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Sample records for excitability modulates dendritic

  1. Modulation of synaptic potentials and cell excitability by dendritic ...

    Indian Academy of Sciences (India)

    Modulation of synaptic potentials and cell excitability by dendritic. KIR and KAs channels in nucleus accumbens medium spiny neurons: A computational study. JESSY JOHN* and ROHIT MANCHANDA. Biomedical Engineering group, Department of Biosciences and Bioengineering, Indian Institute of Technology. Bombay ...

  2. Modulation of synaptic potentials and cell excitability by dendritic ...

    Indian Academy of Sciences (India)

    The nucleus accumbens (NAc), a critical structure of the brain reward circuit, is implicated in normal goal-directed behaviour and learning as well as pathological conditions like schizophrenia and addiction. Its major cellular substrates, the medium spiny (MS) neurons, possess a wide variety of dendritic active conductances ...

  3. Granulocytes as modulators of dendritic cell function.

    Science.gov (United States)

    Breedveld, Annelot; Groot Kormelink, Tom; van Egmond, Marjolein; de Jong, Esther C

    2017-10-01

    Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4+ T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (Tregs). During inflammation, DCs are found in close proximity to other innate immune cells, including all granulocyte subtypes, which potentially influence the immunomodulatory capacities of DCs. Neutrophils, eosinophils, and basophils are rapidly recruited into infected tissues where their main function is to eliminate invading pathogens. Mast cells are tissue-resident granulocytes that also contribute to host defense against pathogens but have, thus far, primarily been associated with their detrimental roles in allergic diseases. Although granulocytes have always been considered essential in innate immunity, their ability to influence the development of adaptive immunity has long been overlooked. This view is now changing, as multiple studies showed significant modulating effects of granulocytes on key players of adaptive immunity, including DCs and lymphocytes. Neutrophils, eosinophils, basophils, and mast cells regulate recruitment and activation of DCs through the release of mediators or via direct cell-cell contact, thereby influencing antigen-specific T cell responses. In this review, we will summarize the current knowledge on the impact of granulocytes on DC functioning and the subsequent putative consequences of this cross-talk on T cell proliferation and polarization. Together, this overview underscores the importance of granulocyte-DC communication to establish optimal immune responses. © Society for Leukocyte Biology.

  4. Modulating STDP Balance Impacts the Dendritic Mosaic

    Directory of Open Access Journals (Sweden)

    Nicolangelo Iannella

    2017-06-01

    Full Text Available The ability for cortical neurons to adapt their input/output characteristics and information processing capabilities ultimately relies on the interplay between synaptic plasticity, synapse location, and the nonlinear properties of the dendrite. Collectively, they shape both the strengths and spatial arrangements of convergent afferent inputs to neuronal dendrites. Recent experimental and theoretical studies support a clustered plasticity model, a view that synaptic plasticity promotes the formation of clusters or hotspots of synapses sharing similar properties. We have previously shown that spike timing-dependent plasticity (STDP can lead to synaptic efficacies being arranged into spatially segregated clusters. This effectively partitions the dendritic tree into a tessellated imprint which we have called a dendritic mosaic. Here, using a biophysically detailed neuron model of a reconstructed layer 2/3 pyramidal cell and STDP learning, we investigated the impact of altered STDP balance on forming such a spatial organization. We show that cluster formation and extend depend on several factors, including the balance between potentiation and depression, the afferents' mean firing rate and crucially on the dendritic morphology. We find that STDP balance has an important role to play for this emergent mode of spatial organization since any imbalances lead to severe degradation- and in some case even destruction- of the mosaic. Our model suggests that, over a broad range of of STDP parameters, synaptic plasticity shapes the spatial arrangement of synapses, favoring the formation of clustered efficacy engrams.

  5. Modulating STDP Balance Impacts the Dendritic Mosaic

    Science.gov (United States)

    Iannella, Nicolangelo; Launey, Thomas

    2017-01-01

    The ability for cortical neurons to adapt their input/output characteristics and information processing capabilities ultimately relies on the interplay between synaptic plasticity, synapse location, and the nonlinear properties of the dendrite. Collectively, they shape both the strengths and spatial arrangements of convergent afferent inputs to neuronal dendrites. Recent experimental and theoretical studies support a clustered plasticity model, a view that synaptic plasticity promotes the formation of clusters or hotspots of synapses sharing similar properties. We have previously shown that spike timing-dependent plasticity (STDP) can lead to synaptic efficacies being arranged into spatially segregated clusters. This effectively partitions the dendritic tree into a tessellated imprint which we have called a dendritic mosaic. Here, using a biophysically detailed neuron model of a reconstructed layer 2/3 pyramidal cell and STDP learning, we investigated the impact of altered STDP balance on forming such a spatial organization. We show that cluster formation and extend depend on several factors, including the balance between potentiation and depression, the afferents' mean firing rate and crucially on the dendritic morphology. We find that STDP balance has an important role to play for this emergent mode of spatial organization since any imbalances lead to severe degradation- and in some case even destruction- of the mosaic. Our model suggests that, over a broad range of of STDP parameters, synaptic plasticity shapes the spatial arrangement of synapses, favoring the formation of clustered efficacy engrams. PMID:28649195

  6. Input-dependent regulation of excitability controls dendritic maturation in somatosensory thalamocortical neurons.

    Science.gov (United States)

    Frangeul, Laura; Kehayas, Vassilis; Sanchez-Mut, Jose V; Fièvre, Sabine; Krishna-K, K; Pouchelon, Gabrielle; Telley, Ludovic; Bellone, Camilla; Holtmaat, Anthony; Gräff, Johannes; Macklis, Jeffrey D; Jabaudon, Denis

    2017-12-08

    Input from the sensory organs is required to pattern neurons into topographical maps during development. Dendritic complexity critically determines this patterning process; yet, how signals from the periphery act to control dendritic maturation is unclear. Here, using genetic and surgical manipulations of sensory input in mouse somatosensory thalamocortical neurons, we show that membrane excitability is a critical component of dendritic development. Using a combination of genetic approaches, we find that ablation of N-methyl-D-aspartate (NMDA) receptors during postnatal development leads to epigenetic repression of Kv1.1-type potassium channels, increased excitability, and impaired dendritic maturation. Lesions to whisker input pathways had similar effects. Overexpression of Kv1.1 was sufficient to enable dendritic maturation in the absence of sensory input. Thus, Kv1.1 acts to tune neuronal excitability and maintain it within a physiological range, allowing dendritic maturation to proceed. Together, these results reveal an input-dependent control over neuronal excitability and dendritic complexity in the development and plasticity of sensory pathways.

  7. Modulation of Dendritic Cell Function by Leishmania Parasites1

    Science.gov (United States)

    Soong, Lynn

    2009-01-01

    The interactions between Leishmania parasites and dendritic cells (DCs) are complex and involve paradoxical functions that can stimulate or halt T cell responses, leading to the control of infection or progression of disease. The magnitude and profile of DC activation vary greatly, depending upon the Leishmania species/strains, developmental stages, DC subsets, serum opsonization, and exogenous DC stimuli involved in the study. In general, the uptake of Leishmania parasites alone can trigger relatively weak and transient DC activation; however, the intracellular parasites (amastigotes) are capable of down-modulating LPS/IFN-γ-stimulated DC activation via multiple mechanisms. This review will highlight current data regarding the initial interaction of DC subsets with invading parasites, the alterations of DC signaling pathways and function by amastigotes, and the impact of DC functions on protective immunity and disease pathogenesis. Available information provides insight into the mechanisms by which DCs discriminate between the types of pathogens and regulate appropriate immune responses. PMID:18354154

  8. Modulation of dendritic cell function by Leishmania parasites.

    Science.gov (United States)

    Soong, Lynn

    2008-04-01

    The interactions between Leishmania parasites and dendritic cells (DCs) are complex and involve paradoxical functions that can stimulate or halt T cell responses, leading to the control of infection or progression of disease. The magnitude and profile of DC activation vary greatly, depending upon the Leishmania species/strains, developmental stages, DC subsets, serum opsonization, and exogenous DC stimuli involved in the study. In general, the uptake of Leishmania parasites alone can trigger relatively weak and transient DC activation; however, the intracellular parasites (amastigotes) are capable of down-modulating LPS/IFN-gamma-stimulated DC activation via multiple mechanisms. This review will highlight current data regarding the initial interaction of DC subsets with invading parasites, the alterations of DC signaling pathways and function by amastigotes, and the impact of DC functions on protective immunity and disease pathogenesis. Available information provides insight into the mechanisms by which DCs discriminate between the types of pathogens and regulate appropriate immune responses.

  9. Corticospinal excitability modulation during action observation.

    Science.gov (United States)

    Sartori, Luisa; Betti, Sonia; Castiello, Umberto

    2013-12-31

    This study used the transcranial magnetic stimulation/motor evoked potential (TMS/MEP) technique to pinpoint when the automatic tendency to mirror someone else's action becomes anticipatory simulation of a complementary act. TMS was delivered to the left primary motor cortex corresponding to the hand to induce the highest level of MEP activity from the abductor digiti minimi (ADM; the muscle serving little finger abduction) as well as the first dorsal interosseus (FDI; the muscle serving index finger flexion/extension) muscles. A neuronavigation system was used to maintain the position of the TMS coil, and electromyographic (EMG) activity was recorded from the right ADM and FDI muscles. Producing original data with regard to motor resonance, the combined TMS/MEP technique has taken research on the perception-action coupling mechanism a step further. Specifically, it has answered the questions of how and when observing another person's actions produces motor facilitation in an onlooker's corresponding muscles and in what way corticospinal excitability is modulated in social contexts.

  10. STDP and mental retardation: dysregulation of dendritic excitability in Fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Rhiannon M Meredith

    2010-06-01

    Full Text Available Development of cognitive function requires the formation and refinement of synaptic networks of neurons in the brain. Morphological abnormalities of synaptic spines occur throughout the brain in a wide variety of syndromic and non-syndromic disorders of mental retardation (MR. In both neurons from human post-mortem tissue and mouse models of retardation, the changes observed in synaptic spine and dendritic morphology can be subtle, in the range of 10-20% alterations for spine protrusion length and density. Functionally, synapses in hippocampus and cortex show deficits in long-term potentiation (LTP and long-term depression (LTD in an array of neurodevelopmental disorders including Down’s, Angelman, Fragile X and Rett syndrome. Recent studies have shown that in principle the machinery for synaptic plasticity is in place in these synapses, but that significant alterations in spike-timing-dependent plasticity (STDP induction rules exist in cortical synaptic pathways of Fragile X MR syndrome. In this model, the threshold for inducing timing-dependent long-term potentiation (tLTP is increased in these synapses. Increased postsynaptic activity can overcome this threshold and induce normal levels of tLTP. In this review, we bring together recent studies investigating STDP in neurodevelopmental learning disorders using Fragile X syndrome as a model and we argue that alterations in dendritic excitability underlie deficits seen in STDP. Known and candidate dendritic mechanisms that may underlie the plasticity deficits are discussed. Studying STDP in monogenic MR syndromes with clear deficits in information processing at the cognitive level also provides the field with an opportunity to make direct links between cognition and processing rules at the synapse during development.

  11. Priming Neural Circuits to Modulate Spinal Reflex Excitability

    OpenAIRE

    Estes, Stephen P.; Iddings, Jennifer A.; Field-Fote, Edelle C.

    2017-01-01

    While priming is most often thought of as a strategy for modulating neural excitability to facilitate voluntary motor control, priming stimulation can also be utilized to target spinal reflex excitability. In this application, priming can be used to modulate the involuntary motor output that often follows central nervous system injury. Individuals with spinal cord injury (SCI) often experience spasticity, for which antispasmodic medications are the most common treatment. Physical therapeutic/...

  12. Modulation of respiratory dendritic cells during Klebsiella pneumonia infection

    Science.gov (United States)

    2013-01-01

    Background Klebsiella pneumoniae is a leading cause of severe hospital-acquired respiratory tract infections and death but little is known regarding the modulation of respiratory dendritic cell (DC) subsets. Plasmacytoid DC (pDC) are specialized type 1 interferon producing cells and considered to be classical mediators of antiviral immunity. Method By using multiparameter flow cytometry analysis we have analysed the modulation of respiratory DC subsets after intratracheal Klebsiella pneumonia infection. Results Data indicate that pDCs and MoDC were markedly elevated in the post acute pneumonia phase when compared to mock-infected controls. Analysis of draining mediastinal lymph nodes revealed a rapid increase of activated CD103+ DC, CD11b+ DC and MoDC within 48 h post infection. Lung pDC identification during bacterial pneumonia was confirmed by extended phenotyping for 120G8, mPDCA-1 and Siglec-H expression and by demonstration of high Interferon-alpha producing capacity after cell sorting. Cytokine expression analysis of ex vivo-sorted respiratory DC subpopulations from infected animals revealed elevated Interferon-alpha in pDC, elevated IFN-gamma, IL-4 and IL-13 in CD103+ DC and IL-19 and IL-12p35 in CD11b+ DC subsets in comparison to CD11c+ MHC-class IIlow cells indicating distinct functional roles. Antigen-specific naive CD4+ T cell stimulatory capacity of purified respiratory DC subsets was analysed in a model system with purified ovalbumin T cell receptor transgenic naive CD4+ responder T cells and respiratory DC subsets, pulsed with ovalbumin and matured with Klebsiella pneumoniae lysate. CD103+ DC and CD11b+ DC subsets represented the most potent naive CD4+ T helper cell activators. Conclusion These results provide novel insight into the activation of respiratory DC subsets during Klebsiella pneumonia infection. The detection of increased respiratory pDC numbers in bacterial pneumonia may indicate possible novel pDC functions with respect to lung repair

  13. Modulation of cytokine production profiles in splenic dendritic cells ...

    African Journals Online (AJOL)

    We examined the role of splenic dendritic cells in immune response to Toxoplasma gondii infection in SAG1 (P30+) transgenic mice by investigating the kinetics of intracellular cytokines expression of IL-4, IL-10, IL-12 and IFN-γ by intracellular cytokine staining (ICS) using flow cytometry, and compared the results to those of ...

  14. Photothermally excited force modulation microscopy for broadband nanomechanical property measurements

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Ryan, E-mail: ryan.wagner@nist.gov; Killgore, Jason P. [Material Measurement Laboratory, National Institute of Standards and Technology, Boulder, Colorado 80305 (United States)

    2015-11-16

    We demonstrate photothermally excited force modulation microscopy (PTE FMM) for mechanical property characterization across a broad frequency range with an atomic force microscope (AFM). Photothermal excitation allows for an AFM cantilever driving force that varies smoothly as a function of drive frequency, thus avoiding the problem of spurious resonant vibrations that hinder piezoelectric excitation schemes. A complication of PTE FMM is that the sub-resonance cantilever vibration shape is fundamentally different compared to piezoelectric excitation. By directly measuring the vibrational shape of the cantilever, we show that PTE FMM is an accurate nanomechanical characterization method. PTE FMM is a pathway towards the characterization of frequency sensitive specimens such as polymers and biomaterials with frequency range limited only by the resonance frequency of the cantilever and the low frequency limit of the AFM.

  15. Probiotic modulation of dendritic cells and T cell responses in the intestine

    NARCIS (Netherlands)

    Meijerink, M.; Wells, J.

    2010-01-01

    Over the past decade it has become clear that probiotic and commensal interactions with mucosal dendritic cells in the lamina propria or epithelial cells lining the mucosa can modulate specific functions of the mucosal immune system. Innate pattern-recognition receptors such as TLRs, NLRs and CLRs

  16. Selective Estrogen Receptor Modulators Regulate Dendritic Spine Plasticity in the Hippocampus of Male Rats

    Directory of Open Access Journals (Sweden)

    Ignacio González-Burgos

    2012-01-01

    Full Text Available Some selective estrogen receptor modulators, such as raloxifene and tamoxifen, are neuroprotective and reduce brain inflammation in several experimental models of neurodegeneration. In addition, raloxifene and tamoxifen counteract cognitive deficits caused by gonadal hormone deprivation in male rats. In this study, we have explored whether raloxifene and tamoxifen may regulate the number and geometry of dendritic spines in CA1 pyramidal neurons of the rat hippocampus. Young adult male rats were injected with raloxifene (1 mg/kg, tamoxifen (1 mg/kg, or vehicle and killed 24 h after the injection. Animals treated with raloxifene or tamoxifen showed an increased numerical density of dendritic spines in CA1 pyramidal neurons compared to animals treated with vehicle. Raloxifene and tamoxifen had also specific effects in the morphology of spines. These findings suggest that raloxifene and tamoxifen may influence the processing of information by hippocampal pyramidal neurons by affecting the number and shape of dendritic spines.

  17. Modulational excitation of inhomogeneities in dusty ionospheric plasma

    Science.gov (United States)

    Kopnin, S. I.; Popel, S. I.; Morozova, T. I.

    2015-02-01

    The mechanism for the formation of inhomogeneities of the electron and ion densities in dusty ionospheric plasma as a result of the modulational instability of a pump electromagnetic wave caused by the excitation of dust acoustic perturbations is considered. The inhomogeneities of the electron density produced by the monochromatic radiation of heating facilities at altitudes of 80 and 100 km are estimated numerically. The possibility of excitation of relatively large inhomogeneities of the electron and ion densities δ n e( i)/ n e( i) ≈ 0.05 at altitudes of 80-100 km as a result of modulational interaction is demonstrated. The applicability domains of the method presented in this work are determined.

  18. Chemical modulation of electronic structure at the excited state

    Science.gov (United States)

    Li, F.; Song, C.; Gu, Y. D.; Saleem, M. S.; Pan, F.

    2017-12-01

    Spin-polarized electronic structures are the cornerstone of spintronics, and have thus attracted a significant amount of interest; in particular, researchers are looking into how to modulate the electronic structure to enable multifunctional spintronics applications, especially in half-metallic systems. However, the control of the spin polarization has only been predicted in limited two-dimensional systems with spin-polarized Dirac structures and is difficult to achieve experimentally. Here, we report the modulation of the electronic structure in the light-induced excited state in a typical half-metal, L a1 /2S r1 /2Mn O3 -δ . According to the spin-transport measurements, there appears a light-induced increase in magnetoresistance due to the enhanced spin scattering, which is closely associated with the excited spin polarization. Strikingly, the light-induced variation can be enhanced via alcohol processing and reduced by oxygen annealing. X-ray photoelectron spectroscopy measurements show that in the chemical process, a redox reaction occurs with a change in the valence of Mn. Furthermore, first-principles calculations reveal that the change in the valence of Mn alters the electronic structure and consequently modulates the spin polarization in the excited state. Our findings thus report a chemically tunable electronic structure, demonstrating interesting physics and the potential for multifunctional applications and ultrafast spintronics.

  19. Solving the Bloch equation with periodic excitation using harmonic balancing: application to Rabi modulated excitation.

    Science.gov (United States)

    Tahayori, Bahman; Johnston, Leigh A; Layton, Kelvin J; Farrell, Peter M; Mareels, Iven M Y

    2015-10-01

    In waveform design for magnetic resonance applications, periodic continuous-wave excitation offers potential advantages that remain largely unexplored because of a lack of understanding of the Bloch equation with periodic continuous-wave excitations. Using harmonic balancing techniques the steady state solutions of the Bloch equation with periodic excitation can be effectively solved. Moreover, the convergence speed of the proposed series approximation is such that a few terms in the series expansion suffice to obtain a very accurate description of the steady state solution. The accuracy of the proposed analytic approximate series solution is verified using both a simulation study as well as experimental data derived from a spherical phantom with doped water under continuous-wave excitation. Typically a five term series suffices to achieve a relative error of less than one percent, allowing for a very effective and efficient analytical design process. The opportunities for Rabi frequency modulated continuous-wave form excitation are then explored, based on a comparison with steady state free precession pulse sequences.

  20. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Roland El Ghazal

    2016-05-01

    Full Text Available In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1 in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4–deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.

  1. Immune modulation by dendritic-cell-based cancer vaccines

    Indian Academy of Sciences (India)

    2017-01-31

    Jan 31, 2017 ... The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells by modulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing the recombinant human immune system components to target the pro-tumour ...

  2. Scanning Ultrasound (SUS Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice.

    Directory of Open Access Journals (Sweden)

    Robert John Hatch

    Full Text Available Scanning ultrasound (SUS is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.

  3. Reward anticipation modulates primary motor cortex excitability during task preparation.

    Science.gov (United States)

    Bundt, Carsten; Abrahamse, Elger L; Braem, Senne; Brass, Marcel; Notebaert, Wim

    2016-11-15

    Task preparation has been associated with a transient suppression of corticospinal excitability (CSE) before target onset, but it is an open question to what extent CSE suppression during task preparation is susceptible to motivational factors. Here, we examined whether CSE suppression is modulated by reward anticipation, and, if so, how this modulation develops over time. We administered a cue-target delay paradigm in which 1000ms before target onset a cue was presented indicating whether or not reward could be obtained for fast and accurate responses in a Simon task. Single-pulse transcranial magnetic stimulation was applied over left primary motor cortex (M1) during the delay period (400, 600, or 800ms after cue onset) or 200ms after target onset, and electromyography was obtained from the right first dorsal interosseous muscle. Behaviorally, the anticipation of reward improved performance (i.e. faster reaction times). Most importantly, during reward anticipation we observed a linear decrease of motor evoked potential amplitudes that was absent when no reward was anticipated. This suggests that reward anticipation modulates CSE during task preparation. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Priming Neural Circuits to Modulate Spinal Reflex Excitability

    Science.gov (United States)

    Estes, Stephen P.; Iddings, Jennifer A.; Field-Fote, Edelle C.

    2017-01-01

    While priming is most often thought of as a strategy for modulating neural excitability to facilitate voluntary motor control, priming stimulation can also be utilized to target spinal reflex excitability. In this application, priming can be used to modulate the involuntary motor output that often follows central nervous system injury. Individuals with spinal cord injury (SCI) often experience spasticity, for which antispasmodic medications are the most common treatment. Physical therapeutic/electroceutic interventions offer an alternative treatment for spasticity, without the deleterious side effects that can accompany pharmacological interventions. While studies of physical therapeutic/electroceutic interventions have been published, a systematic comparison of these approaches has not been performed. The purpose of this study was to compare four non-pharmacological interventions to a sham-control intervention to assess their efficacy for spasticity reduction. Participants were individuals (n = 10) with chronic SCI (≥1 year) who exhibited stretch-induced quadriceps spasticity. Spasticity was quantified using the pendulum test before and at two time points after (immediate, 45 min delayed) each of four different physical therapeutic/electroceutic interventions, plus a sham-control intervention. Interventions included stretching, cyclic passive movement (CPM), transcutaneous spinal cord stimulation (tcSCS), and transcranial direct current stimulation (tDCS). The sham-control intervention consisted of a brief ramp-up and ramp-down of knee and ankle stimulation while reclined with legs extended. The order of interventions was randomized, and each was tested on a separate day with at least 48 h between sessions. Compared to the sham-control intervention, stretching, CPM, and tcSCS were associated with a significantly greater reduction in spasticity immediately after treatment. While the immediate effect was largest for stretching, the reduction persisted

  5. AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC-SIGN.

    Science.gov (United States)

    Serrano-Gómez, Diego; Martínez-Nuñez, Rocío T; Sierra-Filardi, Elena; Izquierdo, Nuria; Colmenares, María; Pla, Jesús; Rivas, Luis; Martinez-Picado, Javier; Jimenez-Barbero, Jesús; Alonso-Lebrero, José Luis; González, Salvador; Corbí, Angel L

    2007-07-01

    AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and (1)D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.

  6. Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells.

    Science.gov (United States)

    Silverman, Judith Maxwell; Clos, Joachim; Horakova, Eva; Wang, Adele Y; Wiesgigl, Martina; Kelly, Isabelle; Lynn, Miriam A; McMaster, W Robert; Foster, Leonard J; Levings, Megan K; Reiner, Neil E

    2010-11-01

    We investigated the properties of leishmania exosomes with respect to influencing innate and adaptive immune responses. Exosomes from Leishmania donovani modulated human monocyte cytokine responses to IFN-γ in a bimodal fashion by promoting IL-10 production and inhibiting that of TNF-α. Moreover, these vesicles were inhibitory with respect to cytokine responses (IL-12p70, TNF-α, and IL-10) by human monocyte-derived dendritic cells. Exosomes from wild-type (WT) L. donovani failed to prime monocyte-derived dendritic cells to drive the differentiation of naive CD4 T cells into IFN-γ-producing Th1 cells. In contrast, vesicles from heat shock protein (HSP)100(-/-) L. donovani showed a gain-of-function and proinflammatory phenotype and promoted the differentiation of naive CD4 lymphocytes into Th1 cells. Proteomic analysis showed that exosomes from WT and HSP100(-/-) leishmania had distinct protein cargo, suggesting that packaging of proteins into exosomes is dependent in part on HSP100. Treatment of C57BL/6 mice with WT L. donovani exosomes prior to challenge with WT organisms exacerbated infection and promoted IL-10 production in the spleen. In contrast, HSP100(-/-) exosomes promoted spleen cell production of IFN-γ and did not adversely affect hepatic parasite burdens. Furthermore, the proparasitic properties of WT exosomes were not species specific because BALB/c mice exposed to Leishmania major exosomes showed increased Th2 polarization and exacerbation of disease in response to infection with L. major. These findings demonstrate that leishmania exosomes are predominantly immunosuppressive. Moreover, to our knowledge, this is the first evidence to suggest that changes in the protein cargo of exosomes may influence the impact of these vesicles on myeloid cell function.

  7. Self-glycolipids modulate dendritic cells changing the cytokine profiles of committed autoreactive T cells.

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    Full Text Available The impact of glycolipids of non-mammalian origin on autoimmune inflammation has become widely recognized. Here we report that the naturally occurring mammalian glycolipids, sulfatide and β-GalCer, affect the differentiation and the quality of antigen presentation by monocyte-derived dendritic cells (DCs. In response to sulfatide and β-GalCer, monocytes develop into immature DCs with higher expression of HLA-DR and CD86 but lower expression of CD80, CD40 and CD1a and lower production of IL-12 compared to non-modulated DCs. Self-glycolipid-modulated DCs responded to lipopolysaccharide (LPS by changing phenotype but preserved low IL-12 production. Sulfatide, in particular, reduced the capacity of DCs to stimulate autoreactive Glutamic Acid Decarboxylase (GAD65 - specific T cell response and promoted IL-10 production by the GAD65-specific clone. Since sulfatide and β-GalCer induced toll-like receptor (TLR-mediated signaling, we hypothesize that self-glycolipids deliver a (tolerogenic polarizing signal to differentiating DCs, facilitating the maintenance of self-tolerance under proinflammatory conditions.

  8. Use of modulated excitation signals in medical ultrasound. Part III: High frame rate imaging

    DEFF Research Database (Denmark)

    Misaridis, Thanassis; Jensen, Jørgen Arendt

    2005-01-01

    For pt.II, see ibid., vol.52, no.2, p.192-207 (2005). This paper, the last from a series of three papers on the application of coded excitation signals in medical ultrasound, investigates the possibility of increasing the frame rate in ultrasound imaging by using modulated excitation signals. Lin...

  9. Dendritic Cell-Based Immunotherapy of Breast Cancer: Modulation by CpG

    National Research Council Canada - National Science Library

    Baar, Joseph

    2004-01-01

    ... in the United States in 2004. Thus, patients with MBC who fail conventional therapies are candidates for clinical trials using novel therapeutic approaches, including immunotherapy. Dendritic cells (DC...

  10. Modulation of motor excitability by metricality of tone sequences

    DEFF Research Database (Denmark)

    Cameron, David; Stewart, Lauren; Pearce, Marcus

    2012-01-01

    amplitude. These results demonstrate that the pure metrical structure of an auditory rhythm presented as generic parametrically varied tone sequences can influence motor excitability but that the picture may be more complex for real recordings of musical pieces. (PsycINFO Database Record (c) 2013 APA, all...

  11. Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

    Science.gov (United States)

    Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

  12. Phase-sensitive electric modulation of photoluminescence upon bichromatic excitation of atoms

    NARCIS (Netherlands)

    Astapenko, VA

    2005-01-01

    A new type of modulation of the photoluminescence intensity of atoms excited by a bichromatic laser radiation with the frequency ratio 1 : 2 is proposed and analysed. The modulation is produced by alternating electric field acting on atoms and occurs due to the quantum interference of the amplitudes

  13. S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification.

    Science.gov (United States)

    Teijaro, John R; Studer, Sean; Leaf, Nora; Kiosses, William B; Nguyen, Nhan; Matsuki, Kosuke; Negishi, Hideo; Taniguchi, Tadatsugu; Oldstone, Michael B A; Rosen, Hugh

    2016-02-02

    Blunting immunopathology without abolishing host defense is the foundation for safe and effective modulation of infectious and autoimmune diseases. Sphingosine 1-phosphate receptor 1 (S1PR1) agonists are effective in treating infectious and multiple autoimmune pathologies; however, mechanisms underlying their clinical efficacy are yet to be fully elucidated. Here, we uncover an unexpected mechanism of convergence between S1PR1 and interferon alpha receptor 1 (IFNAR1) signaling pathways. Activation of S1PR1 signaling by pharmacological tools or endogenous ligand sphingosine-1 phosphate (S1P) inhibits type 1 IFN responses that exacerbate numerous pathogenic conditions. Mechanistically, S1PR1 selectively suppresses the type I IFN autoamplification loop in plasmacytoid dendritic cells (pDCs), a specialized DC subset, for robust type I IFN release. S1PR1 agonist suppression is pertussis toxin-resistant, but inhibited by an S1PR1 C-terminal-derived transactivating transcriptional activator (Tat)-fusion peptide that blocks receptor internalization. S1PR1 agonist treatment accelerates turnover of IFNAR1, suppresses signal transducer and activator of transcription 1 (STAT1) phosphorylation, and down-modulates total STAT1 levels, thereby inactivating the autoamplification loop. Inhibition of S1P-S1PR1 signaling in vivo using the selective antagonist Ex26 significantly elevates IFN-α production in response to CpG-A. Thus, multiple lines of evidence demonstrate that S1PR1 signaling sets the sensitivity of pDC amplification of IFN responses, thereby blunting pathogenic immune responses. These data illustrate a lipid G-protein coupled receptor (GPCR)-IFNAR1 regulatory loop that balances effective and detrimental immune responses and elevated endogenous S1PR1 signaling. This mechanism will likely be advantageous in individuals subject to a range of inflammatory conditions.

  14. Yeast modulation of human dendritic cell cytokine secretion: an in vitro study.

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    Ida M Smith

    Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications

  15. Viewing instructions accompanying action observation modulate corticospinal excitability

    Directory of Open Access Journals (Sweden)

    David James Wright

    2016-02-01

    Full Text Available Action observation interventions may have the potential to contribute to improved motor function in motor (relearning settings by promoting functional activity and plasticity in the motor regions of the brain. Optimal methods for delivering such interventions, however, have yet to be established. This experiment investigated the effect on corticospinal excitability of manipulating the viewing instructions provided to participants (N = 21 prior to action observation. Specifically, motor evoked potential responses measured from the right hand muscles following single-pulse transcranial magnetic stimulation to the left motor cortex were compared when participants were instructed to observe finger-thumb opposition movement sequences: (i passively; (ii with the intent to imitate the observed movement; or (iii whilst simultaneously and actively imagining that they were performing the movement as they observed it. All three action observation viewing instructions facilitated corticospinal excitability to a greater extent than did observation of a static hand. In addition, the extent to which corticospinal excitability was facilitated was greater during combined observation and imagery, compared to passive observation. These findings have important implications for the design of action observation interventions in motor (relearning settings, where instructions that encourage observers to simultaneously imagine themselves performing the observed movement may offer the current optimal method for improving motor function through action observation.

  16. Escherichia coli heat-labile detoxified enterotoxin modulates dendritic cell function and attenuates allergic airway inflammation.

    Directory of Open Access Journals (Sweden)

    I-Ping Lin

    Full Text Available Various mutant forms of Escherichia coli heat-labile enterotoxin (LT have been used as a mucosal adjuvant for vaccines, as it enhances immune responses to specific antigens including antigen-specific IgA antibodies when administrated intranasally or orally. We hypothesized that a detoxified mutant form of LT, LTS61K, could modulate dendritic cell (DC function and alleviate allergen-induced airway inflammation. Two protocols, preventative and therapeutic, were used to evaluate the effects of LTS61K in a Dermatophagoides pteronyssinus (Der p-sensitized and challenged murine model of asthma. LTS61K or Der p-primed bone marrow-derived dendritic cells (BMDCs were also adoptively transferred into Der p-sensitized and challenged mice. Intranasal inoculations with LTS61K or LTS61K/Der p decreased allergen-induced airway inflammation and alleviated systemic TH2-type immune responses. Bronchoalveolar lavage fluid (BALF and sera from LTS61K/Der p-treated mice also had higher concentrations of Der p-specific immunoglobulin (Ig A than those of other groups. In vitro, BMDCs stimulated with Der p underwent cellular maturation and secreted proinflammatory cytokines interleukin (IL-6 and tumor necrosis factor (TNFα In contrast, Der p-stimulated BMDCs that were pretreated with LTS61K showed decreased IL-6 and TNFα production and were less mature. Intratracheal adoptive transfer of LTS61K- or LTS61K/Der p-primed BMDCs into Der p-sensitized mice reduced inflammatory cell infiltration and TH2-type chemokines in BALF and alleviated airway inflammation in treated mice. LTS61K influenced DC maturation and decreased inflammatory cytokine production. Moreover, LTS61K/Der p induced increased Der p-specific IgA production to decrease allergic TH2 cytokine responses and alleviated airway inflammation in Der p-sensitized mice. These results suggest that the immunomodulatory effects of LTS61K may have clinical applications for allergy and asthma treatment.

  17. Parietal transcranial direct current stimulation modulates primary motor cortex excitability.

    Science.gov (United States)

    Rivera-Urbina, Guadalupe Nathzidy; Batsikadze, Giorgi; Molero-Chamizo, Andrés; Paulus, Walter; Kuo, Min-Fang; Nitsche, Michael A

    2015-03-01

    The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto-motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto-motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto-motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short-interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto-motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity-dependent M1 excitability alterations primarily after P3 tDCS. Single-pulse TMS-elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto-motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse-TMS-elicited MEPs, and parieto-motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex-motor cortex connections suggest a relevant connectivity-driven effect. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Science.gov (United States)

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  19. Modulation of Dendritic Cell Responses by Parasites: A Common Strategy to Survive

    Directory of Open Access Journals (Sweden)

    César A. Terrazas

    2010-01-01

    Full Text Available Parasitic infections are one of the most important causes of morbidity and mortality in our planet and the immune responses triggered by these organisms are critical to determine their outcome. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. However, there is evidence showing that parasites can influence and regulate dendritic cell function in order to promote a more permissive environment for their survival. In this review we will focus on the strategies protozoan and helminth parasites have developed to interfere with dendritic cell activities as well as in the possible mechanisms involved.

  20. From single cells and single columns to cortical networks: dendritic excitability, coincidence detection and synaptic transmission in brain slices and brains

    Science.gov (United States)

    2017-01-01

    Although patch pipettes were initially designed to record extracellularly the elementary current events from muscle and neuron membranes, the whole‐cell and loose cell‐attached recording configurations proved to be useful tools for examination of signalling within and between nerve cells. In this Paton Prize Lecture, I will initially summarize work on electrical signalling within single neurons, describing communication between the dendritic compartments, soma and nerve terminals via forward‐ and backward‐propagating action potentials. The newly discovered dendritic excitability endows neurons with the capacity for coincidence detection of spatially separated subthreshold inputs. When these are occurring during a time window of tens of milliseconds, this information is broadcast to other cells by the initiation of bursts of action potentials (AP bursts). The occurrence of AP bursts critically impacts signalling between neurons that are controlled by target‐cell‐specific transmitter release mechanisms at downstream synapses even in different terminals of the same neuron. This can, in turn, induce mechanisms that underly synaptic plasticity when AP bursts occur within a short time window, both presynaptically in terminals and postsynaptically in dendrites. A fundamental question that arises from these findings is: ‘what are the possible functions of active dendritic excitability with respect to network dynamics in the intact cortex of behaving animals?’ To answer this question, I highlight in this review the functional and anatomical architectures of an average cortical column in the vibrissal (whisker) field of the somatosensory cortex (vS1), with an emphasis on the functions of layer 5 thick‐tufted cells (L5tt) embedded in this structure. Sensory‐evoked synaptic and action potential responses of these major cortical output neurons are compared with responses in the afferent pathway, viz. the neurons in primary somatosensory thalamus and in one

  1. Mesothelioma Tumor Cells Modulate Dendritic Cell Lipid Content, Phenotype and Function

    Science.gov (United States)

    Gardner, Joanne K.; Mamotte, Cyril D. S.; Patel, Priya; Yeoh, Teong Ling; Jackaman, Connie; Nelson, Delia J.

    2015-01-01

    Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+CD8α- DCs, CD4-CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses. PMID:25886502

  2. Mesothelioma tumor cells modulate dendritic cell lipid content, phenotype and function.

    Directory of Open Access Journals (Sweden)

    Joanne K Gardner

    Full Text Available Dendritic cells (DCs play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay, upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+ CD8α- DCs, CD4- CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.

  3. Brain transcranial direct current stimulation modulates motor excitability in mice.

    Science.gov (United States)

    Cambiaghi, Marco; Velikova, Svetla; Gonzalez-Rosa, Javier J; Cursi, Marco; Comi, Giancarlo; Leocani, Letizia

    2010-02-01

    Shortly after the application of weak transcranial direct current stimulation (tDCS) to the animal and human brain, changes in corticospinal excitability, which mainly depend on polarity, duration and current density of the stimulation protocol, have been reported. In humans, anodal tDCS has been reported to enhance motor-evoked potentials (MEPs) elicited by transcranial brain stimulation while cathodal tDCS has been shown to decrease them. Here we investigated the effects produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP size was significantly increased immediately after anodal tDCS, and was reduced after cathodal tDCS (approximately 20% vs. sham). Both effects declined towards basal levels in the following 10 min. Although the site and mechanisms of action of tDCS need to be more clearly identified, the directionality of effects of tDCS on mice MEPs is consistent with previous findings in humans. The feasibility of tDCS in mice suggests the potential applicability of this technique to assess the potential therapeutic options of brain polarization in animal models of neurological and neuropsychiatric diseases.

