Sample records for chemotaxis signalling complex

  1. Signal transduction and chemotaxis in mast cells.

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


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

  2. Chemotaxis signaling systems in model beneficial plant-bacteria associations.

    Scharf, Birgit E; Hynes, Michael F; Alexandre, Gladys M


    Beneficial plant-microbe associations play critical roles in plant health. Bacterial chemotaxis provides a competitive advantage to motile flagellated bacteria in colonization of plant root surfaces, which is a prerequisite for the establishment of beneficial associations. Chemotaxis signaling enables motile soil bacteria to sense and respond to gradients of chemical compounds released by plant roots. This process allows bacteria to actively swim towards plant roots and is thus critical for competitive root surface colonization. The complete genome sequences of several plant-associated bacterial species indicate the presence of multiple chemotaxis systems and a large number of chemoreceptors. Further, most soil bacteria are motile and capable of chemotaxis, and chemotaxis-encoding genes are enriched in the bacteria found in the rhizosphere compared to the bulk soil. This review compares the architecture and diversity of chemotaxis signaling systems in model beneficial plant-associated bacteria and discusses their relevance to the rhizosphere lifestyle. While it is unclear how controlling chemotaxis via multiple parallel chemotaxis systems provides a competitive advantage to certain bacterial species, the presence of a larger number of chemoreceptors is likely to contribute to the ability of motile bacteria to survive in the soil and to compete for root surface colonization. PMID:26797793

  3. Protein Connectivity in Chemotaxis Receptor Complexes.

    Stephan Eismann


    Full Text Available The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

  4. DMPD: Cellular signaling in macrophage migration and chemotaxis. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 11073096 Cellular signaling in macrophage migration and chemotaxis. Jones GE. J Leu...koc Biol. 2000 Nov;68(5):593-602. (.png) (.svg) (.html) (.csml) Show Cellular signaling in macrophage migration... and chemotaxis. PubmedID 11073096 Title Cellular signaling in macrophage migration and chemotaxis. Autho

  5. Effects of receptor modification and temperature on dynamics of sensory complexes in Escherichia coli chemotaxis

    Grosse Karin


    Full Text Available Abstract Background Extracellular stimuli in chemotaxis of Escherichia coli and other bacteria are processed by large clusters of sensory complexes. The stable core of these clusters is formed by transmembrane receptors, a kinase CheA, and an adaptor CheW, whereas adaptation enzymes CheR and CheB dynamically associate with the clusters via interactions with receptors and/or CheA. Several biochemical studies have indicated the dependence of the sensory complex stability on the adaptive modification state of receptors and/or on temperature, which may potentially allow environment-dependent tuning of its signalling properties. However, the extent of such regulation in vivo and its significance for chemotaxis remained unclear. Results Here we used fluorescence recovery after photobleaching (FRAP to confirm in vivo that the exchange of CheA and CheW shows a modest dependency on the level of receptor modification/activity. An even more dramatic effect was observed for the exchange kinetics of CheR and CheB, indicating that their association with clusters may depend on the ability to bind substrate sites on receptors and on the regulatory phosphorylation of CheB. In contrast, environmental temperature did not have a discernible effect on stability of the cluster core. Strain-specific loss of E. coli chemotaxis at high temperature could instead be explained by a heat-induced reduction in the chemotaxis protein levels. Nevertheless, high basal levels of chemotaxis and flagellar proteins in common wild type strains MG1655 and W3110 enabled these strains to maintain their chemotactic ability up to 42°C. Conclusions Our results confirmed that clusters formed by less modified receptors are more dynamic, which can explain the previously observed adjustment of the chemotaxis response sensitivity according to the level of background stimulation. We further propose that the dependency of CheR exchange on the availability of unmethylated sites on receptors is

  6. Dictyostelium Chemotaxis studied with fluorescence fluctuation spectroscopy

    Ruchira, A.


    The movement of cells in the direction of a chemical gradient, also known as chemotaxis, is a vital biological process. During chemotaxis, minute extracellular signals are translated into complex cellular responses such as change in morphology and motility. To understand the chemotaxis mechanism at

  7. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.

    Orion D Weiner


    Full Text Available Migrating cells need to make different actin assemblies at the cell's leading and trailing edges and to maintain physical separation of signals for these assemblies. This asymmetric control of activities represents one important form of cell polarity. There are significant gaps in our understanding of the components involved in generating and maintaining polarity during chemotaxis. Here we characterize a family of complexes (which we term leading edge complexes, scaffolded by hematopoietic protein 1 (Hem-1, that organize the neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE2 complex, which mediates activation of actin polymerization by Rac, is only one member of this family. A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins. RNA interference-mediated knockdown of Hem-1-containing complexes in neutrophil-like cells: (a dramatically impairs attractant-induced actin polymerization, polarity, and chemotaxis; (b substantially weakens Rac activation and phosphatidylinositol-(3,4,5-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5-tris-phosphate/Rac/F-actin-mediated feedback circuit that organizes the leading edge; and (c prevents exclusion of activated myosin from the leading edge, perhaps by misregulating leading edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken together, these observations show that versatile Hem-1-containing complexes coordinate diverse regulatory signals at the leading edge of polarized neutrophils, including but not confined to those involving WAVE2-dependent actin polymerization.

  8. The photosensor protein Ppr of Rhodocista centenaria is linked to the chemotaxis signalling pathway

    Kiefer Dorothee


    Full Text Available Abstract Background Rhodocista centenaria is a phototrophic α-proteobacterium exhibiting a phototactic behaviour visible as colony movement on agar plates directed to red light. As many phototrophic purple bacteria R. centenaria possesses a soluble photoactive yellow protein (Pyp. It exists as a long fusion protein, designated Ppr, consisting of three domains, the Pyp domain, a putative bilin binding domain (Bbd and a histidine kinase domain (Pph. The Ppr protein is involved in the regulation of polyketide synthesis but it is still unclear, how this is connected to phototaxis and chemotaxis. Results To elucidate the possible role of Ppr and Pph in the chemotactic network we studied the interaction with chemotactic proteins in vitro as well as in vivo. Matrix-assisted coelution experiments were performed to study the possible communication of the different putative binding partners. The kinase domain of the Ppr protein was found to interact with the chemotactic linker protein CheW. The formation of this complex was clearly ATP-dependent. Further results indicated that the Pph histidine kinase domain and CheW may form a complex with the chemotactic kinase CheAY suggesting a role of Ppr in the chemotaxis signalling pathway. In addition, when Ppr or Pph were expressed in Escherichia coli, the chemotactic response of the cells was dramatically affected. Conclusions The Ppr protein of Rhodocista centenaria directly interacts with the chemotactic protein CheW. This suggests a role of the Ppr protein in the regulation of the chemotactic response in addition to its role in chalcone synthesis.

  9. Moment-flux models for bacterial chemotaxis in large signal gradients.

    Xue, Chuan; Yang, Xige


    Chemotaxis is a fundamental process in the life of many prokaryotic and eukaryotic cells. Chemotaxis of bacterial populations has been modeled by both individual-based stochastic models that take into account the biochemistry of intracellular signaling, and continuum PDE models that track the evolution of the cell density in space and time. Continuum models have been derived from individual-based models that describe intracellular signaling by a system of ODEs. The derivations rely on quasi-steady state approximations of the internal ODE system. While this assumption is valid if cell movement is subject to slowly changing signals, it is often violated if cells are exposed to rapidly changing signals. In the latter case current continuum models break down and do not match the underlying individual-based model quantitatively. In this paper, we derive new PDE models for bacterial chemotaxis in large signal gradients that involve not only the cell density and flux, but also moments of the intracellular signals as a measure of the deviation of cell's internal state from its steady state. The derivation is based on a new moment closure method without calling the quasi-steady state assumption of intracellular signaling. Numerical simulations suggest that the resulting model matches the population dynamics quantitatively for a much larger range of signals. PMID:26922437

  10. The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis

    Constant Stephanie


    Full Text Available Abstract Background Previous studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp. However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression. Results Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA. Conclusions Our results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.

  11. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    Bergin, David A


    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  12. The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis

    Wang, Fei


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

  13. HIV-1 Nef Binds the DOCK2-ELMO1 Complex to Activate Rac and Inhibit Lymphocyte Chemotaxis

    Janardhan Ajit


    Full Text Available The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, yet the mechanisms underlying these effects have remained elusive. Since Nef likely functions as an adaptor protein, we exploited a proteomic approach to directly identify molecules that Nef targets to subvert the signaling machinery in T cells. We purified to near homogeneity a major Nef-associated protein complex from T cells and identified by mass spectroscopy its subunits as DOCK2-ELMO1, a key activator of Rac in antigen- and chemokine-initiated signaling pathways, and Rac. We show that Nef activates Rac in T cell lines and in primary T cells following infection with HIV-1 in the absence of antigenic stimuli. Nef activates Rac by binding the DOCK2-ELMO1 complex, and this interaction is linked to the abilities of Nef to inhibit chemotaxis and promote T cell activation. Our data indicate that Nef targets a critical switch that regulates Rac GTPases downstream of chemokine- and antigen-initiated signaling pathways. This interaction enables Nef to influence multiple aspects of T cell function and thus provides an important mechanism by which Nef impacts pathogenesis by primate lentiviruses.

  14. ELMO1 Directly Interacts with Gβγ Subunit to Transduce GPCR Signaling to Rac1 Activation in Chemotaxis

    Wang, Youhong; Xu, Xuehua; Pan, Miao; Jin, Tian


    Diverse chemokines bind to G protein-coupled receptors (GPCRs) to activate the small GTPase Rac to regulate F-actin dynamics during chemotaxis. ELMO and Dock proteins form complexes that function as guanine nucleotide exchange factors (GEFs) for Rac activation. However, the linkage between GPCR activation and the ELMO/Dock-mediated Rac activation is not fully understood. In the present study, we show that chemoattractants induce dynamic membrane translocation of ELMO1 in mammalian cells. ELMO1 plays an important role in GPCR-mediated chemotaxis. We also reveal that ELMO1 and Dock1 form a stable complex. Importantly, activation of chemokine GPCR promotes the interaction between ELMO1 and Gβγ. The ELMO1-Gβγ interaction is through the N-terminus of ELMO1 protein and is important for the membrane translocation of ELMO1. ELMO1 is required for Rac1 activation upon chemoattractant stimulation. Our results suggest that chemokine GPCR-mediated interaction between Gβγ and ELMO1/Dock1 complex might serve as an evolutionarily conserved mechanism for Rac activation to regulate actin cytoskeleton for chemotaxis of human cells.

  15. Characterization of Cell Surface and EPS Remodeling of Azospirillum brasilense Chemotaxis-like 1 Signal Transduction Pathway mutants by Atomic Force Microscopy

    Billings, Amanda N [ORNL; Siuti, Piro [ORNL; Bible, Amber [University of Tennessee, Knoxville (UTK); Alexandre, Gladys [University of Tennessee, Knoxville (UTK); Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL; Morrell-Falvey, Jennifer L [ORNL


    To compete in complex microbial communities, bacteria must quickly sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the modulation of multiple cellular responses, including motility, EPS production, and cell-to-cell interactions. Recently, the Che1 chemotaxis-like pathway from Azospirillum brasilense was shown to modulate flocculation. In A. brasilense, cell surface properties, including EPS production, are thought to play a direct role in promoting flocculation. Using atomic force microscopy (AFM), we have detected distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains that are absent in the wild type strain. Whereas the wild type strain produces a smooth mucosal extracellular matrix, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition and lectin-binding assays suggest that the composition of EPS components in the extracellular matrix differs between the cheA1 and cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that mutations in the Che1 pathway that result in increased flocculation are correlated with distinctive changes in the extracellular matrix structure produced by the mutants, including likely changes in the EPS structure and/or composition.

  16. Characterization of cell surface and extracellular matrix remodeling of Azospirillum brasilense chemotaxis-like 1 signal transduction pathway mutants by atomic force microscopy

    Doktycz, Mitchel John [ORNL; Morrell-Falvey, Jennifer L [ORNL


    To compete in complex microbial communities, bacteria must sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the regulation of multiple behaviors in response to changes in the environment, including motility patterns, exopolysaccharide production, and cell-to-cell interactions. In Azospirillum brasilense, cell surface properties, including exopolysaccharide production, are thought to play a direct role in promoting flocculation. Recently, the Che1 chemotaxis-like pathway from A. brasilense was shown to modulate flocculation, suggesting an associated modulation of cell surface properties. Using atomic force microscopy, distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains were detected. Whereas the wild-type strain produces a smooth mucosal extracellular matrix after 24 h, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition, lectin-binding assays, and comparison of lipopolysaccharides profiles suggest that the extracellular matrix differs between the cheA1 and the cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that disruption of the Che1 pathway is correlated with distinctive changes in the extracellular matrix, which likely result from changes in surface polysaccharides structure and/or composition.

  17. Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

    Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan


    Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID:27367541

  18. Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum

    Hsu, Ming-Jen; Lee, Shiuh-Sheng; Lee, Sho Tone; Lin, Wan-Wan


    The polysaccharide from Ganoderma lucidum (PS-G) has been reported to enhance immune responses and to elicit antitumor effects. In our previous study, we found that PS-G efficiently inhibited spontaneously and Fas-enhanced neutrophil apoptosis when cultured in vitro. Since phagocytosis and chemotaxis play essential roles in host defense mediated by neutrophils, it is of great interest to know the effect of PS-G on these two cell functions, and the molecular events leading to these actions.Usi...

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

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


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

  20. A model invalidation-based approach for elucidating biological signalling pathways, applied to the chemotaxis pathway in R. sphaeroides

    Hamadeh Abdullah


    Full Text Available Abstract Background Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models. Results In this paper, we developed a novel mathematical model/experiment design cycle to help determine the probable network connectivity by iteratively invalidating models corresponding to competing signalling pathways. To do this, we systematically design experiments in silico that discriminate best between models of the competing signalling pathways. The method determines the inputs and parameter perturbations that will differentiate best between model outputs, corresponding to what can be measured/observed experimentally. We applied our method to the unknown connectivities in the chemotaxis pathway of the bacterium Rhodobacter sphaeroides. We first developed several models of R. sphaeroides chemotaxis corresponding to different signalling networks, all of which are biologically plausible. Parameters in these models were fitted so that they all represented wild type data equally well. The models were then compared to current mutant data and some were invalidated. To discriminate between the remaining models we used ideas from control systems theory to determine efficiently in silico an input profile that would result in the biggest difference in model outputs. However, when we applied this input to the models, we found it to be insufficient for discrimination in silico. Thus, to achieve better discrimination, we determined the best change in initial conditions (total protein concentrations as well as the best change in the input profile. The designed experiments were then performed on live cells and the resulting

  1. Chemotaxis in Densely Populated Tissue Determines Germinal Center Anatomy and Cell Motility: A New Paradigm for the Development of Complex Tissues

    Hawkins, Jared B; Jones, Mark T.; Plassmann, Paul E.; Thorley-Lawson, David A.


    Germinal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly struct...

  2. Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

    Urs B Hagemann

    Full Text Available CC chemokine receptor 4 (CCR4 represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs and on tumor cells in several cancer types and its role in metastasis.Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies.For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing. The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer.

  3. Chemotaxis of crawling and swimming Caenorhabditis Elegans

    Patel, Amar; Bilbao, Alejandro; Padmanabhan, Venkat; Khan, Zeina; Armstrong, Andrew; Rumbaugh, Kendra; Vanapalli, Siva; Blawzdziewicz, Jerzy


    A soil-dwelling nematode Caenorhabditis Elegans efficiently navigates through complex environments, responding to chemical signals to find food or avoid danger. According to previous studies, the nematode uses both gradual-turn and run-and-tumble strategies to move in the direction of the increasing concentration of chemical attractants. We show that both these chemotaxis strategies can be described using our kinematic model [PLoS ONE, 7: e40121 (2012)] in which harmonic-curvature modes represent elementary nematode movements. In our chemotaxis model, the statistics of mode changes is governed by the time history of the chemoattractant concentration at the position of the nematode head. We present results for both nematodes crawling without transverse slip and for swimming nematodes. This work was supported by NSF grant No. CBET 1059745.

  4. Chemotaxis in densely populated tissue determines germinal center anatomy and cell motility: a new paradigm for the development of complex tissues.

    Jared B Hawkins

    Full Text Available Germinal centers (GCs are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.

  5. Fundamental constraints on the abundances of chemotaxis proteins

    Bitbol, Anne-Florence


    Flagellated bacteria, such as Escherichia coli, perform directed motion in gradients of concentration of attractants and repellents in a process called chemotaxis. The E. coli chemotaxis signaling pathway is a model for signal transduction, but it has unique features. We demonstrate that the need for fast signaling necessitates high abundances of the proteins involved in this pathway. We show that further constraints on the abundances of chemotaxis proteins arise from the requirements of self-assembly, both of flagellar motors and of chemoreceptor arrays. All these constraints are specific to chemotaxis, and published data confirm that chemotaxis proteins tend to be more highly expressed than their homologs in other pathways. Employing a chemotaxis pathway model, we show that the gain of the pathway at the level of the response regulator CheY increases with overall chemotaxis protein abundances. This may explain why, at least in one E. coli strain, the abundance of all chemotaxis proteins is higher in media w...

  6. Feedback control architecture and the bacterial chemotaxis network.

    Abdullah Hamadeh


    Full Text Available Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance.

  7. Passive Hindrances Suppression Using Complex Polyphase Signals

    Sumyk, Markiyan; Yankevych, Roman


    Using complex signals we get possibility of indemnification of passive hindrances in the single-channel system of radio monitoring due to the use of correlation and spectral characteristics of certain class of complex signals.

  8. Methylation involved in chemotaxis is regulated during Caulobacter differentiation.

    Shaw, P; Gomes, S L; Sweeney, K; Ely, B; L. Shapiro


    Caulobacter crescentus carries a flagellum and is motile only during a limited time in its cell cycle. We have asked if the biochemical machinery that mediates chemotaxis exists coincident with the cell's structural ability to respond to a chemotactic signal. We first demonstrated that one function of the chemotaxis machinery, the ability to methylate the carboxyl side chains of a specific set of membrane proteins (methyl-accepting chemotaxis proteins, MCPs), is present in C. crescentus. This...

  9. Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway.

    Wang, Yang; Sun, Jintang; Ma, Chao; Gao, Wenjuan; Song, Bingfeng; Xue, Hao; Chen, Weiliang; Chen, Xi; Zhang, Yun; Shao, Qianqian; Wang, Qingjie; Zhao, Lei; Liu, Jia; Wang, Xiuwen; Wang, Huayang; Zhang, Yun; Yang, Meixiang; Qu, Xun


    Galectin-9 is a widely expressed protein that is involved in immune regulation and tumorpathogenesis and serves as a marker of a poor prognosis in various types of cancers. However, the clinical impact and the precise mechanism by which this protein contributes to colon tumor progression are unclear. In the present study, we detected the expression of galectin-9 and CD56 cells using immunohistochemistry. Spearman's rank correlation was used to clarify the association between galectin-9 expression and natural killer (NK) cell infiltration. The influence of galectin-9 on NK-92 cell migration was evaluated in vitro using transwell chemotaxis assays. The role of rh-galectin-9 in F-actin polarization in NK-92 cells was investigated using laser scanning confocal microscopy. We showed that galectin-9 was expressed in 101 (78.91%) colon tumor tissues and that was expressed at lower levels in these tissues than in para-tumor tissues. Low levels of galectin-9 expression were positively correlated with a poor histological grade and lymph node metastasis (Ppolarization through the Rho/ROCK1 signaling pathway. These results suggest that galectin-9 expression potentially represents a novel mechanism for tumors to escape immune surveillance in colon tumors. PMID:27028892

  10. Highlighting the role of Ras and Rap during Dictyostelium chemotaxis

    Kortholt, Arjan; van Haastert, Peter J. M.


    Chemotaxis, the directional movement towards a chemical compound, is an essential property of many cells and has been linked to the development and progression of many diseases. Eukaryotic chemotaxis is a complex process involving gradient sensing, cell polarity, remodelling of the cytoskeleton and

  11. Loss of C-terminal α-helix decreased SDF-1α-mediated signaling and chemotaxis without influencing CXCR4 internalization

    Shao-hui CAI; Yi TAN; Xian-da REN; Xiao-hong LI; Shao-xi CAI; Jun DU


    AIM: To investigate the possibility that a novel α-helix-defective mutant of stromal cell-derived factor-1α (SDF-1α) (SDF-1/54R) acts as an antagonist of CXC chemokine receptor 4 (CXCR4). METHODS: According to the genetic sequence of natural SDF- 1 α, a recombinant α-helix-defective mutant of SDF- 1 α was designed and some biologic characteristics of this mutant were demonstrated. The migration of Jurkat cells was assessed with chemotactic assay. ERK phosphorylation was analyzed by Western blot with a specific anti-phospho-ERK 1/2 antibody.Intracellular calcium influx was examined by flow cytometer with a calcium indicator dye Fluo-3AM. The CXCR4 on the cell surface was detected by flow cytometer with a PE conjoined anti-human CXCR4 antibody. RESULTS:Compared with native SDF-1α, SDF-1/54R displayed apparent decrease in chemotactic ability, ERK 1/2 activation,and intracellular calcium influx in Jurkat cells. However, the binding to CXCR4 and inducing CXCR4 internalization of SDF-1/54R did not change outstandingly. Moreover, a competitive inhibitory effect of SDF-1/54R on the migration of Jurkat cells induced by native SDF-1 α was confirmed. CONCLUSION: α-helix-defective mutant of SDF-1 α, SDF-1/54R that remained both the N-terminus and the central β-sheet region, decreased SDF-1 α-mediated signaling and chemotaxis but did not influence CXCR4 internalization, which suggested that SDF-1/54R might be developed as an anti-CHIV inhibitor with high biological potency and low side-effect.

  12. Metallothionein mediates leukocyte chemotaxis

    Lynes Michael A


    Full Text Available Abstract Background Metallothionein (MT is a cysteine-rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines Ccl17 and Cx3cl1. Cysteine motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor. Results In the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis. Conclusion These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure.

  13. Complex bioimpedance signals in cardiology

    Viščor, Ivo; Halámek, Josef; Vondra, Vlastimil

    Milano: Fondazione Don Carlo Gnocchi, 2008, P1B: 14-16. [Conference of the European Study Group on Cardiovascular Oscillations /5./ - ESGCO 2008. Parma (IT), 07.04.2008-09.04.2008] R&D Projects: GA ČR GP102/07/P425; GA AV ČR IAA200650801 Institutional research plan: CEZ:AV0Z20650511 Keywords : bioimpedance * complex impedance * impedance phase * cardiac output * pulmonary artery Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  14. QRS Complex Detection in Multilead ECG Signals

    Šlancar, M.


    Automated analysis of HRV requires reliable detection of QRS complexes. We propose a detection method based on different combinations of three orthogonal (pseudoorthogonal) leads of human ECG signals. ECG signals were filtered by standard pass-band filter, Teager-Kaiser energy operator (TKEO) was applied on signal as envelope for detection. The most effective combination for QRS detection was a spatial velocity with sensitivity exceeds 99.9 % and positive predictive value near to 99.5 %. Det...

