the sperm cell, to internal cellular processes. The present study describes the use of Fluo-3 for reporting the Ca signal in isolated, single, female sex cells, egg cells and central cells, of tobacco plants. A suitable loading protocol was optimized by loading the cells at pH 5.6 with 2 μM Fluo-3 for 30 min at 30℃. Under theseconditions, several key factors related to in vitro fertilization were also investigated in order to test their possible effects onthe [Ca] of the female sex cells. The results indicated that the bovine serum albumin-fusion system was superior to the polyethlene glycol.fusion system for detecting calcium fluctuations in female sex cells during fertilization. The central cell was fertilized with the sperm cell in bovine serum albumin; however, no evident calcium dynamic was detected, implying that a transient calcium rise might be a specific signal for egg cell fertilization.

  19. Distributed traffic signal control using fuzzy logic

    Science.gov (United States)

    Chiu, Stephen

    1992-01-01

    We present a distributed approach to traffic signal control, where the signal timing parameters at a given intersection are adjusted as functions of the local traffic condition and of the signal timing parameters at adjacent intersections. Thus, the signal timing parameters evolve dynamically using only local information to improve traffic flow. This distributed approach provides for a fault-tolerant, highly responsive traffic management system. The signal timing at an intersection is defined by three parameters: cycle time, phase split, and offset. We use fuzzy decision rules to adjust these three parameters based only on local information. The amount of change in the timing parameters during each cycle is limited to a small fraction of the current parameters to ensure smooth transition. We show the effectiveness of this method through simulation of the traffic flow in a network of controlled intersections.

  20. Detection of differentially regulated subsarcolemmal calcium signals activated by vasoactive agonists in rat pulmonary artery smooth muscle cells

    OpenAIRE

    Subedi, Krishna P; Paudel, Omkar; Sham, James S.K.

    2013-01-01

    Intracellular calcium (Ca2+) plays pivotal roles in distinct cellular functions through global and local signaling in various subcellular compartments, and subcellular Ca2+ signal is the key factor for independent regulation of different cellular functions. In vascular smooth muscle cells, subsarcolemmal Ca2+ is an important regulator of excitation-contraction coupling, and nucleoplasmic Ca2+ is crucial for excitation-transcription coupling. However, information on Ca2+ signals in these subce...

  1. Control of calcium carbonate precipitation in anaerobic reactors.

    NARCIS (Netherlands)

    Langerak, van E.P.A.

    1998-01-01

    Anaerobic treatment of waste waters with a high calcium content may lead to excessive precipitation of calcium carbonate. So far, no proper methods were available to predict or reduce the extent of precipitation in an anaerobic treatment system. Moreover, it also was not clear to what extent precipi

  2. Persistent cellular motion control and trapping using mechanotactic signaling.

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhu

    Full Text Available Chemotactic signaling and the associated directed cell migration have been extensively studied owing to their importance in emergent processes of cellular aggregation. In contrast, mechanotactic signaling has been relatively overlooked despite its potential for unique ways to artificially signal cells with the aim to effectively gain control over their motile behavior. The possibility of mimicking cellular mechanotactic signals offers a fascinating novel strategy to achieve targeted cell delivery for in vitro tissue growth if proven to be effective with mammalian cells. Using (i optimal level of extracellular calcium ([Ca(2+]ext = 3 mM we found, (ii controllable fluid shear stress of low magnitude (σ < 0.5 Pa, and (iii the ability to swiftly reverse flow direction (within one second, we are able to successfully signal Dictyostelium discoideum amoebae and trigger migratory responses with heretofore unreported control and precision. Specifically, we are able to systematically determine the mechanical input signal required to achieve any predetermined sequences of steps including straightforward motion, reversal and trapping. The mechanotactic cellular trapping is achieved for the first time and is associated with a stalling frequency of 0.06 ~ 0.1 Hz for a reversing direction mechanostimulus, above which the cells are effectively trapped while maintaining a high level of directional sensing. The value of this frequency is very close to the stalling frequency recently reported for chemotactic cell trapping [Meier B, et al. (2011 Proc Natl Acad Sci USA 108:11417-11422], suggesting that the limiting factor may be the slowness of the internal chemically-based motility apparatus.

  3. Mango Fruit Extracts Differentially Affect Proliferation and Intracellular Calcium Signalling in MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Meng-Wong Taing

    2015-01-01

    Full Text Available The assessment of human cancer cell proliferation is a common approach in identifying plant extracts that have potential bioactive effects. In this study, we tested the hypothesis that methanolic extracts of peel and flesh from three archetypal mango cultivars, Irwin (IW, Nam Doc Mai (NDM, and Kensington Pride (KP, differentially affect proliferation, extracellular signal-regulated kinase (ERK activity, and intracellular calcium ([Ca2+]I signalling in MCF-7 human breast cancer cells. Mango flesh extracts from all three cultivars did not inhibit cell growth, and of the peel extracts only NDM reduced MCF-7 cell proliferation. Mango cultivar peel and flesh extracts did not significantly change ERK phosphorylation compared to controls; however, some reduced relative maximal peak [Ca2+]I after adenosine triphosphate stimulation, with NDM peel extract having the greatest effect among the treatments. Our results identify mango interfruit and intrafruit (peel and flesh extract variability in antiproliferative effects and [Ca2+]I signalling in MCF-7 breast cancer cells and highlight that parts of the fruit (such as peel and flesh and cultivar differences are important factors to consider when assessing potential chemopreventive bioactive compounds in plants extracts.

  4. Calcium signaling triggered by ouabain protects the embryonic kidney from adverse developmental programming.

    Science.gov (United States)

    Khodus, Georgiy R; Kruusmägi, Markus; Li, Juan; Liu, Xiao-Li; Aperia, Anita

    2011-09-01

    The kidney is extraordinarily sensitive to adverse fetal programming. Malnutrition, the most common form of developmental challenge, retards formation of the kidney's functional units, the nephrons. The resulting low nephron endowment increases susceptibility to renal injury and disease. Using explanted rat embryonic kidneys, we found that the sodium-potassium-adenosine triphosphatase (Na, K-ATPase) ligand ouabain triggers, via the Na, K-ATPase/ inositol 1,4,5-trisphosphate receptor signalosome, a calcium-nuclear factor-kappa B (NF-κB) signal that protects kidney development from adverse effects of malnutrition. Serum deprivation resulted in severe retardation of nephron formation and robust increase in apoptotic rate, but in ouabain-exposed kidneys, no adverse effects of serum deprivation were observed. Depletion of intracellular calcium stores and inhibition of NF-κB activity abolished the rescuing effect of ouabain. Proof of principle that ouabain rescues development of embryonic kidneys exposed to malnutrition was obtained from studies on pregnant rats given low-protein diets and treated with ouabain or vehicle throughout pregnancy. PMID:21424905

  5. Multiple signaling pathways mediated by dopamine and calcium ionophore A23187 in human platelets

    International Nuclear Information System (INIS)

    This study was undertaken to investigate the mechanism(s) of platelet aggregation induced by the synergistic action of dopamine (DA) and a Ca/sup +2/-ionophore, A23187. DA showed non significant effect on platelet aggregation over a wide range of concentrations (up to 500 micro M), but did potentiate the aggregation response of A23187. Aggregation induced by A23187 was inhibited by calcium channel blockers (diltiazem and verpamil), receptor blockers (chlorpromazine and haloperidol) and a cyclo-oxygenase inhibitor (indomethacin). However, the inhibitory effect of these blockers was more pronounced (with a selectivity ratio of 1.5-28) in the aggregation induced by synergistic effect of A23187 and DA. A phosphatidylinositol 3-kinase (P1 3-Kinase) inhibitor, wortmanin (1C/sub 50/. 25-30 nM), inhibited aggregation induced by either A23187 or DA and act synergistically. This synergistic effect on platelet aggregation is mediated through multiple signaling pathways. (author)

  6. Controlled degradation pattern of hydroxyapatite/calcium carbonate composite microspheres.

    Science.gov (United States)

    Yang, Ning; Zhong, Qiwei; Zhou, Ying; Kundu, Subhas C; Yao, Juming; Cai, Yurong

    2016-06-01

    Hydroxyapatite (HAP) is widely used in clinic due to its good biocompatibility and osteoconductivity except for its slow degradation speed. In the present study, spherical calcium carbonate (CaCO3 ) is fabricated in the presence of silk protein sericin, which is transmuted into HAP microsphere in phosphate solution with the assistance of microwave irradiation. The effect of reaction conditions on the conversion of CaCO3 is investigated including reaction time, chemical composition of phosphate solution, and microwave power to get a series of HAP/CaCO3 composites. The degradation property of the composites is evaluated in vitro. Results show the degradation speed of the composite with higher HAP content is slower. The degradation rate of the composite could be changed effectively by modulating the proportion of HAP and CaCO3 . This work provides a feasible method for the preparation of spherical HAP/CaCO3 composite with controllable degradability. The composite thus obtained may be an ideal material for bone tissue engineering application. Microsc. Res. Tech. 79:518-524, 2016. © 2016 Wiley Periodicals, Inc. PMID:27037606

  7. Calcium control of gene regulation in rat hippocampal neuronal cultures.

    Science.gov (United States)

    Pinato, Giulietta; Pegoraro, Silvia; Iacono, Giovanni; Ruaro, Maria Elisabetta; Torre, Vincent

    2009-09-01

    Blockage of GABA-A receptors in hippocampal neuronal cultures triggers synchronous bursts of spikes initiating neuronal plasticity, partly mediated by changes of gene expression. By using specific pharmacological blockers, we have investigated which sources of Ca2+ entry primarily control changes of gene expression induced by 20 microM gabazine applied for 30 min (GabT). Intracellular Ca2+ transients were monitored with Ca2+ imaging while recording electrical activity with patch clamp microelectrodes. Concomitant transcription profiles were obtained using Affymetrix oligonucleotide microarrays and confirmed with quantitative RT-PCR. Blockage of NMDA receptors with 2-amino-5-phosphonovaleric acid (APV) did not reduce significantly somatic Ca2+ transients, which, on the contrary, were reduced by selective blockage of L, N, and P/Q types voltage gated calcium channels (VGCCs). Therefore, we investigated changes of gene expression in the presence of blockers of NMDA receptors and L, N, and P/Q VGCCs. Our results show that: (i) among genes upregulated by GabT, there are genes selectively dependent on NMDA activation, genes selectively dependent on L-type VGCCs and genes dependent on the activation of both channels; (ii) the majority of genes requires the concomitant activation of NMDA receptors and Ca2+ entry through VGCCs; (iii) blockage of N and P/Q VGCCs has an effect similar but not identical to blockage of L-type VGCCs. PMID:19441076

  8. Digital signal processor and energy control

    OpenAIRE

    Nishikori, Yutaka; Nakamura, Yoshimichi; Matsuo, Hirofumi

    2009-01-01

    Power supply was consisted of several analog parts and various circuits had been conventionally researched before. While, digitalization research of power supply is proceeding, but it has some problem of performance and cost to create digital control power supply. Now the revolution is occurred at Energy Control area after appearing DSP (Digital Signal Processor). Until now, a power supply was one of component of system. However, the digital control power supply using DSP can realize more int...

  9. Defense-Related Calcium Signaling Mutants Uncovered via a Quantitative High-Throughput Screen in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Stefanie Ranf; Julia Grimmer; Yvonne P(o)schl; Pascal Pecher; Delphine Chinchilla; Dierk Scheel; Justin Lee

    2012-01-01

    Calcium acts as a second messenger for signaling to a variety of stimuli including MAMPs (Microbe-Associated Molecular Patterns),such as flg22 and elf18 that are derived from bacterial flagellin and elongation factor Tu,respectively.Here,Arabidopsis thaliana mutants with changed calcium elevation (cce) in response to fig22 treatment were isolated and characterized.Besides novel mutant alleles of the flg22 receptor,FLS2 (Flagellin-Sensitive 2),and the receptor-associated kinase,BAK1 (Brassinosteroid receptor 1-Associated Kinase 1),the new cce mutants can be categorized into two main groups—those with a reduced or an enhanced calcium elevation.Moreover,cce mutants from both groups show differential phenotypes to different sets of MAMPs.Thus,these mutants will facilitate the discovery of novel components in early MAMP signaling and bridge the gaps in current knowledge of calcium signaling during plant-microbe interactions.Last but not least,the screening method is optimized for speed (covering 384 plants in 3 or 10 h) and can be adapted to genetically dissect any other stimuli that induce a change in calcium levels.

  10. Regional specificity of exercise and calcium during skeletal growth in girls : A randomized controlled trial

    NARCIS (Netherlands)

    Iuliano-Burns, S; Saxon, L; Naughton, G; Gibbons, K; Bass, SL

    2003-01-01

    Combining exercise with calcium supplementation may produce additive or multiplicative effects at loaded sites; thus, we conducted a single blind, prospective, randomized controlled study in pre- and early-pubertal girls to test the following hypotheses. (1) At the loaded sites, exercise and calcium

  11. Fruit Calcium: Transport and Physiology

    Science.gov (United States)

    Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

    2016-01-01

    -regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID:27200042

  12. Fruit Calcium: Transport and Physiology.

    Science.gov (United States)

    Hocking, Bradleigh; Tyerman, Stephen D; Burton, Rachel A; Gilliham, Matthew

    2016-01-01

    -regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID:27200042

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

    Science.gov (United States)

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

    2013-04-01

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

  14. Mechanical characterization of calcium pectinate hydrogel for controlled drug delivery

    OpenAIRE

    Chung Jin Thau; Zhibing Zhang

    2003-01-01

    Calcium pectinate beads, a paniculate hydrogel system, is an attractive drug carrier for oral delivery. In this study, a poorly water-soluble model drug indomethacin was incorporated into calcium pectinate beads made of different pectin concentrations, which were produced by an extrusion method. The effect of pectin concentration on bead size, circularity, swelling behavior, and mechanical properties, as well as in vitro drug release profile was investigated. The mechanical properties of calc...

  15. Dietary Calcium and Risk for Prostate Cancer: A Case-Control Study Among US Veterans

    OpenAIRE

    Williams, Christina D.; Whitley, Brian M.; Hoyo, Cathrine; Grant, Delores J.; Schwartz, Gary G; Presti, Joseph C.; Iraggi, Jared D.; Newman, Kathryn A.; Gerber, Leah; Taylor, Loretta A.; McKeever, Madeline G.; Freedland, Stephen J.

    2012-01-01

    Introduction The objective of this study was to examine the association between calcium intake and prostate cancer risk. We hypothesized that calcium intake would be positively associated with lower risk for prostate cancer. Methods We used data from a case-control study conducted among veterans between 2007 and 2010 at the Durham Veterans Affairs Medical Center. The study consisted of 108 biopsy-positive prostate cancer cases, 161 biopsy-negative controls, and 237 healthy controls. We also d...

  16. Wnt signaling and stem cell control

    Institute of Scientific and Technical Information of China (English)

    Roel Nusse

    2008-01-01

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

  17. Melatonin sensitivity of type II GnRH-induced calcium signaling and secretion in neonatal rat gonadotrophs

    Czech Academy of Sciences Publication Activity Database

    Jindřichová, Marie; Balík, Aleš; Mazna, Petr; Zemková, Hana

    British Pharmacological Society, 2005. [Focused Meeting on Cell Signalling /4./. 11.04.2005-12.04.2005, Leicester] R&D Projects: GA AV ČR(CZ) IAA5011408 Institutional research plan: CEZ:AV0Z50110509 Keywords : GnRH type II * melatonin * calcium Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  18. Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway

    OpenAIRE

    Haustein, Martin D.; Kracun, Sebastian; Lu, Xiao-Hong; Shih, Tiffany; Jackson-Weaver, Olan; Tong, Xiaoping; Xu, Ji; Yang, X William; O'Dell, Thomas J.; Marvin, Jonathan S.; Ellisman, Mark H.; Bushong, Eric A.; Looger, Loren L.; Khakh, Baljit S.

    2014-01-01

    The spatiotemporal activities of astrocyte Ca2+ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca2+ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localised spontaneous Ca2+ signals in astrocyte branches and territories, but these were not driven by neuronal activity or glutamate. Moreover, evoked astrocyte ...

  19. Polarization of calcium signaling and fluid secretion in salivary gland cells.

    Science.gov (United States)

    Ambudkar, I S

    2012-01-01

    The secretion of fluid, electrolytes, and protein by exocrine gland acinar cells is a vectorial process that requires the coordinated regulation of multiple channel and transporter proteins, signaling components, as well as mechanisms involved in vesicular fusion and water transport. Most critical in this is the regulation of cytosolic free [Ca(2+)] ([Ca(2+)](i)) in response to neurotransmitter stimulation. Control of [Ca(2+)](i) increase in specific regions of the cell is the main determinant of fluid and electrolyte secretion in salivary gland acinar cells as it regulates several major ion flux mechanisms as well as the water channel that are required for this process. Polarized [Ca(2+)](i) signals are also essential for protein secretion in pancreatic acinar cells. Thus, the mechanisms that generate and modulate these compartmentalized [Ca(2+)](i) signals are central to the regulation of exocrine secretion. These mechanisms include membrane receptors for neurotransmitters, intracellular Ca(2+) release channels, Ca(2+) entry channels, as well Ca(2+) as pumps and mitochondria. The spatial arrangement of proteins involved in Ca(2+) signaling is of primary significance in the generation of specific compartmentalized [Ca(2+)](i) signals. Within these domains, both local and global [Ca(2+)](i) changes are tightly controlled. Control of secretion is also dependent on the targeting of ion channels and transporters to specific domains in the cell where their regulation by [Ca(2+)](i) signals is facilitated. Together, the polarized localization of Ca(2+) signaling and secretory components drive vectorial secretion of fluid, electrolytes, and proteins in the exocrine salivary glands and pancreas. This review will discuss recent findings which have led to resolution of the molecular components underlying the spatio-temporal control of [Ca(2+)](i) signals in exocrine gland cells and their role in secretion. PMID:23061636

  20. Predictive Control with Approximately Given Reference Signal

    Czech Academy of Sciences Publication Activity Database

    Belda, Květoslav

    Pardubice : Universita Pardubice, 2008 - (Dušek, F.), s. 1-8 ISBN 978-80-7395-077-4. [Process Control 2008. Kouty nad Desnou (CZ), 09.06.2008-12.06.2008] R&D Projects: GA ČR GP102/06/P275 Institutional research plan: CEZ:AV0Z10750506 Keywords : Predictive state-space control * range-space control * approximate reference signal Subject RIV: BC - Control Systems Theory http://library.utia.cas.cz/separaty/historie/belda-0309031.pdf

  1. Light signals for road traffic control.

    OpenAIRE

    Schreuder, D.A.

    1981-01-01

    Signals for road traffic control are a major constituent of the modern traffic scene, particularly in built-up areas. A vast amount of research has been executed in the last two decennia, resulting in a fairly generally accepted view on what the requirements for effective traffic lights are. For the French translation see B 19780

  2. Control of earphone produced binaural signals

    DEFF Research Database (Denmark)

    Hammershøi, Dorte; Hoffmann, Pablo F.

    2011-01-01

    While most people keep a high attention to the significance of the binaural recording method, whether it is e.g. individual or non-individual (as e.g. artificial head recording), many pay less attention to the type of earphone used to reproduce the binaural signals, and to the accurate control of...

  3. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jorgensen, N R; Geist, S T; Civitelli, R;

    1997-01-01

    stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied...... connexin43 (Cx43), are well dye coupled, and lack P2U receptors, transmitted slow gap junction-dependent calcium waves that did not require release of intracellular calcium stores. UMR 106-01 cells predominantly express the gap junction protein connexin 45 (Cx45), are poorly dye coupled, and express P2U...... receptors; they propagated fast calcium waves that required release of intracellular calcium stores and activation of P2U purinergic receptors, but not gap junctional communication. ROS/P2U transfectants and UMR/Cx43 transfectants expressed both types of calcium waves. Gap junction-independent, ATP...

  4. Digital Signal Controller Based Digital Control of Brushless DC Motor

    OpenAIRE

    Anjana Elizabeth Thomas; Salim Paul

    2013-01-01

    This paper presents the digital control of a brushless dc (BLDC) motor using TMS320F2812 DSP controller and an EPROM. The real-time control of electrical motors is an application area that is not usually the domain of Digital Signal Processors. The TMS320F2812 has got dedicated modules for digital motor control. Control algorithms used for the control has been in TMS320F2812 DSP controller. The output of the driver is 6 independent PWM pulses that have to be given to the corresponding gates o...

  5. Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels

    Czech Academy of Sciences Publication Activity Database

    Zemková, Hana; Tomič, M.; Kučka, M.; Aguilera, G.; Stojilkovic, S. S.

    2016-01-01

    Roč. 157, č. 4 (2016), s. 1576-1589. ISSN 0013-7227 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : action potential * background sodium conductance * bursting activity * cation-conducting channels * cytosolic calcium concentration * resting membrane potential Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.503, year: 2014

  6. FM dyes enter via a store-operated calcium channel and modify calcium signaling of cultured astrocytes

    OpenAIRE

    Li, Dongdong; Hérault, Karine; Oheim, Martin; Ropert, Nicole

    2009-01-01

    The amphiphilic fluorescent styryl pyridinium dyes FM1-43 and FM4-64 are used to probe activity-dependent synaptic vesicle cycling in neurons. Cultured astrocytes can internalize FM1-43 and FM4-64 inside vesicles but their uptake is insensitive to the elevation of cytosolic calcium (Ca2+) concentration and the underlying mechanism remains unclear. Here we used total internal reflection fluorescence microscopy and pharmacological tools to study the mechanisms of FM4-64 uptake into cultured ast...

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

    Directory of Open Access Journals (Sweden)

    Katharine L Dobson

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

  8. Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption

    Science.gov (United States)

    Miyauchi, A.; Hruska, K. A.; Greenfield, E. M.; Duncan, R.; Alvarez, J.; Barattolo, R.; Colucci, S.; Zambonin-Zallone, A.; Teitelbaum, S. L.; Teti, A.

    1990-01-01

    The mechanisms of Ca2+ entry and their effects on cell function were investigated in cultured chicken osteoclasts and putative osteoclasts produced by fusion of mononuclear cell precursors. Voltage-gated Ca2+ channels (VGCC) were detected by the effects of membrane depolarization with K+, BAY K 8644, and dihydropyridine antagonists. K+ produced dose-dependent increases of cytosolic calcium ([Ca2+]i) in osteoclasts on glass coverslips. Half-maximal effects were achieved at 70 mM K+. The effects of K+ were completely inhibited by dihydropyridine derivative Ca2+ channel blocking agents. BAY K 8644 (5 X 10(-6) M), a VGCC agonist, stimulated Ca2+ entry which was inhibited by nicardipine. VGCCs were inactivated by the attachment of osteoclasts to bone, indicating a rapid phenotypic change in Ca2+ entry mechanisms associated with adhesion of osteoclasts to their resorption substrate. Increasing extracellular Ca2+ ([Ca2+]e) induced Ca2+ release from intracellular stores and Ca2+ influx. The Ca2+ release was blocked by dantrolene (10(-5) M), and the influx by La3+. The effects of [Ca2+]e on [Ca2+]i suggests the presence of a Ca2+ receptor on the osteoclast cell membrane that could be coupled to mechanisms regulating cell function. Expression of the [Ca2+]e effect on [Ca2+]i was similar in the presence or absence of bone matrix substrate. Each of the mechanisms producing increases in [Ca2+]i, (membrane depolarization, BAY K 8644, and [Ca2+]e) reduced expression of the osteoclast-specific adhesion structure, the podosome. The decrease in podosome expression was mirrored by a 50% decrease in bone resorptive activity. Thus, stimulated increases of osteoclast [Ca2+]i lead to cytoskeletal changes affecting cell adhesion and decreasing bone resorptive activity.

  9. Preparation of TiO2 nanotubes/mesoporous calcium silicate composites with controllable drug release.

    Science.gov (United States)

    Xie, Chunling; Li, Ping; Liu, Yan; Luo, Fei; Xiao, Xiufeng

    2016-10-01

    Nanotube structures such as TiO2 nanotube (TNT) arrays produced by self-ordering electrochemical anodization have been extensively explored for drug delivery applications. In this study, we presented a new implantable drug delivery system that combined mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The results showed that the TiO2 nanotubes/mesoporous calcium silicate composites were successfully fabricated by a simple template method and the deposition of mesoporous calcium silicate increased with the soaking time. Moreover, the rate of deposition of biological mesoporous calcium silicate on amorphous TNTs was better than that on anatase TNTs. Further, zinc-incorporated mesoporous calcium silicate coating, produced by adding a certain concentration of zinc nitrate into the soaking system, displayed improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release and sustained release was demonstrated. PMID:27287140

  10. Mechanical characterization of calcium pectinate hydrogel for controlled drug delivery

    Directory of Open Access Journals (Sweden)

    Chung Jin Thau

    2003-01-01

    Full Text Available Calcium pectinate beads, a paniculate hydrogel system, is an attractive drug carrier for oral delivery. In this study, a poorly water-soluble model drug indomethacin was incorporated into calcium pectinate beads made of different pectin concentrations, which were produced by an extrusion method. The effect of pectin concentration on bead size, circularity, swelling behavior, and mechanical properties, as well as in vitro drug release profile was investigated. The mechanical properties of calcium pectinate beads were determined by a micromanipulation technique. The drug release profile was measured using a standard British Pharmacopoeia method. It was found that the beads made of higher pectin concentration in general had a less permeable matrix structure and greater mechanical rigidity, although they swelled more after hydration. However, such an effect was not significant when the pectin concentration was increased to above 8%. Micromanipulation measurements showed that there was significant relaxation of the force being imposed on single hydrated beads when they were held, but this phenomenon did not occur on dry beads, which means that the force relaxation was dominated by liquid loss from the beads. The rate of the force relaxation was determined, and has been related to the release rate of the model drug entrapped in the calcium pectinate beads.

  11. Modulation of Intercellular Calcium Signaling by Melatonin, in Avian and Mammalian Astrocytes, is Brain Region Specific

    OpenAIRE

    Peters, Jennifer L.; Earnest, Barbara J.; Tjalkens, Ronald B.; Cassone, Vincent M.; Zoran, Mark J.

    2005-01-01

    Calcium waves among glial cells impact many central nervous system functions, including neural integration and brain metabolism. Here, we have characterized the modulatory effects of melatonin, a pineal neurohormone that mediates circadian and seasonal processes, on glial calcium waves derived from different brain regions and species. Diencephalic and telencephalic astrocytes, from both chick and mouse brains, expressed melatonin receptor proteins. Further, using the calcium-sensitive dye Flu...

  12. Novel function of perforin in negatively regulating CD4+T cell activation by affecting calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Enguang Bi; Kairui Mao; Jia Zou; Yuhan Zheng; Bing Sun; Chunjian Huang; Yu Hu; Xiaodong Wu; Weiwen Deng; Guomei Lin; Zhiduo Liu; Lin Tian; Shuhui Sun

    2009-01-01

    Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic Tlymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4+ T cell func-tion remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4+ T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell prolifera-tion and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD44 T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFATI. Our results indicate that perforin plays a negative role in regulating CD4+ T cell activation and immune response by affecting TCR-dependent Ca2+ signaling.

  13. Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis

    Science.gov (United States)

    Soffe, Rebecca; Baratchi, Sara; Tang, Shi-Yang; Nasabi, Mahyar; McIntyre, Peter; Mitchell, Arnan; Khoshmanesh, Khashayar

    2015-07-01

    Immobilisation of cells is an important feature of many cellular assays, as it enables the physical/chemical stimulation of cells; whilst, monitoring cellular processes using microscopic techniques. Current approaches for immobilising cells, however, are hampered by time-consuming processes, the need for specific antibodies or coatings, and adverse effects on cell integrity. Here, we present a dielectrophoresis-based approach for the robust immobilisation of cells, and analysis of their responses under high shear flows. This approach is quick and label-free, and more importantly, minimises the adverse effects of electric field on the cell integrity, by activating the field for a short duration of 120 s, just long enough to immobilise the cells, after which cell culture media (such as HEPES) is flushed through the platform. In optimal conditions, at least 90% of the cells remained stably immobilised, when exposed to a shear stress of 63 dyn/cm2. This approach was used to examine the shear-induced calcium signalling of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor potential vaniloid type 4 (TRPV4), when exposed to the full physiological range of shear stress.

  14. Oxethazaine inhibits hepatitis B virus capsid assembly by blocking the cytosolic calcium-signalling pathway.

    Science.gov (United States)

    Zhang, Lin; Liu, Chunlan; Xiao, Yu; Chen, Xulin

    2016-05-01

    Chronic hepatitis B virus (HBV) infection is a serious public health problem and may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma. It is currently treated with PEGylated IFN-α2a and nucleoside/nucleotide analogues (NAs). However, PEGylated IFN treatment has problems of high cost, low efficiency and side effects. Long-term administration of NAs is necessary to avoid virus relapse, which can cause drug resistance and side effects. New efforts are now being directed to develop novel anti-HBV drugs targeting either additional viral targets other than viral DNA polymerase or host targets to improve the treatment of chronic hepatitis B. In this study, we discovered that oxethazaine, approved for clinic use in a few countries such as Japan, India, South Africa and Brazil, can dose-dependently reduce the levels of HBV envelope antigen, extracellular HBV DNA in supernatants and intracellular HBV total DNA. However, the levels of HBV cccDNA and HBV RNAs were not affected by oxethazaine treatment. Further study confirmed that oxethazaine acts on the virus assembly stage of the HBV life cycle. A study of the mechanisms of oxethazaine suggested that this drug inhibits HBV replication and capsid assembly by blocking the cytosolic calcium-signalling pathway. Moreover, oxethazaine could inhibit the replication of lamivudine/entecavir-dual-resistant and adefovir-resistant HBV mutants. In conclusion, our study suggests that oxethazaine may serve as a promising drug, or could be used as a starting point for anti-HBV drug discovery. PMID:26838678

  15. Interplay between phosphoinositide lipids and calcium signals at the leading edge of chemotaxing ameboid cells☆

    OpenAIRE

    Falke, Joseph J.; Ziemba, Brian P

    2014-01-01

    The chemotactic migration of eukaryotic ameboid cells up concentration gradients is among the most advanced forms of cellular behavior. Chemotaxis is controlled by a complex network of signaling proteins bound to specific lipids on the cytoplasmic surface of the plasma membrane at the front of the cell, or the leading edge. The central lipid players in this leading edge signaling pathway include the phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), both of which play multiple roles. ...

  16. Control and signal processing by transcriptional interference

    OpenAIRE

    Buetti-Dinh, Antoine; Ungricht, Rosemarie; Kelemen, János Z.; Shetty, Chetak; Ratna, Prasuna; Becskei, Attila

    2009-01-01

    A transcriptional activator can suppress gene expression by interfering with transcription initiated by another activator. Transcriptional interference has been increasingly recognized as a regulatory mechanism of gene expression. The signals received by the two antagonistically acting activators are combined by the polymerase trafficking along the DNA. We have designed a dual-control genetic system in yeast to explore this antagonism systematically. Antagonism by an upstream activator bears ...

  17. Neuroblast migration and P2Y1 receptor mediated calcium signalling depend on 9-O-acetyl GD3 ganglioside

    Directory of Open Access Journals (Sweden)

    Eliana Scemes

    2012-09-01

    Full Text Available Previous studies indicated that a ganglioside 9acGD3 (9-O-acetyl GD3 antibody [the J-Ab (Jones antibody] reduces GCP (granule cell progenitor migration in vitro and in vivo. We here investigated, using cerebellar explants of post-natal day (P 6 mice, the mechanism by which 9acGD3 reduces GCP migration. We found that immunoblockade of the ganglioside with the J-Ab or the lack of GD3 synthase reduced GCP in vitro migration and the frequency of Ca2+ oscillations. Immunocytochemistry and pharmacological assays indicated that GCPs expressed P2Y1Rs (P2Y1 receptors and that deletion or blockade of these receptors decreased the migration rate of GCPs and the frequency of Ca2+ oscillations. The reduction in P2Y1-mediated calcium signals seen in Jones-treated and GD3 synthase-null GCPs were paralleled by P2Y1R internalization. We conclude that 9acGD3 controls GCP migration by influencing P2Y1R cellular distribution and function.

  18. Signal Propagation between Neuronal Populations Controlled by Micropatterning.

    Science.gov (United States)

    Albers, Jonas; Offenhäusser, Andreas

    2016-01-01

    The central nervous system consists of an unfathomable number of functional networks enabling highly sophisticated information processing. Guided neuronal growth with a well-defined connectivity and accompanying polarity is essential for the formation of these networks. To investigate how two-dimensional protein patterns influence neuronal outgrowth with respect to connectivity and functional polarity between adjacent populations of neurons, a microstructured model system was established. Exclusive cell growth on patterned substrates was achieved by transferring a mixture of poly-l-lysine and laminin to a cell-repellent glass surface by microcontact printing. Triangular structures with different opening angle, height, and width were chosen as a pattern to achieve network formation with defined behavior at the junction of adjacent structures. These patterns were populated with dissociated primary cortical embryonic rat neurons and investigated with respect to their impact on neuronal outgrowth by immunofluorescence analysis, as well as their functional connectivity by calcium imaging. Here, we present a highly reproducible technique to devise neuronal networks in vitro with a predefined connectivity induced by the design of the gateway. Daisy-chained neuronal networks with predefined connectivity and functional polarity were produced using the presented micropatterning method. Controlling the direction of signal propagation among populations of neurons provides insights to network communication and offers the chance to investigate more about learning processes in networks by external manipulation of cells and signal cascades. PMID:27379230

  19. Enlightenment on the aequorin-based platform for screening Arabidopsis stress sensory channels related to calcium signaling.

    Science.gov (United States)

    Yu, Zhiming; Taylor, Jemma L; He, Yue; Ni, Jun

    2015-01-01

    Free calcium ions (Ca(2+)) are an important signal molecule in response to a large array of external stimuli encountered by plants. Using the aequorin-based Ca(2+) recording system, tremendous progress has been made in understanding the Ca(2+) responses to biotic or abiotic stresses in dicotyledonous Arabidopsis. However, due to the lack of a similar detection system, little information has been obtained from the monocotyledonous rice (Oryza sativa). Recombinant aequorin has been introduced into rice, and the Ca(2+) responses to NaCl and H2O2 in rice roots were characterized. Although rice calcium signal sensor research has just started, the transgenic rice expressing aequorin provides a good platform to study rice adapted to different environmental conditions. PMID:26336841

  20. Digital Signal Controller Based Digital Control of Brushless DC Motor

    Directory of Open Access Journals (Sweden)

    Anjana Elizabeth Thomas

    2013-07-01

    Full Text Available This paper presents the digital control of a brushless dc (BLDC motor using TMS320F2812 DSP controller and an EPROM. The real-time control of electrical motors is an application area that is not usually the domain of Digital Signal Processors. The TMS320F2812 has got dedicated modules for digital motor control. Control algorithms used for the control has been in TMS320F2812 DSP controller. The output of the driver is 6 independent PWM pulses that have to be given to the corresponding gates of the six MOSFETs power switches used in the three-phase bridge driving circuit whose output is given to the stator of the Brushless DC Motor. The commutation technique used in this work is the trapezoidal commutation owing to its excellent speed and current control and it has been implemented using an EPROM

  1. Polarization of Calcium Signaling and Fluid Secretion in Salivary Gland Cells

    OpenAIRE

    Ambudkar, I.S.

    2012-01-01

    The secretion of fluid, electrolytes, and protein by exocrine gland acinar cells is a vectorial process that requires the coordinated regulation of multiple channel and transporter proteins, signaling components, as well as mechanisms involved in vesicular fusion and water transport. Most critical in this is the regulation of cytosolic free [Ca2+] ([Ca2+]i) in response to neurotransmitter stimulation. Control of [Ca2+]i increase in specific regions of the cell is the main determinant of fluid...

  2. Genome-wide association study knowledge-driven pathway analysis of alcohol dependence implicates the calcium signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Li Danni; Li Jinming; Guo Yanfang

    2014-01-01

    Background Alcohol dependence (AD) is a serious and common public health problem.The identification of genes that contribute to the AD variation will improve our understanding of the genetic mechanism underlying this complex disease.Previous genome-wide association studies (GWAS) and candidate gene genetic association studies identified individual genes as candidates for alcohol phenotypes,but efforts to generate an integrated view of accumulative genetic variants and pathways under alcohol drinking are lacking.Methods We applied enrichment gene set analysis to existing genetic association results to identify pertinent pathways to AD in this study.A total of 1 438 SNPs (P <1.0×10-3) associated to alcohol drinking related traits have been collected from 31 studies (10 candidate gene association studies,19 GWAS of SNPs,and 2 GWAS of copy number variants).Results Among all of the KEGG pathways,the calcium signaling pathway (hsa04020) showed the most significant enrichment of associations (21 genes) to alcohol consumption phenotypes (P=5.4×10-5).Furthermore,the calcium signaling pathway is the only pathway that turned out to be significant after multiple test adjustments,achieving Bonferroni P value of 0.8×10-3 and FDR value of 0.6×10-2,respectively.Interestingly,the calcium signaling pathway was previously found to be essential to regulate brain function,and genes in this pathway link to a depressive effect of alcohol consumption on the body.Conclusions Our findings,together with previous biological evidence,suggest the importance of gene polymorphisms of calcium signaling pathway to AD susceptibility.Still,further investigations are warranted to uncover the role of this pathway in AD and related traits.

  3. Calcium signaling in epithelium:special focus on Hailey-Hailey and Darier diseases, neurofibromatosis 1 and transitional cell carcinoma

    OpenAIRE

    Leinonen, P

    2008-01-01

    Abstract This study utilized normal and defective epithelial cell cultures and epidermal skin samples to examine intra- and intercellular calcium signaling. The main interests of this thesis were Hailey-Hailey disease (HHD), Darier disease (DD), neurofibromatosis 1 (NF1) and transitional cell carcinoma (TCC). HHD and DD diseases are rare autosomal dominant skin disorders characterized by dissociation of epidermal keratinocytes (acantholysis) at the suprabasal layer of the epidermis. HH...

  4. Calcium ingestion and obesity control Ingesta de calcio y control de la obesidad

    Directory of Open Access Journals (Sweden)

    D. M. de Oliveira Freitas

    2012-12-01

    Full Text Available Introduction: Obesity is a risk factor for other nontransmissible chronic diseases. It has been suggested calcium intake helps to control obesity, but there is no consensus about this. Objective: Analyze the studies published on this topic in order to highlight issues to be further explored in future studies. Methods: A literature review was conducted using the PUBMED, Science Direct, Scielo, Scopus, Medline and CAPES electronic scientific basis. Studies, which evaluated the effect of calcium ingestion in energy metabolism, body weight, and body composition, published from 2000 through 2011, were analyzed. Results and discussion: The results of most of the interventional studies selected suggest that calcium ingestion may favor the reduction of the anthropometric measures and improve body composition. The discrepancy in the results of the observational studies is probably due to methodological differences. It seems that the benefits are only detected when a low calcium habitual ingestion (≈ 700 mg/day or lower is increased to about 1,200-1,300 mg/day. Conclusion: When assessing the effect of calcium derived from supplements, the investigators should test higher bioavailability compounds. If the calcium source is the dairy product, it is necessary that to consider and isolate the impact of other nutrients present in these foods. Longer term studies should be conducted to assess the effect of calcium on energy metabolism.Introducción: La obesidad es un factor de riesgo para otras enfermedades crónicas no transmisibles. Se ha sugerido que el consumo de calcio ayuda a controlar la obesidad, pero no hay un consenso al respecto. Objetivo: Analizar los estudios publicados sobre este tema con el fin de destacar los aspectos a investigar en estudios futuros. Métodos: Se realizó una revisión bibliográfica utilizando las bases de datos electrónicas PUBMED, Science Direct, Scielo, Scopus, Medline y CAPES. Se analizaron los estudios que evaluaban el

  5. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  6. In vivo photoacoustic neuronal imaging of odor-evoked calcium signals in the drosophila brain (Conference Presentation)

    Science.gov (United States)

    Zhang, Ruiying; Rao, Bin; Rong, Haoyang; Raman, Baranidharan; Wang, Lihong V.