  4. Corticospinal excitability modulation to hand muscles during movement imagery.

    Science.gov (United States)

    Rossini, P M; Rossi, S; Pasqualetti, P; Tecchio, F

    1999-03-01

    Motor evoked potentials (MEPs) to magnetic transcranial stimulation (TCS) were recorded from right abductor digiti minimi (ADM) and first dorsal interosseous (FDI) muscles, sharing the same peripheral innervation but engaged in two different motor demands. In seven healthy and trained subjects, the latencies, amplitudes and variability of MEPs were investigated under the following, randomly intermingled, conditions: full muscular and mental relaxation; mental simulation of selective index finger or little finger abduction; mental non-motor activity (arithmetical calculation); and real motor task (little and index finger abduction). The whole procedure was performed by continuous audiovisual monitoring of electromyographic 'silence' in the tested muscles. The maximal facilitatory effects (= latency shortening and amplitude increase) on MEPs were induced by the real motor task. An amplitude potentiation of MEPs in both tested muscles was present during non-motor mental activity, in comparison to basal values. A further amplitude potentiation, without latency shifts, was confined to the muscle acting as 'prime mover' for the mentally simulated movement, according to the motor program dispatched but not executed by the subject. Similar results were also found in the F-wave, showing that mental simulation affects spinal motoneuronal excitability as well, although -- due to the lack of MEP and F-wave latency shift -- the main effect takes place at cortical level. The study shows that movement imagery can focus specific facilitation on the prime-mover muscle for the mentally simulated movement. This is mainly evident on FDI muscle, which controls fingers (i.e. the index) with highly corticalized motor representation.

  5. Modulation of Human Corticospinal Excitability by Paired Associative Stimulation

    Directory of Open Access Journals (Sweden)

    Richard G. Carson

    2013-12-01

    Full Text Available Paired Associative Stimulation (PAS has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS delivered to the contralateral primary motor cortex (M1. Repeated pairing of the stimuli (i.e. association over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI. It has been suggested that these effects represent a form of associative long-term potentiation (LTP and depression (LTD that bears resemblance to spike-timing dependent plasticity (STDP as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasising the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation.

  6. Self-modulated dynamics of a relativistic charged particle beam in plasma wake field excitation

    Energy Technology Data Exchange (ETDEWEB)

    Akhter, T.; Fedele, R. [Dipartimento di Fisica ‘Ettore Pancini’, Università di Napoli Federico II and INFN Sezione di Napoli, Napoli (Italy); Nicola, S. De [CNR-SPIN and INFN Sezione di Napoli, Napoli (Italy); Tanjia, F. [Dipartimento di Fisica ‘Ettore Pancini’, Università di Napoli Federico II and INFN Sezione di Napoli, Napoli (Italy); Jovanović, D. [Institute of Physics, University of Belgrade, Belgrade (Serbia); Mannan, A. [Department of Physics, Jahangirnagar University, Savar, Dhaka (Bangladesh)

    2016-09-01

    The self-modulated dynamics of a relativistic charged particle beam is provided within the context of the theory of plasma wake field excitation. The self-consistent description of the beam dynamics is provided by coupling the Vlasov equation with a Poisson-type equation relating the plasma wake potential to the beam density. An analysis of the beam envelope self-modulation is then carried out and the criteria for the occurrence of the instability are discussed thereby.

  7. The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells.

    Directory of Open Access Journals (Sweden)

    Haydn T Kissick

    Full Text Available The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. In silico analysis uncovered major alterations in gene expression in MARCO deficient dendritic cells resulting in dramatic alterations in key dendritic cell-specific pathways and functions. Specifically, changes in CD209, FCGR4 and Complement factors can have major consequences on DC-mediated innate responses. Notably, these perturbations were magnified following activation with the TLR-4 agonist lipopolysaccharide. To validate our in silico data, we challenged DC's with various agonists that recognize all mouse TLRs and assessed expression of a set of immune and inflammatory marker genes. This approach identified a differential contribution of MARCO to TLR activation and validated a major role for MARCO in mounting an inflammatory response. Together, our data demonstrate that MARCO differentially affects TLR-induced DC activation and suggest targeting of MARCO could lead to different outcomes that depend on the inflammatory context encountered by DC.

  8. Memory Deficits Are Associated with Impaired Ability to Modulate Neuronal Excitability in Middle-Aged Mice

    Science.gov (United States)

    Kaczorowski, Catherine C.; Disterhoft, John F.

    2009-01-01

    Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…

  9. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    Science.gov (United States)

    Garcia, Bonnie G.; Neely, M. Diana

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion–induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease. PMID:20118184

  10. Modulations of NeuroD activity contribute to the differential effects of morphine and fentanyl on dendritic spine stability

    Science.gov (United States)

    Hui, Zheng; Zeng, Yan; Chu, Ji; Kam, Angel YuetFang; Loh, Horace H.; Law, Ping-Yee

    2010-01-01

    The cellular level of neurogenic differentiation 1 (NeuroD) is modulated differentially by μ-opioid receptor agonists: fentanyl increases NeuroD level by reducing the amount of miR-190, an inhibitor of NeuroD expression, whereas morphine does not alter NeuroD level. In the current study, NeuroD activity was demonstrated to be also under agonist-dependent regulation. After three-day treatment, morphine and fentanyl decreased the activity of the Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), which phosphorylates and activates NeuroD. Because NeuroD activity is determined by both the CaMKIIα activity and the cellular NeuroD level, the overall NeuroD activity was reduced by morphine, but maintained during fentanyl treatment. The differential effects of agonists on NeuroD activity were further confirmed by measuring the mRNA levels of four NeuroD downstream targets: doublecortin, Notch1, NeuroD4 and Roundabout 1. Decreased dendritic spine stability and μ-opioid receptor signaling capability were also observed when NeuroD activity was attenuated by miR-190 overexpression or treatment with KN93, a CaMKIIα inhibitor. The decrease could be rescued by NeuroD overexpression which restored NeuroD activity to the basal level. Furthermore, elevating NeuroD activity attenuated the morphine-induced decrease in dendritic spine stability. Therefore, by regulating NeuroD activity, μ-opioid receptor agonists modulate the stability of dendritic spines. PMID:20554861

  11. Cigarette smoke differentially modulates dendritic cell maturation and function in time

    NARCIS (Netherlands)

    Givi, Masoumeh Ezzati; Folkerts, Gert; Wagenaar, Gerry T M; Redegeld, Frank A; Mortaz, Esmaeil

    2015-01-01

    BACKGROUND: Dendritic cells (DCs) as professional antigen presenting cells (APCs) play a critical role in the regulation of host immune responses. DCs evolve from immature, antigen-capturing cells, to mature antigen-presenting cells. The relative contribution of DCs to cigarette smoke-induced

  12. Modulation of Dendritic Cell Activation and Subsequent Th1 Cell Polarization by Lidocaine

    Science.gov (United States)

    Chung, Yeonseok

    2015-01-01

    Dendritic cells play an essential role in bridging innate and adaptive immunity by recognizing cellular stress including pathogen- and damage-associated molecular patterns and by shaping the types of antigen-specific T cell immunity. Although lidocaine is widely used in clinical settings that trigger cellular stress, it remains unclear whether such treatment impacts the activation of innate immune cells and subsequent differentiation of T cells. Here we showed that lidocaine inhibited the production of IL–6, TNFα and IL–12 from dendritic cells in response to toll-like receptor ligands including lipopolysaccharide, poly(I:C) and R837 in a dose-dependent manner. Notably, the differentiation of Th1 cells was significantly suppressed by the addition of lidocaine while the same treatment had little effect on the differentiation of Th17, Th2 and regulatory T cells in vitro. Moreover, lidocaine suppressed the ovalbumin-specific Th1 cell responses in vivo induced by the adoptive transfer of ovalbumin-pulsed dendritic cells. These results demonstrate that lidocaine inhibits the activation of dendritic cells in response to toll-like receptor signals and subsequently suppresses the differentiation of Th1 cell responses. PMID:26445366

  13. Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs

    Directory of Open Access Journals (Sweden)

    Abhilash ePonnath

    2014-07-01

    Full Text Available Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds or presented on a sound-by-sound basis (ms, experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses, excitability (spikes / acoustic stimulus to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted < 2 s and, in different cells, excitability either decreased, increased or shifted in latency. Within cells, the modulatory effect of sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene.

  14. Spectral models of additive and modulation noise in speech and phonatory excitation signals

    Science.gov (United States)

    Schoentgen, Jean

    2003-01-01

    The article presents spectral models of additive and modulation noise in speech. The purpose is to learn about the causes of noise in the spectra of normal and disordered voices and to gauge whether the spectral properties of the perturbations of the phonatory excitation signal can be inferred from the spectral properties of the speech signal. The approach to modeling consists of deducing the Fourier series of the perturbed speech, assuming that the Fourier series of the noise and of the clean monocycle-periodic excitation are known. The models explain published data, take into account the effects of supraglottal tremor, demonstrate the modulation distortion owing to vocal tract filtering, establish conditions under which noise cues of different speech signals may be compared, and predict the impossibility of inferring the spectral properties of the frequency modulating noise from the spectral properties of the frequency modulation noise (e.g., phonatory jitter and frequency tremor). The general conclusion is that only phonatory frequency modulation noise is spectrally relevant. Other types of noise in speech are either epiphenomenal, or their spectral effects are masked by the spectral effects of frequency modulation noise.

  15. Damage detection and locating using tone burst and continuous excitation modulation method

    Science.gov (United States)

    Li, Zheng; Wang, Zhi; Xiao, Li; Qu, Wenzhong

    2014-03-01

    Among structural health monitoring techniques, nonlinear ultrasonic spectroscopy methods are found to be effective diagnostic approach to detecting nonlinear damage such as fatigue crack, due to their sensitivity to incipient structural changes. In this paper, a nonlinear ultrasonic modulation method was developed to detect and locate a fatigue crack on an aluminum plate. The method is different with nonlinear wave modulation method which recognizes the modulation of low-frequency vibration and high-frequency ultrasonic wave; it recognizes the modulation of tone burst and high-frequency ultrasonic wave. In the experiment, a Hanning window modulated sinusoidal tone burst and a continuous sinusoidal excitation were simultaneously imposed on the PZT array which was bonded on the surface of an aluminum plate. The modulations of tone burst and continuous sinusoidal excitation was observed in different actuator-sensor paths, indicating the presence and location of fatigue crack. The results of experiments show that the proposed method is capable of detecting and locating the fatigue crack successfully.

  16. Hyaluronic acid graft polymers displaying peptide antigen modulate dendritic cell response in vitro

    Science.gov (United States)

    Chittasupho, Chuda; Sestak, Joshua; Shannon, Laura; Siahaan, Teruna J.; Vines, Charlotte M.; Berkland, Cory

    2014-01-01

    A novel oxime grafting scheme was utilized to conjugate an ICAM-1 ligand (LABL), a cellular antigen ovalbumin (OVA), or both peptides simultaneously to hyaluronic acid (HA). Samples of HA only and the various peptide grafted HA were found to bind to dendritic cells (DCs). HA with grafted LABL and OVA showed the greatest binding to DCs. Dendritic cells treated with HA, HA with grafted LABL, or HA with grafted LABL and OVA, significantly suppressed T cell and DC conjugate formation, T cell proliferation and reduced proinflammatory cytokine production compared to untreated cells. These results suggest that HA serves as an effective backbone for multivalent ligand presentation for inhibiting T cell response to antigen presentation. In addition, multivalent display of both antigen and an ICAM-1inhibitor (LABL) may enhance binding to DCs and could potentially disrupt cellular signaling leading to autoimmunity. PMID:24283935

  17. Activation of Human Dendritic Cells Is Modulated by Components of the Outer Membranes of Neisseria meningitidis

    OpenAIRE

    Al-Bader, Tamara; Christodoulides, Myron; Heckels, John E.; Holloway, Judith; Semper, Amanda E.; Friedmann, Peter S.

    2003-01-01

    Neisseria meningitidis serogroup B is a major cause of life-threatening meningitis and septicemia worldwide, and no effective vaccine is available. Initiation of innate and acquired immune responses to N. meningitidis is likely to be dependent on cellular responses of dendritic cells (DC) to antigens present in the outer membrane (OM) of the meningococcus. In this study, the responses of human monocyte-derived DC (mo-DC) to OM isolated from parent (lipopolysaccharide [LPS]-replete) meningococ...

  18. Dietary cholesterol modulates the excitability of rabbit hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Wang, Desheng; Schreurs, Bernard G

    2010-08-02

    Previous work has shown high dietary cholesterol can affect learning and memory including rabbit eyeblink conditioning and this effect may be due to increased membrane cholesterol and enhanced hippocampal amyloid beta production. This study investigated whether dietary cholesterol modulates rabbit hippocampal CA1 neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2 percent cholesterol or normal chow for 8 weeks revealed changes including decreased after-hyperpolarization amplitudes (AHPs) - an index of membrane excitability shown to be important for rabbit eyeblink conditioning. This index was reversed by adding copper to drinking water - a dietary manipulation that can retard rabbit eyeblink conditioning. Evidence of cholesterol effects on membrane excitability was provided by application of methyl-beta-cyclodextrin, a compound that reduces membrane cholesterol, which increased the excitability of hippocampal CA1 neurons.

  19. Identification of genetic loci in Lactobacillus plantarum that modulate the immune response of dendritic cells using comparative genome hybridization.

    Directory of Open Access Journals (Sweden)

    Marjolein Meijerink

    Full Text Available BACKGROUND: Probiotics can be used to stimulate or regulate epithelial and immune cells of the intestinal mucosa and generate beneficial mucosal immunomodulatory effects. Beneficial effects of specific strains of probiotics have been established in the treatment and prevention of various intestinal disorders, including allergic diseases and diarrhea. However, the precise molecular mechanisms and the strain-dependent factors involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we aimed to identify gene loci in the model probiotic organism Lactobacillus plantarum WCFS1 that modulate the immune response of host dendritic cells. The amounts of IL-10 and IL-12 secreted by dendritic cells (DCs after stimulation with 42 individual L. plantarum strains were measured and correlated with the strain-specific genomic composition using comparative genome hybridisation and the Random Forest algorithm. This in silico "gene-trait matching" approach led to the identification of eight candidate genes in the L. plantarum genome that might modulate the DC cytokine response to L. plantarum. Six of these genes were involved in bacteriocin production or secretion, one encoded a bile salt hydrolase and one encoded a transcription regulator of which the exact function is unknown. Subsequently, gene deletions mutants were constructed in L. plantarum WCFS1 and compared to the wild-type strain in DC stimulation assays. All three bacteriocin mutants as well as the transcription regulator (lp_2991 had the predicted effect on cytokine production confirming their immunomodulatory effect on the DC response to L. plantarum. Transcriptome analysis and qPCR data showed that transcript level of gtcA3, which is predicted to be involved in glycosylation of cell wall teichoic acids, was substantially increased in the lp_2991 deletion mutant (44 and 29 fold respectively. CONCLUSION: Comparative genome hybridization led to the identification of gene loci in L

  20. Improvement of axial excitation confinement in temporal focusing-based multiphoton microscopy via spatially modulated illumination

    Science.gov (United States)

    Chang, Chia-Yuan; Chen, Shean-Jen

    2017-02-01

    Conventional temporal focusing-based multiphoton excitation microscopy (TFMPEM) can offer widefield optical sectioning with an axial excitation confinement (AEC) of a few microns. Herein, a developed TFMPEM with a digital micromirror device (DMD), acting as the blazed grating for light spatial dispersion and simultaneous patterned illumination, has been extended to implement spatially modulated illumination at structured frequency and orientation. By implementing the spatially modulated illumination, the beam coverage at the back-focal aperture of the objective lens can be increased. As a result, the AEC can be condensed from 3.0 μm to 1.5 μm in full width at half maximum for a 2-fold enhancement. Furthermore, by using HiLo microscopy with two structured illuminations at the same spatial frequency but different orientation, biotissue images according to the structured illumination with condensed AEC is obviously superior in contrast and scattering suppression.

  1. Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs.

    Science.gov (United States)

    Ponnath, Abhilash; Farris, Hamilton E

    2014-01-01

    Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds) or presented on a sound-by-sound basis (ms), experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses), excitability (spikes/acoustic stimulus) to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized) auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene.

  2. Modulation of motor cortex excitability by physical similarity with an observed hand action.

    Directory of Open Access Journals (Sweden)

    Marie-Christine Désy

    Full Text Available The passive observation of hand actions is associated with increased motor cortex excitability, presumably reflecting activity within the human mirror neuron system (MNS. Recent data show that in-group ethnic membership increases motor cortex excitability during observation of culturally relevant hand gestures, suggesting that physical similarity with an observed body part may modulate MNS responses. Here, we ask whether the MNS is preferentially activated by passive observation of hand actions that are similar or dissimilar to self in terms of sex and skin color. Transcranial magnetic stimulation-induced motor evoked potentials were recorded from the first dorsal interosseus muscle while participants viewed videos depicting index finger movements made by female or male participants with black or white skin color. Forty-eight participants equally distributed in terms of sex and skin color participated in the study. Results show an interaction between self-attributes and physical attributes of the observed hand in the right motor cortex of female participants, where corticospinal excitability is increased during observation of hand actions in a different skin color than that of the observer. Our data show that specific physical properties of an observed action modulate motor cortex excitability and we hypothesize that in-group/out-group membership and self-related processes underlie these effects.

  3. Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability.

    Science.gov (United States)

    Ziminski, Joseph J; Hessler, Sabine; Margetts-Smith, Gabriella; Sieburg, Meike C; Crombag, Hans S; Koya, Eisuke

    2017-03-22

    Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP- neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell.SIGNIFICANCE STATEMENT Sparsely distributed sets of neurons called "neuronal ensembles" encode learned associations about food and cues predictive of its availability. Widespread changes in neuronal excitability have been observed in limbic brain areas after associative learning, but little is known about the excitability changes that

  4. Modulation of visual cortical excitability by working memory: effect of luminance contrast of mental imagery

    Directory of Open Access Journals (Sweden)

    Zaira eCattaneo

    2011-02-01

    Full Text Available Although much is known about the impact of stimulus properties such as luminance contrast, spatial frequency and orientation on visually evoked neural activity, much less is known about how they modulate neural activity when they are properties of a mental image held in working memory (WM. Here we addressed this question by investigating how a parametric manipulation of an imagined stimulus attribute affects neuronal excitability in the early visual cortex. We manipulated luminance contrast, a stimulus property known to strongly affect the magnitude of neuronal responses in early visual areas. Luminance contrast modulated neuronal excitability, as assessed by the frequency of phosphenes induced by transcranial magnetic stimulation (TMS with the exact nature of this modulation depending on TMS intensity. These results point to a strong overlap in the neuronal processes underlying visual perception and mental imagery: not only does WM maintenance selectively engage neurons which are tuned to the maintained attribute (as has previously been shown, but the extent to which those neurons are activated depends on the luminance contrast (as is the case with visually-evoked responses. From a methodological viewpoint, these results suggest that assessment of visual cortical excitability using TMS is affected by the TMS intensity used to probe the neuronal population.

  5. Noise Spectrum of a Semiconductor Optical Amplifier Excited by a Modulated Signal

    DEFF Research Database (Denmark)

    Blaaberg, Søren; Mørk, Jesper

    2014-01-01

    A detailed analysis of the noise spectrum of a semiconductor optical amplifier excited by an amplitude-modulated input signal is presented. This extends the well-established theory for the case of continuous-wave input signals and is relevant for various applications within optical signal......, and modulation frequency, is investigated and explained. We find several interesting modifications to the spectra compared with the continuous-wave case. In particular, the side-bands present in the input-signal lead via four-wave mixing effects to additional structure in the spectra as well as additional noise...... processing. One important example is the analysis of noise in microwave photonic elements based on slow-light propagation in semiconductor optical amplifiers. Expressions for the noise spectra are derived and the dependence on important operation parameters, such as input power, modulation depth...

  6. The Soil Bacterium Methylococcus capsulatus Bath Interacts with Human Dendritic Cells to Modulate Immune Function.

    Science.gov (United States)

    Indrelid, Stine; Kleiveland, Charlotte; Holst, René; Jacobsen, Morten; Lea, Tor

    2017-01-01

    The prevalence of inflammatory bowel disease (IBD) has increased in Western countries during the course of the twentieth century, and is evolving to be a global disease. Recently we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD. The mechanism behind the effect has this far not been identified. Here, for the first time we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation. We characterize the immune modulatory properties of M. capsulatus and compare its immunological properties to those of another Gram-negative gammaproteobacterium, the commensal Escherichia coli K12, and the immune modulatory Gram-positive probiotic bacterium, Lactobacillus rhamnosus GG in vitro. M. capsulatus induces intermediate phenotypic and functional DC maturation. In a mixed lymphocyte reaction M. capsulatus-primed monocyte-derived dendritic cells (MoDCs) enhance T cell expression of CD25, the γ-chain of the high affinity IL-2 receptor, supports cell proliferation, and induce a T cell cytokine profile different from both E. coli K12 and Lactobacillus rhamnosus GG. M. capsulatus Bath thus interacts specifically with MoDC, affecting MoDC maturation, cytokine profile, and subsequent MoDC directed T cell polarization.

  7. Chlamydia pneumoniae and Chlamydia Trachomatis Infection Differentially Modulates Human Dendritic Cell Line (MUTZ) Differentiation and Activation.

    Science.gov (United States)

    Armitage, C W; O'Meara, C P; Beagley, K W

    2015-07-01

    Chlamydia trachomatis and Chlamydia pneumoniae are important human pathogens that infect the urogenital/anorectal and respiratory tracts, respectively. Whilst the ability of these bacteria to infect epithelia is well defined, there is also considerable evidence of infection of leucocytes, including dendritic cells (DCs). Using a human dendritic cell line (MUTZ), we demonstrate that the infection and replication of chlamydiae inside DCs is species and serovar specific and that live infection with C. pneumoniae is required to upregulate costimulatory markers CD80, CD83 and human leucocyte antigen (HLA)-DR on MUTZ cells, as well as induce secretion of interleukin (IL)-2, IL-6, IL-8, IL-12 (p70), interferon-gamma and tumour necrosis factor-alpha Conversely, C. trachomatis serovar D failed to upregulate DC costimulatory markers, but did induce secretion of high concentrations of IL-8. Interestingly, we also observed that infection of MUTZ cells with C. pneumoniae or C. trachomatis serovar L2, whilst not replicative, remained infectious and upregulated lymph node migratory marker CCR7 mRNA. Taken together, these data confirm the findings of other groups using primary DCs and demonstrate the utility of MUTZ cells for further studies of chlamydial infection. © 2015 John Wiley & Sons Ltd.

  8. Observing object lifting errors modulates cortico-spinal excitability and improves object lifting performance.

    Science.gov (United States)

    Buckingham, Gavin; Wong, Jeremy D; Tang, Minnie; Gribble, Paul L; Goodale, Melvyn A

    2014-01-01

    Observing the actions of others has been shown to modulate cortico-spinal excitability and affect behaviour. However, the sensorimotor consequences of observing errors are not well understood. Here, participants watched actors lift identically weighted large and small cubes which typically elicit expectation-based fingertip force errors. One group of participants observed the standard overestimation and underestimation-style errors that characterise early lifts with these cubes (Error video--EV). Another group watched the same actors performing the well-adapted error-free lifts that characterise later, well-practiced lifts with these cubes (No error video--NEV). We then examined actual object lifting performance in the subjects who watched the EV and NEV. Despite having similar cognitive expectations and perceptions of heaviness, the group that watched novice lifters making errors themselves made fewer overestimation-style errors than those who watched the expert lifts. To determine how the observation of errors alters cortico-spinal excitability, we measured motor evoked potentials in separate group of participants while they passively observed these EV and NEV. Here, we noted a novel size-based modulation of cortico-spinal excitability when observing the expert lifts, which was eradicated when watching errors. Together, these findings suggest that individuals' sensorimotor systems are sensitive to the subtle visual differences between observing novice and expert performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Reciprocal Modulation of IK1-INa Extends Excitability in Cardiac Ventricular Cells.

    Science.gov (United States)

    Varghese, Anthony

    2016-01-01

    excitable at high GK1 values. Reciprocal modulation of the inwardly rectifying potassium current and the fast inward sodium current may have a functional role in allowing cardiac tissue to remain excitable when IK1 is upregulated.

  10. Hearing loss alters serotonergic modulation of intrinsic excitability in auditory cortex.

    Science.gov (United States)

    Rao, Deepti; Basura, Gregory J; Roche, Joseph; Daniels, Scott; Mancilla, Jaime G; Manis, Paul B

    2010-11-01

    early sensorineural hearing loss affects the ability of 5-HT receptor activation to modulate A1 pyramidal cell excitability.

  11. Molecular mechanism of modulation of nociceptive neuron membrane excitability by a tripeptide.

    Science.gov (United States)

    Shelykh, T N; Rogachevsky, I V; Nozdrachev, A D; Veselkina, O S; Podzorova, S A; Krylov, B V; Plakhova, V B

    2016-01-01

    Using the whole-cell patch-clamp method, the ability of arginine-containing tripeptide Ac-RER-NH2, dipeptide Ac-RR-NH2, and free Arg molecule to modulate the membrane excitability of nociceptors was studied. Extracellular Ac-RER-NH2 upon interaction with the outer membrane of the nociceptive neuron decreases the Zeff value of the activation gating system of Nav1.8 channels. Thus, the tripeptide Ac-RER-NH2 can be considered as a new effective and safe analgesic.

  12. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Directory of Open Access Journals (Sweden)

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  13. Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells.

    Science.gov (United States)

    Bosseto, Maira Cegatti; Palma, Patricia Vianna Bonini; Covas, Dimas Tadeu; Giorgio, Selma

    2010-02-01

    Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasite Leishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro-inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response.

  14. Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Eric R. Secor

    2013-01-01

    Full Text Available The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr, a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA-induced murine model of allergic airway disease (AAD. However, sBr’s effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL, spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes. OVA-specific IgE and OVA TET+ cells were decreased. sBr reduced CD11c+ dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena.

  15. Remote modulation of network excitability during deep brain stimulation for epilepsy.

    Science.gov (United States)

    Li, Dong-Hong; Yang, Xiao-Feng

    2017-04-01

    Deep brain stimulation (DBS) has become a well-accepted medical therapy in the treatment of movement disorders such as Parkinson's disease, and is currently under investigation as a treatment for other disorders, including epilepsy. Although DBS is widely used, its therapeutic mechanisms remain poorly understood. Recent research shows that seizures are network-level phenomena, but the incomplete knowledge of neural circuit function has left a gap in our understanding of how disruption at a molecular or cellular level generates epilepsy. In addition, DBS may potentially provide the opportunity to selectively modulate targeted brain regions and related networks. Therefore, a better understanding of the relationship between normal neural networks and epileptogenic networks, as well as the role of DBS in the modulation of neural networks will help us to find the optimal stimulation targets and parameters to achieve a better therapeutic effect. This review will outline the most recent advances in the relationship between normal brain networks and epileptogenic networks, and the modulation of DBS on the excitability of epileptogenic networks. We will then discuss how to optimize DBS stimulation targets and parameters by taking into consideration the concept of network modulation in order to improve treatment of epilepsy in the future. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  16. The Modulation of Corticospinal Excitability during Motor Imagery of Actions with Objects

    Science.gov (United States)

    Mizuguchi, Nobuaki; Sakamoto, Masanori; Muraoka, Tetsuro; Nakagawa, Kento; Kanazawa, Shoichi; Nakata, Hiroki; Moriyama, Noriyoshi; Kanosue, Kazuyuki

    2011-01-01

    We investigated whether corticospinal excitability during motor imagery of actions (the power or the pincer grip) with objects was influenced by actually touching objects (tactile input) and by the congruency of posture with the imagined action (proprioceptive input). Corticospinal excitability was assessed by monitoring motor evoked potentials (MEPs) in the first dorsal interosseous following transcranial magnetic stimulation over the motor cortex. MEPs were recorded during imagery of the power grip of a larger-sized ball (7 cm) or the pincer grip of a smaller-sized ball (3 cm)—with or without passively holding the larger-sized ball with the holding posture or the smaller-sized ball with the pinching posture. During imagery of the power grip, MEPs amplitude was increased only while the actual posture was the same as the imagined action (the holding posture). On the other hand, during imagery of the pincer grip while touching the ball, MEPs amplitude was enhanced in both postures. To examine the pure effect of touching (tactile input), we recorded MEPs during imagery of the power and pincer grip while touching various areas of an open palm with a flat foam pad. The MEPs amplitude was not affected by the palmer touching. These findings suggest that corticospinal excitability during imagery with an object is modulated by actually touching an object through the combination of tactile and proprioceptive inputs. PMID:22022491

  17. Flow angle dependent photoacoustic Doppler power spectra under intensity-modulated continuous wave laser excitation

    Directory of Open Access Journals (Sweden)

    Yu Tong

    2016-02-01

    Full Text Available Photoacoustic Doppler (PAD power spectra showing an evident Doppler shift represent the major characteristics of the continuous wave-excited or burst wave-excited versions of PAD flow measurements. In this paper, the flow angle dependences of the PAD power spectra are investigated using an experiment setup that was established based on intensity-modulated continuous wave laser excitation. The setup has an overall configuration that is similar to a previously reported configuration, but is more sophisticated in that it accurately aligns the laser illumination with the ultrasound detection process, and in that it picks up the correct sample position. In the analysis of the power spectra data, we find that the background power spectra can be extracted by combining the output signals from the two channels of the lock-in amplifier, which is very useful for identification of the PAD power spectra. The power spectra are presented and analyzed in opposite flow directions, at different flow speeds, and at different flow angles. The power spectra at a 90° flow angle show the unique properties of symmetrical shapes due to PAD broadening. For the other flow angles, the smoothed power spectra clearly show a flow angle cosine relationship.

  18. Immune Reactions against Gene Gun Vaccines Are Differentially Modulated by Distinct Dendritic Cell Subsets in the Skin.

    Directory of Open Access Journals (Sweden)

    Corinna Stefanie Weber

    Full Text Available The skin accommodates multiple dendritic cell (DC subsets with remarkable functional diversity. Immune reactions are initiated and modulated by the triggering of DC by pathogen-associated or endogenous danger signals. In contrast to these processes, the influence of intrinsic features of protein antigens on the strength and type of immune responses is much less understood. Therefore, we investigated the involvement of distinct DC subsets in immune reactions against two structurally different model antigens, E. coli beta-galactosidase (betaGal and chicken ovalbumin (OVA under otherwise identical conditions. After epicutaneous administration of the respective DNA vaccines with a gene gun, wild type mice induced robust immune responses against both antigens. However, ablation of langerin+ DC almost abolished IgG1 and cytotoxic T lymphocytes against betaGal but enhanced T cell and antibody responses against OVA. We identified epidermal Langerhans cells (LC as the subset responsible for the suppression of anti-OVA reactions and found regulatory T cells critically involved in this process. In contrast, reactions against betaGal were not affected by the selective elimination of LC, indicating that this antigen required a different langerin+ DC subset. The opposing findings obtained with OVA and betaGal vaccines were not due to immune-modulating activities of either the plasmid DNA or the antigen gene products, nor did the differential cellular localization, size or dose of the two proteins account for the opposite effects. Thus, skin-borne protein antigens may be differentially handled by distinct DC subsets, and, in this way, intrinsic features of the antigen can participate in immune modulation.

  19. Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function.

    Directory of Open Access Journals (Sweden)

    Venkatesh P Kashi

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a well-established murine model of multiple sclerosis, an immune-mediated demyelinating disorder of the central nervous system (CNS. We have previously shown that CNS-specific CD8+ T cells (CNS-CD8+ ameliorate EAE, at least in part through modulation of CNS-specific CD4+ T cell responses. In this study, we show that CNS-CD8+ also modulate the function of CD11c+ dendritic cells (DC, but not other APCs such as CD11b+ monocytes or B220+ B cells. DC from mice receiving either myelin oligodendrocyte glycoprotein-specific CD8+ (MOG-CD8+ or proteolipid protein-specific CD8+ (PLP-CD8+ T cells were rendered inefficient in priming T cell responses from naïve CD4+ T cells (OT-II or supporting recall responses from CNS-specific CD4+ T cells. CNS-CD8+ did not alter DC subset distribution or MHC class II and CD86 expression, suggesting that DC maturation was not affected. However, the cytokine profile of DC from CNS-CD8+ recipients showed lower IL-12 and higher IL-10 production. These functions were not modulated in the absence of immunization with CD8-cognate antigen, suggesting an antigen-specific mechanism likely requiring CNS-CD8-DC interaction. Interestingly, blockade of IL-10 in vitro rescued CD4+ proliferation and in vivo expression of IL-10 was necessary for the suppression of EAE by MOG-CD8+. These studies demonstrate a complex interplay between CNS-specific CD8+ T cells, DC and pathogenic CD4+ T cells, with important implications for therapeutic interventions in this disease.

  20. Fast magnetosonic wave excitation by an array of wires with time-modulated currents

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    G. Sanchez-Arriaga

    2010-02-01

    Full Text Available The excitation of Fast Magnetosonic (FMS waves by a cylindrical array of parallel tethers carrying time-modulated current is discussed. The tethers would fly vertical in the equatorial plane, which is perpendicular to the geomagnetic field when its tilt is ignored, and would be stabilized by the gravity gradient. The tether array would radiate a single FMS wave. In the time-dependent background made of geomagnetic field plus radiated wave, plasma FMS perturbations are excited in the array vicinity through a parametric instability. The growth rate is estimated by truncating the evolution equation for FMS perturbations to the two azimuthal modes of lowest order. Design parameters such as tether length and number, required power and mass are discussed for Low Earth Orbit conditions. The array-attached wave structure would have the radiated wave controlled by the intensity and modulation frequency of the currents, making an active experiment on non-linear low frequency waves possible in real space plasma conditions.

  1. Astrocyte-secreted factors modulate a gradient of primary dendritic arbors in nucleus laminaris of the avian auditory brainstem.

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    Matthew J Korn

    Full Text Available Neurons in nucleus laminaris (NL receive binaural, tonotopically matched input from nucleus magnocelluaris (NM onto bitufted dendrites that display a gradient of dendritic arbor size. These features improve computation of interaural time differences, which are used to determine the locations of sound sources. The dendritic gradient emerges following a period of significant reorganization at embryonic day 15 (E15, which coincides with the emergence of astrocytes that express glial fibrillary acidic protein (GFAP in the auditory brainstem. The major changes include a loss of total dendritic length, a systematic loss of primary dendrites along the tonotopic axis, and lengthening of primary dendrites on caudolateral NL neurons. Here we have tested whether astrocyte-derived molecules contribute to these changes in dendritic morphology. We used an organotypic brainstem slice preparation to perform repeated imaging of individual dye-filled NL neurons to determine the effects of astrocyte-conditioned medium (ACM on dendritic morphology. We found that treatment with ACM induced a decrease in the number of primary dendrites in a tonotopically graded manner similar to that observed during normal development. Our data introduce a new interaction between astrocytes and neurons in the auditory brainstem and suggest that these astrocytes influence multiple aspects of auditory brainstem maturation.

  2. Modulation of corticospinal excitability during acquisition of action sequences by observation.

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    Masanori Sakamoto

    Full Text Available Excitability of the corticospinal pathway increases during observation of an action. However, how corticospinal excitability changes during observation of sequential actions in the course of acquiring novel skills (observational learning remains unexplored. To investigate this, we used a previously unpracticed sequence of ten hand postures. Participants were asked to repeat observation and replication of the sequence. This block of observation and replication was repeated 5 times. During observation of a given hand posture (OK sign, motor-evoked potentials (MEPs elicited by transcranial magnetic stimulation were recorded from hand muscles. In experiment 1, the OK sign appeared in the 9th position of the sequence. Almost all participants could replicate the OK sign only at the 5th block of the experiment. MEP amplitude was greater than that in the control, and decreased with the stages. This suggested that during observational learning of sequential hand postures MEP changed with the progress of the learning. To evaluate this idea, we performed two additional experiments. In experiment 2, the OK sign appeared in the 2nd position. Almost all participants replicated the OK sign even in the 1st block. The MEP amplitude did not change across stages. In experiment 3, the OK sign appeared in the 9th position, but the order of other signs was randomized in every stage. Many participants were not able to replicate the OK sign even during the 5th block of the experiment. The MEP amplitude did not change across stages. These results suggest that: (1 During observational learning modulation of corticospinal excitability is associated with the learning process. (2 Corticospinal excitability decreases as learning progresses.

  3. Brain-robot interface driven plasticity: Distributed modulation of corticospinal excitability.

    Science.gov (United States)

    Kraus, Dominic; Naros, Georgios; Bauer, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

    2016-01-15

    Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the β-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans.

    Science.gov (United States)

    Mercante, B; Pilurzi, G; Ginatempo, F; Manca, A; Follesa, P; Tolu, E; Deriu, F

    2015-11-01

    Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p = 0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets.