  15. Bacterial strategies for chemotaxis response.

    Celani, Antonio; Vergassola, Massimo


    Regular environmental conditions allow for the evolution of specifically adapted responses, whereas complex environments usually lead to conflicting requirements upon the organism's response. A relevant instance of these issues is bacterial chemotaxis, where the evolutionary and functional reasons for the experimentally observed response to chemoattractants remain a riddle. Sensing and motility requirements are in fact optimized by different responses, which strongly depend on the chemoattractant environmental profiles. It is not clear then how those conflicting requirements quantitatively combine and compromise in shaping the chemotaxis response. Here we show that the experimental bacterial response corresponds to the maximin strategy that ensures the highest minimum uptake of chemoattractants for any profile of concentration. We show that the maximin response is the unique one that always outcompetes motile but nonchemotactic bacteria. The maximin strategy is adapted to the variable environments experienced by bacteria, and we explicitly show its emergence in simulations of bacterial populations in a chemostat. Finally, we recast the contrast of evolution in regular vs. complex environments in terms of minimax vs. maximin game-theoretical strategies. Our results are generally relevant to biological optimization principles and provide a systematic possibility to get around the need to know precisely the statistics of environmental fluctuations. PMID:20080704

  16. Travelling Waves in Hybrid Chemotaxis Models

    Franz, Benjamin


    Hybrid models of chemotaxis combine agent-based models of cells with partial differential equation models of extracellular chemical signals. In this paper, travelling wave properties of hybrid models of bacterial chemotaxis are investigated. Bacteria are modelled using an agent-based (individual-based) approach with internal dynamics describing signal transduction. In addition to the chemotactic behaviour of the bacteria, the individual-based model also includes cell proliferation and death. Cells consume the extracellular nutrient field (chemoattractant), which is modelled using a partial differential equation. Mesoscopic and macroscopic equations representing the behaviour of the hybrid model are derived and the existence of travelling wave solutions for these models is established. It is shown that cell proliferation is necessary for the existence of non-transient (stationary) travelling waves in hybrid models. Additionally, a numerical comparison between the wave speeds of the continuum models and the hybrid models shows good agreement in the case of weak chemotaxis and qualitative agreement for the strong chemotaxis case. In the case of slow cell adaptation, we detect oscillating behaviour of the wave, which cannot be explained by mean-field approximations. © 2013 Society for Mathematical Biology.

  17. The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

    Hai-Shu Lin


    Full Text Available MS-275 (entinostat and SAHA (vorinostat, two histone deacetylase (HDAC inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA. To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α  MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1, an endogenous suppressor of p38α  in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation of p38α  was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2, monocyte chemotactic protein-2 (MCP-2 and macrophage migration inhibitory factor (MIF in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.

  18. Perfect and near perfect adaptation in a model of bacterial chemotaxis

    Mello, Bernardo A.; Tu, Yuhai


    The signaling apparatus mediating bacterial chemotaxis can adapt to a wide range of persistent external stimuli. In many cases, the bacterial activity returns to its pre-stimulus level exactly and this "perfect adaptability" is robust against variations in various chemotaxis protein concentrations. We model the bacterial chemotaxis signaling pathway, from ligand binding to CheY phosphorylation. By solving the steady-state equations of the model analytically, we derive a full set of conditions...

  19. Coupled Oscillators with Chemotaxis

    Sawai, S; Sawai, Satoshi; Aizawa, Yoji


    A simple coupled oscillator system with chemotaxis is introduced to study morphogenesis of cellular slime molds. The model successfuly explains the migration of pseudoplasmodium which has been experimentally predicted to be lead by cells with higher intrinsic frequencies. Results obtained predict that its velocity attains its maximum value in the interface region between total locking and partial locking and also suggest possible roles played by partial synchrony during multicellular development.

  20. Travelling waves in hybrid chemotaxis models

    Franz, Benjamin; Painter, Kevin J; Erban, Radek


    Hybrid models of chemotaxis combine agent-based models of cells with partial differential equation models of extracellular chemical signals. In this paper, travelling wave properties of hybrid models of bacterial chemotaxis are investigated. Bacteria are modelled using an agent-based (individual-based) approach with internal dynamics describing signal transduction. In addition to the chemotactic behaviour of the bacteria, the individual-based model also includes cell proliferation and death. Cells consume the extracellular nutrient field (chemoattractant) which is modelled using a partial differential equation. Mesoscopic and macroscopic equations representing the behaviour of the hybrid model are derived and the existence of travelling wave solutions for these models is established. It is shown that cell proliferation is necessary for the existence of non-transient (stationary) travelling waves in hybrid models. Additionally, a numerical comparison between the wave speeds of the continuum models and the hybr...

  1. iPLA2β: front and center in human monocyte chemotaxis to MCP-1

    Mishra, Ravi S.; Carnevale, Kevin A.; Cathcart, Martha K.


    Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca2+-independent phospholipase (iPLA2β) and cytosolic phospholipase (cPLA2α), and subst...

  2. TGF-β1 blockade of microglial chemotaxis toward Aβ aggregates involves SMAD signaling and down-regulation of CCL5

    Huang Fong-Lee


    Full Text Available Abstract Background Overactivated microglia that cluster at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in Alzheimer's disease (AD. Therefore, attenuating microglial clustering can reduce focal neuroinflammation at neuritic plaques. Previously, we identified CCL5 and CCL2 as prominent chemokines that mediate the chemotaxis of microglia toward beta-amyloid (Aβaggregates. Although transforming growth factor-β1 (TGF-β1 has been shown to down-regulate the expression of chemokines in activated microglia, whether TGF-β1 can reduce the chemotaxis of microglia toward neuritic plaques in AD remains unclear. Methods In the present study, we investigated the effects of TGF-β1 on Aβ-induced chemotactic migration of BV-2 microglia using time-lapse recording, transwell assay, real-time PCR, ELISA, and western blotting. Results The cell tracing results suggest that the morphological characteristics and migratory patterns of BV-2 microglia resemble those of microglia in slice cultures. Using this model system, we discovered that TGF-β1 reduces Aβ-induced BV-2 microglial clustering in a dose-dependent manner. Chemotactic migration of these microglial cells toward Aβ aggregates was significantly attenuated by TGF-β1. However, these microglia remained actively moving without any reduction in migration speed. Pharmacological blockade of TGF-β1 receptor I (ALK5 by SB431542 treatment reduced the inhibitory effects of TGF-β1 on Aβ-induced BV-2 microglial clustering, while preventing TGF-β1-mediated cellular events, including SMAD2 phosphorylation and CCL5 down-regulation. Conclusions Our results suggest that TGF-β1 reduces Aβ-induced microglial chemotaxis via the SMAD2 pathway. The down-regulation of CCL5 by TGF-β1 at least partially contributes to the clustering of microglia at Aβ aggregates. The attenuating effects of SB431542 upon TGF-β1-suppressed microglial clustering may be

  3. Chemotaxis: new role for Ras revealed

    Jianshe Yan; Dale Hereld; Tian Jin


    @@ A recent study of chemotaxis revealed a new role for the proto-oncogene Ras in the social ameba Dictyostelium discoideum.Chemotaxis,the directional movement of cells toward chemokines and other chemoattractants,plays critical roles in diverse physiological processes,such as mobilization of immune cells to fight invading microorganisms,targeting of metastatic cancer cells to specific tissues,and guidance of sperm cells to ova during fertilization.This work,published in the July 26 issue of The Journal of Cell Biology,was conducted in Dr.Devreotes' lab at John Hopkins University and Dr.Parent's lab at National Cancer Institute.This research team demonstrated that RasC functions as an upstream regulator of TORC2 and thereby governs the effects of TORC2-PKB signaling on the cytoskeleton and cell migration.

  4. Complex analytic signals applied on time delay estimation

    Veličković Zoran S.; Pavlović Vlastimir D.


    In this paper, we present the concept of the time delay estimation based on the transformation of real sensor signals into analytic ones. We analyze the differential time delay values obtained using real seismic signals, simulated complex analytic signals and simulated complex analytic signals with real parts coming from real seismic signals. The simulation results indicate that the application of complex analytic signals leads to reliable computation of the differential time delay. The influ...

  5. Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell chemotaxis

    Ha-young LEE; Eun-ha SHIN; Yoe-sik BAE


    Aim: To investigate the effects of Sphingosylphosphorylcholine (SPC) on human monocyte-derived dendritic cell (DC) chemotaxis. Methods: Human DC were generated from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4. The effect of SPC on the DC chemotactic migration was measured by chemotaxis assay. Intracellular signaling event involved in the SPC-induced DC chemotaxis was investigated with several inhibitors for specific kinase. The expression of the SPC receptors was examined by reverse transcription polymerase chain reaction. Results: We found that SPC induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms of SPC-induced signaling events, mitogen activated protein kinase activation and Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3-kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do not express any of these receptors. To examine the involvement of sphin-gosine-1-phosphate (SIP) receptors, we checked the effect of an SIP receptor antagonist (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC chemotaxis. Conclusion: The results suggest that SPC may play a role in regulating DC trafficking during phagocytosis and the T cell-stimulating phase, and the unique SPC receptor, which is different from SIP receptors, is involved in SPC-induced chemotaxis.




    We consider a model system for the collective behavior of oxygen-driven swimming bacteria in an aquatic fluid. In certain parameter regimes, such suspensions of bacteria feature large-scale convection patterns as a result of the hydrodynamic interaction between bacteria. The presented model consist of a parabolicparabolic chemotaxis system for the oxygen concentration and the bacteria density coupled to an incompressible Stokes equation for the fluid driven by a gravitational force of the heavier bacteria. We show local existence of weak solutions in a bounded domain in d, d = 2, 3 with no-flux boundary condition and in 2 in the case of inhomogeneous Dirichlet conditions for the oxygen. © 2010 World Scientific Publishing Company.

  7. Normal chemotaxis in Dictyostelium discoideum cells with a depolarized plasma membrane potential

    Duijn, Bert van; Vogelzang, Sake A.; Ypey, Dirk L.; Molen, Loek G. van der; Haastert, Peter J.M. van


    We examined a possible role for the plasma membrane potential in signal transduction during cyclic AMP-induced chemotaxis in the cellular slime mold Dictyostelium discoideum. Chemotaxis, cyclic GMP and cyclic AMP responses in cells with a depolarized membrane potential were measured. Cells can be co

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

    Wad, Paul Emmanuel

    Complex or quadrature Sigma-Delta converters operate on complex signals, i.e. signals consisting of a real and an imaginary component, whereas conventional converters operate only on real signals. The advantage of complex signal processing in the discrete-time domain is that the entire sampling...... frequency bandwidth - not just half of it - is available, and that network zeros and poles can be placed anywhere without having to appear in complex conjugate pairs. This paper demonstrates how these properties can be used to design complex bandpass Sigma-Delta converters with a better noise performance...

  9. T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis

    Cinalli, Ryan M.; Herman, Catherine E.; Lew, Brian O.; Wieman, Heather L.; Thompson, Craig B.; Rathmell, Jeffrey C.


    Signals that regulate T cell homeostasis are not fully understood. G protein-coupled receptors (GPCR), such as the chemokine receptors, may affect homeostasis by direct signaling or by guiding T cell migration to distinct location-restricted signals. Here, we show that blockade of Gαi-associated GPCR signaling by treatment with pertussis toxin led to T cell atrophy and shortened life-span in T cell-replete hosts and prevented T cell homeostatic growth and proliferation in T cell-deficient hos...

  10. Complexity of Receptor Tyrosine Kinase Signal Processing

    Volinsky, Natalia; Kholodenko, Boris N.


    Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the ...

  11. Processing Motion Signals in Complex Environments

    Verghese, Preeti


    Motion information is critical for human locomotion and scene segmentation. Currently we have excellent neurophysiological models that are able to predict human detection and discrimination of local signals. Local motion signals are insufficient by themselves to guide human locomotion and to provide information about depth, object boundaries and surface structure. My research is aimed at understanding the mechanisms underlying the combination of motion signals across space and time. A target moving on an extended trajectory amidst noise dots in Brownian motion is much more detectable than the sum of signals generated by independent motion energy units responding to the trajectory segments. This result suggests that facilitation occurs between motion units tuned to similar directions, lying along the trajectory path. We investigated whether the interaction between local motion units along the motion direction is mediated by contrast. One possibility is that contrast-driven signals from motion units early in the trajectory sequence are added to signals in subsequent units. If this were the case, then units later in the sequence would have a larger signal than those earlier in the sequence. To test this possibility, we compared contrast discrimination thresholds for the first and third patches of a triplet of sequentially presented Gabor patches, aligned along the motion direction. According to this simple additive model, contrast increment thresholds for the third patch should be higher than thresholds for the first patch.The lack of a measurable effect on contrast thresholds for these various manipulations suggests that the pooling of signals along a trajectory is not mediated by contrast-driven signals. Instead, these results are consistent with models that propose that the facilitation of trajectory signals is achieved by a second-level network that chooses the strongest local motion signals and combines them if they occur in a spatio-temporal sequence consistent

  12. Complexity of Receptor Tyrosine Kinase Signal Processing

    Volinsky, Natalia; Kholodenko, Boris N.


    Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the immediate posttranslational and delayed transcriptional controls by multiple feed forward and feedback loops together with pathway cross talk, adapt cells to the combinatorial variety of external cues and conditions. This intricate network circuitry endows cells with emerging capabilities for RTK signal processing and decoding. We illustrate how mathematical modeling facilitates our understanding of RTK network behaviors by unraveling specific systems properties, including bistability, oscillations, excitable responses, and generation of intricate landscapes of signaling activities. PMID:23906711

  13. Precision and Kinetics of Adaptation in Bacterial Chemotaxis

    Meir, Yigal; Jakovljevic, Vladimir; Oleksiuk, Olga; Sourjik, Victor; Wingreen, Ned S.


    The chemotaxis network of the bacterium Escherichia coli is perhaps the most studied model for adaptation of a signaling system to persistent stimuli. Although adaptation in this system is generally considered to be precise, there has been little effort to quantify this precision, or to understand how and when precision fails. Using a Förster resonance energy transfer-based reporter of signaling activity, we undertook a systematic study of adaptation kinetics and precision in E. coli cells ex...

  14. Molecular determinants of receptor binding and signaling by the CX3C chemokine fractalkine

    Mizoue, L S; Sullivan, S K; King, D S; Kledal, T N; Schwartz, T W; Bacon, K B; Handel, T M


    reveal a cluster of basic residues (Lys-8, Lys-15, Lys-37, Arg-45, and Arg-48) and one aromatic (Phe-50) that are critical for binding and/or signaling. The mutant R48A could bind but not induce chemotaxis, demonstrating that Arg-48 is a signaling trigger. This result also shows that signaling residues...... are not confined to chemokine N termini, as generally thought. F50A showed no detectable binding, underscoring its importance to the stability of the complex. K15A displayed unique signaling characteristics, eliciting a wild-type calcium flux but minimal chemotaxis, suggesting that this mutant can...

  15. Sperm chemotaxis promotes individual fertilization success in sea urchins.

    Hussain, Yasmeen H; Guasto, Jeffrey S; Zimmer, Richard K; Stocker, Roman; Riffell, Jeffrey A


    Reproductive success fundamentally shapes an organism's ecology and evolution, and gamete traits mediate fertilization, which is a critical juncture in reproduction. Individual male fertilization success is dependent on the ability of sperm from one male to outcompete the sperm of other males when searching for a conspecific egg. Sperm chemotaxis, the ability of sperm to navigate towards eggs using chemical signals, has been studied for over a century, but such studies have long assumed that this phenomenon improves individual male fitness without explicit evidence to support this claim. Here, we assessed fertilization changes in the presence of a chemoattractant-digesting peptidase and used a microfluidic device coupled with a fertilization assay to determine the effect of sperm chemotaxis on individual male fertilization success in the sea urchin Lytechinus pictus We show that removing chemoattractant from the gametic environment decreases fertilization success. We further found that individual male differences in chemotaxis to a well-defined gradient of attractant correlate with individual male differences in fertilization success. These results demonstrate that sperm chemotaxis is an important contributor to individual reproductive success. PMID:26994183

  16. Maze-solving by chemotaxis

    Reynolds, A. M.


    Here, we report on numerical simulations showing that chemotaxis will take a body through a maze via the shortest possible route to the source of a chemoattractant. This is a robust finding that does not depend on the geometrical makeup of the maze. The predictions are supported by recent experimental studies which have shown that by moving down gradients in pH , a droplet of organic solvent can find the shortest of multiple possible paths through a maze to an acid-soaked exit. They are also consistent with numerical and experimental evidence that plant-parasitic nematodes take the shortest route through the labyrinth of air-filled pores within soil to preferred host plants that produce volatile chemoattractants. The predictions support the view that maze-solving is a robust property of chemotaxis and is not specific to particular kinds of maze or to the fractal structure of air-filled channels within soils.

  17. Complex analytic signals applied on time delay estimation

    Veličković Zoran S.


    Full Text Available In this paper, we present the concept of the time delay estimation based on the transformation of real sensor signals into analytic ones. We analyze the differential time delay values obtained using real seismic signals, simulated complex analytic signals and simulated complex analytic signals with real parts coming from real seismic signals. The simulation results indicate that the application of complex analytic signals leads to reliable computation of the differential time delay. The influence of specific signal parameters on spectral coherence threshold in systems for passive localization and proposed methods for lowering the threshold is analyzed. The computation of all differential time delays with respect to the reference sensor (geophone is based on the application of Generalized Cross-Correlation (GCC applied on corresponding analytic signals. The difficulties to select a peak of cross-correlation function that corresponds to true differential time delay when dealing with real signals are significantly reduced if GCC is applied on analytic signals. The efficiency of the proposed technique on differential delay estimation is performed on deterministic and real-life signals.

  18. Chemotaxis of large granular lymphocytes

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1+ cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML(3H)P, suggesting that LGL bear receptors for the chemotactic peptide

  19. Application of Coarse Integration to Bacterial Chemotaxis

    Setayeshgar, S; Othmer, H G; Kevrekidis, Yu G


    We have developed and implemented a numerical evolution scheme for a class of stochastic problems in which the temporal evolution occurs on widely-separated time scales, and for which the slow evolution can be described in terms of a small number of moments of an underlying probability distribution. We demonstrate this method via a numerical simulation of chemotaxis in a population of motile, independent bacteria swimming in a prescribed gradient of a chemoattractant. The microscopic stochastic model, which is simulated using a Monte Carlo method, uses a simplified deterministic model for excitation/adaptation in signal transduction, coupled to a realistic, stochastic description of the flagellar motor. We show that projective time integration of ``coarse'' variables can be carried out on time scales long compared to that of the microscopic dynamics. Our coarse description is based on the spatial cell density distribution. Thus we are assuming that the system ``closes'' on this variable so that it can be desc...

  20. Neutrophil Chemotaxis Dysfunction in Human Periodontitis

    Van Dyke, T. E.; Horoszewicz, H. U.; Cianciola, L. J.; Genco, R J


    Polymorphonuclear leukocyte (PMNL) chemotaxis studies of 32 patients with localized juvenile periodontitis (periodontosis or LJP), 10 adult patients with a history of LJP (post-LJP), 8 patients with generalized juvenile periodontitis (GJP), and 23 adults with moderate to severe periodontitis were performed: (i) to determine the prevalence of a PMNL chemotaxis defect in a large group of LJP patients; (ii) to study PMNL chemotaxis in patients with other forms of severe periodontal disease; and ...

  1. Chemotaxis of Azospirillum Species to Aromatic Compounds

    Lopez-de-Victoria, Geralyne; Lovell, Charles R.


    Chemotaxis of Azospirillum lipoferum Sp 59b and Azospirillum brasilense Sp 7 and Sp CD to malate and to the aromatic substrates benzoate, protocatechuate, 4-hydroxybenzoate, and catechol was assayed by the capillary method and direct cell counts. A. lipoferum required induction by growth on 4-hydroxybenzoate for positive chemotaxis to this compound. Chemotaxis of Azospirillum spp. to all other substrates did not require induction. Maximum chemotactic responses for most aromatic compounds occu...

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

    Bhattacharya, Joydeep; Lee, Eun-Jeong

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

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

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


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

  4. Complex signal amplitude analysis for complete fusion nuclear reaction products

    Tsyganov, Yu S


    A complex analysis has been performed on the energy amplitude signals corresponding to events of Z=117 element measured in the 249Bk+48Ca complete fusion nuclear reaction. These signals were detected with PIPS position sensitive detector. The significant values of pulse height defect both for recoils (ER) and fission fragments (FF) were measured. Comparison with the computer simulations and empirical formulae has been performed both for ER and FF signals.

  5. Theory of optimal information transmission in E. coli chemotaxis pathway

    Micali, Gabriele; Endres, Robert G.

    Bacteria live in complex microenvironments where they need to make critical decisions fast and reliably. These decisions are inherently affected by noise at all levels of the signaling pathway, and cells are often modeled as an input-output device that transmits extracellular stimuli (input) to internal proteins (channel), which determine the final behavior (output). Increasing the amount of transmitted information between input and output allows cells to better infer extracellular stimuli and respond accordingly. However, in contrast to electronic devices, the separation into input, channel, and output is not always clear in biological systems. Output might feed back into the input, and the channel, made by proteins, normally interacts with the input. Furthermore, a biological channel is affected by mutations and can change under evolutionary pressure. Here, we present a novel approach to maximize information transmission: given cell-external and internal noise, we analytically identify both input distributions and input-output relations that optimally transmit information. Using E. coli chemotaxis as an example, we conclude that its pathway is compatible with an optimal information transmission device despite the ultrasensitive rotary motors.

  6. Mast cell chemotaxis - chemoattractants and signaling pathways

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr


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

  7. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

    Hidekazu Kuwayama

    Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

  8. Amplified Signal Response by Neuronal Diversity on Complex Networks

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

  9. L-fucose influences chemotaxis and biofilm formation in Campylobacter jejuni.

    Dwivedi, Ritika; Nothaft, Harald; Garber, Jolene; Xin Kin, Lin; Stahl, Martin; Flint, Annika; van Vliet, Arnoud H M; Stintzi, Alain; Szymanski, Christine M


    Campylobacter jejuni and Campylobacter coli are zoonotic pathogens once considered asaccharolytic, but are now known to encode pathways for glucose and fucose uptake/metabolism. For C. jejuni, strains with the fuc locus possess a competitive advantage in animal colonization models. We demonstrate that this locus is present in > 50% of genome-sequenced strains and is prevalent in livestock-associated isolates of both species. To better understand how these campylobacters sense nutrient availability, we examined biofilm formation and chemotaxis to fucose. C. jejuni NCTC11168 forms less biofilms in the presence of fucose, although its fucose permease mutant (fucP) shows no change. In a newly developed chemotaxis assay, both wild-type and the fucP mutant are chemotactic towards fucose. C. jejuni 81-176 naturally lacks the fuc locus and is unable to swim towards fucose. Transfer of the NCTC11168 locus into 81-176 activated fucose uptake and chemotaxis. Fucose chemotaxis also correlated with possession of the pathway for C. jejuni RM1221 (fuc+) and 81116 (fuc-). Systematic mutation of the NCTC11168 locus revealed that Cj0485 is necessary for fucose metabolism and chemotaxis. This study suggests that components for fucose chemotaxis are encoded within the fuc locus, but downstream signals only in fuc + strains, are involved in coordinating fucose availability with biofilm development. PMID:27145048

  10. Complex-wave retrieval based on blind signal separation

    Xiaodong Chai; Chengpeng Zhou; Zhaoyan Feng; Yinhua Wang; Yansheng Zuo


    In the process of the reconstruction of digital holography, the traditional methods of diffraction and filtration are commonly adopted to recover the original complex-wave signal. Influenced by twin-image and zero-order terms, the above-mentioned methods, however, either limit the field of vision or result in the loss of the amplitude and phase. A new method for complex-wave retrieval is presented, which is based on blind signal separation. Three frames of holograms are captured by a charge coupled device (CCD)camera to form an observation signal. The term containing only amplitude and phase of complex-wave is separated, by means of independent component analysis, from the observation signal, which effectively eliminates the zero-order term. Finally, the complex-wave retrieval of pure phase wavefront is achieved.Experimental results show that this method can better recover the amplitude and phase of the original complex-wave even when there is a frequency spectrum mixture in the hologram.