    2016-03-01

    Neural scientists can benefit greatly from imaging tools that can penetrate thick brain tissue. Compared with traditional optical microscopy methods, photoacoustic imaging can beat the optical diffusion limit and achieve such deep tissue imaging with high spatial resolution. In this study, we used an optical-resolution photoacoustic microscope to image the odor-evoked neuronal activities in a drosophila model. Drosophila brain neurons stably express GCaMP5G, a calcium-sensitive fluorescent protein whose optical absorption coefficient changes with calcium influx during action potentials. We recorded an ~20% odor-evoked fractional photoacoustic signal increase at all depths of the drosophila brain in vivo, with and without removal of the brain cuticle, at a recording rate of 1 kHz. Our results were confirmed by concurrent fluorescent recordings. Furthermore, by performing fast 2D scanning, we imaged the antenna lobe region, which is of particular interest in neuroscience, at a volumetric rate of ~1 Hz with a sub-neuron resolution of 3 μm. Unlike optical imaging, which requires surgical removal of the scattering brain cuticle, our photoacoustic system can image through the cuticle and measure neuronal signals of the whole drosophila brain without invasive surgery, enabling minimal disturbance to the animal's behaviors. In conclusion, we have demonstrated photoacoustic imaging of calcium signals in drosophila brains for the first time. Utilizing the deep imaging capability of photoacoustic tomography, our methods could potentially be extended to in vivo imaging of neuronal activities from deep brains in other animal models.

  7. Poly(ethylene imine)-controlled Calcium Phosphate mineralization

    OpenAIRE

    Shkilnyy, Andriy; Friedrich, Alwin; Tiersch, Brigitte; Schöne, Stefanie; Fechner, Mabya; Koetz, Joachim; Schläpfer, Carl-Wilhelm; Taubert, Andreas

    2008-01-01

    The current paper shows that poly(ethylene imine) (PEI) is an efficient template for the fabrication of spherical calcium phosphate (CaP)/polymer hybrid particles at pH values above 8. The polymer forms spherical entities, which contain one or a few CaP particles with diameters of ca. 6 nm. The samples contain up to 20 wt % polymer, which appears to be wrapped around the small CaP particles. The particles form via a mineralization-trapping pathway, where at the beginning of the precipitation ...

  8. Ca2+ signals induced from calcium stores in pancreatic islet β cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In single rat pancreatic β cells,using fura-2 microfluorometry to measure [Ca2+]i response upon different stimuli,the ways of calcium regulation have been studied.When the extracellular calcium concentration was 2.5 mmol/L,either 60 mmol/L KCl,20 mmol/L D-glucose or 0.1 mmol/L tolbutamide induced increase in [Ca2+]i.Such increase in [Ca2+]i was absent when the same stimuli were applied under zero extracellular calcium.These results indicate that the increase of [Ca2+]i is induced by the activation of voltage-dependent calcium channels in β cells.The manifold forms of [Ca2+]i change induced by glucose imply that the effects of glucose are complex.5 mmol/L caffeine or 5 mmol/L MCh increase the [Ca2+]i ,which is independent of the external calcium,suggesting that [Ca2+]i can be regulated by Ca2+ release from not only the IP3-sensitive but also the ryanodine sensitive calcium stores in β cells.The latency of Ca responses for IP3 pathway (5 s) is faster than that for ryanodine pathway (30 s).It is concluded that there are multiple calcium stores in rat pancreatic β cells.

  9. Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes

    OpenAIRE

    Devi, Sulochana; Markandeya, Yogananda; Maddodi, Nityanand; Dhingra, Anuradha; Vardi, Noga; Ravi C Balijepalli; Setaluri, Vijayasaradhi

    2013-01-01

    Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6 and treatment of melanocytes with L-AP4, a type I...

  10. Dynamics of intrinsic dendritic calcium signaling during tonic firing of thalamic reticular neurons.

    Directory of Open Access Journals (Sweden)

    Patrick Chausson

    Full Text Available The GABAergic neurons of the nucleus reticularis thalami that control the communication between thalamus and cortex are interconnected not only through axo-dendritic synapses but also through gap junctions and dendro-dendritic synapses. It is still unknown whether these dendritic communication processes may be triggered both by the tonic and the T-type Ca(2+ channel-dependent high frequency burst firing of action potentials displayed by nucleus reticularis neurons during wakefulness and sleep, respectively. Indeed, while it is known that activation of T-type Ca(2+ channels actively propagates throughout the dendritic tree, it is still unclear whether tonic action potential firing can also invade the dendritic arborization. Here, using two-photon microscopy, we demonstrated that dendritic Ca(2+ responses following somatically evoked action potentials that mimic wake-related tonic firing are detected throughout the dendritic arborization. Calcium influx temporally summates to produce dendritic Ca(2+ accumulations that are linearly related to the duration of the action potential trains. Increasing the firing frequency facilitates Ca(2+ influx in the proximal but not in the distal dendritic compartments suggesting that the dendritic arborization acts as a low-pass filter in respect to the back-propagating action potentials. In the more distal compartment of the dendritic tree, T-type Ca(2+ channels play a crucial role in the action potential triggered Ca(2+ influx suggesting that this Ca(2+ influx may be controlled by slight changes in the local dendritic membrane potential that determine the T-type channels' availability. We conclude that by mediating Ca(2+ dynamic in the whole dendritic arborization, both tonic and burst firing of the nucleus reticularis thalami neurons might control their dendro-dendritic and electrical communications.

  11. Controlled environment life support system: Calcium-related leaf injuries on plants

    Science.gov (United States)

    Tibbitts, T. W.

    1986-01-01

    Calcium related injuries to plants grown in controlled environments under conditions which maximize plant growth rates are described. Procedures to encourage movement of calcium into developing leaves of lettuce plants were investigated. The time course and pattern of calcium accumulation was determined to develop effective control procedures for this injury, termed tipburn. Procedures investigated were: (1) increasing the relative humidity to saturation during the dark period and altering root temperatures, (2) maximizing water stress during light and minimizing water stress during dark periods, (3) shortening the light-dark cycle lengths in combination with elevated moisture levels during the dark cycles, (4) reducing nutrient concentrations and (5) vibrating the plants. Saturated humidities at night increased the rate of growth and the large fluctuation in plant water potential encouraged calcium movement to the young leaves and delayed tipburn. Root temperature regulation between 15 and 26 C was not effective in preventing tipburn. Attempts to modulate water stress produced little variation, but no difference in tipburn development. Variations in light-dark cycle lengths also had no effect on calcium concentrations within developing leaves and no variation in tipburn development. Low concentrations of nutrient solution delayed tipburn, presumably because of greater calcium transport in the low concentration plants. Shaking of the plants did not prevent tipburn, but did delay it slightly.

  12. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

    Science.gov (United States)

    Arking, Dan E; Pulit, Sara L; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B; Koopmann, Tamara T; Sotoodehnia, Nona; Rossin, Elizabeth J; Morley, Michael; Wang, Xinchen; Johnson, Andrew D; Lundby, Alicia; Gudbjartsson, Daníel F; Noseworthy, Peter A; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M; Nolte, Ilja M; Smith, Albert Vernon; Bis, Joshua C; Isaacs, Aaron; Newhouse, Stephen J; Evans, Daniel S; Post, Wendy S; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W; Naluai, Åsa T; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D; Harris, Tamara B; Launer, Lenore J; Shuldiner, Alan R; Alonso, Alvaro; Bader, Joel S; Ehret, Georg; Huang, Hailiang; Kao, W H Linda; Strait, James B; Macfarlane, Peter W; Brown, Morris; Caulfield, Mark J; Samani, Nilesh J; Kronenberg, Florian; Willeit, Johann; Smith, J Gustav; Greiser, Karin H; Meyer Zu Schwabedissen, Henriette; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R; Psaty, Bruce M; Rotter, Jerome I; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F; Griffin, Maura; Daly, Mark J; Arnar, David O; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C; Roden, Dan M; Zuvich, Rebecca L; Emilsson, Valur; Plump, Andrew S; Larson, Martin G; O'Donnell, Christopher J; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R; Nalls, Michael A; Jula, Antti; Kontula, Kimmo K; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M; den Hoed, Marcel; Loos, Ruth J F; Thelle, Dag S; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F; Waldenberger, Melanie; de Boer, Rudolf A; Franke, Lude; van der Vleuten, Pieter A; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A M; Behr, Elijah R; Dalageorgou, Chrysoula; Giudicessi, John R; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M; Scherer, Stephen W; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E; del Greco M, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R; Lee, Wai K; Watt, Graham C M; Campbell, Harry; Wild, Sarah H; El Mokhtari, Nour E; Frey, Norbert; Asselbergs, Folkert W; Mateo Leach, Irene; Navis, Gerjan; van den Berg, Maarten P; van Veldhuisen, Dirk J; Kellis, Manolis; Krijthe, Bouwe P; Franco, Oscar H; Hofman, Albert; Kors, Jan A; Uitterlinden, André G; Witteman, Jacqueline C M; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A; Abecasis, Gonçalo R; Lakatta, Edward G; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R P; Völker, Uwe; Snieder, Harold; Spector, Timothy D; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T; Viikari, Jorma S; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F; Nyberg, Fredrik; Whincup, Peter H; Hingorani, Aroon D; Schott, Jean-Jacques; Bezzina, Connie R; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W; Pramstaller, Peter P; Lehtimäki, Terho J; Paterson, Andrew D; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia M; Siscovick, David S; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B; Sanna, Serena; Ritchie, Marylyn D; Stricker, Bruno H; Stefansson, Kari; Boyer, Laurie A; Cappola, Thomas P; Olsen, Jesper V; Lage, Kasper; Schwartz, Peter J; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J; Pfeufer, Arne; de Bakker, Paul I W; Newton-Cheh, Christopher

    2014-08-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. PMID:24952745

  13. Identification of Neuronal Network Properties from the Spectral Analysis of Calcium Imaging Signals in Neuronal Cultures

    Directory of Open Access Journals (Sweden)

    Miguel Valencia

    2013-12-01

    Full Text Available Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

  14. Wnt signaling control of bone cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Peter V N Bodine

    2008-01-01

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

  15. Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

    International Nuclear Information System (INIS)

    Highlights: → A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. → The second zinc finger of LIM domain 1 of testin is critical for interaction. → Testin bound to a region of the receptor tail important for cell signalling. → Testin and receptor interaction was confirmed in mammalian (HEK293) cells. → Overexpression of testin enhanced receptor-mediated Rho signalling in HEK293 cells. -- Abstract: The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton.

  16. Differential regulation of calcium signalling pathways by components of Piper methysticum (‘Awa)

    Science.gov (United States)

    Shimoda, L.M.N; Showman, A.; Baker, J.D.; Lange, I.; Koomoa, D.L.; Stokes, A.J.; Borris, R.P.; Turner, H.

    2015-01-01

    Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally-prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally-prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and –insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava. PMID:25640812

  17. Deoxycholic acid mediates non-canonical EGFR-MAPK activation through the induction of calcium signaling in colon cancer cells.

    Science.gov (United States)

    Centuori, Sara M; Gomes, Cecil J; Trujillo, Jesse; Borg, Jamie; Brownlee, Joshua; Putnam, Charles W; Martinez, Jesse D

    2016-07-01

    Obesity and a western diet have been linked to high levels of bile acids and the development of colon cancer. Specifically, increased levels of the bile acid deoxycholic acid (DCA), an established tumor promoter, has been shown to correlate with increased development of colorectal adenomas and progression to carcinoma. Herein we investigate the mechanism by which DCA leads to EGFR-MAPK activation, a candidate mechanism by which DCA may promote colorectal tumorigenesis. DCA treated colon cancer cells exhibited strong and prolonged activation of ERK1/2 when compared to EGF treatment alone. We also showed that DCA treatment prevents EGFR degradation as opposed to the canonical EGFR recycling observed with EGF treatment. Moreover, the combination of DCA and EGF treatment displayed synergistic activity, suggesting DCA activates MAPK signaling in a non-canonical manner. Further evaluation showed that DCA treatment increased intracellular calcium levels and CAMKII phosphorylation, and that blocking calcium with BAPTA-AM abrogated MAPK activation induced by DCA, but not by EGF. Finally we showed that DCA-induced CAMKII leads to MAPK activation through the recruitment of c-Src. Taken together, we demonstrated that DCA regulates MAPK activation through calcium signaling, an alternative mechanism not previously recognized in human colon cancer cells. Importantly, this mechanism allows for EGFR to escape degradation and thus achieve a constitutively active state, which may explain its tumor promoting effects. PMID:27086143

  18. Virulent Diuraphis noxia Aphids Over-Express Calcium Signaling Proteins to Overcome Defenses of Aphid-Resistant Wheat Plants.

    Directory of Open Access Journals (Sweden)

    Deepak K Sinha

    Full Text Available The Russian wheat aphid, Diuraphis noxia, an invasive phytotoxic pest of wheat, Triticum aestivum, and barley, Hordeum vulgare, causes huge economic losses in Africa, South America, and North America. Most acceptable and ecologically beneficial aphid management strategies include selection and breeding of D. noxia-resistant varieties, and numerous D. noxia resistance genes have been identified in T. aestivum and H. vulgare. North American D. noxia biotype 1 is avirulent to T. aestivum varieties possessing Dn4 or Dn7 genes, while biotype 2 is virulent to Dn4 and avirulent to Dn7. The current investigation utilized next-generation RNAseq technology to reveal that biotype 2 over expresses proteins involved in calcium signaling, which activates phosphoinositide (PI metabolism. Calcium signaling proteins comprised 36% of all transcripts identified in the two D. noxia biotypes. Depending on plant resistance gene-aphid biotype interaction, additional transcript groups included those involved in tissue growth; defense and stress response; zinc ion and related cofactor binding; and apoptosis. Activation of enzymes involved in PI metabolism by D. noxia biotype 2 aphids allows depletion of plant calcium that normally blocks aphid feeding sites in phloem sieve elements and enables successful, continuous feeding on plants resistant to avirulent biotype 1. Inhibition of the key enzyme phospholipase C significantly reduced biotype 2 salivation into phloem and phloem sap ingestion.

  19. Fouling control mechanisms of demineralized water backwash: Reduction of charge screening and calcium bridging effects

    KAUST Repository

    Li, Sheng

    2011-12-01

    This paper investigates the impact of the ionic environment on the charge of colloidal natural organic matter (NOM) and ultrafiltration (UF) membranes (charge screening effect) and the calcium adsorption/bridging on new and fouled membranes (calcium bridging effect) by measuring the zeta potentials of membranes and colloidal NOM. Fouling experiments were conducted with natural water to determine whether the reduction of the charge screening effect and/or calcium bridging effect by backwashing with demineralized water can explain the observed reduction in fouling. Results show that the charge of both membranes and NOM, as measured by the zeta potential, became more negative at a lower pH and a lower concentration of electrolytes, in particular, divalent electrolytes. In addition, calcium also adsorbed onto the membranes, and consequently bridged colloidal NOM and membranes via binding with functional groups. The charge screening effect could be eliminated by flushing NOM and membranes with demineralized water, since a cation-free environment was established. However, only a limited amount of the calcium bridging connection was removed with demineralized water backwashes, so the calcium bridging effect mostly could not be eliminated. As demineralized water backwash was found to be effective in fouling control, it can be concluded that the reduction of the charge screening is the dominant mechanism for this. © 2011 Elsevier Ltd.

  20. Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling

    Directory of Open Access Journals (Sweden)

    S.S. Smaili

    2003-02-01

    Full Text Available Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injury and programmed cell death through the regulation of a number of Ca2+-dependent enzymes such as phospholipases, proteases, and nucleases. Mitochondria along with the endoplasmic reticulum play pivotal roles in regulating intracellular Ca2+ content. Mitochondria are endowed with multiple Ca2+ transport mechanisms by which they take up and release Ca2+ across their inner membrane. During cellular Ca2+ overload, mitochondria take up cytosolic Ca2+, which in turn induces opening of permeability transition pores and disrupts the mitochondrial membrane potential (Dym. The collapse of Dym along with the release of cytochrome c from mitochondria is followed by the activation of caspases, nuclear fragmentation and cell death. Members of the Bcl-2 family are a group of proteins that play important roles in apoptosis regulation. Members of this family appear to differentially regulate intracellular Ca2+ level. Translocation of Bax, an apoptotic signaling protein, from the cytosol to the mitochondrial membrane is another step in this apoptosis signaling pathway.

  1. Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling.

    Science.gov (United States)

    Diaz, Maira; Sanchez-Barrena, Maria Jose; Gonzalez-Rubio, Juana Maria; Rodriguez, Lesia; Fernandez, Daniel; Antoni, Regina; Yunta, Cristina; Belda-Palazon, Borja; Gonzalez-Guzman, Miguel; Peirats-Llobet, Marta; Menendez, Margarita; Boskovic, Jasminka; Marquez, Jose A; Rodriguez, Pedro L; Albert, Armando

    2016-01-19

    Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca(2+) are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca(2+) signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca(2+)-dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca(2+) sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca(2+)-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress. PMID:26719420

  2. Vitamin D, reactive oxygen species and calcium signalling in ageing and disease.

    Science.gov (United States)

    Berridge, Michael J

    2016-08-01

    Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca(2+) and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca(2+) and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer's disease (AD). In cardiac cells, this deficiency alters the Ca(2+) transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca(2+) landscape that initiates amyloid formation, which then elevates the resting level of Ca(2+) to drive the memory loss that progresses to neuronal cell death and dementia.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377727

  3. Intercellular calcium signaling and nitric oxide feedback during constriction of rabbit renal afferent arterioles

    DEFF Research Database (Denmark)

    Uhrenholt, Torben Rene; Schjerning, J; Vanhoutte, Paul M. G.;

    2007-01-01

    Vasoconstriction and increase in the intracellular calcium concentration ([Ca(2+)](i)) of vascular smooth muscle cells may cause an increase of endothelial cell [Ca(2+)](i), which, in turn, augments nitric oxide (NO) production and inhibits smooth muscle cell contraction. This hypothesis was tested...... in microperfused rabbit renal afferent arterioles, using fluorescence imaging microscopy with the calcium-sensitive dye fura-2 and the NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorescein. Both dyes were loaded into smooth muscle and endothelium. Depolarization with 100 mmol/l KCl led to a...... transient vasoconstriction which was converted into a sustained response by N-nitro-l-arginine methyl ester (l-NAME). Depolarization increased smooth muscle cell [Ca(2+)](i) from 162 +/- 15 nmol/l to a peak of 555 +/- 70 nmol/l (n = 7), and this response was inhibited by 80% by the l-type calcium channel...

  4. Migration and Phagocytic Ability of Activated Microglia During Post-natal Development is Mediated by Calcium-Dependent Purinergic Signalling.

    Science.gov (United States)

    Sunkaria, Aditya; Bhardwaj, Supriya; Halder, Avishek; Yadav, Aarti; Sandhir, Rajat

    2016-03-01

    Microglia play an important role in synaptic pruning and controlled phagocytosis of neuronal cells during developmental stages. However, the mechanisms that regulate these functions are not completely understood. The present study was designed to investigate the role of purinergic signalling in microglial migration and phagocytic activity during post-natal brain development. One-day-old BALB/c mice received lipopolysaccharide (LPS) and/or a purinergic analogue (2-methylthioladenosine-5'-diphosphate; 2MeSADP), intracerebroventrically (i.c.v.). Combined administration of LPS and 2MeSADP resulted in activation of microglia as evident from increased expression of ionised calcium-binding adapter molecule 1 (Iba1). Activated microglia showed increased expression of purinergic receptors (P2Y2, P2Y6 and P2Y12). LPS either alone or in combination with 2MeSADP induced the expression of Na(+)/Ca(2+) exchanger (NCX-1) and P/Q-type Ca(2+) channels along with MARCKS-related protein (MRP), which is an integral component of cell migration machinery. In addition, LPS and 2MeSADP administration induced the expression of microglial CD11b and DAP12 (DNAX-activation protein 12), which are known to be involved in phagocytosis of neurons during development. Interestingly, administration of thapsigargin (TG), a specific Ca(2+)-ATPase inhibitor of endoplasmic reticulum, prevented the LPS/2MeSADP-induced microglial activation and migration by down-regulating the expression of Iba1 and MRP, respectively. Moreover, TG also reduced the LPS/2MeSADP-induced expression of CD11b/DAP12. Taken together, the findings reveal for the first time that Ca(2+)-mediated purinergic receptors regulate the migration and phagocytic ability of microglia during post-natal brain development. PMID:25575683

  5. Shape control synthesis of low-dimensional calcium sulfate

    Indian Academy of Sciences (India)

    Li-Xia Yang; Yan-Feng Meng; Ping Yin; Ying-Xia Yang; Ying-Ying Tang; Lai-Fen Qin

    2011-04-01

    Calcium sulfate nanorods, nanowires, nanobelts and sheets had been synthesized via a facile solution reaction of CaCl2 and H2SO4 in mixed solvents of ethanol/, -dimethylformamide and deionized water at 35°C. The results indicated that well-crystallized CaSO4 nanomaterials with different morphology were obtained by adjusting the volume ratio of ethanol/, -dimethylformamide to deionized water and the reaction time. Samples prepared at 35°C in mixed solvents of 50 mL ethanol and 30 mL water for 1 min and 2 h showed nanowire and sheet morphology, respectively. While increasing the volume ratio of ethanol to deionized water to 78/2, only nanorods were obtained. When , -dimethylformamide was employed to substitute ethanol, the sample heating at 35°C for 2 h was composed of nanowires in 50 mL , -dimethylformamide and 30 mL water. Higher volume ratio of , -dimethylformamide to deionized water caused the formation of nanorods.

  6. MERCURY CONTROL WITH CALCIUM-BASED SORBENTS AND OXIDIZING AGENTS

    Energy Technology Data Exchange (ETDEWEB)

    Thomas K. Gale

    2002-06-01

    The initial tasks of this DOE funded project to investigate mercury removal by calcium-based sorbents have been completed, and initial testing results have been obtained. Mercury monitoring capabilities have been obtained and validated. An approximately 1MW (3.4 Mbtu/hr) Combustion Research Facility at Southern Research Institute was used to perform pilot-scale investigations of mercury sorbents, under conditions representative of full-scale boilers. The initial results of ARCADIS G&M proprietary sorbents, showed ineffective removal of either elemental or oxidized mercury. Benchscale tests are currently underway to ascertain the importance of differences between benchscale and pilot-scale experiments. An investigation of mercury-capture temperature dependence using common sorbents has also begun. Ordinary hydrated lime removed 80 to 90% of the mercury from the flue gas, regardless of the temperature of injection. High temperature injection of hydrated lime simultaneously captured SO{sub 2} at high temperatures and Hg at low temperatures, without any deleterious effects on mercury speciation. Future work will explore alternative methods of oxidizing elemental mercury.

  7. A calcium sensor – protein kinase signaling module diversified in plants and is retained in all lineages of Bikonta species

    Science.gov (United States)

    Beckmann, Linda; Edel, Kai H.; Batistič, Oliver; Kudla, Jörg

    2016-01-01

    Calcium (Ca2+) signaling is a universal mechanism of signal transduction and involves Ca2+ signal formation and decoding of information by Ca2+ binding proteins. Calcineurin B-like proteins (CBLs), which upon Ca2+ binding activate CBL-interacting protein kinases (CIPKs) regulate a multitude of physiological processes in plants. Here, we combine phylogenomics and functional analyses to investigate the occurrence and structural conservation of CBL and CIPK proteins in 26 species representing all major clades of eukaryotes. We demonstrate the presence of at least singular CBL-CIPK pairs in representatives of Archaeplastida, Chromalveolates and Excavates and their general absence in Opisthokonta and Amoebozoa. This denotes CBL-CIPK complexes as evolutionary ancient Ca2+ signaling modules that likely evolved in the ancestor of all Bikonta. Furthermore, we functionally characterize the CBLs and CIPK from the parabasalid human pathogen Trichomonas vaginalis. Our results reveal strict evolutionary conservation of functionally important structural features, preservation of biochemical properties and a remarkable cross-kingdom protein-protein interaction potential between CBLs and CIPKs from Arabidopsis thaliana and T. vaginalis. Together our findings suggest an ancient evolutionary origin of a functional CBL-CIPK signaling module close to the root of eukaryotic evolution and provide insights into the initial evolution of signaling networks and Ca2+ signaling specificity. PMID:27538881

  8. A calcium sensor - protein kinase signaling module diversified in plants and is retained in all lineages of Bikonta species.

    Science.gov (United States)

    Beckmann, Linda; Edel, Kai H; Batistič, Oliver; Kudla, Jörg

    2016-01-01

    Calcium (Ca(2+)) signaling is a universal mechanism of signal transduction and involves Ca(2+) signal formation and decoding of information by Ca(2+) binding proteins. Calcineurin B-like proteins (CBLs), which upon Ca(2+) binding activate CBL-interacting protein kinases (CIPKs) regulate a multitude of physiological processes in plants. Here, we combine phylogenomics and functional analyses to investigate the occurrence and structural conservation of CBL and CIPK proteins in 26 species representing all major clades of eukaryotes. We demonstrate the presence of at least singular CBL-CIPK pairs in representatives of Archaeplastida, Chromalveolates and Excavates and their general absence in Opisthokonta and Amoebozoa. This denotes CBL-CIPK complexes as evolutionary ancient Ca(2+) signaling modules that likely evolved in the ancestor of all Bikonta. Furthermore, we functionally characterize the CBLs and CIPK from the parabasalid human pathogen Trichomonas vaginalis. Our results reveal strict evolutionary conservation of functionally important structural features, preservation of biochemical properties and a remarkable cross-kingdom protein-protein interaction potential between CBLs and CIPKs from Arabidopsis thaliana and T. vaginalis. Together our findings suggest an ancient evolutionary origin of a functional CBL-CIPK signaling module close to the root of eukaryotic evolution and provide insights into the initial evolution of signaling networks and Ca(2+) signaling specificity. PMID:27538881

  9. Single-cell mechanics and calcium signalling in organotypic slices of human myometrium ☆

    OpenAIRE

    Loftus, Fiona C.; Richardson, Magnus J. E.; Shmygol, Anatoly

    2015-01-01

    Elucidation of cellular mechanisms regulating myometrial contractility is crucial for improvement in management of many obstetric abnormalities, such as premature delivery, uterine dystocia and post-partum haemorrhage. Myometrial contractions are triggered by periodic synchronous rises in intracellular calcium concentration ([Ca2+]i) elicited by spontaneously generated action potentials propagating throughout the entire myometrium. During labour, hormones like oxytocin and prostaglandins pote...

  10. SIMULTANEOUS CONTROL OF HGO, SO2, AND NOX BY NOVEL OXIDIZED CALCIUM-BASED SORBENTS

    Science.gov (United States)

    The paper gives results of an investigation of two classes of calcium (Ca)-based sorbents (hydrated limes and silicate compounds). (NOTE: Efforts to develop multipollutant control strategies have demonstrated that adding certain oxidants to different classes of Ca-based sorbents...

  11. SIMULTANEOUS CONTROL OF HG(0), SO2, AND NOX BY NOVEL OXIDIZED CALCIUM-BASED SORBENTS

    Science.gov (United States)

    The paper gives results of an investigation of two classes of calcium (Ca)-based sorbents (hydrated limes and silicate compounds). {NOTE: Efforts to develop multipollutant control strategies have demonstrated that adding certain oxidants to different classes of Ca-based sorbents ...

  12. Purinergic receptors have different effects in rat exocrine pancreas. Calcium signals monitored by fura-2 using confocal microscopy

    DEFF Research Database (Denmark)

    Novak, Ivana; Nitschke, Roland; Amstrup, Jan

    microscope. Rat acini and ducts were loaded with various Ca2+ sensing fluorophores (Fluo-4, Fura-Red, Calcium Green-1, Indo-1 and Fura-2). Only Fura-2 loaded evenly into acinar clusters and ducts and UV laser excitation at 351 and 364 nm gave signals showing opposite sensitivity to Ca2+ concentration changes...... pancreas suspensions revealed transcripts for P2Y(2), P2Y(4) and P2X(1), P2X(4) receptors. The low number of functional P2 receptors in acini might be related to the fact that they release ATP. Thereby acini would avoid autocrine stimulation and initiation of autodigestive processes, such as occurs in...

  13. Honey bee dopamine and octopamine receptors linked to intracellular calcium signaling have a close phylogenetic and pharmacological relationship.

    Directory of Open Access Journals (Sweden)

    Kyle T Beggs

    Full Text Available BACKGROUND: Three dopamine receptor genes have been identified that are highly conserved among arthropod species. One of these genes, referred to in honey bees as Amdop2, shows a close phylogenetic relationship to the a-adrenergic-like octopamine receptor family. In this study we examined in parallel the functional and pharmacological properties of AmDOP2 and the honey bee octopamine receptor, AmOA1. For comparison, pharmacological properties of the honey bee dopamine receptors AmDOP1 and AmDOP3, and the tyramine receptor AmTYR1, were also examined. METHODOLOGY/PRINCIPAL FINDINGS: Using HEK293 cells heterologously expressing honey bee biogenic amine receptors, we found that activation of AmDOP2 receptors, like AmOA1 receptors, initiates a rapid increase in intracellular calcium levels. We found no evidence of calcium signaling via AmDOP1, AmDOP3 or AmTYR1 receptors. AmDOP2- and AmOA1-mediated increases in intracellular calcium were inhibited by 10 µM edelfosine indicating a requirement for phospholipase C-β activity in this signaling pathway. Edelfosine treatment had no effect on AmDOP2- or AmOA1-mediated increases in intracellular cAMP. The synthetic compounds mianserin and epinastine, like cis-(Z-flupentixol and spiperone, were found to have significant antagonist activity on AmDOP2 receptors. All 4 compounds were effective antagonists also on AmOA1 receptors. Analysis of putative ligand binding sites offers a possible explanation for why epinastine acts as an antagonist at AmDOP2 receptors, but fails to block responses mediated via AmDOP1. CONCLUSIONS/SIGNIFICANCE: Our results indicate that AmDOP2, like AmOA1, is coupled not only to cAMP, but also to calcium-signalling and moreover, that the two signalling pathways are independent upstream of phospholipase C-β activity. The striking similarity between the pharmacological properties of these 2 receptors suggests an underlying conservation of structural properties related to receptor

  14. 40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

    Science.gov (United States)

    2010-07-01

    ... covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40... FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air Pollution... with wet air pollution control devices subcategory. The provisions of this subpart are applicable...

  15. Effects of adrenalectomy on the control and adrenergic regulation of cytosolic free calcium in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Freudenrich, C.C.

    1987-01-01

    The purpose of this study was to investigate the effects of adrenalectomy on the control and ..cap alpha..-adrenergic regulation of the concentration of cytosolic free calcium (Ca/sub i/) in hepatocytes. In hepatocytes isolated from adrenalectomized (adx) and sham-operated male rats 7-1 days after surgery, Ca/sub i/ at rest and in response to epinephrine (EPI) was measured with the calcium-sensitive photoprotein aequorin, /sup 45/Ca efflux was measured, and Ca/sup 2 +/ release from intracellular stores in response to inositol triphosphate (IP/sub 3/) was measured in saponin-permeabilized cells. Liver calmodulin content was also assayed by radioimmunoassay. It was found in adx rats that the resting Ca/sub i/ was elevated, the rise in Ca/sub i/ during EPI stimulation was reduced at physiological EPI concentrations, and the rise in calcium efflux evoked by EPI was reduced. Furthermore, the slope of the relationship between Ca/sub i/ and calcium efflux was reduced 60% in adx. Adx did not alter the characteristics of Ca/sup 2 +/ release from intracellular calcium pools in response to IP/sub 3/ in permeabilized cells. Finally, the liver calmodulin contents were not significantly different between the 2 groups.

  16. Detection of differentially regulated subsarcolemmal calcium signals activated by vasoactive agonists in rat pulmonary artery smooth muscle cells

    Science.gov (United States)

    Subedi, Krishna P.; Paudel, Omkar

    2013-01-01

    Intracellular calcium (Ca2+) plays pivotal roles in distinct cellular functions through global and local signaling in various subcellular compartments, and subcellular Ca2+ signal is the key factor for independent regulation of different cellular functions. In vascular smooth muscle cells, subsarcolemmal Ca2+ is an important regulator of excitation-contraction coupling, and nucleoplasmic Ca2+ is crucial for excitation-transcription coupling. However, information on Ca2+ signals in these subcellular compartments is limited. To study the regulation of the subcellular Ca2+ signals, genetically encoded Ca2+ indicators (cameleon), D3cpv, targeting the plasma membrane (PM), cytoplasm, and nucleoplasm were transfected into rat pulmonary arterial smooth muscle cells (PASMCs) and Ca2+ signals were monitored using laser scanning confocal microscopy. In situ calibration showed that the Kd for Ca2+ of D3cpv was comparable in the cytoplasm and nucleoplasm, but it was slightly higher in the PM. Stimulation of digitonin-permeabilized cells with 1,4,5-trisphosphate (IP3) elicited a transient elevation of Ca2+ concentration with similar amplitude and kinetics in the nucleoplasm and cytoplasm. Activation of G protein-coupled receptors by endothelin-1 and angiotensin II preferentially elevated the subsarcolemmal Ca2+ signal with higher amplitude in the PM region than the nucleoplasm and cytoplasm. In contrast, the receptor tyrosine kinase activator, platelet-derived growth factor, elicited Ca2+ signals with similar amplitudes in all three regions, except that the rise-time and decay-time were slightly slower in the PM region. These data clearly revealed compartmentalization of Ca2+ signals in the subsarcolemmal regions and provide the basis for further investigations of differential regulation of subcellular Ca2+ signals in PASMCs. PMID:24352334

  17. Signalling and obfuscation for congestion control

    Science.gov (United States)

    Mareček, Jakub; Shorten, Robert; Yu, Jia Yuan

    2015-10-01

    We aim to reduce the social cost of congestion in many smart city applications. In our model of congestion, agents interact over limited resources after receiving signals from a central agent that observes the state of congestion in real time. Under natural models of agent populations, we develop new signalling schemes and show that by introducing a non-trivial amount of uncertainty in the signals, we reduce the social cost of congestion, i.e., improve social welfare. The signalling schemes are efficient in terms of both communication and computation, and are consistent with past observations of the congestion. Moreover, the resulting population dynamics converge under reasonable assumptions.

  18. Modulation of signalling in neutrophils activated by a chemotactic peptide: calcium regulates diacyl glycerol metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Korchak, H.M.; Vosshall, L.B.; Lundquist, K.F.

    1987-05-01

    Neutrophils activated by ligands such as the chemotactic peptide f-Met-Leu-Phe (FMLP) generate superoxide anion (O/sub 2//sup -/) and release specific and azurophil granule contents. The signalling for this response is thought to involve both elevated cytosolic Ca and protein kinase C activity. Receptor-occupation triggers a phospholipase C to cleave phosphatidyl inositol 4,5 bisphosphate (PIP/sub 2/) yielding inositol 1,4,5 trisphosphate, (IP/sub 3/), a trigger for intracellular Ca release, and diacyl glycerol (DG), which together with Ca activates protein kinase C. The DG can be metabolized to phosphatidic acid (PA). FMLP triggered a rapid increase in cytosolic Ca (fura-2). Loading cells with MAPTAM, and intracellular Ca buffer, suppressed this Ca transient in FMLP activated cells and inhibited O/sub 2//sup -/ generation to 12.5% of control, beta-glucuronidase release to 40.3% of control and lysozyme release to 55.1% of control. FMLP triggered a prompt decrease in PIP/sub 2/ in cells pre-labelled with /sup 32/P or /sup 3/H-inositol and an increase in PA and release of /sup 3/H-IP/sub 3/. A rapid increase in /sup 14/C-DG levels was also observed in /sup 14/C-glycerol pre-loaded cells activated by FMLP. Suppression of the Ca transient by buffering with MAPTAM inhibited elevation of /sup 14/C-DG. Breakdown of PIP/sub 2/ was not inhibited and elevation of /sup 32/P-PA was enhanced in MAPTAM loaded cells. Conversely, 200nM ionomycin which elevated cytosolic Ca to an equivalent level to 10/sup -7/M FMLP, triggered a rise in /sup 14/C-DG but not in PA.

  19. Efficiency evaluation of external environments control using bio-signals

    OpenAIRE

    Kawala-Janik, Aleksandra

    2013-01-01

    There are many types of bio-signals with various control application prospects. This dissertation regards possible application domain of electroencephalographic signal. The implementation of EEG signals, as a source of information used for control of external devices, became recently a growing concern in the scientific world. Application of electroencephalographic signals in Brain-Computer Interfaces (BCI) (variant of Human-Computer Interfaces (HCI)) as an implement, which enables direct and ...

  20. The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: A different point of view on the role of aquaporins.

    Science.gov (United States)

    Mola, Maria Grazia; Sparaneo, Angelo; Gargano, Concetta Domenica; Spray, David C; Svelto, Maria; Frigeri, Antonio; Scemes, Eliana; Nicchia, Grazia Paola

    2016-01-01

    Regulatory volume decrease (RVD) is a process by which cells restore their original volume in response to swelling. In this study, we have focused on the role played by two different Aquaporins (AQPs), Aquaporin-4 (AQP4), and Aquaporin-1 (AQP1), in triggering RVD and in mediating calcium signaling in astrocytes under hypotonic stimulus. Using biophysical techniques to measure water flux through the plasma membrane of wild-type (WT) and AQP4 knockout (KO) astrocytes and of an astrocyte cell line (DI TNC1) transfected with AQP4 or AQP1, we here show that AQP-mediated fast swelling kinetics play a key role in triggering and accelerating RVD. Using calcium imaging, we show that AQP-mediated fast swelling kinetics also significantly increases the amplitude of calcium transients inhibited by Gadolinium and Ruthenium Red, two inhibitors of the transient receptor potential vanilloid 4 (TRPV4) channels, and prevented by removing extracellular calcium. Finally, inhibition of TRPV4 or removal of extracellular calcium does not affect RVD. All together our study provides evidence that (1) AQP influenced swelling kinetics is the main trigger for RVD and in mediating calcium signaling after hypotonic stimulus together with TRPV4, and (2) calcium influx from the extracellular space and/or TRPV4 are not essential for RVD to occur in astrocytes. PMID:26413835

  1. Ca2+/Calmodulin-dependent Protein Kinase IV-mediated LIM Kinase Activation Is Critical for Calcium Signal-induced Neurite Outgrowth*

    OpenAIRE

    Takemura, Miyohiko; Mishima, Toshiaki; Wang, Yan; Kasahara, Jiro; Fukunaga, Kohji; Ohashi, Kazumasa; Mizuno, Kensaku

    2009-01-01

    Actin cytoskeletal remodeling is essential for neurite outgrowth. LIM kinase 1 (LIMK1) regulates actin cytoskeletal remodeling by phosphorylating and inactivating cofilin, an actin filament-disassembling factor. In this study, we investigated the role of LIMK1 in calcium signal-induced neurite outgrowth. The calcium ionophore ionomycin induced LIMK1 activation and cofilin phosphorylation in Neuro-2a neuroblastoma cells. Knockdown of LIMK1 or expression of a kinase-dead mutant of LIMK1 suppres...