  5. Modulation of Corticospinal Excitability during Acquisition of Action Sequences by Observation

    Science.gov (United States)

    Sakamoto, Masanori; Moriyama, Noriyoshi; Mizuguchi, Nobuaki; Muraoka, Tetsuro; Kanosue, Kazuyuki

    2012-01-01

    Excitability of the corticospinal pathway increases during observation of an action. However, how corticospinal excitability changes during observation of sequential actions in the course of acquiring novel skills (observational learning) remains unexplored. To investigate this, we used a previously unpracticed sequence of ten hand postures. Participants were asked to repeat observation and replication of the sequence. This block of observation and replication was repeated 5 times. During observation of a given hand posture (OK sign), motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation were recorded from hand muscles. In experiment 1, the OK sign appeared in the 9th position of the sequence. Almost all participants could replicate the OK sign only at the 5th block of the experiment. MEP amplitude was greater than that in the control, and decreased with the stages. This suggested that during observational learning of sequential hand postures MEP changed with the progress of the learning. To evaluate this idea, we performed two additional experiments. In experiment 2, the OK sign appeared in the 2nd position. Almost all participants replicated the OK sign even in the 1st block. The MEP amplitude did not change across stages. In experiment 3, the OK sign appeared in the 9th position, but the order of other signs was randomized in every stage. Many participants were not able to replicate the OK sign even during the 5th block of the experiment. The MEP amplitude did not change across stages. These results suggest that: (1) During observational learning modulation of corticospinal excitability is associated with the learning process. (2) Corticospinal excitability decreases as learning progresses. PMID:22615889

  6. Activation of human dendritic cells is modulated by components of the outer membranes of Neisseria meningitidis.

    Science.gov (United States)

    Al-Bader, Tamara; Christodoulides, Myron; Heckels, John E; Holloway, Judith; Semper, Amanda E; Friedmann, Peter S

    2003-10-01

    Neisseria meningitidis serogroup B is a major cause of life-threatening meningitis and septicemia worldwide, and no effective vaccine is available. Initiation of innate and acquired immune responses to N. meningitidis is likely to be dependent on cellular responses of dendritic cells (DC) to antigens present in the outer membrane (OM) of the meningococcus. In this study, the responses of human monocyte-derived DC (mo-DC) to OM isolated from parent (lipopolysaccharide [LPS]-replete) meningococci and from a mutant deficient in LPS were investigated. Parent OM selectively up-regulated Toll-like receptor 4 (TLR4) mRNA expression and induced mo-DC maturation, as reflected by increased production of chemokines, proinflammatory cytokines, and CD83, CD80, CD86, CD40, and major histocompatibility complex (MHC) class II molecules. In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules. Preexposure to OM, with or without LPS, augmented the allostimulatory properties of mo-DC, which induced proliferation of naive CD4+ CD45RA+ T cells. In addition, LPS-replete OM induced a greater gamma interferon/interleukin-13 ratio in naive T cells, whereas LPS-deficient OM induced the reverse profile. These data demonstrate that components of the OM, other than LPS, are also likely to be involved in determining the levels of DC activation and the nature of the T-helper immune response.

  7. DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation.

    Science.gov (United States)

    Søndergaard, Jonas Nørskov; Poghosyan, Susanna; Hontelez, Saartje; Louche, Pauline; Looman, Maaike W G; Ansems, Marleen; Adema, Gosse J

    2015-08-15

    The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked. Dual-knockdown and inhibition experiments demonstrated that neither GILZ nor glucocorticoid receptor play a role in TLR-induced IL-10 production after DC-SCRIPT knockdown. The NF-κB pathway is another route involved in IL-10 production after DC activation. Strikingly, inhibition of NF-κB led to a decreased TLR-mediated IL-10 production in DC-SCRIPT knockdown DCs. Moreover, DC-SCRIPT knockdown DCs showed enhanced phosphorylation, acetylation, and IL10 enhancer binding of the NF-κB subunit p65. These data demonstrate that besides nuclear receptor regulation, DC-SCRIPT also modulates activation of NF-κBp65 after TLR activation in human DCs. Copyright © 2015 by The American Association of Immunologists, Inc.

  8. Bifidobacterium longum BBMN68-specific modulated dendritic cells alleviate allergic responses to bovine β-lactoglobulin in mice.

    Science.gov (United States)

    Yang, J; Zhang, H; Jiang, L; Guo, H; Luo, X; Ren, F

    2015-10-01

    This study was designed to demonstrate the protective effects of Bifidobacterium longum BBMN68-specific modulated dendritic cells (DCs) on allergic inflammation in β-lactoglobulin (BLG)-sensitized mice. BALB/c mice were sensitized to BLG in accordance with a model of food allergy protocol and given oral BBMN68 daily. BBMN68 was found to significantly reduce BLG-specific hypersensitivity reactions by suppressing the aberrant balance of Th1/Th2 responses with increasing the number of CD4+CD25+Foxp3+ Treg cells in mesenteric lymph nodes (MLN) by 48·1%. The level of CD103+DCs was up-regulated by 136·7 and 56·2% in payer's patches and MLN, respectively, in response to the lower expression levels of cell-surface molecules (CD86 and MHC-II) induced by BBMN68 supplementation. The CD11c+DCs isolated from BBMN68 mice showed 45·6% more Foxp3+ expression in vitro. These data suggest that BBMN68-specific induction of CD11c+CD103+DCs and semi-mature DCs reduce BLG allergic reactions. These data confirm that BBMN68 may be a suitable therapeutic approach to the alleviation of food allergies, and BBMN68-specific induction of CD11c+CD103+DCs and semi-mature DCs are associated with this protection. © 2015 The Society for Applied Microbiology.

  9. Postbiotic Modulation of Retinoic Acid Imprinted Mucosal-like Dendritic Cells by Probiotic Lactobacillus reuteri 17938 In vitro

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    Yeneneh eHaileselassie

    2016-03-01

    Full Text Available Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g. necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here we studied how Lactobacillus reuteri DSM 17938 cell free supernatant (L. reuteri-CFS influenced retinoic acid (RA-driven mucosal-like dendritic cells (DC and their subsequent effect on T regulatory cells (Treg in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression and a down-regulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB and TNF. Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by down-regulating most genes involved in antigen uptake, antigen presentation and signal transduction as well as several chemokine receptors, while up regulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In co-cultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.

  10. Postbiotic Modulation of Retinoic Acid Imprinted Mucosal-like Dendritic Cells by Probiotic Lactobacillus reuteri 17938 In Vitro.

    Science.gov (United States)

    Haileselassie, Yeneneh; Navis, Marit; Vu, Nam; Qazi, Khaleda Rahman; Rethi, Bence; Sverremark-Ekström, Eva

    2016-01-01

    Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g., necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so-called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here, we studied how Lactobacillus reuteri DSM 17938 cell-free supernatant (L. reuteri-CFS) influenced retinoic acid (RA)-driven mucosal-like dendritic cells (DC) and their subsequent effect on T regulatory cells (Treg) in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression, and a downregulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB, and TNF). Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by downregulating most genes involved in antigen uptake, antigen presentation, and signal transduction as well as several chemokine receptors, while upregulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In cocultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.

  11. Phosphatidylserine exposure on the surface of Leishmania amazonensis amastigotes modulates in vivo infection and dendritic cell function

    Science.gov (United States)

    Wanderley, Joao Luiz Mendes; Thorpe, Philip E.; Barcinsn11ki, Marcello Andre; Soong, Lynn

    2012-01-01

    Leishmania amazonensis parasites can cause diverse forms of leishmaniasis in humans and persistent lesions in most inbred strains of mice. In both cases, the infection is characterized by a marked immunosuppression of the host. We previously showed that amastigote forms of the parasite make use of surface-exposed phosphatidylserine (PS) molecules to infect host cells and promote alternative macrophage activation, leading to uncontrolled intracellular proliferation of the parasites. In this study, we demonstrated that treatment of infected mice with an PS-targeting monoclonal antibody ameliorated parasite loads and lesion development, which correlated with increased proliferative responses by lymphocytes. In addition, we observed an enhanced dendritic cell (DC) activation and antigen presentation in vitro. Our data imply that the recognition of PS exposed on the surface of amastigotes plays a role in down-modulating DC functions, in a matter similar to that of apoptotic cell clearance. This study provides new information regarding the mechanism of immune suppression in Leishmania infection. PMID:23163958

  12. Heat loss analysis-based design of a 12 MW wind power generator module having an HTS flux pump exciter

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Hae-Jin, E-mail: haejin0216@gmail.com [Changwon National University, 20 Changwondaehak-ro, Changwon, 641-773 (Korea, Republic of); Go, Byeong-Soo [Changwon National University, 20 Changwondaehak-ro, Changwon, 641-773 (Korea, Republic of); Jiang, Zhenan [Robinson Research Institute, Victoria University of Wellington, PO Box 33436 (New Zealand); Park, Minwon [Changwon National University, 20 Changwondaehak-ro, Changwon, 641-773 (Korea, Republic of); Yu, In-Keun, E-mail: yuik@changwon.ac.kr [Changwon National University, 20 Changwondaehak-ro, Changwon, 641-773 (Korea, Republic of)

    2016-11-15

    Highlights: • A large-scale HTS generator module has been suggested to avoid issues such as a huge vacuum vessel and higher reliability. • The challenging heat loss analysis of a large-scale HTS generator has successfully been performed, enabling the design of an optimal support structure having a total heat loss of 43 W/400 kW. • The results prove the potential of a large-scale superconducting wind-power generator to operate efficiently, and support further development of the concept. - Abstract: The development of an effective high-temperature superconducting (HTS) generator is currently a research focus; however, the reduction of heat loss of a large-scale HTS generator is a challenge. This study deals with a heat loss analysis-based design of a 12 MW wind power generator module having an HTS flux pump exciter. The generator module consists of an HTS rotor of the generator and an HTS flux pump exciter. The specifications of the module were described, and the detailed configuration of the module was illustrated. For the heat loss analysis of the module, the excitation loss of the flux pump exciter, eddy current loss of all of the structures in the module, radiation loss, and conduction loss of an HTS coil supporter were assessed using a 3D finite elements method program. In the case of the conduction loss, different types of the supporters were compared to find out the supporter of the lowest conduction loss in the module. The heat loss analysis results of the module were reflected in the design of the generator module and discussed in detail. The results will be applied to the design of large-scale superconducting generators for wind turbines including a cooling system.

  13. Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

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    Han Seung

    2010-06-01

    Full Text Available Abstract Background Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs. Results Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s. Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin. Conclusion Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

  14. Incoherent population mixing contributions to phase-modulation two-dimensional coherent excitation spectra

    Science.gov (United States)

    Grégoire, Pascal; Srimath Kandada, Ajay Ram; Vella, Eleonora; Tao, Chen; Leonelli, Richard; Silva, Carlos

    2017-09-01

    We present theoretical and experimental results showing the effects of incoherent population mixing on two-dimensional (2D) coherent excitation spectra that are measured via a time-integrated population and phase-sensitive detection. The technique uses four collinear ultrashort pulses and phase modulation to acquire two-dimensional spectra by isolating specific nonlinear contributions to the photoluminescence or photocurrent excitation signal. We demonstrate that an incoherent contribution to the measured line shape, arising from nonlinear population dynamics over the entire photoexcitation lifetime, generates a similar line shape to the expected 2D coherent spectra in condensed-phase systems. In those systems, photoexcitations are mobile such that inter-particle interactions are important on any time scale, including those long compared with the 2D coherent experiment. Measurements on a semicrystalline polymeric semiconductor film at low temperatures show that, in some conditions in which multi-exciton interactions are suppressed, the technique predominantly detects coherent signals and can be used, in our example, to extract homogeneous line widths. The same method used on a lead-halide perovskite photovoltaic cell shows that incoherent population mixing of mobile photocarriers can dominate the measured signal since carrier-carrier bimolecular scattering is active even at low excitation densities, which hides the coherent contribution to the spectral line shape. In this example, the intensity dependence of the signal matches the theoretical predictions over more than two orders of magnitude, confirming the incoherent nature of the signal. While these effects are typically not significant in dilute solution environments, we demonstrate the necessity to characterize, in condensed-phase materials systems, the extent of nonlinear population dynamics of photoexcitations (excitons, charge carriers, etc.) in the execution of this powerful population-detected coherent

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

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    János Brunner

    2014-03-01

    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  16. Cortical excitability is not depressed in movement-modulated stretch response of human thumb flexor.

    Science.gov (United States)

    Wallace, C J; Miles, T S

    2001-08-01

    There is strong evidence that the predominant pathway of the long-latency stretch reflex for flexor pollicis longus crosses the motor cortex. This reflex response is diminished during active thumb movements. We tested the hypothesis that this could be due to a decrease in the excitability of the transcortical component during movement. During isometric, concentric and eccentric thumb movements, transcranial magnetic stimulation (TMS) of the motor cortex was given at a time when the reflex signal was traversing the motor cortex. TMS was also given earlier in separate runs when the signal was traversing the spinal cord under each of the three contractile conditions. The electromyogram was analysed for non-linear summation between stretch responses and the potential evoked by the cortical stimulus. The response to TMS alone was uniform across the three types of contraction, and the lack of cortical involvement in the short-latency reflex was confirmed. The TMS-evoked response summed in a non-linear manner with the long-latency reflex response, confirming that the excitability of the motor cortex was increased as the reflex signal passed through it. The long-latency response was markedly depressed during isotonic compared with isometric contractions. However, the non-linear summation was not greater during the isometric contractions. Thus, the depressed reflex responses during isotonic movements do not stem from reduced motor cortical responsiveness or afferent input to the transcortical pathway, and may instead reflect modulation of cutaneous reflexes during isotonic contractions.

  17. Disruption of Slc4a10 augments neuronal excitability and modulates synaptic short-term plasticity

    Directory of Open Access Journals (Sweden)

    Anne eSinning

    2015-06-01

    Full Text Available Slc4a10 is a Na+-coupled Cl--HCO3- exchanger, which is expressed in principal and inhibitory neurons as well as in choroid plexus epithelial cells of the brain. Slc4a10 knockout mice have collapsed brain ventricles and display an increased seizure threshold, while heterozygous deletions in man have been associated with idiopathic epilepsy and other neurological symptoms. To further characterize the role of Slc4a10 for network excitability, we compared input-output relations as well as short and long term changes of evoked field potentials in Slc4a10 knockout and wildtype mice. While responses of CA1 pyramidal neurons to stimulation of Schaffer collaterals were increased in Slc4a10 knockout mice, evoked field potentials did not differ between genotypes in the stratum radiatum or the neocortical areas analyzed. Paired pulse facilitation was diminished in the hippocampus upon disruption of Slc4a10 and paired pulse depression was increased in the neocortex. Though short term plasticity is modulated via Slc4a10, long term potentiation appears independent of Slc4a10. Our data support that Slc4a10 dampens neuronal excitability and thus sheds light on the pathophysiology of SLC4A10 associated pathologies.

  18. The Use and Abuse of Transcranial Magnetic Stimulation to Modulate Corticospinal Excitability in Humans.

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    Martin E Héroux

    Full Text Available The magnitude and direction of reported physiological effects induced using transcranial magnetic stimulation (TMS to modulate human motor cortical excitability have proven difficult to replicate routinely. We conducted an online survey on the prevalence and possible causes of these reproducibility issues. A total of 153 researchers were identified via their publications and invited to complete an anonymous internet-based survey that asked about their experience trying to reproduce published findings for various TMS protocols. The prevalence of questionable research practices known to contribute to low reproducibility was also determined. We received 47 completed surveys from researchers with an average of 16.4 published papers (95% CI 10.8-22.0 that used TMS to modulate motor cortical excitability. Respondents also had a mean of 4.0 (2.5-5.7 relevant completed studies that would never be published. Across a range of TMS protocols, 45-60% of respondents found similar results to those in the original publications; the other respondents were able to reproduce the original effects only sometimes or not at all. Only 20% of respondents used formal power calculations to determine study sample sizes. Others relied on previously published studies (25%, personal experience (24% or flexible post-hoc criteria (41%. Approximately 44% of respondents knew researchers who engaged in questionable research practices (range 30–81%, yet only 18% admitted to engaging in them (range 6–38% [corrected]. These practices included screening subjects to find those that respond in a desired way to a TMS protocol, selectively reporting results and rejecting data based on a gut feeling. In a sample of 56 published papers that were inspected, not a single questionable research practice was reported. Our survey revealed that approximately 50% of researchers are unable to reproduce published TMS effects. Researchers need to start increasing study sample size and eliminating

  19. Fructose modulates cardiomyocyte excitation-contraction coupling and Ca²⁺ handling in vitro.

    Directory of Open Access Journals (Sweden)

    Kimberley M Mellor

    Full Text Available BACKGROUND: High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated. OBJECTIVE: The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting. METHODS AND RESULTS: The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca²⁺ handling were evaluated under physiological conditions (37°C, 2 mM Ca²⁺, HEPES buffer, 4 Hz stimulation using video edge detection and microfluorimetry (Fura2 methods. Compared with control glucose (11 mM superfusate, 2-deoxyglucose (2 DG, 11 mM substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05 and this effect was completely abrogated with fructose supplementation (11 mM. Similarly, fructose prevented the Ca²⁺ transient delay induced by exposure to 2 DG (time to peak Ca²⁺ transient: 2 DG: 29.0±2.1 ms vs. glucose: 23.6±1.1 ms vs. fructose +2 DG: 23.7±1.0 ms; p<0.05. The presence of the fructose transporter, GLUT5 (Slc2a5 was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT-PCR. CONCLUSION: This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function.

  20. Surface plasmon polariton excitation by electrostatic modulation and phase grating in indium-tin-oxide coated lithium niobate slabs

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hao; Zhang, Jingwen; Zhao, Hua, E-mail: zhaohuaz@hit.edu.cn [Institute of Modern Optics, Department of Physics, Harbin Institute of Technology, Harbin 150001 (China); Key Laboratory of Micro-Optics and Photonics Technology of Heilongjiang Province, Harbin 150001 (China)

    2015-08-14

    Excitation of surface plasmon polaritons (SPPs) in a non-metal system in visible regime is discussed. With the assistance of phase grating resulted from photorefractive effect and electrostatic modulation of ITO induced by strong photovoltaic effect in iron-doped LiNbO{sub 3}, phase matching condition could be satisfied for SPP excitation in this semiconductor/dielectric system. Both the phase grating instead of metal grating and electrostatic modulation of semiconductor could be used for the design of tunable plasmonic devices based on nonlinear photorefractive crystals.

  1. Compact 3D printed module for fluorescence and label-free imaging using evanescent excitation

    Science.gov (United States)

    Pandey, Vikas; Gupta, Shalini; Elangovan, Ravikrishnan

    2018-01-01

    Total internal reflection fluorescence (TIRF) microscopy is widely used for selective excitation and high-resolution imaging of fluorophores, and more recently label-free nanosized objects, with high vertical confinement near a liquid–solid interface. Traditionally, high numerical aperture objectives (>1.4) are used to simultaneously generate evanescent waves and collect fluorescence emission signals which limits their use to small area imaging (3D module called cTIRF that can generate evanescent waves in microscope glass slides via a planar waveguide illumination. The module can be attached as a fixture to any existing optical microscope, converting it into a TIRF and enabling high signal-to-noise ratio (SNR) fluorescence imaging using any magnification objective. As the incidence optics is perpendicular to the detector, label-free evanescent scattering-based imaging of submicron objects can also be performed without using emission filters. SNR is significantly enhanced in this case as compared to cTIRF alone, as seen through our model experiments performed on latex beads and mammalian cells. Extreme flexibility and the low cost of our approach makes it scalable for limited resource settings.

  2. Comparison of photothermal and piezoacoustic excitation methods for frequency and phase modulation atomic force microscopy in liquid environments

    Directory of Open Access Journals (Sweden)

    A. Labuda

    2011-06-01

    Full Text Available In attempting to perform frequency modulation atomic force microscopy (FM-AFM in liquids, a non-flat phase transfer function in the self-excitation system prevents proper tracking of the cantilever natural frequency. This results in frequency-and-phase modulation atomic force microscopy (FPM-AFM which lies in between phase modulation atomic force microscopy (PM-AFM and FM-AFM. We derive the theory necessary to recover the conservative force and damping in such a situation, where standard FM-AFM theory no longer applies. Although our recovery procedure applies to all cantilever excitation methods in principle, its practical implementation may be difficult, or even impossible, if the cantilever is driven piezoacoustically. Specifically, we contrast the piezoacoustic excitation method to the photothermal method in the context of force spectroscopy of hydration structures at the mica-water interface. The results clearly demonstrate that photothermal excitation is superior to piezoacoustic excitation, as it allows for accurate quantitative interpretation of the acquired data.

  3. Rapid phase-modulated water-excitation steady-state free precession for fat-suppressed cine cardiovascular MR

    Directory of Open Access Journals (Sweden)

    Raman Subha V

    2008-05-01

    Full Text Available Abstract Background The purpose of this article is to describe a steady-state free precession (SSFP sequence for fat-suppressed cine cardiovascular magnetic resonance (CMR. A rapid phase-modulated binomial water-excitation (WE pulse is utilized to minimize repetition time and acquisition time. Methods Three different water-excitation pulses were combined with cine-SSFP for evaluation. The frequency response of each sequence was simulated and examined in phantom imaging studies. The ratio of fat to water signal amplitude was measured in phantoms to evaluate the fat-suppression capabilities of each method. Six volunteers underwent CMR of the heart at 1.5T to compare retrospectively-gated cine-SSFP with and without water-excitation. The ratio of fat to myocardium signal amplitude was measured for conventional cine-SSFP and phase-modulated WE-SSFP. The proposed WE-SSFP method was tested in one patient referred for CMR to characterize a cardiac mass. Results and discussion The measured frequency response in a phantom corresponded to the numerical Bloch equation simulation demonstrating the widened stop-band around the fat resonant frequency for all water-excitation pulses tested. In vivo measurements demonstrated that a rapid, phase-modulated water-excitation pulse significantly reduced the signal amplitude ratio of fat to myocardium from 6.92 ± 2.9 to 0.8 ± 0.13 (mean ± SD without inducing any perceptible artifacts in SSFP cine CMR. Conclusion fat-suppression can be achieved in SSFP cine CMR while maintaining steady-state equilibrium using rapid, phase modulated, binomial water-excitation pulses.

  4. Comparison of photothermal and piezoacoustic excitation methods for frequency and phase modulation atomic force microscopy in liquid environments

    OpenAIRE

    Labuda, A.; Kobayashi, K; D. Kiracofe; Suzuki, K; P. H. Grütter; Yamada, H

    2011-01-01

    In attempting to perform frequency modulation atomic force microscopy (FM-AFM) in liquids, a non-flat phase transfer function in the self-excitation system prevents proper tracking of the cantilever natural frequency. This results in frequency-and-phase modulation atomic force microscopy (FPM-AFM) which lies in between phase modulation atomic force microscopy (PM-AFM) and FM-AFM. We derive the theory necessary to recover the conservative force and damping in such a situation, where standard F...

  5. Excitation of earth-ionosphere waveguide in the ELF and lower VLF bands by modulated ionospheric current. Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Field, E.C.; Bloom, R.M.

    1993-05-21

    In this report the authors use the principal of reciprocity in conjunction with a full-wave propagation code to calculate ground-level fields excited by ionospheric currents modulated at frequencies between 50 and 100 Hz with HF heaters. Their results show the dependence on source orientation, altitude, and dimension and therefore pertain to experiments using the HIPAS or HAARP ionospheric heaters. In the end-fire mode, the waveguide excitation efficiency of an ELF HED in the ionosphere is up to 20 dB greater than for a ground-based antenna, provided its altitude does not exceed 80-to-90 km. The highest efficiency occurs for a source altitude of around 70 km; if that altitude is raised to 100 km, the efficiency drops by about 20 dB in the day and 10 dB at night. That efficiency does not account for the greater conductivity modulation that might be achieved at altitudes greater than 70 km, however. The trade-off between the altitude dependencies of the excitation efficiency and maximum achievable modulation depends on the ERP of the HF heater, the optimum altitude increasing with increasing ERP. For HIPAS the best modulation altitude is around 70 km, whereas for HAARP there might be marginal value in modulating at attitudes as high as 100 Km. Ionospheric modification, Ionospheric currents, Ionospheric heating.

  6. Motor cortex excitability is not differentially modulated following skill and strength training.

    Science.gov (United States)

    Leung, M; Rantalainen, T; Teo, W-P; Kidgell, D

    2015-10-01

    A single session of skill or strength training can modulate the primary motor cortex (M1), which manifests as increased corticospinal excitability (CSE) and decreased short-latency intra-cortical inhibition (SICI). We tested the hypothesis that both skill and strength training can propagate the neural mechanisms mediating cross-transfer and modulate the ipsilateral M1 (iM1). Transcranial magnetic stimulation (TMS) measured baseline CSE and SICI in the contralateral motor cortex (cM1) and iM1. Participants completed 4 sets of unilateral training with their dominant arm, either visuomotor tracking, metronome-paced strength training (MPST), self-paced strength training (SPST) or control. Immediately post training, TMS was repeated in both M1s. Motor-evoked potentials (MEPs) increased and inhibition was reduced for skill and MPST training from baseline in both M1s. Self-paced strength training and control did not produce changes in CSE and SICI when compared to baseline in both M1s. After training, skill and MPST increased CSE and decreased SICI in cM1 compared to SPST and control. Skill and MPST training decreased SICI in iM1 compared to SPST and control post intervention; however, CSE in iM1 was not different across groups post training. Both skill training and MPST facilitated an increase in CSE and released SICI in iM1 and cM1 compared to baseline. Our results suggest that synchronizing to an auditory or a visual cue promotes neural adaptations within the iM1, which is thought to mediate cross transfer. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Modulation of left primary motor cortex excitability after bimanual training and intermittent theta burst stimulation to left dorsal premotor cortex.

    Science.gov (United States)

    Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

    2014-03-15

    Bimanual visuomotor movement training (BMT) enhances the excitability of human preparatory premotor and primary motor (M1) cortices compared to unimanual movement. This occurs when BMT involves mirror symmetrical movements of both upper-limbs (in-phase) but not with non-symmetrical movements (anti-phase). The neural mechanisms mediating the effect of BMT is unclear, but may involve interhemispheric connections between homologous M1 representations as well as the dorsal premotor cortices (PMd). The purpose of this study is to assess how intermittent theta burst stimulation (iTBS) of the left PMd affects left M1 excitability, and the possible combined effects of iTBS to left PMd applied before a single session of BMT. Left M1 excitability was quantified using transcranial magnetic stimulation (TMS) in terms of both the amplitudes and spatial extent of motor evoked potentials (MEPs) for the extensor carpi radialis (ECR) before and multiple time points following (1) BMT, (2) iTBS to left PMd or (3) iTBS to left PMd and BMT. Although there was not a greater increase in either specific measure of M1 excitability due to the combination of the interventions, iTBS applied before BMT showed that both the spatial extent and global MEP amplitude for the ECR became larger in parallel, whereas the spatial extent was enhanced with BMT alone and global MEP amplitude was enhanced with iTBS to left PMd alone. These results suggest that the modulation of rapid functional M1 excitability associated with BMT and iTBS of the left PMd could operate under related early markers of neuro-plastic mechanisms, which may be expressed in concurrent and distinct patterns of M1 excitability. Critically, this work may guide rehabilitation training and stimulation techniques that modulate cortical excitability after brain injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Dendritic Cell Stimulation by IFN-β Alters T Cell Function via Modulation of Cytokine Secretion in Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    Abediankenari Saeid

    2009-10-01

    Full Text Available During antigen capture and processing, mature dendritic cells (DC express large amounts of peptide-MHC complexes and accessory molecules on their surface. We investigated the role of IFN-β in induction HLA-G expression on the monocyte derived DC and cytokine profile in diabetes type 1. We accomplished secretary pattern and total cytokine production of the Th1 cytokine (IL-2, γIFN and Th2 cytokines (IL-4, IL-10 before and after mixed leukocyte reaction (MLR of 30 diabetic patients and 30 normal subjects.   In this study a significant increase of IL-10 and γIFN reduction after IFN-β Therapy in culture in presence of HLA-G bearing DC as compared to control were seen. It is seen that dendritic cell causes IL-10 production of T cell in vitro that reduce T cell activation from diabetes patients and normal subjects resulted to the production and expression of HLA-G on these cells from both groups. Using mixed leukocyte reaction, it was found that IFN-β-treated dendritic cell mediated the inhibition of autologous T cell activation via IL-10 production and level of HLA-G on dendritic cell may be correlated to disease activity in diabetes patients and it could also serve as a useful marker for disease progress and treatment.

  9. The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

    Directory of Open Access Journals (Sweden)

    Miranda Arnold

    2016-09-01

    Full Text Available AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3 and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1. Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD and schizophrenia (SZ; yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines, and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse orthologue of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function.

  10. Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.

    Science.gov (United States)

    Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi; Rajguru, Suhrud M

    2014-09-15

    Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses. Copyright © 2014 the American Physiological Society.

  11. Differential modulation of corticospinal excitability during observation, mental imagery and imitation of hand actions.

    Science.gov (United States)

    Clark, Shannon; Tremblay, François; Ste-Marie, Diane

    2004-01-01

    In this study, we attempted to better delineate the changes in corticospinal excitability that accompany perceptual to motor transformations when people are asked to observe, image or imitate actions. Motor evoked potentials (MEP) from transcranial magnetic stimulation were recorded in the first dorsal interosseous (FDI) muscle of the dominant hand (15 right, 4 left) in five different conditions: (1) passive observation; (2) observation to imitate; (3) imagery; (4) imitation; and (5) counting backwards mentally. MEPs were also recorded at rest at the beginning and at the end of the session to establish baseline (BL) values. For the observation conditions, participants (n=19, 18-38 years) watched video sequences (5s) of hand actions performed by a model with the right arm (passive observation: scissors; observation to imitate: OK sign). Active imitation produced the greatest MEP facilitation compared to baseline, followed by the two observation conditions and the imagery conditions, which all produced similar levels of facilitation (post hoc comparisons). Mental counting produced some facilitation, but this effect was inconsistent. Baseline MEPs remained stable at the end of the session. A further comparison between right-handers (n=15) and left-handers (n=4) revealed no difference in the pattern of modulation across conditions. The similarity found between observation and imagery of hand actions in terms of corticospinal facilitation is interpreted in the light of the motor-simulation theory of Jeannerod [Neuroimage 14 (2001)], which proposes that perceiving actions involves neural simulation of the same action by the observer, thereby explaining the parallel between actions observed and actions imaged at the representational level.

  12. Scattered light modulation cancellation method for sub-ppb-level NO2 detection in a LD-excited QEPAS system.

    Science.gov (United States)

    Zheng, Huadan; Dong, Lei; Ma, Ying; Wu, Hongpeng; Liu, Xiaoli; Yin, Xukun; Zhang, Lei; Ma, Weiguang; Yin, Wangbao; Xiao, Liantuan; Jia, Suotang

    2016-05-16

    A sub-ppb-level nitrogen dioxide (NO2) QEPAS sensor is developed by use of a cost-effective wide stripe laser diode (LD) emitting at 450 nm and a novel background noise suppression method called scattered light modulation cancellation method (SL-MOCAM). The SL-MOCAM is a variant of modulation spectroscopy using two light sources: excitation and balance light sources. The background noise caused by the stray light of the excitation light sources can be eliminated by exposing the QEPAS spectrophone to the modulated balance light. The noise in the LD-excited QEPAS system is investigated in detail and the results shows that > ~90% background noise can be effectively eliminated by the SL-MOCAM. For NO2 detection, a 1σ detection limit of ~60 ppb is achieved for 1 s integration time and the detection limit can be improved to 0.6 ppb with an integration time of 360 s. Moreover, the SLMOCAM shows a remote working ability in the preliminary investigation.

  13. A base-sequence-modulated Golay code improves the excitation and measurement of ultrasonic guided waves in long bones.

    Science.gov (United States)

    Song, Xiaojun; Ta, Dean; Wang, Weiqi

    2012-11-01

    Researchers are interested in using ultrasonic guided waves (GWs) to assess long bones. However, GWs suffer high attenuation when they propagate in long bones, resulting in a low SNR. To overcome this limitation, this paper introduces a base-sequence-modulated Golay code (BSGC) to produce larger amplitude and improve the SNR in the ultrasound evaluation of long bones. A 16-bit Golay code was used for excitation in computer simulation. The decoded GWs and the traditional GWs, which were generated by a single pulse, agreed well after decoding the received signals, and the SNR was improved by 26.12 dB. In the experiments using bovine bones, the BSGC excitation produced the amplitudes which were at least 237 times greater than those produced by a single pulse excitation. The BSGC excitation also allowed the GWs to be received over a longer distance between two transducers. The results suggest the BSGC excitation has the potential to measure GWs and assess long bones.

  14. Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

    Science.gov (United States)

    Choo, Eun Ho; Lee, Jun-Ho; Park, Eun-Hye; Park, Hyo Eun; Jung, Nam-Chul; Kim, Tae-Hoon; Koh, Yoon-Seok; Kim, Eunmin; Seung, Ki-Bae; Park, Cheongsoo; Hong, Kwan-Soo; Kang, Kwonyoon; Song, Jie-Young; Seo, Han Geuk; Lim, Dae-Seog; Chang, Kiyuk

    2017-04-11

    Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair. © 2017 American Heart Association, Inc.

  15. Regulating Immunogenicity and Tolerogenicity of Bone Marrow-Derived Dendritic Cells through Modulation of Cell Surface Glycosylation by Dexamethasone Treatment

    Directory of Open Access Journals (Sweden)

    Kevin Lynch

    2017-10-01

    Full Text Available Dendritic cellular therapies and dendritic cell vaccines show promise for the treatment of autoimmune diseases, the prolongation of graft survival in transplantation, and in educating the immune system to fight cancers. Cell surface glycosylation plays a crucial role in the cell–cell interaction, uptake of antigens, migration, and homing of DCs. Glycosylation is known to change with environment and the functional state of DCs. Tolerogenic DCs (tDCs are commonly generated using corticosteroids including dexamethasone, however, to date, little is known on how corticosteroid treatment alters glycosylation and what functional consequences this may have. Here, we present a comprehensive profile of rat bone marrow-derived dendritic cells, examining their cell surface glycosylation profile before and after Dexa treatment as resolved by both lectin microarrays and lectin-coupled flow cytometry. We further examine the functional consequences of altering cell surface glycosylation on immunogenicity and tolerogenicity of DCs. Dexa treatment of rat DCs leads to profoundly reduced expression of markers of immunogenicity (MHC I/II, CD80, CD86 and pro-inflammatory molecules (IL-6, IL-12p40, inducible nitric oxide synthase indicating a tolerogenic phenotype. Moreover, by comprehensive lectin microarray profiling and flow cytometry analysis, we show that sialic acid (Sia is significantly upregulated on tDCs after Dexa treatment, and that this may play a vital role in the therapeutic attributes of these cells. Interestingly, removal of Sia by neuraminidase treatment increases the immunogenicity of immature DCs and also leads to increased expression of pro-inflammatory cytokines while tDCs are moderately protected from this increase in immunogenicity. These findings may have important implications in strategies aimed at increasing tolerogenicity where it is advantageous to reduce immune activation over prolonged periods. These findings are also relevant in

  16. Regulating Immunogenicity and Tolerogenicity of Bone Marrow-Derived Dendritic Cells through Modulation of Cell Surface Glycosylation by Dexamethasone Treatment.

    Science.gov (United States)

    Lynch, Kevin; Treacy, Oliver; Gerlach, Jared Q; Annuk, Heidi; Lohan, Paul; Cabral, Joana; Joshi, Lokesh; Ryan, Aideen E; Ritter, Thomas

    2017-01-01

    Dendritic cellular therapies and dendritic cell vaccines show promise for the treatment of autoimmune diseases, the prolongation of graft survival in transplantation, and in educating the immune system to fight cancers. Cell surface glycosylation plays a crucial role in the cell-cell interaction, uptake of antigens, migration, and homing of DCs. Glycosylation is known to change with environment and the functional state of DCs. Tolerogenic DCs (tDCs) are commonly generated using corticosteroids including dexamethasone, however, to date, little is known on how corticosteroid treatment alters glycosylation and what functional consequences this may have. Here, we present a comprehensive profile of rat bone marrow-derived dendritic cells, examining their cell surface glycosylation profile before and after Dexa treatment as resolved by both lectin microarrays and lectin-coupled flow cytometry. We further examine the functional consequences of altering cell surface glycosylation on immunogenicity and tolerogenicity of DCs. Dexa treatment of rat DCs leads to profoundly reduced expression of markers of immunogenicity (MHC I/II, CD80, CD86) and pro-inflammatory molecules (IL-6, IL-12p40, inducible nitric oxide synthase) indicating a tolerogenic phenotype. Moreover, by comprehensive lectin microarray profiling and flow cytometry analysis, we show that sialic acid (Sia) is significantly upregulated on tDCs after Dexa treatment, and that this may play a vital role in the therapeutic attributes of these cells. Interestingly, removal of Sia by neuraminidase treatment increases the immunogenicity of immature DCs and also leads to increased expression of pro-inflammatory cytokines while tDCs are moderately protected from this increase in immunogenicity. These findings may have important implications in strategies aimed at increasing tolerogenicity where it is advantageous to reduce immune activation over prolonged periods. These findings are also relevant in therapeutic strategies

  17. Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits.

    Science.gov (United States)

    Wahlstrom-Helgren, Sarah; Klyachko, Vitaly A

    2016-12-01

    Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. Copyright © 2016 the American Physiological Society.

  18. The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.

    Science.gov (United States)

    Trabanelli, Sara; La Manna, Federico; Romano, Marco; Salvestrini, Valentina; Cavo, Michele; Ciciarello, Marilena; Lemoli, Roberto M; Curti, Antonio

    2015-01-01

    In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

  19. Atypical excitation-inhibition balance in autism captured by the gamma response to contextual modulation

    NARCIS (Netherlands)

    Snijders, T.M.; Milivojevic, B.; Kemner, C.

    2013-01-01

    Atypical visual perception in people with autism spectrum disorders (ASD) is hypothesized to stem from an imbalance in excitatory and inhibitory processes in the brain. We used neuronal oscillations in the gamma frequency range (30–90 Hz), which emerge from a balanced interaction of excitation and

  20. Differential modulation of corticospinal excitability by different current densities of anodal transcranial direct current stimulation.