  11. FES kinase participates in KIT-ligand induced chemotaxis

    Voisset, Edwige, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Lopez, Sophie, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Chaix, Amandine, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Vita, Marina, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); George, Coralie, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Dubreuil, Patrice, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); De Sepulveda, Paulo, E-mail: [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France)


    FES is a cytoplasmic tyrosine kinase activated by several membrane receptors, originally identified as a viral oncogene product. We have recently identified FES as a crucial effector of oncogenic KIT mutant receptor. However, FES implication in wild-type KIT receptor function was not addressed. We report here that FES interacts with KIT and is phosphorylated following activation by its ligand SCF. Unlike in the context of oncogenic KIT mutant, FES is not involved in wild-type KIT proliferation signal, or in cell adhesion. Instead, FES is required for SCF-induced chemotaxis. In conclusion, FES kinase is a mediator of wild-type KIT signalling implicated in cell migration.

  12. Strenuous physical exercise adversely affects monocyte chemotaxis

    Czepluch, Frauke S; Barres, Romain; Caidahl, Kenneth;


    Physical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating...... in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor...

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

    Bysted, Tommy Kristensen


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

  14. Levels of complexity in scale-invariant neural signals

    Ivanov, Plamen Ch.; Ma, Qianli D. Y.; Bartsch, Ronny P.


    Many physiological systems exhibit complex scale-invariant and nonlinear features characterized long-range power-law correlations, indicating a possibly common control mechanism. It has been suggested that dynamical processes, influenced by inputs and feedback on multiple time scales, may be sufficient to give rise to this complexity. Two examples of physiologic signals that are the output of hierarchical multiscale physiologic systems under neural control are the human heartbeat and human gait. We show that while both cardiac interbeat interval and gait interstride interval time series under healthy conditions have comparable scale-invariant behavior, they still belong to different complexity classes. We compare results from empirical findings and stochastic feedback modeling approaches to cardiac and locomotor dynamics, which provide new insights into the multicomponent neural mechanisms regulating these complex systems.

  15. A Novel Approach for Detecting QRS Complex of ECG signal

    Sameer K Salih


    Full Text Available In this study, an automatic approach for detecting QRS complexes and evaluating related R-R intervals of ECG signals (PNDM is proposed. It reliably recognizes QRS complexes based on the deflection occurred between R S waves as a large positive and negative interval with respect to other ECG signal waves. The proposed detection method follows new fast direct algorithm applied to the entire ECG record itself without additional transformation like discrete wavelet transform (DWT or any filtering sequence. Mostly used records in the online ECG database (MIT-BIH Arrhythmia have been used to evaluate the new technique. Moreover it was compared to seven existing techniques; the results show that PNDM has much detection performances according to 99.95% sensitivity and 99.97% specificity. It is also quickest than comparable methods.

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

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


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

  17. Noise-Induced Increase of Sensitivity in Bacterial Chemotaxis.

    He, Rui; Zhang, Rongjing; Yuan, Junhua


    Flagellated bacteria, like Escherichia coli, can swim toward beneficial environments by modulating the rotational direction of their flagellar motors through a chemotaxis signal transduction network. The noise of this network, the random fluctuation of the intracellular concentration of the signal protein CheY-P with time, has been identified in studies of single cell behavioral variability, and found to be important in coordination of multiple motors in a bacterium and in enhancement of bacterial drift velocity in chemical gradients. Here, by comparing the behavioral difference between motors of wild-type E. coli and mutants without signal noise, we measured the magnitude of this noise in wild-type cells, and found that the noise increases the sensitivity of the bacterial chemotaxis network downstream at the level of the flagellar motor. This provided a simple mechanism for the noise-induced enhancement of chemotactic drift, which we confirmed by simulating the E. coli chemotactic motion in various spatial profiles of chemo-attractant concentration. PMID:27463144

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

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


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

  19. Multilevel complexity of calcium signaling:Modeling angiogenesis

    Luca; Munaron; Marco; Scianna


    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.

  20. Complex courtship displays facilitate male reproductive success and plasticity in signaling across variable environments

    Dustin J. WILGERS, Eileen A. HEBETS


    Effective signal transmission is essential for communication. In environments where signal transmission is highly variable, signalers may utilize complex signals, which incorporate multiple components and modalities, to maintain effective communication. Male Rabidosa rabida wolf spiders produce complex courtship signals, consisting of both visual and seismic components. We test the hypothesis that the complex signaling of R. rabida contributes to male reproductive success in variable signalin...

  1. Complex Interplay of Hormonal Signals during Grape Berry Ripening

    Ana Margarida Fortes


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

  2. The sensory transduction pathways in bacterial chemotaxis

    Taylor, Barry L.


    Bacterial chemotaxis is a useful model for investigating in molecular detail the behavioral response of cells to changes in their environment. Peritrichously flagellated bacteria such as coli and typhimurium swim by rotating helical flagella in a counterclockwise direction. If flagellar rotation is briefly reversed, the bacteria tumble and change the direction of swimming. The bacteria continuously sample the environment and use a temporal sensing mechanism to compare the present and immediate past environments. Bacteria respond to a broad range of stimuli including changes in temperature, oxygen concentration, pH and osmotic strength. Bacteria are attracted to potential sources of nutrition such as sugars and amino acids and are repelled by other chemicals. In the methylation-dependent pathways for sensory transduction and adaptation in E. coli and S. typhimurium, chemoeffectors bind to transducing proteins that span the plasma membrane. The transducing proteins are postulated to control the rate of autophosphorylation of the CheA protein, which in turn phosphorylates the CheY protein. The phospho-CheY protein binds to the switch on the flagellar motor and is the signal for clockwise rotation of the motor. Adaptation to an attractant is achieved by increasing methylation of the transducing protein until the attractant stimulus is cancelled. Responses to oxygen and certain sugars involve methylation-independent pathways in which adaption occurs without methylation of a transducing protein. Taxis toward oxygen is mediated by the electron transport system and changes in the proton motive force. Recent studies have shown that the methylation-independent pathway converges with the methylation-dependent pathway at or before the CheA protein.

  3. Transmembrane signaling through major histocompatibility complex (MHC) encoded molecules

    The importance of the major histocompatibility complex (MHC) encoded molecules has traditionally been ascribed to the role these molecules play as restriction elements for T lymphocytes. This is, in order for T cell activation to occur the T cell must recognize antigen in association with MHC molecules. More controversial, however, is the potential role MHC molecules play as signal transducing receptors/acceptors to the B lymphocyte. In other words, do class II MHC molecules (Ia antigens) actively transduce a signal to the B cell which drives its differentiation into an antibody secreting cell? Two approaches to this question are described. The first involves biochemical characterization of those molecules which consistently copurify with I-A/sup k/ by two dimensional gel electrophoresis. The second approach utilizes two types of analyses: first, an examination of the biochemical changes which occur in the cell as a result of Ia ligation; and second, analysis of changes in the B cell's physiological response as a result of Ia perturbation. Molecules were examined which may couple the antigen binding event in the B lymphocyte to the antigen driven signal transduction cascade which ultimately leads to immunoglobulin secretion. In these experiments, cells were labelled with [32P] and stimulated cells with phorbol myristate acetate. The membrane form of immunoglobulin was then isolated from detergent lysates of whole cells and passed over an anti-k affinity column. The eluates were analyzed by SDS-PAGE

  4. Information theoretical quantification of cooperativity in signalling complexes

    Ferkinghoff-Borg Jesper


    Full Text Available Abstract Background Intra-cellular information exchange, propelled by cascades of interacting signalling proteins, is essential for the proper functioning and survival of cells. Now that the interactome of several organisms is being mapped and several structural mechanisms of cooperativity at the molecular level in proteins have been elucidated, the formalization of this fundamental quantity, i.e. information, in these very diverse biological contexts becomes feasible. Results We show here that Shannon's mutual information quantifies information in biological system and more specifically the cooperativity inherent to the assembly of macromolecular complexes. We show how protein complexes can be considered as particular instances of noisy communication channels. Further we show, using a portion of the p27 regulatory pathway, how classical equilibrium thermodynamic quantities such as binding affinities and chemical potentials can be used to quantify information exchange but also to determine engineering properties such as channel noise and channel capacity. As such, this information measure identifies and quantifies those protein concentrations that render the biochemical system most effective in switching between the active and inactive state of the intracellular process. Conclusion The proposed framework provides a new and original approach to analyse the effects of cooperativity in the assembly of macromolecular complexes. It shows the conditions, provided by the protein concentrations, for which a particular system acts most effectively, i.e. exchanges the most information. As such this framework opens the possibility of grasping biological qualities such as system sensitivity, robustness or plasticity directly in terms of their effect on information exchange. Although these parameters might also be derived using classical thermodynamic parameters, a recasting of biological signalling in terms of information exchange offers an alternative

  5. Biomixing by chemotaxis and enhancement of biological reactions

    Kiselev, Alexander


    Many processes in biology involve both reactions and chemotaxis. However, to the best of our knowledge, the question of interaction between chemotaxis and reactions has not yet been addressed either analytically or numerically. We consider a model with a single density function involving diffusion, advection, chemotaxis, and absorbing reaction. The model is motivated, in particular, by studies of coral broadcast spawning, where experimental observations of the efficiency of fertilization rates significantly exceed the data obtained from numerical models that do not take chemotaxis (attraction of sperm gametes by a chemical secreted by egg gametes) into account. We prove that in the framework of our model, chemotaxis plays a crucial role. There is a rigid limit to how much the fertilization efficiency can be enhanced if there is no chemotaxis but only advection and diffusion. On the other hand, when chemotaxis is present, the fertilization rate can be arbitrarily close to being complete provided that the chemo...

  6. Structural permeability of complex networks to control signals

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


    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.

  7. Transient dynamic phenotypes as criteria for model discrimination: fold-change detection in Rhodobacter sphaeroides chemotaxis.

    Hamadeh, Abdullah; Ingalls, Brian; Sontag, Eduardo


    The chemotaxis pathway of the bacterium Rhodobacter sphaeroides shares many similarities with that of Escherichia coli. It exhibits robust adaptation and has several homologues of the latter's chemotaxis proteins. Recent theoretical results have correctly predicted that the E. coli output behaviour is unchanged under scaling of its ligand input signal; this property is known as fold-change detection (FCD). In the light of recent experimental results suggesting that R. sphaeroides may also show FCD, we present theoretical assumptions on the R. sphaeroides chemosensory dynamics that can be shown to yield FCD behaviour. Furthermore, it is shown that these assumptions make FCD a property of this system that is robust to structural and parametric variations in the chemotaxis pathway, in agreement with experimental results. We construct and examine models of the full chemotaxis pathway that satisfy these assumptions and reproduce experimental time-series data from earlier studies. We then propose experiments in which models satisfying our theoretical assumptions predict robust FCD behaviour where earlier models do not. In this way, we illustrate how transient dynamic phenotypes such as FCD can be used for the purposes of discriminating between models that reproduce the same experimental time-series data. PMID:23293140

  8. Rho GTPases orient directional sensing in chemotaxis

    Wang, Yu; Senoo, Hiroshi; Sesaki, Hiromi; Iijima, Miho


    During chemotaxis, cells recognize an extracellular chemical gradient and produce amplified intracellular responses independently of the actin cytoskeleton. This process is called directional sensing and observed as the activation of Ras GTPase and the production of phosphatidylinositol (3,4,5)-triphosphate (PIP3) toward higher concentrations of chemoattractants. How directional sensing is controlled is largely unknown. In our current study, we demonstrate that a Rho GTPase (RacE) and a Rho g...

  9. Modeling bacterial chemotaxis inside a cell

    Ouannes, Nesrine; Djedi, Noureddine; Luga, Hervé; Duthen, Yves


    This paper describes a bacterial system that reproduces a population of bacteria that behave by simulating the internal reactions of each bacterial cell. The chemotaxis network of a cell is modulated by a hybrid approach that uses an algebraic model for the receptor clusters activity and an ordinary differential equation for the adaptation dynamics. The experiments are defined in order to simulate bacterial growth in an environment where nutrients are regularly added to it. The results show a...

  10. Imprecision of Adaptation in Escherichia coli Chemotaxis

    Silke Neumann; Nikita Vladimirov; Krembel, Anna K.; Wingreen, Ned S.; Victor Sourjik


    Adaptability is an essential property of many sensory systems, enabling maintenance of a sensitive response over a range of background stimulus levels. In bacterial chemotaxis, adaptation to the preset level of pathway activity is achieved through an integral feedback mechanism based on activity-dependent methylation of chemoreceptors. It has been argued that this architecture ensures precise and robust adaptation regardless of the ambient ligand concentration, making perfect adaptation a cel...

  11. Toward Synthetic Spatial Patterns in Engineered Cell Populations with Chemotaxis.

    Duran-Nebreda, Salva; Solé, Ricard V


    A major force shaping form and patterns in biology is based in the presence of amplification mechanisms able to generate ordered, large-scale spatial structures out of local interactions and random initial conditions. Turing patterns are one of the best known candidates for such ordering dynamics, and their existence has been proven in both chemical and physical systems. Their relevance in biology, although strongly supported by indirect evidence, is still under discussion. Extensive modeling approaches have stemmed from Turing's pioneering ideas, but further confirmation from experimental biology is required. An alternative possibility is to engineer cells so that self-organized patterns emerge from local communication. Here we propose a potential synthetic design based on the interaction between population density and a diffusing signal, including also directed motion in the form of chemotaxis. The feasibility of engineering such a system and its implications for developmental biology are also assessed. PMID:27009520

  12. The Pseudomonas aeruginosa chemotaxis methyltransferase CheR1 impacts on bacterial surface sampling.

    Juliane Schmidt

    Full Text Available The characterization of factors contributing to the formation and development of surface-associated bacterial communities known as biofilms has become an area of intense interest since biofilms have a major impact on human health, the environment and industry. Various studies have demonstrated that motility, including swimming, swarming and twitching, seems to play an important role in the surface colonization and establishment of structured biofilms. Thereby, the impact of chemotaxis on biofilm formation has been less intensively studied. Pseudomonas aeruginosa has a very complex chemosensory system with two Che systems implicated in flagella-mediated motility. In this study, we demonstrate that the chemotaxis protein CheR1 is a methyltransferase that binds S-adenosylmethionine and transfers a methyl group from this methyl donor to the chemoreceptor PctA, an activity which can be stimulated by the attractant serine but not by glutamine. We furthermore demonstrate that CheR1 does not only play a role in flagella-mediated chemotaxis but that its activity is essential for the formation and maintenance of bacterial biofilm structures. We propose a model in which motility and chemotaxis impact on initial attachment processes, dispersion and reattachment and increase the efficiency and frequency of surface sampling in P. aeruginosa.

  13. Complex courtship displays facilitate male reproductive success and plasticity in signaling across variable environments

    Dustin J.WILGERS; Eileen A.HEBETS


    Effective signal transmission is essential for communication.In environments where signal transmission is highly variable,signalers may utilize complex signals,which incorporate multiple components and modalities,to maintain effective communication.Male Rabidosa rabida wolf spiders produce complex courtship signals,consisting of both visual and seismic components.We test the hypothesis that the complex signaling of R.rabida contributes to male reproductive success in variable signaling environments.We first examine the condition-dependence of foreleg ornamentation(a presumed visual signal)and seismic signal components and find that both may provide potentially redundant information on foraging history.Next,we assessed reproductive success across manipulated signaling environments that varied in the effectiveness of visual and/or seismic signal environmenis where only one signal could be successfully transmitted(e.g.,visual or seismic),pairs were still able to successfully copulate.Additionally,we found that males altered their courtship display depending on the current signaling environment.Specifically,males reduced their use of a visual display component in signaling environments where visual signal transmission was ablated.Incorporating signals in multiple modalities not only enables R.rabida males to maintain copulation success across variable signaiing environments,but it also enables males to adjust their composite courtship display to current signaling conditions.

  14. Seismic signal analysis based on the dual-tree complex wavelet packet transform

    谢周敏; 王恩福; 张国宏; 赵国存; 陈旭庚


    We tried to apply the dual-tree complex wavelet packet transform in seismic signal analysis. The complex waveletpacket transform (CWPT) combine the merits of real wavelet packet transform with that of complex continuouswavelet transform (CCWT). It can not only pick up the phase information of signal, but also produce better "focalizing" function if it matches the phase spectrum of signals analyzed. We here described the dual-tree CWPT algorithm, and gave the examples of simulation and actual seismic signals analysis. As shown by our results, thedual-tree CWPT is a very efecfive method in analyzing seismic signals with non-linear phase.

  15. Computational Chemotaxis in Ants and Bacteria over Dynamic Environments

    Ramos, Vitorino; Rosa, A C; Abraham, A


    Chemotaxis can be defined as an innate behavioural response by an organism to a directional stimulus, in which bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food (e.g., glucose) by swimming towards the highest concentration of food molecules, or to flee from poisons. Based on self-organized computational approaches and similar stigmergic concepts we derive a novel swarm intelligent algorithm. What strikes from these observations is that both eusocial insects as ant colonies and bacteria have similar natural mechanisms based on stigmergy in order to emerge coherent and sophisticated patterns of global collective behaviour. Keeping in mind the above characteristics we will present a simple model to tackle the collective adaptation of a social swarm based on real ant colony behaviors (SSA algorithm) for tracking extrema in dynamic environments and highly multimodal complex functions des...

  16. GPCR – G protein complexes – the fundamental signaling assembly

    Jastrzebska, Beata


    G protein coupled receptors (GPCR) constitute the largest group of cell surface receptors that transmit various signals across biological membranes through the binding and activation of heterotrimeric G proteins, which amplify the signal and activate downstream effectors leading to the biological responses. Thus, the first critical step in this signaling cascade is the interaction between receptor and its cognate G protein. Understanding this critical event at the molecular level is of high i...

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


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

  18. Quantifying the complexity of human colonic pressure signals using an entropy measure.

    Xu, Fei; Yan, Guozheng; Zhao, Kai; Lu, Li; Wang, Zhiwu; Gao, Jinyang


    Studying the complexity of human colonic pressure signals is important in understanding this intricate, evolved, dynamic system. This article presents a method for quantifying the complexity of colonic pressure signals using an entropy measure. As a self-adaptive non-stationary signal analysis algorithm, empirical mode decomposition can decompose a complex pressure signal into a set of intrinsic mode functions (IMFs). Considering that IMF2, IMF3, and IMF4 represent crucial characteristics of colonic motility, a new signal was reconstructed with these three signals. Then, the time entropy (TE), power spectral entropy (PSE), and approximate entropy (AE) of the reconstructed signal were calculated. For subjects with constipation and healthy individuals, experimental results showed that the entropies of reconstructed signals between these two classes were distinguishable. Moreover, the TE, PSE, and AE can be extracted as features for further subject classification. PMID:26043437

  19. Differential maturation of brain signal complexity in the human auditory and visual system

    Sarah Lippe


    Full Text Available Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in complexity were not equivalent for the two responses. Infants’ signal complexity for the visual condition was greater than auditory signal complexity, whereas adults showed the same level of complexity to both types of stimuli. The differential rates of complexity change may reflect a combination of innate and experiential factors on the structure and function of the two sensory systems.

  20. Cytokinin signal transduction: Known simplicity and unknown complexity

    ZHENG Binglian; SUN Jiaqiang; ZHANG Suzhi; DENG Yan; ZUO Jianru


    Cytokinin plays a critical role in plant growth and development by regulating cell divisions and cell differentiation. Recent studies suggest that cytokinin signaling is presumably mediated by a two-component system analogous to those found in bacteria and fungi, which transduces an external signal via a phosphorelay from the plasma membrane-anchored receptors to downstream effectors andregulators. Moreover, cytokinin signaling is highly interactive with other pathways, and many components of the pathway appear to be functionally redundant. Proper address of these questions will be crucial for our further understanding onthis important network.

  1. Self-similar dynamics of bacterial chemotaxis

    Ngamsaad, Waipot


    We investigate the pattern formation of colony generated by chemotactic bacteria through a continuum model. In a simplified case, the dynamics of system is governed by a density-dependent convection-reaction-diffusion equation, $u_t = (u^{m})_{xx} - 2\\kappa(u^m)_{x}+ u - u^{m}$. This equation admits the analytical solutions that show the self-similarity of the bacterial colony's morphogenesis. In addition, we found that the colony evolves long time as the sharp traveling wave. The roles of chemotaxis on the regulation of pattern formation in these results are also discussed.


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


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


    LI Hong; ZHOU Zhiyuan; DAI Rongyang; LUO Bo; ZHENG Xiaoli; YANG Wenli; HE Tao; WU Minglu


    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.

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

    Pedersen, Anders Elm; Skov, S; Bregenholt, S; Ruhwald, M; Claesson, M H


    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...... immediately after and at later intervals following MHC-I ligation. It is hypothesized that MHC-I expression, both ontogenically and in evolution, is driven by a cell-mediated selection pressure advantageous to the MHC-I-expressing cell. Accordingly, in addition to their role in T-cell selection and...

  5. The Two Channels Complex Bioimpedance Signals in Cardiology

    Halámek, Josef; Vondra, Vlastimil; Jurák, Pavel; Verner, Petr

    Brno: University of Technology, 2006, s. 137-139. ISBN 80-214-3152-0. ISSN 1211-412X. [BIOSIGNAL 2006 /18./. Brno (CZ), 28.06.2006-30.06.2006] R&D Projects: GA ČR GA102/06/0136 Institutional research plan: CEZ:AV0Z20650511 Keywords : bioimpedance * compex signal Subject RIV: FS - Medical Facilities ; Equipment

  6. Nonlinear signal processing for ultrasonic imaging of material complexity

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


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

  7. Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the Pathogenic Life Cycle of the Spirochete.

    Moon, Ki Hwan; Hobbs, Gerry; Motaleb, M A


    Borrelia burgdorferi possesses a sophisticated chemotaxis signaling system; however, the roles of the majority of the chemotaxis proteins in the infectious life cycle have not yet been demonstrated. Specifically, the role of CheD during host colonization has not been demonstrated in any bacterium. Here, we systematically characterized the B. burgdorferi CheD homolog using genetics and biochemical and mouse-tick-mouse infection cycle studies. Bacillus subtilis CheD plays an important role in chemotaxis by deamidation of methyl-accepting chemotaxis protein receptors (MCPs) and by increasing the receptor kinase activity or enhancing CheC phosphatase activity, thereby regulating the levels of the CheY response regulator. Our biochemical analysis indicates that B. burgdorferi CheD significantly enhances CheX phosphatase activity by specifically interacting with the phosphatase. Moreover, CheD specifically binds two of the six MCPs, indicating that CheD may also modulate the receptor proteins. Although the motility of the cheD mutant cells was indistinguishable from that of the wild-type cells, the mutant did exhibit reduced chemotaxis. Importantly, the mutant showed significantly reduced infectivity in C3H/HeN mice via needle inoculation. Mouse-tick-mouse infection assays indicated that CheD is dispensable for acquisition or transmission of spirochetes; however, the viability of cheD mutants in ticks is marginally reduced compared to that of the wild-type or complemented cheD spirochetes. These data suggest that CheD plays an important role in the chemotaxis and pathogenesis of B. burgdorferi We propose potential connections between CheD, CheX, and MCPs and discuss how these interactions play critical roles during the infectious life cycle of the spirochete. PMID:27021244

  8. Computational modeling reveals that a combination of chemotaxis and differential adhesion leads to robust cell sorting during tissue patterning.