  2. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials

    DEFF Research Database (Denmark)

    Christensen, R.; Lorenzen, Janne Kunchel; Svith, Carina Roholm;

    2009-01-01

    Observational studies have found that dietary calcium intake is inversely related to body weight and body fat mass. One explanatory mechanism is that dietary calcium increases faecal fat excretion. To examine the effect of calcium from dietary supplements or dairy products on quantitative faecal...... fat excretion, we performed a systematic review with meta-analysis. We included randomized, controlled trials of calcium (supplements or dairy) in healthy subjects, where faecal fat excretion was measured. Meta-analyses used random-effects models with changes in faecal fat excreted expressed as...

  3. Randomized, placebo-controlled, calcium supplementation trial in pregnant Gambian women accustomed to a low calcium intake: effects on maternal blood pressure and infant growth 1 2 3 4

    OpenAIRE

    Goldberg, Gail R.; Jarjou, Landing MA; Tim J Cole; Prentice, Ann

    2013-01-01

    Background: Dietary calcium intake in rural Gambian women is very low (∼350 mg/d) compared with international recommendations. Studies have suggested that calcium supplementation of women receiving low-calcium diets significantly reduces risk of pregnancy hypertension. Objective: We tested the effects on blood pressure (BP) of calcium carbonate supplementation (1500 mg Ca/d) in pregnant, rural Gambian women. Design: The study was a randomized, double-blind, parallel, placebo-controlled supple...

  4. Corrosion Effects of Calcium Chloride Injection for Mercury Control on the Pollution Control Equipment

    Energy Technology Data Exchange (ETDEWEB)

    Vijay Sethi; M.P. Sharma

    2009-02-28

    In response to the Clean Air Mercury Rule (CAMR) of 2005, Black Hills Power (BHP) initiated testing of a calcium chloride (CaCl{sub 2}) injection method in their Wygen 1 (Gillette, WY) coal-fired power plant to help lower mercury emissions. In 2006, Babcock & Wilcox (B&W) was contracted to test their CaCl{sub 2} technology in-situ by adding a CaCl{sub 2} solution onto the raw, pre-pulverized coal during normal operation of Wygen 1. Follow-up tests were conducted by BHP in 2007. Data were collected from these two time periods and analyzed by a collaborative investigation team from Western Research Institute (WRI) and the University of Wyoming (UW) to see if there were any effects on the current air pollution control systems. During a CaCl{sub 2} injection period in 2007, corrosion was monitored in the flue and recycle ash system by placing corrosion coupons in strategic locations to test if corrosion was enhanced by the CaCl{sub 2} injection. While the CaCl{sub 2} produced a reduction in stack mercury levels, there was some evidence of beneficial impacts on the removal of SO{sub 2} from the flue gas during CaCl{sub 2} injection. Data on NOx remained inconclusive. It was also discovered that corrosion was enhanced significantly in the Spray Drier Absorber (SDA) vessel and corresponding outlet ductwork during CaCl{sub 2} injections. Further studies are being carried out in the field and lab to better understand the corrosive effects of CaCl{sub 2} to help formulate operation controls to manage the increased corrosion rates.

  5. Climbing Fiber Signaling and Cerebellar Gain Control

    OpenAIRE

    Ohtsuki, Gen; Piochon, Claire; Hansel, Christian

    2009-01-01

    The physiology of climbing fiber signals in cerebellar Purkinje cells has been studied since the early days of electrophysiology. Both the climbing fiber-evoked complex spike and the role of climbing fiber activity in the induction of long-term depression (LTD) at parallel fiber-Purkinje cell synapses have become hallmark features of cerebellar physiology. However, the key role of climbing fiber signaling in cerebellar motor learning has been challenged by recent reports of forms of synaptic ...

  6. STIM and Orai isoform expression in pregnant human myometrium: a potential role in calcium signaling during pregnancy.

    Directory of Open Access Journals (Sweden)

    Evonne eChin-Smith

    2014-05-01

    Full Text Available Store-operated calcium (Ca2+ entry (SOCE can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3 have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at caesarean section from women at the time of preterm no labor (PTNL, preterm labor (PTL, term non-labor (TNL and term with labor (TL; primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM. STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy.

  7. The Polarized Effect of Intracellular Calcium on the Renal Epithelial Sodium Channel Occurs as a Result of Subcellular Calcium Signaling Domains Maintained by Mitochondria.

    Science.gov (United States)

    Thai, Tiffany L; Yu, Ling; Galarza-Paez, Laura; Wu, Ming Ming; Lam, Ho Yin Colin; Bao, Hui Fang; Duke, Billie Jeanne; Al-Khalili, Otor; Ma, He-Ping; Liu, Bingchen; Eaton, Douglas C

    2015-11-27

    The renal epithelial sodium channel (ENaC) provides regulated sodium transport in the distal nephron. The effects of intracellular calcium ([Ca(2+)]i) on this channel are only beginning to be elucidated. It appears from previous studies that the [Ca(2+)]i increases downstream of ATP administration may have a polarized effect on ENaC, where apical application of ATP and the subsequent [Ca(2+)]i increase have an inhibitory effect on the channel, whereas basolateral ATP and [Ca(2+)]i have a stimulatory effect. We asked whether this polarized effect of ATP is, in fact, reflective of a polarized effect of increased [Ca(2+)]i on ENaC and what underlying mechanism is responsible. We began by performing patch clamp experiments in which ENaC activity was measured during apical or basolateral application of ionomycin to increase [Ca(2+)]i near the apical or basolateral membrane, respectively. We found that ENaC does indeed respond to increased [Ca(2+)]i in a polarized fashion, with apical increases being inhibitory and basolateral increases stimulating channel activity. In other epithelial cell types, mitochondria sequester [Ca(2+)]i, creating [Ca(2+)]i signaling microdomains within the cell that are dependent on mitochondrial localization. We found that mitochondria localize in bands just beneath the apical and basolateral membranes in two different cortical collecting duct principal cell lines and in cortical collecting duct principal cells in mouse kidney tissue. We found that inhibiting mitochondrial [Ca(2+)]i uptake destroyed the polarized response of ENaC to [Ca(2+)]i. Overall, our data suggest that ENaC is regulated by [Ca(2+)]i in a polarized fashion and that this polarization is maintained by mitochondrial [Ca(2+)]i sequestration. PMID:26451045

  8. Model-free reconstruction of excitatory neuronal connectivity from calcium imaging signals.

    Directory of Open Access Journals (Sweden)

    Olav Stetter

    Full Text Available A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible, even in simpler systems like dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connectivity from network activity monitored through calcium imaging. We focus in this study on the inference of excitatory synaptic links. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the functional network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (bursting or non-bursting. Thus by conditioning with respect to the global mean activity, we improve the performance of our method. This allows us to focus the analysis to specific dynamical regimes of the network in which the inferred functional connectivity is shaped by monosynaptic excitatory connections, rather than by collective synchrony. Our method can discriminate between actual causal influences between neurons and spurious non-causal correlations due to light scattering artifacts, which inherently affect the quality of fluorescence imaging. Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good estimation of the excitatory network clustering coefficient, allowing for discrimination between weakly and strongly clustered topologies. Finally, we demonstrate the applicability of our method to analyses of real recordings of in vitro disinhibited cortical cultures where we suggest that excitatory connections

  9. Calcium sensing receptor suppresses human pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway.

    Science.gov (United States)

    Tang, Bo; Chow, Jimmy Y C; Dong, Tobias Xiao; Yang, Shi-Ming; Lu, De-Sheng; Carethers, John M; Dong, Hui

    2016-07-10

    The calcium sensing receptor (CaSR) is functionally expressed in normal human pancreases, but its pathological role in pancreatic tumorigenesis is currently unknown. We sought to investigate the role of CaSR in pancreatic cancer (PC) and the underlying molecular mechanisms. We revealed that the expression of CaSR was consistently downregulated in the primary cancer tissues from PC patients, which was correlated with tumor size, differentiation and poor survival of the patients. CaSR activation markedly suppressed pancreatic tumorigenesis in vitro and in vivo likely through the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger 1 (NCX1) to induce Ca(2+) entry into PC cells. Moreover, NCX1-mediated Ca(2+) entry resulted in Ca(2+)-dependent inhibition of β-catenin signaling in PC cells, eventually leading to the inhibition of pancreatic tumorigenesis. Collectively, we demonstrate for the first time that CaSR exerts a suppressive function in pancreatic tumorigenesis through a novel NCX1/Ca(2+)/β-catenin signaling pathway. Targeting this specific signaling pathway could be a potential therapeutic strategy for PC. PMID:27108064

  10. Odontogenic differentiation of human dental pulp cells by calcium silicate materials stimulating via FGFR/ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chao-Hsin [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Hung, Chi-Jr; Huang, Tsui-Hsien [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan (China); Lin, Chi-Chang [Department of Chemical and Materials Engineering, Tunghai University, Taichung City, Taiwan (China); Kao, Chia-Tze [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung City, Taiwan (China); Shie, Ming-You, E-mail: eviltacasi@gmail.com [Department of Chemical and Materials Engineering, Tunghai University, Taichung City, Taiwan (China)

    2014-10-01

    Bone healing needs a complex interaction of growth factors that establishes an environment for efficient bone formation. We examine how calcium silicate (CS) and tricalcium phosphate (β-TCP) cements influence the behavior of human dental pulp cells (hDPCs) through fibroblast growth factor receptor (FGFR) and active MAPK pathways, in particular ERK. The hDPCs are cultured with β-TCP and CS, after which the cells' viability and odontogenic differentiation markers are determined by using PrestoBlue® assay and western blot, respectively. The effect of small interfering RNA (siRNA) transfection targeting FGFR was also evaluated. The results showed that CS promoted cell proliferation and enhances FGFR expression. It was also found that CS increases ERK and p38 activity in hDPCs, and furthermore, raises the expression and secretion of DSP, and DMP-1. Additionally, statistically significant differences (p < 0.05) have been found in the calcium deposition in si-FGFR transfection and ERK inhibitor between CS and β-TCP; these variations indicated that ERK/MAPK signaling is involved in the silicon-induced odontogenic differentiation of hDPCs. The current study shows that CS substrates play a key role in odontoblastic differentiation of hDPCs through FGFR and modulate ERK/MAPK activation. - Highlights: • CS influences the behavior of hDPCs through fibroblast growth factor receptor. • CS increases ERK and p38 activity in hDPCs. • ERK/MAPK signaling is involved in the Si-induced odontogenic differentiation of hDPCs. • Ca staining shows that FGFR regulates hDPC differentiation on CS, but not on β-TCP.

  11. Odontogenic differentiation of human dental pulp cells by calcium silicate materials stimulating via FGFR/ERK signaling pathway

    International Nuclear Information System (INIS)

    Bone healing needs a complex interaction of growth factors that establishes an environment for efficient bone formation. We examine how calcium silicate (CS) and tricalcium phosphate (β-TCP) cements influence the behavior of human dental pulp cells (hDPCs) through fibroblast growth factor receptor (FGFR) and active MAPK pathways, in particular ERK. The hDPCs are cultured with β-TCP and CS, after which the cells' viability and odontogenic differentiation markers are determined by using PrestoBlue® assay and western blot, respectively. The effect of small interfering RNA (siRNA) transfection targeting FGFR was also evaluated. The results showed that CS promoted cell proliferation and enhances FGFR expression. It was also found that CS increases ERK and p38 activity in hDPCs, and furthermore, raises the expression and secretion of DSP, and DMP-1. Additionally, statistically significant differences (p < 0.05) have been found in the calcium deposition in si-FGFR transfection and ERK inhibitor between CS and β-TCP; these variations indicated that ERK/MAPK signaling is involved in the silicon-induced odontogenic differentiation of hDPCs. The current study shows that CS substrates play a key role in odontoblastic differentiation of hDPCs through FGFR and modulate ERK/MAPK activation. - Highlights: • CS influences the behavior of hDPCs through fibroblast growth factor receptor. • CS increases ERK and p38 activity in hDPCs. • ERK/MAPK signaling is involved in the Si-induced odontogenic differentiation of hDPCs. • Ca staining shows that FGFR regulates hDPC differentiation on CS, but not on β-TCP

  12. Regulation of Arabidopsis defense responses against Spodoptera littoralis by CPK-mediated calcium signaling

    Directory of Open Access Journals (Sweden)

    Ishihama Nobuaki

    2010-05-01

    Full Text Available Abstract Background Plant Ca2+ signals are involved in a wide array of intracellular signaling pathways after pest invasion. Ca2+-binding sensory proteins such as Ca2+-dependent protein kinases (CPKs have been predicted to mediate the signaling following Ca2+ influx after insect herbivory. However, until now this prediction was not testable. Results To investigate the roles CPKs play in a herbivore response-signaling pathway, we screened the characteristics of Arabidopsis CPK mutants damaged by a feeding generalist herbivore, Spodoptera littoralis. Following insect attack, the cpk3 and cpk13 mutants showed lower transcript levels of plant defensin gene PDF1.2 compared to wild-type plants. The CPK cascade was not directly linked to the herbivory-induced signaling pathways that were mediated by defense-related phytohormones such as jasmonic acid and ethylene. CPK3 was also suggested to be involved in a negative feedback regulation of the cytosolic Ca2+ levels after herbivory and wounding damage. In vitro kinase assays of CPK3 protein with a suite of substrates demonstrated that the protein phosphorylates transcription factors (including ERF1, HsfB2a and CZF1/ZFAR1 in the presence of Ca2+. CPK13 strongly phosphorylated only HsfB2a, irrespective of the presence of Ca2+. Furthermore, in vivo agroinfiltration assays showed that CPK3-or CPK13-derived phosphorylation of a heat shock factor (HsfB2a promotes PDF1.2 transcriptional activation in the defense response. Conclusions These results reveal the involvement of two Arabidopsis CPKs (CPK3 and CPK13 in the herbivory-induced signaling network via HsfB2a-mediated regulation of the defense-related transcriptional machinery. This cascade is not involved in the phytohormone-related signaling pathways, but rather directly impacts transcription factors for defense responses.

  13. Pheromonal control: reconciling physiological mechanism with signalling theory.

    Science.gov (United States)

    Peso, Marianne; Elgar, Mark A; Barron, Andrew B

    2015-05-01

    Pheromones are intraspecific chemical signals. They can have profound effects on the behaviour and/or physiology of the receiver, and it is still common to hear pheromones described as controlling of the behaviour of the receiver. The discussion of pheromonal control arose initially from a close association between hormones and pheromones in the comparative physiological literature, but the concept of a controlling pheromone is at odds with contemporary signal evolution theory, which predicts that a manipulative pheromonal signal negatively affecting the receiver's fitness should not be stable over evolutionary time. Here we discuss the meaning of pheromonal control, and the ecological circumstances by which it might be supported. We argue that in discussing pheromonal control it is important to differentiate between control applied to the effects of a pheromone on a receiver's physiology (proximate control), and control applied to the effects of a pheromone on a receiver's fitness (ultimate control). Critically, a pheromone signal affecting change in the receiver's behaviour or physiology need not necessarily manipulate the fitness of a receiver. In cases where pheromonal signalling does lead to a reduction in the fitness of the receiver, the signalling system would be stable if the pheromone were an honest signal of a social environment that disadvantages the receiver, and the physiological and behavioural changes observed in the receiver were an adaptive response to the new social circumstances communicated by the pheromone. PMID:24925630

  14. Calcium signalling toolkits in astrocytes and spatio-temporal progression of Alzheimer's disease.

    Science.gov (United States)

    Lim, Dmitry; Rodríguez-Arellano, J J; Parpura, Vladimir; Zorec, Robert; Zeidán-Chuliá, Fares; Genazzani, Armando A; Verkhratsky, Alexei

    2016-01-01

    Pathological remodelling of astroglia represents an important component of the pathogenesis of Alzheimer's disease (AD). In AD astrocytes undergo both atrophy and reactivity; which may be specific for different stages of the disease evolution. Astroglial reactivity represents the generic defensive mechanism, and inhibition of astrogliotic response exacerbates b-amyloid pathology associated with AD. In animal models of AD astroglial reactivity is different in different brain regions, and the deficits of reactive response observed in entorhinal and prefrontal cortices may be linked to their vulnerability to AD progression. Reactive astrogliosis is linked to astroglial Ca(2+) signalling, this latter being widely regarded as a mechanism of astroglial excitability. The AD pathology evolving in animal models as well as acute or chronic exposure to β-amyloid induce pathological remodelling of Ca(2+) signalling toolkit in astrocytes. This remodelling modifies astroglial Ca(2+) signalling and may be linked to cellular mechanisms of AD pathogenesis. PMID:26567740

  15. Novel strategies in drug discovery of the calcium-sensing receptor based on biased signaling

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Smajilovic, Sanela; Bräuner-Osborne, Hans

    2012-01-01

    A hallmark of chronic kidney disease is hyperphosphatemia due to renal phosphate retention. Prolonged parathyroid gland exposure to hyperphosphatemia leads to secondary hyperparathyroidism characterized by hyperplasia of the glands and excessive secretion of parathyroid hormone (PTH), which cause...... of hypocalcemia by virtue of it not affecting calcitonin secretion. The present review will focus on recent advancements in understanding signaling and biased signaling of the CaSR, and how that may be utilized to discover new and smarter drugs targeting the CaSR....

  16. Cellular signaling underlying atrial tachycardia remodeling of L-type calcium current

    NARCIS (Netherlands)

    Qi, Xiao Yan; Yeh, Yung-Hsin; Xiao, Ling; Burstein, Brett; Maguy, Ange; Chartier, Denis; Villeneuve, Louis R.; Brundel, Bianca J. J. M.; Dobrev, Dobromir; Nattel, Stanley

    2008-01-01

    Atrial tachycardia (AT) downregulates L-type Ca2+ current (I-CaL) and causes atrial fibrillation -promoting electric remodeling. This study assessed potential underlying signal transduction. Cultured adult canine atrial cardiomyocytes were paced at 0, 1, or 3 Hz (P0, P1, P3) for up to 24 hours. Cell

  17. Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

    Directory of Open Access Journals (Sweden)

    Emri Zsuzsa

    2011-10-01

    Full Text Available Abstract Background Accumulating evidence suggests that glial signalling is activated by different brain functions. However, knowledge regarding molecular mechanisms of activation or their relation to neuronal activity is limited. The purpose of the present study is to identify the characteristics of ATP-evoked glial signalling in the brain reward area, the nucleus accumbens (NAc, and thereby to explore the action of citric acid cycle intermediate succinate (SUC. Results We described the burst-like propagation of Ca2+ transients evoked by ATP in acute NAc slices from rat brain. Co-localization of the ATP-evoked Ca2+ signalling with immunoreactivities of the astroglia-specific gap junction forming channel protein connexin43 (Cx43 and the glial fibrillary acidic protein (GFAP indicated that the responsive cells were a subpopulation of Cx43 and GFAP immunoreactive astrocytes. The ATP-evoked Ca2+ transients were present under the blockade of neuronal activity, but were inhibited by Ca2+ store depletion and antagonism of the G protein coupled purinergic P2Y1 receptor subtype-specific antagonist MRS2179. Similarly, Ca2+ transients evoked by the P2Y1 receptor subtype-specific agonist 2-(Methylthioadenosine 5'-diphosphate were also blocked by MRS2179. These characteristics implied that intercellular Ca2+ signalling originated from the release of Ca2+ from internal stores, triggered by the activation of P2Y1 receptors. Inhibition by the gap junction blockers carbenoxolone and flufenamic acid and by an antibody raised against the gating-associated segment of Cx43 suggested that intercellular Ca2+ signalling proceeded through gap junctions. We demonstrated for the first time that extracellular SUC also evoked Ca2+ transients (EC50 = 50-60 μM in about 15% of the ATP-responsive NAc astrocytes. By contrast to glial cells, electrophysiologically identified NAc neurons surrounded by ATP-responsive astrocytes were not activated simultaneously. Conclusions We

  18. Sensory Flask Cells in Sponge Larvae Regulate Metamorphosis via Calcium Signaling.

    Science.gov (United States)

    Nakanishi, Nagayasu; Stoupin, Daniel; Degnan, Sandie M; Degnan, Bernard M

    2015-12-01

    The Porifera (sponges) is one of the earliest phyletic lineages to branch off the metazoan tree. Although the body-plan of sponges is among the simplest in the animal kingdom and sponges lack nervous systems that communicate environmental signals to other cells, their larvae have sensory systems that generate coordinated responses to environmental cues. In eumetazoans (Cnidaria and Bilateria), the nervous systems of larvae often regulate metamorphosis through Ca(2+)-dependent signal transduction. In sponges, neither the identity of the receptor system that detects an inductive environmental cue (hereafter "metamorphic cues") nor the signaling system that mediates settlement and metamorphosis are known. Using a combination of behavioral assays and surgical manipulations, we show here that specialized epithelial cells-referred to as flask cells-enriched in the anterior third of the Amphimedon queenslandica larva are most likely to be the sensory cells that detect the metamorphic cues. Surgical removal of the region enriched in flask cells in a larva inhibits the initiation of metamorphosis. The flask cell has an apical sensory apparatus with a cilium surrounded by an apical F-actin-rich protrusion, and numerous vesicles, hallmarks of eumetazoan sensory-neurosecretory cells. We demonstrate that these flask cells respond to metamorphic cues by elevating intracellular Ca(2+) levels, and that this elevation is necessary for the initiation of metamorphosis. Taken together, these analyses suggest that sponge larvae have sensory-secretory epithelial cells capable of converting exogenous cues into internal signals via Ca(2+)-mediated signaling, which is necessary for the initiation of metamorphosis. Similarities in the morphology, physiology, and function of the sensory flask cells in sponge larvae with the sensory/neurosecretory cells in eumetazoan larvae suggest this sensory system predates the divergence of Porifera and Eumetazoa. PMID:25898842

  19. Coupling calcium/calmodulin-mediated signaling and herbivore-induced plant response calmodulin-binding transcription factor AtSR1/CAMTA3

    Science.gov (United States)

    Calcium/calmodulin (Ca2+/CaM) has long been considered a crucial component in wound signaling pathway. However, no functional significance of Ca2+/CaM-binding proteins has been identified in plant responses to herbivore attack/wounding stress. We have reported earlier that a family of Ca2+/CaM-bindi...

  20. 49 CFR 236.13 - Spring switch; selection of signal control circuits through circuit controller.

    Science.gov (United States)

    2010-10-01

    ... circuits through circuit controller. 236.13 Section 236.13 Transportation Other Regulations Relating to...; selection of signal control circuits through circuit controller. The control circuits of signals governing... circuit controller, or through the contacts of relay repeating the position of such circuit...

  1. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    Full Text Available The paper gives the review on the role of calcium in many physiological processes of plant organisms, including growth and development, protection from pathogenic influences, response to changing environmental factors, and many other aspects of plant physiology. Initial intake of calcium ions is carried out by Ca2+-channels of plasma membrane and they are further transported by the xylem owing to auxins’ attractive ability. The level of intake and selectivity of calcium transport to ove-ground parts of the plant is controlled by a symplast. Ca2+enters to the cytoplasm of endoderm cells through calcium channels on the cortical side of Kaspary bands, and is redistributed inside the stele by the symplast, with the use of Ca2+-АТPases and Ca2+/Н+-antiports. Owing to regulated expression and activity of these calcium transporters, calclum can be selectively delivered to the xylem. Important role in supporting calcium homeostasis is given to the vacuole which is the largest depo of calcium. Regulated quantity of calcium movement through the tonoplast is provided by a number of potential-, ligand-gated active transporters and channels, like Ca2+-ATPase and Ca2+/H+ exchanger. They are actively involved in the inactivation of the calcium signal by pumping Ca2+ to the depo of cells. Calcium ATPases are high affinity pumps that efficiently transfer calcium ions against the concentration gradient in their presence in the solution in nanomolar concentrations. Calcium exchangers are low affinity, high capacity Ca2+ transporters that are effectively transporting calcium after raising its concentration in the cell cytosol through the use of protons gradients. Maintaining constant concentration and participation in the response to stimuli of different types also involves EPR, plastids, mitochondria, and cell wall. Calcium binding proteins contain several conserved sequences that provide sensitivity to changes in the concentration of Ca2+ and when you

  2. A novel role of the L-type calcium channel α1D subunit as a gatekeeper for intracellular zinc signaling: zinc wave.

    Directory of Open Access Journals (Sweden)

    Satoru Yamasaki

    Full Text Available Recent studies have shown that zinc ion (Zn can behave as an intracellular signaling molecule. We previously demonstrated that mast cells stimulated through the high-affinity IgE receptor (FcεRI rapidly release intracellular Zn from the endoplasmic reticulum (ER, and we named this phenomenon the "Zn wave". However, the molecules responsible for releasing Zn and the roles of the Zn wave were elusive. Here we identified the pore-forming α(1 subunit of the Cav1.3 (α(1D L-type calcium channel (LTCC as the gatekeeper for the Zn wave. LTCC antagonists inhibited the Zn wave, and an agonist was sufficient to induce it. Notably, α(1D was mainly localized to the ER rather than the plasma membrane in mast cells, and the Zn wave was impaired by α(1D knockdown. We further found that the LTCC-mediated Zn wave positively controlled cytokine gene induction by enhancing the DNA-binding activity of NF-κB. Consistent with this finding, LTCC antagonists inhibited the cytokine-mediated delayed-type allergic reaction in mice without affecting the immediate-type allergic reaction. These findings indicated that the LTCC α(1D subunit located on the ER membrane has a novel function as a gatekeeper for the Zn wave, which is involved in regulating NF-κB signaling and the delayed-type allergic reaction.

  3. Digital signal processing in power system protection and control

    CERN Document Server

    Rebizant, Waldemar; Wiszniewski, Andrzej

    2011-01-01

    Digital Signal Processing in Power System Protection and Control bridges the gap between the theory of protection and control and the practical applications of protection equipment. Understanding how protection functions is crucial not only for equipment developers and manufacturers, but also for their users who need to install, set and operate the protection devices in an appropriate manner. After introductory chapters related to protection technology and functions, Digital Signal Processing in Power System Protection and Control presents the digital algorithms for signal filtering, followed

  4. Membrane wounding triggers ATP release and dysferlin-mediated intercellular calcium signaling

    OpenAIRE

    Covian-Nares, J. Fernando; Koushik, Srinagesh V.; Puhl, Henry L.; Vogel, Steven S.

    2010-01-01

    Dysferlin is a Ca2+-binding protein found in many different cell types. It is required for membrane wound repair in muscle, but it is not known whether it has the same function in other cells. Here we report the activation of an intercellular signaling pathway in sea urchin embryos by membrane wounding that evokes Ca2+ spikes in neighboring cells. This pathway was mimicked by ATP application, and inhibited by apyrase, cadmium, and ω-agatoxin-IVA. Microinjection of dysferlin antisense phosphor...

  5. Transient Enhancement of Spike-Evoked Calcium Signaling by a Serotonergic Interneuron

    OpenAIRE

    Hill, Evan S.; Sakurai, Akira; Katz, Paul S.

    2008-01-01

    Enhancement of presynaptic Ca2+ signals is widely recognized as a potential mechanism for heterosynaptic potentiation of neurotransmitter release. Here we show that stimulation of a serotonergic interneuron increased spike-evoked Ca2+ in a manner consistent with its neuromodulatory effect on synaptic transmission. In the gastropod mollusk, Tritonia diomedea, stimulation of a serotonergic dorsal swim interneuron (DSI) at physiological rates heterosynaptically enhances the strength of output sy...

  6. Unique responsiveness of angiosperm stomata to elevated CO2 explained by calcium signalling.

    Directory of Open Access Journals (Sweden)

    Timothy J Brodribb

    Full Text Available Angiosperm and conifer tree species respond differently when exposed to elevated CO2, with angiosperms found to dynamically reduce water loss while conifers appear insensitive. Such distinct responses are likely to affect competition between these tree groups as atmospheric CO2 concentration rises. Seeking the mechanism behind this globally important phenomenon we targeted the Ca(2+-dependent signalling pathway, a mediator of stomatal closure in response to elevated CO2, as a possible explanation for the differentiation of stomatal behaviours. Sampling across the diversity of vascular plants including lycophytes, ferns, gymnosperms and angiosperms we show that only angiosperms possess the stomatal behaviour and prerequisite genetic coding, linked to Ca(2+-dependent stomatal signalling. We conclude that the evolution of Ca(2+-dependent stomatal signalling gives angiosperms adaptive benefits in terms of highly efficient water use, but that stomatal sensitivity to high CO2 may penalise angiosperm productivity relative to other plant groups in the current era of soaring atmospheric CO2.

  7. Human ECG signal parameters estimation during controlled physical activity

    Science.gov (United States)

    Maciejewski, Marcin; Surtel, Wojciech; Dzida, Grzegorz

    2015-09-01

    ECG signal parameters are commonly used indicators of human health condition. In most cases the patient should remain stationary during the examination to decrease the influence of muscle artifacts. During physical activity, the noise level increases significantly. The ECG signals were acquired during controlled physical activity on a stationary bicycle and during rest. Afterwards, the signals were processed using a method based on Pan-Tompkins algorithms to estimate their parameters and to test the method.

  8. Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Kristen E Boyle

    Full Text Available The rising prevalence of gestational diabetes mellitus (GDM affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM and obese pregnant women with normal glucose tolerance (ONGT. Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I subunits (NDUFS3, NDUFV2 and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4 in OGDM (n = 6 vs. ONGT (n = 6. Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (-60-75% in the OGDM (n = 8 compared with ONGT (n = 10 subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

  9. Calcium-sensing receptors regulate cardiomyocyte Ca2+ signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia/reoxygenation

    Directory of Open Access Journals (Sweden)

    Lu Fang-hao

    2010-06-01

    Full Text Available Abstract Communication between the SR (sarcoplasmic reticulum, SR and mitochondria is important for cell survival and apoptosis. The SR supplies Ca2+ directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM. Although it has been demonstrated that CaR (calcium sensing receptor activation is involved in intracellular calcium overload during hypoxia/reoxygenation (H/Re, the role of CaR activation in the cardiomyocyte apoptotic pathway remains unclear. We postulated that CaR activation plays a role in the regulation of SR-mitochondrial inter-organelle Ca2+ signaling, causing apoptosis during H/Re. To investigate the above hypothesis, cultured cardiomyocytes were subjected to H/Re. We examined the distribution of IP3Rs in cardiomyocytes via immunofluorescence and Western blotting and found that type 3 IP3Rs were located in the SR. [Ca2+]i, [Ca2+]m and [Ca2+]SR were determined using Fluo-4, x-rhod-1 and Fluo 5N, respectively, and the mitochondrial membrane potential was detected with JC-1 during reoxygenation using laser confocal microscopy. We found that activation of CaR reduced [Ca2+]SR, increased [Ca2+]i and [Ca2+]m and decreased the mitochondrial membrane potential during reoxygenation. We found that the activation of CaR caused the cleavage of BAP31, thus generating the pro-apoptotic p20 fragment, which induced the release of cytochrome c from mitochondria and the translocation of bak/bax to mitochondria. Taken together, these results reveal that CaR activation causes Ca2+ release from the SR into the mitochondria through IP3Rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation.

  10. Measuring workload weak resilience signals at a rail control post

    NARCIS (Netherlands)

    Siegel, A.W.; Schraagen, J.M.C.

    2014-01-01

    This paper describes an observational study at a rail control post to measure workload weak-resilience-signals (WRS). 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 with unexpected and un

  11. 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

  12. IGF-1 induces IP3 -dependent calcium signal involved in the regulation of myostatin gene expression mediated by NFAT during myoblast differentiation.

    Science.gov (United States)

    Valdés, Juan A; Flores, Sylvia; Fuentes, Eduardo N; Osorio-Fuentealba, Cesar; Jaimovich, Enrique; Molina, Alfredo

    2013-07-01

    Skeletal muscle differentiation is a complex and highly regulated process characterized by cell cycle arrest, which is associated with morphological changes including myoblast alignment, elongation, and fusion into multinucleated myotubes. This is a balanced process dynamically coordinated by positive and negative signals such as the insulin-like growth factor I (IGF-1) and myostatin (MSTN), respectively. In this study, we report that the stimulation of skeletal myoblasts during differentiation with IGF-1 induces a rapid and transient calcium increase from intracellular stores, which are principally mediated through the phospholipase C gamma (PLC γ)/inositol 1,4,5-triphosphate (IP3 )-dependent signaling pathways. This response was completely blocked when myoblasts were incubated with LY294002 or transfected with the dominant-negative p110 gamma, suggesting a fundamental role of phosphatidylinositol 3-kinase (PI3K) in PLCγ activation. Additionally, we show that calcium released via IP3 and induced by IGF-1 stimulates NFAT-dependent gene transcription and nuclear translocation of the GFP-labeled NFATc3 isoform. This activation was independent of extracellular calcium influx and calcium release mediated by ryanodine receptor (RyR). Finally, we examined mstn mRNA levels and mstn promoter activity in myoblasts stimulated with IGF-1. We found a significant increase in mRNA contents and in reporter activity, which was inhibited by cyclosporin A, 11R-VIVIT, and by inhibitors of the PI3Kγ, PLCγ, and IP3 receptor. Our results strongly suggest that IGF-1 regulates myostatin transcription through the activation of the NFAT transcription factor in an IP3 /calcium-dependent manner. This is the first study to demonstrate a role of calcium-dependent signaling pathways in the mRNA expression of myostatin. PMID:23255067

  13. Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Pommergaard, Hans Christian; Burcharth, Jakob; Rosenberg, Jacob;

    2016-01-01

    BACKGROUND & AIMS: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and...... current smokers OR, 1.70; 95% CI, 0.70-4.09; P value interaction < .05). However, the overall interaction was not significant. CONCLUSIONS: In a prospective study, the combination of calcitriol, aspirin, and calcium carbonate did not prevent recurrence of colorectal adenomas over a 3-year period. The...

  14. Signaling Network of Environmental Sensing and Adaptation in Plants:. Key Roles of Calcium Ion

    Science.gov (United States)

    Kurusu, Takamitsu; Kuchitsu, Kazuyuki

    2011-01-01

    Considering the important issues concerning food, environment, and energy that humans are facing in the 21st century, humans mostly depend on plants. Unlike animals which move from an inappropriate environment, plants do not move, but rapidly sense diverse environmental changes or invasion by other organisms such as pathogens and insects in the place they root, and adapt themselves by changing their own bodies, through which they developed adaptability. Whole genetic information corresponding to the blueprints of many biological systems has recently been analyzed, and comparative genomic studies facilitated tracing strategies of each organism in their evolutional processes. Comparison of factors involved in intracellular signal transduction between animals and plants indicated diversification of different gene sets. Reversible binding of Ca2+ to sensor proteins play key roles as a molecular switch both in animals and plants. Molecular mechanisms for signaling network of environmental sensing and adaptation in plants will be discussed with special reference to Ca2+ as a key element in information processing.

  15. Brushless DC motor control system responsive to control signals generated by a computer or the like

    Science.gov (United States)

    Packard, Douglas T. (Inventor); Schmitt, Donald E. (Inventor)

    1987-01-01

    A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The rotor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor may be regulated by applying a separate control signal to each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.

  16. Brushless DC motor control system responsive to control signals generated by a computer or the like

    Science.gov (United States)

    Packard, D. T. (Inventor)

    1985-01-01

    A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The motor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor be regulated by applying a separate control signal and each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.

  17. Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

    International Nuclear Information System (INIS)

    Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle

  18. Serca1 Truncated Proteins Unable to Pump Calcium Reduce the Endoplasmic Reticulum Calcium Concentration and Induce Apoptosis

    OpenAIRE

    Chami, Mounia; Gozuacik, Devrim; Lagorce, David; Brini, Marisa; Falson, Pierre; Peaucellier, Gérard; Pinton, Paolo; Lecoeur, Hervé; Gougeon, Marie-Lyse; le Maire, Marc; Rizzuto, Rosario; Bréchot, Christian; Paterlini-Bréchot, Patrizia

    2001-01-01

    By pumping calcium from the cytosol to the ER, sarco/endoplasmic reticulum calcium ATPases (SERCAs) play a major role in the control of calcium signaling. We describe two SERCA1 splice variants (S1Ts) characterized by exon 4 and/or exon 11 splicing, encoding COOH terminally truncated proteins, having only one of the seven calcium-binding residues, and thus unable to pump calcium. As shown by semiquantitative RT-PCR, S1T transcripts are differentially expressed in several adult and fetal human...

  19. Autonomous Traffic Signal Control Model with Neural Network Analogy

    CERN Document Server

    Ohira, T

    1997-01-01

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

  20. Signal Groups of Compatible Graph in Traffic Control Problems

    Directory of Open Access Journals (Sweden)

    Arun Kumar Baruah

    2012-07-01

    Full Text Available Signal Groups of a compatibility graph is used to solve conflict between the traffic streams and hence can be used as a solution for traffic control problem at an intersection. In this paper we have considered cliques of the compatible graph as signal groups and the set of signal groups which can simultaneously move at an intersection is taken in a phase. Phasing of traffic lights is done by splitting the cycle time among these phases so that each set of signal group is allowed to move once in the cycle.

  1. A maize calcium-dependent protein kinase gene, ZmCPK4, positively regulated abscisic acid signaling and enhanced drought stress tolerance in transgenic Arabidopsis.

    Science.gov (United States)

    Jiang, Shanshan; Zhang, Dan; Wang, Li; Pan, Jiaowen; Liu, Yang; Kong, Xiangpei; Zhou, Yan; Li, Dequan

    2013-10-01

    Calcium-dependent protein kinases (CDPKs) play essential roles in calcium-mediated signal transductions in plant response to abiotic stress. Several members have been identified to be regulators for plants response to abscisic acid (ABA) signaling. Here, we isolated a subgroup I CDPK gene, ZmCPK4, from maize. Quantitative real time PCR (qRT-PCR) analysis revealed that the ZmCPK4 transcripts were induced by various stresses and signal molecules. Transient and stable expression of the ZmCPK4-GFP fusion proteins revealed ZmCPK4 localized to the membrane. Moreover, overexpression of ZmCPK4 in the transgenic Arabidopsis enhanced ABA sensitivity in seed germination, seedling growth and stomatal movement. The transgenic plants also enhanced drought stress tolerance. Taken together, the results suggest that ZmCPK4 might be involved in ABA-mediated regulation of stomatal closure in response to drought stress. PMID:23911729

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

    Science.gov (United States)

    Yan, Fei; Tian, Fuli; Shi, Zhongke

    2016-03-01

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

  3. Adaptive Traffic Signalization Model using Neuro-Fuzzy Controllers

    Directory of Open Access Journals (Sweden)

    Devesh Batra*

    2014-07-01

    Full Text Available Current traffic lights are pre-programmed and use daily signal timing schedules, which contribute to traffic congestion and delay. Thus, with the increase in the number of vehicles on road, need for adaptive signal technology arises which has the potential to adjust the timing of red, yellow and green lights in order to accommodate changing traffic patterns and ease traffic congestion. In this paper, we present a model for adaptive traffic signalization, which uses fuzzy neural network for designing traffic signal controller. The controllers use vehicle detectors in order to detect the number of incoming vehicles. Based on the number of approaching vehicles, the current signal phase is either extended or terminated. The traffic volume at one particular region in an intersection is compared with that in the competing regions of the same intersection. The decision made is thus robust and results in less congestion and delays.