    Directory of Open Access Journals (Sweden)

    Andisheh Bastani

    Full Text Available BACKGROUND: Novel non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS have been developed in recent years. TDCS-induced corticospinal excitability changes depend on two important factors current intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set. OBJECTIVE/HYPOTHESIS: The current study aimed to investigate the effects of four different anodal tDCS (a-tDCS current densities on corticospinal excitability. METHODS: Four current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs of 0.013, 0.029, 0.058 and 0.083 mA/cm(2 were applied on twelve right-handed (mean age 34.5±10.32 yrs healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm(2 respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter. RESULTS: Post hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm(2 and 0.029 mA/cm(2 (P = 0.003. There were no significant differences between excitability changes for the 0.013 mA/cm(2 and 0.058 mA/cm(2 (P = 0.080 or 0.013 mA/cm(2 and 0.083 mA/cm(2 (P = 0.484 conditions. CONCLUSION: This study found that a-tDCS with a current density of 0.013 mA/cm(2 induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm(2. The implication is that might help to avoid applying unwanted amount of current to the cortical areas.

  1. Use of modulated excitation signals in ultrasound. Part II: Design and performance for medical imaging applications

    DEFF Research Database (Denmark)

    Misaridis, Thanassis; Jensen, Jørgen Arendt

    2005-01-01

    For pt.I, see ibid., vol.52, no.2, p.177-91 (2005). In the first paper, the superiority of linear FM signals was shown in terms of signal-to-noise ratio and robustness to tissue attenuation. This second paper in the series of three papers on the application of coded excitation signals in medical....... The method is evaluated first for resolution performance and axial sidelobes through simulations with the program Field II. A coded excitation ultrasound imaging system based on a commercial scanner and a 4 MHz probe driven by coded sequences is presented and used for the clinical evaluation of the coded....... The paper also presents acquired images, using complementary Golay codes, that show the deleterious effects of attenuation on binary codes when processed with a matched filter, als- - o confirmed by the presented simulated images....

  2. Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.

    Science.gov (United States)

    Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

    2017-01-01

    Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

  3. 5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Tobias Müller

    Full Text Available Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT, commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs. In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1 and 5-HTR(2 receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3, 5-HTR(4 and 5-HTR(7 receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.

  4. Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

    Science.gov (United States)

    Rudolph, Stephanie; Hull, Court; Regehr, Wade G

    2015-11-25

    Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

  5. Interferons modulate Fc epsilon RI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells.

    Science.gov (United States)

    Le, Trong; Tversky, Jody; Chichester, Kristin L; Bieneman, Anja P; Huang, Shau-Ku; Wood, Robert A; Schroeder, John T

    2009-01-01

    Immature human blood monocytoid dendritic cells (mDCs) express high-affinity receptors for IgE (Fc epsilon RI), yet their exact function and regulation remain poorly understood. We sought to characterize Fc epsilon RI-dependent cytokine responses and their regulation in circulating human blood mDCs. Fc epsilon RI-dependent cytokine responses of circulating mDCs were studied by using anti-Fc epsilon RI alpha stimulation. Plasmacytoid dendritic cell (pDC) cross-regulation through Toll-like receptor 9 on these responses was investigated by examining the effects of exogenous IFN-alpha pretreatment and by coculturing pDCs and mDCs stimulated with CpG. Culture supernatants were analyzed by means of ELISA to determine cytokine levels. Cell markers were determined by means of flow cytometry. mDCs express marked levels of Fc epsilon RI (net mean fluorescence intensity, 196 +/- 49; n = 4). After Fc epsilon RI-dependent activation in mDCs, TNF-alpha (2189 +/- 864 pg/10(6) mDCs, n = 3) levels were upregulated within 4 hours, whereas IL-10 (112 +/- 47 pg/10(6) mDCs, n = 3) levels were detectable only after 24 hours of incubation. After adding IL-10-neutralizing antibody, TNF-alpha Fc epsilon RI-dependent responses were significantly augmented (3903 +/- 197 pg/10(6) mDCs, P RI-mediated TNF-alpha responses up to 86% +/- 3% (n = 3, P RI-dependent secretion of IL-10 by 3.2-fold (183 +/- 11 pg/10(6) mDCs, n = 4) compared with that seen in untreated cells (57 +/- 33 pg/10(6) mDCs, P RI-dependent IL-10 secretion by mDCs was similarly augmented by 3-fold. Autocrine secretion of IL-10, a critical autoregulator of Fc epsilon RI-dependent proinflammatory responses in mDCs, is cross-regulated by IFN-alpha, a major product of Toll-like receptor 9 responses in pDCs that normally promotes T(H)1 immunity.

  6. Use of modulated excitation signals in ultrasound. Part I: Basic concepts and expected benefits

    DEFF Research Database (Denmark)

    Misaridis, Thanassis; Jensen, Jørgen Arendt

    2005-01-01

    of attenuation relates the matched filter response with the ambiguity function, known from radar. Based on this analysis and the properties of the ambiguity function, the selection of coded waveforms suitable for ultrasound imaging is discussed. It is shown that linear frequency modulation (FM) signals have...

  7. Ligand binding and signaling of dendritic cell immunoreceptor (DCIR is modulated by the glycosylation of the carbohydrate recognition domain.

    Directory of Open Access Journals (Sweden)

    Karien Bloem

    Full Text Available C-type lectins are innate receptors expressed on antigen-presenting cells that are involved in the recognition of glycosylated pathogens and self-glycoproteins. Upon ligand binding, internalization and/or signaling often occur. Little is known on the glycan specificity and ligands of the Dendritic Cell Immunoreceptor (DCIR, the only classical C-type lectin that contains an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM. Here we show that purified DCIR binds the glycan structures Lewis(b and Man3. Interestingly, binding could not be detected when DCIR was expressed on cells. Since DCIR has an N-glycosylation site inside its carbohydrate recognition domain (CRD, we investigated the effect of this glycan in ligand recognition. Removing or truncating the glycans present on purified DCIR increased the affinity for DCIR-binding glycans. Nevertheless, altering the glycosylation status of the DCIR expressing cell or mutating the N-glycosylation site of DCIR itself did not increase glycan binding. In contrast, cis and trans interactions with glycans induced DCIR mediated signaling, resulting in a decreased phosphorylation of the ITIM sequence. These results show that glycan binding to DCIR is influenced by the glycosylation of the CRD region in DCIR and that interaction with its ligands result in signaling via its ITIM motif.

  8. Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

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    Yan Zhou

    2016-01-01

    Full Text Available It is well known that dendritic cells (DCs play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs, a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG- specific experimental autoimmune encephalomyelitis (EAE model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS. Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs. Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.

  9. 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation.

    Science.gov (United States)

    Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

    2017-02-10

    Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis. Here we demonstrated that 3-bromopyruvate (BrPA), a specific HK2 inhibitor, significantly decreased the arthritis scores and the histological scores in SKG mice, with a significant increase in Treg cells, decrease in Th17 cells, and decrease in activated DCs in the spleen. In vitro, BrPA facilitated the differentiation of Treg cells, suppressed Th17 cells, and inhibited the activation of DCs. These results suggested that BrPA may be a therapeutic target of murine arthritis. Although the role of IL-17 is not clarified in the treatment of RA, targeting cell metabolism to alter the immune cell functions might lead to a new therapeutic strategy for RA.

  10. Immune-modulating effects in mouse dendritic cells of lactobacilli and bifidobacteria isolated from individuals following omnivorous, vegetarian and vegan diets.

    Science.gov (United States)

    Luongo, Diomira; Treppiccione, Lucia; Sorrentino, Alida; Ferrocino, Ilario; Turroni, Silvia; Gatti, Monica; Di Cagno, Raffaella; Sanz, Yolanda; Rossi, Mauro

    2017-09-01

    Lactobacilli and bifidobacteria play a primary role in modulation of gut immunity. By considering that microbiota composition depends on various factors, including diet, we asked whether functional differences could characterize faecal populations of lactobacilli and bifidobacteria isolated from individuals with different dietary habits. 155 healthy volunteers who followed omnivorous, ovo-lacto-vegetarian or vegan diets were recruited at four Italian centres (Turin, Parma, Bologna and Bari). Faecal samples were collected; lactobacilli and bifidobacteria were isolated on selective media and their immunomodulatory activity was tested in mouse dendritic cells (DCs). Pre-incubation with lactobacilli increased LPS-induced expression of the maturation markers CD80 and CD86, whereas pre-incubation with bifidobacteria decreased such expression. Analysis of the cytokine profile indicated that strains of both genera induced down-regulation of IL-12 and up-regulation of IL-10, whereas expression of TNF-α was not modulated. Notably, analysis of anti-inflammatory potential (IL-10/IL-12 ratio) showed that lactobacilli evoked a greater anti-inflammatory effect than did bifidobacteria in the omnivorous group (P<0.05). We also found significantly reduced anti-inflammatory potential in the bacterial strains isolated from Bari's volunteers in comparison with those from the cognate groups from the other centres. In conclusion, lactobacilli and bifidobacteria showed a genus-specific ability of modulating in vitro innate immunity associated with a specific dietary habit. Furthermore, the geographical area had a significant impact on the anti-inflammatory potential of some components of faecal microbiota. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production.

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    Alejandro Escobar

    Full Text Available Natural rubber latex (NRL; Hevea brasiliensis allergy is an IgE-mediated reaction to latex proteins. When latex glove exposure is the main sensitizing agent, Hev b 5 is one of the major allergens. Dendritic cells (DC, the main antigen presenting cells, modulated with pharmacological agents can restore tolerance in several experimental models, including allergy. In the current study, we aimed to generate DC with tolerogenic properties from NRL-allergic patients and evaluate their ability to modulate allergen-specific T and B cell responses. Here we show that dexamethasone-treated DC (dxDC differentiated into a subset of DC, characterized by low expression of MHC class II, CD40, CD80, CD86 and CD83 molecules. Compared with LPS-matured DC, dxDC secreted lower IL-12 and higher IL-10 after CD40L activation, and induced lower alloantigenic T cell proliferation. We also show that dxDC pulsed with the dominant Hev b 5 T-cell epitope peptide, Hev b 5(46-65, inhibited both proliferation of Hev b 5-specific T-cell lines and the production of Hev b 5-specific IgE. Additionally, dxDC induced a subpopulation of IL-10-producing regulatory T cells that suppressed proliferation of Hev b 5-primed T cells. In conclusion, dxDC generated from NRL-allergic patients can modulate allergen-specific T-cell responses and IgE production, supporting their potential use in allergen-specific immunotherapy.

  12. Dexamethasone and Monophosphoryl Lipid A Induce a Distinctive Profile on Monocyte-Derived Dendritic Cells through Transcriptional Modulation of Genes Associated With Essential Processes of the Immune Response

    Directory of Open Access Journals (Sweden)

    Paulina A. García-González

    2017-10-01

    Full Text Available There is growing interest in the use of tolerogenic dendritic cells (tolDCs as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex and activated with monophosphoryl lipid A (MPLA, referred to as Dex-modulated and MPLA-activated DCs (DM-DCs, as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs. We found that DM-DCs exhibit a distinctive transcriptional profile compared to untreated (DCs and MPLA-matured DCs. Differentially expressed genes downregulated by DM included MMP12, CD1c, IL-1B, and FCER1A involved in DC maturation/inflammation and genes upregulated by DM included JAG1, MERTK, IL-10, and IDO1 involved in tolerance. Genes related to chemotactic responses, cell-to-cell signaling and interaction, fatty acid oxidation, metal homeostasis, and free radical scavenging were strongly enriched, predicting the activation of alternative metabolic processes than those driven by counterpart DCs. Furthermore, we identified a set of genes that were regulated exclusively by the combined action of Dex and MPLA, which are mainly involved in the control of zinc homeostasis and reactive oxygen species production. These data further support the important role of metabolic processes on the control of the DC-driven regulatory immune response. Thus, Dex and MPLA treatments modify gene expression in moDCs by inducing a particular transcriptional profile characterized by the activation of tolerance-associated genes and suppression of the expression of inflammatory genes, conferring the potential to exert regulatory functions and immune response modulation.

  13. Dexamethasone and Monophosphoryl Lipid A Induce a Distinctive Profile on Monocyte-Derived Dendritic Cells through Transcriptional Modulation of Genes Associated With Essential Processes of the Immune Response.

    Science.gov (United States)

    García-González, Paulina A; Schinnerling, Katina; Sepúlveda-Gutiérrez, Alejandro; Maggi, Jaxaira; Mehdi, Ahmed M; Nel, Hendrik J; Pesce, Bárbara; Larrondo, Milton L; Aravena, Octavio; Molina, María C; Catalán, Diego; Thomas, Ranjeny; Verdugo, Ricardo A; Aguillón, Juan C

    2017-01-01

    There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs) toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), referred to as Dex-modulated and MPLA-activated DCs (DM-DCs), as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs. We found that DM-DCs exhibit a distinctive transcriptional profile compared to untreated (DCs) and MPLA-matured DCs. Differentially expressed genes downregulated by DM included MMP12, CD1c, IL-1B, and FCER1A involved in DC maturation/inflammation and genes upregulated by DM included JAG1, MERTK, IL-10, and IDO1 involved in tolerance. Genes related to chemotactic responses, cell-to-cell signaling and interaction, fatty acid oxidation, metal homeostasis, and free radical scavenging were strongly enriched, predicting the activation of alternative metabolic processes than those driven by counterpart DCs. Furthermore, we identified a set of genes that were regulated exclusively by the combined action of Dex and MPLA, which are mainly involved in the control of zinc homeostasis and reactive oxygen species production. These data further support the important role of metabolic processes on the control of the DC-driven regulatory immune response. Thus, Dex and MPLA treatments modify gene expression in moDCs by inducing a particular transcriptional profile characterized by the activation of tolerance-associated genes and suppression of the expression of inflammatory genes, conferring the potential to exert regulatory functions and immune response modulation.

  14. Dietary cholesterol modulates the excitability of rabbit hippocampal CA1 pyramidal neurons

    OpenAIRE

    Wang, Desheng; Schreurs, Bernard G.

    2010-01-01

    Previous work has shown high dietary cholesterol can affect learning and memory including rabbit eyeblink conditioning and this effect may be due to increased membrane cholesterol and enhanced hippocampal amyloid beta production. This study investigated whether dietary cholesterol modulates rabbit hippocampal CA1 neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2% cholesterol or normal ...

  15. Endocytosis of GABAB receptors modulates membrane excitability in the single-celled organism Paramecium.

    Science.gov (United States)

    Ramoino, Paola; Gallus, Lorenzo; Beltrame, Francesco; Diaspro, Alberto; Fato, Marco; Rubini, Patrizia; Stigliani, Sara; Bonanno, Giambattista; Usai, Cesare

    2006-05-15

    GABAB receptors modulate swimming behavior in Paramecium by inhibiting dihydropyridine-sensitive Ca2+ channels via G-proteins. Prolonged occupancy of GABAB receptors by baclofen results in a decrease in GABAB receptor functions. Since changes in the number of cell-surface GABAA receptors have been postulated to be of importance in modulating inhibitory synaptic transmission in neurons, we have studied the cell-surface expression and maintenance of GABAB receptors in P. primaurelia. In this study, we use immunostaining in electron and confocal microscopy to demonstrate that constitutive internalization of GABAB receptors in P. primaurelia is mediated by clathrin-dependent and -independent endocytosis. Indeed, GABAB receptors colocalize with the adaptin complex AP2, which is implicated in the selective recruitment of integral membrane proteins to clathrin-coated vesicles, and with caveolin 1, which is associated with uncoated membrane invaginations. Furthermore, when endocytosis is blocked with hypertonic medium, cytosol acidification, filipin or with a peptide that disrupts the association between amphiphysin and dynamin, the effect of baclofen on swimming is increased. These results suggest that GABAB receptor endocytosis into clathrin-coated and -uncoated vesicles represents an important mechanism in the modulation of swimming behavior in Paramecium.

  16. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.

    Science.gov (United States)

    den Boon, Femke S; Chameau, Pascal; Schaafsma-Zhao, Qiluan; van Aken, Willem; Bari, Monica; Oddi, Sergio; Kruse, Chris G; Maccarrone, Mauro; Wadman, Wytse J; Werkman, Taco R

    2012-02-28

    The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) channels. To investigate the functional role of CB(2)R activation, we induced neuronal firing and observed a CB(2)R-mediated reduction in firing frequency. The description of this unique CB(2)R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.

  17. TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury

    Directory of Open Access Journals (Sweden)

    Serra Jordi

    2011-04-01

    Full Text Available Abstract Background Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals. Results Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1 expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71% also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking, in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.

  18. Tannic acid modulates excitability of sensory neurons and nociceptive behavior and the Ionic mechanism.

    Science.gov (United States)

    Zhang, Xuan; Zhang, Huiran; Zhou, Najing; Xu, Jiaxi; Si, Man; Jia, Zhanfeng; Du, Xiaona; Zhang, Hailin

    2015-10-05

    M/Kv7 K(+) channels, Ca(2+)-activated Cl(-) channels (CaCCs) and voltage gated Na(+) channels expressed in dorsal root ganglia (DRG) play an important role in nociception. Tannic acid has been proposed to be involved in multiple beneficial health effects; tannic acid has also been described to be analgesic. However the underlying mechanism is unknown. In this study, we investigated the effects of tannic acid on M/Kv7 K(+), Na(+) currents and CaCCs, and the effects on bradykinin-induced nociceptive behavior. A perforated patch technique was used. The bradykinin-induced rat pain model was used to assess the analgesic effect of tannic acid. We demonstrated that tannic acid enhanced M/Kv7 K(+) currents but inhibited bradykinin-induced activation of CaCC/TMEM16A currents in rat small DRG neurons. Tannic acid potentiated Kv7.2/7.3 and Kv7.2 currents expressed in HEK293B cells, with an EC50 of 7.38 and 5.40 µM, respectively. Tannic acid inhibited TTX-sensitive and TTX-insensitive currents of small DRG neurons with IC50 of 5.25 and 8.43 µM, respectively. Tannic acid also potently suppressed the excitability of small DRG neurons. Furthermore, tannic acid greatly reduced bradykinin-induced pain behavior of rats. This study thus demonstrates that tannic acid is an activator of M/Kv7 K(+) and an inhibitor of voltage-gated Na(+) channels and CaCC/TMEM16A, which may underlie its inhibitory effects on excitability of DRG neurons and its analgesic effect. Tannic acid could be a useful agent in treatment of inflammatory pain conditions such as osteoarthritis, rheumatic arthritis and burn pain. Copyright © 2015. Published by Elsevier B.V.

  19. Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

    Science.gov (United States)

    Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

    2017-10-01

    Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS, but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

  20. Predicting Modulation in Corticomotor Excitability and in Transcallosal Inhibition in Response to Anodal Transcranial Direct Current Stimulation

    Science.gov (United States)

    Davidson, Travis W.; Bolic, Miodrag; Tremblay, François

    2016-01-01

    Introduction: Responses to neuromodulatory protocols based either on transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) are known to be highly variable between individuals. In this study, we examined whether variability of responses to anodal tDCS (a-tDCS) could be predicted from individual differences in the ability to recruit early or late indirect waves (I-waves), as reflected in latency differences of motor evoked potentials (MEPs) evoked by TMS of different coil orientation. Methods: Participants (n = 20) first underwent TMS to measure latency of MEPs elicited at different coil orientations (i.e., PA, posterior-anterior; AP, anterior-posterior; LM, latero-medial). Then, participants underwent a-tDCS (20 min @ 2 mA) targeting the primary motor cortex of the contralateral preferred hand (right, n = 18). Individual responses to a-tDCS were determined by monitoring changes in MEP amplitude at rest and in the duration of the contralateral silent period (cSP) and ipsilateral silent period (iSP) during contraction; the latter providing an index of the latency and duration of transcallosal inhibition (LTI and DTI). Results: Consistent with previous reports, individual responses to a-tDCS were highly variable when expressed in terms of changes in MEP amplitude or in cSP duration with ~50% of the participants showing either little or no modulation. In contrast, individual variations in measures of transcallosal inhibition were less variable, allowing detection of significant after-effects. The reduced LTI and prolonged DTI observed post-tDCS were indicative of an enhanced excitability of the transcallosal pathway in the stimulated hemisphere. In terms of predictions, AP-LM latency differences proved to be good predictors of responses to a-tDCS when considering MEP modulation. Conclusion: The present results corroborate the predictive value of latency differences derived from TMS to determine who is likely to express

  1. Predicting Modulation in Corticomotor Excitability and in Transcallosal Inhibition in Response to Anodal Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    Travis W Davidson

    2016-02-01

    Full Text Available Responses to neuromodulatory protocols based either on transcranial direct current stimulation (tDCS or transcranial magnetic stimulation (TMS are known to be highly variable between individuals. In this study, we examined whether variability of responses to anodal tDCS (a-tDCS could be predicted from individual differences in the ability to recruit early or late indirect waves (I-waves, as reflected in latency differences of motor evoked potentials (MEPs evoked by TMS of different coil orientation. Methods: Participants (n=20 first underwent TMS to measure latency of MEPs elicited at different coil orientations (i.e., PA: posterior-anterior; AP: anterior-posterior; LM: latero-medial. Then, participants underwent a-tDCS (20 min @ 2 mA targeting the primary motor cortex of the contralateral preferred hand (right, n=18. Individual responses to a-tDCS were determined by monitoring changes in MEP amplitude at rest and in the duration of the contralateral silent period (cSP and ipsilateral silent period (iSP during contraction; the latter providing an index of the latency and duration of transcallosal inhibition (LTI and DTI. Results: Consistent with previous reports, individual responses to a-tDCS were highly variable when expressed in terms of changes in MEP amplitude or in cSP duration with ~50% of the participants showing either little or no modulation. In contrast, individual variations in measures of transcallosal inhibition were less variable, allowing detection of significant after-effects. The reduced LTI and prolonged DTI observed post-tDCS were indicative of an enhanced excitability of the transcallosal pathway in the stimulated hemisphere. In terms of predictions, AP-LM latency differences proved to be good predictors of responses to a-tDCS when considering MEP modulation. Conclusion: The present results corroborate the predictive value of latency differences derived from TMS to determine who is likely to express canonical responses to a

  2. Hyperpolarization-activated cyclic-nucleotide-gated channels potentially modulate axonal excitability at different thresholds.

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    Weerasinghe, Dinushi; Menon, Parvathi; Vucic, Steve

    2017-12-01

    Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels mediate differences in sensory and motor axonal excitability at different thresholds in animal models. Importantly, HCN channels are responsible for voltage-gated inward rectifying (Ih) currents activated during hyperpolarization. The Ih currents exert a crucial role in determining the resting membrane potential and have been implicated in a variety of neurological disorders, including neuropathic pain. In humans, differences in biophysical properties of motor and sensory axons at different thresholds remain to be elucidated and could provide crucial pathophysiological insights in peripheral neurological diseases. Consequently, the aim of this study was to characterize sensory and motor axonal function at different threshold. Median nerve motor and sensory axonal excitability studies were undertaken in 15 healthy subjects (45 studies in total). Tracking targets were set to 20, 40, and 60% of maximum for sensory and motor axons. Hyperpolarizing threshold electrotonus (TEh) at 90-100 ms was significantly increased in lower threshold sensory axons times (F = 11.195, P sensory axons. In conclusion, variation in the kinetics of HCN isoforms could account for the findings in motor and sensory axons. Importantly, assessing the function of HCN channels in sensory and motor axons of different thresholds may provide insights into the pathophysiological processes underlying peripheral neurological diseases in humans, particularly focusing on the role of HCN channels with the potential of identifying novel treatment targets.NEW & NOTEWORTHY Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which underlie inward rectifying currents (Ih), appear to mediate differences in sensory and motor axonal properties. Inward rectifying currents are increased in lower threshold motor and sensory axons, although different HCN channel isoforms appear to underlie these changes. While faster activating HCN

  3. Role of heterogeneous cell population on modulation of dendritic cell phenotype and activation of CD8 T cells for use in cell-based immunotherapies.

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    Frizzell, Hannah; Park, Jaehyung; Comandante Lou, Natacha; Woodrow, Kim A

    2017-01-01

    Dendritic cell (DC)-based immunotherapies have much utility in their ability to prime antigen-specific adaptive immune responses. However, there does not yet exist a consensus standard to how DCs should be primed. In this study, we aimed to determine the role of heterogeneous co-cultures, composed of both CD11c+ (DCs) and CD11c- cells, in combination with monophosphoryl lipid A (MPLA) stimulation on DC phenotype and function. Upon DC priming in different co-culture ratios, we observed reduced expression of MHCII and CD86 and increased antigen uptake among CD11c+ cells in a CD11c- dependent manner. DCs from all culture conditions were induced to mature by MPLA treatment, as determined by secretion of pro-inflammatory cytokines IL-12 and TNF-α. Antigen-specific stimulation of CD4+ T cells was not modulated by co-culture composition, in terms of proliferation nor levels of IFN-γ. However, the presence of CD11c- cells enhanced cross-presentation to CD8+ T cells compared to purified CD11c+ cells, resulting in increased cell proliferation along with higher IFN-γ production. These findings demonstrate the impact of cell populations present during DC priming, and point to the use of heterogeneous cultures of DCs and innate immune cells to enhance cell-mediated immunity. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Trichomonas vaginalis α-Actinin 2 Modulates Host Immune Responses by Inducing Tolerogenic Dendritic Cells via IL-10 Production from Regulatory T Cells

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    Lee, Hye-Yeon; Kim, Juri; Ryu, Jae-Sook; Park, Soon-Jung

    2017-01-01

    Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2, Tvα-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of Tvα-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-Tvα-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or Tvα-actinin 2 protein. Both T. vaginalis and rTvα-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, CD4+CD25− regulatory T cells (Treg cells) incubated with rTvα-actinin 2-treated DCs produced high levels of IL-10. These data indicate that Tvα-actinin 2 modulates immune responses via IL-10 production by Treg cells. PMID:28877568

  5. Diametric Role of the Latency-Associated Protein Acr1 of Mycobacterium tuberculosis in Modulating the Functionality of Pre- and Post-maturational Stages of Dendritic Cells

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    Mohammed Amir

    2017-05-01

    Full Text Available It is instrumental for the Mycobacterium tuberculosis (Mtb to persist within its host in dormancy. Mtb represses most of its metabolic machinery during latency, but upregulates the expression of latency-associated protein alpha-crystallin protein (Acr1. Therefore, it is imperative to understand how throughout dormancy, Mtb employs Acr1 to regulate the host immunity. This study reveals that Acr1 exhibits divergent effect on the pre- and post-maturation stages of dendritic cells (DCs. In the current study, we demonstrate that early encounter of bone marrow cells with Acr1 while differentiating into DCs (AcrDCpre, leads to impairment in their maturation. In contrast, when exposed to Acr1 after maturation (AcrDCpost, DCs show augmentation in their activity, secretion of TNF-α, IL-12, IL-6, and activation of T cells. Additionally, AcrDCpost promoted the polarization of naïve CD4 T cells to Th1 cells and Th17 cells and restricted the intracellular growth of Mtb. Furthermore, these DCs upregulated the expression of CCR7 and exhibited enhanced migratory capabilities. The discrete impact of Acr1 on DCs is mediated through a mechanism involving STAT-1, SOCS-3, ERK, TLR-4, and NF-κB signaling pathways. This study reveals the unprecedented role of Acr1 in distinctly modulating the function of DCs at different stages of maturation.

  6. Propolis modulates miRNAs involved in TLR-4 pathway, NF-κB activation, cytokine production and in the bactericidal activity of human dendritic cells.

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    Conti, Bruno J; Santiago, Karina B; Cardoso, Eliza O; Freire, Paula P; Carvalho, Robson F; Golim, Marjorie A; Sforcin, José M

    2016-12-01

    Dendritic cells (DCs) are antigen-presenting cells, essential for recognition and presentation of pathogens to T cells. Propolis, a resinous material produced by bees from various plants, exhibits numerous biological properties, highlighting its immunomodulatory action. Here, we assayed the effects of propolis on the maturation and function of human DCs. DCs were generated from human monocytes and incubated with propolis and LPS. NF-κB and cytokines production were determined by ELISA. microRNA's expression was analysed by RT-qPCR and cell markers detection by flow cytometry. Colony-forming units were obtained to assess the bactericidal activity of propolis-treated DCs. Propolis activated DCs in the presence of LPS, inducing NF-kB, TNF-α, IL-6 and IL-10 production. The inhibition of hsa-miR-148a and hsa-miR-148b abolished the inhibitory effects on HLA-DR and pro-inflammatory cytokines. The increased expression of hsa-miR-155 may be correlated to the increase in TLR-4 and CD86 expression, maintaining LPS-induced expression of HLA-DR and CD40. Such parameters may be involved in the increased bactericidal activity of DCs against Streptococcus mutans. Propolis modulated the maturation and function of DCs and may be useful in the initial steps of the immune response, providing a novel approach to the development of DC-based strategies and for the discovery of new immunomodulators. © 2016 Royal Pharmaceutical Society.

  7. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

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    Chen-Chen Lee

    2015-01-01

    Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

  8. Trichomonas vaginalis α-Actinin 2 Modulates Host Immune Responses by Inducing Tolerogenic Dendritic Cells via IL-10 Production from Regulatory T Cells.

    Science.gov (United States)

    Lee, Hye-Yeon; Kim, Juri; Ryu, Jae-Sook; Park, Soon-Jung

    2017-08-01

    Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2, Tvα-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of Tvα-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-Tvα-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or Tvα-actinin 2 protein. Both T. vaginalis and rTvα-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, CD4+CD25- regulatory T cells (Treg cells) incubated with rTvα-actinin 2-treated DCs produced high levels of IL-10. These data indicate that Tvα-actinin 2 modulates immune responses via IL-10 production by Treg cells.

  9. Enhanced cortical excitability in grapheme-color synesthesia and its modulation.

    Science.gov (United States)

    Terhune, Devin Blair; Tai, Sarah; Cowey, Alan; Popescu, Tudor; Cohen Kadosh, Roi

    2011-12-06

    Synesthesia is an unusual condition characterized by the over-binding of two or more features and the concomitant automatic and conscious experience of atypical, ancillary images or perceptions. Previous research suggests that synesthetes display enhanced modality-specific perceptual processing, but it remains unclear whether enhanced processing contributes to conscious awareness of color photisms. In three experiments, we investigated whether grapheme-color synesthesia is characterized by enhanced cortical excitability in primary visual cortex and the role played by this hyperexcitability in the expression of synesthesia. Using transcranial magnetic stimulation, we show that synesthetes display 3-fold lower phosphene thresholds than controls during stimulation of the primary visual cortex. We next used transcranial direct current stimulation to discriminate between two competing hypotheses of the role of hyperexcitability in the expression of synesthesia. We demonstrate that synesthesia can be selectively augmented with cathodal stimulation and attenuated with anodal stimulation of primary visual cortex. A control task revealed that the effect of the brain stimulation was specific to the experience of synesthesia. These results indicate that hyperexcitability acts as a source of noise in visual cortex that influences the availability of the neuronal signals underlying conscious awareness of synesthetic photisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Extrasynaptic α6 subunit-containing GABAA receptors modulate excitability in turtle spinal motoneurons.

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    Carmen Andres

    Full Text Available Motoneurons are furnished with a vast repertoire of ionotropic and metabotropic receptors as well as ion channels responsible for maintaining the resting membrane potential and involved in the regulation of the mechanisms underlying its membrane excitability and firing properties. Among them, the GABAA receptors, which respond to GABA binding by allowing the flow of Cl- ions across the membrane, mediate two distinct forms of inhibition in the mature nervous system, phasic and tonic, upon activation of synaptic or extrasynaptic receptors, respectively. In a previous work we showed that furosemide facilitates the monosynaptic reflex without affecting the dorsal root potential. Our data also revealed a tonic inhibition mediated by GABAA receptors activated in motoneurons by ambient GABA. These data suggested that the high affinity GABAA extrasynaptic receptors may have an important role in motor control, though the molecular nature of these receptors was not determined. By combining electrophysiological, immunofluorescence and molecular biology techniques with pharmacological tools here we show that GABAA receptors containing the α6 subunit are expressed in adult turtle spinal motoneurons and can function as extrasynaptic receptors responsible for tonic inhibition. These results expand our understanding of the role of GABAA receptors in motoneuron tonic inhibition.

  11. A SOFTWARE FOR SIMULATING ELECTRICAL PROPERTIES OF PASSIVE DENDRITES

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    Yalçın İŞLER

    2006-01-01

    Full Text Available In this study, a software is introduced for simulating the electrical properties of passive dendrite based on the cable theory. Dendrites along which the synaptic information is conveyed are the largest component of a neuron in surface area. The Cable theory for dendritic neurons addresses to current-voltage relations in a continuous passive dendritic tree. It is briefly summarized that the cable theory related to passive cables and dendrites, which is a useful approximation and an important reference for excitable cases. The proposed software can be used to construct user-defined dendritic tree model. The user can define the model in detail, display the constructed dendritic tree, and examine the basic electrical properties of the dendritic tree.

  12. Empathy or Ownership? Evidence from Corticospinal Excitability Modulation during Pain Observation.

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    Bucchioni, Giulia; Fossataro, Carlotta; Cavallo, Andrea; Mouras, Harold; Neppi-Modona, Marco; Garbarini, Francesca

    2016-11-01

    Recent studies show that motor responses similar to those present in one's own pain (freezing effect) occur as a result of observation of pain in others. This finding has been interpreted as the physiological basis of empathy. Alternatively, it can represent the physiological counterpart of an embodiment phenomenon related to the sense of body ownership. We compared the empathy and the ownership hypotheses by manipulating the perspective of the observed hand model receiving pain so that it could be a first-person perspective, the one in which embodiment occurs, or a third-person perspective, the one in which we usually perceive the others. Motor-evoked potentials (MEPs) by TMS over M1 were recorded from first dorsal interosseous muscle, whereas participants observed video clips showing (a) a needle penetrating or (b) a Q-tip touching a hand model, presented either in first-person or in third-person perspective. We found that a pain-specific inhibition of MEP amplitude (a significantly greater MEP reduction in the "pain" compared with the "touch" conditions) only pertains to the first-person perspective, and it is related to the strength of the self-reported embodiment. We interpreted this corticospinal modulation according to an "affective" conception of body ownership, suggesting that the body I feel as my own is the body I care more about.

  13. Modulation of phenotypic and functional maturation of murine dendritic cells (DCs) by purified Achyranthes bidentata polysaccharide (ABP).

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    Zou, Yaxuan; Meng, Jingjuan; Chen, Wenna; Liu, Jingling; Li, Xuan; Li, Weiwei; Lu, Changlong; Shan, Fengping

    2011-08-01

    There are a large number of interactions at molecular and cellular levels between the plant polysaccharides and immune system. Plant polysaccharides present an interesting effects as immunomodulators, particularly in the induction of the cells both in innate and adaptive immune systems. Activation of DCs could improve antitumoral responses usually diminished in cancer patients, and natural adjuvants provide a possibility of inducing this activation. ABP is a purified polysaccharide isolated from Achyranthes bidentata, a traditional Chinese medicine (TCM). The aim of this study is to investigate modulation of phenotypic and functional maturation of murine DCs by ABP. Both phenotypic and functional activities were assessed with use of conventional scanning electronic microscopy (SEM) for the morphology of the DC, transmitted electron microscopy (TEM) for intracellular lysosomes inside the DC, cellular immunohistochemistry for phagocytosis by the DCs, flow cytometry (FCM) for the changes in key surface molecules, bio-assay for the activity of acidic phosphatases (ACP), and ELISA for the production of pro-inflammatory cytokine IL-12. In fact, we found that purified ABP induced phenotypic maturation revealed by increased expression of CD86, CD40, and MHC II. Functional experiments showed the down-regulation of ACP inside DCs (which occurs when phagocytosis of DCs is decreased, and antigen presentation increased with maturation). Finally, ABP increased the production of IL-12. These data reveal that ABP promotes effective activation of murine DCs. This adjuvant-like activity may have therapeutic applications in clinical settings where immune responses need boosting. It is therefore concluded that ABP can exert positive modulation to murine DCs. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Active dendritic integration as a mechanism for robust and precise grid cell firing.

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    Schmidt-Hieber, Christoph; Toleikyte, Gabija; Aitchison, Laurence; Roth, Arnd; Clark, Beverley A; Branco, Tiago; Häusser, Michael

    2017-08-01

    Understanding how active dendrites are exploited for behaviorally relevant computations is a fundamental challenge in neuroscience. Grid cells in medial entorhinal cortex are an attractive model system for addressing this question, as the computation they perform is clear: they convert synaptic inputs into spatially modulated, periodic firing. Whether active dendrites contribute to the generation of the dual temporal and rate codes characteristic of grid cell output is unknown. We show that dendrites of medial entorhinal cortex neurons are highly excitable and exhibit a supralinear input-output function in vitro, while in vivo recordings reveal membrane potential signatures consistent with recruitment of active dendritic conductances. By incorporating these nonlinear dynamics into grid cell models, we show that they can sharpen the precision of the temporal code and enhance the robustness of the rate code, thereby supporting a stable, accurate representation of space under varying environmental conditions. Our results suggest that active dendrites may therefore constitute a key cellular mechanism for ensuring reliable spatial navigation.

  15. a. Structural Perturbations of the Electronic Excited States of Zinc Complexes. B. Construction of a Thermal Modulation Emission Apparatus.

    Science.gov (United States)

    Jordan, Kevin James

    Zinc(II) complexes containing both 2,9-dimethyl -1,10,-phenanthroline and substituted benzenethiol ligands were found to crystallize in different phases. Subtle changes in emission lifetimes and bandshapes recorded over periods of months from the same batch were manifestations of slow interphase conversions. Heating the crystals to near their melting points generated the unique high temperature phases. Two phases of the benzenethiol complex were characterized by x-ray crystallography. The 2500 cm^ {-1} energy difference between the peak of the 77 K emission from the ligand-ligand charge-transfer (LLCT) transition in the two phases was considered to arise from the sensitivities of the donor orbitals to rotation of the benzene rings about the sulfur-carbon bonds. The energy of the ^3pipi^ * emission from the nitrogen heterocycle was found to be insensitive both to complexation with Zn(II) and to the presence of the LLCT transitions. The intensity decrease of the ^3pipi^ * phosphorescence in alcoholic glasses with UV exposure was related to the generation of free radicals. Multiple LLCT lifetimes and emission bands with the longer-lived components at higher energies were found in the rigid glasses. LLCT emissions from an analogous dithiol complex revealed similar characteristics. Also the relative intensities of the LLCT components were independent of excitation wavelength. These results indicated that the multiple emissions were not attributable to multiple geometrical conformations. Thermally -modulated emission (TME) spectra were obtained from compounds dispersed in rigid glasses. For bis(cis-1,2-bis(diphenylphosphino)ethylene)Rh(I) perchlorate the maximum temperature excursion was 3.5 and 4.5 K for the resistive and infra-red absorption heating methods respectively. The TME spectrum of crystalline (Cr(urea)_6) Cl_3 .3H_2O demonstrated the technique's advantages for the vibronic analysis of emissions from near-degenerate excited states. The negative signal of the

  16. Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells

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    Federico Battisti

    2017-09-01

    Full Text Available Dendritic cells (DCs are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

  17. Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease.