    Tan, Rui Zhen; Chiam, Keng-Hwee


    Robust tissue patterning is crucial to many processes during development. The "French Flag" model of patterning, whereby naïve cells in a gradient of diffusible morphogen signal adopt different fates due to exposure to different amounts of morphogen concentration, has been the most widely proposed model for tissue patterning. However, recently, using time-lapse experiments, cell sorting has been found to be an alternative model for tissue patterning in the zebrafish neural tube. But it remains unclear what the sorting mechanism is. In this article, we used computational modeling to show that two mechanisms, chemotaxis and differential adhesion, are needed for robust cell sorting. We assessed the performance of each of the two mechanisms by quantifying the fraction of correct sorting, the fraction of stable clusters formed after correct sorting, the time needed to achieve correct sorting, and the size variations of the cells having different fates. We found that chemotaxis and differential adhesion confer different advantages to the sorting process. Chemotaxis leads to high fraction of correct sorting as individual cells will either migrate towards or away from the source depending on its cell type. However after the cells have sorted correctly, there is no interaction among cells of the same type to stabilize the sorted boundaries, leading to cell clusters that are unstable. On the other hand, differential adhesion results in low fraction of correct clusters that are more stable. In the absence of morphogen gradient noise, a combination of both chemotaxis and differential adhesion yields cell sorting that is both accurate and robust. However, in the presence of gradient noise, the simple combination of chemotaxis and differential adhesion is insufficient for cell sorting; instead, chemotaxis coupled with delayed differential adhesion is required to yield optimal sorting. PMID:25302949

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

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


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

  10. Modelling the optical bleaching of a complex TL signal

    Thermoluminescence (TL) intensity decrease is observed in many materials after optical stimulation and is called optical bleaching of TL. The optical bleaching of a TL peak does not always mean that the traps responsible for this peak are emptied by stimulating light. The McKeever model explains TL bleaching by the emptying of deep thermally disconnected traps. The modification of this model is used for simulating the optical bleaching of complex TL curves in the case of complex TL spectrum. Some characteristic outcomes important for interpreting the results of TL optical bleaching measurements are reported

  11. Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases

    Kampen, G T; Stafford, S; Adachi, T;


    Eotaxin and other CC chemokines acting via CC chemokine receptor-3 (CCR3) are believed to play an integral role in the development of eosinophilic inflammation in asthma and allergic inflammatory diseases. However, little is known about the intracellular events following agonist binding to CCR3 and...... the relationship of these events to the functional response of the cell. The objectives of this study were to investigate CCR3-mediated activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase-2 (ERK2), p38, and c-jun N-terminal kinase (JNK) in eosinophils and to...... assess the requirement for MAP kinases in eotaxin-induced eosinophil cationic protein (ECP) release and chemotaxis. MAP kinase activation was studied in eotaxin-stimulated eosinophils (more than 97% purity) by Western blotting and immune-complex kinase assays. ECP release was measured by radioimmunoassay...

  12. A Sensitive Chemotaxis Assay Using a Novel Microfluidic Device

    Chen Zhang


    Full Text Available Existing chemotaxis assays do not generate stable chemotactic gradients and thus—over time—functionally measure only nonspecific random motion (chemokinesis. In comparison, microfluidic technology has the capacity to generate a tightly controlled microenvironment that can be stably maintained for extended periods of time and is, therefore, amenable to adaptation for assaying chemotaxis. We describe here a novel microfluidic device for sensitive assay of cellular migration and show its application for evaluating the chemotaxis of smooth muscle cells in a chemokine gradient.

  13. A coupled chemotaxis-fluid model: Global existence

    Liu, Jian-Guo


    We consider a model arising from biology, consisting of chemotaxis equations coupled to viscous incompressible fluid equations through transport and external forcing. Global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the chemotaxis-Navier- Stokes system in two space dimensions, we obtain global existence for large data. In three space dimensions, we prove global existence of weak solutions for the chemotaxis-Stokes system with nonlinear diffusion for the cell density.© 2011 Elsevier Masson SAS. All rights reserved.

  14. Chemotaxis of Azospirillum species to aromatic compounds

    Lopez-de-Victoria, G.; Lovell, C.R. (Univ. of South Carolina, Columbia, SC (United States))


    Azospirillum sspeciesare free-living nitrogen fixing bacteria commonly found in soils and in association with plant roots, including important agricultural crops. Rhizosphere colonization my Azospirillum species has been shown to stimulate growth of a variety of plant species. Chemotaxis is one of the properties which may contribute to survival, rhizosphere colonization and the initiation of mutualistic interactions by Azospirillum species. This study evaluates the chemotactic responses of three Azospirillum stains to a variety of aromatic compounds:benzoate, catechol, 4-HB, and PCA. Results indicate that the same aromatic substance can elicit different chemotactic responses from different Azospirillum species, and that Azospirillum can detect aromatic substrates at concentrations similar to those they encounter naturally. 36 refs., 1 fig., 6 tabs.

  15. Two different mechanisms mediate chemotaxis to inorganic phosphate in Pseudomonas aeruginosa

    Rico-Jiménez, Miriam; Reyes-Darias, Jose Antonio; Ortega, Álvaro; Díez Peña, Ana Isabel; Morel, Bertrand; Krell, Tino


    Inorganic phosphate (Pi) is a central signaling molecule that modulates virulence in various pathogens. In Pseudomonas aeruginosa, low Pi concentrations induce transcriptional alterations that increase virulence. Also, under low Pi levels, P. aeruginosa exhibits Pi chemotaxis—a process mediated by the two non-paralogous receptors CtpH and CtpL. Here we show that the two receptors operate via different mechanisms. We demonstrate that the ligand binding domain (LBD) of CtpH but not CtpL binds Pi directly. We identify the periplasmic ligand binding protein PstS as the protein that binds in its Pi loaded state to CtpL, resulting in receptor stimulation. PstS forms part of the Pi transporter and has thus a double function in Pi transport and chemotaxis. The affinity of Pi for CtpH was modest whereas that for PstS very high, which may explain why CtpH and CtpL mediate chemotaxis to high and low Pi concentrations, respectively. The pstS/ctpH double mutant was almost devoid of Pi taxis, indicating that PstS is the only CtpL Pi-shuttle. Chemotaxis mechanisms based on indirect ligand recognition were unambiguously identified in enterobacteria. The discovery of a similar mechanism in a different bacterial order, involving a different chemoreceptor type and chemoeffector suggests that such systems are widespread. PMID:27353565

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

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


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

  17. Modeling and Rotor Current Control of Doubly-fed Induction Machine with Complex Signal Flow Graphs

    Khambadkone, AM; Datta, Rajib; Ranganathan, VT


    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...

  18. Wnt signalling induces accumulation of phosphorylated β-catenin in two distinct cytosolic complexes

    Gerlach, Jan P.; Emmink, Benjamin L; Nojima, Hisashi; Kranenburg, Onno; Maurice, Madelon M.


    Wnt/β-catenin signalling controls development and adult tissue homeostasis and causes cancer when inappropriately activated. In unstimulated cells, an Axin1-centred multi-protein complex phosphorylates the transcriptional co-activator β-catenin, marking it for degradation. Wnt signalling antagonizes β-catenin proteolysis, leading to its accumulation and target gene expression. How Wnt stimulation alters the size distribution, composition and activity of endogenous Axin1 complexes remains poor...

  19. Differential maturation of brain signal complexity in the human auditory and visual system

    Sarah Lippe; Randy McIntosh


    Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in...

  20. Differential Maturation of Brain Signal Complexity in the Human Auditory and Visual System

    Lippé, Sarah; Kovacevic, Natasa; McIntosh, Anthony Randal


    Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in c...

  1. Modulation of EEG Theta Band Signal Complexity by Music Therapy [Forthcoming

    Bhattacharya, Joydeep; Lee, Eun-Jeong


    The primary goal of this study was to investigate the impact of monochord (MC) sounds, a type of archaic sounds used in music therapy, on the neural complexity of EEG signals obtained from patients undergoing chemotherapy. The secondary goal was to compare the EEG signal complexity values for monochords with those for progressive muscle relaxation (PMR), an alternative therapy for relaxation. Forty cancer patients were randomly allocated to one of the two relaxation groups, MC and PMR, over a...

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

    Heemers, Hannelore V.; Tindall, Donald J.


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

  3. Observing Chemotaxis in Vibrio fischeri Using Soft Agar Assays in an Undergraduate Microbiology Laboratory

    Cindy R. DeLoney-Marino


    Full Text Available Chemotaxis, the directed movement of cells towards or away from a chemical, is both an exciting and complicated behavior observed in many bacterial species. Attempting to adequately visualize or demonstrate the chemotaxic response of bacteria in the classroom is difficult at best, with good models to illustrate the concept lacking. The BSL-1 marine bacterium Vibrio fischeri (a.k.a. Aliivibrio fischeri is easy to culture, making it an ideal candidate for experiments in an undergraduate microbiology course. A number of chemoattractants for V. fischeri have been identified, including a variety of sugars, nucleosides, and amino acids (1, 2. Below presents how the soft agar-based chemotaxis assay can be implemented in the undergraduate laboratory. As bacterial cells migrate towards one or more attractants in soft agar, students can directly observe the chemotaxic behavior of V. fischeri without the need to learn complicated techniques or use specialized equipment. Once the bands of bacterial cells are observed, the migration can then be disrupted by the addition of excess attractant to the soft agar, thereby visualizing what happens once cells are no longer in a gradient of attractant. In addition, soft agar plates lacking attractants can be used to visualize the random movements of bacterial cells that are non-chemotaxing. These exercises can be used in the microbiology laboratory to help students understand the complex behavior of bacterial chemotaxis.

  4. Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix.

    Stout, David A; Toyjanova, Jennet; Franck, Christian


    The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis. PMID:26131645

  5. A population-level model from the microscopic dynamics in Escherichia coli chemotaxis via Langevin approximation

    Recent extensive studies of Escherichia coli (E. coli) chemotaxis have achieved a deep understanding of its microscopic control dynamics. As a result, various quantitatively predictive models have been developed to describe the chemotactic behavior of E. coli motion. However, a population-level partial differential equation (PDE) that rationally incorporates such microscopic dynamics is still insufficient. Apart from the traditional Keller–Segel (K–S) equation, many existing population-level models developed from the microscopic dynamics are integro-PDEs. The difficulty comes mainly from cell tumbles which yield a velocity jumping process. Here, we propose a Langevin approximation method that avoids such a difficulty without appreciable loss of precision. The resulting model not only quantitatively reproduces the results of pathway-based single-cell simulators, but also provides new inside information on the mechanism of E. coli chemotaxis. Our study demonstrates a possible alternative in establishing a simple population-level model that allows for the complex microscopic mechanisms in bacterial chemotaxis

  6. Role of chemotaxis in the transport of bacteria through saturated porous media

    Ford, R.M.; Harvey, R.W.


    Populations of chemotactic bacteria are able to sense and respond to chemical gradients in their surroundings and direct their migration toward increasing concentrations of chemicals that they perceive to be beneficial to their survival. It has been suggested that this phenomenon may facilitate bioremediation processes by bringing bacteria into closer proximity to the chemical contaminants that they degrade. To determine the significance of chemotaxis in these processes it is necessary to quantify the magnitude of the response and compare it to other groundwater processes that affect the fate and transport of bacteria. We present a systematic approach toward quantifying the chemotactic response of bacteria in laboratory scale experiments by starting with simple, well-defined systems and gradually increasing their complexity. Swimming properties of individual cells were assessed from trajectories recorded by a tracking microscope. These properties were used to calculate motility and chemotaxis coefficients of bacterial populations in bulk aqueous media which were compared to experimental results of diffusion studies. Then effective values of motility and chemotaxis coefficients in single pores, pore networks and packed columns were analyzed. These were used to estimate the magnitude of the chemotactic response in porous media and to compare with dispersion coefficients reported in the field. This represents a compilation of many studies over a number of years. While there are certainly limitations with this approach for ultimately quantifying motility and chemotaxis in granular aquifer media, it does provide insight into what order of magnitude responses are possible and which characteristics of the bacteria and media are expected to be important. ?? 2006 Elsevier Ltd. All rights reserved.

  7. Transport genes and chemotaxis in Laribacter hongkongensis: a genome-wide analysis

    Lau Susanna KP


    Full Text Available Abstract Background Laribacter hongkongensis is a Gram-negative, sea gull-shaped rod associated with community-acquired gastroenteritis. The bacterium has been found in diverse freshwater environments including fish, frogs and drinking water reservoirs. Using the complete genome sequence data of L. hongkongensis, we performed a comprehensive analysis of putative transport-related genes and genes related to chemotaxis, motility and quorum sensing, which may help the bacterium adapt to the changing environments and combat harmful substances. Results A genome-wide analysis using Transport Classification Database TCDB, similarity and keyword searches revealed the presence of a large diversity of transporters (n = 457 and genes related to chemotaxis (n = 52 and flagellar biosynthesis (n = 40 in the L. hongkongensis genome. The transporters included those from all seven major transporter categories, which may allow the uptake of essential nutrients or ions, and extrusion of metabolic end products and hazardous substances. L. hongkongensis is unique among closely related members of Neisseriaceae family in possessing higher number of proteins related to transport of ammonium, urea and dicarboxylate, which may reflect the importance of nitrogen and dicarboxylate metabolism in this assacharolytic bacterium. Structural modeling of two C4-dicarboxylate transporters showed that they possessed similar structures to the determined structures of other DctP-TRAP transporters, with one having an unusual disulfide bond. Diverse mechanisms for iron transport, including hemin transporters for iron acquisition from host proteins, were also identified. In addition to the chemotaxis and flagella-related genes, the L. hongkongensis genome also contained two copies of qseB/qseC homologues of the AI-3 quorum sensing system. Conclusions The large number of diverse transporters and genes involved in chemotaxis, motility and quorum sensing suggested that the bacterium may

  8. An Improved Chamber for Direct Visualisation of Chemotaxis

    Andrew J Muinonen-Martin; Douwe M Veltman; Gabriela Kalna; Insall, Robert H.


    There has been a growing appreciation over the last decade that chemotaxis plays an important role in cancer migration, invasion and metastasis. Research into the field of cancer cell chemotaxis is still in its infancy and traditional investigative tools have been developed with other cell types and purposes in mind. Direct visualisation chambers are considered the gold standard for investigating the behaviour of cells migrating in a chemotactic gradient. We therefore drew up a list of key at...

  9. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

    Lee, W. L.; Shalita, A R; Suntharalingam, K; Fikrig, S M


    The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorph...

  10. Mutation of a Src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis

    Hansen, Klaus; Johnell, M; Siegbahn, A; Rorsman, C; Engström, U; Wernstedt, C; Heldin, C H; Rönnstrand, L


    phosphorylated by Src. Cell lines expressing a beta-receptor mutant, in which Tyr934 was replaced with a phenyalanine residue, showed reduced mitogenic signaling in response to PDGF-BB. In contrast, the mutant receptor mediated increased signals for chemotaxis and actin reorganization. Whereas the motility...... responses of cells expressing wild-type beta-receptors were attenuated by inhibition of phosphatidylinositol 3'-kinase, those of cells expressing the mutant receptor were only slightly influenced. In contrast, PDGF-BB-induced chemotaxis of the cells with the mutant receptor was attenuated by inhibition of...... protein kinase C, whereas the chemotaxis of cells expressing the wild-type beta-receptor was less affected. Moreover, the PDGF-BB-stimulated tyrosine phosphorylation of phospholipase C-gamma was increased in the mutant receptor cells compared with wild-type receptor cells. In conclusion, the...

  11. An improved chamber for direct visualisation of chemotaxis.

    Andrew J Muinonen-Martin

    Full Text Available There has been a growing appreciation over the last decade that chemotaxis plays an important role in cancer migration, invasion and metastasis. Research into the field of cancer cell chemotaxis is still in its infancy and traditional investigative tools have been developed with other cell types and purposes in mind. Direct visualisation chambers are considered the gold standard for investigating the behaviour of cells migrating in a chemotactic gradient. We therefore drew up a list of key attributes that a chemotaxis chamber should have for investigating cancer cell chemotaxis. These include (1 compatibility with thin cover slips for optimal optical properties and to allow use of high numerical aperture (NA oil immersion objectives; (2 gradients that are relatively stable for at least 24 hours due to the slow migration of cancer cells; (3 gradients of different steepnesses in a single experiment, with defined, consistent directions to avoid the need for complicated analysis; and (4 simple handling and disposability for use with medical samples. Here we describe and characterise the Insall chamber, a novel direct visualisation chamber. We use it to show GFP-lifeact transfected MV3 melanoma cells chemotaxing using a 60x high NA oil immersion objective, which cannot usually be done with other chemotaxis chambers. Linear gradients gave very efficient chemotaxis, contradicting earlier results suggesting that only polynomial gradients were effective. In conclusion, the chamber satisfies our design criteria, most importantly allowing high NA oil immersion microscopy to track chemotaxing cancer cells in detail over 24 hours.

  12. Performance Analysis of a Hardware Implemented Complex Signal Kurtosis Radio-Frequency Interference Detector

    Schoenwald, Adam J.; Bradley, Damon C.; Mohammed, Priscilla N.; Piepmeier, Jeffrey R.; Wong, Mark


    In the field of microwave radiometry, Radio Frequency Interference (RFI) consistently degrades the value of scientific results. Through the use of digital receivers and signal processing, the effects of RFI on scientific measurements can be reduced depending on certain circumstances. As technology allows us to implement wider band digital receivers for radiometry, the problem of RFI mitigation changes. Our work focuses on finding a detector that outperforms real kurtosis in wide band scenarios. The algorithm implemented is a complex signal kurtosis detector which was modeled and simulated. The performance of both complex and real signal kurtosis is evaluated for continuous wave, pulsed continuous wave, and wide band quadrature phase shift keying (QPSK) modulations. The use of complex signal kurtosis increased the detectability of interference.

  13. Reiteration of Hankel singular value decomposition for modeling of complex-valued signal

    Staniszewski, Michał; Skorupa, Agnieszka; Boguszewicz, Łukasz; Wicher, Magdalena; Konopka, Marek; Sokół, Maria; Polański, Andrzej


    Modeling signal which forms complex values is a common scientific problem, which is present in many applications, i.e. in medical signals, computer graphics and vision. One of the possible solution is utilization of Hankel Singular Value Decomposition. In the first step complex-valued signal is arranged in a special form called Hankel matrix, which is in the next step decomposed in operation of Singular Value Decomposition. Obtained matrices can be then reformulated in order to get parameters describing system. Basic method can be applied for fitting whole signal but it fails in modeling each particular component of signal. Modification of basic HSVD method, which relies on reiteration and is used for main components, and application of prior knowledge solves presented problem.

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

    Lee Dong-Sup


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

  15. Bacterial Chemotaxis with a Moving Target

    Dominick, Corey


    Most chemotaxis studies so far have been conducted in a quiescent fluid with a well-defined chemical gradient. Such experiments may be appropriate for studying enteric bacteria, such as Escherichia coli, but the environment it provides is very different from that typically encountered by marine bacteria. Herein we describe an experiment in which marine bacterium Vibrio alginolyticusis subject to stimulation by a small moving target. A micropipette of the tip size <1 ?m is used to slowly release a chemoattractant, serine, at different concentrations. The pipette is made to move with different patterns and speeds, ranging from 0 to 100 ?m/s; the latter is about twice the bacterial swimming speed. We found that if the pipette is moved slowly, with 1/4 of bacterial swimming speed, cells accumulate near the tip region but when it is moved with speed greater than 1/2 the bacterial swimming speed, cells trail behind the pipette over a large distance. The behaviors observed in V. alginolyticusare significantly different from E. coli, suggesting that the former is a better chemotaxer in a changing environment.

  16. External and internal constraints on eukaryotic chemotaxis.

    Fuller, Danny; Chen, Wen; Adler, Micha; Groisman, Alex; Levine, Herbert; Rappel, Wouter-Jan; Loomis, William F


    Chemotaxis, the chemically guided movement of cells, plays an important role in several biological processes including cancer, wound healing, and embryogenesis. Chemotacting cells are able to sense shallow chemical gradients where the concentration of chemoattractant differs by only a few percent from one side of the cell to the other, over a wide range of local concentrations. Exactly what limits the chemotactic ability of these cells is presently unclear. Here we determine the chemotactic response of Dictyostelium cells to exponential gradients of varying steepness and local concentration of the chemoattractant cAMP. We find that the cells are sensitive to the steepness of the gradient as well as to the local concentration. Using information theory techniques, we derive a formula for the mutual information between the input gradient and the spatial distribution of bound receptors and also compute the mutual information between the input gradient and the motility direction in the experiments. A comparison between these quantities reveals that for shallow gradients, in which the concentration difference between the back and the front of a 10-mum-diameter cell is <5%, and for small local concentrations (<10 nM) the intracellular information loss is insignificant. Thus, external fluctuations due to the finite number of receptors dominate and limit the chemotactic response. For steeper gradients and higher local concentrations, the intracellular information processing is suboptimal and results in a smaller mutual information between the input gradient and the motility direction than would have been predicted from the ligand-receptor binding process. PMID:20457897

  17. Forget-me-not:Complex floral displays,inter-signal interactions,and pollinator cognition



    Flowers are multisensory displays used by plants to influence the behavior of pollinators.Although we know a great deal about how individual signal components are preduced by plants and detected or learned by pollinators,very few experiments directly address the function of floral signal complexity, the multicompenent nature of these signals benefits plant or pollinator.Yet,experimental psychology suggests that increasing complexity can enhance subjects'ability to deteCt,learn and remember stimuli,and the plant,sreproductive success depends upon ensuring that pollinators learn their signals and so transport pollen to other similar(conspecific)flowers.Here we explore functional hypotheses for why plants invest in complex floral displays focusing on hypotheses in which floral signals interact to promote pollinator learning and memory'Specifically,we discuss how an attention-altering or context-providing function of one signal may promote acquisition or recall of a second signal.Although we focus on communication between plants and poilinators,these process-based hypotheses should apply to any situation where a sender benefits from enhancing a receiver's acquisition or recall of informtion.

  18. Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex.

    Li, Vivian S W; Ng, Ser Sue; Boersema, Paul J; Low, Teck Y; Karthaus, Wouter R; Gerlach, Jan P; Mohammed, Shabaz; Heck, Albert J R; Maurice, Madelon M; Mahmoudi, Tokameh; Clevers, Hans


    Degradation of cytosolic β-catenin by the APC/Axin1 destruction complex represents the key regulated step of the Wnt pathway. It is incompletely understood how the Axin1 complex exerts its Wnt-regulated function. Here, we examine the mechanism of Wnt signaling under endogenous levels of the Axin1 complex. Our results demonstrate that β-catenin is not only phosphorylated inside the Axin1 complex, but also ubiquinated and degraded via the proteasome, all within an intact Axin1 complex. In disagreement with current views, we find neither a disassembly of the complex nor an inhibition of phosphorylation of Axin1-bound β-catenin upon Wnt signaling. Similar observations are made in primary intestinal epithelium and in colorectal cancer cell lines carrying activating Wnt pathway mutations. Wnt signaling suppresses β-catenin ubiquitination normally occurring within the complex, leading to complex saturation by accumulated phospho-β-catenin. Subsequently, newly synthesized β-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors. PMID:22682247

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

    Keranen, Soile V.E.