  4. Calcium-dependent and calcium-independent signals in the conglutinin-binding assay (KgBa) for immune complexes. Influence of anti-collagen-antibodies

    DEFF Research Database (Denmark)

    Holmskov, U; Haas, Henning de; Teisner, B;

    1992-01-01

    of IgG to solid phase bovine conglutinin was also observed to a variable degree in normal and pathological sera. However, in this situation the IgG binding was largely calcium-independent, was not inhibited by GlcNAc and did not decrease after prolonged incubation of the serum at 37 degrees C. The...

  5. Chaos control applied to cardiac rhythms represented by ECG signals

    International Nuclear Information System (INIS)

    The control of irregular or chaotic heartbeats is a key issue in cardiology. In this regard, chaos control techniques represent a good alternative since they suggest treatments different from those traditionally used. This paper deals with the application of the extended time-delayed feedback control method to stabilize pathological chaotic heart rhythms. Electrocardiogram (ECG) signals are employed to represent the cardiovascular behavior. A mathematical model is employed to generate ECG signals using three modified Van der Pol oscillators connected with time delay couplings. This model provides results that qualitatively capture the general behavior of the heart. Controlled ECG signals show the ability of the strategy either to control or to suppress the chaotic heart dynamics generating less-critical behaviors. (paper)

  6. Chaos control applied to cardiac rhythms represented by ECG signals

    Science.gov (United States)

    Borem Ferreira, Bianca; Amorim Savi, Marcelo; Souza de Paula, Aline

    2014-10-01

    The control of irregular or chaotic heartbeats is a key issue in cardiology. In this regard, chaos control techniques represent a good alternative since they suggest treatments different from those traditionally used. This paper deals with the application of the extended time-delayed feedback control method to stabilize pathological chaotic heart rhythms. Electrocardiogram (ECG) signals are employed to represent the cardiovascular behavior. A mathematical model is employed to generate ECG signals using three modified Van der Pol oscillators connected with time delay couplings. This model provides results that qualitatively capture the general behavior of the heart. Controlled ECG signals show the ability of the strategy either to control or to suppress the chaotic heart dynamics generating less-critical behaviors.

  7. Signal differentiation in position tracking control of dc motors

    International Nuclear Information System (INIS)

    An asymptotic differentiation approach with respect to time is used for on-line estimation of velocity and acceleration signals in controlled dc motors. The attractive feature of this differentiator of signals is that it does not require any system mathematical model, which allows its use in engineering systems that require the signal differentiation for its control, identification, fault detection, among other applications. Moreover, it is shown that the differentiation approach can be applied for output signals showing a chaotic behavior. In addition a differential flatness control scheme with additional integral compensation of the output error is proposed for tracking tasks of position reference trajectories for direct current electric motors using angular position measurements only

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

    Energy Technology Data Exchange (ETDEWEB)

    Walleczek, J.

    1991-07-01

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

  9. Purinergic receptors and calcium signalling in human pancreatic duct cell lines

    DEFF Research Database (Denmark)

    Hansen, Mette R; Krabbe, Simon; Novak, Ivana

    2008-01-01

    expression of P2X4 and P2X7 receptors. Expression of P2Y2, P2X4 and P2X7 receptors was confirmed by immunocytochemistry. This fingerprint of P2 receptors in human pancreatic duct models forms the basis for studying effect of nucleotides on ion and fluid secretion, as well as on Ca(2+) and tissue homeostasis...... pancreatic duct cell lines PANC-1 and CFPAC-1. Expression of P2 receptors was examined using RT-PCR and immunocytochemistry. Both cell lines, and also Capan-1 cells, express RNA transcripts for the following receptors: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11-14 and P2X1, P2X2, P2X4, P2X5, P2X6 and P2X7. Using Fura-2...... and single-cell imaging we tested effects of various nucleotide analogues on intracellular Ca(2+) signals in PANC-1 and CFPAC-1 cells. The cell lines responded to all nucleotides with the following efficiency: UTP >or= ATP = ATPgammaS > BzATP. ATP, UTP and ATPgammaS elicited oscillatory responses. Bz...

  10. NSAIDs, Mitochondria and Calcium Signaling: Special Focus on Aspirin/Salicylates

    Directory of Open Access Journals (Sweden)

    Yoshihiro Suzuki

    2010-05-01

    Full Text Available Aspirin (acetylsalicylic acid is a well-known nonsteroidal anti-inflammatory drug (NSAID that has long been used as an anti-pyretic and analgesic drug. Recently, much attention has been paid to the chemopreventive and apoptosis-inducing effects of NSAIDs in cancer cells. These effects have been thought to be primarily attributed to the inhibition of cyclooxygenase activity and prostaglandin synthesis. However, recent studies have demonstrated unequivocally that certain NSAIDs, including aspirin and its metabolite salicylic acid, exert their anti-inflammatory and chemopreventive effects independently of cyclooxygenase activity and prostaglandin synthesis inhibition. It is becoming increasingly evident that two potential common targets of NSAIDs are mitochondria and the Ca2+ signaling pathway. In this review, we provide an overview of the current knowledge regarding the roles of mitochondria and Ca2+ in the apoptosis-inducing effects as well as some side effects of aspirin, salicylates and other NSAIDs, and introducing the emerging role of L-type Ca2+ channels, a new Ca2+ entry pathway in non-excitable cells that is up-regulated in human cancer cells.

  11. Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering.

    Science.gov (United States)

    Haws, Hillary J; McNeil, Melissa A; Hansen, Marc D H

    2016-01-01

    Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelial-mesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases. PMID:27583192

  12. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  13. Signalization system with remote notification and control

    OpenAIRE

    Bachynskyy, R

    2013-01-01

    This article presents alarm system, which sends voice messages to appropriate responder via telephone line, when some problems occur on the controlled area. Only one PSoC is used to rich functionality implementation. Наведено систему сигналізації тривожних подій, яка передає голосові повідомлення відповідному отримувачу через провідну телефонну мережу загального призначення, у разі виникнення проблем на контрольованій території. У цій системі використано тільки один програмований мікроконтрол...

  14. Stimulation of Odontogenesis and Angiogenesis via Bioactive Nanocomposite Calcium Phosphate Cements Through Integrin and VEGF Signaling Pathways.

    Science.gov (United States)

    Lee, Sang-Im; Lee, Eui-Suk; El-Fiqi, Ahmed; Lee, So-Youn; Eun-Cheol Kim; Kim, Hae-Won

    2016-05-01

    Formulating self-setting calcium phosphate cements (CPCs) with secondary phases particularly in the nanoscale order holds great promise to improve biological properties. Here, we focus on the effect that bioactive glass nanoparticles (BGN) incorporated in CPC compositions can have on the proliferation, odontogenic differentiation, and angiogenic stimulation of stem cells derived from human dental pulp (HDPSCs). These odontogenic and angiogenic events are of special importance in the dentin-pulp regeneration processes. In comparison to pure CPCs, nanocomposite cements exhibit a significantly improved proliferation of HDPSCs, and the improvement is more significant as the BGN content increases. The nanocomposite cements substantially enhance the adhesion of cells, and significantly up-regulate odontogenic differentiation, including alkaline phosphatase (ALP) activity and the expressions of odontogenic genes (sialophosphoprotein, dentin matrix protein I, ALP, osteopontin and osteocalcin). Furthermore, the use of nanocomposite cements result in stimulation of angiogenic gene expression (VEGF, FGF-2, VEGFRs, PECAM-1, and VE-cadherin) and protein production (VEGF, VEGFR-1). The angiogenic stimulation by the HDPSCs significantly affects the endothelial cell behaviors, that is, the endothelial cell migration and the tubular network formation are substantially improved when treated with HDPSC-conditioned medium, particularly with the help of nanocomposite cements. The integrin and VEGF signaling pathways are reasoned for the stimulation of the odontogenesis and angiogenesis of cells, where the nanocomposite cements up-regulate the integrin subsets α1, α2, α3, and β1, and activate the integrin downstream signal pathways, such as p-FAK, p-Akt, p-paxillin, JNK, EK, and NF-κB, as well as other nuclear transcriptional factors, including CREB, STAT-3, and ELK-1. The current results indicate that the new formulation of the nanocomposite self-setting cements might provide some

  15. Regulation of calcium signaling in dendritic cells by 1,25-dihydroxyvitamin D3.

    Science.gov (United States)

    Shumilina, Ekaterina; Xuan, Nguyen Thi; Matzner, Nicole; Bhandaru, Madhuri; Zemtsova, Irina M; Lang, Florian

    2010-06-01

    Dendritic cells (DCs) are antigen-presenting cells that provide a link between innate and adaptive immunity. Ca(2+)-dependent signaling plays a central regulatory role in DC responses to diverse antigens. DCs are a primary target of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a secosteroid hormone, that, in addition to its well-established action on Ca(2+) homeostasis, possesses immunomodulatory properties. Surprisingly, nothing is known about its effects on DC cytosolic Ca(2+) activity. The present study explored whether 1,25(OH)(2)D(3) modifies the intracellular Ca(2+) concentration ([Ca(2+)](i)) in DCs. Here we show that mouse DCs expressed K(+)-independent (NCX1-3) and K(+)-dependent (NCKX1, 3, 4, and 5) Na(+)/Ca(2+) exchangers. Acute application of LPS (100 ng/ml) to DCs increased [Ca(2+)](i), an effect significantly blunted by prior incubation with 1,25(OH)(2)D(3). 1,25(OH)(2)D(3) increased the membrane abundance of the NCKX1 protein, up-regulated the K(+)- and Na(+)-dependent Ca(2+) entry and enhanced the K(+)-dependent Na(+)/Ca(2+) exchanger currents. The NCKX blocker 3',4'-dichlorobenzamyl (DBZ) reversed the inhibitory effect of 1,25(OH)(2)D(3) on the LPS-induced increase of [Ca(2+)](i). Expression of the costimulatory molecule CD86 was down-regulated by 1,25(OH)(2)D(3), an effect reversed by DBZ. In summary, 1,25(OH)(2)D(3) blunts the LPS-induced increase in [Ca(2+)](i) by stimulation of Na(+)/Ca(2+) exchanger-dependent Ca(2+) extrusion, an effect that contributes to 1,25(OH)(2)D(3)-mediated immunosuppression. The results disclose completely novel mechanisms in the regulation of DC maturation and function. PMID:20124438

  16. Power system small signal stability analysis and control

    CERN Document Server

    Mondal, Debasish; Sengupta, Aparajita

    2014-01-01

    Power System Small Signal Stability Analysis and Control presents a detailed analysis of the problem of severe outages due to the sustained growth of small signal oscillations in modern interconnected power systems. The ever-expanding nature of power systems and the rapid upgrade to smart grid technologies call for the implementation of robust and optimal controls. Power systems that are forced to operate close to their stability limit have resulted in the use of control devices by utility companies to improve the performance of the transmission system against commonly occurring power system

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

    Science.gov (United States)

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

    2014-04-01

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

  18. Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation

    OpenAIRE

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K.; Varani, James

    2012-01-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable ef...

  19. Controlled processing of signal stored in metamaterial with tripod structure

    CERN Document Server

    Zielińska-Raczyńska, S

    2016-01-01

    In the present paper we have discussed in detail electromagnetically induced transparency and signal storing in the case of one signal pulses propagating in a classical electric medium resembling this of four-level atoms in the tripod configuration. Our theoretical results confirm recently observed dependence of transparency windows position on coupling parameters. In the process of storing the pulse energy is confined inside the metamaterial as electric charge oscillations and after required time it is possible to switch the control fields on again and to release the trapped signal. By manipulating the driving fields one can thus control the parameters of the released signal and even to divide it on demand into arbitrary parts.

  20. Coordinated signal control for arterial intersections using fuzzy logic

    Science.gov (United States)

    Kermanian, Davood; Zare, Assef; Balochian, Saeed

    2013-09-01

    Every day growth of the vehicles has become one of the biggest problems of urbanism especially in major cities. This can waste people's time, increase the fuel consumption, air pollution, and increase the density of cars and vehicles. Fuzzy controllers have been widely used in many consumer products and industrial applications with success over the past two decades. This article proposes a comprehensive model of urban traffic network using state space equations and then using Fuzzy Logic Tool Box and SIMULINK Program MATLAB a fuzzy controller in order to optimize and coordinate signal control at two intersections at an arterial road. The fuzzy controller decides to extend, early cut or terminate a signal phase and phase sequence to ensure smooth flow of traffic with minimal waiting time and length of queue. Results show that the performance of the proposed traffic controller at novel fuzzy model is better that of conventional controllers under normal and abnormal traffic conditions.

  1. Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse

    Science.gov (United States)

    Hartzell, Catherine A; Jankowska, Katarzyna I; Burkhardt, Janis K; Lewis, Richard S

    2016-01-01

    T cell receptor (TCR) engagement opens Ca2+ release-activated Ca2+ (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca2+ influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere. Ca2+-dependent retrograde actin flow corrals ER tubule extensions and STIM1/Orai1 complexes to the synapse center, creating a self-organizing process for CRAC channel localization. Our results demonstrate a new role for Ca2+ as a critical regulator of actin organization and dynamics at the synapse, and reveal potential feedback loops through which Ca2+ influx may modulate TCR signaling. DOI: http://dx.doi.org/10.7554/eLife.14850.001 PMID:27440222

  2. Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse.

    Science.gov (United States)

    Hartzell, Catherine A; Jankowska, Katarzyna I; Burkhardt, Janis K; Lewis, Richard S

    2016-01-01

    T cell receptor (TCR) engagement opens Ca(2+) release-activated Ca(2+) (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca(2+) influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere. Ca(2+)-dependent retrograde actin flow corrals ER tubule extensions and STIM1/Orai1 complexes to the synapse center, creating a self-organizing process for CRAC channel localization. Our results demonstrate a new role for Ca(2+) as a critical regulator of actin organization and dynamics at the synapse, and reveal potential feedback loops through which Ca(2+) influx may modulate TCR signaling. PMID:27440222

  3. OUTPUT FEEDBACK CONTROL FOR MIMO NONLINEAR SYSTEMS WITH EXOGENOUS SIGNALS

    Institute of Scientific and Technical Information of China (English)

    Ying ZHOU; Yuqiang WU

    2006-01-01

    The paper addresses the global output tracking of a class of multi-input multi-output(MIMO) nonlinear systems affected by disturbances, which are generated by a known exosystem. An adaptive controller is designed based on the proposed observer and the backstepping approach to asymptotically track arbitrary reference signal and to guarantee the boundedness of all the signals in the closed loop system. Finally, the numerical simulation results illustrate the effectiveness of the proposed scheme.

  4. Controlled synthesis of crystalline calcium carbonate aggregates with unusual morphologies involving the phase transformation from amorphous calcium carbonate

    International Nuclear Information System (INIS)

    Peanut-shaped CaCO3 aggregates, featured of two dandelion-like heads built up from rod-like subunits, have been synthesized via a facile precipitation reaction between Na2CO3 and CaCl2 at ambient temperature in the presence of magnesium ions and ethanol solvent. The as-prepared products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and inductively coupled plasma atomic emission spectrometry (ICP-AES). The results show that a high magnesium concentration and ethanol solvent are necessary for the formation of the unusual peanut-like aggregates. In addition, a multistep phase transformation process from amorphous calcium carbonate (ACC) to a mixture of ACC and calcite and ultimately to calcite and aragonite was observed in the formation process of the unusual structures. A possible mechanism for the formation of the unusual peanut-shape aggregates has been proposed and discussed

  5. Phospho-control of TGF-β superfamily signaling

    Institute of Scientific and Technical Information of China (English)

    Katharine H Wrighton; Xia Lin; Xin-Hua Feng

    2009-01-01

    Members of the transforming growth factor-β(TGF-β)family control a broad range of cellular responses in metazoan organisms via autocrine,paracrine,and endocrine modes.Thus,aberrant TGF-β signaling can play a key role in the pathogenesis of several diseases.including cancer.TGF-βsignaling pathways are activated by a short phospho-cascade,from receptor phosphorylation to the subsequent phosphorylation and activation of downstream signal transducers called R-Smads.R-Smad phosphorylation state determines Smad complex assembly/disassembly,nuclear import/export,transcriptional activity and stability,and iS thus the most critical event in TGF-β signaling.Dephosphorylation of R-Smads by specific phosphatases prevents or terminates TGF-β signaling,highlighting the need to consider Smad(de)phosphorylation as a tightly controlled and dynamic event.This article illustrates the es-sential roles of reversible phosphorylation in controlling the strength and duration of TGF-β signaling and the eusu-ing physiological responses.

  6. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N;

    2005-01-01

    Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL) secretion in various vertebrates including the tilapia, Oreochromis mossambicus. The mechanism by which GnRH regulates lactotroph cell function is poorly understood. Using the advantageous characteristics of the teleost...... pituitary gland from which a nearly pure population of PRL cells can be isolated, we examined whether GnRH might stimulate PRL release through an increase in phospholipase C (PLC), inositol triphosphate (IP3), and intracellular calcium (Ca(i)2+) signaling. Using Ca(i)2+ imaging and the calcium-sensitive dye...... fura-2, we found that chicken GnRH-II (cGnRH-II) induced a rapid dose-dependent increase in Ca(i)2+ in dispersed tilapia lactotrophs. The Ca(i)2+ signal was abolished by U-73122, an inhibitor of PLC-dependent phosphoinositide hydrolysis. Correspondingly, cGnRH-II-induced tPRL188 secretion was inhibited...

  7. Dietary calcium intake and Renin Angiotensin System polymorphisms alter the blood pressure response to aerobic exercise: a randomized control design

    Directory of Open Access Journals (Sweden)

    Tsongalis Gregory J

    2007-01-01

    Full Text Available Abstract Background Dietary calcium intake and the renin angiotensin system (RAS regulate blood pressure (BP by modulating calcium homeostasis. Despite similar BP regulatory effects, the influence of dietary calcium intake alone and combined with RAS polymorphisms on the BP response following acute aerobic exercise (i.e., postexercise hypotension has not been studied. Thus, we examined the effect of dietary calcium intake and selected RAS polymorphisms on postexercise hypotension. Methods Subjects were men (n = 50, 43.8 ± 1.3 yr with high BP (145.3 ± 1.5/85.9 ± 1.1 mm Hg. They completed three experiments: non-exercise control and two cycle bouts at 40% and 60% of maximal oxygen consumption (VO2max. Subjects provided 3 d food records on five protocol-specific occasions. Dietary calcium intake was averaged and categorized as low (1R A/C were analyzed with molecular methods. Genotypes were reduced from three to two: ACE II/ID and ACE DD; or AT1R AA and AT1R CC/AC. Repeated measure ANCOVA tested if BP differed among experiments, dietary calcium intake level and RAS polymorphisms. Results Systolic BP (SBP decreased 6 mm Hg after 40% and 60% VO2max compared to non-exercise control for 10 h with LowCa (p 2max versus non-exercise control for 10 h among ACE II/ID (6 mm Hg and AT1R AA (8 mm Hg; and by 8 mm Hg after 40% VO2max among ACE DD and AT1R CC/CA (p 2max compared to non-exercise control for 10 h (p 2max (p ≥ 0.05. Conclusion SBP decreased after exercise compared to non-exercise control among men with low but not high dietary calcium intake. Dietary calcium intake interacted with the ACE I/D and AT1R A/C polymorphisms to further modulate postexercise hypotension. Interactions among dietary calcium intake, exercise intensity and RAS polymorphisms account for some of the variability in the BP response to exercise.

  8. Structure-activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 4: Role of acyl side chains on d-mannose.

    Science.gov (United States)

    Tsutsui, Nozomi; Tanabe, Genzoh; Ikeda, Nami; Okamura, Saika; Ogawa, Marika; Miyazaki, Kuniko; Kita, Ayako; Sugiura, Reiko; Muraoka, Osamu

    2016-10-01

    As part of an ongoing study on the structure-activity relationship of acremomannolipin A (1)-the novel glycolipid isolated from Acremonium strictum possessing potent calcium signal-modulating activity-the role of acyl substituents on the d-mannose moiety was examined. Three partially deacylated homologs (2a-2c) and 20 homologs (2d-2w) bearing different acyloxy side chains were synthesized via the stereoselective β-mannosylation of appropriately protected mannosyl sulfoxides (3) with d-mannitol derivatives (4), and their calcium signal-modulating activities were examined. The activities of 2a-2c were completely lost. Homologs bearing relatively short acyloxy groups at C-3, C-4, and C-6 positions (2t-2v) exhibited less activity than 1, whereas a heptanoyl homolog (2w: C7) maintained activity nearly equal to that of 1. When the acyl groups at these three positions were substituted by an octanoyl group (2i: C8), the activity was completely lost. On the other hand, of the 10 homologs in which the octanoyl at C-2 was substituted by other acyloxy moieties (2j-2s), three (2m: C7, 2n: C9, 2o: C10) maintained potent activity. These results suggested that peracylated mannose structure is critical for calcium signal-modulating activity, and this activity is precisely dependent on the length of four acyl side chains on d-mannose. PMID:27243802

  9. Tunable Signal Processing through a Kinase Control Cycle: the IKK Signaling Node

    Science.gov (United States)

    Behar, Marcelo; Hoffmann, Alexander

    2013-01-01

    The transcription factor NFκB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. Those dynamics are thought to play a role in controlling the physiological response to cytokines and pathogens. Biochemical evidence suggests that the NFκB inducing kinase, IKK, a signaling hub onto which many signaling pathways converge, is regulated via a regulatory cycle comprising a poised, an active, and an inactive state. We hypothesize that it operates as a modulator of signal dynamics, actively reshaping the signals generated at the receptor proximal level. Here we show that a regulatory cycle can function in at least three dynamical regimes, tunable by regulating a single kinetic parameter. In particular, the simplest three-state regulatory cycle can generate signals with two well-defined phases, each with distinct coding capabilities in terms of the information they can carry about the stimulus. We also demonstrate that such a kinase cycle can function as a signal categorizer classifying diverse incoming signals into outputs with a limited set of temporal activity profiles. Finally, we discuss the extension of the results to other regulatory motifs that could be understood in terms of the regimes of the three-state cycle. PMID:23823243

  10. Cross-talk between calcium-calmodulin and nitric oxide in abscisic acid signaling in leaves of maize plants

    Institute of Scientific and Technical Information of China (English)

    Jianrong Sang; Aying Zhang; Fan Lin; Mingpu Tan; Mingyi Jiang

    2008-01-01

    Using pharmacological and biochemical approaches,the signaling pathways between hydrogen peroxide (H2O2),calcium (Ca2+)-calmodulin (CAM),and nitric oxide (NO) in abscisic acid (ABA)-induced antioxidant defense were investigated in leaves of maize (Zea mays L.) plants.Treatments with ABA,H2O2,and CaCI2 induced increases in the generation of NO in maize mesophyll cells and the activity of nitric oxide synthase (NOS) in the cytosolic and microsomal fractions of maize leaves.However,such increases were blocked by the pretreatments with Ca2+ inhibitors and CaM antagonists.Meanwhile,pretreatments with two NOS inhibitors also suppressed the Ca2+-induced increase in the production of NO.On the other hand,treatments with ABA and the NO donor sodium nitroprusside (SNP) also led to increases in the concentration of cytosolic Ca2+ in protoplasts of mesophyll cells and in the expression of calmodulin 1 (CaMI) gene and the contents of CaM in leaves of maize plants,and the increases induced by ABA were reduced by the pretreatments with a NO scavenger and a NOS inhibitor.Moreover,SNP-induced increases in the expression of the antioxidant genes superoxide dismutase 4 (SOD4),cytosolic ascorbate peroxidase (cAPX),and glutathione reductase 1 (GRI) and the activities of the chloroplastic and cytosolic antioxidant enzymes were arrested by the pretreatments with Ca2+ inhibitors and CaM antagonists.Our results suggest that Ca2+-CaM functions both upstream and downstream of NO production,which is mainly from NOS,in ABA- and H2O2-induced antioxidant defense in leaves of maize plants.

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

    Science.gov (United States)

    Wang, Dingjie; Jin, Suoqin; Zou, Xiufen

    2016-02-01

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

  12. Digital signal processing in power electronics control circuits

    CERN Document Server

    Sozanski, Krzysztof

    2013-01-01

    Many digital control circuits in current literature are described using analog transmittance. This may not always be acceptable, especially if the sampling frequency and power transistor switching frequencies are close to the band of interest. Therefore, a digital circuit is considered as a digital controller rather than an analog circuit. This helps to avoid errors and instability in high frequency components. Digital Signal Processing in Power Electronics Control Circuits covers problems concerning the design and realization of digital control algorithms for power electronics circuits using

  13. Efficient Information Aggregation Strategies for Distributed Control and Signal Processing

    CERN Document Server

    Olshevsky, Alex

    2010-01-01

    This thesis is concerned with distributed control and coordination of networks consisting of multiple, potentially mobile, agents. This is motivated mainly by the emergence of large scale networks characterized by the lack of centralized access to information and time-varying connectivity. Control and optimization algorithms deployed in such networks should be completely distributed, relying only on local observations and information, and robust against unexpected changes in topology such as link failures. We will describe protocols to solve certain control and signal processing problems in this setting. We will demonstrate that a key challenge for such systems is the problem of computing averages in a decentralized way. Namely, we will show that a number of distributed control and signal processing problems can be solved straightforwardly if solutions to the averaging problem are available. The rest of the thesis will be concerned with algorithms for the averaging problem and its generalizations. We will (i)...

  14. Optimal coherent control of CARS: signal enhancement and background elimination

    CERN Document Server

    Gao, Fang; Shi, JunHui; Rabitz, Herschel; Wang, HaiFeng; Cheng, JiXin

    2011-01-01

    The resonant signal enhancement and nonresonant background elimination of Coherent Anti-Stokes Raman Scattering(CARS) process using femtosecond pulse-shaping techniques is analyzed. From the comparison of probe-pulse and three-pulse shaping schemes, it is certified that shaping probe pulse alone is sufficient for the optimal signal and background control separately, while keeping pump and Stokes pulses in transform limited forms. The optimal control of two-pulse CARS is also discussed. The variation method is used to gain an analytic solution for proble-pulse shaping scheme to maximize the difference of signal and background. Furthermore, the optimal broadband background suppression is studied with an appropriate objective funtional, and it shows that the well-known probe delay method is a quite good approximation to the optimal phase shaping scheme. Our results could help improve the performance of CARS spectroscopy and microscopy.

  15. Robust Bio-Signal Based Control of an Intelligent Wheelchair

    Directory of Open Access Journals (Sweden)

    Dongyi Chen

    2013-09-01

    Full Text Available In this paper, an adaptive human-machine interaction (HMI method that is based on surface electromyography (sEMG signals is proposed for the hands-free control of an intelligent wheelchair. sEMG signals generated by the facial movements are obtained by a convenient dry electrodes sensing device. After the signals features are extracted from the autoregressive model, control data samples are updated and trained by an incremental online learning algorithm in real-time. Experimental results show that the proposed method can significantly improve the classification accuracy and training speed. Moreover, this method can effectively reduce the influence of muscle fatigue during a long time operation of sEMG-based HMI.

  16. FireSignal Application Node for Subsystem Control

    Czech Academy of Sciences Publication Activity Database

    Duarte, A.; Santos, B.; Pereira, T.; Carvalho, B.; Fernandes, H.; Cahyna, Pavel; Písačka, Jan; Hron, Martin

    Aix-en-Provence: IAEA, 2009. s. 58-58. ISBN N. [Seventh IAEATechnical Meeting on Control, Data Acquisition, and Remote Participation for Fusion Research. 15.06.2009-19.06.2009, Aix-en-Provence] Institutional research plan: CEZ:AV0Z20430508 Keywords : FireSignal * Sub-system control * Java * Remote monitoring Subject RIV: BL - Plasma and Gas Discharge Physics http://www-fusion-magnetique.cea.fr/tmiaea2009/website/data/articles/000058.pdf

  17. Simulation of signalized intersection functioning with fuzzy control algorithm

    Directory of Open Access Journals (Sweden)

    Zinoviy STOTSKO

    2013-01-01

    Full Text Available In the course of research the fuzzy algorithm for traffic control at signalized intersection has been developed. Based on the results of simulating of intersection functioning during an hour and a day it has been established that using of developed fuzzy algorithm enables to reduce average and maximal queue lengths of vehicles before the intersection owing to adaptation of control system parameters to traffic flow volumes.

  18. Control of protein trafficking by reversible masking of transport signals.

    Science.gov (United States)

    Abraham, Omer; Gotliv, Karnit; Parnis, Anna; Boncompain, Gaelle; Perez, Franck; Cassel, Dan

    2016-04-15

    Systems that allow the control of protein traffic between subcellular compartments have been valuable in elucidating trafficking mechanisms. Most current approaches rely on ligand or light-controlled dimerization, which results in either retardation or enhancement of the transport of a reporter. We developed an alternative approach for trafficking regulation that we term "controlled unmasking of targeting elements" (CUTE). Regulated trafficking is achieved by reversible masking of the signal that directs the reporter to its target organelle, relying on the streptavidin-biotin system. The targeting signal is generated within or immediately after a 38-amino acid streptavidin-binding peptide (SBP) that is appended to the reporter. The binding of coexpressed streptavidin to SBP causes signal masking, whereas addition of biotin causes complex dissociation and triggers protein transport to the target organelle. We demonstrate the application of this approach to the control of nuclear and peroxisomal protein import and the generation of biotin-dependent trafficking through the endocytic and COPI systems. By simultaneous masking of COPI and endocytic signals, we were able to generate a synthetic pathway for efficient transport of a reporter from the plasma membrane to the endoplasmic reticulum. PMID:26941332

  19. Relationships between digital signal processing and control and estimation theory

    Science.gov (United States)

    Willsky, A. S.

    1978-01-01

    Research areas associated with digital signal processing and control and estimation theory are identified. Particular attention is given to image processing, system identification problems (parameter identification, linear prediction, least squares, Kalman filtering), stability analyses (the use of the Liapunov theory, frequency domain criteria, passivity), and multiparameter systems, distributed processes, and random fields.

  20. Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation

    Science.gov (United States)

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K.

    2013-01-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet. PMID:23008064

  1. Use of dairy products, lactose, and calcium and risk of ovarian cancer - results from a Danish case-control study

    DEFF Research Database (Denmark)

    Faber, Mette Tuxen; Jensen, Allan; Søgaard, Marie;

    2012-01-01

    A number of epidemiological studies have examined the association between use of dairy products and risk of ovarian cancer, but results are conflicting. Using data from a large Danish population-based case-control study we here further examined the association between dairy consumption, lactose......, and calcium and risk of overall ovarian cancer and histological types of ovarian cancer....

  2. Comparison of serum calcium, copper and iron levels in serum samples from gallstone patients and control subjects

    International Nuclear Information System (INIS)

    Objective: Present study was designed to investigate the levels of calcium, copper and iron in the serum samples of gallstone patients and control subjects with no personal or family history of gallstones. Methodology: Sera of 109 gallstone patients and 100 control subjects were obtained during January 2010 to November 2010 from Memon Charitable Hospital, Hyderabad. The serum calcium, copper and iron concentrations were determined by Hitachi double beam atomic absorption spectrophotometer 180 - 50. Results: Comparison of serum calcium, copper, and iron levels between gallstone patients and control subjects showed that all these variables were significantly (p0.01) was found when mean serum concentrations for these variables were compared between male and female gallstone patients, between female gallstone patients of up to 45 and over 45 years age and between female gallstone patients having up to 3 and more than 3 children. Conclusions: The higher levels of calcium, copper and iron in blood samples of gallstone patients compared to controls suggest that these metals do play a contributory role in the pathogenesis of human gallstones. (author)

  3. Solution combustion synthesis of calcium phosphate particles for controlled release of bovine serum albumin

    International Nuclear Information System (INIS)

    Four different phase compositions of calcium phosphate (CaP) particles were prepared via a solution combustion method. X-ray diffraction (XRD) and Rietveld analysis results revealed that the variations in the nominal Ca/P (molar) ratios were found to provide a favorable control in the different proportions of CaP materials. Bovine serum albumin (BSA) was used as a model protein to study the loading and release behavior. The release profile indicated that the BSA release rates depended on the phase compositions of the CaP particles, and showed an order of TCP-BSA > BCP-1-BSA > BCP-2-BSA > HA-BSA. The results suggested that the BSA protein release rate can be controlled by varying the phase compositions of CaP carriers. Moreover, the release process involved two stages: firstly surface diffusion via ion exchange and secondly intraparticle diffusion. - Highlights: • Solution combustion method was an efficient way to produced CaP powders. • Ca/P (molar) ratios provided a favorable control in the different proportions of phase composition. • BSA release rate varied depending on the phase composition of the CaP particles. • Two kinetic models were chosen to simulate the release kinetics of the drugs from CaP carriers

  4. Solution combustion synthesis of calcium phosphate particles for controlled release of bovine serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Junfeng, E-mail: daidai02304@163.com [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China); Jiangsu Laboratory of Advanced Functional Materials, Changshu Institute of Technology, Changshu (China); Zhao, Junjie; Qian, Yu; Zhang, Xiali; Zhou, Feifei; Zhang, Hong [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China); Lu, Hongbin [National Laboratory of Solid State Microstructures, College of Engineering and Applied Sciences, Nanjing University, Nanjing (China); Chen, JianHua; Wang, XuHong [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China); Jiangsu Laboratory of Advanced Functional Materials, Changshu Institute of Technology, Changshu (China); Yu, Wencong [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China)

    2015-05-01

    Four different phase compositions of calcium phosphate (CaP) particles were prepared via a solution combustion method. X-ray diffraction (XRD) and Rietveld analysis results revealed that the variations in the nominal Ca/P (molar) ratios were found to provide a favorable control in the different proportions of CaP materials. Bovine serum albumin (BSA) was used as a model protein to study the loading and release behavior. The release profile indicated that the BSA release rates depended on the phase compositions of the CaP particles, and showed an order of TCP-BSA > BCP-1-BSA > BCP-2-BSA > HA-BSA. The results suggested that the BSA protein release rate can be controlled by varying the phase compositions of CaP carriers. Moreover, the release process involved two stages: firstly surface diffusion via ion exchange and secondly intraparticle diffusion. - Highlights: • Solution combustion method was an efficient way to produced CaP powders. • Ca/P (molar) ratios provided a favorable control in the different proportions of phase composition. • BSA release rate varied depending on the phase composition of the CaP particles. • Two kinetic models were chosen to simulate the release kinetics of the drugs from CaP carriers.

  5. Postprandial effects of calcium phosphate supplementation on plasma concentration-double-blind, placebo-controlled cross-over human study

    OpenAIRE

    Trautvetter, Ulrike; Kiehntopf, Michael; Jahreis, Gerhard

    2013-01-01

    Background The aim of the present study was to examine the postprandial calcium and phosphate concentrations after supplementation with pentacalcium hydroxy-triphosphate (CaP). Methods Ten men participated in this double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. One group consumed bread enriched with CaP (plus 1 g calcium/d) and the other group a placebo product for three weeks. After a two week wash-out, the intervention was switched between ...

  6. A SIGNALING MODEL OF CONTROL BLOCK SALES BY ENTREPRENEURS

    OpenAIRE

    Lynda S. Livingston

    2007-01-01

    In this paper, we present a model in which higher-valued managers signal their value by voluntarily submitting to shareholder oversight. If a manager is willing to sell enough stock to release voting control, he is perceived to be of higher quality than if he had defensively maintained control. The implication of the model is that voluntary/control sales by insiders can be good news for the firm. This is consistent with the share-price increases that follow the deaths of entrenched managers.

  7. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Galtier, F., E-mail: f-galtier@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); CPID, Faculté de Pharmacie, 15 Av. Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, Montpellier (France); Mura, T., E-mail: t-mura@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Raynaud de Mauverger, E., E-mail: eric.raynaud-de-mauverger@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); Université Montpellier 1, 5 bd Henri IV CS 19044, 34967 Montpellier Cedex 2 (France); Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France); INSERM, U1046, 371 Avenue du Doyen G. Giraud, CHU Arnaud de Villeneuve, Bâtiment INSERM Crastes de Paulet, 34295 Montpellier Cedex 5 (France); Chevassus, H., E-mail: h-chevassus@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Farret, A., E-mail: a-farret@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Gagnol, J.-P., E-mail: jp-gagnol@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Costa, F., E-mail: francoisecosta@sfr.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Dupuy, A., E-mail: am-dupuy@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); and others

    2012-09-15

    Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca{sup 2+} homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca{sup 2+} spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P < 0.001) and CK (− 24.3 ± 99.1 ± 189.3vs 48.3 UI/L, P = 0.01) and a trend to an elevation of isoprostanes (193 ± 408 vs12 ± 53 pmol/mmol creatinine, P = 0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca{sup 2+} sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca{sup 2+} spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca{sup 2+} spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks. ► CK

  8. A sensor for calcium uptake

    OpenAIRE

    Collins, Sean; Meyer, Tobias

    2010-01-01

    Mitochondria — the cell’s power plants — increase their energy production in response to calcium signals in the cytoplasm. A regulator of the elusive mitochondrial calcium channel has now been identified.

  9. Controlled analogue experiments on propagation of seismic electromagnetic signals

    Institute of Scientific and Technical Information of China (English)

    HUANG Qinghua

    2005-01-01

    This study presented a method of laboratory analogue experiments based on a geographical scaling model and a waveguide model to investigate the characteristics of the propagation of seismic electromagnetic signals in the crust and the atmosphere. Some controlled experiments were done to evaluate the possible influence on the experimental results from the background electromagnetic field, geographical conditions, boundary effects, the source of electromagnetic signals (position, magnitude, and frequency), and media conductivity. The reliability and the extensibility of the above analogue experimental method were also investigated. This study indicated that such kind of analogue experimental method provided an intuitionistic way of studying the propagation of seismic electromagnetic signals, which is one of the most difficult research topics in seismo-electro- magnetism.