    Science.gov (United States)

    Karuppuchamy, T; Behrens, E-H; González-Cabrera, P; Sarkisyan, G; Gima, L; Boyer, J D; Bamias, G; Jedlicka, P; Veny, M; Clark, D; Peach, R; Scott, F; Rosen, H; Rivera-Nieves, J

    2017-01-01

    The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4(+)CD45RB(hi) cells, and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.

  18. Bordetella adenylate cyclase toxin differentially modulates toll-like receptor-stimulated activation, migration and T cell stimulatory capacity of dendritic cells.

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    Irena Adkins

    Full Text Available Adenylate cyclase toxin (CyaA is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR-activated murine and human dendritic cells (DCs. cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+ and CD8(+ T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+CD25(+Foxp3(+ T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+ T cell proliferation and limited the induction of IFN-γ producing CD8(+ T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.

  19. Nocardia brasiliensis cell wall lipids modulate macrophage and dendritic responses that favor development of experimental actinomycetoma in BALB/c mice.

    Science.gov (United States)

    Trevino-Villarreal, J Humberto; Vera-Cabrera, Lucio; Valero-Guillén, Pedro L; Salinas-Carmona, Mario C

    2012-10-01

    Nocardia brasiliensis is a Gram-positive facultative intracellular bacterium frequently isolated from human actinomycetoma. However, the pathogenesis of this infection remains unknown. Here, we used a model of bacterial delipidation with benzine to investigate the role of N. brasiliensis cell wall-associated lipids in experimental actinomycetoma. Delipidation of N. brasiliensis with benzine resulted in complete abolition of actinomycetoma without affecting bacterial viability. Chemical analyses revealed that trehalose dimycolate and an unidentified hydrophobic compound were the principal compounds extracted from N. brasiliensis with benzine. By electron microscopy, the extracted lipids were found to be located in the outermost membrane layer of the N. brasiliensis cell wall. They also appeared to confer acid-fastness. In vitro, the extractable lipids from the N. brasiliensis cell wall induced the production of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and CCL-2 in macrophages. The N. brasiliensis cell wall extractable lipids inhibited important macrophage microbicidal effects, such as tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) production, phagocytosis, bacterial killing, and major histocompatibility complex class II (MHC-II) expression in response to gamma interferon (IFN-γ). In dendritic cells (DCs), N. brasiliensis cell wall-associated extractable lipids suppressed MHC-II, CD80, and CD40 expression while inducing tumor growth factor β (TGF-β) production. Immunization with delipidated N. brasiliensis induced partial protection preventing actinomycetoma. These findings suggest that N. brasiliensis cell wall-associated lipids are important for actinomycetoma development by inducing inflammation and modulating the responses of macrophages and DCs to N. brasiliensis.

  20. Nocardia brasiliensis Cell Wall Lipids Modulate Macrophage and Dendritic Responses That Favor Development of Experimental Actinomycetoma in BALB/c Mice

    Science.gov (United States)

    Trevino-Villarreal, J. Humberto; Vera-Cabrera, Lucio; Valero-Guillén, Pedro L.

    2012-01-01

    Nocardia brasiliensis is a Gram-positive facultative intracellular bacterium frequently isolated from human actinomycetoma. However, the pathogenesis of this infection remains unknown. Here, we used a model of bacterial delipidation with benzine to investigate the role of N. brasiliensis cell wall-associated lipids in experimental actinomycetoma. Delipidation of N. brasiliensis with benzine resulted in complete abolition of actinomycetoma without affecting bacterial viability. Chemical analyses revealed that trehalose dimycolate and an unidentified hydrophobic compound were the principal compounds extracted from N. brasiliensis with benzine. By electron microscopy, the extracted lipids were found to be located in the outermost membrane layer of the N. brasiliensis cell wall. They also appeared to confer acid-fastness. In vitro, the extractable lipids from the N. brasiliensis cell wall induced the production of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and CCL-2 in macrophages. The N. brasiliensis cell wall extractable lipids inhibited important macrophage microbicidal effects, such as tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) production, phagocytosis, bacterial killing, and major histocompatibility complex class II (MHC-II) expression in response to gamma interferon (IFN-γ). In dendritic cells (DCs), N. brasiliensis cell wall-associated extractable lipids suppressed MHC-II, CD80, and CD40 expression while inducing tumor growth factor β (TGF-β) production. Immunization with delipidated N. brasiliensis induced partial protection preventing actinomycetoma. These findings suggest that N. brasiliensis cell wall-associated lipids are important for actinomycetoma development by inducing inflammation and modulating the responses of macrophages and DCs to N. brasiliensis. PMID:22851755

  1. Modulation of pro-inflammatory activation of monocytes and dendritic cells by aza-bis-phosphonate dendrimer as an experimental therapeutic agent

    Science.gov (United States)

    2014-01-01

    Introduction Our objective was to assess the capacity of dendrimer aza-bis-phosphonate (ABP) to modulate phenotype of monocytes (Mo) and monocytes derived dendritic cells (MoDC) activated in response to toll-like receptor 4 (TLR4) and interferon γ (IFN- γ) stimulation. Methods Mo (n = 12) and MoDC (n = 11) from peripheral blood of healthy donors were prepared. Cells were preincubated or not for 1 hour with dendrimer ABP, then incubated with lipopolysaccharide (LPS; as a TLR4 ligand) and (IFN-γ) for 38 hours. Secretion of tumor necrosis factor α (TNFα), interleukin (IL) -1, IL-6, IL-12, IL-10 and IL-23 in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA) and Cytokine Bead Array. Differentiation and subsequent maturation of MoDC from nine donors in the presence of LPS were analyzed by flow cytometry using CD80, CD86, CD83 and CD1a surface expression as markers. Results Mo and MoDC were orientated to a pro-inflammatory state. In activated Mo, TNFα, IL-1β and IL-23 levels were significantly lower after prior incubation with dendrimer ABP. In activated MoDC, dendrimer ABP promoted IL-10 secretion while decreasing dramatically the level of IL-12. TNFα and IL-6 secretion were significantly lower in the presence of dendrimer ABP. LPS driven maturation of MoDC was impaired by dendrimer ABP treatment, as attested by the significantly lower expression of CD80 and CD86. Conclusion Our data indicate that dendrimer ABP possesses immunomodulatory properties on human Mo and MoDC, in TLR4 + IFN-γ stimulation model, by inducing M2 alternative activation of Mo and promoting tolerogenic MoDC. PMID:24745366

  2. ZSTK474, a novel PI3K inhibitor, modulates human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Xue, Zhenyi; Li, Wen; Wang, Huafeng; Huang, Biao; Ge, Zhenzhen; Gu, Chao; Liu, Ying; Zhang, Kai; Yang, Juhong; Han, Rong; Peng, Meiyu; Li, Yan; Zhang, Da; Da, Yurong; Yao, Zhi; Zhang, Rongxin

    2014-10-01

    ZSTK474 [2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine] is a novel phosphatidylinositol 3-kinase (PI3K) inhibitor that exhibits potent antitumor effects. Recent studies have shown that ZSTK474 is also with anti-inflammatory properties in collagen-induced arthritis. However, the effects of ZSTK474 on dendritic cells and inflammatory Th17 cell-mediated autoimmune central nervous system inflammation are not understood. In this study, we demonstrated that ZSTK474 suppressed human CD14(+) monocyte-derived dendritic cell differentiation, maturation, and endocytosis, and further inhibited the stimulatory function of mature dendritic cell on allogeneic T cell proliferation. In addition, ZSTK474 inhibited the expression of dendritic cell-derived Th1 and Th17 cells polarizing cytokines interferon-γ/interleukin (IL)-12 and IL-6/IL-23. Furthermore, our results indicated that the in vivo administration of ZSTK474, which targets the dendritic cell and inflammatory Th1 and Th17 cell, led to a reduction of clinical score, central nervous system inflammation, and demyelination of mouse experimental autoimmune encephalomyelitis. Therefore, ZSTK474 significantly suppressed the human CD14(+) monocyte-derived dendritic cell functions and ameliorated mouse experimental autoimmune encephalomyelitis. We further found that ZSTK474 inhibited the phosphorylation of PI3K downstream signaling Akt and glycogen synthase kinase 3 beta in the dendritic cell. These data suggested that ZSTK474 exerted potent anti-inflammatory and immunosuppressive properties via PI3K signaling and may serve as a potential therapeutic drug for multiple sclerosis and other autoimmune inflammatory diseases. Key messages: STK474 inhibits dendritic cell (DC) differentiation and maturation. ZSTK474 inhibits DC-derived Th1 and Th17-polarizing cytokines. ZSTK474 ameliorates EAE and suppresses DCs, Th1, and Th17 cells in EAE. ZSTK474 reduces CNS inflammation and demyelination of EAE mice. ZSTK474

  3. Early events in axon/dendrite polarization.

    Science.gov (United States)

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.

  4. Modulation of Atmospheric Nonisothermality and Wind Shears on the Propagation of Seismic Tsunami-Excited Gravity Waves

    Directory of Open Access Journals (Sweden)

    John Z. G. Ma

    2016-01-01

    Full Text Available We study the modulation of atmospheric nonisothermality and wind shears on the propagation of seismic tsunami-excited gravity waves by virtue of the vertical wavenumber, m (with its imaginary and real parts, m i and m r , respectively, within a correlated characteristic range of tsunami wave periods in tens of minutes. A generalized dispersion relation of inertio-acoustic-gravity (IAG waves is obtained by relaxing constraints on Hines’ idealized locally-isothermal, shear-free and rotation-free model to accommodate a realistic atmosphere featured by altitude-dependent nonisothermality (up to 100 K/km and wind shears (up to 100 m/s per km. The obtained solutions recover all of the known wave modes below the 200-km altitude where dissipative terms are assumed negligible. Results include: (1 nonisothermality and wind shears divide the atmosphere into a sandwich-like structure of five layers within the 200-km altitude in view of the wave growth in amplitudes: Layer I (0–18 km, Layer II (18–87 km, Layer III (87–125 km, Layer IV (125–175 km and Layer V (175–200 km; (2 in Layers I, III and V, the magnitude of m i is smaller than Hines’ imaginary vertical wavenumber ( m i H , referring to an attenuated growth in the amplitudes of upward propagating waves; on the contrary, in Layers II and IV, the magnitude of m i is larger than that of m i H , providing a pumped growth from Hines’ model; (3 nonisothermality and wind shears enhance m r substantially at an ∼100-km altitude for a tsunami wave period T t s longer than 30 min. While Hines’ model provides that the maximal value of m r 2 is ∼0.05 (1/km 2 , this magnitude is doubled by the nonisothermal effect and quadrupled by the joint nonisothermal and wind shear effect. The modulations are weaker at altitudes outside 80–140-km heights; (4 nonisothermality and wind shears expand the definition of the observation-defined “damping factor”, β: relative to Hines’ classical wave

  5. News from dendritic cells in atopic dermatitis.

    Science.gov (United States)

    Schäkel, Knut; Hänsel, Anja

    2011-10-01

    Dendritic cells are essential for the generation of innate and adaptive immune responses, which makes them stay on center stage when studying the immuno pathogenesis of atopic dermatitis. This review will discuss recent findings on the role of dendritic cells subsets in atopic dermatitis and will report novel findings on how the microenvironment conditions dendritic cells to fuel atopic dermatitis. Several microenvironmental factors characteristic for atopic dermatitis and with direct relevance for the disease have been defined. We now increasingly understand how thymic stromal lymphopoietin and histamine contribute to the disease by modulating the function of dendritic cells. We have learned much about the pathogenesis of atopic dermatitis by the studies on inflammatory dendritic epidermal cells. However, the current analysis on the functional and phenotypic heterogeneity of dendritic cells in eczematous skin lesions may lead to the definition of additional dendritic cell types relevant in the pathogenesis of atopic dermatitis. In this respect, it appears interesting to further discuss the parallels and differences in atopic dermatitis and psoriasis. Understanding the heterogeneity of dendritic cells and their functional alteration by local factors in the inflamed skin will provide essential clues to the immunopathogenesis of atopic dermatitis.

  6. Midazolam and atropine alter theta oscillations in the hippocampal CA1 region by modulating both the somatic and distal dendritic dipoles.

    Science.gov (United States)

    Balakrishnan, Shilpashree; Pearce, Robert A

    2014-10-01

    Theta (4-12 Hz) oscillations in the hippocampus play an important role in learning and memory. They are altered by a wide variety of drugs that impair memory, and these effects may underlie or contribute to drug-induced amnesia. However, the network mechanisms linking drug actions with changes in memory formation remain poorly defined. Here, we used a multisite linear electrode array to measure local field potentials simultaneously across the CA1 layers of the hippocampus during active exploration, and employed current source density analysis and computational modeling to investigate how midazolam and atropine-two amnestic drugs that are used clinically and experimentally-change the relative timing and strength of the drivers of θ-oscillations. We found that two dipoles are present, with active inputs that are centered at the soma and the distal apical dendrite and passive return pathways that overlap in the mid-apical dendrite. Both drugs shifted the position of the phase reversal in the local field potential that occurred in the mid-apical dendritic region, but in opposite directions, by changing the strength of the dendritic pole, without altering the somatic pole or relative timing. Computational modeling showed that this constellation of changes, as well as an additional effect on a variably present mid-apical pole, could be produced by simultaneous changes in the active somatic and distal dendritic inputs. These network-level changes, produced by two amnestic drugs that target different types of receptors, may thus serve as a common basis for impaired memory encoding. © 2014 Wiley Periodicals, Inc.

  7. Virus-Like Particle Vaccine Containing the F Protein of Respiratory Syncytial Virus Confers Protection without Pulmonary Disease by Modulating Specific Subsets of Dendritic Cells and Effector T Cells.

    Science.gov (United States)

    Kim, Ki-Hye; Lee, Young-Tae; Hwang, Hye Suk; Kwon, Young-Man; Kim, Min-Chul; Ko, Eun-Ju; Lee, Jong Seok; Lee, Youri; Kang, Sang-Moo

    2015-11-01

    There is no licensed vaccine against respiratory syncytial virus (RSV) since the failure of formalin-inactivated RSV (FI-RSV) due to its vaccine-enhanced disease. We investigated immune correlates conferring protection without causing disease after intranasal immunization with virus-like particle vaccine containing the RSV fusion protein (F VLP) in comparison to FI-RSV and live RSV. Upon RSV challenge, FI-RSV immune mice showed severe weight loss, eosinophilia, and histopathology, and RSV reinfection also caused substantial RSV disease despite their viral clearance. In contrast, F VLP immune mice showed least weight loss and no sign of histopathology and eosinophilia. High levels of interleukin-4-positive (IL-4(+)) and tumor necrosis factor alpha-positive (TNF-α(+)) CD4(+) T cells were found in FI-RSV immune mice, whereas gamma interferon-positive (IFN-γ(+)) and TNF-α(+) CD4(+) T cells were predominantly detected in live RSV-infected mice. More importantly, in contrast to FI-RSV and live RSV that induced higher levels of CD11b(+) dendritic cells, F VLP immunization induced CD8α(+) and CD103(+) dendritic cells, as well as F-specific IFN-γ(+) and TNF-α(+) CD8(+) T cells. These results suggest that F VLP can induce protection without causing pulmonary RSV disease by inducing RSV neutralizing antibodies, as well as modulating specific subsets of dendritic cells and CD8 T cell immunity. It has been a difficult challenge to develop an effective and safe vaccine against respiratory syncytial virus (RSV), a leading cause of respiratory disease. Immune correlates conferring protection but preventing vaccine-enhanced disease remain poorly understood. RSV F virus-like particle (VLP) would be an efficient vaccine platform conferring protection. Here, we investigated the protective immune correlates without causing disease after intranasal immunization with RSV F VLP in comparison to FI-RSV and live RSV. In addition to inducing RSV neutralizing antibodies responsible for

  8. ANALYSIS OF PROCESSES IN AN INDEPENDENT GENERATOR WITH A NONCONTACT CASCADE THREE-PHASE MODULATED EXCITER VIA A STAR-CONNECTED CIRCUIT WITH A COMMON MODULATOR PHASE CONNECTION UNDER OPERATION TO AN INDUCTION MOTORS SITE

    Directory of Open Access Journals (Sweden)

    K.M. Vasyliv

    2013-04-01

    Full Text Available By means of a mathematical experiment, electromagnetic and electromechanical processes in an independent electric power supply system based on an asynchronized generator with a three-phase modulated exciter are investigated. The processes are analyzed to specify the working capacity of the power supply system during its operation to an induction motors site. Regularities of the electromagnetic and electromechanical processes behavior versus load intensity and the switch control system parameters are identified.

  9. Octopamine increases the excitability of neurons in the snail feeding system by modulation of inward sodium current but not outward potassium currents

    Directory of Open Access Journals (Sweden)

    Szabó Henriette

    2005-12-01

    Full Text Available Abstract Background Although octopamine has long been known to have major roles as both transmitter and modulator in arthropods, it has only recently been shown to be functionally important in molluscs, playing a role as a neurotransmitter in the feeding network of the snail Lymnaea stagnalis. The synaptic potentials cannot explain all the effects of octopamine-containing neurons on the feeding network, and here we test the hypothesis that octopamine is also a neuromodulator. Results The excitability of the B1 and B4 motoneurons in the buccal ganglia to depolarising current clamp pulses is significantly (P IA current and a sustained IK delayed-rectifier current, but neither was modulated by octopamine in any of these three buccal neurons. The fast inward current was eliminated in sodium – free saline and so is likely to be carried by sodium ions. 10 μM octopamine enhanced this current by 33 and 45% in the B1 and B4 motoneurons respectively (P Conclusion We conclude that octopamine is also a neuromodulator in snails, changing the excitability of the buccal neurons. This is supported by the close relationship from the voltage clamp data, through the quantitative simulation, to the action potential threshold, changing the properties of neurons in a rhythmic network. The increase in inward sodium current provides an explanation for the polycyclic modulation of the feeding system by the octopamine-containing interneurons, making feeding easier to initiate and making the feeding bursts more intense.

  10. Twisting in the excited state of an N-methylpyridinium fluorescent dye modulated by nano-heterogeneous micellar systems.

    Science.gov (United States)

    Cesaretti, A; Carlotti, B; Gentili, P L; Germani, R; Spalletti, A; Elisei, F

    2016-04-01

    A push-pull N-methylpyridinium fluorescent dye with a pyrenyl group as the electron-donor portion was investigated within the nano-heterogeneous media provided by some micellar systems. The molecule was studied by stationary and time-resolved spectroscopic techniques in spherical micellar solutions and viscoelastic hydrogels, in order to throw light on the role played by twisting in its excited state deactivation. As proven by femtosecond fluorescence up-conversion and transient absorption experiments, the excited state dynamics of the molecule is ruled by charge transfer and twisting processes, which, from the locally excited (LE) state initially populated upon excitation, progressively lead to twisted (TICT) and planar (PICT) intramolecular charge transfer states. The inclusion within micellar aggregates was found to slow down and/or limit the rotation of the molecule with respect to what had previously been observed in water, while its confinement within the hydrophobic domains of the gel matrixes prevents any molecular torsion. The increasing viscosity of the medium, when passing from water to micellar systems, implies that the detected steady-state fluorescence comes from an excited state which is not fully relaxed, as is the case with the TICT state in micelles or the LE state in hydrogels, where the detected emission changes its usual orange colour to yellow.

  11. Modulation of voltage-gated conductances of retinal horizontal cells by UV-excited TiO2nanoparticles.

    Science.gov (United States)

    Meshik, Xenia; Choi, Min; Baker, Adam; Malchow, R Paul; Covnot, Leigha; Doan, Samuel; Mukherjee, Souvik; Farid, Sidra; Dutta, Mitra; Stroscio, Michael A

    2017-04-01

    This study examines the ability of optically-excited titanium dioxide nanoparticles to influence voltage-gated ion channels in retinal horizontal cells. Voltage clamp recordings were obtained in the presence and absence of TiO 2 and ultraviolet laser excitation. Significant current changes were observed in response to UV light, particularly in the -40 mV to +40 mV region where voltage-gated Na + and K + channels have the highest conductance. Cells in proximity to UV-excited TiO 2 exhibited a left-shift in the current-voltage relation of around 10 mV in the activation of Na + currents. These trends were not observed in control experiments where cells were excited with UV light without being exposed to TiO 2 . Electrostatic force microscopy confirmed that electric fields can be induced in TiO 2 with UV light. Simulations using the Hodgkin-Huxley model yielded results which agreed with the experimental data and showed the I-V characteristics of individual ion channels in the presence of UV-excited TiO 2 . Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial Prefrontal Cortex–Basolateral Complex of Amygdala Projection Neurons in Infralimbic and Prelimbic Cortices

    Science.gov (United States)

    Song, Chenghui; Ehlers, Vanessa L.

    2015-01-01

    Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC–BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted conditioning. SIGNIFICANCE STATEMENT Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel combination of electrophysiological recordings from fluorescently labeled mPFC-to-amygdala projection neurons in rats with acquisition and extinction of trace fear conditioning to determine how specific neurons change during

  13. Control of Green and Red Upconversion in NaYF4:Yb3+,Er3+ Nanoparticles by Excitation Modulation

    OpenAIRE

    Gainer, Christian F.; Joshua, Gihan S.; De Silva, Channa R.; Romanowski, Marek

    2011-01-01

    Control of the two strongest upconversion emission lines in NaYF4:Yb3+, Er3+ nanoparticles is demonstrated by varying the excitation repetition rate. This technique may enable new multiplexed sensing modalities based on multicolor luminescent nanoparticles, currently contemplated for biomedical imaging and diagnostics.

  14. Rapid thermal annealing and modulation-doping effects on InAs/GaAs quantum dots photoluminescence dependence on excitation power

    Energy Technology Data Exchange (ETDEWEB)

    Chaâbani, W. [Laboratoire Matériaux-Molécules et Applications, Institut Préparatoire aux Etudes Scientifiques et Techniques, Université de Carthage, La Marsa 2070 (Tunisia); Melliti, A., E-mail: adnenmelliti@yahoo.fr [Laboratoire Matériaux-Molécules et Applications, Institut Préparatoire aux Etudes Scientifiques et Techniques, Université de Carthage, La Marsa 2070 (Tunisia); Maaref, M.A. [Laboratoire Matériaux-Molécules et Applications, Institut Préparatoire aux Etudes Scientifiques et Techniques, Université de Carthage, La Marsa 2070 (Tunisia); Testelin, C. [Institut des NanoSciences de Paris, UPMC Univ., Paris 06, UMR 7588, F-75005 Paris (France); CNRS, UMR 7588, INSP, F-75005 Paris (France); Lemaître, A. [Laboratoire de Photonique et Nanostructures (LPN), CNRS, Route de Nozay, F-91460 Marcoussis (France)

    2016-07-15

    The optical properties of p-doped and annealed InAs/GaAs quantum dots (QDs) was investigated by photoluminescence (PL) as a function of temperature and excitation power density (P{sub exc}). At low-T, PL spectra of rapid thermal annealing (RTA) and p-modulation doped QDs show an energy blueshift and redshift, respectively. A superlinear dependence of integrated PL intensity on P{sub exc} at high-T was found only for undoped QD. The superlinearity was suppressed by modulation-doping and RTA effects. A linear dependence of I{sub PL} at all temperatures and a decrease of the carrier-carrier Coulomb interaction at high-T was found after RTA.

  15. Nesfatin-1 in the Lateral Parabrachial Nucleus Inhibits Food Intake, Modulates Excitability of Glucosensing Neurons, and Enhances UCP1 Expression in Brown Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Jing Dong

    2017-04-01

    Full Text Available Nesfatin-1, an 82-amino acid neuropeptide, has been shown to induce anorexia and energy expenditure. Food intake is decreased in ad libitum-fed rats following injections of nesfatin-1 into the lateral, third, or fourth ventricles of the brain. Although the lateral parabrachial nucleus (LPBN is a key regulator of feeding behavior and thermogenesis, the role of nesfatin-1 in this structure has not yet been delineated. We found that intra-LPBN microinjections of nesfatin-1 significantly reduced nocturnal cumulative food intake and average meal sizes without affecting meal numbers in rats. Because glucose sensitive neurons are involved in glucoprivic feeding and glucose homeostasis, we examined the effect of nesfatin-1 on the excitability of LPBN glucosensing neurons. In vivo electrophysiological recordings from LPBN glucose sensitive neurons showed that nesfatin-1 (1.5 × 10−8 M excited most of the glucose-inhibited neurons. Chronic administration of nesfatin-1 into the LPBN of rats reduced body weight gain and enhanced the expression of uncoupling protein 1 (UCP1 in brown adipose tissue (BAT over a 10-day period. Furthermore, the effects of nesfatin-1 on food intake, body weight, and BAT were attenuated by treatment with the melanocortin antagonist SHU9119. These results demonstrate that nesfatin-1 in LPBN inhibited food intake, modulated excitability of glucosensing neurons and enhanced UCP1 expression in BAT via the melanocortin system.

  16. Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than Premotor Cortex or Primary Motor Cortex Stimulation Alone.

    Science.gov (United States)

    Chen, Mo; Deng, Huiqiong; Schmidt, Rebekah L; Kimberley, Teresa J

    2015-12-01

    The excitability of primary motor cortex (M1) can be modulated by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) over M1 or premotor cortex (PMC). A comparison of inhibitory effect between the two locations has been reported with inconsistent results. This study compared the response secondary to rTMS applied over M1, PMC, and a combined PMC + M1 stimulation approach which first targets stimulation over PMC then M1. Ten healthy participants were recruited for a randomized, cross-over design with a one-week washout between visits. Each visit consisted of a pretest, an rTMS intervention, and a post-test. Outcome measures included short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Participants received one of the three interventions in random order at each visit including: 1-Hz rTMS at 90% of resting motor threshold to: M1 (1200 pulses), PMC (1200 pulses), and PMC + M1 (600 pulses each, 1200 total). PMC + M1 stimulation resulted in significantly greater inhibition than the other locations for ICF (P = 0.005) and CSP (P stimulation may modulate brain excitability differently from PMC or M1 alone. CSP was the assessment measure most sensitive to changes in inhibition and was able to distinguish between different inhibitory protocols. This work presents a novel procedure that may have positive implications for therapeutic interventions. © 2015 International Neuromodulation Society.

  17. Plasmon-modulated photoluminescence from gold nanostructures and its dependence on plasmon resonance, excitation energy, and band structure

    NARCIS (Netherlands)

    Le Thi Ngoc, Loan; Wiedemair, Justyna; van den Berg, Albert; Carlen, Edwin

    2015-01-01

    Two distinct single-photon plasmon-modulated photoluminescence processes are generated from nanostructured gold surfaces by tuning the spectral overlap of the incident laser source, localized surface plasmon resonance band, and the interband transitions between the d and sp bands, near the X-and

  18. Strategic modulation of the photonic properties of conjugated organometallic Pt-Ir polymers exhibiting hybrid CT-excited states.

    Science.gov (United States)

    Soliman, Ahmed M; Zysman-Colman, Eli; Harvey, Pierre D

    2015-04-01

    Polymer 6, ([trans-Pt(PBu3 )2 (C≡C)2 ]-[Ir(dFMeppy)2 (N^N)](PF6 ))n , (([Pt]-[Ir](PF6 ))n ; N^N = 5,5'-disubstituted-2,2'-bipyridyl; dFMeppy = 2-(2,4-difluoro-phenyl)-5-methylpyridine) is prepared along with model compounds. These complexes are investigated by absorption and emission spectroscopy and their photophysical and electrochemical properties are measured and compared with their corresponding non fluorinated complexes. Density functional theory (DFT) and time-dependent DFT computations corroborate the nature of the excited state as being a hybrid between the metal-to-ligand charge transfer ((1,3) MLCT) for the trans-Pt(PBu3 )2 (C≡CAr)2 unit, [Pt] and the metal-to-ligand/ligand-to-ligand' charge transfer ((1,3) ML'CT/LL'CT) for [Ir] with L = dFMeppy. Overall, the fluorination of the phenylpyridine group expectedly does not change the nature of the excited state but desirably induces a small blue shift of the absorption and emission bands along a slight decrease in emission quantum yields and lifetimes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Protease-activated receptors modulate excitability of murine colonic smooth muscles by differential effects on interstitial cells.

    Science.gov (United States)

    Sung, Tae Sik; Kim, Heung Up; Kim, Jeong Hwan; Lu, Hongli; Sanders, Kenton M; Koh, Sang Don

    2015-03-01

    Protease-activated receptors (PARs) are G protein-coupled receptors activated by proteolytic cleavage at their amino termini by serine proteases. PAR activation contributes to the inflammatory response in the gastrointestinal (GI) tract and alters GI motility, but little is known about the specific cells within the tunica muscularis that express PARs and the mechanisms leading to contractile responses. Using real time PCR, we found PARs to be expressed in smooth muscle cells (SMCs), interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor α positive (PDGFRα(+)) cells. The latter cell-type showed dominant expression of F2r (encodes PAR1) and F2rl1 (encodes PAR2). Contractile and intracellular electrical activities were measured to characterize the integrated responses to PAR activation in whole muscles. Cells were isolated and ICC and PDGFRα(+) cells were identified by constitutive expression of fluorescent reporters. Thrombin (PAR1 agonist) and trypsin (PAR2 agonist) caused biphasic responses in colonic muscles: transient hyperpolarization and relaxation followed by repolarization and excitation. The inhibitory phase was blocked by apamin, revealing a distinct excitatory component. Patch clamp studies showed that the inhibitory response was mediated by activation of small conductance calcium-activated K(+) channels in PDGFRα(+) cells, and the excitatory response was mediated by activation of a Cl(-) conductance in ICC. SMCs contributed little to PAR responses in colonic muscles. In summary, PARs regulate the excitability of colonic muscles; different conductances are activated in each cell type of the SMC-ICC-PDGFRα(+) cell (SIP) syncytium. Motor responses to PAR agonists are integrated responses of the SIP syncytium. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  20. Dendritic solidification in binary alloys

    Science.gov (United States)

    Chopra, M. A.; Glicksman, M. E.; Singh, N. B.

    1988-01-01

    Alloys generally solidify dendritically, and associated with that is the microsegregation of impurities. Pure metals also solidify in dendritic form as 'thermal' dendrites, which actually segregate the system's enthalpy. In this investigation, small additions of solute to succinonitrile have been studied and dendritic growth observed in a supercooled melt. This free dendritic growth-mode is similar to that experienced by equiaxed dendrites found in alloy castings. Observations of these free dendrites include measurement of velocity and tip radius of the dendrites at different supercoolings and solute concentrations.

  1. Glial cell line-derived neurotrophic factor modulates the excitability of nociceptive trigeminal ganglion neurons via a paracrine mechanism following inflammation.

    Science.gov (United States)

    Takeda, Mamoru; Takahashi, Masayuki; Hara, Norifumi; Matsumoto, Shigeji

    2013-02-01

    Previous our report indicated that acute application of glial cell line-derived neurotrophic factor (GDNF) enhances the neuronal excitability of adult rat small-diameter trigeminal ganglion (TRG) neurons, which innervate the facial skin in the absence of neuropathic and inflammatory conditions. This study investigated whether under in vivo conditions, GDNF modulates the excitability of nociceptive Aδ-TRG neurons innervating the facial skin via a paracrine mechanism following inflammation. We used extracellular electrophysiological recording with multibarrel-electrodes in this study. Spontaneous Aδ-TRG neuronal activity was induced in control rats after iontophoretic application of GDNF into the trigeminal ganglia (TRGs). Noxious and non-noxious mechanical stimuli evoked Aδ-TRG neuronal firing rate were significantly increased by iontophoretic application of GDNF. The mean mechanical threshold of nociceptive TRG neurons was significantly decreased by GDNF application. The increased discharge frequency and decreased mechanical threshold induced by GDNF were antagonized by application of the protein tyrosine kinase inhibitor, K252b. The number of Aδ-TRG neurons with spontaneous firings and their firing rates in rats with inflammation induced by Complete Freund's Adjuvant were significantly higher than control rats. The firing rates of Aδ-TRG spontaneous neuronal activity were significantly decreased by iontophoretic application of K252b in inflamed rats. K252b also inhibited Aδ-TRG neuron activity evoked by mechanical stimulation in inflamed rats. These results suggest that in vivo GDNF enhances the excitability of nociceptive Aδ-TRG neurons via a paracrine mechanism within TRGs following inflammation. GDNF paracrine mechanism could be important as a therapeutic target for trigeminal inflammatory hyperalgesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. FPGA-based photon-counting phase-modulation fluorometer and a brief comparison with that operated in a pulsed-excitation mode

    Science.gov (United States)

    Iwata, Tetsuo; Taga, Takanori; Mizuno, Takahiko

    2017-12-01

    We have constructed a high-efficiency, photon-counting phase-modulation fluorometer (PC-PMF) using a field-programmable gate array, which is a modified version of the photon-counting fluorometer (PCF) that works in a pulsed-excitation mode (Iwata and Mizuno in Meas Sci Technol 28:075501, 2017). The common working principle for both is the simultaneous detection of the photoelectron pulse train, which covers 64 ns with a 1.0-ns resolution time (1.0 ns/channel). The signal-gathering efficiency was improved more than 100 times over that of conventional time-correlated single-photon-counting at the expense of resolution time depending on the number of channels. The system dead time for building a histogram was eliminated, markedly shortening the measurement time for fluorescent samples with moderately high quantum yields. We describe the PC-PMF and make a brief comparison with the pulsed-excitation PCF in precision, demonstrating the potential advantage of PC-PMF.

  3. Ibogaine and a total alkaloidal extract of Voacanga africana modulate neuronal excitability and synaptic transmission in the rat parabrachial nucleus in vitro.

    Science.gov (United States)

    Kombian, S B; Saleh, T M; Fiagbe, N I; Chen, X; Akabutu, J J; Buolamwini, J K; Pittman, Q J

    1997-01-01

    Ibogaine is a natural alkaloid of Voacanga africana that is effective in the treatment of withdrawal symptoms and craving in drug addicts. As the synaptic and cellular basis of ibogaine's actions are not well understood, this study tested the hypothesis that ibogaine and Voacanga africana extract modulate neuronal excitability and synaptic transmission in the parabrachial nucleus using the nystatin perforated patch-recording technique. Ibogaine and Voacanga africana extract dose dependently, reversibly, and consistently attenuate evoked excitatory synaptic currents recorded in parabrachial neurons. The ED50 of ibogaine's effect is 5 microM, while that of Voacanga africana extract is 170 micrograms/ml. At higher concentrations, ibogaine and Voacanga africana extract induce inward currents or depolarization that are accompanied by increases in evoked and spontaneous firing rate. The depolarization or inward current is also accompanied by an increase in input resistance and reverses polarity around 0 mV. The depolarization and synaptic depression were blocked by the dopamine receptor antagonist haloperidol. These results indicate that ibogaine and Voacanga africana extract 1) depolarize parabrachial neurons with increased excitability and firing rate; 2) depress non-NMDA receptor-mediated fast synaptic transmission; 3) involve dopamine receptor activation in their actions. These results further reveal that the Voacanga africana extract has one-hundredth the activity of ibogaine in depressing synaptic responses. Thus, ibogaine and Voacanga africana extract may produce their central effects by altering dopaminergic and glutamatergic processes.

  4. Excitation of Alfvén waves by modulated HF heating of the ionosphere, with application to FAST observations

    Directory of Open Access Journals (Sweden)

    E. Kolesnikova

    Full Text Available During the operation of the EISCAT high power facility (heater at Tromsø, Norway, on 8 October 1998, the FAST spacecraft made electric field and particle observations in the inner magnetosphere at 0.39 Earth radii above the heated ionospheric region. Measurements of the direct current electric field clearly exhibit oscillations with a frequency close to the modulated frequency of heater ( ~ 3 Hz and an amplitude of ~ 2 - 5 mV m-1. Thermal electron data from the electrostatic analyser show the modulation at the same frequency of the downward electron fluxes. During this period the EISCAT UHF incoherent scatter radar, sited also at Tromsø, measured a significant enhancement of the electron density in E-layer up to 2 · 1012 m-3. These observations have prompted us to make quantitative estimates of the expected pulsations in the inner magnetosphere caused by the modulated HF heating of lower ionosphere. Under the conditions of the strong electron precipitation in the ionosphere, which took place during the FAST observations, the primary current caused by the perturbation of the conductivity in the heated region is closed entirely by the parallel current which leaks into the magnetosphere. In such circumstances the conditions at the ionosphere-magnetosphere boundary are most favourable for the launching of an Alfvén wave: it is launched from the node in the gradient of the scalar potential which is proportional to the parallel current. The parallel electric field of the Alfvén wave is significant in the region where the electron inertial length is of order of the transverse wavelength of the Alfvén wave or larger and may effectively accelerate superthermal electrons downward into the ionosphere.