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

  20. A novel feature extracting method of QRS complex classification for mobile ECG signals

    Zhu, Lingyun; Wang, Dong; Huang, Xianying; Wang, Yue


    The conventional classification parameters of QRS complex suffer from larger activity rang of patients and lower signal to noise ratio in mobile cardiac telemonitoring system and can not meet the identification needs of ECG signal. Based on individual sinus heart rhythm template built with mobile ECG signals in time window, we present semblance index to extract the classification features of QRS complex precisely and expeditiously. Relative approximation r2 and absolute error r3 are used as estimating parameters of semblance between testing QRS complex and template. The evaluate parameters corresponding to QRS width and types are demonstrated to choose the proper index. The results show that 99.99 percent of the QRS complex for sinus and superventricular ECG signals can be distinguished through r2 but its average accurate ratio is only 46.16%. More than 97.84 percent of QRS complexes are identified using r3 but its accurate ratio to the sinus and superventricular is not better than r2. By the feature parameter of width, only 42.65 percent of QRS complexes are classified correctly, but its accurate ratio to the ventricular is superior to r2. To combine the respective superiority of three parameters, a nonlinear weighing computation of QRS width, r2 and r3 is introduced and the total classification accuracy up to 99.48% by combing indexes.

  1. N-WASP has the Ability to Compensate for the Loss of WASP in Macrophage Podosome Formation and Chemotaxis

    Isaac, Beth M.; Ishihara, Dan; Nusblat, Leora M.; Gevrey, Jean-Claude; Dovas, Athanassios; Condeelis, John; Cox, Dianne


    Wiskott-Aldrich syndrome protein (WASP) and its homologue neural-WASP (N-WASP) are nucleation promoting factors that integrate receptor signaling with actin cytoskeleton rearrangement. While hematopoietic cells express both WASP and N-WASP, WASP deficiency results in altered cell morphology, loss of podosomes and defective chemotaxis. It was determined that cells from a mouse derived monocyte/macrophage cell line and primary cells of myeloid lineage expressed approximately 15-fold higher leve...

  2. Performance Analysis of a Hardware Implemented Complex Signal Kurtosis Radio-Frequency Interference Detector

    Schoenwald, Adam J.; Bradley, Damon C.; Mohammed, Priscilla N.; Piepmeier, Jeffrey R.; Wong, Mark


    Radio-frequency interference (RFI) is a known problem for passive remote sensing as evidenced in the L-band radiometers SMOS, Aquarius and more recently, SMAP. Various algorithms have been developed and implemented on SMAP to improve science measurements. This was achieved by the use of a digital microwave radiometer. RFI mitigation becomes more challenging for microwave radiometers operating at higher frequencies in shared allocations. At higher frequencies larger bandwidths are also desirable for lower measurement noise further adding to processing challenges. This work focuses on finding improved RFI mitigation techniques that will be effective at additional frequencies and at higher bandwidths. To aid the development and testing of applicable detection and mitigation techniques, a wide-band RFI algorithm testing environment has been developed using the Reconfigurable Open Architecture Computing Hardware System (ROACH) built by the Collaboration for Astronomy Signal Processing and Electronics Research (CASPER) Group. The testing environment also consists of various test equipment used to reproduce typical signals that a radiometer may see including those with and without RFI. The testing environment permits quick evaluations of RFI mitigation algorithms as well as show that they are implementable in hardware. The algorithm implemented is a complex signal kurtosis detector which was modeled and simulated. The complex signal kurtosis detector showed improved performance over the real kurtosis detector under certain conditions. The real kurtosis is implemented on SMAP at 24 MHz bandwidth. The complex signal kurtosis algorithm was then implemented in hardware at 200 MHz bandwidth using the ROACH. In this work, performance of the complex signal kurtosis and the real signal kurtosis are compared. Performance evaluations and comparisons in both simulation as well as experimental hardware implementations were done with the use of receiver operating characteristic (ROC

  3. Wnt signalling induces accumulation of phosphorylated β-catenin in two distinct cytosolic complexes.

    Gerlach, Jan P; Emmink, Benjamin L; Nojima, Hisashi; Kranenburg, Onno; Maurice, Madelon M


    Wnt/β-catenin signalling controls development and adult tissue homeostasis and causes cancer when inappropriately activated. In unstimulated cells, an Axin1-centred multi-protein complex phosphorylates the transcriptional co-activator β-catenin, marking it for degradation. Wnt signalling antagonizes β-catenin proteolysis, leading to its accumulation and target gene expression. How Wnt stimulation alters the size distribution, composition and activity of endogenous Axin1 complexes remains poorly understood. Here, we employed two-dimensional blue native/SDS-PAGE to analyse endogenous Axin1 and β-catenin complexes during Wnt signalling. We show that the size range of Axin1 complexes is conserved between species and remains largely unaffected by Wnt stimulation. We detect a striking Wnt-dependent, cytosolic accumulation of both non-phosphorylated and phosphorylated β-catenin within a 450 kDa Axin1-based complex and in a distinct, Axin1-free complex of 200 kDa. These results argue that during Wnt stimulation, phosphorylated β-catenin is released from the Axin1 complex but fails to undergo immediate degradation. Importantly, in APC-mutant cancer cells, the distribution of Axin1 and β-catenin complexes strongly resembles that of Wnt-stimulated cells. Our findings argue that Wnt signals and APC mutations interfere with the turnover of phosphorylated β-catenin. Furthermore, our results suggest that the accumulation of small-sized β-catenin complexes may serve as an indicator of Wnt pathway activity in primary cancer cells. PMID:25392450

  4. Processing of simple and complex acoustic signals in a tonotopically organized ear.

    Hummel, Jennifer; Wolf, Konstantin; Kössl, Manfred; Nowotny, Manuela


    Processing of complex signals in the hearing organ remains poorly understood. This paper aims to contribute to this topic by presenting investigations on the mechanical and neuronal response of the hearing organ of the tropical bushcricket species Mecopoda elongata to simple pure tone signals as well as to the conspecific song as a complex acoustic signal. The high-frequency hearing organ of bushcrickets, the crista acustica (CA), is tonotopically tuned to frequencies between about 4 and 70 kHz. Laser Doppler vibrometer measurements revealed a strong and dominant low-frequency-induced motion of the CA when stimulated with either pure tone or complex stimuli. Consequently, the high-frequency distal area of the CA is more strongly deflected by low-frequency-induced waves than by high-frequency-induced waves. This low-frequency dominance will have strong effects on the processing of complex signals. Therefore, we additionally studied the neuronal response of the CA to native and frequency-manipulated chirps. Again, we found a dominant influence of low-frequency components within the conspecific song, indicating that the mechanical vibration pattern highly determines the neuronal response of the sensory cells. Thus, we conclude that the encoding of communication signals is modulated by ear mechanics. PMID:25339727

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

    Zalay, Osbert C; Bardakjian, Berj L


    We propose an approach to synthesizing high-complexity rhythmic signals for closed-loop electrical neuromodulation using cognitive rhythm generator (CRG) networks, wherein the CRG is a hybrid oscillator comprised of (1) a bank of neuronal modes, (2) a ring device (clock), and (3) a static output nonlinearity (mapper). Networks of coupled CRGs have been previously implemented to simulate the electrical activity of biological neural networks, including in silico models of epilepsy, producing outputs of similar waveform and complexity to the biological system. This has enabled CRG network models to be used as platforms for testing seizure control strategies. Presently, we take the application one step further, envisioning therapeutic CRG networks as rhythmic signal generators creating neuromimetic signals for stimulation purposes, motivated by recent research indicating that stimulus complexity and waveform characteristics influence neuromodulation efficacy. To demonstrate this concept, an epileptiform CRG network generating spontaneous seizure-like events (SLEs) was coupled to a therapeutic CRG network, forming a closed-loop neuromodulation system. SLEs are associated with low-complexity dynamics and high phase coherence in the network. The tuned therapeutic network generated a high-complexity, multi-banded rhythmic stimulation signal with prominent theta and gamma-frequency power that suppressed SLEs and increased dynamic complexity in the epileptiform network, as measured by a relative increase in the maximum Lyapunov exponent and decrease in phase coherence. CRG-based neuromodulation outperformed both low and high-frequency periodic pulse stimulation, suggesting that neuromodulation using complex, biomimetic signals may provide an improvement over conventional electrical stimulation techniques for treating neurological disorders such as epilepsy. PMID:23501170

  6. Biomedical image and signal de-noising using dual tree complex wavelet transform

    Rizi, F. Yousefi; Noubari, H. Ahmadi; Setarehdan, S. K.


    Dual tree complex wavelet transform(DTCWT) is a form of discrete wavelet transform, which generates complex coefficients by using a dual tree of wavelet filters to obtain their real and imaginary parts. The purposes of de-noising are reducing noise level and improving signal to noise ratio (SNR) without distorting the signal or image. This paper proposes a method for removing white Gaussian noise from ECG signals and biomedical images. The discrete wavelet transform (DWT) is very valuable in a large scope of de-noising problems. However, it has limitations such as oscillations of the coefficients at a singularity, lack of directional selectivity in higher dimensions, aliasing and consequent shift variance. The complex wavelet transform CWT strategy that we focus on in this paper is Kingsbury's and Selesnick's dual tree CWT (DTCWT) which outperforms the critically decimated DWT in a range of applications, such as de-noising. Each complex wavelet is oriented along one of six possible directions, and the magnitude of each complex wavelet has a smooth bell-shape. In the final part of this paper, we present biomedical image and signal de-noising by the means of thresholding magnitude of the wavelet coefficients.

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

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


    the intensity speckle pattern, which converts the original real-valued signal into a complex signal. In closest analogy to the polarisation of a vector wave, the Stokes-like vector constructed from the spatial derivative of the generated complex signal has been applied for correlation. Experimental...

  8. Directional dual-tree complex wavelet packet transforms for processing quadrature signals.

    Serbes, Gorkem; Gulcur, Halil Ozcan; Aydin, Nizamettin


    Quadrature signals containing in-phase and quadrature-phase components are used in many signal processing applications in every field of science and engineering. Specifically, Doppler ultrasound systems used to evaluate cardiovascular disorders noninvasively also result in quadrature format signals. In order to obtain directional blood flow information, the quadrature outputs have to be preprocessed using methods such as asymmetrical and symmetrical phasing filter techniques. These resultant directional signals can be employed in order to detect asymptomatic embolic signals caused by small emboli, which are indicators of a possible future stroke, in the cerebral circulation. Various transform-based methods such as Fourier and wavelet were frequently used in processing embolic signals. However, most of the times, the Fourier and discrete wavelet transforms are not appropriate for the analysis of embolic signals due to their non-stationary time-frequency behavior. Alternatively, discrete wavelet packet transform can perform an adaptive decomposition of the time-frequency axis. In this study, directional discrete wavelet packet transforms, which have the ability to map directional information while processing quadrature signals and have less computational complexity than the existing wavelet packet-based methods, are introduced. The performances of proposed methods are examined in detail by using single-frequency, synthetic narrow-band, and embolic quadrature signals. PMID:25388779

  9. Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FcepsilonRI dimers: aggregated dimers can dissociate from Lyn and form signaling complexes with Syk.

    Lara, M; Ortega, E; Pecht, I; Pfeiffer, J R; Martinez, A M; Lee, R J; Surviladze, Z; Wilson, B S; Oliver, J M


    Clustering the tetrameric (alphabetagamma(2)) IgE receptor, FcepsilonRI, on basophils and mast cells activates the Src-family tyrosine kinase, Lyn, which phosphorylates FcepsilonRI beta and gamma subunit tyrosines, creating binding sites for the recruitment and activation of Syk. We reported previously that FcepsilonRI dimers formed by a particular anti-FcepsilonRI alpha mAb (H10) initiate signaling through Lyn activation and FcepsilonRI subunit phosphorylation, but cause only modest activation of Syk and little Ca(2+) mobilization and secretion. Curtailed signaling was linked to the formation of unusual, detergent-resistant complexes between Lyn and phosphorylated receptor subunits. Here, we show that H10-FcepsilonRI multimers, induced by adding F(ab')(2) of goat anti-mouse IgG to H10-treated cells, support strong Ca(2+) mobilization and secretion. Accompanying the recovery of signaling, H10-FcepsilonRI multimers do not form stable complexes with Lyn and do support the phosphorylation of Syk and phospholipase Cgamma2. Immunogold electron microscopy showed that H10-FcepsilonRI dimers colocalize preferentially with Lyn and are rarely within the osmiophilic "signaling domains" that accumulate FcepsilonRI and Syk in Ag-treated cells. In contrast, H10-FcepsilonRI multimers frequently colocalize with Syk within osmiophilic patches. In sucrose gradient centrifugation analyses of detergent-extracted cells, H10-treated cells show a more complete redistribution of FcepsilonRI beta from heavy (detergent-soluble) to light (Lyn-enriched, detergent-resistant) fractions than cells activated with FcepsilonRI multimers. We hypothesize that restraints imposed by the particular orientation of H10-FcepsilonRI dimers traps them in signal-initiating Lyn microdomains, and that converting the dimers to multimers permits receptors to dissociate from Lyn and redistribute to separate membrane domains that support Syk-dependent signal propagation. PMID:11591756

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

    Martinez, Josue G.


    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.

  11. Dataflow/Actor-Oriented language for the design of complex signal processing systems

    Lucarz, Christophe; Mattavelli, Marco; Wipliez, Matthieu; Roquier, Ghislain; Raulet, Mickael; Janneck, Jörn W.; Miller, Ian D.; Parlour, David B.


    International audience Signal processing algorithms become more and more complex and the algorithm architecture adaptation and design processes cannot any longer rely only on the intuition of the designers to build efficient systems. Specific tools and methods are needed to cope with the increasing complexity of both algorithms and platforms. This paper presents a new framework which allows the specification, design, simulation and implementation of a system operating at a higher level of ...

  12. Performance Analysis of a Hardware Implemented Complex Signal Kurtosis Radio-Frequency Interference Detector

    Bradley, Damon C.; Mohammed, Priscilla N.; Schoenwald, Adam J.; Piepmeier, Jeffrey R.; Wong, Mark


    Radio-frequency interference (RFI) is a known problem for passive remote sensing as evidenced in the L-band radiometers SMOS, Aquarius and more recently, SMAP. Various algorithms have been developed and implemented on SMAP to improve science measurements. This was achieved by the use of a digital microwave radiometer. RFI mitigation becomes more challenging for microwave radiometers operating at higher frequencies in shared allocations. At higher frequencies larger bandwidths are also desirable for lower measurement noise further adding to processing challenges. This work focuses on finding improved RFI mitigation techniques that will be effective at additional frequencies and at higher bandwidths. To aid the development and testing of applicable detection and mitigation techniques, a wide-band RFI algorithm testing environment has been developed using the Reconfigurable Open Architecture Computing Hardware System (ROACH) built by the Collaboration for Astronomy Signal Processing and Electronics Research (CASPER) Group. The testing environment also consists of various test equipment used to reproduce typical signals that a radiometer may see including those with and without RFI. The testing environment permits quick evaluations of RFI mitigation algorithms as well as show that they are implementable in hardware. The algorithm implemented is a complex signal kurtosis detector which was modeled and simulated. The complex signal kurtosis detector showed improved performance over the real kurtosis detector under certain conditions. The real kurtosis is implemented on SMAP at 24 MHz bandwidth. The complex signal kurtosis algorithm was then implemented in hardware at 200 MHz bandwidth using the ROACH. In this work, performance of the complex signal kurtosis and the real signal kurtosis are compared. Performance evaluations and comparisons in both simulation as well as experimental hardware implementations were done with the use of receiver operating characteristic (ROC

  13. Chemotaxis on the Move – Active Learning Teaching Tool

    Ann H. Williams


    Full Text Available In Microbiology courses, concepts such as chemotaxis can be difficult to visualize for students. Described here is a short visual playacting activity where students simulate E.coli moving towards an attractant source using a biased random walk. This short interactive activity is performed in the lecture course of General Microbiology that contains mostly Biology major juniors or seniors prior to the lecture on the subject of chemotaxis and flagellar movements. It is utilized to help students (class of 30–40 understand and visualize the process of chemotaxis and the concepts of random walk, biased random walk, runs, tumbles and directed movement of flagella in response to attractants and repellents.

  14. Single-cell twitching chemotaxis in developing biofilms.

    Oliveira, Nuno M; Foster, Kevin R; Durham, William M


    Bacteria form surface-attached communities, known as biofilms, which are central to bacterial biology and how they affect us. Although surface-attached bacteria often experience strong chemical gradients, it remains unclear whether single cells can effectively perform chemotaxis on surfaces. Here we use microfluidic chemical gradients and massively parallel automated tracking to study the behavior of the pathogen Pseudomonas aeruginosa during early biofilm development. We show that individual cells can efficiently move toward chemoattractants using pili-based "twitching" motility and the Chp chemosensory system. Moreover, we discovered the behavioral mechanism underlying this surface chemotaxis: Cells reverse direction more frequently when moving away from chemoattractant sources. These corrective maneuvers are triggered rapidly, typically before a wayward cell has ventured a fraction of a micron. Our work shows that single bacteria can direct their motion with submicron precision and reveals the hidden potential for chemotaxis within bacterial biofilms. PMID:27222583

  15. Active targeting in a random porous medium by chemical swarm robots with secondary chemical signaling

    Grančič, Peter; Štěpánek, František


    The multibody dynamics of a system of chemical swarm robots in a porous environment is investigated. The chemical swarm robots are modeled as Brownian particles capable of delivering an encapsulated chemical payload toward a given target location and releasing it in response to an external stimulus. The presence of chemical signals (chemo-attractant) in the system plays a crucial role in coordinating the collective movement of the particles via chemotaxis. For a number of applications, such as distributed chemical processing and targeted drug delivery, the understanding of factors that govern the collective behavior of the particles, especially their ability to localize a given target, is of immense importance. A hybrid modeling methodology based on the combination of the Brownian dynamics method and diffusion problem coupled through the chemotaxis phenomena is used to analyze the impact of a varying signaling threshold and the strength of chemotaxis on the ability of the chemical robots to fulfill their target localization mission. The results demonstrate that the selected performance criteria (the localization half time and the success rate) can be improved when an appropriate signaling process is chosen. Furthermore, for an optimum target localization strategy, the topological complexity of the porous environment needs to be reflected.

  16. Histamine H3 receptor in primary mouse microglia inhibits chemotaxis, phagocytosis, and cytokine secretion.

    Iida, Tomomitsu; Yoshikawa, Takeo; Matsuzawa, Takuro; Naganuma, Fumito; Nakamura, Tadaho; Miura, Yamato; Mohsen, Attayeb S; Harada, Ryuichi; Iwata, Ren; Yanai, Kazuhiko


    Histamine is a physiological amine which initiates a multitude of physiological responses by binding to four known G-protein coupled histamine receptor subtypes as follows: histamine H1 receptor (H1 R), H2 R, H3 R, and H4 R. Brain histamine elicits neuronal excitation and regulates a variety of physiological processes such as learning and memory, sleep-awake cycle and appetite regulation. Microglia, the resident macrophages in the brain, express histamine receptors; however, the effects of histamine on critical microglial functions such as chemotaxis, phagocytosis, and cytokine secretion have not been examined in primary cells. We demonstrated that mouse primary microglia express H2 R, H3 R, histidine decarboxylase, a histamine synthase, and histamine N-methyltransferase, a histamine metabolizing enzyme. Both forskolin-induced cAMP accumulation and ATP-induced intracellular Ca(2+) transients were reduced by the H3 R agonist imetit but not the H2 R agonist amthamine. H3 R activation on two ubiquitous second messenger signalling pathways suggests that H3 R can regulate various microglial functions. In fact, histamine and imetit dose-dependently inhibited microglial chemotaxis, phagocytosis, and lipopolysaccharide (LPS)-induced cytokine production. Furthermore, we confirmed that microglia produced histamine in the presence of LPS, suggesting that H3 R activation regulate microglial function by autocrine and/or paracrine signalling. In conclusion, we demonstrate the involvement of histamine in primary microglial functions, providing the novel insight into physiological roles of brain histamine. PMID:25754956

  17. Piracy on the molecular level: human herpesviruses manipulate cellular chemotaxis.

    Cornaby, Caleb; Tanner, Anne; Stutz, Eric W; Poole, Brian D; Berges, Bradford K


    Cellular chemotaxis is important to tissue homeostasis and proper development. Human herpesvirus species influence cellular chemotaxis by regulating cellular chemokines and chemokine receptors. Herpesviruses also express various viral chemokines and chemokine receptors during infection. These changes to chemokine concentrations and receptor availability assist in the pathogenesis of herpesviruses and contribute to a variety of diseases and malignancies. By interfering with the positioning of host cells during herpesvirus infection, viral spread is assisted, latency can be established and the immune system is prevented from eradicating viral infection. PMID:26669819

  18. Chemotaxis plays multiple roles during Helicobacter pylori animal infection

    Terry, K; S. M. Williams; Connolly, L.; Ottemann, K M


    Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as specific gastric cancers. H. pylori infects approximately 50% of the world's population, and infections can persist throughout the lifetime of the host. Motility and chemotaxis have been shown to be important in the infection process of H. pylori. We sought to address the specific roles of chemotaxis in infection of a mouse model system. We found that mutants lacking cheW, cheA, or cheY are ...

  19. Suppressor of cytokine Signaling-3 inhibits interleukin-1 signaling by targeting the TRAF-6/TAK1 complex

    Frobøse, Helle; Rønn, Sif Groth; Heding, Peter E; Mendoza, Heidi; Cohen, Philip; Mandrup-Poulsen, Thomas; Billestrup, Nils


    IL-1 plays a major role in inflammation and autoimmunity through activation of nuclear factor kappa B (NFkappaB) and MAPKs. Although a great deal is known about the mechanism of activation of NFkappaB and MAPKs by IL-1, much less is known about the down-regulation of this pathway. Suppressor of...... cytokine signaling (SOCS)-3 was shown to inhibit IL-1-induced transcription and activation of NFkappaB and the MAPKs JNK and p38, but the mechanism is unknown. We show here that SOCS-3 inhibits NFkappaB-dependent transcription induced by overexpression of the upstream IL-1 signaling molecules MyD88, IL-1R......-activated kinase 1, TNF receptor-associated factor (TRAF)6, and TGFbeta-activated kinase (TAK)1, but not when the MAP3K MAPK/ERK kinase kinase-1 is used instead of TAK1, indicating that the target for SOCS-3 is the TRAF6/TAK1 signaling complex. By coimmunoprecipitation, it was shown that SOCS-3 inhibited the...

  20. p38 MAPK is involved in human neutrophil chemotaxis induced by L-amino acid oxidase from Calloselasma rhodosthoma.