  10. Traffic Signals Control with Adaptive Fuzzy Controller in Urban Road Network

    Institute of Scientific and Technical Information of China (English)

    LI Yan; FAN Xiao-ping

    2008-01-01

    An adaptive fuzzy logic controller (AFC) is presented for the signal control of the urban traffic network.The AFC is composed of the signal control system-oriented control level and the signal controller-oriented fuzzy rules regulation level.The control level decides the signal tunings in an intersection with a fuzzy logic controller.The regulation level optimizes the fuzzy rules by the Adaptive Rule Module in AFC according to both the system performance index in current control period and the traffic flows in the last one.Consequently the system performances are improved.A weight coefficient controller (WCC) is also developed to describe the interactions of traffic flow among the adjacent intersections.So the AFC combined with the WCC can be applied in a road network for signal timings.Simulations of the AFC on a real traffic scenario have been conducted.Simulation results indicate that the adaptive controller for traffic control shows better performance than the actuated one.

  11. Serum Calcium Level in Hypertension

    OpenAIRE

    Hazari, Mohammed Abdul Hannan; Arifuddin, Mehnaaz Sameera; Muzzakar, Syed; Reddy, Vontela Devender

    2012-01-01

    Background: The alterations in extracellular calcium level may influence intracellular calcium level and possibly play a role in the pathogenesis of essential hypertension. Aim: The purpose was to find out the association between serum calcium levels and hypertension; and to compare the serum calcium levels between normotensive controls, hypertensive subjects on calcium channel blockers, and hypertensive subjects on antihypertensive medication other than calcium channel blockers. Materials an...

  12. Structural permeability of complex networks to control signals

    Science.gov (United States)

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

    2015-09-01

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

  13. FireSignal application Node for subsystem control

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, A.S., E-mail: andre.duarte@ipfn.ist.utl.p [Instituto de Plasmas e Fusao Nuclear - Instituto Superior Tecnico, Avenida Rovisco Pais 1, 1049-001 Lisbon (Portugal); Santos, B.; Pereira, T.; Carvalho, B.B.; Fernandes, H.; Neto, A. [Instituto de Plasmas e Fusao Nuclear - Instituto Superior Tecnico, Avenida Rovisco Pais 1, 1049-001 Lisbon (Portugal); Janky, F.; Cahyna, P.; Pisacka, J.; Hron, M. [Institute of Plasma Physics AS CR, Association EURATOM/IPP.CR, Za Slovankou 3, 182 00 Prague (Czech Republic)

    2010-07-15

    Modern fusion experiments require the presence of several subsystems, responsible for the different parameters involved in the operation of the machine. With the migration from the pre-programmed to the real-time control paradigm, their integration in Control, Data Acquisition, and Communication (CODAC) systems became an important issue, as this implies not only the connection to a main central coordination system, but also communications with related diagnostics and actuators. A subsystem for the control and operation of the vacuum, gas injection and baking was developed and installed in the COMPASS tokamak. These tasks are performed by dsPIC microcontrollers that receive commands from a hub computer and send information regarding the status of the operation. Communications are done in the serial protocol RS-232 through fibre optics. Java software, with an intuitive graphical user interface, for controlling and monitoring of the subsystem was developed and installed in a hub computer. In order to allow operators to perform these tasks remotely besides locally, this was integrated in the FireSignal system. Taking advantage of FireSignal features, it was possible to provide the users with, not only the same functionalities of the local application but also a similar user interface. An independent FireSignal Java Node bridges the central server and the control application. This design makes possible to easily reuse the Node for other subsystems or integrate the vacuum slow control in the other CODAC systems. The complete system, with local and remote control, has been installed successfully on COMPASS and has been in operation since April this year.

  14. FireSignal application Node for subsystem control

    International Nuclear Information System (INIS)

    Modern fusion experiments require the presence of several subsystems, responsible for the different parameters involved in the operation of the machine. With the migration from the pre-programmed to the real-time control paradigm, their integration in Control, Data Acquisition, and Communication (CODAC) systems became an important issue, as this implies not only the connection to a main central coordination system, but also communications with related diagnostics and actuators. A subsystem for the control and operation of the vacuum, gas injection and baking was developed and installed in the COMPASS tokamak. These tasks are performed by dsPIC microcontrollers that receive commands from a hub computer and send information regarding the status of the operation. Communications are done in the serial protocol RS-232 through fibre optics. Java software, with an intuitive graphical user interface, for controlling and monitoring of the subsystem was developed and installed in a hub computer. In order to allow operators to perform these tasks remotely besides locally, this was integrated in the FireSignal system. Taking advantage of FireSignal features, it was possible to provide the users with, not only the same functionalities of the local application but also a similar user interface. An independent FireSignal Java Node bridges the central server and the control application. This design makes possible to easily reuse the Node for other subsystems or integrate the vacuum slow control in the other CODAC systems. The complete system, with local and remote control, has been installed successfully on COMPASS and has been in operation since April this year.

  15. FireSignal Application Node for Subsystem Control

    International Nuclear Information System (INIS)

    Modern fusion experiments require the presence of several sub-systems, responsible for the different parameters involved in the operation of the machine. With the migration from the pre-programmed to the real-time control paradigm, their integration in Control, Data Acquisition, and Communication (CODAC) systems became an important issue, as this implies not only the connection to a main central coordination system, but also communications with related diagnostics and actuators. A sub-system for the control and operation of the vacuum, gas injection and baking was developed and installed in the COMPASS tokamak. These tasks are performed by 'dsPIC' micro-controllers that receive commands from a computer and send information regarding the status of the operation. Communications are done in the serial protocol RS-232 through fibre optics at speeds up to 1 Mbaud. A Java software, with an intuitive graphical user interface, for controlling and monitoring the sub-system was developed and installed in a hub computer. In order to allow operators to perform these tasks remotely besides locally, this was integrated in the FireSignal system. Taking advantage of FireSignal features, it was possible to provide the users with, not only the same functionalities of the local application but also a similar user interface. An independent FireSignal Java node bridges the central server and the control application. This design makes possible to easily reuse the node for other subsystems or integrate the vacuum slow control in the other CODAC systems. This document is composed of an abstract and a poster. (authors)

  16. Signal functions in delayed discriminative stimulus control by reinforcement sources.

    Science.gov (United States)

    Kuroda, Toshikazu; Lattal, Kennon A

    2014-05-01

    The discriminative functions of the response-reinforcer relation may contribute to the changes in response rates that occur when reinforcement is delayed. These properties were investigated in three experiments with pigeons using a discrete-trials conditional discrimination procedure. A concurrent variable-interval schedule was arranged on two side keys during a sample component. The key peck that ended the schedule (the sample response) initiated a delay with either a stimulus present throughout the delay interval (full signal), a stimulus present only during the first second of the interval (partial signal), or no stimulus present (unsignaled delay). The delay was followed by a choice component where one alternative was reinforced if the left sample response produced the choice component and the other if the right sample response produced the choice component. Accuracy was high with a full signal; slightly lower with a partial signal; and lowest without a signal. The results parallel the effects of similar delays programmed in conventional reinforcement schedules. This in turn suggests a possible discriminative effect of the response-reinforcer relation in the control of behavior by (delayed) reinforcement. PMID:24700527

  17. New technology in digital signal controllers, study & applications

    OpenAIRE

    Jaime Fonseca Beltrán; Gerardo Cazarez Ayala; Flor Kalíope Lomeli Dablantes

    2012-01-01

    This paper addresses the new technologies of digital signal controllers (DSC), is a general reference of the different companies making this type of device, in order that the reader has a general idea of the various products available market, highlighting thedifferences it with its predecessors, so as to identify in a clear and precise differences. This work was conceived in order to provide the user, a transition in the management of PIC ® microcontrollers general purpose, to the management ...

  18. Modelling of signal uncertainty and control objectives in robust controller design

    OpenAIRE

    Bates, Declan G

    1996-01-01

    This work develops a new paradigm for optimal robust controller synthesis in the frequency domain. A detailed examination is made of the engineering motivation and engineering efficacy underlying the various strands of robust control theory. The modelling of (a) signal uncertainty and (b) control system objectives in both Tioo and C\\ control theories is considered in particular detail. Based on this examination, a theory which can fa irly be described as ‘a m odified 7ioo control theory’ or ‘...

  19. Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control

    Institute of Scientific and Technical Information of China (English)

    Stefano Ginanni Corradini; Edoardo Poli; Adriano De Santis; Aldo Roda; Carolina Colliva; Patrizia Simoni; Adolfo Francesco Attili; Flaminia Ferri; Michela Mordenti; Luigi Iuliano; Maria Siciliano; Maria Antonella Burza; Bruno Sordi; Barbara Caciotti; Maria Pacini

    2012-01-01

    AIM:To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease.METHODS:Postmenopausal women with functional dyspepsia and/or constipation underwent a 12 d cycle of thermal (n =20) or tap (n =20) water controlled drinking.Gallbladder fasting volume at ultrasound,blood vitamin E,oxysterols (7-β-hydroxycholesterol.and 7-ketocholesterol),bile acid (BA),triglycerides,total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study.Food consumption,stool frequency and body weight were recorded daily.RESULTS:Blood lipids,oxysterols and vitamin E were not affected by either thermal or tap water consumption.Fasting gallbladder volume was significantly (P <0.005) smaller at the end of the study than at baseline in the TW (15.7 ± 1.1 mL vs 20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL).Total serum BA concentration was significantly (P <0.05) higher at the end of the study than at baseline in the TW (5.83-1.24 μmol vs 4.25 ± 1.00 μmol) but not in the tap water group (3.41 ± 0.46 μmol vs 2.91 ± 0.56 μmol).The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid.The number of pasta (P < 0.001),meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group.Body weight did not change at the end of the study as compared to baseline in both groups.CONCLUSION:Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake.

  20. Calcium-controlled conformational choreography in the N-terminal half of adseverin

    Science.gov (United States)

    Chumnarnsilpa, Sakesit; Robinson, Robert C.; Grimes, Jonathan M.; Leyrat, Cedric

    2015-09-01

    Adseverin is a member of the calcium-regulated gelsolin superfamily of actin-binding proteins. Here we report the crystal structure of the calcium-free N-terminal half of adseverin (iA1-A3) and the Ca2+-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small-angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca2+-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1-A3 provided insights into Ca2+-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca2+-independent F-actin severing by A1-A3, albeit at a lower efficiency than observed for gelsolin domains G1-G3. Together, these data address the calcium dependency of A1-A3 activity in relation to the calcium-independent activity of G1-G3.

  1. Nacre-like calcium carbonate controlled by ionic liquid/graphene oxide composite template

    International Nuclear Information System (INIS)

    Nacre-like calcium carbonate nanostructures have been mediated by an ionic liquid (IL)-graphene oxide (GO) composite template. The resultant crystals were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, and X-ray powder diffractometry (XRD). The results showed that either 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) or graphene oxide can act as a soft template for calcium carbonate formation with unusual morphologies. Based on the time-dependent morphology changes of calcium carbonate particles, it is concluded that nacre-like calcium carbonate nanostructures can be formed gradually utilizing [BMIM]BF4/GO composite template. During the process of calcium carbonate formation, [BMIM]BF4 acted not only as solvents but also as morphology templates for the fabrication of calcium carbonate materials with nacre-like morphology. Based on the observations, the possible mechanisms were also discussed. - Highlights: • Nacre-like CaCO3/GO were prepared by gas diffusion. • Ionic liquid/GO served as composite templates. • The interaction of Ca2+ ions and GO played a very important role in the formation of nacre-like CaCO3

  2. How salicylic acid takes transcriptional control over jasmonic acid signaling

    Directory of Open Access Journals (Sweden)

    Lotte eCaarls

    2015-03-01

    Full Text Available Transcriptional regulation is a central process in plant immunity. The induction or repression of defense genes is orchestrated by signaling networks that are directed by plant hormones of which salicylic acid (SA and jasmonic acid (JA are the major players. Extensive cross-communication between the hormone signaling pathways allows for fine tuning of transcriptional programs, determining resistance to invaders and trade-offs with plant development. Here, we give an overview of how SA can control transcriptional reprogramming of JA-induced genes in Arabidopsis thaliana. SA can influence activity and/or localization of transcriptional regulators by post-translational modifications of transcription factors and co-regulators. SA-induced redox changes, mediated by thioredoxins and glutaredoxins, modify transcriptional regulators that are involved in suppression of JA-dependent genes, such as NPR1 and TGA transcription factors, which affects their localization or DNA binding activity. Furthermore, SA can mediate sequestering of JA-responsive transcription factors away from their target genes by stalling them in the cytosol or in complexes with repressor proteins in the nucleus. SA also affects JA-induced transcription by inducing degradation of transcription factors with an activating role in JA signaling, as was shown for the ERF transcription factor ORA59. Additionally, SA can induce negative regulators, among which WRKY transcription factors, that can directly or indirectly inhibit JA-responsive gene expression. Finally, at the DNA level, modification of histones by SA-dependent factors can result in repression of JA-responsive genes. These diverse and complex regulatory mechanisms affect important signaling hubs in the integration of hormone signaling networks. Some pathogens have evolved effectors that highjack hormone crosstalk mechanisms for their own good, which are described in this review as well.

  3. Comparison of salivary calcium level in smokers and non-smokers with chronic periodontitis, aggressive periodontitis, and healthy controls

    OpenAIRE

    Kambalyal, Preeti; Kambalyal, Prabhuraj; Hungund, Shital

    2015-01-01

    Objective: The purpose of this study was to compare salivary calcium (Ca) level in smokers and non-smokers with chronic periodontitis, aggressive periodontitis, and healthy controls. Materials and Methods: 56 subjects were included in the study and were grouped as follows: 12 subjects who were periodontally healthy (Group I), 12 subjects having chronic periodontitis who were non-smokers (Group II), 12 non-smokers having aggressive periodontitis (Group III), 12 smokers with chronic periodontit...

  4. FireSignal - Data Acquisition and Control System Software

    International Nuclear Information System (INIS)

    Control of fusion devices requires good, non-ambiguous, easy to use user-interfaces to configure hardware devices. To solve this problem a highly generic system for data control and acquisition has been developed. Among the main features it allows remote hardware configuration, shot launching, data sharing between connected users and experiment monitoring. The system is fully distributed: the hardware driver nodes, clients and server are completely independent from each other and might be running in different operating systems and programmed in different languages. All the communication is provided through the Common Object Request Broker Architecture (CORBA) protocol. FireSignal was designed from the beginning to be as independent as possible from any kind of constraints as it's a plugin based system. Database, data viewers and the security system are some examples of what can easily be changed and adapted to the target machine's needs. All hardware is described in eXtendend Markup Language (XML) and from this information the FireSignal client application can build automatically Graphical User Interfaces (GUI) and validate the user's parameter configuration. Any type of hardware can be integrated in the system as long as it is described in XML and the respective driver is developed. Any modern programming language can be used to develop these drivers, and currently we use Python and Java generic drivers. All data storage and indexing is time stamped event-based s. Nodes are responsible for tagging the acquired samples with the absolute time stamps and to react to machine events. FireSignal is currently being used to control the ISTTOK/PT and CASTOR/CZ tokamaks. (author)

  5. New technology in digital signal controllers, study & applications

    Directory of Open Access Journals (Sweden)

    Jaime Fonseca Beltrán

    2012-05-01

    Full Text Available This paper addresses the new technologies of digital signal controllers (DSC, is a general reference of the different companies making this type of device, in order that the reader has a general idea of the various products available market, highlighting thedifferences it with its predecessors, so as to identify in a clear and precise differences. This work was conceived in order to provide the user, a transition in the management of PIC ® microcontrollers general purpose, to the management of advanced microcontrollerssuch as the dsPIC., Same to be found from the use of general purpose, even those who have special features designed to more specialized applications.

  6. Calcium's Role in Mechanotransduction during Muscle Development

    Directory of Open Access Journals (Sweden)

    Tatiana Benavides Damm

    2014-01-01

    Full Text Available Mechanotransduction is a process where cells sense their surroundings and convert the physical forces in their environment into an appropriate response. Calcium plays a crucial role in the translation of such forces to biochemical signals that control various biological processes fundamental in muscle development. The mechanical stimulation of muscle cells may for example result from stretch, electric and magnetic stimulation, shear stress, and altered gravity exposure. The response, mainly involving changes in intracellular calcium concentration then leads to a cascade of events by the activation of downstream signaling pathways. The key calcium-dependent pathways described here include the nuclear factor of activated T cells (NFAT and mitogen-activated protein kinase (MAPK activation. The subsequent effects in cellular homeostasis consist of cytoskeletal remodeling, cell cycle progression, growth, differentiation, and apoptosis, all necessary for healthy muscle development, repair, and regeneration. A deregulation from the normal process due to disuse, trauma, or disease can result in a clinical condition such as muscle atrophy, which entails a significant loss of muscle mass. In order to develop therapies against such diseased states, we need to better understand the relevance of calcium signaling and the downstream responses to mechanical forces in skeletal muscle. The purpose of this review is to discuss in detail how diverse mechanical stimuli cause changes in calcium homeostasis by affecting membrane channels and the intracellular stores, which in turn regulate multiple pathways that impart these effects and control the fate of muscle tissue.

  7. Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases

    Institute of Scientific and Technical Information of China (English)

    Nasrin NFJATBAKHSH; Zhong-ping FENG

    2011-01-01

    Calcium ion entry through voltage-gated calcium channels is essential for cellular signalling in a wide variety of cells and multiple physiological processes. Perturbations of voltage-gated calcium channel function can lead to pathophysiological consequences. Calcium binding proteins serve as calcium sensors and regulate the calcium channel properties via feedback mechanisms. This review highlights the current evidences of calcium binding protein-mediated channel regulation in human diseases.

  8. A study on hormonal control of calcium homeostasis in egyptian women

    International Nuclear Information System (INIS)

    This investigation was conducted to study the possible role of circulating hormones that regulate the calcium flux, in addition to serum levels of the inorganic mineral contents, calcium and phosphorus, on the pathogenesis of post-menopausal osteoporosis in egyptian women. The investigation studied also the response of these variables to both of estradiol withdrawal and age progress. Five groups of 11 postmenopausal osteoporotic (mean age 73 -+ 2.3 years), 26 postmenopausal women (mean age 56.2 -+ 2.4 years), 17 premenopausal women (mean age 48.8 -+ 0.7 years), 26 premenopausal women (mean age 41.5 -+ o.7 years) and 11 young adult premenopausal women(mean age 27.3 -+ 0.9 years) were recruited for this study. The post-peri- and pre- groups were further classified into subgroups according to their chronological age. Serum was assayed for parathyroid hormone (PTH), 25-hydroxyvitamin D, (25-OHD3), calcitonin (CT) total calcium (Ca), and inorganic phosphorus (ph), concentrations of estradiol (E2) in all subjects were also assayed for further correlation. The obtained data showed that the levels of hormones were not significantly changed among the different groups and subgroups leading to normal calcium homeostasis. PTH and total calcium were significantly correlated with both estrodial levels and chronological age

  9. The other side of cardiac Ca2+ signaling: transcriptional control

    Directory of Open Access Journals (Sweden)

    Alejandro eDomínguez-Rodríquez

    2012-11-01

    Full Text Available Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling, but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling. ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII and phosphatase calcineurin, both of which are activated by the complex Ca2+/ /Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n or cytoplasmic ([Ca2+]c, and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs in [Ca2+]c, needed to activate calcineurin.

  10. Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro?

    Science.gov (United States)

    Weems, Y S; Randel, R D; Carstens, G E; Welsh, T H; Weems, C W

    2004-04-01

    The major objective of this experiment was to determine whether the bovine placenta could be stimulated to secrete progesterone, since the bovine placenta secretes little progesterone when the corpus luteum is functional. Secondly, we wanted to determine whether reported abortifacients or progesterone or estrogen receptor antagonists affected bovine placental prostaglandin secretion. The ovine placenta secretes half of the circulating progesterone at day 90 of pregnancy and PGE2 appears to regulate ovine placental progesterone secretion. Calcium has been reported to regulate placental progesterone secretion in cattle. Diced 186-245-day placental slice explants from six Brahman and six Angus cows were incubated in vitro at 39.5 degrees C under 95% air: 5% CO2 at pH 7.2 in 5 ml of M-199 for 1 h in the absence of treatments and for 4 and 8 h in the presence of treatments. Treatments were: vehicle; R24571; compound 48/80; IP3; PGE2; CaCl2; cyclosporin A; lipopolysaccharide (endotoxin) from Salmonella abortus equi., enteriditis, and typhimurium; monensin; ionomycin; arachidonic acid; mimosine; palmitic acid; progesterone, androstenedione; estradiol-17beta; A23187; RU-486; or MER-25. Jugular and uterine venous plasma and culture media were analyzed for progesterone, PGE2 and PGF2alpha by radioimmunoassay (RIA). Plasma hormone data were analyzed by a One-Way Analysis of Variance (ANOVA). Hormone data in culture media were analyzed for breed and treatment effects by a Factorial Design (2 breeds, 2-range of days, 21 treatments) for ANOVA (2 x 2 x 21). Since hormone data secreted by placental tissue in vitro did not differ (P > or = 0.05) by breed or range of days of pregnancy, data were pooled and analyzed by a One-Way ANOVA. Concentrations of PGE2 in uterine venous blood were two-fold greater (P Angus than Brahman cows. PGE2 and PGF2alpha in vehicle controls increased from 4 to 8h (P or = 0.05) Progesterone in culture media treated with RU-486 increased (P or = 0

  11. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  12. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  13. Endocytic control of growth factor signalling: multivesicular bodies as signalling organelles

    Science.gov (United States)

    Dobrowolski, Radek; De Robertis, Edward M.

    2012-01-01

    Signal transduction and endocytosis are intertwined processes. The internalization of ligand-activated receptors by endocytosis has classically been thought to attenuate signals by targeting receptors for degradation in lysosomes, but it can also maintain signals in early signalling endosomes. In both cases, localization to multivesicular endosomes en route to lysosomes is thought to terminate signalling. However, during WNT signal transduction, sequestration of the enzyme glycogen synthase kinase 3 (GSK3) inside multivesicular endosomes results in the stabilization of many cytosolic proteins. Thus, the role of endocytosis during signal transduction may be more diverse than anticipated, and multivesicular endosomes may constitute a crucial signalling organelle. PMID:22108513

  14. Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

    OpenAIRE

    Britschgi, Adrian; Bill, Anke; Brinkhaus, Heike; Rothwell, Christopher; Clay, Ieuan; Duss, Stephan; Rebhan, Michael; Raman, Pichai; Guy, Chantale T.; Wetzel, Kristie; George, Elizabeth; Popa, M. Oana; Lilley, Sarah; Choudhury, Hedaythul; Gosling, Martin

    2013-01-01

    The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. The 11q13 region is amplified in ∼15% of breast cancers. Whether ANO1 is amplified in breast tumors, the extent to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained unkn...

  15. FireSignal-Data acquisition and control system software

    International Nuclear Information System (INIS)

    Control of fusion experiments requires non-ambiguous, easy to use, user-interfaces to configure hardware devices. With that aim, a highly generic system for data control and acquisition has been developed. Among the main features it allows remote hardware configuration, shot launching, data sharing between connected users and experiment monitoring. The system is fully distributed: the hardware driver nodes, clients and servers are completely independent from each other and might run in different operating systems and programmed in different languages. All the communication is provided through the Common Object Request Broker Architecture (CORBA) protocol. FireSignal is designed to be as independent as possible from any kind of constraints as it is a plugin based system. Database, data viewers and the security system are some examples of what can easily be changed and adapted to the target machine's needs. In this system, every hardware is described in eXtensible Markup Language (XML) and with this information Graphical User Interfaces (GUI) are automatically built and user's parameter configuration validated. Any type of hardware device can be integrated in the system as long as it is described in XML and the respective driver developed. Any modern programming language can be used to develop these drivers. Currently Python and Java generic drivers are used. Data storage and indexing is time stamp event-based. Nodes are responsible for tagging the acquired samples with the absolute time stamps and to react to machine events. FireSignal is currently being used to control the ISTTOK/PT and CASTOR/CZ tokamaks

  16. Calcium - urine

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003603.htm Calcium - urine To use the sharing features on this ... enable JavaScript. This test measures the amount of calcium in urine. All cells need calcium in order ...

  17. Calcium supplements

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007477.htm Calcium supplements To use the sharing features on this page, please enable JavaScript. WHO SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the ...

  18. 细菌中钙信号的作用%An update of calcium signaling in bacteria - A review

    Institute of Scientific and Technical Information of China (English)

    任晓慧; 王胜兰; 文莹; 杨克迁

    2009-01-01

    In eukaryotes, Ca~(2+) is an important second messenger and regulates diverse cellular activities ranging from muscle contraction to fertilization. In bacteria, growing evidence suggests that Ca~(2+) also plays important regulatory roles in various physiological processes. Here we review current understanding of calcium regulation in bacteria from the following aspects: 1) the concept of bacterial[Ca~(2+)]I and its determination; 2)cellular processes affected by[Ca~(2+)]; changes; 3) transportation of Ca~(2+) across bacterial membrane; 4)eukaryotic calcium binding proteins in bacteria and their functions.%越来越多的实验证明二价钙离子(Ca~2+)在细菌中有重要调控作用.本文从Ca~(2+)信号对细菌生理的影响、细胞内Ca~(2+)浓度及测定方法、细菌中Ca~(2+)的运输和Ca~(2+)结合蛋白四个方面综述了目前细菌中钙信号的研究进展.

  19. Viral infection controlled by a calcium-dependent lipid-binding module in ALIX.

    Science.gov (United States)

    Bissig, Christin; Lenoir, Marc; Velluz, Marie-Claire; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael; Gruenberg, Jean

    2013-05-28

    ALIX plays a role in nucleocapsid release during viral infection, as does lysobisphosphatidic acid (LBPA). However, the mechanism remains unclear. Here we report that LBPA is recognized within an exposed site in ALIX Bro1 domain predicted by MODA, an algorithm for discovering membrane-docking areas in proteins. LBPA interactions revealed a strict requirement for a structural calcium tightly bound near the lipid interaction site. Unlike other calcium- and phospholipid-binding proteins, the all-helical triangle-shaped fold of the Bro1 domain confers selectivity for LBPA via a pair of hydrophobic residues in a flexible loop, which undergoes a conformational change upon membrane association. Both LBPA and calcium binding are necessary for endosome association and virus infection, as are ALIX ESCRT binding and dimerization capacity. We conclude that LBPA recruits ALIX onto late endosomes via the calcium-bound Bro1 domain, triggering a conformational change in ALIX to mediate the delivery of viral nucleocapsids to the cytosol during infection. PMID:23664863

  20. Differential mitochondrial calcium responses in different cell types detected with a mitochondrial calcium fluorescent indicator, mito-GCaMP2

    Institute of Scientific and Technical Information of China (English)

    Min Chen; Yanru Wang; Tingting Hou; Huiliang Zhang; Aijuan Qu; Xianhua Wang

    2011-01-01

    Mitochondrial calcium plays a crucial role in mitochondriai metabolism,cell calcium handling,and cell death.However,some mechanisms concerning mitochondrial calcium regulation are still unknown,especially how mitochondrial calcium couples with cytosolic calcium.In this work,we constructed a novel mitochondrial calcium fluorescent indicator (mito-GCaMP2) by genetic manipulation.Mito-GCaMP2 was imported into mitochondria with high efficiency and the fluorescent signals co-localized with that of tetramethyl rhodamine methyl ester,a mitochondrial membrane potential indicator.The mitochondrial inhibitors specifically decreased the signals of mito-GCaMP2.The apparent Kd of mito-GCaMP2 was 195.0 nmol/L at pH 8.0 in adult rat cardiomyocytes.Furthermore,we observed that mito-GCaMP2 preferred the alkaline pH surrounding of mitochondria.In HeLa cells,we found that mitochondrial calcium ([Ca2+]mito)responded to the changes of cytosolic calcium ([Ca2+]cyto)induced by histamine or thapasigargin.Moreover,external Ca2+ (100 μmol/L) directly induced an increase of [Ca2+]mito in permeabilized HeLa cells.However,in rat cardiomyocytes [Ca2+]mito did not respond to cytosolic calcium transients stimulated by electric pacing or caffeine.In permeabilized cardiomyocytes,600 nmol/L free Ca2+ repeatedly increased the fluorescent signals of mito-GCaMP2,which excluded the possibility that mito-GCaMP2 lost its function in cardiomyocytes mitochondria.These results showed that the response of mitochondrial calcium is diverse in different cell lineages and suggested that mitochondria in cardiomyocytes may have a special defense mechanism to control calcium flux.

  1. Microglia Control Neuronal Network Excitability via BDNF Signalling

    Directory of Open Access Journals (Sweden)

    Francesco Ferrini

    2013-01-01

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

  2. Signalling and the control of skeletal muscle size

    Energy Technology Data Exchange (ETDEWEB)

    Otto, Anthony [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom); Patel, Ketan, E-mail: ketan.patel@reading.ac.uk [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom)

    2010-11-01

    Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

  3. Signalling and the control of skeletal muscle size

    International Nuclear Information System (INIS)

    Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

  4. FireSignal application Node for subsystem control

    Czech Academy of Sciences Publication Activity Database

    Duarte, A.S.; Santos, B.; Pereira, T.; Carvalho, B.B.; Fernandes, H.; Neto, A.; Janky, Filip; Cahyna, Pavel; Písačka, Jan; Hron, Martin

    2010-01-01

    Roč. 85, 3-4 (2010), s. 496-499. ISSN 0920-3796. [IAEA Technical Meeting on Control, Data Acquisition and Remote Participation for Fusion Research /7th./. Aix – en – Provence, 15.06.2009-19.06.2009] Institutional research plan: CEZ:AV0Z20430508 Keywords : Subsystems * CODAC * FireSignal * Java * Remote operation Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.143, year: 2010 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6V3C-4YYGPR8-4&_user=6542793&_coverDate=07%2F31%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000070123&_version=1&_urlVersion=0&_userid=6542793&md5=899631b6e2f4d05b21b04bde3cfb8e65&searchtype=a

  5. The mechanism of hetero-synaptic interaction based on spatiotemporal intracellular calcium dynamics.

    Directory of Open Access Journals (Sweden)

    Daiki Futagi

    2014-03-01

    Full Text Available In recent physiological experiments focusing on synaptic plasticity, it is shown that synaptic modifications induced at one synapse are accompanied by hetero-synaptic changes at neighbor sites (Bi, 2002. These evidences imply that the hetero-synaptic interaction plays an important role in reconfiguration of synaptic connections to form and maintain functional neural circuits (Takahashi et al., 2012. Although the mechanism of the interaction is still unclear, some physiological studies suggest that the hetero-synaptic interaction could be caused by propagation of intracellular calcium signals (Nishiyama et al., 2000. Concretely, a spike-triggered calcium increase initiates calcium ion propagation along a dendrite through activation of molecular processes at neighboring sites. Here we hypothesized that the mechanism of the hetero-synaptic interaction was based on the intracellular calcium signaling, which is regulated by interactions between NMDA receptors (NMDARs, voltage-dependent calcium channels (VDCCs and Ryanodine receptors (RyRs on endoplasmic reticulum (ER. To assess realizability of the hypothesized interaction mechanism, we simulated intracellular calcium dynamics at a cellular level, using the computational model that integrated the model of intracellular calcium dynamics (Keizer and Levine, 1996 and the multi-compartment neuron model (Poirazi et al., 2003. Using the proposed computational model, we induced calcium influxes at a local site in postsynaptic dendrite by controlling the spike timings of pre- and postsynaptic neurons. As a result, synchronized calcium influxes through NMDARs and VDCCs caused calcium release from ER. According to the phase plane analysis, RyR-mediated calcium release occurred when the calcium concentration in cytoplasm sufficiently increased under the condition of a high calcium concentration in ER. An NMDAR-mediated calcium influx was slow and persistent, consequently responsible for maintaining a high

  6. Tunable signal processing through modular control of transcription factor translocation

    Science.gov (United States)

    Hao, Nan; Budnik, Bogdan A.; Gunawardena, Jeremy; O’Shea, Erin K.

    2013-01-01

    Signaling pathways can induce different dynamics of transcription factor (TF) activation. We explored how TFs process signaling inputs to generate diverse dynamic responses. The budding yeast general stress responsive TF Msn2 acted as a tunable signal processor that could track, filter, or integrate signals in an input dependent manner. This tunable signal processing appears to originate from dual regulation of both nuclear import and export by phosphorylation, as mutants with one form of regulation sustained only one signal processing function. Versatile signal processing by Msn2 is crucial for generating distinct dynamic responses to different natural stresses. Our findings reveal how complex signal processing functions are integrated into a single molecule and provide a guide for the design of TFs with “programmable” signal processing functions. PMID:23349292

  7. Comparison of Physicochemical Properties of Nano- and Microsized Crystals in the Urine of Calcium Oxalate Stone Patients and Control Subjects

    Directory of Open Access Journals (Sweden)

    Jie Gao

    2014-01-01

    Full Text Available Purpose. To compare the properties of different sizes of urinary crystallites between calcium oxalate (CaOx calculi patients and healthy controls. Methods. We studied the average particle size, size distribution, intensity-autocorrelation curve, zeta potential (ζ, conductivity, mobility, aggregation state, and stability of different sizes of urinary crystallites by nanoparticle size analysis and transmission electron microscopy after filtration through a microporous membrane with an aperture size from 0.22 μm to 0.45, 1.2, 3, and 10 μm. Results. The urinary crystallites of the CaOx calculi patients were uneven and much easy to aggregate than those of controls. The number of large-sized crystallites of the patients was significantly more than that of the controls. The main components of the nanosized urinary crystallites in patients were CaOx monohydrate (COM, uric acid, and β-calcium phosphate, and these components were basically similar to those of the microsized urinary crystallites. The urinary crystallites of the calculi patients were easier to aggregate than that of the controls, and the small-sized urinary crystallites were much easier to agglomerate. Conclusions. The urinary system of CaOx calculi patients is unstable and highly susceptible to urinary crystallite aggregation. The rapid aggregation of urinary crystallites may be the key factor affecting urolithiasis formation.

  8. Measurements of intracellular calcium

    International Nuclear Information System (INIS)

    Intracellular calcium concentration ([Ca2+]i) has been measured in cultured cells by using Fura-2 load cells and a computer-controlled Perkin Elmer LS-5B spectrofluorometer. Increased [Ca2+]i in cells exposed to extracellular bilirubin was observed both with and without extracellular calcium. However, the increase was considerable larger with extracellular calcium. The enhancement of [Ca2+]i became smaller with decreasing bilirubin/BSA (bovine serum albumine) ratio. 5 refs., 5 figs

  9. Viral infection controlled by a calcium-dependent lipid-binding module in ALIX

    OpenAIRE

    Bissig, Christin; Lenoir, Marc; Velluz, Marie-Claire; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael; Gruenberg, Jean

    2013-01-01

    ALIX plays a role in nucleocapsid release during viral infection, as does lysobisphosphatidic acid (LBPA). However, the mechanism remains unclear. Here we report that LBPA is recognized within an exposed site in ALIX Bro1 domain predicted by MODA, an algorithm for discovering membrane-docking areas in proteins. LBPA interactions revealed a strict requirement for a structural calcium tightly bound near the lipid interaction site. Unlike other calcium– and phospholipid-binding proteins, the all...

  10. KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes.

    Science.gov (United States)

    McKenzie, Andrew J; Hoshino, Daisuke; Hong, Nan Hyung; Cha, Diana J; Franklin, Jeffrey L; Coffey, Robert J; Patton, James G; Weaver, Alissa M

    2016-05-01

    Secretion of RNAs in extracellular vesicles is a newly recognized form of intercellular communication. A potential regulatory protein for microRNA (miRNA) secretion is the critical RNA-induced silencing complex (RISC) component Argonaute 2 (Ago2). Here, we use isogenic colon cancer cell lines to show that overactivity of KRAS due to mutation inhibits localization of Ago2 to multivesicular endosomes (MVEs) and decreases Ago2 secretion in exosomes. Mechanistically, inhibition of mitogen-activated protein kinase kinases (MEKs) I and II, but not Akt, reverses the effect of the activating KRAS mutation and leads to increased Ago2-MVE association and increased exosomal secretion of Ago2. Analysis of cells expressing mutant Ago2 constructs revealed that phosphorylation of Ago2 on serine 387 prevents Ago2-MVE interactions and reduces Ago2 secretion into exosomes. Furthermore, regulation of Ago2 exosomal sorting controls the levels of three candidate miRNAs in exosomes. These data identify a key regulatory signaling event that controls Ago2 secretion in exosomes. PMID:27117408

  11. A model for signal processing and predictive control of semi-active structural control system

    Indian Academy of Sciences (India)

    M-H Shih; W-P Sung; Ching-Jong Wang

    2009-06-01

    The theory for structural control has been well developed and applied to perform excellent energy dissipation using dampers. Both active and semi-active control systems may be used to decide on the optimal switch point of the damper based on the current and past structural responses to the excitation of external forces. However, numerous noises may occur when the control signals are accessed and transported thus causing a delay of the damper. Therefore, a predictive control technique that integrates an improved method of detecting the control signal based on the direction of the structural motion, and a calculator for detecting the velocity using the least-square polynomial regression is proposed in this research. Comparisons of the analytical data and experimental results show that this predictor is effective in switching the moving direction of the semi-active damper. This conclusion is further verified using the component and shaking table test with constant amplitude but various frequencies, and the El Centro earthquake test. All tests confirm that this predictive control technique is effective to alleviate the time delay problem of semi-active dampers. This predictive control technique promotes about 30% to 40% reduction of the structural displacement response and about 35% to 45% reduction of the structural acceleration response.

  12. Movement Control of Robot Using Surface Electromyogram Signal

    Directory of Open Access Journals (Sweden)

    Mr. S. K. Pahuja Sachin Sharma

    2011-12-01

    Full Text Available The Electromyogram signals or EMG signals are generated whenever there is any muscular activity. These signals can be detected easily over the surface of the body. As these signals are generated whenever there is any muscular activity, so, we can recognize any muscular activity made by the human by measuring the amplitude of the signal. Based on decision made upon the amplitude of the EMG signal we can take many decisions or we can make machine of our interest. In simplest form any disabled person can turn on or turn of the machines just by contracting his fist. In this paper we have made an offline prototype of such machine which, in our case, will move the robot in one direction whenever there will be a sign of muscle contraction in the recorded EMG signal.

  13. Calcium-calmodulin signalling is involved in light-induced acidification by epidermal leaf cells of pea, Pisum sativum L.

    NARCIS (Netherlands)

    Elzenga, JTM; Staal, M; Prins, HBA

    1997-01-01

    Pathways of signal transduction of red and blue light-dependent acidification by leaf epidermal cells were studied using epidermal strips of the Argenteum mutant of Pisum sativum. In these preparations the contribution of guard cells to the acidification is minimal. The hydroxypyridine nifedipine, a

  14. Novel Genetic Loci Control Calcium Absorption and Femur Bone Mass as Well as Their Response to Low Calcium Intake in Male BXD Recombinant Inbred Mice.