    Key words. Ionosphere (active experiments; ionosphere – magnetosphere interactions; particle acceleration

  5. Excitation of Alfvén waves by modulated HF heating of the ionosphere, with application to FAST observations

    Directory of Open Access Journals (Sweden)

    E. Kolesnikova

    2002-01-01

    Full Text Available During the operation of the EISCAT high power facility (heater at Tromsø, Norway, on 8 October 1998, the FAST spacecraft made electric field and particle observations in the inner magnetosphere at 0.39 Earth radii above the heated ionospheric region. Measurements of the direct current electric field clearly exhibit oscillations with a frequency close to the modulated frequency of heater ( ~ 3 Hz and an amplitude of ~ 2 - 5 mV m-1. Thermal electron data from the electrostatic analyser show the modulation at the same frequency of the downward electron fluxes. During this period the EISCAT UHF incoherent scatter radar, sited also at Tromsø, measured a significant enhancement of the electron density in E-layer up to 2 · 1012 m-3. These observations have prompted us to make quantitative estimates of the expected pulsations in the inner magnetosphere caused by the modulated HF heating of lower ionosphere. Under the conditions of the strong electron precipitation in the ionosphere, which took place during the FAST observations, the primary current caused by the perturbation of the conductivity in the heated region is closed entirely by the parallel current which leaks into the magnetosphere. In such circumstances the conditions at the ionosphere-magnetosphere boundary are most favourable for the launching of an Alfvén wave: it is launched from the node in the gradient of the scalar potential which is proportional to the parallel current. The parallel electric field of the Alfvén wave is significant in the region where the electron inertial length is of order of the transverse wavelength of the Alfvén wave or larger and may effectively accelerate superthermal electrons downward into the ionosphere.Key words. Ionosphere (active experiments; ionosphere – magnetosphere interactions; particle acceleration

  6. The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4

    Science.gov (United States)

    Lee, Su Jung; Noh, Kyung Tae; Kang, Tae Heung; Han, Hee Dong; Shin, Sung Jae; Soh, Byoung Yul; Park, Jung Hee; Shin, Yong Kyoo; Kim, Han Wool; Yun, Cheol-Heui; Park, Won Sun; Jung, In Duk; Park, Yeong-Min

    2014-01-01

    In this study, we show that Mycobacterium avium subsp. Paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-α, and IL-1β) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naïve T cells to polarized CD4+ and CD8+ T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. Paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of CD4+ and CD8+ T cells. [BMB Reports 2014; 47(2): 115-120] PMID:24393523

  7. A COMPARATIVE ANALYSIS OF PROCESSES IN AN INDEPENDENT GENERATOR WITH A NONCONTACT CASCADE THREE-PHASE MODULATED EXCITER VIA A STAR-CONNECTED CIRCUIT UNDER ACTIVE-INDUCTIVE LOADING

    Directory of Open Access Journals (Sweden)

    K.M. Vasyliv

    2013-02-01

    Full Text Available By means of mathematical experiment, the author investigates electromagnetic and electromechanical processes in an independent electric power supply system based on an asynchronized generator with a three-phase modulated exciter. The processes are analyzed to specify the working capacity of the power supply system during its operation under active-inductive loading. Regularities of the electromagnetic and electromechanical processes behavior versus load intensity and the modulator scheme are identified.

  8. Novel Immune Modulating Cellular Vaccine for Prostate Cancer Immunotherapy

    Science.gov (United States)

    2016-10-01

    cellular vaccine product. 15. SUBJECT TERMS dendritic cell vaccine, dendritic cells electroporated with RNA, immune checkpoint blockade, local CTLA-4...dendritic cell vaccine, dendritic cells electroporated with RNA, immune checkpoint blockade, local CTLA4 modulation, prostate cancer...7: Monitor tumor burden (time to palpable tumor) and monitor survival. Harvest prostate complex/tumor and analyze tumor weight , tumor grade

  9. Murein Lytic Enzyme TgaA of Bifidobacterium bifidum MIMBb75 Modulates Dendritic Cell Maturation through Its Cysteine- and Histidine-Dependent Amidohydrolase/Peptidase (CHAP) Amidase Domain

    Science.gov (United States)

    Zanoni, Ivan; Balzaretti, Silvia; Miriani, Matteo; Taverniti, Valentina; De Noni, Ivano; Presti, Ilaria; Stuknyte, Milda; Scarafoni, Alessio; Arioli, Stefania; Iametti, Stefania; Bonomi, Francesco; Mora, Diego; Karp, Matti; Granucci, Francesca

    2014-01-01

    Bifidobacteria are Gram-positive inhabitants of the human gastrointestinal tract that have evolved close interaction with their host and especially with the host's immune system. The molecular mechanisms underlying such interactions, however, are largely unidentified. In this study, we investigated the immunomodulatory potential of Bifidobacterium bifidum MIMBb75, a bacterium of human intestinal origin commercially used as a probiotic. Particularly, we focused our attention on TgaA, a protein expressed on the outer surface of MIMBb75's cells and homologous to other known bacterial immunoactive proteins. TgaA is a peptidoglycan lytic enzyme containing two active domains: lytic murein transglycosylase (LT) and cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP). We ran immunological experiments stimulating dendritic cells (DCs) with the B. bifidum MIMBb75 and TgaA, with the result that both the bacterium and the protein activated DCs and triggered interleukin-2 (IL-2) production. In addition, we observed that the heterologous expression of TgaA in Bifidobacterium longum transferred to the bacterium the ability to induce IL-2. Subsequently, immunological experiments performed using two purified recombinant proteins corresponding to the single domains LT and CHAP demonstrated that the CHAP domain is the immune-reactive region of TgaA. Finally, we also showed that TgaA-dependent activation of DCs requires the protein CD14, marginally involves TRIF, and is independent of Toll-like receptor 4 (TLR4) and MyD88. In conclusion, our study suggests that the bacterial CHAP domain is a novel microbe-associated molecular pattern actively participating in the cross talk mechanisms between bifidobacteria and the host's immune system. PMID:24814791

  10. MD-1 deficiency attenuates dextran sodium sulfate (DSS)-induced colitis through modulating the function of colonic lamina propria dendritic cells.

    Science.gov (United States)

    Pan, Huaqin; Zhang, Guqin; Zhang, Lin; Wang, Wei; Shang, Jian; Wang, Xiaobing; Zhao, Qiu; Li, Jin

    2016-07-01

    Available evidence suggests that both dysregulated innate and adaptive immune pathways contribute to the aberrant intestinal inflammatory response in patients with inflammatory bowel disease (IBD). Myeloid Differentiation 1 (MD-1), also known as Lymphocyte Antigen 86 (Ly86), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signaling pathway. Previous studies showed that MD-1 may be involved in the (patho) physiological regulation of the innate immune system and inflammation. In this study, we reported for the first time that MD-1 mRNA expression was up-regulated in both human IBD patients and DSS-treated WT mice. We showed that MD-1(-/-) mice were less susceptible to the development of colitis than WT controls as demonstrated by significantly reduced weight loss, disease activity index, colon histological scores, cellular infiltration and expression of inflammatory mediators. In addition, mucosal barrier function seemed to be intact in response to the loss of MD-1. Finally, lamina propria dendritic cells (LPDCs) from the colon of MD-1(-/-) mice after DSS exposure not only decreased in number but also significantly down-regulated the expression of surface maturation co-stimulatory molecules MHC-II, CD40 and CD86 compared with those from WT mice. Taken together, our results reveal that MD-1 deficiency is of critical importance in down-regulating induction and progression of DSS colitis, thereby suggesting that MD-1 might be a target for future interventional therapies of IBD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. From atoms to dendrites

    Science.gov (United States)

    Hoyt, J. J.; Karma, Alain; Asta, M. A.; Sun, D. Y.

    2004-04-01

    Dendritic microstructures control the properties of a wide range of advanced materials ranging from nickel-based superalloys used in turbine blades to lightweight aluminum-based alloys for the automotive industry. This article reviews recent progress in quantitative modeling dendritic growth through the combination of state-of-the-art atomistic and phase field simulations. Also shown is how the combination of these two distinct length-scale modeling approaches can yield a parameter-free prediction of the dendrite growth velocity as a function of undercooling for deeply undercooled nickel melts.

  12. The microvesicle component of HIV-1 inocula modulates dendritic cell infection and maturation and enhances adhesion to and activation of T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Sarah K Mercier

    2013-10-01

    Full Text Available HIV-1 is taken up by immature monocyte derived dendritic cells (iMDDCs into tetraspanin rich caves from which the virus can either be transferred to T lymphocytes or enter into endosomes resulting in degradation. HIV-1 binding and fusion with the DC membrane results in low level de novo infection that can also be transferred to T lymphocytes at a later stage. We have previously reported that HIV-1 can induce partial maturation of iMDDCs at both stages of trafficking. Here we show that CD45⁺ microvesicles (MV which contaminate purified HIV-1 inocula due to similar size and density, affect DC maturation, de novo HIV-1 infection and transfer to T lymphocytes. Comparing iMDDCs infected with CD45-depleted HIV-1BaL or matched non-depleted preparations, the presence of CD45⁺ MVs was shown to enhance DC maturation and ICAM-1 (CD54 expression, which is involved in DC∶T lymphocyte interactions, while restricting HIV-1 infection of MDDCs. Furthermore, in the DC culture HIV-1 infected (p24⁺ MDDCs were more mature than bystander cells. Depletion of MVs from the HIV-1 inoculum markedly inhibited DC∶T lymphocyte clustering and the induction of alloproliferation as well as limiting HIV-1 transfer from DCs to T lymphocytes. The effects of MV depletion on these functions were reversed by the re-addition of purified MVs from activated but not non-activated SUPT1.CCR5-CL.30 or primary T cells. Analysis of the protein complement of these MVs and of these HIV-1 inocula before and after MV depletion showed that Heat Shock Proteins (HSPs and nef were the likely DC maturation candidates. Recombinant HSP90α and β and nef all induced DC maturation and ICAM-1 expression, greater when combined. These results suggest that MVs contaminating HIV-1 released from infected T lymphocytes may be biologically important, especially in enhancing T cell activation, during uptake by DCs in vitro and in vivo, particularly as MVs have been detected in the circulation of HIV-1

  13. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  14. Differential gating of dendritic spikes by compartmentalized inhibition

    Directory of Open Access Journals (Sweden)

    Katharina Anna Wilmes

    2014-03-01

    Full Text Available Different types of local inhibitory interneurons innervate different dendritic sites of pyramidal neurons in cortex and hippocampus (Klausberger 2009. What could be the functional role of compartmentalized inhibition? Pyramidal cell dendrites support different forms of active signal propagation, which are important not only for dendritic and neuronal signal processing (Smith et al. 2013, but also for synaptic plasticity. While back-propagating action potentials signal post-synaptic activity to synapses in apical oblique and basal dendrites (Markram et al. 1997, Cho et al. 2006, calcium spikes cause plasticity of distal apical tuft synapses (Golding et al. 2002. Suspiciously, the associated regions of the dendrite are targeted by different interneuron populations. Parvalbumin-positive interneurons typically target the proximal dendritic and somatic parts of the neuron, while somatostatin-positive interneurons target the apical dendrite. The matching compartmentalization in terms of dendritic spikes and inhibitory control suggests that inhibition could differentially regulate different dendritic spikes and thereby introduce a compartment-specific modulation of synaptic plasticity. We evaluate this hypothesis in a biophysical multi-compartment model of a pyramidal neuron, receiving shunting inhibition at different locations on the dendrite. The model shows that, first, inhibition can gate dendritic spikes in an all-or-none manner. Second, spatially selective inhibition can individually suppress back-propagating action potentials and calcium spikes, thereby allowing a compartment-specific switch for synaptic plasticity. In our model, proximal inhibition on the apical dendrite eliminated both the back-propagating action potential and the calcium spike, thus influencing plasticity in the whole apical dendrite. Distal apical inhibition could selectively affect calcium spikes and thus distal plasticity, without suppressing back­propagation of action

  15. Supramolecular effects in dendritic systems containing photoactive groups

    Directory of Open Access Journals (Sweden)

    GIANLUCA CAMILLO AZZELLINI

    2000-03-01

    Full Text Available In this article are described dendritic structures containing photoactive groups at the surface or in the core. The observed supramolecular effects can be attributed to the nature of the photoactive group and their location in the dendritic architecture. The peripheric azobenzene groups in these dendrimeric compounds can be regarded as single residues that retain the spectroscopic and photochemical properties of free azobenzene moiety. The E and Z forms of higher generation dendrimer, functionalized with azobenzene groups, show different host ability towards eosin dye, suggesting the possibility of using such dendrimer in photocontrolled host-guest systems. The photophysical properties of many dendritic-bipyridine ruthenium complexes have been investigated. Particularly in aerated medium more intense emission and a longer excited-state lifetime are observed as compared to the parent unsubstituted bipyridine ruthenium complexes. These differences can be attributed to a shielding effect towards dioxygen quenching originated by the dendritic branches.

  16. Dendritic inhibition in the hippocampus supports fear learning.

    Science.gov (United States)

    Lovett-Barron, Matthew; Kaifosh, Patrick; Kheirbek, Mazen A; Danielson, Nathan; Zaremba, Jeffrey D; Reardon, Thomas R; Turi, Gergely F; Hen, René; Zemelman, Boris V; Losonczy, Attila

    2014-02-21

    Fear memories guide adaptive behavior in contexts associated with aversive events. The hippocampus forms a neural representation of the context that predicts aversive events. Representations of context incorporate multisensory features of the environment, but must somehow exclude sensory features of the aversive event itself. We investigated this selectivity using cell type-specific imaging and inactivation in hippocampal area CA1 of behaving mice. Aversive stimuli activated CA1 dendrite-targeting interneurons via cholinergic input, leading to inhibition of pyramidal cell distal dendrites receiving aversive sensory excitation from the entorhinal cortex. Inactivating dendrite-targeting interneurons during aversive stimuli increased CA1 pyramidal cell population responses and prevented fear learning. We propose subcortical activation of dendritic inhibition as a mechanism for exclusion of aversive stimuli from hippocampal contextual representations during fear learning.

  17. Diverse impact of acute and long-term extracellular proteolytic activity on plasticity of neuronal excitability

    Directory of Open Access Journals (Sweden)

    Tomasz eWójtowicz

    2015-08-01

    Full Text Available Learning and memory require alteration in number and strength of existing synaptic connections. Extracellular proteolysis within the synapses has been shown to play a pivotal role in synaptic plasticity by determining synapse structure, function, and number. Although synaptic plasticity of excitatory synapses is generally acknowledged to play a crucial role in formation of memory traces, some components of neural plasticity are reflected by nonsynaptic changes. Since information in neural networks is ultimately conveyed with action potentials, scaling of neuronal excitability could significantly enhance or dampen the outcome of dendritic integration, boost neuronal information storage capacity and ultimately learning. However, the underlying mechanism is poorly understood. With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses. Here we review the most recent studies addressing the impact of extracellular proteolysis on plasticity of neuronal excitability and discuss how enzymatic activity may alter input-output/transfer function of neurons, supporting cognitive processes. Interestingly, extracellular proteolysis may alter intrinsic neuronal excitability and excitation/inhibition balance both rapidly (time of minutes to hours and in long-term window. Moreover, it appears that by cleavage of extracellular matrix constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments in adjusting neuronal input/output function. Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic

  18. Optimization principles of dendritic structure

    Directory of Open Access Journals (Sweden)

    Borst Alexander

    2007-06-01

    Full Text Available Abstract Background Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip – a feature of many neurons – optimizes charge transfer from all dendritic synapses to the dendritic root while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely reconstructed based on these two principles alone.

  19. The RhoGEF trio functions in sculpting class specific dendrite morphogenesis in Drosophila sensory neurons.

    Directory of Open Access Journals (Sweden)

    Srividya Chandramouli Iyer

    Full Text Available As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures.Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da sensory neurons of the Drosophila peripheral nervous system (PNS. Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis.Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia

  20. CD4+ T‐cell activation is differentially modulated by bacteria‐primed dendritic cells, but is generally down‐regulated by n‐3 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Lund, Pia; Kjær, Tanja

    2010-01-01

    cells, while the presence of CD40 and CD86 on DCs inversely affected inducible costimulator (ICOS) and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) levels in CD4+ T cells. For all DC stimuli, cells high in n‐3 PUFAs showed reduced ability to respond to CD28 stimulation, to proliferate, and to express ICOS...... and CTLA‐4. Diminished T‐cell receptor (TCR) and CD28 signalling was found to be responsible for n‐3 PUFA effects. Thus, the dietary fatty acid composition influences the overall level of CD4+ T‐cell activation induced by DCs, while the priming effect of the DC stimuli modulates CD80, CD86 and CD40 levels...

  1. Modulation of Proinflammatory Cytokines in Monocyte-Derived Dendritic Cells by Porcine Reproductive and Respiratory Syndrome Virus Through Interaction with the Porcine Intercellular-Adhesion-Molecule-3-Grabbing Nonintegrin.

    Science.gov (United States)

    Piñeyro, Pablo E; Subramaniam, Sakthivel; Kenney, Scott P; Heffron, C Lynn; Giménez-Lirola, Luis G; Meng, Xiang-Jin

    2016-12-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important global swine pathogen. PRRSV infects porcine dendritic cells (DCs), but the effects of the interactions with DCs are largely unknown. Current research focuses on the production and regulation of interferons and selected inflammatory cytokines in DCs, which may play key roles in immune modulation. In addition, PRRSV also downregulates swine leukocyte antigen class I (SLA-I), SLA-II, and CD80/86 costimulatory molecules in DCs. In this study, we aim to evaluate the PRRSV immunomodulatory effects on monocyte-derived DCs (MoDCs) through interactions with porcine DC-SIGN (pDC-SIGN) receptor. We demonstrated that blocking the PRRSV and pDC-SIGN interactions in MoDCs with recombinant hICAM-3 did not affect the regulatory effects of PRRSV on SLA-I, SLA-II, or CD80/86 molecules. The hICAM-3 did not affect the morphological changes on MoDCs associated with their activation and maturation after PRRSV infection, and did not impair the virus infectivity in these cells either. The mRNA levels of tumor necrosis factor alpha (TNF-α), IL-12p35, IL-1β, and IL-6 were upregulated after hICAM-3 treatment or PRRSV infection, but in the presence of the blockage of pDC-SIGN in MoDCs with hICAM-3, PRRSV did not modulate the expression of these genes. However, in the presence of an anti-pDC-SIGN monoclonal antibody (mAb), we showed that PRRSV infection significantly reduced the mRNA expression levels of TNF-α and IL-1α, but enhanced the expression of IL-12p35 in MoDCs. Both hICAM-3-Fc and pDC-SIGN mAb treatments did not modulate proinflammatory cytokine protein levels in the culture supernatants of PRRSV-infected MoDCs. The results indicate that blocking the PRRSV-pDC-SIGN interactions by recombinant hICAM-3-Fc did not significantly affect virus infectivity, DC maturation, and proinflammatory cytokine gene expression in infected MoDCs. However, blocking the PRRSV-pDC-SIGN interactions on MoDCs with

  2. Dendritic Polymers for Theranostics.

    Science.gov (United States)

    Ma, Yuan; Mou, Quanbing; Wang, Dali; Zhu, Xinyuan; Yan, Deyue

    2016-01-01

    Dendritic polymers are highly branched polymers with controllable structures, which possess a large population of terminal functional groups, low solution or melt viscosity, and good solubility. Their size, degree of branching and functionality can be adjusted and controlled through the synthetic procedures. These tunable structures correspond to application-related properties, such as biodegradability, biocompatibility, stimuli-responsiveness and self-assembly ability, which are the key points for theranostic applications, including chemotherapeutic theranostics, biotherapeutic theranostics, phototherapeutic theranostics, radiotherapeutic theranostics and combined therapeutic theranostics. Up to now, significant progress has been made for the dendritic polymers in solving some of the fundamental and technical questions toward their theranostic applications. In this review, we briefly summarize how to control the structures of dendritic polymers, the theranostics-related properties derived from their structures and their theranostics-related applications.

  3. Developing Sensitive and Selective Nanosensors: A Single Molecule - Multiple Excitation Source Approach. Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing

    Science.gov (United States)

    2012-03-13

    REPORT FINAL REPORT - contract No. W911NF-09-C-0135 Part I. Developing Sensitive and Selective Nanosensors: A Single Molecule - Multiple Excitation...W911NF-09-C-0135 Part I. Developing Sensitive and Selective Nanosensors: A Single Molecule - Multiple Excitation Source Approach Part II. Altairnano...Nanosensors" A Single Molecule – Multiple Excitation Source Approach. The partnership of Altairnano, Inc. and Western Michigan University produced one

  4. Cryotherapy in Dendritic Keratitis.

    African Journals Online (AJOL)

    This study evaluates the effectiveness of cryotherapy in the treatment of dendritic Keratitis where antiviral agents are not available. The results show some improvement in visual acuity while one patient has a drop in vision. The extent of corneal scarring appears to depend on the duration of the disease and extent of stroma.

  5. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  6. Ubiquitous Over-Expression of Chromatin Remodeling Factor SRG3 Ameliorates the T Cell-Mediated Exacerbation of EAE by Modulating the Phenotypes of both Dendritic Cells and Macrophages.

    Science.gov (United States)

    Lee, Sung Won; Park, Hyun Jung; Jeon, Sung Ho; Lee, Changjin; Seong, Rho Hyun; Park, Se-Ho; Hong, Seokmann

    2015-01-01

    Although SWI3-related gene (SRG3), a chromatin remodeling factor, is critical for various biological processes including early embryogenesis and thymocyte development, it is unclear whether SRG3 is involved in the differentiation of CD4+ T cells, the key mediator of adaptive immune responses. Because it is known that experimental autoimmune encephalomyelitis (EAE) development is determined by the activation of CD4+ T helper cells, here, we investigated the role of SRG3 in EAE development using SRG3 transgenic mouse models exhibiting two distinct SRG3 expression patterns: SRG3 expression driven by either the CD2 or β-actin promoter. We found that the outcome of EAE development was completely different depending on the expression pattern of SRG3. The specific over-expression of SRG3 using the CD2 promoter facilitated EAE via the induction of Th1 and Th17 cells, whereas the ubiquitous over-expression of SRG3 using the β-actin promoter inhibited EAE by promoting Th2 differentiation and suppressing Th1 and Th17 differentiation. In addition, the ubiquitous over-expression of SRG3 polarized CD4+ T cell differentiation towards the Th2 phenotype by converting dendritic cells (DCs) or macrophages to Th2 types. SRG3 over-expression not only reduced pro-inflammatory cytokine production by DCs but also shifted macrophages from the inducible nitric oxide synthase (iNOS)-expressing M1 phenotype to the arginase-1-expressing M2 phenotype during EAE. In addition, Th2 differentiation in β-actin-SRG3 Tg mice during EAE was associated with an increase in the basophil and mast cell populations and in IL4 production. Furthermore, the increased frequency of Treg cells in the spinal cord of β-actin-SRG3 Tg mice might induce the suppression of and accelerate the recovery from EAE symptoms. Taken together, our results provide the first evidence supporting the development of a new therapeutic strategy for EAE involving the modulation of SRG3 expression to induce M2 and Th2 polarization

  7. Dendritic Polymers for Theranostics

    OpenAIRE

    Ma, Yuan; Mou, Quanbing; Wang, Dali; Zhu, Xinyuan; Yan, Deyue

    2016-01-01

    Dendritic polymers are highly branched polymers with controllable structures, which possess a large population of terminal functional groups, low solution or melt viscosity, and good solubility. Their size, degree of branching and functionality can be adjusted and controlled through the synthetic procedures. These tunable structures correspond to application-related properties, such as biodegradability, biocompatibility, stimuli-responsiveness and self-assembly ability, which are the key poin...

  8. Excited states

    CERN Document Server

    Lim, Edward C

    1974-01-01

    Excited States, Volume I reviews radiationless transitions, phosphorescence microwave double resonance through optical spectra in molecular solids, dipole moments in excited states, luminescence of polar molecules, and the problem of interstate interaction in aromatic carbonyl compounds. The book discusses the molecular electronic radiationless transitions; the double resonance techniques and the relaxation mechanisms involving the lowest triplet state of aromatic compounds; as well as the optical spectra and relaxation in molecular solids. The text also describes dipole moments and polarizab

  9. Orientation selection in dendritic evolution

    Science.gov (United States)

    Haxhimali, Tomorr; Karma, Alain; Gonzales, Frédéric; Rappaz, Michel

    2006-08-01

    Dendritic crystal growth patterns have fascinated scientists for several centuries. Much of the aesthetic appeal of these patterns stems from the hierarchical structure of primary-, secondary-, and higher-order branches, which typically grow along principal crystallographic axes. Atypical growth directions have also been observed. Here, we demonstrate both computationally and experimentally that the range of possible dendrite growth directions, and hence the morphological diversity of the resulting dendritic structures, is much richer than previously anticipated. In particular, we show that primary dendrite growth directions can vary continuously between different crystallographic directions as a function of the composition-dependent anisotropy parameters. The study combines phase-field simulations of equiaxed dendritic growth and directional freezing of Al-Zn alloys. Both simulations and experiments exhibit continuous changes of direction from to for an underlying cubic symmetry. These results have important implications for controlling the microstructure of a wide range of cast alloys that solidify dendritically.

  10. Frequency-Dependent Habituation Deficit of the Nociceptive Blink Reflex in Aura With Migraine Headache. Can Migraine Aura Modulate Trigeminal Excitability?

    Science.gov (United States)

    Perrotta, Armando; Anastasio, Maria Grazia; De Icco, Roberto; Coppola, Gianluca; Ambrosini, Anna; Serrao, Mariano; Sandrini, Giorgio; Pierelli, Francesco

    2017-06-01

    that AwMH and MWoA share some pathogenetic aspects, and also that migraine aura physiopathology may play a modulating role on the excitability of the nociceptive trigeminal pathways. © 2017 American Headache Society.

  11. Dendritic Alloy Solidification Experiment (DASE)

    Science.gov (United States)

    Beckermann, C.; Karma, A.; Steinbach, I.; deGroh, H. C., III

    2001-01-01

    A space experiment, and supporting ground-based research, is proposed to study the microstructural evolution in free dendritic growth from a supercooled melt of the transparent model alloy succinonitrile-acetone (SCN-ACE). The research is relevant to equiaxed solidification of metal alloy castings. The microgravity experiment will establish a benchmark for testing of equiaxed dendritic growth theories, scaling laws, and models in the presence of purely diffusive, coupled heat and solute transport, without the complicating influences of melt convection. The specific objectives are to: determine the selection of the dendrite tip operating state, i.e. the growth velocity and tip radius, for free dendritic growth of succinonitrile-acetone alloys; determine the growth morphology and sidebranching behavior for freely grown alloy dendrites; determine the effects of the thermal/solutal interactions in the growth of an assemblage of equiaxed alloy crystals; determine the effects of melt convection on the free growth of alloy dendrites; measure the surface tension anisotropy strength of succinon itrile -acetone alloys establish a theoretical and modeling framework for the experiments. Microgravity experiments on equiaxed dendritic growth of alloy dendrites have not been performed in the past. The proposed experiment builds on the Isothermal Dendritic Growth Experiment (IDGE) of Glicksman and coworkers, which focused on the steady growth of a single crystal from pure supercooled melts (succinonitrile and pivalic acid). It also extends the Equiaxed Dendritic Solidification Experiment (EDSE) of the present investigators, which is concerned with the interactions and transients arising in the growth of an assemblage of equiaxed crystals (succinonitrile). However, these experiments with pure substances are not able to address the issues related to coupled heat and solute transport in growth of alloy dendrites.

  12. Impurity effects in dendritic solidification

    Science.gov (United States)

    Karma, A.; Langer, J. S.

    1984-01-01

    A quantitative calculation of growth rates and tip radii is presented for dendrites growing in undercooled dilute solutions. Included in the calculations are the capillary corrections to the steady-state Ivantsov needle-crystal solutions. The results show good agreement with available experimental data and support the validity of the marginal-stability theory of dendritic growth.

  13. The shaping of two distinct dendritic spikes by A-type voltage-gated K+ channels

    Directory of Open Access Journals (Sweden)

    Sungchil eYang

    2015-12-01

    Full Text Available Dendritic ion channels have been a subject of intense research in neuroscience because active ion channels in dendrites shape input signals. Ca2+-permeable channels including NMDA receptors (NMDARs have been implicated in supralinear dendritic integration, and the IA conductance in sublinear integration. Despite their essential roles in dendritic integration, it has remained uncertain whether these conductances coordinate with, or counteract, each other in the process of dendritic integration. To address this question, experiments were designed in hippocampal CA1 neurons with a recent 3D digital holography system that has shown excellent performance for spatial photoactivation. The results demonstrated a role of IA as a key contributor to two distinct dendritic spikes, low- and high-threshold Ca2+ spikes, through a preferential action of IA on Ca2+-permeable channel-mediated currents, over fast AMPAR-mediated currents. It is likely that the rapid kinetics of IA provides feed-forward inhibition to counteract the delayed Ca2+ channel-mediated dendritic excitability. This research reveals one dynamic ionic mechanism of dendritic integration, and may contribute to a new understanding of neuronal hyperexcitability embedded in several neural diseases such as epilepsy, fragile X syndrome and Alzheimer's disease.

  14. Targeted pruning of a neuron’s dendritic tree via femtosecond laser dendrotomy

    Science.gov (United States)

    Go, Mary Ann; Choy, Julian Min Chiang; Colibaba, Alexandru Serban; Redman, Stephen; Bachor, Hans-A.; Stricker, Christian; Daria, Vincent Ricardo

    2016-01-01

    Neurons are classified according to action potential firing in response to current injection. While such firing patterns are shaped by the composition and distribution of ion channels, modelling studies suggest that the geometry of dendritic branches also influences temporal firing patterns. Verifying this link is crucial to understanding how neurons transform their inputs to output but has so far been technically challenging. Here, we investigate branching-dependent firing by pruning the dendritic tree of pyramidal neurons. We use a focused ultrafast laser to achieve highly localized and minimally invasive cutting of dendrites, thus keeping the rest of the dendritic tree intact and the neuron functional. We verify successful dendrotomy via two-photon uncaging of neurotransmitters before and after dendrotomy at sites around the cut region and via biocytin staining. Our results show that significantly altering the dendritic arborisation, such as by severing the apical trunk, enhances excitability in layer V cortical pyramidal neurons as predicted by simulations. This method may be applied to the analysis of specific relationships between dendritic structure and neuronal function. The capacity to dynamically manipulate dendritic topology or isolate inputs from various dendritic domains can provide a fresh perspective on the roles they play in shaping neuronal output.

  15. Active action potential propagation but not initiation in thalamic interneuron dendrites

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  16. Axonal Excitability in Amyotrophic Lateral Sclerosis : Axonal Excitability in ALS.

    Science.gov (United States)

    Park, Susanna B; Kiernan, Matthew C; Vucic, Steve

    2017-01-01

    Axonal excitability testing provides in vivo assessment of axonal ion channel function and membrane potential. Excitability techniques have provided insights into the pathophysiological mechanisms underlying the development of neurodegeneration and clinical features of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Specifically, abnormalities of Na+ and K+ conductances contribute to development of membrane hyperexcitability in ALS, thereby leading to symptom generation of muscle cramps and fasciculations, in addition to promoting a neurodegenerative cascade via Ca2+-mediated processes. Modulation of axonal ion channel function in ALS has resulted in significant symptomatic improvement that has been accompanied by stabilization of axonal excitability parameters. Separately, axonal ion channel dysfunction evolves with disease progression and correlates with survival, thereby serving as a potential therapeutic biomarker in ALS. The present review provides an overview of axonal excitability techniques and the physiological mechanisms underlying membrane excitability, with a focus on the role of axonal ion channel dysfunction in motor neuron disease and related neuromuscular diseases.

  17. Controllable optical modulation of blue/green up-conversion fluorescence from Tm3+ (Er3+) single-doped glass ceramics upon two-step excitation of two-wavelengths.

    Science.gov (United States)

    Chen, Zhi; Kang, Shiliang; Zhang, Hang; Wang, Ting; Lv, Shichao; Chen, Qiuqun; Dong, Guoping; Qiu, Jianrong

    2017-04-03

    Optical modulation is a crucial operation in photonics for network data processing with the aim to overcome information bottleneck in terms of speed, energy consumption, dispersion and cross-talking from conventional electronic interconnection approach. However, due to the weak interactions between photons, a facile physical approach is required to efficiently manipulate photon-photon interactions. Herein, we demonstrate that transparent glass ceramics containing LaF3: Tm3+ (Er3+) nanocrystals can enable fast-slow optical modulation of blue/green up-conversion fluorescence upon two-step excitation of two-wavelengths at telecom windows (0.8-1.8 μm). We show an optical modulation of more than 1500% (800%) of the green (blue) up-conversion fluorescence intensity, and fast response of 280 μs (367 μs) as well as slow response of 5.82 ms (618 μs) in the green (blue) up-conversion fluorescence signal, respectively. The success of manipulating laser at telecom windows for fast-slow optical modulation from rear-earth single-doped glass ceramics may find application in all-optical fiber telecommunication areas.

  18. Controllable optical modulation of blue/green up-conversion fluorescence from Tm3+ (Er3+) single-doped glass ceramics upon two-step excitation of two-wavelengths

    Science.gov (United States)

    Chen, Zhi; Kang, Shiliang; Zhang, Hang; Wang, Ting; Lv, Shichao; Chen, Qiuqun; Dong, Guoping; Qiu, Jianrong

    2017-04-01

    Optical modulation is a crucial operation in photonics for network data processing with the aim to overcome information bottleneck in terms of speed, energy consumption, dispersion and cross-talking from conventional electronic interconnection approach. However, due to the weak interactions between photons, a facile physical approach is required to efficiently manipulate photon-photon interactions. Herein, we demonstrate that transparent glass ceramics containing LaF3: Tm3+ (Er3+) nanocrystals can enable fast-slow optical modulation of blue/green up-conversion fluorescence upon two-step excitation of two-wavelengths at telecom windows (0.8-1.8 μm). We show an optical modulation of more than 1500% (800%) of the green (blue) up-conversion fluorescence intensity, and fast response of 280 μs (367 μs) as well as slow response of 5.82 ms (618 μs) in the green (blue) up-conversion fluorescence signal, respectively. The success of manipulating laser at telecom windows for fast-slow optical modulation from rear-earth single-doped glass ceramics may find application in all-optical fiber telecommunication areas.

  19. Regulation of neuronal input transformations by tunable dendritic inhibition.

    Science.gov (United States)

    Lovett-Barron, Matthew; Turi, Gergely F; Kaifosh, Patrick; Lee, Peter H; Bolze, Frédéric; Sun, Xiao-Hua; Nicoud, Jean-François; Zemelman, Boris V; Sternson, Scott M; Losonczy, Attila

    2012-01-15

    Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type-specific pharmacogenetic silencing in vitro, we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons.

  20. Dopamine Induces LTP Differentially in Apical and Basal Dendrites through BDNF and Voltage-Dependent Calcium Channels

    Science.gov (United States)

    Navakkode, Sheeja; Sajikumar, Sreedharan; Korte, Martin; Soong, Tuck Wah

    2012-01-01

    The dopaminergic modulation of long-term potentiation (LTP) has been studied well, but the mechanism by which dopamine induces LTP (DA-LTP) in CA1 pyramidal neurons is unknown. Here, we report that DA-LTP in basal dendrites is dependent while in apical dendrites it is independent of activation of L-type voltage-gated calcium channels (VDCC).…

  1. Excited Delirium

    Directory of Open Access Journals (Sweden)

    Takeuchi, Asia

    2011-02-01

    Full Text Available Excited (or agitated delirium is characterized by agitation, aggression, acute distress and sudden death, often in the pre-hospital care setting. It is typically associated with the use of drugs that alter dopamine processing, hyperthermia, and, most notably, sometimes with death of the affected person in the custody of law enforcement. Subjects typically die from cardiopulmonary arrest, although the cause is debated. Unfortunately an adequate treatment plan has yet to be established, in part due to the fact that most patients die before hospital arrival. While there is still much to be discovered about the pathophysiology and treatment, it is hoped that this extensive review will provide both police and medical personnel with the information necessary to recognize and respond appropriately to excited delirium. [West J Emerg Med. 2011;12(1:77-83.

  2. Development of dendrite polarity in Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Hill Sarah E

    2012-10-01

    Full Text Available Abstract Background Drosophila neurons have dendrites that contain minus-end-out microtubules. This microtubule arrangement is different from that of cultured mammalian neurons, which have mixed polarity microtubules in dendrites. Results To determine whether Drosophila and mammalian dendrites have a common microtubule organization during development, we analyzed microtubule polarity in Drosophila dendritic arborization neuron dendrites at different stages of outgrowth from the cell body in vivo. As dendrites initially extended, they contained mixed polarity microtubules, like mammalian neurons developing in culture. Over a period of several days this mixed microtubule array gradually matured to a minus-end-out array. To determine whether features characteristic of dendrites were localized before uniform polarity was attained, we analyzed dendritic markers as dendrites developed. In all cases the markers took on their characteristic distribution while dendrites had mixed polarity. An axonal marker was also quite well excluded from dendrites throughout development, although this was perhaps more efficient in mature neurons. To confirm that dendrite character could be acquired in Drosophila while microtubules were mixed, we genetically disrupted uniform dendritic microtubule organization. Dendritic markers also localized correctly in this case. Conclusions We conclude that developing Drosophila dendrites initially have mixed microtubule polarity. Over time they mature to uniform microtubule polarity. Dendrite identity is established before the mature microtubule arrangement is attained, during the period of mixed microtubule polarity.

  3. Equiaxed Dendritic Solidification Experiment (EDSE)

    Science.gov (United States)

    Beckermann, C.; Karma, A.; Steinbach, I.; deGroh, H. C., III

    2001-01-01

    The objective of the research is to quantitatively determine and understand the fundamental mechanisms that control the microstructural evolution during equiaxed dendritic solidification. A microgravity experiment will be conducted to obtain benchmark data on the transient growth and interaction of up to four equiaxed crystals of a pure and transparent metal analog (succinonitrile, SCN) under strictly diffusion-dominated conditions. Of interest in the experiment are the transient evolution of the primary and secondary dendrite tip speeds, the dendrite morphology and solid fraction, the tip selection criterion, and the temperature field in the melt for a range of interaction "strengths" between the crystals. The experiment extends the microgravity measurements of Glicksman and co-workers isothermal dendritic growth experiment (IDGE) for steady growth of a single dendrite to a case where growth transients are introduced due to thermal interactions between neighboring dendrites - a situation closer to actual casting conditions. Corresponding Earth-based experiments will be conducted to ascertain the influence of melt convection. The experiments are supported by a variety of analytical models and numerical simulations. The data will be used to develop and test theories of transient dendritic growth and the solidification of multiple interacting equiaxed crystals in a supercooled melt.