    Pontes, Adriana S; Setúbal, Sulamita da S; Nery, Neriane Monteiro; da Silva, Francisquinha Souza; da Silva, Silvana D; Fernandes, Carla F C; Stábeli, Rodrigo G; Soares, Andreimar M; Zuliani, Juliana P


    The action of LAAO, an L-amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, on isolated human neutrophil function was investigated. Cr-LAAO showed no toxicity on neutrophils. Cr-LAAO in its native form induced the neutrophil chemotaxis, suggesting that its primary structure is essential for stimulation the cell. p38 MAPK and PI3K have a role as signaling pathways of CR-LAAO induced chemotaxis. This toxin also induced the production of hydrogen peroxide and stimulated phagocytosis in neutrophils. Furthermore, Cr-LAAO was able to stimulate neutrophils to release IL-6, IL-8, MPO, LTB4 and PGE2. Together, the data showed that the Cr-LAAO triggers relevant proinflammatory events. PMID:27242041

  1. Quantitative investigation of bacterial chemotaxis at the single-cell level

    Min, Taejin

    Living cells sense and respond to constantly changing environmental conditions. Depending on the type of stimuli, the cell may response by altering gene expression pattern, secreting molecules, or migrating to a different environment. Directed movement of cells in response to chemical stimuli is called chemotaxis. In bacterial chemotaxis, small extracellular molecules bind receptor proteins embedded in the cell membrane, which then transmit the signal inside the cell through a cascade of protein-protein interactions. This chain of events influences the behavior of motor proteins that drive the rotation of helical filaments called flagella. Individual cells of the gut-dwelling bacteria Escherichia coli (E. coli) have many such flagella, whose collective action results in the swimming behavior of the cell. A recent study found that in absence of chemical stimuli, fluctuations in the protein cascade can cause non-Poissonian switching behavior in the flagellar motor (2). A corollary was that extension of such behavior to the whole-cell swimming level would have implications for E. coli's foraging strategy. However, existence of such behavior at the swimming cell level could not be predicted a priori, since the mapping from single flagellum behavior to the swimming behavior of a multi-flagellated cell is complex and poorly understood (3, 4). Here we characterize the chemotactic behavior of swimming E. coli cells using a novel optical trap-based measurement technique. This technique allows us to trap individual cells and monitor their swimming behavior over long time periods with high temporal resolution. We find that swimming cells exhibit non-Poissonian switching statistics between different swimming states, in a manner similar to the rotational direction-switching behavior seen in individual flagella. Furthermore, we develop a data analysis routine that allows us to characterize higher order swimming features such as reversal of swimming direction and existence of

  2. Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth.

    Roeland M H Merks

    Full Text Available Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully formed blood vessels organize into a vessel network (vasculogenesis, or by sprouting or splitting of existing blood vessels (angiogenesis. Although they are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting. We present a cell-based, Glazier-Graner-Hogeweg model (also called Cellular Potts Model simulation of the initial patterning before the vascular cords form lumens, based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller-Segel model, chemotaxis by itself causes cells to aggregate into isolated clusters. However, including experimentally observed VE-cadherin-mediated contact inhibition of chemotaxis in the simulation causes randomly distributed cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results. Cells at the surfaces of cell clusters attempting to migrate to the centers of the clusters produce a buckling instability. In a model variant that eliminates the surface-normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattractant and as an inhibitor of pseudopod extension. Both mechanisms would also apply if force transmission through the extracellular matrix rather than chemical signaling mediated cell-cell interactions. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual patterning instabilities.

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

    Liang, Xiaoming; Liu, Zonghua; Li, Baowen


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

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

    Kuwahara, Hiroyuki


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

  5. Effect of SXWS/WSXWS peptides on chemotaxis and adhesion of the macrophage-like cell line J774.

    Szabó, Rita; Láng, Orsolya; Láng, Júlia; Illyés, Eszter; Kőhidai, László; Hudecz, Ferenc


    WSXWS motif is a conserved amino acid sequence that is present in type I cytokine receptors. This motif that can be found both in the ligand binding chains and signal transducer molecule of the receptors with different amino acids at the position "X" plays a role in the receptor folding, ligand binding and signal transduction as well. Structural analysis proved that WSEWS motif of IL-6R is located in a highly accessible location in the protein. Structural properties and chemotaxis of a tetrapeptide library with SXWS sequence, where X was the 19 proteinogenic amino acids except cystein were systematically studied earlier. It has been proved that C-terminal amidation and the identity of amino acid X had a pronounced influence on the chemotactic properties but less of the structure of the peptides. Here, we present our findings on the effect of a tetrapeptide and a pentapeptide library with the sequence of SXWS and WSXWS on the chemotaxis and adhesion of J774 murine macrophage cell line. We studied the effect of the presence/absence of N-terminal tryptophan and the different amino acids at the X position on these physiological responses. Results indicated that amino acid X had a marked influence on chemotaxis, adhesion as well as on proliferation induced by (W)SXWS peptides. Elongation of SXWS sequence with a tryptophan at the N terminus also altered pronouncedly all the physiological responses of the cells studied. A good correlation could be observed between the chemotaxis and the proliferation and physicochemical parameters of the amino acid X. PMID:25683456

  6. ECG Signal Compression Technique Based on Discrete Wavelet Transform and QRS-Complex Estimation

    Ahmed Zakaria


    Full Text Available In this paper, an Electrocardiogram (ECG signal is compressed based on discrete wavelet transform (DWT and QRS-complex estimation. The ECG signal is preprocessed by normalization and mean removal. Then, an error signal is formed as the difference between the preprocessed ECG signal and the estimated QRS-complex waveform. This error signal is wavelet transformed and the resulting wavelet coefficients are thresholded by setting to zero all coefficients that are smaller than certain threshold levels. The threshold levels of all subbands are calculated based on Energy Packing Efficiency (EPE such that minimum percentage root mean square difference (PRD and maximum compression ratio (CR are obtained. The resulted thresholded DWT coefficients are coded using the coding technique given in [1], [20]. The compression algorithm was implemented and tested upon records selected from the MIT - BIH arrhythmia database [2]. Simulation results show that the proposed algorithm leads to high CR associated with low distortion level relative to previously reported compression algorithms [1], [14] and [18]. For example, the compression of record 100 using the proposed algorithm yields to CR = 25.15 associated with PRD = 0.7% and PSNR = 45 dB. This achieves compression rate of nearly 128 bit/sec. The main features of this compression algorithm are the high efficiency, high speed and simplicity in design.

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

    Falke, Joseph J.; Ziemba, Brian P


    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. ...

  8. Evidence for bacterial chemotaxis to cyanobacteria from a radioassay technique

    Lyngbya birgei and Aphanizomenon flos-aquae elicited a significant chemotactic attraction of Aeromonas hydrophila compared with controls lacking cyanobacteria. There was a positive exponential relationship between biomass (chlorophyll a) of L. birgei and A. flos-aquae and chemotactic attraction of A. hydrophila. The assay equipment was simple and reliable and could be used to study bacterial chemotaxis in other species in situ

  9. Cutting the Gordian knot:Complex signaling in African cichlids is more than multimodal



    The active transmission of information from sender to recelver is a fundamental component of communication,and is therefore a primary facet in evolutionary models of sexual selection.Research in several systetms has underlined the importance of multiple sensory modalities in courtship signals.However,we still tend to think of individuals as having a relatively static signal in consecutive communicative events.While this may be true for certain traits such as body size or coloration,behaviorally modulated signals can quickly violate this assumption.In this work,we explore how intraspecific variation may be an important component of interspeclfic signal divergence using cichlid fishes from Lake Maiawi.Behavloral analyses were made using six species of Malawian cichlids from two divergent genera.while interspecific differences were found between congeners based on species-level analyses of both acoustic and audiovisual signais,intraspecific variation was of a similar magnitude.Specifically,individual fishes were found to possess highiy plastic signal repertoires.This finding was ubiquitous across all species and resulted in a great deal of overlap between heterospecific individuals,despite statistically distinct species means.These results demonstrate that some aspects of courtship in Malawian cichlids are more plastic than previously proposed,and that studies must account for signal variability within individuals.We propose here that bebavioral variability in signaling is important in determining the communication landscape on which signals are perceived.We review potential complexity deriving from multimodal signaling,discuss the sources for such lability,and suggest ways in which is issue may be approached experimentally.

  10. Low complexity method for spreading sequence estimation of DSSS signal in non-cooperative communication systems*

    Chang Liang; Wang Fuping; Wang Zanji


    It is a necessary step to estimate the spreading sequence of direct sequence spread spectrum (DSSS) signal for blind despreading and demodulation in non-cooperative communications. Two innovative and effective detection statistics axe proposed to implement the synchronization and spreading sequence estimation procedure. The proposed algorithm also has a low computational complexity with only linear additions and modifications. Theoretical analysis and simulation results show that the algorithm performs quite well in low SNR environment, and is much better than all the existing typical algorithms with a comprehensive consideration both in performance and computational complexity.

  11. Complexity, signal detection, and the application of ergonomics: reflections on a healthcare case study.

    Dekker, Sidney


    Complexity is a defining characteristic of healthcare, and ergonomic interventions in clinical practice need to take into account aspects vital for the success or failure of new technology. The introduction of new monitoring technology, for example, creates many ripple effects through clinical relationships and agents' cross-adaptations. This paper uses the signal detection paradigm to account for a case in which multiple clinical decision makers, across power hierarchies and gender gaps, manipulate each others' sensitivities to evidence and decision criteria. These are possible to analyze and predict with an applied ergonomics that is sensitive to the social complexities of the workplace, including power, gender, hierarchy and fuzzy system boundaries. PMID:21813110

  12. Multifractal analysis of sEMG signal of the complex muscle activity

    Trybek, Paulina; Nowakowski, Michal; Machura, Lukasz


    The neuro--muscular activity while working on laparoscopic trainer is the example of the complex (and complicated) movement. This class of problems are still waiting for the proper theory which will be able to describe the actual properties of the muscle performance. Here we consider the signals obtained from three states of muscle activity: at maximum contraction, during complex movements (at actual work) and in the completely relaxed state. In addition the difference between a professional and an amateur is presented. The Multifractal Detrended Fluctuation Analysis was used in description of the properties the kinesiological surface electromyographic signals (sEMG). We demonstrate the dissimilarity between each state of work for the selected group of muscles as well as between trained and untrained individuals.

  13. Direct Modulation of Heterotrimeric G Protein-coupled Signaling by a Receptor Kinase Complex.

    Tunc-Ozdemir, Meral; Urano, Daisuke; Jaiswal, Dinesh Kumar; Clouse, Steven D; Jones, Alan M


    Plants and some protists have heterotrimeric G protein complexes that activate spontaneously without canonical G protein-coupled receptors (GPCRs). In Arabidopsis, the sole 7-transmembrane regulator of G protein signaling 1 (AtRGS1) modulates the G protein complex by keeping it in the resting state (GDP-bound). However, it remains unknown how a myriad of biological responses is achieved with a single G protein modulator. We propose that in complete contrast to G protein activation in animals, plant leucine-rich repeat receptor-like kinases (LRR RLKs), not GPCRs, provide this discrimination through phosphorylation of AtRGS1 in a ligand-dependent manner. G protein signaling is directly activated by the pathogen-associated molecular pattern flagellin peptide 22 through its LRR RLK, FLS2, and co-receptor BAK1. PMID:27235398

  14. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

    Brown, David J.; Proulx, Michael J.


    Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specifi...

  15. The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.

    Reijntjes, Daniël O J; Pyott, Sonja J


    The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss. PMID:27018296

  16. Correlations between the Signal Complexity of Cerebral and Cardiac Electrical Activity: A Multiscale Entropy Analysis

    Pei-Feng Lin; Men-Tzung Lo; Jenho Tsao; Yi-Chung Chang; Chen Lin; Yi-Lwun Ho


    The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencepha...

  17. Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-β signaling and metastasis

    Wendt, Michael K.; William P. Schiemann


    Introduction Mammary tumorigenesis is associated with the increased expression of several proteins in the focal adhesion complex, including focal adhesion kinase (FAK) and various integrins. Aberrant expression of these molecules occurs concomitant with the conversion of TGF-β function from a tumor suppressor to a tumor promoter. We previously showed that interaction between β3 integrin and TβR-II facilitates TGF-β-mediated oncogenic signaling, epithelial-mesenchymal transition (EMT), and met...

  18. Enterococcal Sex Pheromones: Evolutionary Pathways to Complex, Two-Signal Systems.

    Dunny, Gary M; Berntsson, Ronnie Per-Arne


    Gram-positive bacteria carry out intercellular communication using secreted peptides. Important examples of this type of communication are the enterococcal sex pheromone systems, in which the transfer of conjugative plasmids is controlled by intercellular signaling among populations of donors and recipients. This review focuses on the pheromone response system of the conjugative plasmid pCF10. The peptide pheromones regulating pCF10 transfer act by modulating the ability of the PrgX transcription factor to repress the transcription of an operon encoding conjugation functions. Many Gram-positive bacteria regulate important processes, including the production of virulence factors, biofilm formation, sporulation, and genetic exchange using peptide-mediated signaling systems. The key master regulators of these systems comprise the RRNPP (RggRap/NprR/PlcR/PrgX) family of intracellular peptide receptors; these regulators show conserved structures. While many RRNPP systems include a core module of two linked genes encoding the regulatory protein and its cognate signaling peptide, the enterococcal sex pheromone plasmids have evolved to a complex system that also recognizes a second host-encoded signaling peptide. Additional regulatory genes not found in most RRNPP systems also modulate signal production and signal import in the enterococcal pheromone plasmids. This review summarizes several structural studies that cumulatively demonstrate that the ability of three pCF10 regulatory proteins to recognize the same 7-amino-acid pheromone peptide arose by convergent evolution of unrelated proteins from different families. We also focus on the selective pressures and structure/function constraints that have driven the evolution of pCF10 from a simple, single-peptide system resembling current RRNPPs in other bacteria to the current complex inducible plasmid transfer system. PMID:27021562

  19. Receiver discriminability drives the evolution of complex sexual signals by sexual selection.

    Cui, Jianguo; Song, Xiaowei; Zhu, Bicheng; Fang, Guangzhan; Tang, Yezhong; Ryan, Michael J


    A hallmark of sexual selection by mate choice is the evolution of exaggerated traits, such as longer tails in birds and more acoustic components in the calls of birds and frogs. Trait elaboration can be opposed by costs such as increased metabolism and greater predation risk, but cognitive processes of the receiver can also put a brake on trait elaboration. For example, according to Weber's Law traits of a fixed absolute difference will be more difficult to discriminate as the absolute magnitude increases. Here, we show that in the Emei music frog (Babina daunchina) increases in the fundamental frequency between successive notes in the male advertisement call, which increases the spectral complexity of the call, facilitates the female's ability to compare the number of notes between calls. These results suggest that female's discriminability provides the impetus to switch from enhancement of signaling magnitude (i.e., adding more notes into calls) to employing a new signal feature (i.e., increasing frequency among notes) to increase complexity. We suggest that increasing the spectral complexity of notes ameliorates some of the effects of Weber's Law, and highlights how perceptual and cognitive biases of choosers can have important influences on the evolution of courtship signals. PMID:26920078

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

    Brad J. Niles


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

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

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


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

  2. Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles

    Bo Zhao; Hai-Bo Wang; Ying-Jin Lu; Jian-Wen Hu; Lan Bao; Xu Zhang


    Stimulus-induced exocytosis of large dense-core vesicles(LDCVs)leads to discharge of neuropeptides and fusion of LDCV membranes with the plasma membrane. However, the contribution of LDCVs to the properties of the neuronal membrane remains largely unclear. The present study found that LDCVs were associated with multiple receptors, channels and signaling molecules, suggesting that neuronal sensitivity is modulated by an LDCV-mediated mechanism. Liquid chromatography-mass spectrometry combined with immunoblotting of subcellular fractions identified 298 proteins in LDCV membranes purified from the dorsal spinal cord, including Gprotein-coupled receptors, Gproteins and other signaling molecules, ion channels and trafficking-related proteins. Morphological assays showed that δ-opioid receptor 1(DORI), β2 adrenergic receptor(AR), Gα12,voltage-gated calcium channel a2δ1subunit and P2X purinoceptor 2 were localized in substance P(SP)-positive LDCVs in small-diameter dorsal root ganglion neurons, whereas β1 AR, Wnt receptor frizzled 8 and dishevelled 1 were present in SP-negative LDCVs.Furthermore, DOR1/α12/Gβ1γ5/phospholipase C β2 complexes were associated with LDCVs. Blockade of the DOR1/Gαi2 interaction largely abolished the LDCV localization of Gαi2 and impaired stimulation-induced surface expression of Gαi2. Thus, LDCVs serve as carriers of receptors, ion channels and preassembled receptor signaling complexes, enabling a rapid, activity-dependent modulation of neuronal sensitivity.

  3. A high-content imaging workflow to study Grb2 signaling complexes by expression cloning.

    Freeman, Jamie; Kriston-Vizi, Janos; Seed, Brian; Ketteler, Robin


    Signal transduction by growth factor receptors is essential for cells to maintain proliferation and differentiation and requires tight control. Signal transduction is initiated by binding of an external ligand to a transmembrane receptor and activation of downstream signaling cascades. A key regulator of mitogenic signaling is Grb2, a modular protein composed of an internal SH2 (Src Homology 2) domain flanked by two SH3 domains that lacks enzymatic activity. Grb2 is constitutively associated with the GTPase Son-Of-Sevenless (SOS) via its N-terminal SH3 domain. The SH2 domain of Grb2 binds to growth factor receptors at phosphorylated tyrosine residues thus coupling receptor activation to the SOS-Ras-MAP kinase signaling cascade. In addition, other roles for Grb2 as a positive or negative regulator of signaling and receptor endocytosis have been described. The modular composition of Grb2 suggests that it can dock to a variety of receptors and transduce signals along a multitude of different pathways(1-3). Described here is a simple microscopy assay that monitors recruitment of Grb2 to the plasma membrane. It is adapted from an assay that measures changes in sub-cellular localization of green-fluorescent protein (GFP)-tagged Grb2 in response to a stimulus(4-6). Plasma membrane receptors that bind Grb2 such as activated Epidermal Growth Factor Receptor (EGFR) recruit GFP-Grb2 to the plasma membrane upon cDNA expression and subsequently relocate to endosomal compartments in the cell. In order to identify in vivo protein complexes of Grb2, this technique can be used to perform a genome-wide high-content screen based on changes in Grb2 sub-cellular localization. The preparation of cDNA expression clones, transfection and image acquisition are described in detail below. Compared to other genomic methods used to identify protein interaction partners, such as yeast-two-hybrid, this technique allows the visualization of protein complexes in mammalian cells at the sub

  4. Feeding ducks, bacterial chemotaxis, and the Gini index

    Peaudecerf, Francois J


    Classic experiments on the distribution of ducks around separated food sources found consistency with the `ideal free' distribution in which the local population is proportional to the local supply rate. Motivated by this experiment and others, we examine the analogous problem in the microbial world: the distribution of chemotactic bacteria around multiple nearby food sources. In contrast to the optimization of uptake rate that may hold at the level of a single cell in a spatially varying nutrient field, nutrient consumption by a population of chemotactic cells will modify the nutrient field, and the uptake rate will generally vary throughout the population. Through a simple model we study the distribution of resource uptake in the presence of chemotaxis, consumption, and diffusion of both bacteria and nutrients. Borrowing from the field of theoretical economics, we explore how the Gini index can be used as a means to quantify the inequalities of uptake. The redistributive effect of chemotaxis can lead to a p...

  5. Emergent collective chemotaxis without single-cell gradient sensing

    Camley, Brian A; Levine, Herbert; Rappel, Wouter-Jan


    Many eukaryotic cells chemotax, sensing and following chemical gradients. However, even if single cells do not chemotax significantly, small clusters may still follow a gradient; this behavior is observed in neural crest cells and during border cell migration in Drosophila, but its origin remains puzzling. Here, we study this "collective guidance" analytically and computationally. We show collective chemotaxis can exist without single-cell chemotaxis if contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. We present explicit formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. Pairs of cells will have velocities that are strongly dependent on the cell pair's orientation: this provides a simple test for the presence of collective guidance in neural crest cells and other systems. We also study cluster-level adaptation, amplification, and cohesion via co-attraction.

  6. Global Solutions to the Coupled Chemotaxis-Fluid Equations

    Duan, Renjun


    In this paper, we are concerned with a model arising from biology, which is a coupled system of the chemotaxis equations and the viscous incompressible fluid equations through transport and external forcing. The global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the Chemotaxis-Navier-Stokes system over three space dimensions, we obtain global existence and rates of convergence on classical solutions near constant states. When the fluid motion is described by the simpler Stokes equations, we prove global existence of weak solutions in two space dimensions for cell density with finite mass, first-order spatial moment and entropy provided that the external forcing is weak or the substrate concentration is small. © Taylor & Francis Group, LLC.

  7. Bacillus subtilis Hfq: A role in chemotaxis and motility



    Hfq is a global post-transcriptional regulator that modulates the translation and stability of target mRNAs and therebyregulates pleiotropic functions, such as growth, stress, virulence and motility, in many Gram-negative bacteria.However, comparatively little is known about the regulation and function(s) of Hfq in Gram-positive bacteria.Recently, in Bacillus subtilis, a role for Hfq in stationary phase survival has been suggested, although the possibilityof Hfq having an additional role(s) cannot be ruled out. In this study we show that an ortholog of Hfq in B. subtilis isregulated by the stress sigma factor, σB, in addition to the stationary phase sigma factor, σH. We further demonstratethat Hfq positively regulates the expression of flagellum and chemotaxis genes (fla/che) that control chemotaxis andmotility, thus assigning a new function for Hfq in B. subtilis.

  8. Mass exponent spectrum analysis of human ECG signals and its application to complexity detection

    Yang, Xiaodong; Du, Sidan; Ning, Xinbao; Bian, Chunhua


    The complexity of electrocardiogram (ECG) signal may reflect the physiological function and healthy status of the heart. In this paper, we introduced two novel intermediate parameters of multifractality, the mass exponent spectrum curvature and area, to characterize the nonlinear complexity of ECG signal. These indicators express the nonlinear superposition of the discrepancies of singularity strengths from all the adjacent points of the spectrum curve and thus overall subsets of original fractal structure. The evaluation of binomial multifractal sets validated these two variables were entirely effective in exploring the complexity of this time series. We then studied the ECG mass exponent spectra taken from the cohorts of healthy, ischemia and myocardial infarction (MI) sufferer based on a large sets of 12 leads’ recordings, and took the statistical averages among each crowd. Experimental results suggest the two values from healthy ECG are apparently larger than those from the heart diseased. While the values from ECG of MI sufferer are much smaller than those from the other two groups. As for the ischemia sufferer, they are almost of moderate magnitude. Afterward, we compared these new indicators with the nonlinear parameters of singularity spectrum. The classification indexes and results of total separating ratios (TSR, defined in the paper) both indicated that our method could achieve a better effect. These conclusions may be of some values in early diagnoses and clinical applications.