    Science.gov (United States)

    Reyes Fernandez, Perla C; Replogle, Rebecca A; Wang, Libo; Zhang, Min; Fleet, James C

    2016-05-01

    Low dietary calcium (Ca) intake during growth limits peak bone mass but physiological adaptation can prevent this adverse effect. To assess the genetic control on the physiologic response to dietary Ca restriction (RCR), we conducted a study in 51 BXD lines fed either 0.5% (basal) or 0.25% (low) Ca diets from ages 4 to 12 weeks (n = 8/line/diet). Ca absorption (CaAbs), femur bone mineral density (BMD), and bone mineral content (BMC) were examined. ANCOVA with body size as covariate was used to detect significant line and diet main effects, and line-by-diet interactions. Body size-corrected residuals were used for linkage mapping and to estimate heritability (h(2) ). Loci controlling the phenotypes were identified using composite interval mapping on each diet and for the RCR. h(2) of basal phenotypes (0.37-0.43) and their RCR (0.32-0.38) was moderate. For each phenotype, we identified multiple quantitative trait loci (QTL) on each diet and for the RCR. Several loci affected multiple traits: Chr 1 (88.3-90.6 cM, CaAbs, BMC), Chr 4 (45.8-49.2 cM, CaAbs, BMD, BMC), Chr 8 (28.6-31.6 cM, CaAbs, BMD, RCR), and Chr 15 (13.6-24 cM, BMD, BMC; 32.3-36 cM, CaAbs RCR, BMD). This suggests that gene clusters may regulate interdependent bone-related phenotypes. Using in silico expression QTL (eQTL) mapping and bioinformatic tools, we identified novel candidates for the regulation of bone under Ca stress (Ext1, Deptor), and for the first time, we report genes modulating Ca absorption (Inadl, Sc4mol, Sh3rf1, and Dennd3), and both Ca and bone metabolism (Tceanc2, Tll1, and Aadat). Our data reveal gene-by-diet interactions and the existence of novel relationships between bone and Ca metabolism during growth. © 2015 American Society for Bone and Mineral Research. PMID:26636428

  15. Impaired control of L-type voltage-dependent calcium channels in experimental hypertension

    Czech Academy of Sciences Publication Activity Database

    Pintérová, Mária; Líšková, Silvia; Dobešová, Zdenka; Behuliak, M.; Kuneš, Jaroslav; Zicha, Josef

    2009-01-01

    Roč. 58, Suppl.2 (2009), S43-S54. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/08/0139; GA ČR(CZ) GA305/09/0336; GA AV ČR(CZ) IAA500110902; GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : calcium-activated K+ and Cl- channels * vasoactive systems * EDCF Subject RIV: ED - Physiology Impact factor: 1.430, year: 2009

  16. Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption

    OpenAIRE

    Zhu-Yun Cai; Fan Peng; Yun-Peng Zi; Feng Chen; Qi-Rong Qian

    2015-01-01

    Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to ...

  17. A practical method to determine background signals in dynamic control rod reactivity measurement

    International Nuclear Information System (INIS)

    A practical method to eliminate background signals from measured detector signals was developed for the Dynamic Control rod Reactivity Measurement (DCRM). The developed method is applied to determine the rod worth of Nuclear Power Plants in KOREA. (author)

  18. Diverse FGF receptor signaling controls astrocyte specification and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Kyungjun [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Song, Mi-Ryoung, E-mail: msong@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Bioimaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of)

    2010-05-07

    During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS.

  19. Diverse FGF receptor signaling controls astrocyte specification and proliferation

    International Nuclear Information System (INIS)

    During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS.

  20. Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density

    Science.gov (United States)

    Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S.; Dolphin, Annette C.

    2014-04-01

    Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS.

  1. CALCIUM SIGNALING, ION CHANNELS AND MORE: THE DT40 SYSTEM AS A MODEL OF VERTEBRATE ION HOMEOSTASIS AND CELL PHYSIOLOGY

    OpenAIRE

    Perraud, Anne-Laure; Schmitz, Carsten; Scharenberg, Andrew M.

    2006-01-01

    The DT40 B-lymphocyte cell line is a chicken bursal lymphocyte tumor cell line which grows rapidly, expresses a variety of types of constitutive and signal dependent ion transport systems., and supports the efficient use of stable and conditional genetic manipulations. Below, we review the use of DT40 cells in dissecting molecular mechanisms involved in Ca2+, Mg2+, and Zn2+ transport physiology. These studies highlight the flexibility and advantages the DT40 environment offers to investigator...

  2. Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens

    OpenAIRE

    Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Ágnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neur...

  3. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens

    OpenAIRE

    Zsuzsa Emri; Julianna Kardos

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signalling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neu...

  4. Intrarenal purinergic signaling in the control of renal tubular transport

    DEFF Research Database (Denmark)

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    Renal tubular epithelial cells receive hormonal input that regulates volume and electrolyte homeostasis. In addition, numerous intrarenal, local signaling agonists have appeared on the stage of renal physiology. One such system is that of intrarenal purinergic signaling. This system involves all ...... of NaCl at the macula densa. This review describes the relevant aspects of local, intrarenal purinergic signaling and outlines its integrative concepts....

  5. Adaptive Traffic Signalization Model using Neuro-Fuzzy Controllers

    OpenAIRE

    Devesh Batra; Pragya Verma

    2014-01-01

    Current traffic lights are pre-programmed and use daily signal timing schedules, which contribute to traffic congestion and delay. Thus, with the increase in the number of vehicles on road, need for adaptive signal technology arises which has the potential to adjust the timing of red, yellow and green lights in order to accommodate changing traffic patterns and ease traffic congestion. In this paper, we present a model for adaptive traffic signalization, which uses fuzzy neura...

  6. The Steam Boiler Controller Problem in Signal-Coq

    OpenAIRE

    Kerboeuf, Mickaël; Nowak, David; Talpin, Jean-Pierre

    1999-01-01

    Among the various formalisms for the design of reactive systems, the SIGNAL-CO- Q formal approach, i.e. the combined use of the synchronous dataflow language SIGNAL and the proof assistant COQ, seems to be especially suited and practical. Indeed, the deterministic concurrency implied by the synchronous model on which SIGNAL is founded strongly simplifies the specification and the verification of such systems. Moreover, COQ is not limited to some kind of properties and so, its use enables to d...

  7. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    OpenAIRE

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2015-01-01

    At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dy...

  8. Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption

    Directory of Open Access Journals (Sweden)

    Zhu-Yun Cai

    2015-07-01

    Full Text Available Synthetic calcium phosphate (CaP-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP nanostructure was prepared under weak acidic conditions (pH 5, while the HAP nanorod was prepared under neutral (pH 7 and weak alkali (pH 9 condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption.

  9. SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce apoptosis.

    Science.gov (United States)

    Chami, M; Gozuacik, D; Lagorce, D; Brini, M; Falson, P; Peaucellier, G; Pinton, P; Lecoeur, H; Gougeon, M L; le Maire, M; Rizzuto, R; Bréchot, C; Paterlini-Bréchot, P

    2001-06-11

    By pumping calcium from the cytosol to the ER, sarco/endoplasmic reticulum calcium ATPases (SERCAs) play a major role in the control of calcium signaling. We describe two SERCA1 splice variants (S1Ts) characterized by exon 4 and/or exon 11 splicing, encoding COOH terminally truncated proteins, having only one of the seven calcium-binding residues, and thus unable to pump calcium. As shown by semiquantitative RT-PCR, S1T transcripts are differentially expressed in several adult and fetal human tissues, but not in skeletal muscle and heart. S1T proteins expression was detected by Western blot in nontransfected cell lines. In transiently transfected cells, S1T homodimers were revealed by Western blot using mildly denaturing conditions. S1T proteins were shown, by confocal scanning microscopy, to colocalize with endogenous SERCA2b into the ER membrane. Using ER-targeted aequorin (erAEQ), we have found that S1T proteins reduce ER calcium and reverse elevation of ER calcium loading induced by SERCA1 and SERCA2b. Our results also show that SERCA1 variants increase ER calcium leakage and are consistent with the hypothesis of a cation channel formed by S1T homodimers. Finally, when overexpressed in liver-derived cells, S1T proteins significantly induce apoptosis. These data reveal a further mechanism modulating Ca(2+) accumulation into the ER of nonmuscle cells and highlight the relevance of S1T proteins to the control of apoptosis. PMID:11402072

  10. Utilization of excitation signal harmonics for control of nonlinear systems

    DEFF Research Database (Denmark)

    Vinther, Kasper; Rasmussen, Henrik; Izadi-Zamanabadi, Roozbeh; Stoustrup, Jakob

    signal together with Fourier analysis to generate a feedback signal and simulations have shown that different system gains and time constants does not change the global equilibrium/operating point. An evaporator in a refrigeration system was used as example in the simulations, however, it is anticipated...

  11. Automatic analysis of signals during Eddy currents controls

    International Nuclear Information System (INIS)

    A method and the corresponding instrument have been developed for automatic analysis of Eddy currents testing signals. This apparatus enables at the same time the analysis, every 2 milliseconds, of two signals at two different frequencies. It can be used either on line with an Eddy Current testing instrument or with a magnetic tape recorder

  12. Coupling calcium/calmodulin-mediated signaling and herbivore-induced plant response through calmodulin-binding transcription factor AtSR1/CAMTA3.

    Science.gov (United States)

    Qiu, Yongjian; Xi, Jing; Du, Liqun; Suttle, Jeffrey C; Poovaiah, B W

    2012-05-01

    Calcium/calmodulin (Ca(2+)/CaM) has long been considered a crucial component in wound signaling pathway. However, very few Ca(2+)/CaM-binding proteins have been identified which regulate plant responses to herbivore attack/wounding stress. We have reported earlier that a family of Ca(2+)/CaM-binding transcription factors designated as AtSRs (also known as AtCAMTAs) can respond differentially to wounding stress. Further studies revealed that AtSR1/CAMTA3 is a negative regulator of plant defense, and Ca(2+)/CaM-binding to AtSR1 is indispensable for the suppression of salicylic acid (SA) accumulation and disease resistance. Here we report that Ca(2+)/CaM-binding is also critical for AtSR1-mediated herbivore-induced wound response. Interestingly, atsr1 mutant plants are more susceptible to herbivore attack than wild-type plants. Complementation of atsr1 mutant plants by overexpressing wild-type AtSR1 protein can effectively restore plant resistance to herbivore attack. However, when mutants of AtSR1 with impaired CaM-binding ability were overexpressed in atsr1 mutant plants, plant resistance to herbivore attack was not restored, suggesting a key role for Ca(2+)/CaM-binding in wound signaling. Furthermore, it was observed that elevated SA levels in atsr1 mutant plants have a negative impact on both basal and induced biosynthesis of jasmonates (JA). These results revealed that Ca(2+)/CaM-mediated signaling regulates plant response to herbivore attack/wounding by modulating the SA-JA crosstalk through AtSR1. PMID:22371088

  13. Comparative proteomics of root plasma membrane proteins reveals the involvement of calcium signalling in NaCl-facilitated nitrate uptake in Salicornia europaea.

    Science.gov (United States)

    Nie, Lingling; Feng, Juanjuan; Fan, Pengxiang; Chen, Xianyang; Guo, Jie; Lv, Sulian; Bao, Hexigeduleng; Jia, Weitao; Tai, Fang; Jiang, Ping; Wang, Jinhui; Li, Yinxin

    2015-08-01

    Improving crop nitrogen (N) use efficiency under salinity is essential for the development of sustainable agriculture in marginal lands. Salicornia europaea is a succulent euhalophyte that can survive under high salinity and N-deficient habitat conditions, implying that a special N assimilation mechanism may exist in this plant. In this study, phenotypic and physiological changes of S. europaea were investigated under different nitrate and NaCl levels. The results showed that NaCl had a synergetic effect with nitrate on the growth of S. europaea. In addition, the shoot nitrate concentration and nitrate uptake rate of S. europaea were increased by NaCl treatment under both low N and high N conditions, suggesting that nitrate uptake in S. europaea was NaCl facilitated. Comparative proteomic analysis of root plasma membrane (PM) proteins revealed 81 proteins, whose abundance changed significantly in response to NaCl and nitrate. These proteins are involved in metabolism, cell signalling, transport, protein folding, membrane trafficking, and cell structure. Among them, eight proteins were calcium signalling components, and the accumulation of seven of the above-mentioned proteins was significantly elevated by NaCl treatment. Furthermore, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was significantly elevated in S. europaea under NaCl treatment. The application of the Ca(2+) channel blocker LaCl3 not only caused a decrease in nitrate uptake rate, but also attenuated the promoting effects of NaCl on nitrate uptake rates. Based on these results, a possible regulatory network of NaCl-facilitated nitrate uptake in S. europaea focusing on the involvement of Ca(2+) signalling was proposed. PMID:25956883

  14. A Two-Stage Fuzzy Logic Control Method of Traffic Signal Based on Traffic Urgency Degree

    OpenAIRE

    Yan Ge

    2014-01-01

    City intersection traffic signal control is an important method to improve the efficiency of road network and alleviate traffic congestion. This paper researches traffic signal fuzzy control method on a single intersection. A two-stage traffic signal control method based on traffic urgency degree is proposed according to two-stage fuzzy inference on single intersection. At the first stage, calculate traffic urgency degree for all red phases using traffic urgency evaluation module and select t...

  15. Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing

    Science.gov (United States)

    Alhadeff, Amber L.; Grill, Harvey J.

    2015-01-01

    Central oxytocin (OT) administration reduces food intake and its effects are mediated, in part, by hindbrain oxytocin receptor (OT-R) signaling. The neural substrate and mechanisms mediating the intake inhibitory effects of hindbrain OT-R signaling are undefined. We examined the hypothesis that hindbrain OT-R-mediated feeding inhibition results from an interaction between medial nucleus tractus solitarius (mNTS) OT-R signaling and the processing of gastrointestinal (GI) satiation signals by neurons of the mNTS. Here, we demonstrated that mNTS or fourth ventricle (4V) microinjections of OT in rats reduced chow intake in a dose-dependent manner. To examine whether the intake suppressive effects of mNTS OT-R signaling is mediated by GI signal processing, rats were injected with OT to the 4V (1 μg) or mNTS (0.3 μg), followed by self-ingestion of a nutrient preload, where either treatment was designed to be without effect on chow intake. Results showed that the combination of mNTS OT-R signaling and GI signaling processing by preload ingestion reduced chow intake significantly and to a greater extent than either stimulus alone. Using enzyme immunoassay, endogenous OT content in mNTS-enriched dorsal vagal complex (DVC) in response to ingestion of nutrient preload was measured. Results revealed that preload ingestion significantly elevated endogenous DVC OT content. Taken together, these findings provide evidence that mNTS neurons are a site of action for hindbrain OT-R signaling in food intake control and that the intake inhibitory effects of hindbrain mNTS OT-R signaling are mediated by interactions with GI satiation signal processing by mNTS neurons. PMID:25740340

  16. Two Dimensional Finite Element Model to Study Calcium Distribution in Oocytes

    Science.gov (United States)

    Naik, Parvaiz Ahmad; Pardasani, Kamal Raj

    2015-06-01

    Cytosolic free calcium concentration is a key regulatory factor and perhaps the most widely used means of controlling cellular function. Calcium can enter cells through different pathways which are activated by specific stimuli including membrane depolarization, chemical signals and calcium depletion of intracellular stores. One of the important components of oocyte maturation is differentiation of the Ca2+ signaling machinery which is essential for egg activation after fertilization. Eggs acquire the ability to produce the fertilization-specific calcium signal during oocyte maturation. The calcium concentration patterns required during different stages of oocyte maturation are still not completely known. Also the mechanisms involved in calcium dynamics in oocyte cell are still not well understood. In view of above a two dimensional FEM model has been proposed to study calcium distribution in an oocyte cell. The parameters such as buffers, ryanodine receptor, SERCA pump and voltage gated calcium channel are incorporated in the model. Based on the biophysical conditions the initial and boundary conditions have been framed. The model is transformed into variational form and Ritz finite element method has been employed to obtain the solution. A program has been developed in MATLAB 7.10 for the entire problem and executed to obtain numerical results. The numerical results have been used to study the effect of buffers, RyR, SERCA pump and VGCC on calcium distribution in an oocyte cell.

  17. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens.

    Science.gov (United States)

    Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Agnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca(2+) transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca(2+) transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca(2+) dynamics evoked by GHB suggested that Ca(2+) was released from internal stores. Similarly to SUC, the GHB response was also characterized by an effective concentration of 50 μM. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca(2+) signal remained in mice lacking GABA(B) receptor type 1 subunit in the presence and absence of the N-Methyl-d-Aspartate (NMDA) receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV), indicating action mechanisms independent of the GABA(B) or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252, and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91) also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca(2+) signaling in astrocytic networks. PMID:22180742

  18. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Zsuzsa Emri

    2011-12-01

    Full Text Available Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signalling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC and gamma-hydroxybutyrate (GHB that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc. Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca2+ transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca2+ dynamics evoked by GHB suggested that Ca2+ was released from internal stores. Similarly to SUC, the GHB-response was also characterized by an effective concentration of 50 µM. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca2+ signal remained in mice lacking GABAB receptor type 1 subunit in the presence and absence of the N-Methyl-D-Aspartate (NMDA receptor antagonist (2R-amino-5-phosphonovaleric acid (APV, indicating action mechanisms independent of the GABAB or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252 and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91 also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca2+ signalling in astrocytic networks.

  19. Controlled superficial assembly of DNA-amorphous calcium phosphate nanocomposite spheres for surface-mediated gene delivery.

    Science.gov (United States)

    Oyane, Ayako; Araki, Hiroko; Nakamura, Maki; Shimizu, Yoshiki; Shubhra, Quazi T H; Ito, Atsuo; Tsurushima, Hideo

    2016-05-01

    Surface-mediated gene delivery systems have many potential applications in tissue engineering. We recently fabricated an assembly consisting of DNA-amorphous calcium phosphate (DNA-ACP) nanocomposite spheres on a polymer substrate via coprecipitation in a labile supersaturated calcium phosphate (CaP) solution and demonstrated the assembly's high gene delivery efficacy. In this study, we conducted a detailed investigation of the coprecipitation process in solution and revealed that the negatively charged DNA molecules were immobilized in the ACP spheres during the initial stage of coprecipitation and functioned as both sphere-dispersing and size-regulating agents. As a result, the DNA-ACP nanocomposites grew into size-regulated submicrospheres in solution and assembled onto the substrate via gravity sedimentation. The assembled nanocomposite spheres were chemically anchored to the substrate surface through an intermediate layer of CaP-based nanoparticles that was formed heterogeneously at the substrate surface. The coprecipitation conditions, i.e., coprecipitation time and Ca and P concentrations in solution, greatly affected the state of assembly of the nanocomposite spheres, thereby influencing the gene expression level of the cells cultured on the substrate. Increasing the number density and decreasing the size of the nanocomposite spheres did not always increase the assembly's gene delivery efficacy (per surface area of the substrate) due to adverse effects on cellular viability. As demonstrated herein, controlling the coprecipitation conditions is important for designing a cell-stimulating and biocompatible scaffold surface consisting of an assembly of DNA-ACP nanocomposite spheres. PMID:26896659

  20. Calcium and the role of motoneuronal doublets in skeletal muscle control

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2009-01-01

    + resources and the dynamics of calcium transport is proposed. The model correctly accounts for catch-like effects in slow and fast-twitch fibers during long-train stimulations and force-frequency relations in different muscle types. Results obtained from the model compare favorably to experiments showing......This work presents a novel structural model of skeletal muscle activation, providing a physiologically based account of frequency-dependent muscle responses like the catch-like effect. Numerous Ca2+ reservoirs within muscle fibers are considered, and a simplified analysis of the allocation of Ca2...... onset amplitude of the catch-like effect. This suggests that a plausible physiological function for the inclusion of doublets or the exclusion of individual spikes within a regular motor-neuronal spike-train is to rapidly bring skeletal muscles to predefined target forces according to prespecified motor...

  1. Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.

    Directory of Open Access Journals (Sweden)

    Limin Liu

    Full Text Available Estrogen is traditionally thought to exert genomic actions through members of the nuclear receptor family. Here, we investigated the rapid nongenomic effects of 17β-estradiol (E2 on tumor necrosis factor α (TNF-α production following lipopolysaccharide (LPS stimulation in mouse bone marrow-derived macrophages (BMMs. We found that LPS induced TNF-α production in BMMs via phosphorylation of p38 mitogen-activated protein kinase (MAPK. E2 itself did not affect the MAPK pathway, although it attenuated LPS-induced TNF-α production through suppression of p38 MAPK activation. Recently, G protein-coupled receptor 30 (GPR30 was suggested to be a membrane estrogen receptor (mER that can mediate nongenomic estradiol signaling. We found that BMMs expressed both intracellular estrogen receptors (iER and mER GPR30. The specific GPR30 antagonist G-15 significantly blocked effects of estradiol on LPS-induced TNF-α production, whereas an iER antagonist did not. Moreover, E2 induced a rapid rise in intracellular free Ca(2+ that was due to the influx of extracellular Ca(2+ and was not inhibited by an iER antagonist or silencing of iER. Ca(2+ influx was also induced by an impermeable E2 conjugated to BSA (E2-BSA, which has been used to investigate the nongenomic effects of estrogen. Consequently, Ca(2+, a pivotal factor in E2-stimulated nongenomic action, was identified as the key mediator. The inhibitory effects of E2 on LPS-induced TNF-α production and p38 MAPK phosphorylation were dependent on E2-triggered Ca(2+ influx because BAPTA, an intracellular Ca(2+ chelator, prevented these effects. Taken together, these data indicate that E2 can down-regulate LPS-induced TNF-α production via blockade of p38 MAPK phosphorylation through the mER-mediated nongenomic Ca(2+ signaling pathway in BMMs.

  2. Effect of calcium-vitamin D supplementation on metabolic profiles in pregnant women at risk for pre-eclampsia: a randomized placebo-controlled trial.

    Science.gov (United States)

    Asemi, Zatollah; Tabassi, Zohreh; Heidarzadeh, Zahra; Khorammian, Hassan; Sabihi, Sima-Sadat; Samimi, Mansooreh

    2012-04-01

    Increased metabolic profiles during pregnancy are associated with an increased risk of maternal and neonatal morbidity and remain a significant medical challenge. To our knowledge, no reports are available indicating the effects of calcium-vitamin D supplementation on metabolic profiles among pregnant women at risk for pre-eclampsia. This study was designed to determine the effects of consumption calcium-vitamin D supplements on metabolic profiles among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was performed among 49 pregnant women at risk for pre-eclampsia, primigravida, aged 18-35 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to consume the placebo (n = 25) or calcium-vitamin D supplements (n = 24) for 9 weeks. Calcium-vitamin D supplements were containing 500 mg carbonate calcium plus 200 IU vitamin D3. Fasting blood samples were taken at baseline and after 9 week intervention to measures of Fasting Plasma Glucose (FPG) and serum lipid profiles. Consumption of calcium-vitamin D supplements resulted in decreased FPG and serum triglycerides levels as compared to the placebo (-9.1 vs. 0.5 mg dL(-1); p = 0.03, -11.7 vs. 49.9 mg dL(-1); p = 0.001, respectively). No significant differences were found comparing calcium-vitamin D supplements and the placebo in terms of their effect on serum total-, HDL-, LDL-cholesterol levels. Within-group differences in the placebo group revealed a significant increase in serum triglycerides levels (+49.9 mg dL(-1), p < 0.0001). In conclusion, consumption of calcium-vitamin D supplements for 9 weeks during pregnancy among pregnant women at risk for pre-eclampsia resulted in decreased FPG and serum triglycerides levels as compared to the placebo group, but could not affect serum total-, HDL-, LDL-cholesterol levels. PMID:24163957

  3. Control of polarization signal distortion by frequency domain phase conjugation in optical fiber systems

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Optical frequency domain phase conjugation(FDPC) is based on phase conjuga-tion of spectrum of an input signal.It is equivalent to the phase conjugation and the time reversal of the temporal envelope of an input signal.The use of FDPC to con-trol polarization signal distortion in birefringent optical fiber systems is proposed.Evolution of polarization signals in the system using midway FDPC is analyzed theoretically and simulated numerically.It is shown that the distortion of polariza-tion signals can be controlled effectively by FDPC.The impairments due to disper-sion and nonlinear effects can be suppressed simultaneously.

  4. Control of polarization signal distortion by frequency domain phase conjusation in optical fiber systems

    Institute of Scientific and Technical Information of China (English)

    BU Yang; WANG XiangZhao

    2008-01-01

    Optical frequency domain phase conjugation (FDPC) is based on phase conjugation of spectrum of an input signal. It is equivalent to the phase conjugation and the time reversal of the temporal envelope of an input signal. The use of FDPC to con-trol polarization signal distortion in birefringent optical fiber systems is proposed. Evolution of polarization signals in the system using midway FDPC is analyzed theoretically and simulated numerically. It is shown that the distortion of polariza-tion signals can be controlled effectively by FDPC. The impairments due to disper-sion and nonlinear effects can be suppressed simultaneously.

  5. SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

    Institute of Scientific and Technical Information of China (English)

    LI Hong; ZHOU Zhiyuan; DAI Rongyang; LUO Bo; ZHENG Xiaoli; YANG Wenli; HE Tao; WU Minglu

    2004-01-01

    In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as "signal scattering", "positive feedback", "negative feedback" and "B-Raf shunt". Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

  6. TTCScope - An analysis tool for the Trigger, Timing and Control signals of the LHC experiments

    CERN Document Server

    Moosavi, P; Pauly, T

    2013-01-01

    This document describes a scope-based signal analysis tool for the Trigger, Timing and Control system of the LHC experiments. The TTC signal is digitized and read out using a digital sampling oscilloscope, and then analyzed in software. From the sampled signal, the BC clock is recovered along with the signal contents: level-1 accepts, commands, and trigger types. Two common use-cases in the ATLAS experiment are addressed: analysis of TTC signals and calibration of TTC crates. The latter includes calibration schemes for two determining the optimal signal phase for two types of messages, level-1 accepts and commands.

  7. Digital signal processing for NDT; Traitement numerique du signal en controle non destructif

    Energy Technology Data Exchange (ETDEWEB)

    Georgel, B.

    1994-12-31

    NDT begins to adapt and use the most recent developments of digital signal and image processing. We briefly sum up the main characteristics of NDT situations (particularly noise and inverse problem formulation) and comment on techniques already used or just emerging (SAFT, split spectrum, adaptive learning network, noise reference filtering, stochastic models, neural networks). This survey is focused on ultrasonics, eddy currents and X-ray radiography. The final objective of end users (availability of automatic diagnosis systems) cannot be achieved only by signal processing algorithms. A close cooperation with other techniques such as artificial intelligence has therefore to be implemented. (author). 20 refs.

  8. Effect of Poly(γ-glutamic acid) on the Physiological Responses and Calcium Signaling of Rape Seedlings (Brassica napus L.) under Cold Stress.

    Science.gov (United States)

    Lei, Peng; Xu, Zongqi; Ding, Yan; Tang, Bao; Zhang, Yunxia; Li, Huashan; Feng, Xiaohai; Xu, Hong

    2015-12-01

    Cold stress adversely affects plant growth and development. Poly(γ-glutamic acid) (γ-PGA) is a potential plant growth regulator that may be an effective cryoprotectant that prevents crops from damage during cold weather. In this study, the effects of γ-PGA on the physiological responses of rape seedlings subject to cold stress were investigated using hydroponic experiments. We determined that the malondialdehyde content was decreased by 33.4% and the proline content was increased by 62.5% by γ-PGA after 144 h under cold stress. Antioxidant enzymes activities were also evidently enhanced after treatment with γ-PGA. These responses counteracted increases in the fresh weight and chlorophyll content of rape seedlings, which increased by 24.5 and 50.9%, respectively, after 144 h, which meant that growth inhibition caused by cold was mitigated by γ-PGA. Our results also showed that γ-PGA also regulated Ca(2+) concentrations in the cytoplasm and calcium-dependent protein kinases, which are associated with cold resistance. In conclusion, we suggest that the Ca(2+)/CPKs signal pathway is involved in the γ-PGA-mediated enhancement of cold resistance in rape seedlings. PMID:26585291

  9. A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ho Chiang-Hong

    2011-02-01

    Full Text Available Abstract Background Hyperphosphatemia in patients with chronic kidney disease (CKD contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. Methods In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR 2 and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH levels. Results At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04. The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p p Conclusions In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. Trial Registration www.clinicaltrials.gov NCT00211978.

  10. A feedback control perspective on models of apoptosis signal transduction

    International Nuclear Information System (INIS)

    Apoptosis is a key regulator for replacing unused, old and damaged cells. Here we analyse three models of apoptosis. We deconstruct these models by linearising the models about the life steady state and applying methods from linear control theory. This control viewpoint uncovers a decentralised control scheme with a clear separation of plant and controller and reveals that the caspase inhibitors act as decentralised phase lead controllers

  11. Comparison of two different high performance mixed signal controllers for DC/DC converters

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2006-01-01

    This paper describes how mixed signal controllers combining a cheap microcontroller with a simple analogue circuit can offer high performance digital control for DC/DC converters. Mixed signal controllers have the same versatility and performance as DSP based controllers. It is important to have an...... engineer experienced in microcontroller programming write the software algorithms to achieve optimal performance. Two mixed signal controller designs based on the same 8-bit microcontroller are compared both theoretically and experimentally. A 16-bit PID compensator with a sampling frequency of 200 k...

  12. Comparison of two different high performance mixed signal controllers for DC/DC converters

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2006-01-01

    This paper describes how mixed signal controllers combining a cheap microcontroller with a simple analogue circuit can offer high performance digital control for DC/DC converters. Mixed signal controllers have the same versatility and performance as DSP based controllers. It is important to have an...... engineer experienced in microcontroller programming write the software algorithms to achieve optimal performance. Two mixed signal controller designs based on the same 8-bit microcontroller are compared both theoretically and experimentally. A 16-bit PID compensator with a sampling frequency of 200 k......Hz implemented in the 16 MIPS, 8-bit ATTiny26 microcontroller is demonstrated....

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

    Science.gov (United States)

    Shin, Yong-Jun

    2016-01-01

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

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

    Science.gov (United States)

    Shin, Yong-Jun

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  16. Modeling and Rotor Current Control of Doubly-fed Induction Machine with Complex Signal Flow Graphs

    OpenAIRE

    Khambadkone, AM; Datta, Rajib; Ranganathan, VT

    1998-01-01

    Doubly fed induction machine can be used for wind energy generation. The control of rotor currents can facilitate variable speed constant frequency operation at unity power factor. A model based on complex signal flow graph is developed. This leads to a physically insightful control structure of the machine. A rotor current control strategy based on the complex signal flow graph is developed to facilitate fast current control. The paper gives the analysis, design and simulation for rotor curr...

  17. Beyond microarrays: Finding key transcription factors controlling signal transduction pathways

    Science.gov (United States)

    Kel, Alexdander; Voss, Nico; Jauregui, Ruy; Kel-Margoulis, Olga; Wingender, Edgar

    2006-01-01

    Background Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments. Results We developed a novel approach to find key transcription factors that may explain concerted expression changes of specific components of the signal transduction network. The approach aims at revealing evidence of positive feedback loops in the signal transduction circuits through activation of pathway-specific transcription factors. We demonstrate that promoters of genes encoding components of many known signal transduction pathways are enriched by binding sites of those transcription factors that are endpoints of the considered pathways. Application of the approach to the microarray gene expression data on TNF-alpha stimulated primary human endothelial cells helped to reveal novel key transcription factors potentially involved in the regulation of the signal transduction pathways of the cells. Conclusion We developed a novel computational approach for revealing key transcription factors by knowledge-based analysis of gene expression data with the help of databases on gene regulatory networks (TRANSFAC® and TRANSPATH®). The corresponding software and databases are available at . PMID:17118134

  18. Control of word processing environment using myoelectric signals

    Czech Academy of Sciences Publication Activity Database

    Pošusta, Antonín; Sporka, A. J.; Poláček, O.; Rudolf, Š.; Otáhal, Jakub

    2015-01-01

    Roč. 9, č. 4 (2015), s. 299-311. ISSN 1783-7677 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : assistive technology * text input * myoelectric signals * user study Subject RIV: FH - Neurology Impact factor: 0.797, year: 2014

  19. Sliding mode controller for signal input multiple state submarine system

    International Nuclear Information System (INIS)

    Sliding mode control design has become a popular choice for controlling non-linear dynamical systems. This paper, explores the dynamics of a submarine and represents the same in state space form. It also investigates the potential of sliding mode controller for a single input multiple state system of a submarine. Mathematical derivation of the controller is presented and it is proved that the sliding mode controllers is robust to changes in operating conditions. The problem of chattering in sliding mode controller design is discussed and remedy of this problem is suggested. Simulation studies are carried out which demonstrate that the sliding mode controller can efficiency be used as a heading controller for the submarine under investigation. (author)

  20. Small-signal modelling and control of photovoltaic based water pumping system.

    Science.gov (United States)

    Ghosh, Arun; Ganesh Malla, Siva; Narayan Bhende, Chandrasekhar

    2015-07-01

    This paper studies small-signal modelling and control design for a photovoltaic (PV) based water pumping system without energy storage. First, the small-signal model is obtained and then, using this model, two proportional-integral (PI) controllers, where one controller is used to control the dc-link voltage and the other one to control the speed of induction motor, are designed to meet control goals such as settling time and peak overshoot of the closed loop responses. The loop robustness of the design is also studied. For a given set of system parameters, simulations are carried out to validate the modelling and the control design. PMID:25707717

  1. Study on a Method to Improve the Stability of the Sensor Signal Based on PD Controller

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2013-06-01

    Full Text Available In order to solve the high frequency oscillation generated from the video signal of the camera, the study proposes a method to improve the stability of high frequency oscillation of common sensor signal, which means the high frequency oscillation signal generated from the sensor module can increase the phase margin of the unstable signal through PD controller, thus produces a stable video signal and then through the circuit of AGC (Automatic Gain Control, the automatic compensation of the frequency can be achieved and finally the fourth-order low-pass circuit is used to meet the requirement of cutoff frequency of the sensor signal processing and the stability of the signal and the high frequency performance can be ultimately improved.

  2. Road Impedance Model Study under the Control of Intersection Signal

    Directory of Open Access Journals (Sweden)

    Yunlin Luo

    2015-01-01

    Full Text Available Road traffic impedance model is a difficult and critical point in urban traffic assignment and route guidance. The paper takes a signalized intersection as the research object. On the basis of traditional traffic wave theory including the implementation of traffic wave model and the analysis of vehicles’ gathering and dissipating, the road traffic impedance model is researched by determining the basic travel time and waiting delay time. Numerical example results have proved that the proposed model in this paper has received better calculation performance compared to existing model, especially in flat hours. The values of mean absolute percentage error (MAPE and mean absolute deviation (MAD are separately reduced by 3.78% and 2.62 s. It shows that the proposed model has feasibility and availability in road traffic impedance under intersection signal.

  3. The Signal Detection and Control Circuit Design for Confocal Auto-Focus System

    Directory of Open Access Journals (Sweden)

    Yin Liu

    2016-01-01

    Full Text Available Based on the demands of Confocal Auto-Focus system, the implementation method of signal measurement circuit and control circuit is given. Using the high performance instrumental amplifier AD620BN, low noise precision FET Op amplifier AD795JRZ and ultralow offset voltage Op amplifier OP07EP, a signal measurement circuit used to converse the two differential light intensity signal to electric signal is designed. And a control circuit which takes MCU MSP430F149 as core processes the former signal and generate a control signal driving the platform for auto-focusing. The experimental results proved the feasibility and correctness of circuits. And the system meets the design requirement.

  4. Modelling Signal Controlled Traffic Based on Driving Behaviors

    OpenAIRE

    Yang Wang; Yanyan Chen; Ning Chen

    2015-01-01

    In urban traffic, of particular interest the traffic breakdown which is primarily resulted from the driving behaviors is emerged to respond to the traffic signal. To investigate the influences of driving behaviors on the traffic breakdown, a cellular automaton model has been developed by incorporating a number of driving behaviors typically manifesting during the different stages when the vehicle approaching a traffic light. Numerical simulations have been performed based on a road segment co...

  5. Mechanisms of integration of de novo-synthesized polypeptides into membranes: Signal-recognition particle is required for integration into microsomal membranes of calcium ATPase and of lens MP26 but not of cytochrome b_5

    OpenAIRE

    Anderson, D J; Mostov, K E; Blobel, G

    1983-01-01

    We have investigated the in vitro integration into dog pancreas microsomal membranes of three integral membrane proteins that were synthesized de novo in a wheat germ cell-free translation system: calcium ATPase of rabbit sarcoplasmic reticulum, MP26 of bovine lens fiber plasma membrane, and rat liver cytochrome b_5. Biosynthetically these proteins show a common feature in that they are synthesized without a transient NH_2-terminal signal sequence. Two of these proteins, ATPase and MP26, were...

  6. Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast

    Science.gov (United States)

    Busti, Stefano; Mapelli, Valeria; Tripodi, Farida; Sanvito, Rossella; Magni, Fulvio; Coccetti, Paola; Rocchetti, Marcella; Nielsen, Jens; Alberghina, Lilia; Vanoni, Marco

    2016-01-01

    Calcium homeostasis is crucial to eukaryotic cell survival. By acting as an enzyme cofactor and a second messenger in several signal transduction pathways, the calcium ion controls many essential biological processes. Inside the endoplasmic reticulum (ER) calcium concentration is carefully regulated to safeguard the correct folding and processing of secretory proteins. By using the model organism Saccharomyces cerevisiae we show that calcium shortage leads to a slowdown of cell growth and metabolism. Accumulation of unfolded proteins within the calcium-depleted lumen of the endoplasmic reticulum (ER stress) triggers the unfolded protein response (UPR) and generates a state of oxidative stress that decreases cell viability. These effects are severe during growth on rapidly fermentable carbon sources and can be mitigated by decreasing the protein synthesis rate or by inducing cellular respiration. Calcium homeostasis, protein biosynthesis and the unfolded protein response are tightly intertwined and the consequences of facing calcium starvation are determined by whether cellular energy production is balanced with demands for anabolic functions. Our findings confirm that the connections linking disturbance of ER calcium equilibrium to ER stress and UPR signaling are evolutionary conserved and highlight the crucial role of metabolism in modulating the effects induced by calcium shortage. PMID:27305947

  7. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  8. POSITION CONTROL OF BRUSHLESS DC MOTOR BASED ON DIGITAL SIGNAL PROCESSING

    OpenAIRE

    GENÇER, Çetin; İsmail COŞKUN

    2006-01-01

    Brushless DC Motors (BLDC) have been used widely high performance control systems which are depended on to development of power electronic and control technology. In these motors to fed commutated supply, the control of position without oscilation has been required. In this study, position control of BLDC with digital signal processing has been implemented by a proportional-derivative (PD) controller because of its simple structure. It has been seen that the controller which is proposed from ...

  9. Hedonic and incentive signals for body weight control

    OpenAIRE

    Egecioglu, Emil; Skibicka, Karolina P; Hansson, Caroline; Alvarez-Crespo, Mayte; Friberg, P. Anders; Jerlhag, Elisabet; Engel, Jörgen A.; Dickson, Suzanne L.

    2011-01-01

    Here we review the emerging neurobiological understanding of the role of the brain’s reward system in the regulation of body weight in health and in disease. Common obesity is characterized by the over-consumption of palatable/rewarding foods, reflecting an imbalance in the relative importance of hedonic versus homeostatic signals. The popular ‘incentive salience theory’ of food reward recognises not only a hedonic/pleasure component (‘liking’) but also an incentive motivation component (‘wan...