  4. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  5. Dendrite Injury Triggers DLK-Independent Regeneration

    Directory of Open Access Journals (Sweden)

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  6. Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

    Directory of Open Access Journals (Sweden)

    Hermann Cuntz

    2014-03-01

    Full Text Available Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL. ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of

  7. Make immunological peace not war: Potential applications of tolerogenic dendritic cells

    Directory of Open Access Journals (Sweden)

    Emma Louise Walton

    2017-04-01

    Full Text Available In this issue of the Biomedical Journal, we explore the powerful immunosuppressive properties of tolerogenic dendritic cells and discuss their potential to bring about lifelong tolerance in transplantation and autoimmune disease. We also highlight an exciting new development in the field of malaria diagnosis that could facilitate early detection of the disease.

  8. Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Hallermann, Stefan; Stuart, Greg J.

    2006-01-01

    The hyperpolarization-activated cation current (Ih) plays an important role in regulating neuronal excitability, yet its native single-channel properties in the brain are essentially unknown. Here we use variance-mean analysis to study the properties of single Ih channels in the apical dendrites of

  9. Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor.

    Science.gov (United States)

    van der Velden, Luuk; van Hooft, Johannes A; Chameau, Pascal

    2012-09-01

    We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT(3) receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT(3A) receptor showed exuberant apical dendrites of these cortical pyramidal neurons. Because model studies have shown the role of dendritic morphology on neuronal firing pattern, we used the 5-HT(3A) knockout mouse to explore the impact of dendritic hypercomplexity on the electrophysiological properties of this specific class of neurons. Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex.

  10. Elevated neuronal excitability due to modulation of the voltage-gated sodium channel Nav1.6 by Aβ1-42

    Directory of Open Access Journals (Sweden)

    Xi eWang

    2016-03-01

    Full Text Available Aberrant increases in neuronal network excitability may contribute to the cognitive deficits in Alzheimer’s disease (AD. However, the mechanisms underlying hyperexcitability are not fully understood. Such overexcitation of neuronal networks has been detected in the brains of APP/PS1 mice. In the present study, using current-clamp recording techniques, we observed that 12 days in vitro (DIV primary cultured pyramidal neurons from P0 APP/PS1 mice exhibited a more prominent action potential burst and a lower threshold than WT littermates. Moreover, after treatment with Aβ1-42 peptide, 12 DIV primary cultured neurons showed similar changes, to a greater degree than in controls. Voltage-clamp recordings revealed that the voltage-dependent sodium current density of neurons incubated with Aβ1-42 was significantly increased, without change in the voltage-dependent sodium channel kinetic characteristics. Immunohistochemistry and western blot results showed that, after treatment with Aβ1-42, expressions of Nav and Nav1.6 subtype increased in cultured neurons or APP/PS1 brains compared to control groups. The intrinsic neuronal hyperexcitability of APP/PS1 mice might thus be due to an increased expression of voltage-dependent sodium channels induced by Aβ1-42. These results may illuminate the mechanism of aberrant neuronal networks in AD.

  11. Spectroscopic and quantum mechanical approach of solvatochromic immobilization: modulation of electronic structure and excited-state properties of 1,8-naphthalimide derivative.

    Science.gov (United States)

    Mati, Soumya Sundar; Chall, Sayantani; Rakshit, Soumyadipta; Bhattacharya, Subhash Chandra

    2015-03-01

    Photophysical and spectroscopic properties of a fluorescent analogue, 2-(5-selenocyanato-pentyl)-6-chlorobenzo- [de]isoquinoline-1,3-dione (NP) in different solvents has been described in this paper using steady-state, time resolved spectroscopy and density functional theory (DFT) calculation. Stoke's shifted emission band in different solvents clearly demonstrate the highly polar character of the excited state, which is also supported by the enhancement of dipole moment of the molecule upon photoexcitation. Spectroscopic studies and multiple linear regression analysis method reveal that the solvatochromic behavior of the probe depends not only on the polarity of the medium but also on the hydrogen bonding interaction with the solvents. When the solvent effect was taken into account, the computed results show encouraging agreement with known experimental data. This article reveals the excellent correlation between the predicted and experimental spectral data of 1,8-naphthalimide derivative, providing a useful tool in the design of new fluorogenic probes having potential therapeutic activity.

  12. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  13. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Adriana J Michielsen

    Full Text Available Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5 could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  14. Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

    Science.gov (United States)

    Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

    2015-01-21

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

  15. Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior

    Directory of Open Access Journals (Sweden)

    Alex M. Dopico

    2014-12-01

    Full Text Available In most tissues, the function of calcium- and voltage-gated potassium (BK channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium, BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1 subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus, acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.

  16. Gravitational effects in dendritic growth

    Science.gov (United States)

    Glicksman, M. E.; Singh, N. B.; Chopra, M.

    1983-01-01

    The theories of diffusion-controlled dendritic crystallization will be reviewed briefly, along with recently published critical experiments on the kinetics and morphology of dendritic growth in pure substances. The influence of the gravitational body force on dendrite growth kinetics will be shown to be highly dependent on the growth orientation with respect to the gravity vector and on the level of the thermal supercooling. In fact, an abrupt transition occurs at a critical supercooling, above which diffusional transport dominates the growth process and below which convective transport dominates. Our most recent work on binary mixtures shows that dilute solute additions influence the crystallization process indirectly, by altering the interfacial stability, rather than by directly affecting the transport mode. Directions for future studies in this field will also be discussed.

  17. Mechanisms and Function of Dendritic Exocytosis

    OpenAIRE

    Kennedy, Matthew J.; Ehlers, Michael D.

    2011-01-01

    Dendritic exocytosis is required for a broad array of neuronal functions including retrograde signaling, neurotransmitter release, synaptic plasticity, and establishment of neuronal morphology. While the details of synaptic vesicle exocytosis from presynaptic terminals have been intensely studied for decades, the mechanisms of dendritic exocytosis are only now emerging. Here we review the molecules and mechanisms of dendritic exocytosis, and discuss how exocytosis from dendrites influences ne...

  18. Dendritic mRNAs encode diversified functionalities in hippocampal pyramidal neurons

    Directory of Open Access Journals (Sweden)

    Bloch Lisa M

    2006-02-01

    Full Text Available Abstract Background Targeted transport of messenger RNA and local protein synthesis near the synapse are important for synaptic plasticity. In order to gain an overview of the composition of the dendritic mRNA pool, we dissected out stratum radiatum (dendritic lamina from rat hippocampal CA1 region and compared its mRNA content with that of stratum pyramidale (cell body layer using a set of cDNA microarrays. RNAs that have over-representation in the dendritic fraction were annotated and sorted into function groups. Results We have identified 154 dendritic mRNA candidates, which can be arranged into the categories of receptors and channels, signaling molecules, cytoskeleton and adhesion molecules, and factors that are involved in membrane trafficking, in protein synthesis, in posttranslational protein modification, and in protein degradation. Previously known dendritic mRNAs such as MAP2, calmodulin, and G protein gamma subunit were identified from our screening, as were mRNAs that encode proteins known to be important for synaptic plasticity and memory, such as spinophilin, Pumilio, eEF1A, and MHC class I molecules. Furthermore, mRNAs coding for ribosomal proteins were also found in dendrites. Conclusion Our results suggest that neurons transport a variety of mRNAs to dendrites, not only those directly involved in modulating synaptic plasticity, but also others that play more common roles in cellular metabolism.

  19. 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Lucia eCiranna

    2014-08-01

    Full Text Available Serotonin type 7 receptors (5-HT7 are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD, including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.

  20. Low-threshold Ca2+ current amplifies distal dendritic signaling in thalamic reticular neurons.

    Science.gov (United States)

    Crandall, Shane R; Govindaiah, G; Cox, Charles L

    2010-11-17

    The low-threshold transient calcium current (I(T)) plays a critical role in modulating the firing behavior of thalamic neurons; however, the role of I(T) in the integration of afferent information within the thalamus is virtually unknown. We have used two-photon laser scanning microscopy coupled with whole-cell recordings to examine calcium dynamics in the neurons of the strategically located thalamic reticular nucleus (TRN). We now report that a single somatic burst discharge evokes large-magnitude calcium responses, via I(T), in distal TRN dendrites. The magnitude of the burst-evoked calcium response was larger than those observed in thalamocortical projection neurons under the same conditions. We also demonstrate that direct stimulation of distal TRN dendrites, via focal glutamate application and synaptic activation, can locally activate distal I(T), producing a large distal calcium response independent of the soma/proximal dendrites. These findings strongly suggest that distally located I(T) may function to amplify afferent inputs. Boosting the magnitude ensures integration at the somatic level by compensating for attenuation that would normally occur attributable to passive cable properties. Considering the functional architecture of the TRN, elongated nature of their dendrites, and robust dendritic signaling, these distal dendrites could serve as sites of intense intra-modal/cross-modal integration and/or top-down modulation, leading to focused thalamocortical communication.

  1. Reciprocal Interaction of Dendrite Geometry and Nuclear Calcium-VEGFD Signaling Gates Memory Consolidation and Extinction.

    Science.gov (United States)

    Hemstedt, Thekla J; Bengtson, C Peter; Ramírez, Omar; Oliveira, Ana M M; Bading, Hilmar

    2017-07-19

    Nuclear calcium is an important signaling end point in synaptic excitation-transcription coupling that is critical for long-term neuroadaptations. Here, we show that nuclear calcium acting via a target gene, VEGFD, is required for hippocampus-dependent fear memory consolidation and extinction in mice. Nuclear calcium-VEGFD signaling upholds the structural integrity and complexity of the dendritic arbor of CA1 neurons that renders those cells permissive for the efficient generation of synaptic input-evoked nuclear calcium transients driving the expression of plasticity-related genes. Therefore, the gating of memory functions rests on the reciprocally reinforcing maintenance of an intact dendrite geometry and a functional synapse-to-nucleus communication axis. In psychiatric and neurodegenerative disorders, therapeutic application of VEGFD may help to stabilize dendritic structures and network connectivity, which may prevent cognitive decline and could boost the efficacy of extinction-based exposure therapies. SIGNIFICANCE STATEMENT This study uncovers a reciprocal relationship between dendrite geometry, the ability to generate nuclear calcium transients in response to synaptic inputs, and the subsequent induction of expression of plasticity-related and dendritic structure-preserving genes. Insufficient nuclear calcium signaling in CA1 hippocampal neurons and, consequently, reduced expression of the nuclear calcium target gene VEGFD, a dendrite maintenance factor, leads to reduced-complexity basal dendrites of CA1 neurons, which severely compromises the animals' consolidation of both memory and extinction memory. The structure-protective function of VEGFD may prove beneficial in psychiatric disorders as well as neurodegenerative and aging-related conditions that are associated with loss of neuronal structures, dysfunctional excitation-transcription coupling, and cognitive decline. Copyright © 2017 the authors 0270-6474/17/376946-10$15.00/0.

  2. Assisted morphogenesis: glial control of dendrite shapes.

    Science.gov (United States)

    Procko, Carl; Shaham, Shai

    2010-10-01

    Neurons display a myriad of dendritic architectures, reflecting their diverse roles in information processing and transduction in the nervous system. Recent findings suggest that neuronal signals may not account for all aspects of dendrite morphogenesis. Observations from C. elegans and other organisms suggest that glial cells can affect dendrite length and guidance, as well as localization and shapes of dendritic receptive structures, such as dendritic spines and sensory cilia. Thus, besides direct roles in controlling neuronal activity, glia contribute to neuron function by ensuring that neurons attain their proper shapes. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x.

    NARCIS (Netherlands)

    Die, van I.M.; Vliet, van SJ; Nyame, AK; Cummings, RD; Bank, CM; Appelmelk, B.J.; Geijtenbeek, T.B.H.; Kooijk, van Y.

    2003-01-01

    Schistosoma mansoni soluble egg antigens (SEAs) are crucially involved in modulating the host immune response to infection by S. mansoni. We report that human dendritic cells bind SEAs through the C-type lectin dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN). Monoclonal antibodies

  4. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x

    NARCIS (Netherlands)

    van Die, Irma; van Vliet, Sandra J.; Nyame, A. Kwame; Cummings, Richard D.; Bank, Christine M. C.; Appelmelk, Ben; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2003-01-01

    Schistosoma mansoni soluble egg antigens (SEAs) are crucially involved in modulating the host immune response to infection by S. mansoni. We report that human dendritic cells bind SEAs through the C-type lectin dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN). Monoclonal antibodies

  5. Advanced dendritic web growth development

    Science.gov (United States)

    Hopkins, R. H.

    1985-01-01

    A program to develop the technology of the silicon dendritic web ribbon growth process is examined. The effort is being concentrated on the area rate and quality requirements necessary to meet the JPL/DOE goals for terrestrial PV applications. Closed loop web growth system development and stress reduction for high area rate growth is considered.

  6. Intracellular correlates of acquisition and long-term memory of classical conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule HVI.

    Science.gov (United States)

    Schreurs, B G; Gusev, P A; Tomsic, D; Alkon, D L; Shi, T

    1998-07-15

    Intradendritic recordings in Purkinje cells from a defined area in parasaggital slices of cerebellar lobule HVI, obtained after rabbits were given either paired (classical conditioning) or explicitly unpaired (control) presentations of tone and periorbital electrical stimulation, were used to assess the nature and duration of conditioning-specific changes in Purkinje cell dendritic membrane excitability. We found a strong relationship between the level of conditioning and Purkinje cell dendritic membrane excitability after initial acquisition of the conditioned response. Moreover, conditioning-specific increases in Purkinje cell excitability were still present 1 month after classical conditioning. Although dendritically recorded membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in cells from paired or control animals, the size of a potassium channel-mediated transient hyperpolarization was significantly smaller in cells from animals that received classical conditioning. In slices of lobule HVI obtained from naive rabbits, the conditioning-related increases in membrane excitability could be mimicked by application of potassium channel antagonist tetraethylammonium chloride, iberiotoxin, or 4-aminopyridine. However, only 4-aminopyridine was able to reduce the transient hyperpolarization. The pharmacological data suggest a role for potassium channels and, possibly, channels mediating an IA-like current, in learning-specific changes in membrane excitability. The conditioning-specific increase in Purkinje cell dendritic excitability produces an afterhyperpolarization, which is hypothesized to release the cerebellar deep nuclei from inhibition, allowing conditioned responses to be elicited via the red nucleus and accessory abducens motorneurons.

  7. Fluorescence imaging of dendritic spines of Golgi-Cox-stained neurons using brightening background

    Science.gov (United States)

    Ai, Min; Xiong, Hanqing; Yang, Tao; Shang, Zhenhua; Chen, Muqing; Liu, Xiuli; Zeng, Shaoqun

    2015-01-01

    We report a novel fluorescence imaging approach to imaging nonfluorescence-labeled biological tissue samples. The method was demonstrated by imaging neurons in Golgi-Cox-stained and epoxy-resin-embedded samples through the excitation of the background fluorescence of the specimens. The dark neurons stood out clearly against background fluorescence in the images, enabling the tracing of a single dendritic spine using both confocal and wide-field fluorescence microscopy. The results suggest that the reported fluorescence imaging method would provide an effective alternative solution to image nonfluorescence-labeled samples, and it allows tracing the dendritic spine structure of neurons.

  8. Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells.

    Science.gov (United States)

    Szabo, Attila; Kovacs, Attila; Frecska, Ede; Rajnavolgyi, Eva

    2014-01-01

    The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.

  9. Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells.

    Directory of Open Access Journals (Sweden)

    Attila Szabo

    Full Text Available The orphan receptor sigma-1 (sigmar-1 is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT, its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.

  10. Modulation of regulatory T cell function by monocyte-derived dendritic cells matured through electroporation with mRNA encoding CD40 ligand, constitutively active TLR4, and CD70.

    Science.gov (United States)

    Pen, Joeri J; De Keersmaecker, Brenda; Maenhout, Sarah K; Van Nuffel, An M T; Heirman, Carlo; Corthals, Jurgen; Escors, David; Bonehill, Aude; Thielemans, Kris; Breckpot, Karine; Aerts, Joeri L

    2013-08-15

    Regulatory T cells (Tregs) counteract anticancer immune responses through a number of mechanisms, limiting dendritic cell (DC)-based anticancer immunotherapy. In this study, we investigated the influence of various DC activation stimuli on the Treg functionality. We compared DCs activated by electroporation with mRNA encoding constitutively active TLR4 (caTLR4) and CD40 ligand (DiMix-DCs), or these factors together with mRNA encoding the costimulatory molecule CD70 (TriMix-DCs) with DCs maturated in the presence of a mixture of inflammatory cytokines (DCs maturated with a combination of the cytokines IL-1β, IL-6, TNF-α, and PGE2) for their ability to counteract Tregs on different levels. We first demonstrated that there was no difference in the extent of Treg induction starting from CD4(+)CD25(-) T cells under the influence of the different DC maturation stimuli. Second, we showed that both DiMix- and TriMix-DCs could partly alleviate Treg inhibition of CD8(+) T cells. Third, we observed that CD8(+) T cells that had been precultured with DiMix-DCs or TriMix-DCs were partially protected against subsequent Treg suppression. Finally, we showed that Tregs cocultured in the presence of TriMix-DCs, but not DiMix-DCs, partially lost their suppressive capacity. This was accompanied by a decrease in CD27 and CD25 expression on Tregs, as well as an increase in the expression of T-bet and secretion of IFN-γ, TNF-α, and IL-10, suggesting a shift of the Treg phenotype toward a Th1 phenotype. In conclusion, these data suggest that TriMix-DCs are not only able to suppress Treg functions, but moreover could be able to reprogram Tregs to Th1 cells under certain circumstances.

  11. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum.

    Science.gov (United States)

    Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

    2016-11-15

    Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including horses. Currently, the gold standard protocol for generating dendritic cells from monocytes across various species relies upon a combination of GM-CSF and IL-4 added to cell culture medium which is supplemented with FBS. The aim of this study was to substitute FBS with heterologous horse serum. For this purpose, equine monocyte-derived dendritic cells (eqMoDC) were generated in the presence of horse serum or FBS and analysed for the effect on morphology, phenotype and immunological properties. Changes in the expression of phenotypic markers (CD14, CD86, CD206) were assessed during dendritic cell maturation by flow cytometry. To obtain a more complete picture of the eqMoDC differentiation and assess possible differences between FBS- and horse serum-driven cultures, a transcriptomic microarray analysis was performed. Lastly, immature eqMoDC were primed with a primary antigen (ovalbumin) or a recall antigen (tetanus toxoid) and, after maturation, were co-cultured with freshly isolated autologous CD5 + T lymphocytes to assess their T cell stimulatory capacity. The microarray analysis demonstrated that eqMoDC generated with horse serum were indistinguishable from those generated with FBS. However, eqMoDC incubated with horse serum-supplemented medium exhibited a more characteristic dendritic cell morphology during differentiation from monocytes. A significant increase in cell viability was also observed in eqMoDC cultured with horse serum. Furthermore, eqMoDC generated in the presence of horse serum

  12. Deciphering dendritic cell heterogenity in immunity

    Directory of Open Access Journals (Sweden)

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  13. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  14. Preferential control of basal dendritic protrusions by EphB2.

    Directory of Open Access Journals (Sweden)

    Matthew S Kayser

    2011-02-01

    Full Text Available The flow of information between neurons in many neural circuits is controlled by a highly specialized site of cell-cell contact known as a synapse. A number of molecules have been identified that are involved in central nervous system synapse development, but knowledge is limited regarding whether these cues direct organization of specific synapse types or on particular regions of individual neurons. Glutamate is the primary excitatory neurotransmitter in the brain, and the majority of glutamatergic synapses occur on mushroom-shaped protrusions called dendritic spines. Changes in the morphology of these structures are associated with long-lasting modulation of synaptic strength thought to underlie learning and memory, and can be abnormal in neuropsychiatric disease. Here, we use rat cortical slice cultures to examine how a previously-described synaptogenic molecule, the EphB2 receptor tyrosine kinase, regulates dendritic protrusion morphology in specific regions of the dendritic arbor in cortical pyramidal neurons. We find that alterations in EphB2 signaling can bidirectionally control protrusion length, and knockdown of EphB2 expression levels reduces the number of dendritic spines and filopodia. Expression of wild-type or dominant negative EphB2 reveals that EphB2 preferentially regulates dendritic protrusion structure in basal dendrites. Our findings suggest that EphB2 may act to specify synapse formation in a particular subcellular region of cortical pyramidal neurons.

  15. Cell-intrinsic drivers of dendrite morphogenesis.

    Science.gov (United States)

    Puram, Sidharth V; Bonni, Azad

    2013-12-01

    The proper formation and morphogenesis of dendrites is fundamental to the establishment of neural circuits in the brain. Following cell cycle exit and migration, neurons undergo organized stages of dendrite morphogenesis, which include dendritic arbor growth and elaboration followed by retraction and pruning. Although these developmental stages were characterized over a century ago, molecular regulators of dendrite morphogenesis have only recently been defined. In particular, studies in Drosophila and mammalian neurons have identified numerous cell-intrinsic drivers of dendrite morphogenesis that include transcriptional regulators, cytoskeletal and motor proteins, secretory and endocytic pathways, cell cycle-regulated ubiquitin ligases, and components of other signaling cascades. Here, we review cell-intrinsic drivers of dendrite patterning and discuss how the characterization of such crucial regulators advances our understanding of normal brain development and pathogenesis of diverse cognitive disorders.

  16. Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3)

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Gad, Monika; Walter, Mark R

    2004-01-01

    Dendritic cells (DC) modulated to induce T cell hyporesponsiveness have promising potential in immunotherapy of autoimmune disorders and for the prevention of allograft rejection. While studying the effect of immunosuppressive agents on the maturation of DC we found that 1alpha,25-Dihydroxyvitami...... immunosuppressive drug combination for the induction of DCs capable of inducing T cell hyporesponsiveness....

  17. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-01-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This

  18. Genetically modified lactococcus lactis for delivery of human interleukin-10 to dendritic cells

    NARCIS (Netherlands)

    H. Braat (Henri); I.L. Huibregtse (Inge ); S.A.J. Zaat (Sebastiaan); M.L. Kapsenberg (Martien ); M.A. Sartori da Silva; M.P. Peppelenbosch (Maikel); S. van Deventer (Sander)

    2012-01-01

    textabstractInterleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.lacti s IL-10) on DC function in vitro. Monocyte-derived DC incubated

  19. Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells

    NARCIS (Netherlands)

    Huibregtse, Inge L.; Zaat, Sebatian A.; Kapsenberg, Martien L.; Sartori da Silva, Maria A.; Peppelenbosch, Maikel P.; van Deventer, Sander J. H.; Braat, Henri

    2012-01-01

    Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L. lactis(IL-10)) on DC function in vitro. Monocyte-derived DC incubated with L.

  20. Reelin Supplementation Enhances Cognitive Ability, Synaptic Plasticity, and Dendritic Spine Density

    Science.gov (United States)

    Rogers, Justin T.; Rusiana, Ian; Trotter, Justin; Zhao, Lisa; Donaldson, Erika; Pak, Daniel T.S.; Babus, Lenard W.; Peters, Melinda; Banko, Jessica L.; Chavis, Pascale; Rebeck, G. William; Hoe, Hyang-Sook; Weeber, Edwin J.

    2011-01-01

    Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive…

  1. Analyzing Dendritic Morphology in Columns and Layers.

    Science.gov (United States)

    Ting, Chun-Yuan; McQueen, Philip G; Pandya, Nishith; McCreedy, Evan S; McAuliffe, Matthew; Lee, Chi-Hon

    2017-03-23

    In many regions of the central nervous systems, such as the fly optic lobes and the vertebrate cortex, synaptic circuits are organized in layers and columns to facilitate brain wiring during development and information processing in developed animals. Postsynaptic neurons elaborate dendrites in type-specific patterns in specific layers to synapse with appropriate presynaptic terminals. The fly medulla neuropil is composed of 10 layers and about 750 columns; each column is innervated by dendrites of over 38 types of medulla neurons, which match with the axonal terminals of some 7 types of afferents in a type-specific fashion. This report details the procedures to image and analyze dendrites of medulla neurons. The workflow includes three sections: (i) the dual-view imaging section combines two confocal image stacks collected at orthogonal orientations into a high-resolution 3D image of dendrites; (ii) the dendrite tracing and registration section traces dendritic arbors in 3D and registers dendritic traces to the reference column array; (iii) the dendritic analysis section analyzes dendritic patterns with respect to columns and layers, including layer-specific termination and planar projection direction of dendritic arbors, and derives estimates of dendritic branching and termination frequencies. The protocols utilize custom plugins built on the open-source MIPAV (Medical Imaging Processing, Analysis, and Visualization) platform and custom toolboxes in the matrix laboratory language. Together, these protocols provide a complete workflow to analyze the dendritic routing of Drosophila medulla neurons in layers and columns, to identify cell types, and to determine defects in mutants.

  2. Neuromodulation impact on nonlinear firing behavior of a reduced model motoneuron with the active dendrite

    Science.gov (United States)

    Kim, Hojeong; Heckman, C. J.

    2014-01-01

    Neuromodulatory inputs from brainstem systems modulate the normal function of spinal motoneurons by altering the activation properties of persistent inward currents (PICs) in their dendrites. However, the effect of the PIC on firing outputs also depends on its location in the dendritic tree. To investigate the interaction between PIC neuromodulation and PIC location dependence, we used a two-compartment model that was biologically realistic in that it retains directional and frequency-dependent electrical coupling between the soma and the dendrites, as seen in multi-compartment models based on full anatomical reconstructions of motoneurons. Our two-compartment approach allowed us to systematically vary the coupling parameters between the soma and the dendrite to accurately reproduce the effect of location of the dendritic PIC on the generation of nonlinear (hysteretic) motoneuron firing patterns. Our results show that as a single parameter value for PIC activation was either increased or decreased by 20% from its default value, the solution space of the coupling parameter values for nonlinear firing outputs was drastically reduced by approximately 80%. As a result, the model tended to fire only in a linear mode at the majority of dendritic PIC sites. The same results were obtained when all parameters for the PIC activation simultaneously changed only by approximately ±10%. Our results suggest the democratization effect of neuromodulation: the neuromodulation by the brainstem systems may play a role in switching the motoneurons with PICs at different dendritic locations to a similar mode of firing by reducing the effect of the dendritic location of PICs on the firing behavior. PMID:25309410

  3. Low Power Dendritic Computation for Wordspotting

    Directory of Open Access Journals (Sweden)

    Stephen Nease

    2013-05-01

    Full Text Available In this paper, we demonstrate how a network of dendrites can be used to build the state decoding block of a wordspotter similar to a Hidden Markov Model (HMM classifier structure. We present simulation and experimental data for a single line dendrite and also experimental results for a dendrite-based classifier structure. This work builds on previously demonstrated building blocks of a neural network: the channel, synapses and dendrites using CMOS circuits. These structures can be used for speech and pattern recognition. The computational efficiency of such a system is >10 MMACs/μW as compared to Digital Systems which perform 10 MMACs/mW.

  4. Data for spatial characterization of AC signal propagation over primary neuron dendrites

    Directory of Open Access Journals (Sweden)

    Hojeong Kim

    2016-03-01

    Full Text Available Action potentials generated near the soma propagate not only into the axonal nerve connecting to the adjacent neurons but also into the dendrites interacting with a diversity of synaptic inputs as well as voltage gated ion channels. Measuring voltage attenuation factors between the soma and all single points of the dendrites in the anatomically reconstructed primary neurons with the same cable properties, we report the signal propagation data showing how the alternating current (AC signal such as action potentials back-propagates over the dendrites among different types of primary neurons. Fitting equations and their parameter values for the data are also presented to quantitatively capture the spatial profile of AC signal propagation from the soma to the dendrites in primary neurons. Our data is supplemental to our original study for the dependency of dendritic signal propagation and excitability, and their relationship on the cell type-specific structure in primary neurons (DOI: 10.1016/j.neulet.2015.10.017 [1].

  5. Nitric oxide and the autonomic regulation of cardiac excitability. The G.L. Brown Prize Lecture.

    Science.gov (United States)

    Paterson, D

    2001-01-01

    Cardiac sympathetic imbalance and arrhythmia; Nitric oxide-cGMP pathway and the cholinergic modulation of cardiac excitability; Nitric oxide-cGMP pathway and the sympathetic modulation of cardiac excitability; Functional significance of nitric oxide in the autonomic regulation of cardiac excitability; Summary; References. Experimental Physiology (2001) 86.1, 1-12.

  6. Make immunological peace not war: Potential applications of tolerogenic dendritic cells.

    Science.gov (United States)

    Walton, Emma Louise

    2017-04-01

    In this issue of the Biomedical Journal, we explore the powerful immunosuppressive properties of tolerogenic dendritic cells and discuss their potential to bring about lifelong tolerance in transplantation and autoimmune disease. We also highlight an exciting new development in the field of malaria diagnosis that could facilitate early detection of the disease. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  7. Histamine regulates murine primary dendritic cell functions.

    Science.gov (United States)

    Schenk, Heiko; Neumann, Detlef; Kloth, Christina

    2016-10-01

    The modulation of antigen uptake and activation of dendritic cells (DCs) by histamine may function as a regulator of inflammation. Therefore, we sought to determine the impact of histamine on antigen uptake by and activation of murine DCs. DCs from spleen and lung were either identified by flow cytometry or were immunomagnetically enriched. Cells were stimulated with histamine, and the regulation of MHC-II and co-stimulatory molecule expression (CD80, CD86, and ICOS-L) and antigen uptake were quantified by flow cytometry. Individual contributions of the histamine receptor subtypes were determined by using the antagonists mepyramine (histamine H1-receptor: H1R), famotidine (H2R), and JNJ 7777120 (H4R). Histamine accelerated the uptake of soluble antigen via the H1R, H2R, and H4R in splenic DCs. Co-stimulatory molecule expression was enhanced already by enrichment procedures, thus, the analyses were performed in unseparated cell populations. Histamine enhanced the expression of CD86 and ICOS-L while expression of CD80 was unaffected. Antagonism at H1R, H2R, and H4R and at H1R and H4R reduced the histamine-induced enhanced expression of CD86 and ICOS-L, respectively. Histamine contributes to the regulation of the immunological synapse by stimulation of antigen uptake and activation of DCs via H1R, H2R, and H4R.

  8. Fast generation of dendritic cells

    DEFF Research Database (Denmark)

    Kvistborg, P; Bøgh, Marie; Pedersen, A W

    2009-01-01

    Dendritic cells (DC) are potent antigen presenting cells capable of inducing immune responses. DC are widely used as vaccine adjuvant in experimental clinical settings. DC-based vaccines are normally generated using a standard 8day DC protocol (SDDC). In attempts to shorten the vaccine production...... SDDC to the IL-10 inducing stimulus of TLR ligands (R848 and LPS). Thus to determine the clinical relevance of fast DC protocols in cancer settings, small phase I trials should be conducted monitoring regulatory T cells carefully....

  9. XOR at a Single Vertex -- Artificial Dendrites

    OpenAIRE

    Burger, John Robert

    2010-01-01

    New to neuroscience with implications for AI, the exclusive OR, or any other Boolean gate may be biologically accomplished within a single region where active dendrites merge. This is demonstrated below using dynamic circuit analysis. Medical knowledge aside, this observation points to the possibility of specially coated conductors to accomplish artificial dendrites.

  10. Dendrite fragmentation: an experiment-driven simulation.

    Science.gov (United States)

    Cool, T; Voorhees, P W

    2018-02-28

    The processes leading to the fragmentation of secondary dendrite arms are studied using a three-dimensional Sn dendritic structure that was measured experimentally as an initial condition in a phase-field simulation. The phase-field model replicates the kinetics of the coarsening process seen experimentally. Consistent with the experiment, the simulations of the Sn-rich dendrite show that secondary dendrite arm coalescence is prevalent and that fragmentation is not. The lack of fragmentation is due to the non-axisymmetric morphology and comparatively small spacing of the dendrite arms. A model for the coalescence process is proposed, and, consistent with the model, the radius of the contact region following coalescence increases as t1/3 We find that small changes in the width and spacing of the dendrite arms can lead to a very different fragmentation-dominated coarsening process. Thus, the alloy system and growth conditions of the dendrite can have a major impact on the fragmentation process.This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'. © 2018 The Author(s).

  11. Dendrite fragmentation: an experiment-driven simulation

    Science.gov (United States)

    Cool, T.; Voorhees, P. W.

    2018-01-01

    The processes leading to the fragmentation of secondary dendrite arms are studied using a three-dimensional Sn dendritic structure that was measured experimentally as an initial condition in a phase-field simulation. The phase-field model replicates the kinetics of the coarsening process seen experimentally. Consistent with the experiment, the simulations of the Sn-rich dendrite show that secondary dendrite arm coalescence is prevalent and that fragmentation is not. The lack of fragmentation is due to the non-axisymmetric morphology and comparatively small spacing of the dendrite arms. A model for the coalescence process is proposed, and, consistent with the model, the radius of the contact region following coalescence increases as t1/3. We find that small changes in the width and spacing of the dendrite arms can lead to a very different fragmentation-dominated coarsening process. Thus, the alloy system and growth conditions of the dendrite can have a major impact on the fragmentation process. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  12. Isovector monopole excitation energies

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, J.D.; Lipparini, E.; Stringary, S.

    1987-11-05

    Using a hydrodynamical model whose parameters have been adjusted to fit the polarizability and excitation energy of the giant dipole nuclear resonance we predict excitation energies of the isovector monopole resonance. The predicted values are in good agreement with experimental data. The mass dependence of the excitation energy is strongly influenced by nuclear geometry.

  13. Full restoration of Brucella-infected dendritic cell functionality through Vγ9Vδ2 T helper type 1 crosstalk.

    Directory of Open Access Journals (Sweden)

    Ming Ni

    Full Text Available Vγ9Vδ2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, Vγ9Vδ2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically impairs dendritic cell maturation and their capacity to present antigens to T cells. Herein, we investigated whether V T cells have the ability to restore the full functional capacities of Brucella-infected dendritic cells. Using an in vitro multicellular infection model, we showed that: 1/Brucella-infected dendritic cells activate Vγ9Vδ2 T cells through contact-dependent mechanisms, 2/activated Vγ9Vδ2 T cells induce full differentiation into IL-12 producing cells of Brucella-infected dendritic cells with functional antigen presentation activity. Furthermore, phosphoantigen-activated Vγ9Vδ2 T cells also play a role in triggering the maturation process of dendritic cells already infected for 24 h. This suggests that activated Vγ9Vδ2 T cells could be used to modulate the outcome of infectious diseases by promoting an adjuvant effect in dendritic cell-based cellular therapies.

  14. Differential distribution and function of GABABRs in somato-dendritic and axonal compartments of principal cells and interneurons in cortical circuits.

    Science.gov (United States)

    Kulik, Ákos; Booker, Sam A; Vida, Imre

    2017-10-14

    GABABRs are highly expressed in cortical circuits, controlling neuronal excitability and synaptic transmission in both principal cells and inhibitory interneurons. Light and electron microscopic studies confirmed the wide distribution of receptors and revealed cell type-specific quantitative differences in their cellular and subcellular distributions. At the subcellular level, GABABRs are abundant at the peri- and extrasynaptic membrane of somato-dendritic compartments and to lower levels in the axon terminals of both cortical excitatory principal cells and inhibitory interneurons. Differences in the surface densities are particularly prominent between neurochemically-defined interneuron types. Whole-cell recordings further demonstrated that GABABRs differentially mediate post- and presynaptic inhibition in principal cells and various GABAergic interneurons by preferentially modulating postsynaptic G-protein-coupled inwardly rectifying K+ (Kir3) channels and presynaptic high voltage-activated Ca2+ (Cav) channels. These data convergently indicate that GABABRs not only control the overall level of neuronal excitability and activity, but can also fine tune the activation and interactions of excitatory and inhibitory neurons in cortical circuits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Multi-frequency excitation

    KAUST Repository

    Younis, Mohammad I.

    2016-03-10

    Embodiments of multi-frequency excitation are described. In various embodiments, a natural frequency of a device may be determined. In turn, a first voltage amplitude and first fixed frequency of a first source of excitation can be selected for the device based on the natural frequency. Additionally, a second voltage amplitude of a second source of excitation can be selected for the device, and the first and second sources of excitation can be applied to the device. After applying the first and second sources of excitation, a frequency of the second source of excitation can be swept. Using the methods of multi- frequency excitation described herein, new operating frequencies, operating frequency ranges, resonance frequencies, resonance frequency ranges, and/or resonance responses can be achieved for devices and systems.

  16. Dendritic Cell Regulation by Cannabinoid-Based Drugs

    Directory of Open Access Journals (Sweden)

    Mattias Svensson

    2010-08-01

    Full Text Available Cannabinoid pharmacology has made important advances in recent years after the cannabinoid system was discovered. Studies in experimental models and in humans have produced promising results using cannabinoid-based drugs for the treatment of obesity and cancer, as well as neuroinflammatory and chronic inflammatory diseases. Moreover, as we discuss here, additional studies also indicates that these drugs have immunosuppressive and anti-inflammatory properties including modulation of immune cell function. Thus, manipulation of the endocannabinoid system in vivo may provide novel therapeutic strategies against inflammatory disorders. At least two types of cannabinoid receptors, cannabinoid 1 and cannabinoid 2 receptors are expressed on immune cells such as dendritic cells (DC. Dendritic cells are recognized for their critical role in initiating and maintaining immune responses. Therefore, DC are potential targets for cannabinoid-mediated modulation. Here, we review the effects of cannabinoids on DC and provide some perspective concerning the therapeutic potential of cannabinoids for the treatment of human diseases involving aberrant inflammatory processes.