  9. HGF-MET signals via the MLL-ETS2 complex in hepatocellular carcinoma.

    Takeda, Shugaku; Liu, Han; Sasagawa, Satoru; Dong, Yiyu; Trainor, Paul A; Cheng, Emily H; Hsieh, James J


    HGF signals through its cognate receptor, MET, to orchestrate diverse biological processes, including cell proliferation, cell fate specification, organogenesis, and epithelial-mesenchymal transition. Mixed-lineage leukemia (MLL), an epigenetic regulator, plays critical roles in cell fate, stem cell, and cell cycle decisions. Here, we describe a role for MLL in the HGF-MET signaling pathway. We found a shared phenotype among Mll(-/-), Hgf(-/-), and Met(-/-) mice with common cranial nerve XII (CNXII) outgrowth and myoblast migration defects. Phenotypic analysis demonstrated that MLL was required for HGF-induced invasion and metastatic growth of hepatocellular carcinoma cell lines. HGF-MET signaling resulted in the accumulation of ETS2, which interacted with MLL to transactivate MMP1 and MMP3. ChIP assays demonstrated that activation of the HGF-MET pathway resulted in increased occupancy of the MLL-ETS2 complex on MMP1 and MMP3 promoters, where MLL trimethylated histone H3 lysine 4 (H3K4), activating transcription. Our results present an epigenetic link between MLL and the HGF-MET signaling pathway, which may suggest new strategies for therapeutic intervention. PMID:23934123

  10. The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex.

    Tee, Andrew R; Sampson, Julian R; Pal, Deb K; Bateman, Joseph M


    Understanding the development and function of the nervous system is one of the foremost aims of current biomedical research. The nervous system is generated during a relatively short period of intense neurogenesis that is orchestrated by a number of key molecular signalling pathways. Even subtle defects in the activity of these molecules can have serious repercussions resulting in neurological, neurodevelopmental and neurocognitive problems including epilepsy, intellectual disability and autism. Tuberous sclerosis complex (TSC) is a monogenic disease characterised by these problems and by the formation of benign tumours in multiple organs, including the brain. TSC is caused by mutations in the TSC1 or TSC2 gene leading to activation of the mechanistic target of rapamycin (mTOR) signalling pathway. A desire to understand the neurological manifestations of TSC has stimulated research into the role of the mTOR pathway in neurogenesis. In this review we describe TSC neurobiology and how the use of animal model systems has provided insights into the roles of mTOR signalling in neuronal differentiation and migration. Recent progress in this field has identified novel mTOR pathway components regulating neuronal differentiation. The roles of mTOR signalling and aberrant neurogenesis in epilepsy are also discussed. Continuing efforts to understand mTOR neurobiology will help to identify new therapeutic targets for TSC and other neurological diseases. PMID:26849906

  11. On-Chip Open Microfluidic Devices for Chemotaxis Studies

    Wright, Gus A.; Costa, Lino; Terekhov, Alexander; Jowhar, Dawit; Hofmeister, William; Janetopoulos, Christopher


    Microfluidic devices can provide unique control over both the chemoattractant gradient and the migration environment of the cells. Our work incorporates laser-machined micro and nanofluidic channels into bulk fused silica and cover slip-sized silica wafers. We have designed “open” chemotaxis devices that produce passive chemoattractant gradients without an external micropipette system. Since the migration area is unobstructed, cells can be easily loaded and strategically placed into the devic...

  12. The unique paradigm of spirochete motility and chemotaxis

    Charon, Nyles W.; Cockburn, Andrew; Li, Chunhao; Liu, Jun; Miller, Kelly A.; MILLER, MICHAEL R.; Motaleb, Md.; Wolgemuth, Charles W.


    Spirochete motility is enigmatic: It differs from the motility of most other bacteria in that the entire bacterium is involved in translocation in the absence of external appendages. Using the Lyme disease spirochete Borrelia burgdorferi (Bb) as a model system, we explore the current research on spirochete motility and chemotaxis. Bb has periplasmic flagella (PFs) subterminally attached to each end of the protoplasmic cell cylinder, and surrounding the cell is an outer membrane. These interna...

  13. Travelling Waves in Hyperbolic Chemotaxis Equations

    Xue, Chuan


    Mathematical models of bacterial populations are often written as systems of partial differential equations for the densities of bacteria and concentrations of extracellular (signal) chemicals. This approach has been employed since the seminal work of Keller and Segel in the 1970s (Keller and Segel, J. Theor. Biol. 30:235-248, 1971). The system has been shown to permit travelling wave solutions which correspond to travelling band formation in bacterial colonies, yet only under specific criteria, such as a singularity in the chemotactic sensitivity function as the signal approaches zero. Such a singularity generates infinite macroscopic velocities which are biologically unrealistic. In this paper, we formulate a model that takes into consideration relevant details of the intracellular processes while avoiding the singularity in the chemotactic sensitivity. We prove the global existence of solutions and then show the existence of travelling wave solutions both numerically and analytically. © 2010 Society for Mathematical Biology.

  14. Characterizing asthma from a drop of blood using neutrophil chemotaxis.

    Sackmann, Eric Karl-Heinz; Berthier, Erwin; Schwantes, Elizabeth A; Fichtinger, Paul S; Evans, Michael D; Dziadzio, Laura L; Huttenlocher, Anna; Mathur, Sameer K; Beebe, David J


    Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient's neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements. PMID:24711384

  15. Denitrification and chemotaxis of Pseudomonas stutzeri KC in porous media.

    Roush, Caroline J; Lastoskie, Christian M; Worden, R Mark


    Chemotaxis is an important mechanism by which microorganisms are dispersed in porous media. A vigorous chemotactic response to concentration gradients formed by microbial consumption of chemoattractants can accelerate transport of bacteria to highly contaminated regions of soils and sediments, enhancing the efficiency of in situ bioremediation operations. Although chemotaxis plays a key role in establishment of biodegradation zones in the subsurface, the effects of physical heterogeneity on bacterial motility are poorly understood. To investigate the influence of porous media heterogeneity on microbial chemotaxis, swarm plate migration experiments were conducted using Pseudomonas stutzeri strain KC, a denitrifying bacterium used for in situ biodegradation of carbon tetrachloride in groundwater. Swarm plate measurements indicate that strain KC is strongly chemotactic toward both acetate and nitrate. A three-component mathematical model was developed to describe the migration of strain KC. Estimates of chemotactic sensitivity were obtained in the homogeneous (agar) phase and in a heterogeneous medium of aquifer solids extracted from the Schoolcraft bioremediation field site in western Michigan. Interestingly, the motility of strain KC is significantly larger in the porous medium than in the aqueous phase. We hypothesize that chemotactic response is enhanced within the heterogeneous medium because chemoattractant gradients formed by nitrate consumption are larger in the confined spaces of the porous medium than in unconfined agar solution. PMID:16760079

  16. Modeling Transitions in Complex Systems by Multiplicative Effect of Temporal Patterns Extracted from Signal Flows

    Ezzat G. Bakhoum


    for characterizing suddenly emerging phenomena as nonlinear transitions. Newly created temporal patterns extracted from internal signal flow (mathematically represented as oscillations with long period interact as new entities in a multiplicative manner with subsequent pulses from the external time series (already existing entities in order to generate nonlinear transitions within the system. Such effects are enhanced when the period of external pulses creating new patterns is similar to the settling time of the complex system (this being the condition for an efficient external action. For complex systems where both classical and quantum phenomena generated by external time series are involved, this mathematical model can correctly explain the transition from classical to quantum behaviour (corresponding to a more ordered structure avoiding typical contradictions generated by analysis performed on transient time intervals or by wave superposition.

  17. Chromogenic signaling of water traces by 1,8-naphthalohydrazone-anion complex in organic solvents

    Veikko Uahengo


    Full Text Available A naphthalo-1, 8-bis[(2,4-dinitrophenylhydrazone] sensor (K was synthesized and characterized using UV–vis, 1H NMR and fluorescence spectroscopy. The sensor showed strong colorimetric and spectral response upon the molar addition of acetate or fluoride ion (AcO− or F− in acetonitrile. The complexed state (KF or KAcO of the system showed significant reversibility properties, both in color and spectra, upon the addition of small traces of water. Subsequently, in addition to sensing of fluoride or acetate ions, the complexed KF or KAcO adducts can be used in colorimetric signaling of water traces in different organic mediums. In order to have more understanding of the interaction between K and the anions, the study was supplemented using density functional theory computations.

  18. Complex patterns of signalling to convey different social goals of sex in bonobos, Pan paniscus

    Genty, Emilie; Neumann, Christof; Zuberbühler, Klaus


    Sexual behaviour in bonobos (Pan paniscus) functions beyond mere reproduction to mediate social interactions and relationships. In this study, we assessed the signalling behaviour in relation to four social goals of sex in this species: appeasement after conflict, tension reduction, social bonding and reproduction. Overall, sexual behaviour was strongly decoupled from its ancestral reproductive function with habitual use in the social domain, which was accompanied by a corresponding complexity in communication behaviour. We found that signalling behaviour varied systematically depending on the initiator’s goals and gender. Although all gestures and vocalisations were part of the species-typical communication repertoire, they were often combined and produced flexibly. Generally, gestures and multi-modal combinations were more flexibly used to communicate a goal than vocalisations. There was no clear relation between signalling behaviour and success of sexual initiations, suggesting that communication was primarily used to indicate the signaller’s intention, and not to influence a recipient’s willingness to interact sexually. We discuss these findings in light of the larger question of what may have caused, in humans, the evolutionary transition from primate-like communication to language. PMID:26538281

  19. Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules.

    Copple, Bryan L; Li, Tiangang


    For many years, bile acids were thought to only function as detergents which solubilize fats and facilitate the uptake of fat-soluble vitamins in the intestine. Many early observations; however, demonstrated that bile acids regulate more complex processes, such as bile acids synthesis and immune cell function through activation of signal transduction pathways. These studies were the first to suggest that receptors may exist for bile acids. Ultimately, seminal studies by many investigators led to the discovery of several bile acid-activated receptors including the farnesoid X receptor, the vitamin D receptor, the pregnane X receptor, TGR5, α5 β1 integrin, and sphingosine-1-phosphate receptor 2. Several of these receptors are expressed outside of the gastrointestinal system, indicating that bile acids may have diverse functions throughout the body. Characterization of the functions of these receptors over the last two decades has identified many important roles for these receptors in regulation of bile acid synthesis, transport, and detoxification; regulation of glucose utilization; regulation of fatty acid synthesis and oxidation; regulation of immune cell function; regulation of energy expenditure; and regulation of neural processes such as gastric motility. Through these many functions, bile acids regulate many aspects of digestion ranging from uptake of essential vitamins to proper utilization of nutrients. Accordingly, within a short time period, bile acids moved beyond simple detergents and into the realm of complex signaling molecules. Because of the important processes that bile acids regulate through activation of receptors, drugs that target these receptors are under development for the treatment of several diseases, including cholestatic liver disease and metabolic syndrome. In this review, we will describe the various bile acid receptors, the signal transduction pathways activated by these receptors, and briefly discuss the physiological processes that

  20. Analysis of periplasmic sensor domains from Anaeromyxobacter dehalogenans 2CP-C: Structure of one sensor domain from a histidine kinase and another from a chemotaxis protein

    Pokkuluri, P. Raj; Dwulit-Smith, Jeff; Duke, Norma E; Wilton, Rosemarie; Mack, Jamey C; Bearden, Jessica; Rakowski, Ella; Babnigg, Gyorgy; Szurmant, Hendrik; Joachimiak, Andrzej; Schiffer, Marianne


    Anaeromyxobacter dehalogenans is a δ-proteobacterium found in diverse soils and sediments. It is of interest in bioremediation efforts due to its dechlorination and metal-reducing capabilities. To gain an understanding on A. dehalogenans' abilities to adapt to diverse environments we analyzed its signal transduction proteins. The A. dehalogenans genome codes for a large number of sensor histidine kinases (HK) and methyl-accepting chemotaxis proteins (MCP); among these 23 HK and 11 MCP protein...

  1. Coupling the phosphotransferase system and the methyl-accepting chemotaxis protein-dependent chemotaxis signaling pathways of Escherichia coli.

    Lux, R.; Jahreis, K; Bettenbrock, K.; Parkinson, J S; Lengeler, J W


    Chemotactic responses in Escherichia coli are typically mediated by transmembrane receptors that monitor chemoeffector levels with periplasmic binding domains and communicate with the flagellar motors through two cytoplasmic proteins, CheA and CheY. CheA autophosphorylates and then donates its phosphate to CheY, which in turn controls flagellar rotation. E. coli also exhibits chemotactic responses to substrates that are transported by the phosphoenolpyruvate (PEP)-dependent carbohydrate phosp...

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

    Zeke, András; Misheva, Mariya; Reményi, Attila; Bogoyevitch, Marie A


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

  3. Miniaturized Swimming Soft Robot with Complex Movement Actuated and Controlled by Remote Light Signals

    Huang, Chaolei; Lv, Jiu-An; Tian, Xiaojun; Wang, Yuechao; Yu, Yanlei; Liu, Jie


    Powering and communication with micro robots to enable complex functions is a long-standing challenge as the size of robots continues to shrink. Physical connection of wires or components needed for wireless communication are complex and limited by the size of electronic and energy storage devices, making miniaturization of robots difficult. To explore an alternative solution, we designed and fabricated a micro soft swimming robot with both powering and controlling functions provided by remote light, which does not carry any electronic devices and batteries. In this approach, a polymer film containing azobenzene chromophore which is sensitive to ultra-violet (UV) light works as “motor”, and the UV light and visible light work as “power and signal lines”. Periodically flashing UV light and white light drives the robot flagellum periodically to swing to eventually push forward the robot in the glass tube filled with liquid. The gripper on robot head can be opened or closed by lights to grab and carry the load. This kind of remotely light-driven approach realizes complex driving and controlling of micro robotic structures, making it possible to design and fabricate even smaller robots. It will have great potential among applications in the micro machine and robot fields.

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

    Hélène Chanut-Delalande

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

  5. The Study of Properties of n-D Analytic Signals and Their Spectra in Complex and Hypercomplex Domains

    K. M. Snopek


    Full Text Available In the paper, two various representations of a n-dimensional (n-D real signal u(x1,x2,…,xn are investigated. The first one is the n-D complex analytic signal with a single-orthant spectrum defined by Hahn in 1992 as the extension of the 1-D Gabor’s analytic signal. It is compared with two hypercomplex approaches: the known n-D Clifford analytic signal and the Cayley-Dickson analytic signal defined by the Author in 2009. The signal-domain and frequency-domain definitions of these signals are presented and compared in 2-D and 3-D. Some new relations between the spectra in 2-D and 3-D hypercomplex domains are presented. The paper is illustrated with the example of a 2-D separable Cauchy pulse.

  6. A low complexity, low spur digital IF conversion circuit for high-fidelity GNSS signal playback

    Su, Fei; Ying, Rendong


    A low complexity high efficiency and low spur digital intermediate frequency (IF) conversion circuit is discussed in the paper. This circuit is key element in high-fidelity GNSS signal playback instrument. We analyze the spur performance of a finite state machine (FSM) based numerically controlled oscillators (NCO), by optimization of the control algorithm, a FSM based NCO with 3 quantization stage can achieves 65dB SFDR in the range of the seventh harmonic. Compare with traditional lookup table based NCO design with the same Spurious Free Dynamic Range (SFDR) performance, the logic resource require to implemented the NCO is reduced to 1/3. The proposed design method can be extended to the IF conversion system with good SFDR in the range of higher harmonic components by increasing the quantization stage.

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

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


    Background Experiments under controlled laboratory conditions can produce decisive evidence for testing biological hypotheses, provided they are representative of the more complex natural conditions. However, whether this requirement is fulfilled is seldom tested explicitly. Here we provide a lab....../field comparison to investigate the identity of an egg-marking signal of ant queens. Our study was based on ant workers resolving conflict over male production by destroying each other's eggs, but leaving queen eggs unharmed. For this, the workers need a proximate cue to discriminate between the two egg types....... Earlier correlative evidence indicated that, in the ant Pachycondyla inversa, the hydrocarbon 3,11-dimethylheptacosane (3,11-diMeC27) is more abundant on the surface of queen-laid eggs. Methodology We first tested the hypothesis that 3,11-diMeC27 functions as a queen egg-marking pheromone using laboratory...

  8. On chip complex signal processing devices using coupled phononic crystal slab resonators and waveguides

    Saeed Mohammadi


    Full Text Available In this paper, we report the evidence for the possibility of achieving complex signal processing functionalities such as multiplexing/demultiplexing at high frequencies using phononic crystal (PnC slabs. It is shown that such functionalities can be obtained by appropriate cross-coupling of PnC resonators and waveguides. PnC waveguides and waveguide-based resonators are realized and cross-coupled through two different methods of mechanical coupling (i.e., direct coupling and side coupling. Waveguide-based PnC resonators are employed because of their high-Q, compactness, large spurious-free spectral ranges, and the possibility of better control over coupling to PnC waveguides. It is shown that by modifying the defects in the formation of the resonators, the frequency of the resonance can be tuned.

  9. Exact solutions of certain nonlinear chemotaxis diffusion reaction equations



    Using the auxiliary equation method, we obtain exact solutions of certain nonlinear chemotaxis diffusion reaction equations in the presence of a stimulant. In particular, we account for the nonlinearities arising not only from the density-dependent source terms contributed by the particles and the stimulant but also from the coupling term of the stimulant. In addition to this, the diffusion of the stimulant and the effect of long-range interactions are also accounted for in theconstructed coupled differential equations. The results obtained here could be useful in the studies of several biological systems and processes, e.g., in bacterial infection, chemotherapy, etc.

  10. The Impact of Odor--Reward Memory on Chemotaxis in Larval "Drosophila"

    Schleyer, Michael; Reid, Samuel F.; Pamir, Evren; Saumweber, Timo; Paisios, Emmanouil; Davies, Alexander; Gerber, Bertram; Louis, Matthieu


    How do animals adaptively integrate innate with learned behavioral tendencies? We tackle this question using chemotaxis as a paradigm. Chemotaxis in the "Drosophila" larva largely results from a sequence of runs and oriented turns. Thus, the larvae minimally need to determine (i) how fast to run, (ii) when to initiate a turn, and (iii)…

  11. A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

    Royer, J F; Schratl, P; Lorenz, S;


    (2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast...

  12. Inhibition of Escherichia coli chemotaxis by omega-conotoxin, a calcium ion channel blocker.

    Tisa, L S; Olivera, B M; Adler, J


    Escherichia coli chemotaxis was inhibited by omega-conotoxin, a calcium ion channel blocker. With Tris-EDTA-permeabilized cells, nanomolar levels of omega-conotoxin inhibited chemotaxis without loss of motility. Cells treated with omega-conotoxin swam with a smooth bias, i.e., tumbling was inhibited.

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

    Firmansyah, Rizky, E-mail: [Geophysical Engineering, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Nugraha, Andri Dian, E-mail: [Global Geophysical Group, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Kristianto, E-mail: [Center for Volcanology and Geological Hazard Mitigation (CVGHM), Geological Agency, Bandung, 40122 (Indonesia)


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

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

    Firmansyah, Rizky; Nugraha, Andri Dian; Kristianto


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

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

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

  16. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Gallin, J.I.


    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  17. Structure of PqsD, a Pseudomonas quinolone signal biosynthetic enzyme, in complex with anthranilate.

    Bera, Asim K; Atanasova, Vesna; Robinson, Howard; Eisenstein, Edward; Coleman, James P; Pesci, Everett C; Parsons, James F


    Pseudomonas quinolone signal (PQS), 2-heptyl-3-hydroxy-4-quinolone, is an intercellular alkyl quinolone signaling molecule produced by the opportunistic pathogen Pseudomonas aeruginosa. Alkyl quinolone signaling is an atypical system that, in P. aeruginosa, controls the expression of numerous virulence factors. PQS is synthesized from the tryptophan pathway intermediate, anthranilate, which is derived either from the kynurenine pathway or from an alkyl quinolone specific anthranilate synthase encoded by phnAB. Anthranilate is converted to PQS by the enzymes encoded by the pqsABCDE operon and pqsH. PqsA forms an activated anthraniloyl-CoA thioester that shuttles anthranilate to the PqsD active site where it is transferred to Cys112 of PqsD. In the only biochemically characterized reaction, a condensation then occurs between anthraniloyl-PqsD and malonyl-CoA or malonyl-ACP, a second PqsD substrate, forming 2,4-dihydroxyquinoline (DHQ). The role PqsD plays in the biosynthesis of other alkyl quinolones, such as PQS, is unclear, though it has been reported to be required for their production. No evidence exists that DHQ is a PQS precursor, however. Here we present a structural and biophysical characterization of PqsD that includes several crystal structures of the enzyme, including that of the PqsD-anthranilate covalent intermediate and the inactive Cys112Ala active site mutant in complex with anthranilate. The structure reveals that PqsD is structurally similar to the FabH and chalcone synthase families of fatty acid and polyketide synthases. The crystallographic asymmetric unit contains a PqsD dimer. The PqsD monomer is composed of two nearly identical approximately 170-residue alphabetaalphabetaalpha domains. The structures show anthranilate-liganded Cys112 is positioned deep in the protein interior at the bottom of an approximately 15 A long channel while a second anthraniloyl-CoA molecule is waiting in the cleft leading to the protein surface. Cys112, His257, and

  18. Biomixing by chemotaxis and efficiency of biological reactions: the critical reaction case

    Kiselev, Alexander


    Many phenomena in biology involve both reactions and chemotaxis. These processes can clearly influence each other, and chemotaxis can play an important role in sustaining and speeding up the reaction. In continuation of our earlier work, we consider a model with a single density function involving diffusion, advection, chemotaxis, and absorbing reaction. The model is motivated, in particular, by the studies of coral broadcast spawning, where experimental observations of the efficiency of fertilization rates significantly exceed the data obtained from numerical models that do not take chemotaxis (attraction of sperm gametes by a chemical secreted by egg gametes) into account. We consider the case of the weakly coupled quadratic reaction term, which is the most natural from the biological point of view and was left open. The result is that similarly to higher power coupling, the chemotaxis plays a crucial role in ensuring efficiency of reaction. However, mathematically, the picture is quite different in the qua...

  19. Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

    Nielsen, H; Kharazmi, A; Theander, T G


    tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the...... suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No...... significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of...

  20. Cylinder pressure reconstruction based on complex radial basis function networks from vibration and speed signals

    Johnsson, Roger


    Methods to measure and monitor the cylinder pressure in internal combustion engines can contribute to reduced fuel consumption, noise and exhaust emissions. As direct measurements of the cylinder pressure are expensive and not suitable for measurements in vehicles on the road indirect methods which measure cylinder pressure have great potential value. In this paper, a non-linear model based on complex radial basis function (RBF) networks is proposed for the reconstruction of in-cylinder pressure pulse waveforms. Input to the network is the Fourier transforms of both engine structure vibration and crankshaft speed fluctuation. The primary reason for the use of Fourier transforms is that different frequency regions of the signals are used for the reconstruction process. This approach also makes it easier to reduce the amount of information that is used as input to the RBF network. The complex RBF network was applied to measurements from a 6-cylinder ethanol powered diesel engine over a wide range of running conditions. Prediction accuracy was validated by comparing a number of parameters between the measured and predicted cylinder pressure waveform such as maximum pressure, maximum rate of pressure rise and indicated mean effective pressure. The performance of the network was also evaluated for a number of untrained running conditions that differ both in speed and load from the trained ones. The results for the validation set were comparable to the trained conditions.