  10. Effects of improved glycaemic control on calcium and magnesium homeostasis in type II diabetes.

    OpenAIRE

    McBain, A M; Brown, I R; Menzies, D G; Campbell, I W

    1988-01-01

    Poorly controlled type II diabetic patients with hypomagnesaemia, hypermagnesuria, and hypercalciuria were allocated to treatment with either metformin or glipizide, to determine the effects on some indices of mineral metabolism. Despite comparable improvement in glycaemic control, assessed by glucose and haemoglobin A1, there were significant differences between the two groups in the handling of magnesium. Patients receiving metformin showed a reduction in magnesium excretion but remained hy...

  11. Multilayer control for inverters in parallel operation without signal interconnection

    DEFF Research Database (Denmark)

    Hua, Ming; Hu, Haibing; Xing, Yan;

    2011-01-01

    adjusting the phase and amplitude of the output voltage respectively. The second layer is to compensate the droop voltage caused by the droop control and thus improve the load regulation performance of the inverter. The third layer limits the phase deviation between the inverter and the shared ac bus in......A multilayer control is proposed for inverters with wireless parallel operation in this paper. The control is embedded in every inverter respectively and consists of three layers. The first layer is based on an improved droop method, which shares the active and reactive power in each module by...

  12. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Devkanya Dutta

    2000-12-01

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the store-operated calcium entry or capacitative calcium entry. Capacitative calcium current plays a key role in replenishing calcium stores and activating various physiological processes. Despite considerable efforts, very little is known about the molecular nature of the capacitative channel and the signalling pathway that activates it. This review summarizes our current knowledge about store operated calcium entry and suggests possible hypotheses for its mode of activation.

  13. A New Approach to Diagnosing Signals from Multivariate EWMA Control Chart

    Institute of Scientific and Technical Information of China (English)

    MA Yi-zhong; ZHAO Feng-yu

    2003-01-01

    Since Lowry et al. [1992] proposed a multivariate version of the exponentially weighted moving average (EWMA) control chart, the multivariate EWMA control chart has become more and more popular in monitoring production processes, especially in chemical processes. A major advantage of multivariate EWMA statistics is that it is sensitive to small and moderate shifts in the mean vector. However, when a multivariate EWMA chart issues a signal, it is difficult to identify which variable or set of variables is out of control. In this paper, we introduce a new approach to diagnosing signals from a multivariate EWMA control chart. The implementation procedure is that when the multivariate EWMA control chart issues a signal, we adopt a univariate diagnostic procedure to identify the variables or/and the principal components that caused the signal.

  14. Combined Use of Command-Proportional Control of External Robotic Devices Based on Electromyography Signals

    Directory of Open Access Journals (Sweden)

    S.А. Lobov

    2015-12-01

    Full Text Available The aim of the investigation was to develop a control system combining command and proportional control of robotic devices based on electromyography (EMG signals. Materials and Methods. EMG signals were recorded using 8-channel bracelet MYO Thalmic (Thalmic Labs, Canada. Command control of robotic devices was exercised by EMG patterns associated with 6 static hand gestures. The patterns were classified by periodic calculation of a root mean square value of an EMG signal for all channels with further recognition by a two-layer neural network based on back propagation algorithm. Proportional control was performed by calculating the mean absolute value of an EMG signal, and command execution speed adjustment proportional to this value. The software of the control unit was connected via wireless Bluetooth interface with a mobile robot assembled from a set of LEGO NXT Mindstorms (LEGO, Denmark. Results. We presented a soft and hardware platform combining command and proportional control of robotic devices based on EMG signals, and determined the parameters providing optimal characteristics of classification accuracy of EMG patterns, as well as the speed and accuracy of proportional control. We put forward and studied the following schemes combining command and proportional control: 1 the use of independent channels of different control types with recording EMG signals from both hands, 2 the use of independent channels of different control types with recording EMG signals from one hand only, 3 the use of all channels recording an EMG signal from one hand for classification and dynamic selection of a channel for proportional control, and 4 the use of all channels recording an EMG signal from one hand for classification with an average signal across all channels for proportional control. Conclusion. We proposed a novel system of combined command-proportional control of robotic devices based on the neuromuscular activity signals. We studies several

  15. Active regulation of receptor ratios controls integration of quorum-sensing signals in Vibrio harveyi

    Science.gov (United States)

    Teng, Shu-Wen; Schaffer, Jessica N; Tu, Kimberly C; Mehta, Pankaj; Lu, Wenyun; Ong, N P; Bassler, Bonnie L; Wingreen, Ned S

    2011-01-01

    Quorum sensing is a chemical signaling mechanism used by bacteria to communicate and orchestrate group behaviors. Multiple feedback loops exist in the quorum-sensing circuit of the model bacterium Vibrio harveyi. Using fluorescence microscopy of individual cells, we assayed the activity of the quorum-sensing circuit, with a focus on defining the functions of the feedback loops. We quantitatively investigated the signaling input–output relation both in cells with all feedback loops present as well as in mutants with specific feedback loops disrupted. We found that one of the feedback loops regulates receptor ratios to control the integration of multiple signals. Together, the feedback loops affect the input–output dynamic range of signal transmission and the noise in the output. We conclude that V. harveyi employs multiple feedback loops to simultaneously control quorum-sensing signal integration and to ensure signal transmission fidelity. PMID:21613980

  16. Model predictive control for hybrid vehicle ecological driving using traffic signal and road slope information

    Institute of Scientific and Technical Information of China (English)

    Kaijiang YU; Junqi YANG; Daisuke YAMAGUCHI

    2015-01-01

    This paper presents development of a control system for ecological driving of a hybrid vehicle. Prediction using traffic signal and road slope information is considered to improve the fuel economy. It is assumed that the automobile receives traffic signal information from intelligent transportation systems (ITS). Model predictive control is used to calculate optimal vehicle control inputs using traffic signal and road slope information. The performance of the proposed method was analyzed through computer simulation results. Both the fuel economy and the driving profile are optimized using the proposed approach. It was observed that fuel economy was improved compared with driving of a typical human driving model.

  17. The effect of organolead and -tin compounds on signal transduction in vitro: Investigations on the cytosolic free calcium concentration; Der Einfluss von organischen Blei- und Zinnverbindungen auf die Signaltransduktion in vitro: Untersuchungen zur Veraenderung der zytosolischen freien Calciumkonzentration

    Energy Technology Data Exchange (ETDEWEB)

    Ade, T.

    1996-03-01

    The cellular effects of organolead and -tin compounds are not yet precisely understood. However, on the basis of their immuno- and neurotoxicity it is most likely that these substances interfere with cellular signal transduction. For this reason the effect on cytosolic free calcium concentration was investigated in this study. The organometals used induce a persistent increase in cytosolic free calcium concentration in human leukaemia HL-60 cells as well as in neuroblastoma NG-108-15 cells. Studies of the mechanism of the organometal effect with EGTA and calcium channel blockers revealed that an influx of calcium from the extracellular space is responsible for the organometal-induced calcium elevation in HL-60 cells. The effect of the investigated lead compounds and tributyltin is due to calcium channel opening in the plasma membrane. The same is true for the NG108-15 cells. Activation of distinct receptor-mediated signal transduction is not the reason for channel opening. The regulation of cytosolic free calcium concentration was affected by inhibition of plasmamembrane Ca{sup 2+}-ATPases as well as by disturbance of other ion gradients. A consequence of the organometal effect on the cytosolic calcium concentration is the activation of a cPLA{sub 2} and perhaps the induction of apoptosis. These results contribute towards the understanding of biochemical mechanisms causing the injury of vells by organometals. (orig.) [Deutsch] Die zellulaeren Wirkungsmechanismen organischer Blei- und Zinnverbindungen sind zum grossen Teil nicht verstanden. Die immuno- und neurotoxischen Effekte dieser Xenobiotika lassen jedoch die Beeinflussung der Signalwege in den Zellen vermuten. Daher lag der Schwerpunkt dieser Arbeit in der Untersuchung der Signaluebertragungswege und der damit verbundenen Regulation des Calciums. Sowohl in immunkompetenten Zellen (HL-60) wie auch in neuronalen Zellen (NG108-15) induzierten die untersuchten Organometalle eine persistente Erhoehung der

  18. Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

    KAUST Repository

    Flegg, Mark B.

    2013-01-01

    The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reaction-diffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed two-regime method [M. B. Flegg, S. J. Chapman, and R. Erban, "The two-regime method for optimizing stochastic reaction-diffusion simulations," J. R. Soc., Interface 9, 859-868 (2012)] in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic non-spatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cell-physiological first-passage time problems with small ligand concentration

  19. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  20. Calcium channel blockers and Alzheimer's disease★

    OpenAIRE

    Tan, Yi; Deng, Yulin; Qing, Hong

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in...

  1. Transport of Calcium Ions into Mitochondria.

    Science.gov (United States)

    Xu, Zhaolong; Zhang, Dayong; He, Xiaolan; Huang, Yihong; Shao, Hongbo

    2016-06-01

    To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles in plant productivity and quality. Cytoplasmic calcium ions access into outer mitochondrial membrane (OMM) from voltage dependent anion-selective channel (VDAC) and were absorbed into inner mitochondrial membrane (IMM) by mitochondrial calcium uniporter (MCU), rapid mitochondrial calcium uptake (RaM) or mitochondrial ryanodine receptor (mRyR). Although both mitochondria and the mechanisms of calcium transport have been extensively studied, but there are still long-standing or even new challenges. Here we review the history and recent discoveries of the mitochondria calcium ions channel complex involved calcium assimilation, and discuss the role of calcium ions into mitochondria. PMID:27252588

  2. Time synchronization and carrier frequency control of CAPS navigation signals generated on the ground

    Institute of Scientific and Technical Information of China (English)

    WU HaiTao; BIAN YuJing; LU XiaoChun; LI XiaoHui; WANG DanNi

    2009-01-01

    The Chinese Area Positioning System (CAPS) works without atomic clocks on the satellite,and the CAPS navigation signals transmitted on the ground may achieve the same effect as that with high-performance atomic clocks on the satellite.The primary means of achieving that effect is through the time synchronization and carrier frequency control of the CAPS navigation signals generated on the ground.In this paper the synchronization requirements of different time signals are analyzed by the formation of navigation signals,and the theories and methods of the time synchronization of the CAPS navigation signals generated on the ground are also introduced.According to the conditions of the high-precision satellite velocity-measurement signal source,the carrier frequency and its chains of the navigation signals are constructed.CAPS velocity measurement is realized by the expected deviation of real time control to the carrier frequency,end the precision degree of this method is also analyzed.The experimental results show that the time synchronization precision of CAPS generating signals is about 0.3 ns and the precision of the velocity measurement signal source is about 4 cm/s.This proves that the theories and methods of the generating time synchronization and carrier frequency control are workable.

  3. Time synchronization and carrier frequency control of CAPS navigation signals generated on the ground

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The Chinese Area Positioning System (CAPS) works without atomic clocks on the satellite, and the CAPS navigation signals transmitted on the ground may achieve the same effect as that with high-performance atomic clocks on the satellite. The primary means of achieving that effect is through the time synchronization and carrier frequency control of the CAPS navigation signals generated on the ground. In this paper the synchronization requirements of different time signals are analyzed by the formation of navigation signals, and the theories and methods of the time synchronization of the CAPS navigation signals generated on the ground are also introduced. According to the conditions of the high-precision satellite velocitymeasurement signal source, the carrier frequency and its chains of the navigation signals are constructed. CAPS velocity measurement is realized by the expected deviation of real time control to the carrier frequency, and the precision degree of this method is also analyzed. The experimental results show that the time synchronization precision of CAPS generating signals is about 0.3 ns and the precision of the velocity measurement signal source is about 4 cm/s. This proves that the theories and methods of the generating time synchronization and carrier frequency control are workable.

  4. The Effect of Vitamin D and Calcium plus Vitamin D during Pregnancy on Pregnancy and Birth Outcomes: a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Sakineh Mohammad-Alizadeh-Charandabi

    2015-03-01

    Full Text Available Introduction: Evidence suggests a high prevalence of calcium and vitamin D deficiencies exists in both pregnant women and babies. Adequate intake of micronutrients has great importance especially during pregnancy and lactation period. Thus, the present study aimed at assessing the effect of vitamin D and calcium-vitamin D on pregnancy and birth outcomes (including duration of pregnancy, type of delivery and infant anthropometric indicators. Methods: A randomized, controlled, clinical, triple-blind trial conducted on 126 pregnant women referring to Tabriz health centers in 2013-14. Subjects were allocated into three groups using block randomization. Interventional groups received vitamin D, calcium-vitamin D and placebo pills daily for 60 days. ANCOVA and Chi-square tests were used for data analysis. Results: By controlling BMI before and during pregnancy, there were no significant differences between the group in average neonatal weight, height and head circumference, duration of pregnancy, type of delivery and gestational age at the time of delivery. Conclusion: The results show that calcium-vitamin D and vitamin D have no effect on duration of pregnancy, type of delivery and infant anthropometric indicators.

  5. FireSignal – Data Acquisition and Control System Software

    Czech Academy of Sciences Publication Activity Database

    Neto, A.; Fernandes, H.; Duarte, A.; Carvalho, B.; Sousa, J.; Valcárcel, D.; Varandas, C.; Hron, Martin

    Varšava: Warsaw University of Technology, Euratom - IPPLM Association, 2006, P1-D-466. [Symposium on Fusion Technology/24th./. Varšava (PL), 11.09.2006-15.09.2006] Institutional research plan: CEZ:AV0Z20430508 Keywords : tokamak * fusion * data acquisition * data storage * control Subject RIV: JC - Computer Hardware ; Software

  6. Rap1 spatially controls ArhGAP29 to inhibit Rho signaling during endothelial barrier regulation

    NARCIS (Netherlands)

    Post, A.; Pannekoek, W. J.; Ponsioen, B.; Vliem, M. J.; Bos, J. L.

    2015-01-01

    The small GTPase Rap1 controls the actin cytoskeleton by regulating Rho GTPase signaling. We recently established that the Rap1 effectors Radil and Rasip1, together with the Rho GTPase activating protein ArhGAP29, mediate Rap1-induced inhibition of Rho signaling in the processes of epithelial cell s

  7. Initial Experimental Result of Accurately Controlled Routinely Operated Signal System (ACROSS)

    Institute of Scientific and Technical Information of China (English)

    Liao Chengwang; Zhuang Cantao; Liang Hongsen

    2003-01-01

    The principle of Accurately Controlled Routinely Operated Signal System (ACROSS) isintroduced in this paper. A sample machine is made and tested. The experiment shows that thesignal-stacking technique is effective in improving signal-to-noise ratio and the sompi cepstrummethod is applicable to deconvolute a set of travel times of wave elements from accuratetransfer function data in frequency domain.

  8. Calcium Homeostasis and ER Stress in Control of Autophagy in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elżbieta Kania

    2015-01-01

    Full Text Available Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca2+ homeostasis perturbation and starvation. Several Ca2+ channels like voltage-gated T- and L-type channels, IP3 receptors, or CRAC are involved in autophagy regulation. Glucose transporters, mainly from GLUT family, which are often upregulated in cancer, are also prominent targets for autophagy induction. Signals from both Ca2+ perturbations and glucose transport blockage might be integrated at UPR and ER stress activation. Molecular pathways such as IRE 1-JNK-Bcl-2, PERK-eIF2α-ATF4, or ATF6-XBP 1-ATG are related to autophagy induced through ER stress. Moreover ER molecular chaperones such as GRP78/BiP and transcription factors like CHOP participate in regulation of ER stress-mediated autophagy. Autophagy modulation might be promising in anticancer therapies; however, it is a context-dependent matter whether inhibition or activation of autophagy leads to tumor cell death.

  9. Active control of shocks and sonic boom ground signal

    Science.gov (United States)

    Yagiz, Bedri

    The manipulation of a flow field to obtain a desired change is a much heightened subject. Active flow control has been the subject of the major research areas in fluid mechanics for the past two decades. It offers new solutions for mitigation of shock strength, sonic boom alleviation, drag minimization, reducing blade-vortex interaction noise in helicopters, stall control and the performance maximization of existing designs to meet the increasing requirements of the aircraft industries. Despite the wide variety of the potential applications of active flow control, the majority of studies have been performed at subsonic speeds. The active flow control cases were investigated in transonic speed in this study. Although the active flow control provides significant improvements, the sensibility of aerodynamic performance to design parameters makes it a nontrivial and expensive problem, so the designer has to optimize a number of different parameters. For the purpose of gaining understanding of the active flow control concepts, an automated optimization cycle process was generated. Also, the optimization cycle reduces cost and turnaround time. The mass flow coefficient, location, width and angle were chosen as design parameters to maximize the aerodynamic performance of an aircraft. As the main contribution of this study, a detailed parametric study and optimization process were presented. The second step is to appraise the practicability of weakening the shock wave and thereby reducing the wave drag in transonic flight regime using flow control devices such as two dimensional contour bump, individual jet actuator, and also the hybrid control which includes both control devices together, thereby gaining the desired improvements in aerodynamic performance of the air-vehicle. After this study, to improve the aerodynamic performance, the flow control and shape parameters are optimized separately, combined, and in a serial combination. The remarkable part of all these

  10. Wide Area Prosumption Control and Sensitivities of Aperiodic Small Signal Stability Indicators

    DEFF Research Database (Denmark)

    Wittrock, Martin Lindholm; Jóhannsson, Hjörtur; Nielsen, Arne Hejde

    This paper introduces the concept of prosumption control where intelligent loads and distributed generation are aggregated and controlled to improve power system security. It is expected that intelligent load and generation units can respond to control / market signals and thus present an opportu....... The resulting sensitivities are described and their suitability to be used to search for a prosumption pattern is evaluated....

  11. A Signal Coordination Control Based on Traversing Empty between Mid-Block Street Crossing and Intersection

    Directory of Open Access Journals (Sweden)

    Changjiang Zheng

    2012-01-01

    Full Text Available To solve the problem in pedestrian Mid-Block street crossing, the method of signal coordination control between mid-block street crossing and intersection is researched in this paper. The paper proposes to use “distance-flow rate-time” graph as the tool for building coordination control system model which is for different situations of traffic control. Through alternating the linear optimization model, the system outputs the distribution of signal timing and system operational factors (delays in vehicles and mid-block street crossing. Finally, taking one section on the Taiping North Road in Nanjing as an example, the signal coordination control is carried out. And the results which are delays in the vehicles and mid-block street crossing are compared to those in the current distribution of signal timing.

  12. Allergen-encoded signals that control allergic responses

    Science.gov (United States)

    Tung, Hui-Ying; Landers, Cameron; Li, Evan; Porter, Paul; Kheradmand, Farrah; Corry, David B.

    2016-01-01

    Purpose of review The purpose is to review the important recent advances made in how innate immune cells, microbes, and the environment contribute to the expression of allergic disease, emphasizing the allergen-related signals that drive allergic responses. Recent findings The last few years have seen crucial advances in how innate immune cells such as innate lymphoid cells group 2 and airway epithelial cells and related molecular pathways through organismal proteinases and innate immune cytokines, such as thymic stromal lymphopoietin, IL-25, and IL-33 contribute to allergy and asthma. Simultaneously with these advances, important progress has been made in our understanding of how the environment, and especially pathogenic organisms, such as bacteria, viruses, helminths, and especially fungi derived from the natural and built environments, either promote or inhibit allergic inflammation and disease. Of specific interest are how lipopolysaccharide mediates its antiallergic effect through the ubiquitin modifying factor A20 and the antiallergic activity of both helminths and protozoa. Summary Innate immune cells and molecular pathways, often activated by allergen-derived proteinases acting on airway epithelium and macrophages as well as additional unknown factors, are essential to the expression of allergic inflammation and disease. These findings suggest numerous future research opportunities and new opportunities for therapeutic intervention in allergic disease. PMID:26658015

  13. Droplet pairing and coalescence control for generation of combinatorial signals

    Science.gov (United States)

    Um, Eujin; Rogers, Matthew; Stone, Howard

    2013-03-01

    A co-flowing aqueous phase with an immiscible oil phase in a microchannel generates uniformly spaced, monodisperse droplets, which retain their shape by not touching each other or by being stabilized with surfactants at the oil-water interface. However, droplet coalescence is required in many advanced applications, which can be achieved by a complex channel geometry or size differences in the droplets, and as well as by procedures to reduce the effect of a surfactant. These approaches, again, hinder the stability of droplets further downstream. We designed a microchannel which consistently inserts gas-bubble between droplets so that pairing and coalescence of droplets occurs even in the presence of surfactant, and yet prevents unwanted merging with other droplets. Aqueous droplets placed between the bubbles alter their relative speeds and spacing, and consequently we study the change in the number of droplet pairings in relation to the characteristics of the bubbles and the volume of aqueous droplets. By integrating this approach with droplets of different materials, we can program the output sequence of droplet compositions, and such complex combinatorial signals generated are aimed for concentration gradient generation and dynamic stimulation of biological cells with chemicals.

  14. Kalman filtering to suppress spurious signals in Adaptive Optics control

    Energy Technology Data Exchange (ETDEWEB)

    Poyneer, L; Veran, J P

    2010-03-29

    In many scenarios, an Adaptive Optics (AO) control system operates in the presence of temporally non-white noise. We use a Kalman filter with a state space formulation that allows suppression of this colored noise, hence improving residual error over the case where the noise is assumed to be white. We demonstrate the effectiveness of this new filter in the case of the estimated Gemini Planet Imager tip-tilt environment, where there are both common-path and non-common path vibrations. We discuss how this same framework can also be used to suppress spatial aliasing during predictive wavefront control assuming frozen flow in a low-order AO system without a spatially filtered wavefront sensor, and present experimental measurements from Altair that clearly reveal these aliased components.

  15. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

    Science.gov (United States)

    Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

    2016-08-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377732

  16. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

    Science.gov (United States)

    Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

    2016-01-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

  17. Glucose and Auxin Signaling Interaction in Controlling Arabidopsis thaliana Seedlings Root Growth and Development

    OpenAIRE

    Mishra, Bhuwaneshwar S.; Manjul Singh; Priyanka Aggrawal; Ashverya Laxmi

    2009-01-01

    BACKGROUND: Plant root growth and development is highly plastic and can adapt to many environmental conditions. Sugar signaling has been shown to affect root growth and development by interacting with phytohormones such as gibberellins, cytokinin and abscisic acid. Auxin signaling and transport has been earlier shown to be controlling plant root length, number of lateral roots, root hair and root growth direction. PRINCIPAL FINDINGS: Increasing concentration of glucose not only controls root ...

  18. Signal Flow Graph Analysis of Linearized Takagi-Sugeno Fuzzy PI Controller

    OpenAIRE

    B. Amarendra Reddy; Praveen Adimulam; Sujatha, M.

    2012-01-01

    A systematic procedure for developing the signal flow graph model of linearized Takagi-Sugeno (TS) fuzzy PI controller is presented in this paper. This proposed method provides ease of model formulation and avoids the mathematical complexity involved in obtaining the linearized model from a non-linear model. As a first step in constructing the signal flow graph, the analytical structures of TS-fuzzy PI controller is needed. Triangular/trapezoidal membership functions are considered for input ...

  19. Calculation features of traffic light regulation regimesat the signal group control

    OpenAIRE

    Єресов, Володимир Іванович; Трушевський, Вячеслав Едуардович

    2014-01-01

    The differences between the existing technologies of traffic light control by phases and signal groups were determined in the paper. It was proved that the signal group control technology is more perfect and to a greater extent corresponds to the changing traffic conditions at intersections. Approach for compiling the traffic light regulation cycle structure based on the analysis of conflict of traffic and pedestrian flows, taking into account traffic volume, the number of road accidents in t...

  20. Vector Field Driven Design for Lightweight Signal Processing and Control Schemes for Autonomous Robotic Navigation

    OpenAIRE

    Nebu John Mathai; Takis Zourntos; Deepa Kundur

    2009-01-01

    We address the problem of realizing lightweight signal processing and control architectures for agents in multirobot systems. Motivated by the promising results of neuromorphic engineering which suggest the efficacy of analog as an implementation substrate for computation, we present the design of an analog-amenable signal processing scheme. We use control and dynamical systems theory both as a description language and as a synthesis toolset to rigorously develop our computational machinery; ...

  1. The control of deliberate waiting strategies in a stop-signal task

    OpenAIRE

    R.P. Sylwan

    2004-01-01

    To inhibit an ongoing flow of thoughts or actions has been largely considered to be a crucial executive function, and the stop-signal paradigm makes inhibitory control measurable. Stop-signal tasks usually combine two concurrent tasks, i.e., manual responses to a primary task (go-task) are occasionally countermanded by a stimulus which signals participants to inhibit their response in that trial (stop-task). Participants are always instructed not to wait for the stop-signal, since waiting str...

  2. Instrumentation and signal processing in core monitoring and control systems

    International Nuclear Information System (INIS)

    First test results of temperature endurance tests are available on the development of materials to be used for permanent magnet flowmeters. Of the fully magnetized specimens only those examined at 6000 C furnace temperature exhibit a decrease in the field strength after 100 days already. For continuous examination of the performance of the neutron detector system a method based on noise analysis was developed which uses permanent reactivity modulation through the control system. This is to increase the reliability of detection of an incipient excursion. (orig.)

  3. Real-Time Discrete Adaptive Control of Robot Arm Based on Digital Signal Processing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A discrete model reference adaptive controller of robot arm is obtained by integrating the reduced dynamic model of robot, model reference adaptive control (MRAC) and digital signal processing (DSP) computer system into an electromechanical system. With the DSP computer system, the control signal of each joint of the robot arm can be processed in real time and independently. The simulation and experiment results show that with the control strategy, the robot achieved a good trajectory following precision, a good decoupling performance and a high real-time adaptivity.

  4. Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

    OpenAIRE

    Müller, M. N.; Barcelos e Ramos, J.; Schulz, K. G.; U. Riebesell; J. Kaźmierczak; Gallo, F.; Mackinder, L.; Li, Y; P. N. Nesterenko; T. W. Trull; Hallegraeff, G.M.

    2015-01-01

    Marine phytoplankton have developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L−1 in the presence of seawater Ca2+ concentrations of 10 mmol L−1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, ...

  5. Phytoplankton calcification as an effective mechanism to prevent cellular calcium poisoning

    OpenAIRE

    Müller, M. N.; J. Barcelos e Ramos; Schulz, K. G.; U. Riebesell; J. Kaźmierczak; Gallo, F.; Mackinder, L.; Y. Li; P. N. Nesterenko; T. W. Trull; Hallegraeff, G.M.

    2015-01-01

    Marine phytoplankton has developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L−1 in the presence of seawater Ca2+ concentrations of 10 mmol L−1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, ...

  6. Controlled synthesis of calcium carbonate in a mixed aqueous solution of PSMA and CTAB

    International Nuclear Information System (INIS)

    A mixed system of poly (styrene-alt-maleic acid) (PSMA) and cetyltrimethylammonium bromide (CTAB) was used as a very effective crystal growth modifier to direct the controlled synthesis of CaCO3 crystals with various morphologies and polymorphs. The as-prepared products were characterized with scanning electron microscopy and X-ray diffraction. It was found that the concentrations and relative ratios of PSMA and CTAB in the mixed aqueous solution were turned out to be important parameters for the morphology and polymorph of CaCO3 crystals. Various morphologies of CaCO3 crystals, such as hollow microsphere, peanut and so on, were produced depending on the concentrations and relative ratios of PSMA and CTAB. Moreover, the formation mechanisms of CaCO3 crystals with different morphologies were discussed

  7. Coordinating gene expression and axon assembly to control axon growth: potential role of GSK3 signaling

    Directory of Open Access Journals (Sweden)

    Fengquan Zhou

    2012-02-01

    Full Text Available Axon growth requires coordinated regulation of gene expression in the neuronal soma, anterograde transport of synthesized raw materials along the axon, and assembly of cytoskeleton and membranes in the nerve growth cone. Glycogen synthase kinase 3 (GSK3 signaling has recently been shown to play key roles in regulation of axonal transport and cytoskeletal assembly during axon growth. GSK3 signaling is also known to regulate gene expression via controlling the functions of many transcription factors, suggesting that GSK3 may be an important regulator of gene transcription supporting axon growth. Here we will review signaling pathways that control local axon assembly at the growth cone and gene expression in the soma during developmental or regenerative axon growth and discuss the potential involvement of GSK3 signaling in these processes, with a particular focus on how GSK3 signaling modulates the function of axon growth-associated transcription factors.

  8. Upgrade of control signal distribution system at J-PARC linac

    International Nuclear Information System (INIS)

    Three kinds of timing signals, 12-MHz clock, 25-Hz trigger, and type code (control word), are used in the timing system of J-PARC. The timing signals are generated in the central control room (CCR) and are delivered to each facilities. In the klystron gallery of the linac, these signals are received, divided, and distributed to each station. However, in this distribution system, an optical signal from CCR is transformed to an electrical one by a O/E module and divided by a FANOUT module, and then re-transformed to an optical by E/O module. This system is a source of troubles such as the module failure, the timing trouble of LLRF for temperature drift and so on. Therefore, we would like to update the timing signal distribution system for use of the optical amplifiers and the optical couplers. (author)

  9. Task control signals in pediatric Tourette syndrome show evidence of immature and anomalous functional activity

    Directory of Open Access Journals (Sweden)

    Francis M Miezin

    2009-11-01

    Full Text Available Tourette Syndrome (TS is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008. A prior resting-state functional connectivity MRI (rs-fcMRI analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e. correlations outside the typical developmental range limited to the adaptive control network (Church et al., 2009. The present study used functional MRI (fMRI to study brain activity related to adaptive control (by studying start-cues signals, and to task-maintenance (by studying signals sustained across a task set. Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue activity will be altered in TS, including activity inconsistent with typical development (“anomalous”. Second, group differences found in task maintenance (i.e., sustained activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents

  10. Does dietary calcium interact with dietary fiber against colorectal cancer? A case–control study in Central Europe

    OpenAIRE

    Galas, Aleksander; Augustyniak, Malgorzata; Sochacka-Tatara, Elzbieta

    2013-01-01

    Background An unfavorable trend of increasing rates of colorectal cancer has been observed across modern societies. In general, dietary factors are understood to be responsible for up to 70% of the disease’s incidence, though there are still many inconsistencies regarding the impact of specific dietary items. Among the dietary minerals, calcium intake may play a crucial role in the prevention. The purpose of this study was to assess the effect of intake of higher levels of dietary calcium on ...

  11. Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF-κB Signaling Pathway.

    Science.gov (United States)

    Zeng, Jing-Ya; Du, Jing-Jing; Pan, Ying; Wu, Jian; Bi, Hai-Liang; Cui, Bao-Hong; Zhai, Tai-Yu; Sun, Yong; Sun, Yi-Hua

    2016-01-01

    Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-κB pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD(3+), CD(4+) and CD(8+) T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-κB pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-κB pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment. PMID:27563892

  12. Fyn kinase controls Fc{epsilon}RI receptor-operated calcium entry necessary for full degranulation in mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Miranda, Elizabeth; Ibarra-Sanchez, Alfredo [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico); Gonzalez-Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico)

    2010-01-22

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc{epsilon}RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca{sup 2+}) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc{epsilon}RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc{epsilon}RI-dependent Ca{sup 2+} mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca{sup 2+} influx after Fc{epsilon}RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd{sup 3+}) partially blocked Fc{epsilon}RI-induced Ca{sup 2+} influx in WT cells but, in contrast, completely inhibited Ca{sup 2+} mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca{sup 2+} channels (2-aminoethoxyphenyl-borane, 2-APB) blocked Fc{epsilon}RI-induced maximal Ca{sup 2+} rise in WT but not in Fyn -/- cells. Ca{sup 2+} entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc{epsilon}RI-stimulated mast cells.

  13. Fyn kinase controls FcεRI receptor-operated calcium entry necessary for full degranulation in mast cells

    International Nuclear Information System (INIS)

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (FcεRI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca2+) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls FcεRI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed FcεRI-dependent Ca2+ mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca2+ influx after FcεRI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd3+) partially blocked FcεRI-induced Ca2+ influx in WT cells but, in contrast, completely inhibited Ca2+ mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca2+ channels (2-aminoethoxyphenyl-borane, 2-APB) blocked FcεRI-induced maximal Ca2+ rise in WT but not in Fyn -/- cells. Ca2+ entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in FcεRI-stimulated mast cells.

  14. Genetic control and transgressive segregation of zinc, iron, potassium, phosphorus, calcium, and sodium accumulation in cowpea (Vigna unguiculata) seeds.

    Science.gov (United States)

    Fernandes Santos, C A; Boiteux, L S

    2015-01-01

    Cowpea crop, through combining a range of essential minerals with high quality proteins, plays an important role in providing nutritional security to human population living in semi-arid regions. Studies on genetics of biofortification with essential minerals are still quite scarce, and the major objective of the present study was to provide genetic information on development of cowpea cultivars with high seed mineral contents. Genetic parameters heritability and minimum number of genes were estimated for seed accumulation of zinc (Zn), iron (Fe), calcium (Ca), phosphorus (P), potassium (K), and sodium (Na). Generation mean and variance analyses were conducted using contrasting parental lines, F₁, F₂, and backcross populations derived from IT97K-1042-3 x BRS Tapaihum and IT97K-1042-3 x Canapu crosses. High narrow-sense heritability (h²) values were found for accumulation of Fe (65-86%), P (74-77%), and K (77-88%), whereas moderate h(2) values were observed for accumulation of Ca (41-56%), Zn (51-83%), and Na (50-55%) in seeds. Significant additive genetic effects as well as parental mean effects were detected in both crosses for all minerals, whereas epistasis was important genetic component in Zn content. The minimum number of genes controlling the accumulation of minerals ranged from two (K) to 11 (P). Transgressive segregation was observed in F2 populations of both crosses for all minerals analyzed. The results suggest that, although under either oligogenic or polygenic control, the seed content of these six minerals in cowpea can be improved via standard breeding methods largely used for self-pollinated crops. PMID:25729958

  15. Experimental identification of mechanisms controlling calcium isotopic fractionations by the vegetation.

    Science.gov (United States)

    Cobert, Florian; Schimtt, Anne-Désirée.; Bourgeade, Pascale; Stille, Peter; Chabaux, François; Badot, Pierre-Marie; Jaegler, Thomas

    2010-05-01

    This study aims to better understand the role of vegetation on the Ca cycle at the level of the critical zone of the Earth, in order to specify the mechanisms controlling the Ca absorption by plants at the rock/plant interface. To do this, we performed experiments using hydroponic plant cultures in a way that we could control the co-occuring geochemical and physiological process and determine the impact of the nutritive solution on the Ca cycle within plants. A dicotyledon and calcicole plant with rapid growth, the French bean (Phaseolus vulgaris L.), has been chosen to have access to one complete growth cycle. Several experiments have been conducted with two Ca concentrations, 6 (L) and 60 (H) ppm and two pH values (4 and 6) in the nutritive solution, for which the Ca concentration was maintained constant, so its Ca content is considered as infinite. A second experiment (non infinite L6) allowed Ca depletion in the solution through time; therefore, response effects on the Ca isotopic signatures in the plant organs and in the nutritive solution were observed. We determined Ca concentrations and isotopic ratios in the nutritive solution and in different organs (main roots, secondary roots, old and young stems, old and young leaves and fruits) at two different growth stages (10 days and 6 weeks). Preliminary results show that: (1) the roots (main and secondary) were enriched in the light isotope (40Ca) compared to the nutritive solution, and leaves were enriched in the heavy isotope (44Ca) compared to stems. These results are in accord with previously published field studies (Wigand et al., 2005; Page et al., 2008; Cenki-Tok et al., 2009; Holmden and Bélanger, 2010). Leaves and secondary roots were however enriched in the heavy isotope (44Ca) compared to bean pods, stems and main roots. These results could be related to kinetic fractionation processes occurring either during the Ca root uptake, or during the Ca transport within the plant, or physiological mechanisms

  16. Roles of mitochondria and temperature in the control of intracellular calcium in adult rat sensory neurons.

    Science.gov (United States)

    Kang, S H; Carl, A; McHugh, J M; Goff, H R; Kenyon, J L

    2008-04-01

    We recorded Ca2+ current and intracellular Ca2+ ([Ca2+](i)) in isolated adult rat dorsal root ganglion (DRG) neurons at 20 and 30 degrees C. In neurons bathed in tetraethylammonium and dialyzed with cesium, warming reduced resting [Ca2+](i) from 87 to 49 nM and the time constant of the decay of [Ca2+](i) transients (tau(r)) from 1.3 to 0.99s (Q(10)=1.4). The Buffer Index, the ratio between Ca2+ influx and Delta[Ca2+](i) (f I(ca)d(t)/Delta[Ca2+]i) , increased two- to threefold with warming. Neither inhibition of the plasma membrane Ca2+ -ATPase by intracellular sodium orthovanadate nor inhibition of Ca2+ uptake by the endoplasmic reticulum by thapsigargin plus ryanodine were necessary for the effects of warming on these parameters. In contrast, inhibition of the mitochondrial Ca2+ uniporter by intracellular ruthenium red largely reversed the effects of warming. Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP, 500 nM) increased resting [Ca2+](i) at 30 degrees C. Ten millimolar intracellular sodium prolonged the recovery of [Ca2+](i) transients to 10-40s. This effect was reversed by an inhibitor of mitochondrial Na(+)/Ca2+ -exchange (CGP 37157, 10 microM). Thus, mitochondrial Ca2+ uptake is necessary for the temperature-dependent increase in Ca2+ buffering and mitochondrial Ca2+ fluxes contribute to the control of [Ca2+](i) between 50 and 150 nM at 30 degrees C. PMID:17716728

  17. Autonomous aerial vehicles : guidance, control, signal and image processing platform

    International Nuclear Information System (INIS)

    The use of unmanned systems is gaining momentum in civil applications after successful use by the armed forces around the globe. Autonomous aerial vehicles are important for providing assistance in monitoring highways, power grid lines, borders, and surveillance of critical infrastructures. It is envisioned that cargo shipping will be completely handled by UAVs by the 2025. Civil use of unmanned autonomous systems brings serious challenges. The need for cost effectiveness, reliability, operation simplicity, safety, and cooperation with human and with other agents are among these challenges. Aerial vehicles operating in the civilian aerospace is the ultimate goal which requires these systems to achieve the reliability of manned aircraft while maintaining their cost effectiveness. In this presentation the development of an autonomous fixed and rotary wing aerial vehicle will be discussed. The architecture of the system from the mission requirements to low level auto pilot control laws will be discussed. Trajectory tracking and path following guidance and control algorithms commonly used and their implementation using of the shelf low cost components will be presented. Autonomous takeo? landing is a key feature that was implemented onboard the vehicle to complete its degree of autonomy. This is implemented based on accurate air-data system designed and fused with sonar measurements, INS/GPS measurements, and vector field method guidance laws. The outcomes of the proposed research is that the AUS-UAV platform named MAZARI is capable of autonomous takeoff and landing based on a pre scheduled flight path using way point navigation and sensor fusion of the inertial navigation system (INS) and global positioning system (GPS). Several technologies need to be mastered when developing a UAV. The navigation task and the need to fuse sensory information to estimate the location of the vehicle is critical to successful autonomous vehicle. Currently extended Kalman filtering is

  18. Control of calcium carbonate crystallization by using anionic polymethylsiloxanes as templates

    International Nuclear Information System (INIS)

    Sulfonated (SO3H-PMS) and carboxylated (CO2H-PMS) polymethylsiloxanes were synthesized and their effects as anionic template modifier on the CaCO3 crystal morphologies were evaluated. In vitro crystallization assays of CaCO3 were performed at room temperature by using gas diffusion method at different concentration, pH and time. SEM images of CaCO3 showed well-defined short calcite piles (ca. 5 μm) and elongated calcite (ca. 20 μm) when SO3H-PMS was used. When CO2H-PMS was used, the morphology of CaCO3 crystals was single-truncated at pH 7–9 and aggregated-modified calcite at pH 10–11. However, at pH 12 the least stable donut-shaped vaterite crystals were formed. EDS and XRD confirmed the presence of Si from anionic PMS templates on the CaCO3 surfaces and its polymorphism, respectively. Results showed that the selective morphologies of CaCO3 reflect the electrostatic interaction of anionic groups of functionalized PMS with Ca2+ adsorbed on CaCO3 crystals. Rounded and truncated-modified fluorescent CaCO3 was also produced by the inclusion of functionalized PMS into the lattice of CaCO3 matrix. We demonstrated that the anionic PMS offer a good modifier for polymer-controlled crystallization and a convenient approach for understanding the biomineralization field. - Graphical abstract: Optical photographs of rounded and truncated-modified fluorescent CaCO3 produced by the inclusion of sulfonated (SO3H-PMS) polymethylsiloxanes into the lattice of CaCO3 matrix. Insert represents the simulation of modified and fluorescent CaCO3 crystals using Software JCrystal, (2008). Highlights: ► We prepared two anionic polymethylsiloxanes (PMS) as templates. ► Their modifier capacity on the CaCO3 crystal morphologies was demonstrated. ► At pH 12, the least stable donut-shaped vaterite, was formed. ► EDS confirmed the presence of Si from anionic PMS templates on the CaCO3 surfaces. ► Fluorescent CaCO3 was produced by the inclusion of PMS into the CaCO3 matrix.