  1. Structural Basis for Conserved Regulation and Adaptation of the Signal Recognition Particle Targeting Complex.

    Wild, Klemens; Bange, Gert; Motiejunas, Domantas; Kribelbauer, Judith; Hendricks, Astrid; Segnitz, Bernd; Wade, Rebecca C; Sinning, Irmgard


    The signal recognition particle (SRP) is a ribonucleoprotein complex with a key role in targeting and insertion of membrane proteins. The two SRP GTPases, SRP54 (Ffh in bacteria) and FtsY (SRα in eukaryotes), form the core of the targeting complex (TC) regulating the SRP cycle. The architecture of the TC and its stimulation by RNA has been described for the bacterial SRP system while this information is lacking for other domains of life. Here, we present the crystal structures of the GTPase heterodimers of archaeal (Sulfolobus solfataricus), eukaryotic (Homo sapiens), and chloroplast (Arabidopsis thaliana) SRP systems. The comprehensive structural comparison combined with Brownian dynamics simulations of TC formation allows for the description of the general blueprint and of specific adaptations of the quasi-symmetric heterodimer. Our work defines conserved external nucleotide-binding sites for SRP GTPase activation by RNA. Structural analyses of the GDP-bound, post-hydrolysis states reveal a conserved, magnesium-sensitive switch within the I-box. Overall, we provide a general model for SRP cycle regulation by RNA. PMID:27241309

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

    Joaquin J Torres

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

  3. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

    David J. Brown


    Full Text Available Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specific learning and breadth of generalization over the time course. In comparison with previous research using simple stimuli, the speed of perceptual learning and breadth of generalization were more rapid and greater in magnitude, including novel generalization to an alternate temporal interval within stimulus type. We also investigated the long term maintenance of learning and found that specific and generalized learning was maintained over 3 and 6 months. We discuss these findings regarding stimulus complexity in perceptual learning and how they can inform the development of effective training protocols.

  4. Design of complex-valued variable FIR digital filters and its application to the realization of arbitrary sampling rate conversion for complex signals

    Tsui, KM; Chan, SC; Tse, KW


    This brief studies the design of complex-valued variable digital filters (CVDFs) and their applications to the efficient arbitrary sample rate conversion for complex signals. The design of CVDFs using either the minimax or least-squares criteria is formulated as a convex optimization problem and solved using the second-order cone programming (SOCP). In addition, linear and convex quadratic inequality constraints can be readily incorporated. Design examples are given to demonstrate the effecti...

  5. Feeding ducks, bacterial chemotaxis, and the Gini index

    Peaudecerf, François J.; Goldstein, Raymond E.


    Classic experiments on the distribution of ducks around separated food sources found consistency with the "ideal free" distribution in which the local population is proportional to the local supply rate. Motivated by this experiment and others, we examine the analogous problem in the microbial world: the distribution of chemotactic bacteria around multiple nearby food sources. In contrast to the optimization of uptake rate that may hold at the level of a single cell in a spatially varying nutrient field, nutrient consumption by a population of chemotactic cells will modify the nutrient field, and the uptake rate will generally vary throughout the population. Through a simple model we study the distribution of resource uptake in the presence of chemotaxis, consumption, and diffusion of both bacteria and nutrients. Borrowing from the field of theoretical economics, we explore how the Gini index can be used as a means to quantify the inequalities of uptake. The redistributive effect of chemotaxis can lead to a phenomenon we term "chemotactic levelling," and the influence of these results on population fitness are briefly considered.

  6. From PII Signaling to Metabolite Sensing: A Novel 2-Oxoglutarate Sensor That Details PII - NAGK Complex Formation

    Lüddecke, Jan; Forchhammer, Karl


    The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK) in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specific...

  7. RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling

    Lindsey-Boltz, Laura A.; Kemp, Michael G.; Capp, Christopher; Sancar, Aziz


    The ATR-Chk1 signaling pathway mediates cellular responses to DNA damage and replication stress and is composed of a number of core factors that are conserved throughout eukaryotic organisms. However, humans and other higher eukaryotic species possess additional factors that are implicated in the regulation of this signaling network but that have not been extensively studied. Here we show that RHINO (for Rad9, Rad1, Hus1 interacting nuclear orphan) forms complexes with both the 9-1-1 checkpoi...

  8. Regulatory Networks and Complex Interactions between the Insulin and Angiotensin II Signalling Systems: Models and Implications for Hypertension and Diabetes

    Çizmeci, Deniz; Arkun, Yaman


    Regulatory Networks and Complex Interactions between the Insulin and Angiotensin II Signalling Systems: Models and Implications for Hypertension and Diabetes Deniz Cizmeci, Yaman Arkun* Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey Abstract The cross-talk between insulin and angiotensin II signalling pathways plays a significant role in the co-occurrence of diabetes and hypertension. We developed a mathematical model of the system of ...

  9. tlpA gene expression is required for arginine and bicarbonate chemotaxis in Helicobacter pylori

    Oscar A Cerda


    Full Text Available About half of the human population is infected with Helicobacter pylori, a bacterium causing gastritis, peptic ulcer and progression to gastric cancer. Chemotaxis and flagellar motility are required for colonization and persistence of H. pylori in the gastric mucus layer. It is not completely clear which chemical gradients are used by H. pylori to maintain its position. TlpA, a chemotaxis receptor for arginine/ bicarbonate, has been identified. This study aimed to find out whether tlpA gene expression is required for the chemotactic response to arginine/bicarbonate. Wild-type motile H. pylori ATCC 700392 and H. pylori ATCC 43504, a strain having an interrupted tlpA gene, were used. Also, a tlpA-knockout mutant of H. pylori 700392 (H. pylori 700-tlpA::cat was produced by homologous recombination. Expression of tlpA was assessed by a Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR assay. Chemotaxis was measured as a Relative Chemotaxis Response (RCR by a modified capillary assay. H. pylori 700392 presented chemotaxis to arginine and sodium bicarbonate. H. pylori 700-tlpA::cat showed neither tlpA gene expression nor chemotaxis towards arginine and bicarbonate. Besides confirming that TlpA is a chemotactic receptor for arginine/bicarbonate in H. pylori, this study showed that tlpA gene expression is required for arginine/bicarbonate chemotaxis.

  10. Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement Component C5a.

    Taylor, Lewis; Brodermann, Maximillian Hugo; McCaffary, David; Iqbal, Asif Jilani; Greaves, David R


    Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies. Treatment of RAW264.7 macrophages, BMDMs and human monocytes with netrin-1 inhibited their chemotaxis towards C5a, as measured using two different real-time methods. This inhibitory effect was found to be dependent on netrin-1 receptor signalling, as an UNC5b blocking antibody was able to reverse netrin-1 inhibition of C5a induced BMDM migration. Treatment of BMDMs with netrin-1 had no effect on C5aR1 proximal signalling events, as surface C5aR1 expression, internalisation and intracellular Ca2+ release following C5aR1 ligation remained unaffected after netrin-1 exposure. We next examined receptor distal events that occur following C5aR1 activation, but found that netrin-1 was unable to inhibit C5a induced phosphorylation of ERK1/2, Akt and p38, pathways important for cellular migration. Furthermore, netrin-1 treatment had no effect on BMDM cytoskeletal rearrangement following C5a stimulation as determined by microscopy and real-time electrical impedance sensing. Taken together these data highlight that netrin-1 inhibits monocyte and macrophage cell migration, but that the mechanism behind this effect remains unresolved. Nevertheless, netrin-1 and its cognate receptors warrant further investigation as they may represent a potential avenue for the development of

  11. Signaling pathways regulating production of hyaluronic acid in pig oocyte-cumulus cell-complexes

    Procházka, Radek; Nagyová, Eva

    Luxembourg: Recherches Scientifiques Luxembourg, 2006. s. 647. [Cell Signaling World 2006, Signal Transduction Pathways therapeutic targets. 25.01.2006-28.01.2006, Luxembourg] R&D Projects: GA ČR GA523/04/0574 Institutional research plan: CEZ:AV0Z50450515 Keywords : signaling pathways Subject RIV: EB - Genetics ; Molecular Biology

  12. The domain dependence of chemotaxis in two-dimensional turbulence

    Tang, Wenbo; Jones, Kimberly; Walker, Phillip


    Coherent structures are ubiquitous in environmental and geophysical flows and they affect reaction-diffusion processes in profound ways. In this presentation, we show an example of the domain dependence of chemotaxis process in a two-dimensional turbulent flow. The flow has coherent structures that form barriers that prohibit long-range transport of tracers. Accordingly, the uptake advantage of nutrient by motile and nonmotile species differs significantly if the process start in different locations of the flow. Interestingly, the conventional diagnostic of Finite-time Lyapunov exponents alone is not sufficient to explain the variability -- methods to extract elliptic transport barriers are essential to relate to the explanation. We also offer some explanations of the observed scalar behaviors via analyses of bulk quantities. Support: NSF-DMS-1212144.

  13. Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

    Liptak Amy R


    Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

  14. Singularity formation in chemotaxis systems with volume-filling effect

    A parabolic–elliptic model of chemotaxis which takes into account volume-filling effects is considered under the assumption that there is an a priori threshold for the cell density. For a wide range of nonlinear diffusion operators including singular and degenerate ones it is proved that if the taxis force is strong enough with respect to diffusion and the initial data are chosen properly then there exists a classical solution which reaches the threshold at the maximal time of its existence, no matter whether the latter is finite or infinite. Moreover, we prove that the threshold may even be reached in finite time provided the diffusion of cells is non-degenerate

  15. Boundedness in a chemotaxis-haptotaxis model with nonlinear diffusion

    Li, Yan; Lankeit, Johannes


    This article deals with an initial-boundary value problem for the coupled chemotaxis-haptotaxis system with nonlinear diffusion under homogeneous Neumann boundary conditions in a bounded smooth domain Ω \\subset {{{R}}n} , n  =  2, 3, 4, where χ,ξ and μ are given nonnegative parameters. The diffusivity D(u) is assumed to satisfy D(u)≥slant δ {{u}m-1} for all u  >  0 with some δ >0 . It is proved that for sufficiently regular initial data global bounded solutions exist whenever m>2-\\frac{2}{n} . For the case of non-degenerate diffusion (i.e. D(0)  >  0) the solutions are classical; for the case of possibly degenerate diffusion (D(0)≥slant 0 ), the existence of bounded weak solutions is shown.

  16. Boundedness in a three-dimensional chemotaxis-haptotaxis model

    Cao, Xinru


    This paper studies the chemotaxis-haptotaxis system left\\{begin{array}{lll} u_t = Δ u - χnabla \\cdot (unabla v) - ξnabla \\cdot (unabla w) + μ u(1 - u - w), &quad(x, t)in Ω × (0, T),\\ v_t = Δ v - v + u, &quad(x, t) in Ω × (0, T),\\ w_t= - vw, &quad(x, t)in Ω × (0,T) right.quadquad(star) under Neumann boundary conditions. Here, {Ω subset {{R}}^3} is a bounded domain with smooth boundary and the parameters {ξ,χ,μ > 0}. We prove that for nonnegative and suitably smooth initial data {(u_0, v_0, w_0)}, if {χ/μ} is sufficiently small, ({star}) possesses a global classical solution, which is bounded in {Ω × (0, infty)}. We underline that the result fully parallels the corresponding parabolic-elliptic-ODE system.

  17. Negative chemotaxis does not control quail neural crest cell dispersion.

    Erickson, C A; Olivier, K R


    Negative chemotaxis has been proposed to direct dispersion of amphibian neural crest cells away from the neural tube (V. C. Twitty, 1949, Growth 13(Suppl. 9), 133-161). We have reexamined this hypothesis using quail neural crest and do not find evidence for it. When pigmented or freshly isolated neural crest cells are covered by glass shards to prevent diffusion of a "putative" chemotactic agent away from the cells and into the medium, we find a decrease in density of cells beneath the coverslip as did Twitty and Niu (1948, J. Exp. Zool. 108, 405-437). Unlike those investigators, however, we find the covered cells move slower than uncovered cells and that the decrease in density can be attributed to cessation of cell division and increased cell death in older cultures, rather than directed migration away from each other. In cell systems where negative chemotaxis has been demonstrated, a "no man's land" forms between two confronted explants (Oldfield, 1963, Exp. Cell Res. 30, 125-138). No such cell-free space forms between confronted neural crest explants, even if the explants are closely covered to prevent diffusion of the negative chemotactic material. If crest cell aggregates are drawn into capillary tubes to allow accumulation of the putative material, the cells disperse farther, the wider the capillary tube bore. This is contrary to what would be expected if dispersion depended on accumulation of this material. Also, no difference in dispersion is noted between cells in the center of the tubes versus cells near the mouth of the tubes where the tube medium is freely exchanging with external fresh medium. Alternative hypotheses for directionality of crest migration in vivo are discussed. PMID:6832483

  18. Comment on 'Interpretation of the Lempel-Ziv Complexity Measure in the context of Biomedical Signal Analysis'

    Balasubramanian, Karthi


    In this Communication, we express our reservations on some aspects of the interpretation of the Lempel-Ziv Complexity measure (LZ) by Mateo et al. in "Interpretation of the Lempel-Ziv complexity measure in the context of biomedical signal analysis," IEEE Trans. Biomed. Eng., vol. 53, no. 11, pp. 2282-2288, Nov. 2006. In particular, we comment on the dependence of the LZ complexity measure on number of harmonics, frequency content and amplitude modulation. We disagree with the following statements made by Mateo et al. 1. "LZ is not sensitive to the number of harmonics in periodic signals." 2. "LZ increases as the frequency of a sinusoid increases." 3. "Amplitude modulation of a signal doesnot result in an increase in LZ." We show the dependence of LZ complexity measure on harmonics and amplitude modulation by using a modified version of the synthetic signal that has been used in the original paper. Also, the second statement is a generic statement which is not entirely true. This is true only in the low freque...

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

    Douglas Scott C


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

  20. Signal recognition particle receptor is a complex that contains two distinct polypeptide chains

    Signal recognition particle (SRP) and SRP receptor are known to be essential components of the cellular machinery that targets nascent secretory proteins to the endoplasmic reticulum (ER) membrane. Here the authors report that the SRP receptor contains, in addition to the previously identified and sequenced 69-kD polypeptide (α-subunit, SRα), a 30-kD β-subunit SRβ). When SRP receptor was purified by SRP-Sepharose affinity chromatography, they observed the co-purification of two other ER membrane proteins. Both proteins are ∼30 kD in size and are immunologically distinct from each other, as well as from SRα and SRP proteins. One of the 30-kD proteins (SRβ) forms a tight complex with SRα in detergent solution that is stable to high salt and can be immunoprecipitated with antibodies to either SRα or SRβ. Both subunits are present in the ER membrane in equimolar amounts and co-fractionate in constant stoichiometry when rough and smooth liver microsomes are separated on sucrose gradients. They therefore conclude that SRβ is an integral component of SRP receptor. The presence of SRβ was previously masked by proteolytic breakdown products of SRα observed by others and by the presence of another 30-kD ER membrane protein (mp30) which co-purifies with SRα. Mp30 binds to SRP-Sepharose directly and is present in the ER membrane in several-fold molar excess of SRα and SRβ. The affinity of mp30 for SRP suggests that it may serve a yet unknown function in protein translocation

  1. Maneuverability and chemotaxis of Caenorhabditis elegans in three-dimensional environments

    Blawzdziewicz, Jerzy; Bilbao, Alejandro; Patel, Amar; Vanapalli, Siva


    Locomotion of the nematode C. elegans in water and complex fluids has recently been investigated to gain insight into neuromuscular control of locomotion and to shed light on nematode evolutionary adaptation to environments with varying mechanical properties. Previous studies focused mainly on locomotion efficiency and on adaptation of the nematode gait to the surrounding medium. Much less attention has been devoted to nematode maneuverability, in spite of its crucial role in the survival of the animal. Recently we have provided a quantitative analysis of turning maneuvers of crawling and swimming nematodes on flat surfaces and in 2D fluid layers. Based on this work, we follow with the first full 3D description of how C. elegans moves in complex 3D environments. We show that by superposing body twist and 2D undulations, a burrowing or swimming nematode can rotate the undulation plane and change the direction of motion within that plane by varying undulation-wave parameters. A combination of these corkscrew maneuvers and 2D turns allows the nematode to explore 3D space. We conclude by analyzing 3D chemotaxis of nematodes burrowing in gel and swimming in water, which demonstrates an important application of our maneuverability model. This work was supported by NSF grant CBET-1059745.

  2. Site-specific and synergistic stimulation of methylation on the bacterial chemotaxis receptor Tsr by serine and CheW

    Weis Robert M


    Full Text Available Abstract Background Specific glutamates in the methyl-accepting chemotaxis proteins (MCPs of Escherichia coli are modified during sensory adaptation. Attractants that bind to MCPs are known to increase the rate of receptor modification, as with serine and the serine receptor (Tsr, which contributes to an increase in the steady-state (adapted methylation level. However, MCPs form ternary complexes with two cytoplasmic signaling proteins, the kinase (CheA and an adaptor protein (CheW, but their influences on receptor methylation are unknown. Here, the influence of CheW on the rate of Tsr methylation has been studied to identify contributions to the process of adaptation. Results Methyl group incorporation was measured in a series of membrane samples in which the Tsr molecules were engineered to have one available methyl-accepting glutamate residue (297, 304, 311 or 493. The relative rates at these sites (0.14, 0.05, 0.05 and 1, respectively differed from those found previously for the aspartate receptor (Tar, which was in part due to sequence differences between Tar and Tsr near site four. The addition of CheW generated unexpectedly large and site-specific rate increases, equal to or larger than the increases produced by serine. The increases produced by serine and CheW (added separately were the largest at site one, ~3 and 6-fold, respectively, and the least at site four, no change and ~2-fold, respectively. The rate increases were even larger when serine and CheW were added together, larger than the sums of the increases produced by serine and CheW added separately (except site four. This resulted in substantially larger serine-stimulated increases when CheW was present. Also, CheW enhanced methylation rates when either two or all four sites were available. Conclusion The increase in the rate of receptor methylation upon CheW binding contributes significantly to the ligand specificity and kinetics of sensory adaptation. The synergistic effect of

  3. Numerical study of plume patterns in the chemotaxis-diffusion-convection coupling system

    Deleuze, Yannick; Thiriet, Marc; Sheu, Tony W H


    A chemotaxis-diffusion-convection coupling system for describing a form of buoyant convection in which the fluid develops convection cells and plume patterns will be investigated numerically in this study. Based on the two-dimensional convective chemotaxis-fluid model proposed in the literature, we developed an upwind finite element method to investigate the pattern formation and the hydrodynamical stability of the system. The numerical simulations illustrate different predicted physical regimes in the system. In the convective regime, the predicted plumes resemble B\\'enard instabilities. Our numerical results show how structured layers of bacteria are formed before bacterium rich plumes fall in the fluid. The plumes have a well defined spectrum of wavelengths and have an exponential growth rate, yet their position can only be predicted in very simple examples. In the chemotactic and diffusive regimes, the effects of chemotaxis are investigated. Our results indicate that the chemotaxis can stabilize the overa...

  4. Qualitative analysis of stationary Keller-Segel chemotaxis models with logistic growth

    Wang, Qi; Yan, Jingda; Gai, Chunyi


    We study the stationary Keller-Segel chemotaxis models with logistic cellular growth over a one-dimensional region subject to the Neumann boundary condition. We show that nonconstant solutions emerge in the sense of Turing's instability as the chemotaxis rate {χ} surpasses a threshold number. By taking the chemotaxis rate as the bifurcation parameter, we carry out bifurcation analysis on the system to obtain the explicit formulas of bifurcation values and small amplitude nonconstant positive solutions. Moreover, we show that solutions stay strictly positive in the continuum of each branch. The stabilities of these steady-state solutions are well studied when the creation and degradation rate of the chemical is assumed to be a linear function. Finally, we investigate the asymptotic behaviors of the monotone steady states. We construct solutions with interesting patterns such as a boundary spike when the chemotaxis rate is large enough and/or the cell motility is small.

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

    Lüddecke, Jan; Forchhammer, Karl


    The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK) in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specifically responded to 2-oxoglutarate. The impact of the fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon resonance spectroscopy and isothermal calorimetric experiments. The developed FRET sensor provides real-time data on PII - NAGK interaction and its modulation by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel insights into PII - NAGK complex formation: (i) It revealed the formation of an encounter-complex between PII and NAGK, which holds the proteins in proximity even in the presence of inhibitors of complex formation; (ii) It revealed that the PII T-loop residue Ser49 is neither essential for complex formation with NAGK nor for activation of the enzyme but necessary to form a stable complex and efficiently relieve NAGK from arginine inhibition; (iii) It showed that arginine stabilizes the NAGK hexamer and stimulates PII - NAGK interaction. PMID:24349456

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

    Jan Lüddecke

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

  7. Regulation by Light of Chemotaxis to Nitrite during the Sexual Life Cycle in Chlamydomonas reinhardtii

    Elena Ermilova; Zhanneta Zalutskaya


    Nitrite plays an important role in the nitrogen metabolism of most cells, including Chlamydomonas reinhardtii. We have shown that vegetative cells of C. reinhardtii are attracted by nitrite. The Nia1nit2 mutant with defects in genes encoding the nitrate reductase and regulatory protein NIT2 respectively was found to exhibit normal chemotaxis to nitrite. The data suggest that chemotaxis events appear to be specific and independent of those involved in nitrate assimilation. Unlike vegetative ce...

  8. Helicobacter pylori Requires TlpD-Driven Chemotaxis To Proliferate in the Antrum

    Rolig, Annah S.; Shanks, James; Carter, J. Elliot; Ottemann, Karen M.


    Different disease outcomes of Helicobacter pylori infection correlate with distinct inflammation patterns. These different inflammatory distributions may be initiated by differences in bacterial localization. One H. pylori property known to affect murine stomach localization is chemotaxis, the ability to move in response to chemical cues. In this report, we used nonchemotactic mutants (Che−) to analyze whether chemotaxis is required for initial colonization of particular stomach regions or fo...

  9. Assessing the chemotaxis behavior of Physarum polycephalum to a range of simple volatile organic chemicals

    de Lacy Costello, Ben P.J.; Adamatzky, Andrew I.


    The chemotaxis behavior of the plasmodial stage of the true slime mold Physarum Polycephalum was assessed when given a binary choice between two volatile organic chemicals (VOCs) placed in its environment. All possible binary combinations were tested between 19 separate VOCs selected due to their prevalence and biological activity in common plant and insect species. The slime mold exhibited positive chemotaxis toward a number of VOCs with the following order of preference:   Farnesene > β-myr...

  10. The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development

    Liu, Min; Li, Yajuan; Liu, Aiguo; Li, Ruifeng; Su, Ying; Du, Juan; Li, Cheng; Zhu, Alan Jian


    Wingless (Wg)/Wnt signaling is conserved in all metazoan animals and plays critical roles in development. The Wg/Wnt morphogen reception is essential for signal activation, whose activity is mediated through the receptor complex and a scaffold protein Dishevelled (Dsh). We report here that the exon junction complex (EJC) activity is indispensable for Wg signaling by maintaining an appropriate level of Dsh protein for Wg ligand reception in Drosophila. Transcriptome analyses in Drosophila wing imaginal discs indicate that the EJC controls the splicing of the cell polarity gene discs large 1 (dlg1), whose coding protein directly interacts with Dsh. Genetic and biochemical experiments demonstrate that Dlg1 protein acts independently from its role in cell polarity to protect Dsh protein from lysosomal degradation. More importantly, human orthologous Dlg protein is sufficient to promote Dvl protein stabilization and Wnt signaling activity, thus revealing a conserved regulatory mechanism of Wg/Wnt signaling by Dlg and EJC. DOI: PMID:27536874