  19. Calcium Carbonate

    Science.gov (United States)

    ... before being swallowed; do not swallow them whole. Drink a full glass of water after taking either the regular or chewable tablets or capsules. Some liquid forms of calcium carbonate must be shaken well before use.Do not ...

  20. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha;

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p<0.0001) or...

  1. Calcium Calculator

    Science.gov (United States)

    ... Latvia - Lebanon - Libya - Lithuania - Luxembourg - Macedonia, Republic of - Malaysia - Malta - Mexico - Moldova - Morocco - Netherlands - New Zealand - Nigeria - ... and Statistics Popular content Calcium content of common foods What is Osteoporosis? The Board Introduction to Bone ...

  2. Social control of unreliable signals of strength in male but not female crayfish, Cherax destructor.

    Science.gov (United States)

    Walter, Gregory M; van Uitregt, Vincent O; Wilson, Robbie S

    2011-10-01

    The maintenance of unreliable signals within animal populations remains a highly controversial subject in studies of animal communication. Crustaceans are an ideal group for studying unreliable signals of strength because their chela muscles are cryptically concealed beneath an exoskeleton, making it difficult for competitors to visually assess an opponent's strength. In this study, we examined the importance of social avenues for mediating the possible advantages gained by unreliable signals of strength in crustaceans. To do this, we investigated the factors that determine social dominance and the relative importance of signalling and fighting during aggressive encounters in male and female freshwater crayfish, Cherax destructor. Like other species of crayfish, we expected substantial variation in weapon force for a given weapon size, making the assessment of actual fighting ability of an opponent difficult from signalling alone. In addition, we expected fighting would be used to ensure that individuals that are weak for their signal (i.e. chela) size would not achieve higher than expected dominance. For both male and female C. destructor, we found large variation in the actual force of their chela for any given weapon size, indicating that it is difficult for competitors to accurately assess an opponent's force on signal size alone. For males, these unreliable signals of strength were controlled socially through increased levels of fighting and a decreased reliance on signalling, thus directly limiting the benefits accrued to individuals employing high-quality signals (large chelae) with only low resource holding potential. However, in contrast to our predictions, we found that females primarily relied on signalling to settle disputes, resulting in unreliable signals of strength being routinely used to establish dominance. The reliance by females on unreliable signals to determine dominance highlights our poor current understanding of the prevalence and

  3. Control of stochastic resonance in bistable systems by using periodic signals

    Institute of Scientific and Technical Information of China (English)

    Lin Min; Fang Li-Min; Zheng Yong-Jun

    2009-01-01

    According to the characteristic structure of double wells in bistable systems, this paper analyses stochastic fluctu-ations in the single potential well and probability transitions between the two potential wells and proposes a method of controlling stochastic resonance by using a periodic signal. Results of theoretical analysis and numerical simulation show that the phenomenon of stochastic resonance happens when the time scales of the periodic signal and the noise-induced probability transitions between the two potential wells achieve stochastic synchronization. By adding a bistable system with a controllable periodic signal, fluctuations in the single potential well can be effectively controlled, thus affecting the probability transitions between the two potential wells. In this way, an effective control can be achieved which allows one to either enhance or realize stochastic resonance.

  4. Control of stochastic resonance in bistable systems by using periodic signals

    International Nuclear Information System (INIS)

    According to the characteristic structure of double wells in bistable systems, this paper analyses stochastic fluctuations in the single potential well and probability transitions between the two potential wells and proposes a method of controlling stochastic resonance by using a periodic signal. Results of theoretical analysis and numerical simulation show that the phenomenon of stochastic resonance happens when the time scales of the periodic signal and the noise-induced probability transitions between the two potential wells achieve stochastic synchronization. By adding a bistable system with a controllable periodic signal, fluctuations in the single potential well can be effectively controlled, thus affecting the probability transitions between the two potential wells. In this way, an effective control can be achieved which allows one to either enhance or realize stochastic resonance

  5. POSITION CONTROL OF BRUSHLESS DC MOTOR BASED ON DIGITAL SIGNAL PROCESSING

    Directory of Open Access Journals (Sweden)

    Çetin GENÇER

    2006-01-01

    Full Text Available Brushless DC Motors (BLDC have been used widely high performance control systems which are depended on to development of power electronic and control technology. In these motors to fed commutated supply, the control of position without oscilation has been required. In this study, position control of BLDC with digital signal processing has been implemented by a proportional-derivative (PD controller because of its simple structure. It has been seen that the controller which is proposed from simulation and experimental studies, has a quick dynamic responce with nonoscillation.

  6. Learning tensegrity locomotion using open-loop control signals and coevolutionary algorithms.

    Science.gov (United States)

    Iscen, Atil; Caluwaerts, Ken; Bruce, Jonathan; Agogino, Adrian; SunSpiral, Vytas; Tumer, Kagan

    2015-01-01

    Soft robots offer many advantages over traditional rigid robots. However, soft robots can be difficult to control with standard control methods. Fortunately, evolutionary algorithms can offer an elegant solution to this problem. Instead of creating controls to handle the intricate dynamics of these robots, we can simply evolve the controls using a simulation to provide an evaluation function. In this article, we show how such a control paradigm can be applied to an emerging field within soft robotics: robots based on tensegrity structures. We take the model of the Spherical Underactuated Planetary Exploration Robot ball (SUPERball), an icosahedron tensegrity robot under production at NASA Ames Research Center, develop a rolling locomotion algorithm, and study the learned behavior using an accurate model of the SUPERball simulated in the NASA Tensegrity Robotics Toolkit. We first present the historical-average fitness-shaping algorithm for coevolutionary algorithms to speed up learning while favoring robustness over optimality. Second, we use a distributed control approach by coevolving open-loop control signals for each controller. Being simple and distributed, open-loop controllers can be readily implemented on SUPERball hardware without the need for sensor information or precise coordination. We analyze signals of different complexities and frequencies. Among the learned policies, we take one of the best and use it to analyze different aspects of the rolling gait, such as lengths, tensions, and energy consumption. We also discuss the correlation between the signals controlling different parts of the tensegrity robot. PMID:25951199

  7. Controlling chaos with weak periodic signals optimized by a genetic algorithm.

    Science.gov (United States)

    Soong, C Y; Huang, W T; Lin, F P; Tzeng, P Y

    2004-01-01

    In the present study we develop a relatively novel and effective chaos control approach with a multimode periodic disturbance applied as a control signal and perform an in-depth analysis on this nonfeedback chaos control strategy. Different from previous chaos control schemes, the present method is of two characteristic features: (1) the parameters of the controlling signal are optimized by a genetic algorithm (GA) with the largest Lyapunov exponent used as an index of the stability, and (2) the optimization is justified by a fitness function defined with the target Lyapunov exponent and the controlling power. This novel method is then tested on the noted Rössler and Lorenz systems with and without the presence of noise. The results disclosed that, compared to the existing chaos control methods, the present GA-based control needs only significantly reduced signal power and a shorter transient stage to achieve the preset control goal. The switching control ability and the robustness of the proposed method for cases with sudden change in a system parameter and/or with the presence of noise environment are also demonstrated. PMID:15324156

  8. A simple approach to eliminate background signals in dynamic control rod reactivity measurements for LWRs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, E. K.; Woo, I. T.; Shin, H. C.; Ryu, S. J.; Bae, S. M. [Korea Electric Power Research Institute, Taejon (Korea, Republic of)

    2003-07-01

    Dynamic rod worth measurement (DRWM{sup TM}) methodology commercialized by Westinghouse was successfully applied to many nuclear power plants in USA to measure the control rod worth at Low Power Physics Tests. But in Korea, to increase the capacity of nuclear power plant, KEPRI has developed Dynamic Control rod Reactivity Measurement (DCRM) system using more rapid and sophisticated reactivity measurement methodology without the change of boron concentration. The object of this paper is to consider the practical method to eliminate background signals from measured ex-core detector signals. Because of relatively low rod insertion speed (40 {approx} 48 steps/min), the background signals affect the final results severely. Therefore a simple and practical method based on the behavior of integral rod worth curve was developed and applied. A total of 26 experimental results show that the proposed approach works to figure out the background signals.

  9. Multiobjective Traffic Signal Control Model for Intersection Based on Dynamic Turning Movements Estimation

    Directory of Open Access Journals (Sweden)

    Pengpeng Jiao

    2014-01-01

    Full Text Available The real-time traffic signal control for intersection requires dynamic turning movements as the basic input data. It is impossible to detect dynamic turning movements directly through current traffic surveillance systems, but dynamic origin-destination (O-D estimation can obtain it. However, the combined models of dynamic O-D estimation and real-time traffic signal control are rare in the literature. A framework for the multiobjective traffic signal control model for intersection based on dynamic O-D estimation (MSC-DODE is presented. A state-space model using Kalman filtering is first formulated to estimate the dynamic turning movements; then a revised sequential Kalman filtering algorithm is designed to solve the model, and the root mean square error and mean percentage error are used to evaluate the accuracy of estimated dynamic turning proportions. Furthermore, a multiobjective traffic signal control model is put forward to achieve real-time signal control parameters and evaluation indices. Finally, based on practical survey data, the evaluation indices from MSC-DODE are compared with those from Webster method. The actual and estimated turning movements are further input into MSC-DODE, respectively, and results are also compared. Case studies show that results of MSC-DODE are better than those of Webster method and are very close to unavailable actual values.

  10. Combined Analysis of Cortical (EEG) and Nerve Stump Signals Improves Robotic Hand Control

    OpenAIRE

    Tombini, Mario; Rigosa, Jacopo; Zappasodi, Filippo; Porcaro, Camillo; Citi, Luca; Carpaneto, Jacopo; Rossini, Paolo Maria; Micera, Silvestro

    2012-01-01

    Background. Interfacing an amputee's upper-extremity stump nerves to control a robotic hand requires training of the individual and algorithms to process interactions between cortical and peripheral signals. Objective. To evaluate for the first time whether EEG-driven analysis of peripheral neural signals as an amputee practices could improve the classification of motor commands. Methods. Four thin-film longitudinal intrafascicular electrodes (tf-LIFEs-4) were implanted in the median and ulna...

  11. Fuzzy urban traffic signal control - an overview: Mehko upravljanje mestne prometne signalizacije - pregled:

    OpenAIRE

    Brodnik, Andrej; Malej, Alenka

    2007-01-01

    In the last years, there have been many attempts made to improve urban traffic signal contol systems as this is one of the most cost-effective ways to improve the traffic flow through a network intersections. Besides the traditional method for traffic signal control that are usually based on a traffic flow model, the development of new system started to consider the various emerging technologies including artifical intelligence. Application of metaheuristic methods has proven to be worth of b...

  12. Positive Switched System Approach to Traffic Signal Control for Oversaturated Intersection

    OpenAIRE

    Lin Du; Yun Zhang

    2014-01-01

    The online traffic signalization for intersection is addressed. A new model for intersection called positive switched system is presented. Then, based on the dissipativity analysis results for positive switched system, an online state-feedback control strategy for traffic signal in two-phase intersection section is proposed. A numerical example is provided to illustrate the effectiveness of our theoretical findings. Finally, in order to extend to more general cases, multiphase intersection is...

  13. Critical Roles of Intestinal Epithelial Vitamin D Receptor Signaling in Controlling Gut Mucosal Inflammation

    OpenAIRE

    Li, Yan Chun; Chen, Yunzi; Du, Jie

    2015-01-01

    Although vitamin D receptor (VDR) is highly expressed in the intestine, the role of VDR signaling in the gut is not fully understood. Our recent studies unveil a regulatory circuit that centers gut epithelial VDR as a key molecule in the control of mucosal inflammation and colitis development. On the one hand, intestinal epithelial VDR signaling protects the integrity of the mucosal barrier by inhibiting inflammation-induced epithelial cell apoptosis. This barrier-protecting, anti-colitic act...

  14. Calcium and ER stress mediate hepatic apoptosis after burn injury

    Science.gov (United States)

    Gauglitz, Gerd G.; Song, Juquan; Kulp, Gabriela A.; Finnerty, Celeste C.; Cox, Robert A.; Barral, José M.; Herndon, David N.; Boehning, Darren

    2009-01-01

    Abstract A hallmark of the disease state following severe burn injury is decreased liver function, which results in gross metabolic derangements that compromise patient survival. The underlying mechanisms leading to hepatocyte dysfunction after burn are essentially unknown. The aim of the present study was to determine the underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn. Rats were randomized to either control (no burn) or burn (60% total body surface area burn) and sacrificed at various time‐points. Liver was either perfused to isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or liver was harvested and processed for immunohistology, transmission electron microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to determine the hepatic response to burn injury in vivo. We found that thermal injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and consequent elevated cytosolic calcium concentrations in primary hepatocytes in vitro. Burn‐induced ER calcium depletion caused depressed hepatocyte responsiveness to signalling molecules that regulate hepatic homeostasis, such as vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in activation of the ER stress response and major alterations in mitochondrial structure and function – effects which may be mediated by increased calcium release by inositol 1,4,5‐trisphosphate receptors. Our results reveal that thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and resultant ER stress leading to mitochondrial abnormalities contributing to hepatic dysfunction and apoptosis after burn injury. PMID:20141609

  15. TOR signaling regulates planarian stem cells and controls localized and organismal growth.

    Science.gov (United States)

    Peiris, T Harshani; Weckerle, Frank; Ozamoto, Elyse; Ramirez, Daniel; Davidian, Devon; García-Ojeda, Marcos E; Oviedo, Néstor J

    2012-04-01

    Target of Rapamycin (TOR) controls an evolutionarily conserved signaling pathway that modulates cellular growth and division by sensing levels of nutrients, energy and stress. As such, TOR signaling is a crucial component of tissues and organs that translates systemic signals into cellular behavior. The ubiquitous nature of TOR signaling, together with the difficulty of analyzing tissue during cellular turnover and repair, have limited our understanding of how this kinase operates throughout the body. Here, we use the planarian model system to address TOR regulation at the organismal level. The planarian TOR homolog (Smed-TOR) is ubiquitously expressed, including stem cells (neoblasts) and differentiated tissues. Inhibition of TOR with RNA interference severely restricts cell proliferation, allowing the study of neoblasts with restricted proliferative capacity during regeneration and systemic cell turnover. Strikingly, TOR signaling is required for neoblast response to amputation and localized growth (blastema). However, in the absence of TOR signaling, regeneration takes place only within differentiated tissues. In addition, TOR is essential for maintaining the balance between cell division and cell death, and its dysfunction leads to tissue degeneration and lack of organismal growth in the presence of nutrients. Finally, TOR function is likely to be mediated through TOR Complex 1 as its disruption recapitulates signs of the TOR phenotype. Our data reveal novel roles for TOR signaling in controlling adult stem cells at a systemic level and suggest a new paradigm for studying TOR function during physiological turnover and regeneration. PMID:22427692

  16. Hippo signaling: A hub of growth control, tumor suppression andpluripotency maintenance

    Institute of Scientific and Technical Information of China (English)

    Mengxin Yin; Lei Zhang

    2011-01-01

    The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology.Almost a decade ago,the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue.The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates,and plays critical roles in animal development.It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis.Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis.Although the core of the signaling pathway is well understood,the upstream inputs and downstream transcriptional regulation are still obscure to us.In this review,we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals.We underline the crosstalk between the Hippo signaling pathway and other signaling pathways,and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal.

  17. Calcium pyrophosphate arthritis

    Science.gov (United States)

    Calcium pyrophosphate dihydrate deposition disease; CPPD disease; Acute CPPD arthritis; Pseudogout ... Calcium pyrophosphate arthritis is caused by the collection of salt called calcium pyrophosphate dihydrate (CPPD). The buildup ...

  18. PULSE REFERENCED CONTROL METHOD FOR ENHANCED POWER AMPLIFICATION OF A PULSE MODULATED SIGNAL

    DEFF Research Database (Denmark)

    1998-01-01

    To correct for any source of non-linearity and noise introduced in the power amplification of a pulse modulated signal, a correction unit is applied in-between the pulse modulator and the switching power amplification stage. The correction unit is controlled to have a compensating effect, by...... introducing continuous delays on the individual pulse edges on the basis of error information provided by an error processing block. One preferred embodiment of the invention comprises: a Correction Unit with means to control the delays of the individual pulse edges as a function of a control input signal $i......(v¿e?); a state feedback block A with compensation; a reference shaping block $i(R) to modify the pulsed reference $i(v¿r?) for optimized error estimation; a difference block to generate an error signal and a compensator $i(C) to shape this error. The invention makes it possible to implement practical...

  19. Signal frequency based self-tuning fuzzy controller for semi-active suspension system

    Institute of Scientific and Technical Information of China (English)

    孙涛; 黄震宇; 陈大跃; 汤磊

    2003-01-01

    A new kind of fuzzy control scheme, based on the identification of the signal' s main frequency and the behavior of the ER damper, is proposed to control the semi-active suspension system. This method ad-justs the fuzzy controller to achieve the best isolation effect by analyzing the main frequency' s characters and inspecting the change of system parameters. The input of the fuzzy controller is the main frequency and the op-timal damping ratio is the output. Simulation results indicated that the proposed control method is very effec-tive in isolating the vibration.

  20. Coordinated Power Control Strategy based on Primary-Frequency-Signaling for Islanded Microgrids

    DEFF Research Database (Denmark)

    Wu, Dan; Guerrero, Josep M.; Vasquez, Juan Carlos;

    2013-01-01

    In a flexible microgrid, the power regulation of each electronic-converter-based unit should be not only determined by the load demand, but also controlled according to the power and energy available in each unit. This paper proposes a coordinated control strategy in which each unit can operate in...... different operation modes taking into account the resource limitation. Firstly, a Primary-Frequency-Signaling (PFS) is introduced to realize coordinated control between units in a distributed way. Then the whole control structure of system is descripted in detail, which includes innerloop control with...

  1. Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with Abnormal Calcium Handling.

    Science.gov (United States)

    Opel, Aaisha; Nobles, Muriel; Montaigne, David; Finlay, Malcolm; Anderson, Naomi; Breckenridge, Ross; Tinker, Andrew

    2015-07-31

    The description of potential molecular substrates for predisposition to atrial fibrillation (AF) is incomplete, and it is unknown what role regulators of G-protein signaling might play. We address whether the attenuation of RGS4 function may promote AF and the mechanism through which this occurs. For this purpose, we studied a mouse with global genetic deletion of RGS4 (RGS4(-/-)) and the normal littermate controls (RGS4(+/+)). In vivo electrophysiology using atrial burst pacing revealed that mice with global RGS4 deletion developed AF more frequently than control littermates. Isolated atrial cells from RGS4(-/-) mice show an increase in Ca(2+) spark frequency under basal conditions and after the addition of endothelin-1 and abnormal spontaneous Ca(2+) release events after field stimulation. Isolated left atria studied on a multielectrode array revealed modest changes in path length for re-entry but abnormal electrical events after a pacing train in RGS4(-/-) mice. RGS4 deletion results in a predisposition to atrial fibrillation from enhanced activity in the Gαq/11-IP3 pathway, resulting in abnormal Ca(2+) release and corresponding electrical events. PMID:26088132

  2. Designing signal conditioning circuit for stability control system of LINAC modulator

    International Nuclear Information System (INIS)

    Background: Shanghai Soft X-ray FEL is under design and construction at Shanghai Institute of Applied Physics (SINAP). Purpose: The stability of the existing SSRF Linac modulator has achieved 500 ppm. But the Soft X-FEL requires 100 PPM. Methods: This paper describes control strategy based on pulse amplitude feedback technology, and gives the design of signal conditioning circuit in more details. The signal conditioning circuit contains amplitude fading, LPF and cutting etc. Results: The relevant experiments show that the circuit reaches required function and stability. Conclusions: Feedback control strategy is useful for the existing modulator. (authors)

  3. Low power and self-reconfigurable WBAN controller for continuous bio-signal monitoring system.

    Science.gov (United States)

    Lee, Seulki; Yoo, Hoi-Jun

    2013-04-01

    The WBAN controller with Branched Bus (BB) topology and Continuous Data Transmission (CDT) protocol with low power consumption and self-reconfigurability is proposed for wearable healthcare applications. The BB topology and CDT protocol is a combination of conventional Bus and Star topology and a variation from TDMA protocol, respectively, while they are able to compensate for the electrical fault in bio-signal monitoring system caused by the electrode deformation. Thanks to them, the proposed WBAN controller enables more reliable operation in continuous bio-signal monitoring applications such as sleep monitoring. PMID:23853300

  4. Control, command and signalling. Market set to remain steady while technical structural changes continue

    Energy Technology Data Exchange (ETDEWEB)

    Strang, K. [SCI Verkehr GmbH, Koeln (Germany)

    2006-07-01

    The European market for products and services for control, command and signalling is currently worth around EUR 5.7 billion. It ought to be possible for international companies who habe decided to extend their portfolios or their distribution areas to open up a maximum of 40 % or so of this potential. The market is forecast to remain steady until 2010, but the opening-up process will continue. These are the most important findings of a market study called ''European Control Command and Signalling 2005-2010'', which was presented by SCI Verkehr GmbH in July 2005. (Orig.)

  5. Synthesis of calcium carbonate using extract components of croaker gill as morphology and polymorph adjust control agent.

    Science.gov (United States)

    Chen, Hao; Qing, Chengsong; Zheng, Jiaoling; Liu, Yuxi; Wu, Gang

    2016-06-01

    Biomimetic synthesis of calcium carbonate with various polymorphs, sizes and morphologies by using organic substrates has become an interesting topic for the last years. Calcium carbonate has been synthesized by the reaction of Na2CO3 and CaCl2 in the presence of extract components of croaker gill. The products were characterized by powder X-ray diffraction (PXRD) and Fourier transform infrared (FT-IR) spectrum, and particle morphologies were observed by scanning electron microscope (SEM). The results show that at lower concentration yellow croaker gill extract has no effect on calcium carbonate crystal polymorph. Calcite was obtained only. But the morphologies of calcite particle change with the increase of the concentration. The corners of the particle change from angular to curved. However, with the further increase of the concentration of yellow croaker gill extract, the calcium carbonate obtained is a mixture of calcite and vaterite. The vaterite component in the mixture rises with increasing concentration of extract solution, indicating that the proteins from the yellow croaker gill during growth play a crucial role in stabilizing and directing the crystal growth. PMID:27040242

  6. The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling.

    Science.gov (United States)

    Takashima, Shigeo; Mkrtchyan, Marianna; Younossi-Hartenstein, Amelia; Merriam, John R; Hartenstein, Volker

    2008-07-31

    The intestinal tract maintains proper function by replacing aged cells with freshly produced cells that arise from a population of self-renewing intestinal stem cells (ISCs). In the mammalian intestine, ISC self renewal, amplification and differentiation take place along the crypt-villus axis, and are controlled by the Wnt and hedgehog (Hh) signalling pathways. However, little is known about the mechanisms that specify ISCs within the developing intestinal epithelium, or about the signalling centres that help maintain them in their self-renewing stem cell state. Here we show that in adult Drosophila melanogaster, ISCs of the posterior intestine (hindgut) are confined to an anterior narrow segment, which we name the hindgut proliferation zone (HPZ). Within the HPZ, self renewal of ISCs, as well as subsequent proliferation and differentiation of ISC descendants, are controlled by locally emanating Wingless (Wg, a Drosophila Wnt homologue) and Hh signals. The anteriorly restricted expression of Wg in the HPZ acts as a niche signal that maintains cells in a slow-cycling, self-renewing mode. As cells divide and move posteriorly away from the Wg source, they enter a phase of rapid proliferation. During this phase, Hh signal is required for exiting the cell cycle and the onset of differentiation. The HPZ, with its characteristic proliferation dynamics and signalling properties, is set up during the embryonic phase and becomes active in the larva, where it generates all adult hindgut cells including ISCs. The mechanism and genetic control of cell renewal in the Drosophila HPZ exhibits a large degree of similarity with what is seen in the mammalian intestine. Our analysis of the Drosophila HPZ provides an insight into the specification and control of stem cells, highlighting the way in which the spatial pattern of signals that promote self renewal, growth and differentiation is set up within a genetically tractable model system. PMID:18633350

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

    Science.gov (United States)

    Lambert, Charles C

    2011-01-01

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

  8. FEU-30 photoelectron multiplier operation in the key mode at nanosecond control signal duration

    International Nuclear Information System (INIS)

    The problem of controlling the sensitivity of the FEhU-30 photomultipllier has been studied at a nanosecond duration of control signals. The flowsheet of the installation applied for studying the time characteristics of the FEhU control regime is considered. The dependence of the sensitivity modulation depth on the control signal amplitude and time diagrams of FEhU operation have been determined upon switching from a cut-off state to an open one. The measurements presented show that in the key regime the sensitivity modulation depth accounts for 104, the time of switching is 20 ns, a stray signal on the FEhU anode does not exceed 0.3 V at the 50 Ohm load and the amplitude of control signals equal to 140 V. A conclusion has been drawn on the applicability of the FEhU-30, operating in a key regime, for investigation of weak light fluxes, which for a time of 100 ns are preceded by a pulse light fluxes with about 104 times stronger intensity

  9. Remote controlled signal conditioner and fiber optic data link system development CPRF (Confinement Physics Research Facility)

    International Nuclear Information System (INIS)

    The ZTH reversed-field pinch to be installed in the Confinement Physics Research Facility (CPRF) will produce a significant ambient magnetic field. To avoid ground-loop and other electrical problems, the diagnostics in direct or possible contact with the experiment will be accessed through a fiber optic data way. The frequency-modulated analog links developed for this system have a bandwidth of dc to 100 kHz and a signal-to-noise ratio of better than 60 dB. The fiber optic transmitter units include a signal conditioner and a microprocessor controller. The conditioners can be configured as dc-coupled, low-noise differential amplifiers, or as high-gain, low-drift differential integrators with a very long droop time constant. Magnetic field pickup is minimized by balancing sensitive circuit areas to within 5 mm2 in all three planes of the PC boards. The gain, offset, and integrator reset are controlled and monitored by the microprocessor, and their status is displayed on the front panel of the transmitter unit. The signal conditioner can be controlled locally, or by way of a fiber optic coupled control network. The system allows fast, convenient, noise-immune control of a large number of signal conditioners from a central host computer. By varying the offset, the computer can verify the operational integrity of the data links. 2 refs., 6 figs

  10. Mercury-induced apoptosis and necrosis in murine macrophages: role of calcium-induced reactive oxygen species and p38 mitogen-activated protein kinase signaling

    International Nuclear Information System (INIS)

    The current study characterizes the mechanism by which mercury, a toxic metal, induces death in murine macrophages. The cytotoxic EC50 of mercury ranged from 62.7 to 81.1 μM by various assays in J774A.1 cultures; accordingly, we employed 70 μM of mercuric chloride in most experiments. Mercury-induced intracellular calcium modulated reactive oxygen species (ROS) production, which resulted in both cell apoptosis and necrosis indicated by annexin V binding and caspase-3 activity, and propidium-iodide binding. Calcium antagonists abolished ROS production. Mercury stimulated p38 mitogen-activated protein kinase (MAPK) and additively stimulated lipopolysaccharide-activated p38. Mercury-activated p38 was decreased by pretreatment of cells with antioxidants, N-acetylcysteine (NAC) and silymarin, indicating that mercury-induced ROS were involved in p38 activation. Mercury increased the expression of tumor necrosis factor α (TNFα); antioxidants and a specific p38 inhibitor decreased this effect. Pretreatment with antioxidants, p38 inhibitor, and anti-TNFα antibody decreased mercury-induced necrosis; however, anti-TNFα antibody did not decrease mercury-induced apoptosis. Results suggest that mercury-induced macrophage death is a mix of apoptosis and necrosis employing different pathways. P38-mediated caspase activation regulates mercury-induced apoptosis and p38-mediated TNFα regulates necrosis in these cells. Calcium regulates ROS production and mercury-induced ROS modulate downstream p38 that regulates both apoptosis and necrosis

  11. Clinical and radiographic assessment of the efficacy of calcium silicate indirect pulp capping: a randomized controlled clinical trial.

    Science.gov (United States)

    Hashem, D; Mannocci, F; Patel, S; Manoharan, A; Brown, J E; Watson, T F; Banerjee, A

    2015-04-01

    The aims of this study were to assess the effectiveness of calcium silicate cement (Biodentine) versus glass ionomer cement (GIC; control group) as indirect pulp capping materials in patients with reversible pulpitis and to compare the effectiveness of cone beam computed tomography (CBCT) versus periapical (PA) radiographs in detecting PA changes at baseline (T0) and at 12 mo (T12) postoperatively. Seventy-two restorations (36 Biodentine, 36 Fuji IX) were placed randomly in 53 patients. CBCT/PA radiographs were taken at T0 and T12. Two calibrated examiners assessed the presence/absence and increase/decrease in the size of existing PA radiolucencies under standardized conditions. The Kappa coefficient evaluated statistically the effectiveness of CBCT versus PA radiographs in detecting PA changes. Chi-square/Mann-Whitney tests were used to evaluate the association between PA changes in CBCT with various clinical measures. Significance was predetermined at α = 0.05. Clinical success rates for Biodentine and Fuji IX GIC were 83.3%. CBCT was significantly more effective in detecting PA radiolucencies compared with radiographs (P = 0.0069). Of the teeth, 65.4% and 90.4% were deemed healthy using CBCT and PA radiographs, respectively, at T12. Healing/healed rates were 17.3%/0%, while new/progressed radiolucency were 30.8%/9.6% with CBCT/PA radiographs, respectively. Seventy-one percent of healed lesions had received Biodentine; 88% of new/progressed lesions received Fuji IX GIC. Teeth presenting with an initial CBCT PA lesion had a failure rate of 63%, whereas teeth with no initial lesion had a failure rate of 16%. Although no statistically significant difference was detected in the clinical efficacy of Biodentine/Fuji IX when used as indirect pulp capping materials in patients with reversible pulpitis, CBCT showed a significant difference in that most healed CBCT lesions had received Biodentine while most that did not heal received Fuji IX. Longer-term follow-up is

  12. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    Science.gov (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. PMID:27341758

  13. Trapping of Weak Signal Pulses by Soliton and Trajectory Control in a Coherent Atomic Gas

    CERN Document Server

    Chen, Zhiming

    2016-01-01

    We propose a method for trapping weak signal pulses by soliton and realizing its trajectory control via electromagnetically induced transparency (EIT). The system we consider is a cold, coherent atomic gas with a tripod or multipod level configuration. We show that, due to the giant enhancement of Kerr nonlinearity contributed by EIT, several weak signal pulses can be effectively trapped by a soliton and cotravel stably with ultraslow propagating velocity. Furthermore, we demonstrate that the trajectories of the soliton and the trapped signal pulses can be manipulated by using a Stern-Gerlach gradient magnetic field. As a result, the soliton and the trapped signal pulses display a Stern-Gerlach deflection and both of them can bypass an obstacle together. The results predicted here may be used to design all-optical switching at very low light level.

  14. A Railway Signal Control System by Optical LAN and Design Simplification

    Directory of Open Access Journals (Sweden)

    Takashi Kunifuji

    2008-07-01

    Full Text Available When replace railway interlocking devices, setting up of large number of signal cables and confirming of wiring connections are required. So, it is worried that serious transport disorder caused by human error in wiring works would occur. We have developed a railway signal control system utilized optical LAN to reduce the signal cables and wiring works. Moreover, all signal devices operate independently, designers have to handle all devices one by one and pay great attention to avoid causing harmful influence each other. We propose the data-driven method to make easy to replace interlocking device. This logic is rearranged according to the field device in order to simplify and decrease design duties of designers. In this paper, we introduce this system, and describe network transmission, safety-related communication and software configuration of the system.

  15. Extraembryonic signals under the control of MGA, Max, and Smad4 are required for dorsoventral patterning.

    Science.gov (United States)

    Sun, Yuhua; Tseng, Wei-Chia; Fan, Xiang; Ball, Rebecca; Dougan, Scott T

    2014-02-10

    In vertebrates, extraembryonic tissues can act as signaling centers that impose a reproducible pattern of cell types upon the embryo. Here, we show that the zebrafish yolk syncytial layer (YSL) secretes a ventralizing signal during gastrulation. This activity is mediated by Bmp2b/Swirl (Swr) expressed under the control of Max's giant associated protein (MGA) and its binding partners, Max and Smad4. MGA coimmunoprecipitates with both Max and Smad4 in embryo extracts, and the three proteins form a complex in vitro. Furthermore, all three proteins bind to a DNA fragment upstream of the bmp2b transcription start site. Targeted depletion of MGA, its binding partners, or Bmp2b/Swr from the YSL reduces BMP signaling throughout the embryo, resulting in a mildly dorsalized phenotype. We conclude that MGA, Max, and Smad4 act in the extraembryonic YSL to initiate a positive feedback loop of Bmp signaling within the embryo. PMID:24525188

  16. Reuse of MgCl2 as Crystal Controlling Agent in the Synthesis Process of Needle―like Calcium Carbonate

    Directory of Open Access Journals (Sweden)

    MA Jun, LIU Hua-Yan, CHEN Yin-Fei

    2011-11-01

    Full Text Available MgCl2 was used as crystal controlling agent for the synthesis of regular needle―like calcium carbonate with diameter of 2.5―5μm and aspect ratio of 10―20. Complexometric titrating method was employed to determine the contents of Ca2+ and Mg2+ in filtrated solution after carbonization and the fresh MgCl2 was added to balance the Mg2+ content as same as the raw solution. The morphology, particle size and polymorphs of calcium carbonate were characterized by SEM and XRD. The results show that the content of aragonite phase CaCO3 decreases with the recycle time increasing. When the content of aragonite phase CaCO3 is lower than 80%, the aspect ratio of need―like calcium carbonate decreases significantly companied with the production of calcite cubic CaCO3 particles, thus the filtrated MgCl2 solution is unsuitable to recycled anymore. The direct recycle filtrate can be used for only once while the reused time by the MgCl2 filtrate can reach 12 by optimizing the recycle process through the addition of Mg2+ and the justification of pH of the filtrate.

  17. Bio-hybrid silk fibroin/calcium phosphate/PLGA nanocomposite scaffold to control the delivery of vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Farokhi, Mehdi, E-mail: mehdi13294@yahoo.com [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Mottaghitalab, Fatemeh, E-mail: fatemeh.motaghi@gmail.com [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University (TMU), Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: mashokrgozar@pasteur.ac.ir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: jafar_ai@tums.ac.ir [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Hadjati, Jamshid; Azami, Mahmoud [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2014-02-01

    This study investigated the efficacy of bio-hybrid silk fibroin/Calcium phosphate/PLGA nanocomposite scaffold as vascular endothelial growth factor (VEGF) delivery system. The scaffold was fabricated using freeze-drying and electrospinning. Here, we highlight the structural changes of the scaffold using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and differential scanning calorimetry (DSC). The uniform dispersion of calcium phosohate (CaP) powder within silk fibroin (SF) solution was also confirmed using Zeta potential analysis. Moreover, good biocompatibility of osteoblast cells next to the scaffold was approved by cell adhesion, proliferation and alkaline phosphatase production. The release profile of VEGF during 28 days has established the efficacy of the scaffold as a sustained delivery system. The bioactivity of the released VEGF was maintained about 83%. The histology analysis has shown that the new bone tissue formation happened in the defected site after 10 weeks of implantation. Generally, our data showed that the fabricated scaffold could be considered as an effective scaffold for bone tissue engineering applications. - Highlights: • Silk fibroin/calcium phosphate/PLGA scaffold was successfully fabricated using freeze-drying and electrospinning. • The scaffold could control the release of VEGF during 28 days. • The bioactivity of electrospun VEGF was above 80%. • VEGF loaded scaffold could induce bone regeneration after 10 weeks in rabbit.

  18. Bio-hybrid silk fibroin/calcium phosphate/PLGA nanocomposite scaffold to control the delivery of vascular endothelial growth factor

    International Nuclear Information System (INIS)

    This study investigated the efficacy of bio-hybrid silk fibroin/Calcium phosphate/PLGA nanocomposite scaffold as vascular endothelial growth factor (VEGF) delivery system. The scaffold was fabricated using freeze-drying and electrospinning. Here, we highlight the structural changes of the scaffold using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and differential scanning calorimetry (DSC). The uniform dispersion of calcium phosohate (CaP) powder within silk fibroin (SF) solution was also confirmed using Zeta potential analysis. Moreover, good biocompatibility of osteoblast cells next to the scaffold was approved by cell adhesion, proliferation and alkaline phosphatase production. The release profile of VEGF during 28 days has established the efficacy of the scaffold as a sustained delivery system. The bioactivity of the released VEGF was maintained about 83%. The histology analysis has shown that the new bone tissue formation happened in the defected site after 10 weeks of implantation. Generally, our data showed that the fabricated scaffold could be considered as an effective scaffold for bone tissue engineering applications. - Highlights: • Silk fibroin/calcium phosphate/PLGA scaffold was successfully fabricated using freeze-drying and electrospinning. • The scaffold could control the release of VEGF during 28 days. • The bioactivity of electrospun VEGF was above 80%. • VEGF loaded scaffold could induce bone regeneration after 10 weeks in rabbit

  19. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  20. Get Enough Calcium

    Science.gov (United States)

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of calcium ...