  17. Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations

    Directory of Open Access Journals (Sweden)

    Anja Konietzny

    2017-05-01

    Full Text Available Actin is a versatile and ubiquitous cytoskeletal protein that plays a major role in both the establishment and the maintenance of neuronal polarity. For a long time, the most prominent roles that were attributed to actin in neurons were the movement of growth cones, polarized cargo sorting at the axon initial segment, and the dynamic plasticity of dendritic spines, since those compartments contain large accumulations of actin filaments (F-actin that can be readily visualized using electron- and fluorescence microscopy. With the development of super-resolution microscopy in the past few years, previously unknown structures of the actin cytoskeleton have been uncovered: a periodic lattice consisting of actin and spectrin seems to pervade not only the whole axon, but also dendrites and even the necks of dendritic spines. Apart from that striking feature, patches of F-actin and deep actin filament bundles have been described along the lengths of neurites. So far, research has been focused on the specific roles of actin in the axon, while it is becoming more and more apparent that in the dendrite, actin is not only confined to dendritic spines, but serves many additional and important functions. In this review, we focus on recent developments regarding the role of actin in dendrite morphology, the regulation of actin dynamics by internal and external factors, and the role of F-actin in dendritic protein trafficking.

  18. From atomistic interfaces to dendritic patterns

    Science.gov (United States)

    Galenko, P. K.; Alexandrov, D. V.

    2018-01-01

    Transport processes around phase interfaces, together with thermodynamic properties and kinetic phenomena, control the formation of dendritic patterns. Using the thermodynamic and kinetic data of phase interfaces obtained on the atomic scale, one can analyse the formation of a single dendrite and the growth of a dendritic ensemble. This is the result of recent progress in theoretical methods and computational algorithms calculated using powerful computer clusters. Great benefits can be attained from the development of micro-, meso- and macro-levels of analysis when investigating the dynamics of interfaces, interpreting experimental data and designing the macrostructure of samples. The review and research articles in this theme issue cover the spectrum of scales (from nano- to macro-length scales) in order to exhibit recently developing trends in the theoretical analysis and computational modelling of dendrite pattern formation. Atomistic modelling, the flow effect on interface dynamics, the transition from diffusion-limited to thermally controlled growth existing at a considerable driving force, two-phase (mushy) layer formation, the growth of eutectic dendrites, the formation of a secondary dendritic network due to coalescence, computational methods, including boundary integral and phase-field methods, and experimental tests for theoretical models-all these themes are highlighted in the present issue. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  19. The morphological identity of insect dendrites.

    Directory of Open Access Journals (Sweden)

    Hermann Cuntz

    2008-12-01

    Full Text Available Dendrite morphology, a neuron's anatomical fingerprint, is a neuroscientist's asset in unveiling organizational principles in the brain. However, the genetic program encoding the morphological identity of a single dendrite remains a mystery. In order to obtain a formal understanding of dendritic branching, we studied distributions of morphological parameters in a group of four individually identifiable neurons of the fly visual system. We found that parameters relating to the branching topology were similar throughout all cells. Only parameters relating to the area covered by the dendrite were cell type specific. With these areas, artificial dendrites were grown based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy. Although the same branching rule was used for all cells, this yielded dendritic structures virtually indistinguishable from their real counterparts. From these principles we derived a fully-automated model-based neuron reconstruction procedure validating the artificial branching rule. In conclusion, we suggest that the genetic program implementing neuronal branching could be constant in all cells whereas the one responsible for the dendrite spanning field should be cell specific.

  20. Clinical Comparison of Pulse and Chirp Excitation

    DEFF Research Database (Denmark)

    Pedersen, Morten Høgholm; Misaridis, T.; Jensen, Jørgen Arendt

    2002-01-01

    Coded excitation (CE) using frequency modulated signals (chirps) combined with modified matched filtering has earlier been presented showing promising results in simulations and in-vitro. In this study an experimental ultrasound system is evaluated in a clinical setting, where image sequences are...

  1. Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells

    Directory of Open Access Journals (Sweden)

    Fabian eSalazar

    2013-11-01

    Full Text Available Allergy is an exacerbated response of the immune system against non-self-proteins called allergens and is typically characterized by biased type-2 T helper cell and deleterious IgE mediated immune responses. The allergic cascade starts with the recognition of allergens by antigen presenting cells, mainly dendritic cells, culminating in mast cell sensitization and triggering. Dendritic cells have been demonstrated to play a crucial role in orchestrating allergic diseases. Using different C-type lectin receptors dendritic cells are able to recognize and internalize a number of allergens from diverse sources leading to sensitization. Furthermore, there is increasing evidence highlighting the role of epithelial cells in triggering and modulating immune responses to allergens. As well as providing a physical barrier, epithelial cells can interact with allergens and influence dendritic cells behaviour through the release of a number of Th2 promoting cytokines. In this review we will summarise current understanding of how allergens are recognised by dendritic cells and epithelial cells and what are the consequences of such interaction in the context of allergic sensitisation and downstream events leading to allergic inflammation. Better understanding of the molecular mechanisms of allergen recognition and associated signalling pathways could enable developing more effective therapeutic strategies that target the initial steps of allergic sensitisation hence hindering development or progression of allergic diseases.

  2. Plasmacytoid dendritic cells are crucial in Bifidobacterium adolescentis-mediated inhibition of Yersinia enterocolitica infection.

    Science.gov (United States)

    Wittmann, Alexandra; Autenrieth, Ingo B; Frick, Julia-Stefanie

    2013-01-01

    In industrialized countries bacterial intestinal infections are commonly caused by enteropathogenic Enterobacteriaceae. The interaction of the microbiota with the host immune system determines the adequacy of an appropriate response against pathogens. In this study we addressed whether the probiotic Bifidobacterium adolescentis is protective during intestinal Yersinia enterocolitica infection. Female C57BL/6 mice were fed with B. adolescentis, infected with Yersinia enterocolitica, or B. adolescentis fed and subsequently infected with Yersinia enterocolitica. B. adolescentis fed and Yersinia infected mice were protected from Yersinia infection as indicated by a significantly reduced weight loss and splenic Yersinia load when compared to Yersinia infected mice. Moreover, protection from infection was associated with increased intestinal plasmacytoid dendritic cell and regulatory T-cell frequencies. Plasmacytoid dendritic cell function was investigated using depletion experiments by injecting B. adolescentis fed, Yersinia infected C57BL/6 mice with anti-mouse PDCA-1 antibody, to deplete plasmacytoid dendritic cells, or respective isotype control. The B. adolescentis-mediated protection from Yersinia dissemination to the spleen was abrogated after plasmacytoid dendritic cell depletion indicating a crucial function for pDC in control of intestinal Yersinia infection. We suggest that feeding of B. adolescentis modulates the intestinal immune system in terms of increased plasmacytoid dendritic cell and regulatory T-cell frequencies, which might account for the B. adolescentis-mediated protection from Yersinia enterocolitica infection.

  3. Sigma-1 Receptor and Neuronal Excitability.

    Science.gov (United States)

    Kourrich, Saïd

    2017-01-01

    The sigma-1 receptor (Sig-1R), via interaction with various proteins, including voltage-gated and ligand-gated ion channels (VGICs and LGICs), is involved in a plethora of neuronal functions. This capability to regulate a variety of ion channel targets endows the Sig-1R with a powerful capability to fine tune neuronal excitability, and thereby the transmission of information within brain circuits. This versatility may also explain why the Sig-1R is associated to numerous diseases at both peripheral and central levels. To date, how the Sig-1R chooses its targets and how the combinations of target modulations alter overall neuronal excitability is one of the challenges in the field of Sig-1R-dependent regulation of neuronal activity. Here, we will describe and discuss the latest findings on Sig-1R-dependent modulation of VGICs and LGICs, and provide hypotheses that may explain the diverse excitability outcomes that have been reported so far.

  4. Non-linear dendrites can tune neurons

    Directory of Open Access Journals (Sweden)

    Romain Daniel Cazé

    2014-03-01

    Full Text Available A signature of visual, auditory, and motor cortices is the presence of neurons tuned to distinct features of the environment. While neuronal tuning can be observed in most brain areas, its origin remains enigmatic, and new calcium imaging data complicate this problem. Dendritic calcium signals, in a L2/3 neuron from the mouse visual cortex, display a wide range of tunings that could be different from the neuronal tuning (Jia et al 2010. To elucidate this observation we use multi-compartmental models of increasing complexity, from a binary to a realistic biophysical model of L2/3 neuron. These models possess non-linear dendritic subunits inside which the result of multiple excitatory inputs is smaller than their arithmetic sum. While dendritic non-linear subunits are ad-hoc in the binary model, non-linearities in the realistic model come from the passive saturation of synaptic currents. Because of these non-linearities our neuron models are scatter sensitive: the somatic membrane voltage is higher when presynaptic inputs target different dendrites than when they target a single dendrite. This spatial bias in synaptic integration is, in our models, the origin of neuronal tuning. Indeed, assemblies of presynaptic inputs encode the stimulus property through an increase in correlation or activity, and only the assembly that encodes the preferred stimulus targets different dendrites. Assemblies coding for the non-preferred stimuli target single dendrites, explaining the wide range of observed tunings and the possible difference between dendritic and somatic tuning. We thus propose, in accordance with the latest experimental observations, that non-linear integration in dendrites can generate neuronal tuning independently of the coding regime.

  5. Strings on a Violin: Location Dependence of Frequency Tuning in Active Dendrites.

    Science.gov (United States)

    Das, Anindita; Rathour, Rahul K; Narayanan, Rishikesh

    2017-01-01

    Strings on a violin are tuned to generate distinct sound frequencies in a manner that is firmly dependent on finger location along the fingerboard. Sound frequencies emerging from different violins could be very different based on their architecture, the nature of strings and their tuning. Analogously, active neuronal dendrites, dendrites endowed with active channel conductances, are tuned to distinct input frequencies in a manner that is dependent on the dendritic location of the synaptic inputs. Further, disparate channel expression profiles and differences in morphological characteristics could result in dendrites on different neurons of the same subtype tuned to distinct frequency ranges. Alternately, similar location-dependence along dendritic structures could be achieved through disparate combinations of channel profiles and morphological characteristics, leading to degeneracy in active dendritic spectral tuning. Akin to strings on a violin being tuned to different frequencies than those on a viola or a cello, different neuronal subtypes exhibit distinct channel profiles and disparate morphological characteristics endowing each neuronal subtype with unique location-dependent frequency selectivity. Finally, similar to the tunability of musical instruments to elicit distinct location-dependent sounds, neuronal frequency selectivity and its location-dependence are tunable through activity-dependent plasticity of ion channels and morphology. In this morceau, we explore the origins of neuronal frequency selectivity, and survey the literature on the mechanisms behind the emergence of location-dependence in distinct forms of frequency tuning. As a coda to this composition, we present some future directions for this exciting convergence of biophysical mechanisms that endow a neuron with frequency multiplexing capabilities.

  6. Saturated excitation of Fluorescence to quantify excitation enhancement in aperture antennas

    KAUST Repository

    Aouani, Heykel

    2012-07-23

    Fluorescence spectroscopy is widely used to probe the electromagnetic intensity amplification on optical antennas, yet measuring the excitation intensity amplification is a challenge, as the detected fluorescence signal is an intricate combination of excitation and emission. Here, we describe a novel approach to quantify the electromagnetic amplification in aperture antennas by taking advantage of the intrinsic non linear properties of the fluorescence process. Experimental measurements of the fundamental f and second harmonic 2f amplitudes of the fluorescence signal upon excitation modulation are used to quantify the electromagnetic intensity amplification with plasmonic aperture antennas. © 2012 Optical Society of America.

  7. Excited states 2

    CERN Document Server

    Lim, Edward C

    2013-01-01

    Excited States, Volume 2 is a collection of papers that deals with molecules in the excited states. The book describes the geometries of molecules in the excited electronic states. One paper describes the geometries of a diatomic molecule and of polyatomic molecules; it also discusses the determination of the many excited state geometries of molecules with two, three, or four atoms by techniques similar to diatomic spectroscopy. Another paper introduces an ordered theory related to excitons in pure and mixed molecular crystals. This paper also presents some experimental data such as those invo

  8. Dendritic ion channelopathy in acquired epilepsy

    Science.gov (United States)

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  9. Dendritic polymers: Universal glue for cells

    Science.gov (United States)

    Frey, Holger

    2012-05-01

    A dendritic polymer consisting of inversely oriented lipid head groups on a polyvalent polyglycerol scaffold makes an effective reversible biomembrane adhesive that may find use as a tissue sealant and a drug-delivery vehicle.

  10. Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum.

    Science.gov (United States)

    González-Tapia, D; González-Ramírez, M M; Vázquez-Hernández, N; González-Burgos, I

    2017-12-14

    The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Dendritic cells in autoimmune thyroid disease.

    Science.gov (United States)

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  13. Immune modulation by dendritic-cell-based cancer vaccines

    Indian Academy of Sciences (India)

    The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells bymodulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing therecombinant human immune system components to target the pro-tumour microenvironment or by ...

  14. Dendritic cells and immuno-modulation in autoimmune arthritis

    NARCIS (Netherlands)

    Spiering, R.

    2013-01-01

    The immune system consists of a broad array of immune cells to protect the body against invasive pathogenic microorganisms. Immune responses should however, be tightly controlled to ensure tolerance to the body’s own cells and proteins in order to limit damage to the host own cells and tissue.

  15. ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Alonso, Mariana; Medina, Jorge H.; Pozzo-Miller, Lucas

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling…

  16. Rapamycin reverses status epilepticus-induced memory deficits and dendritic damage.

    Directory of Open Access Journals (Sweden)

    Amy L Brewster

    Full Text Available Cognitive impairments are prominent sequelae of prolonged continuous seizures (status epilepticus; SE in humans and animal models. While often associated with dendritic injury, the underlying mechanisms remain elusive. The mammalian target of rapamycin complex 1 (mTORC1 pathway is hyperactivated following SE. This pathway modulates learning and memory and is associated with regulation of neuronal, dendritic, and glial properties. Thus, in the present study we tested the hypothesis that SE-induced mTORC1 hyperactivation is a candidate mechanism underlying cognitive deficits and dendritic pathology seen following SE. We examined the effects of rapamycin, an mTORC1 inhibitor, on the early hippocampal-dependent spatial learning and memory deficits associated with an episode of pilocarpine-induced SE. Rapamycin-treated SE rats performed significantly better than the vehicle-treated rats in two spatial memory tasks, the Morris water maze and the novel object recognition test. At the molecular level, we found that the SE-induced increase in mTORC1 signaling was localized in neurons and microglia. Rapamycin decreased the SE-induced mTOR activation and attenuated microgliosis which was mostly localized within the CA1 area. These findings paralleled a reversal of the SE-induced decreases in dendritic Map2 and ion channels levels as well as improved dendritic branching and spine density in area CA1 following rapamycin treatment. Taken together, these findings suggest that mTORC1 hyperactivity contributes to early hippocampal-dependent spatial learning and memory deficits and dendritic dysregulation associated with SE.

  17. A role for tolerogenic dendritic cell-induced B-regulatory cells in type 1 diabetes mellitus.

    Science.gov (United States)

    Giannoukakis, Nick; Trucco, Massimo

    2012-08-01

    To review the important recent findings on the nature, characteristics and function of novel populations of immunosuppressive B-lymphocytes (Bregs) and their possible role as a regulatory cell population, potentially responsive to dendritic cells, in preventing and possibly controlling type 1 diabetes mellitus. Although almost all of the experimental work in immunosuppressive B-lymphocyte biology has focused on their role in arthritis and experimental inflammatory bowel disease, only recently has a role for Bregs in the regulation of type 1 diabetes been looked at more extensively. IL-10-producing Bregs are of significant interest, more so because of their potential modulation by tolerogenic dendritic cells. Additionally, novel populations have been discovered that could also be relevant in the regulation of diabetes autoimmunity. The unexpected discovery of a novel population of Bregs, whose frequency was upregulated in our phase I clinical trial of tolerogenic autologous dendritic cell administration in humans, opens a new frontier for basic and translational research into these novel cell populations. Bregs are a recently rediscovered population of suppressive lymphocytes whose activation, differentiation and function could be sensitive to tolerogenic dendritic cell networks. Modulation of these dendritic cell networks, or the Bregs directly, offers novel options to attenuate and reverse type 1 diabetes autoimmunity as a possible cure for the disease.

  18. The dynamic lives of macrophage and dendritic cell subsets in atherosclerosis

    Science.gov (United States)

    Taghavie-Moghadam, Paresa L.; Butcher, Matthew J.; Galkina, Elena V.

    2014-01-01

    Atherosclerosis, the major pathological process through which arterial plaques are formed, is a dynamic chronic inflammatory disease of large and medium sized arteries in which the vasculature, lipid metabolism, and the immune system all play integral roles. Both the innate and adaptive immune systems are involved in the development and progression of atherosclerosis but myeloid cells represent the major component of the burgeoning atherosclerotic plaque. Various myeloid cells, including monocytes, macrophages, and dendritic cells can be found within the healthy and atherosclerotic arterial wall, where they can contribute to or regulate inflammation. However, the precise behaviors and functions of these cells in situ are still active areas of investigation that continue to yield exciting and surprising new data. Here, we review recent progress in understanding of the complex biology of macrophages and dendritic cells, focusing particularly on the dynamic regulation of these subsets in the arterial wall and novel, emerging functions of these cells during atherogenesis. PMID:24628328

  19. Excited states 4

    CERN Document Server

    Lim, Edward C

    2013-01-01

    Excited States, Volume 4 is a collection of papers that deals with the excited states of molecular activity. One paper investigates the resonance Raman spectroscopy as the key to vibrational-electronic coupling. This paper reviews the basic theory of Raman scattering; it also explains the derivation of the Raman spectra, excitation profiles, and depolarization ratios for simple resonance systems. Another paper reviews the magnetic properties of triplet states, including the zero-field resonance techniques, the high-field experiments, and the spin Hamiltonian. This paper focuses on the magnetic

  20. Nuclear expansion with excitation

    Energy Technology Data Exchange (ETDEWEB)

    De, J.N. [Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Departament d' Estructura i Constituents de la Materia, Facultat de Fisica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain); Samaddar, S.K. [Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Vinas, X. [Departament d' Estructura i Constituents de la Materia, Facultat de Fisica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain); Centelles, M. [Departament d' Estructura i Constituents de la Materia, Facultat de Fisica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain)]. E-mail: mario@ecm.ub.es

    2006-07-06

    The expansion of an isolated hot spherical nucleus with excitation energy and its caloric curve are studied in a thermodynamic model with the SkM{sup *} force as the nuclear effective two-body interaction. The calted results are shown to compare well with the recent experimental data from energetic nuclear collisions. The fluctuations in temperature and density are also studied. They are seen to build up very rapidly beyond an excitation energy of {approx}9 MeV/u. Volume-conserving quadrupole deformation in addition to expansion indicates, however, nuclear disassembly above an excitation energy of {approx}4 MeV/u.

  1. Excitability of motor cortices as a function of emotional sounds.

    Science.gov (United States)

    Komeilipoor, Naeem; Pizzolato, Fabio; Daffertshofer, Andreas; Cesari, Paola

    2013-01-01

    We used transcranial magnetic stimulation (TMS) to clarify how non-verbal emotionally-characterized sounds modulate the excitability of the corticospinal motor tract (CST). While subjects were listening to sounds (monaurally and binaurally), single TMS pulses were delivered to either left or right primary motor cortex (M1), and electromyographic activities were recorded from the contralateral abductor pollicis brevis muscle. We found a significant increase in CST excitability in response to unpleasant as compared to neutral sounds. The increased excitability was lateralized as a function of stimulus valence: Unpleasant stimuli resulted in a significantly higher facilitation of motor potentials evoked in the left hemisphere, while pleasant stimuli yielded a greater CST excitability in the right one. Furthermore, TMS induced higher motor evoked potentials when listening to unpleasant sounds with the left than with the right ear. Taken together, our findings provide compelling evidence for an asymmetric modulation of CST excitability as a function of emotional sounds along with ear laterality.

  2. RuBi-Glutamate: Two-photon and visible-light photoactivation of neurons and dendritic spines

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    2009-05-01

    Full Text Available We describe neurobiological applications of RuBi-Glutamate, a novel caged-glutamate compound based on ruthenium photochemistry. RuBi-Glutamate can be excited with visible wavelengths and releases glutamate after one- or two-photon excitation. It has high quantum efficiency and can be used at low concentrations, partly avoiding the blockade of GABAergic transmission present with other caged compounds. Two-photon uncaging of RuBi-glutamate has a high spatial resolution and generates excitatory responses in individual dendritic spines with physiological kinetics. With laser beam multiplexing, RuBi-Glutamate uncaging can also be used to depolarize and fire pyramidal neurons with single-cell resolution. RuBi-Glutamate therefore enables the photo-activation of neuronal dendrites and circuits with visible or two-photon light sources, achieving single spine, or single cell, precision.

  3. Nerve Conduction Through Dendrites via Proton Hopping.

    Science.gov (United States)

    Kier, Lemont B

    2017-01-01

    In our previous studies of nerve conduction conducted by proton hopping, we have considered the axon, soma, synapse and the nodes of Ranvier. The role of proton hopping described the passage of information through each of these units of a typical nerve system. The synapse projects information from the axon to the dendrite and their associated spines. We have invoked the passage of protons via a hopping mechanism to illustrate the continuum of the impulse through the system, via the soma following the dendrites. This is proposed to be a continuum invoked by the proton hopping method. With the proposal of the activity through the dendrites, via proton hopping, a complete model of the nerve function is invoked. At each step to the way, a water pathway is present and is invoked in the proposed model as the carrier of the message via proton hopping. The importance of the dendrites is evident by the presence of a vast number of spines, each possessing the possibility to carry unique messages through the nervous system. With this model of the role of dendrites, functioning with the presence of proton hopping, a complete model of the nerve system is presented. The validity of this model will be available for further studies and models to assess it's validity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Membrane properties of striatal direct and indirect pathway neurons in mouse and rat slices and their modulation by dopamine.

    Directory of Open Access Journals (Sweden)

    Henrike Planert

    Full Text Available D1 and D2 receptor expressing striatal medium spiny neurons (MSNs are ascribed to striatonigral ("direct" and striatopallidal ("indirect" pathways, respectively, that are believed to function antagonistically in motor control. Glutamatergic synaptic transmission onto the two types is differentially affected by Dopamine (DA, however, less is known about the effects on MSN intrinsic electrical properties. Using patch clamp recordings, we comprehensively characterized the two pathways in rats and mice, and investigated their DA modulation. We identified the direct pathway by retrograde labeling in rats, and in mice we used transgenic animals in which EGFP is expressed in D1 MSNs. MSNs were subjected to a series of current injections to pinpoint differences between the populations, and in mice also following bath application of DA. In both animal models, most electrical properties were similar, however, membrane excitability as measured by step and ramp current injections consistently differed, with direct pathway MSNs being less excitable than their counterparts. DA had opposite effects on excitability of D1 and D2 MSNs, counteracting the initial differences. Pronounced changes in AP shape were seen in D2 MSNs. In direct pathway MSNs, excitability increased across experimental conditions and parameters, and also when applying DA or the D1 agonist SKF-81297 in presence of blockers of cholinergic, GABAergic, and glutamatergic receptors. Thus, DA induced changes in excitability were D1 R mediated and intrinsic to direct pathway MSNs, and not a secondary network effect of altered synaptic transmission. DAergic modulation of intrinsic properties therefore acts in a synergistic manner with previously reported effects of DA on afferent synaptic transmission and dendritic processing, supporting the antagonistic model for direct vs. indirect striatal pathway function.

  5. Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites.

    Science.gov (United States)

    Cohen, Michael S; Bas Orth, Carlos; Kim, Hyung Joon; Jeon, Noo Li; Jaffrey, Samie R

    2011-07-05

    Signaling from dendritic synapses to the nucleus regulates important aspects of neuronal function, including synaptic plasticity. The neurotrophin brain-derived neurotrophic factor (BDNF) can induce long-lasting strengthening of synapses in vivo and this effect is dependent on transcription. However, the mechanism of signaling to the nucleus is not well understood. Here we describe a microfluidic culture device to investigate dendrite-to-nucleus signaling. Using these microfluidic devices, we demonstrate that BDNF can act directly on dendrites to elicit an anterograde signal that induces transcription of the immediate early genes, Arc and c-Fos. Induction of Arc is dependent on dendrite- and cell body-derived calcium, whereas induction of c-Fos is calcium-independent. In contrast to retrograde neurotrophin-mediated axon-to-nucleus signaling, which is MEK5-dependent, BDNF-mediated anterograde dendrite-to-nucleus signaling is dependent on MEK1/2. Intriguingly, the activity of TrkB, the BDNF receptor, is required in the cell body for the induction of Arc and c-Fos mediated by dendritically applied BDNF. These results are consistent with the involvement of a signaling endosome-like pathway that conveys BDNF signals from the dendrite to the nucleus.

  6. Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity.

    Science.gov (United States)

    Wang, Ying; Li, Wen-Yuan; Li, Zhi-Gang; Guan, Li-Xin; Deng, Ling-Xiao

    2017-02-01

    Injury to the nervous system induces localized damage in neural structures and neuronal death through the primary insult, as well as delayed atrophy and impaired plasticity of the delicate dendritic fields necessary for interneuronal communication. Excitotoxicity and other secondary biochemical events contribute to morphological changes in neurons following injury. Evidence suggests that various transcription factors are involved in the dendritic response to injury and potential therapies. Transcription factors play critical roles in the intracellular regulation of neuronal morphological plasticity and dendritic growth and patterning. Mounting evidence supports a crucial role for epigenetic modifications via histone deacetylases, histone acetyltransferases, and DNA methyltransferases that modify gene expression in neuronal injury and repair processes. Gene regulation through epigenetic modification is of great interest in neurotrauma research, and an early picture is beginning to emerge concerning how injury triggers intracellular events that modulate such responses. This review provides an overview of injury-mediated influences on transcriptional regulation through epigenetic modification, the intracellular processes involved in the morphological consequences of such changes, and potential approaches to the therapeutic manipulation of neuronal epigenetics for regulating gene expression to facilitate growth and signaling through dendritic arborization following injury.

  7. Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Jimcy Platholi

    Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

  8. Collective excitations of a Bose-Einstein condensate in a magnetic trap

    NARCIS (Netherlands)

    Mewes, M.O.; Andrews, M.R.; van Druten, N.J.; Kurn, D.M.; Durfee, D.S.; Townsend, C.G.; Ketterle, W.

    1996-01-01

    Collective excitations of a dilute Bose condensate have been observed. These excitations are analogous to phonons in superfluid helium. Bose condensates were created by evaporatively cooling magnetically trapped sodium atoms. Excitations were induced by a modulation of the trapping potential, and

  9. Coherent acoustic excitation of cavity polaritons

    DEFF Research Database (Denmark)

    Poel, Mike van der; de Lima, M. M.; Hey, R.

    . In the strong-coupling regime the cavityand quantum-well excitonic resonance display new cavity-polariton eigenstates that arejoint electronic and photonic excitations of the system2. These new eigenstates havestrongly modified in-plane dispersion and due to their composite light-matter nature theyhave a fast......, modulates the refractive index and displaces the material causing a harmonicmodulation of the PBG structure1. This periodic modulation of the cavity-exciton systemleads to in-plane mini-Brillouin zone (MBZ) formation. The very high vacuum-Rabisplitting of our sample enables us to clearly resolve...

  10. Convection Effects in Three-dimensional Dendritic Growth

    Science.gov (United States)

    Lu, Yili; Beckermann, C.; Karma, A.

    2003-01-01

    A phase-field model is developed to simulate free dendritic growth coupled with fluid flow for a pure material in three dimensions. The preliminary results presented here illustrate the strong influence of convection on the three-dimensional (3D) dendrite growth morphology. The detailed knowledge of the flow and temperature fields in the melt around the dendrite from the simulations allows for a detailed understanding of the convection effects on dendritic growth.

  11. Single dendrite-targeting interneurons generate branch-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Caleb eStokes

    2014-11-01

    Full Text Available Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence pyramidal cells in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

  12. Excitation Dynamics and Relaxation in a Molecular Heterodimer

    CERN Document Server

    Balevicius, V; Abramavicius, D; Mancal, T; Valkunas, L

    2011-01-01

    The exciton dynamics in a molecular heterodimer is studied as a function of differences in excitation and reorganization energies, asymmetry in transition dipole moments and excited state lifetimes. The heterodimer is composed of two molecules modeled as two-level systems coupled by the resonance interaction. The system-bath coupling is taken into account as a modulating factor of the energy gap of the molecular excitation, while the relaxation to the ground state is treated phenomenologically. Comparison of the description of the excitation dynamics modeled using either the Redfield equations (secular and full forms) or the Hierarchical quantum master equation (HQME) is demonstrated and discussed. Possible role of the dimer as an excitation quenching center in photosynthesis self-regulation is discussed. It is concluded that the system-bath interaction rather than the excitonic effect determines the excitation quenching ability of such a dimer.

  13. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  14. Developmental study of dendritic bundles in layer 1 of the rat granular retrosplenial cortex with special reference to a cell adhesion molecule, OCAM.

    Science.gov (United States)

    Ichinohe, Noritaka; Yoshihara, Yoshihiro; Hashikawa, Tsutomu; Rockland, Kathleen S

    2003-10-01

    In the granular retrosplenial cortex (GRS) of adult rats, callosally projecting pyramidal neurons in layer 2 form dendritic bundles, 30-100 micro m wide, in layer 1. The distinctness of these bundles makes the GRS an attractive model system for investigating the developmental, microcircuitry, and basic organizational features related to dendritic modularity. In this report, we investigate the developmental time course of the dendritic bundles, visualized by immunohistochemistry for microtubule-associated protein 2 (MAP2) and glutamate receptor subunits 2/3 (GluR2/3). Bundles in layer 1 are apparent as early as postnatal day 5, first with GluR2/3 and then, from postnatal day 14, with MAP2. As a step toward understanding the mechanisms of dendritic aggregation, we further investigated the ontogeny of expression of the cell adhesion molecule OCAM. OCAM exhibits a patchy distribution in layer 1 from postnatal day 3 to adult, and the regions of weak OCAM immunoreactivity selectively correspond to the dendritic bundles (in both GluR2/3 and MAP2). The periodic geometry of OCAM-immunoreactive regions, the time course of their appearance and the distinct localization complementary to the bundles support the possibility that this molecule is one contributor to the establishment and maintenance of dendritic modules. The interdigitating relationship between regions of high OCAM immunoreactivity and the dendritic bundles in layer 1 suggests that OCAM may have a repellent influence on the formation of these bundles.

  15. Adult Drosophila sensory neurons specify dendritic territories independently of dendritic contacts through the Wnt5-Drl signaling pathway.

    Science.gov (United States)

    Yasunaga, Kei-ichiro; Tezuka, Akane; Ishikawa, Natsuko; Dairyo, Yusuke; Togashi, Kazuya; Koizumi, Hiroyuki; Emoto, Kazuo

    2015-08-15

    Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories in stereotypic spatial patterns throughout the nervous system, yet molecular mechanisms of how neurons specify dendritic territories remain largely unknown. In Drosophila larvae, dendrites of class IV sensory (C4da) neurons completely but nonredundantly cover the whole epidermis, and the boundaries of these tiled dendritic fields are specified through repulsive interactions between homotypic dendrites. Here we report that, unlike the larval C4da neurons, adult C4da neurons rely on both dendritic repulsive interactions and external positional cues to delimit the boundaries of their dendritic fields. We identify Wnt5 derived from sternites, the ventral-most part of the adult abdominal epidermis, as the critical determinant for the ventral boundaries. Further genetic data indicate that Wnt5 promotes dendrite termination on the periphery of sternites through the Ryk receptor family kinase Derailed (Drl) and the Rho GTPase guanine nucleotide exchange factor Trio in C4da neurons. Our findings thus uncover the dendritic contact-independent mechanism that is required for dendritic boundary specification and suggest that combinatory actions of the dendritic contact-dependent and -independent mechanisms may ensure appropriate dendritic territories of a given neuron. © 2015 Yasunaga et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Layer 5 Pyramidal Neurons’ Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

    Directory of Open Access Journals (Sweden)

    Diana Urrego

    2015-01-01

    Full Text Available This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans.

  17. Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

    Science.gov (United States)

    Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

    2015-01-01

    This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

  18. Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells.

    Science.gov (United States)

    Gerlini, G; Hefti, H P; Kleinhans, M; Nickoloff, B J; Burg, G; Nestle, F O

    2001-09-01

    CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.

  19. Excitations in organic solids

    CERN Document Server

    Agranovich, Vladimir M

    2009-01-01

    During the last decade our expertise in nanotechnology has advanced considerably. The possibility of incorporating in the same nanostructure different organic and inorganic materials has opened up a promising field of research, and has greatly increased the interest in the study of properties of excitations in organic materials. In this book not only the fundamentals of Frenkel exciton and polariton theory are described, but also the electronic excitations and electronic energytransfers in quantum wells, quantum wires and quantum dots, at surfaces, at interfaces, in thin films, in multilayers,

  20. Dendritic outgrowth of myenteric plexus neurons in primary culture.

    Science.gov (United States)

    Mulholland, M W; Romanchuk, G; Flowe, K

    1992-04-01

    Myenteric plexus neurons derived from neonatal guinea pigs, when exposed to serum, demonstrated a characteristic pattern of growth, including a proliferating outgrowth zone of glial cells, peripheral extension of dendritic processes, and progressive dendritic growth. Serum effects upon dendritic growth, measured morphometrically, was strongly dose- and temporally dependent. Dendritic density was increased 10-fold (120 hr) by the addition of 6% serum, while mean dendritic length was increased 3-fold. Development of cholinergic function was reflected by release of [3H]ACh in response to cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide (10(-10) and 10(-8) M).

  1. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular......, the role of DCs in the generation of regulatory T cells is highlighted....

  2. Dendritic Solidification in a Copper Nickel Alloy

    OpenAIRE

    DÜNDAR, Sacit

    2014-01-01

    The distribution of nickel in dendrite arms and in interdendritic regions of copper-10% nickel alloy solidified under production conditions designed to provide 4 different cooling rates was investigated. The results indicate that at different rates of solidification undercooling, diffusion and convection mechanisms affect the microsegregation of nickel and copper in the cast materials to various extents.

  3. Amyloid plaque formation precedes dendritic spine loss.

    Science.gov (United States)

    Bittner, Tobias; Burgold, Steffen; Dorostkar, Mario M; Fuhrmann, Martin; Wegenast-Braun, Bettina M; Schmidt, Boris; Kretzschmar, Hans; Herms, Jochen

    2012-12-01

    Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer's disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswered. To address this question, and to learn more about the underlying kinetics, we simultaneously imaged amyloid plaque deposition and dendritic spine loss by applying two-photon in vivo microscopy through a cranial window in double transgenic APPPS1 mice. As a result, we first observed that the rate of dendritic spine loss in proximity to plaques is the same in both young and aged animals. However, plaque size only increased significantly in the young cohort, indicating that spine loss persists even many months after initial plaque appearance. Tracking the fate of individual spines revealed that net spine loss is caused by increased spine elimination, with the rate of spine formation remaining constant. Imaging of dendritic spines before and during plaque formation demonstrated that spine loss around plaques commences at least 4 weeks after initial plaque formation. In conclusion, spine loss occurs, shortly but with a significant time delay, after the birth of new plaques, and persists in the vicinity of amyloid plaques over many months. These findings hence give further hope to the possibility that there is a therapeutic window between initial amyloid plaque deposition and the onset of structural damage at spines.

  4. Nanodiamonds suppress the growth of lithium dendrites.

    Science.gov (United States)

    Cheng, Xin-Bing; Zhao, Meng-Qiang; Chen, Chi; Pentecost, Amanda; Maleski, Kathleen; Mathis, Tyler; Zhang, Xue-Qiang; Zhang, Qiang; Jiang, Jianjun; Gogotsi, Yury

    2017-08-25

    Lithium metal has been regarded as the future anode material for high-energy-density rechargeable batteries due to its favorable combination of negative electrochemical potential and high theoretical capacity. However, uncontrolled lithium deposition during lithium plating/stripping results in low Coulombic efficiency and severe safety hazards. Herein, we report that nanodiamonds work as an electrolyte additive to co-deposit with lithium ions and produce dendrite-free lithium deposits. First-principles calculations indicate that lithium prefers to adsorb onto nanodiamond surfaces with a low diffusion energy barrier, leading to uniformly deposited lithium arrays. The uniform lithium deposition morphology renders enhanced electrochemical cycling performance. The nanodiamond-modified electrolyte can lead to a stable cycling of lithium | lithium symmetrical cells up to 150 and 200 h at 2.0 and 1.0 mA cm-2, respectively. The nanodiamond co-deposition can significantly alter the lithium plating behavior, affording a promising route to suppress lithium dendrite growth in lithium metal-based batteries.Lithium metal is an ideal anode material for rechargeable batteries but suffer from the growth of lithium dendrites and low Coulombic efficiency. Here the authors show that nanodiamonds serve as an electrolyte additive to co-deposit with lithium metal and suppress the formation of dendrites.

  5. Excitation Methods for Bridge Structures

    Energy Technology Data Exchange (ETDEWEB)

    Farrar, C.R.; Duffy, T.A.; Cornwell, P.J.; Doebling, S.W.

    1999-02-08

    This paper summarizes the various methods that have been used to excited bridge structures during dynamic testing. The excitation methods fall into the general categories of ambient excitation methods and measured-input excitation methods. During ambient excitation the input to the bridge is not directly measured. In contrast, as the category label implies, measured-input excitations are usually applied at a single location where the force input to the structure can be monitored. Issues associated with using these various types of measurements are discussed along with a general description of the various excitation methods.

  6. Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons.

    Science.gov (United States)

    Wang, Desheng; Zheng, Wen

    2015-10-05

    Previous studies have shown dietary cholesterol can enhance learning but retard memory which may be partly due to increased cholesterol levels in hippocampus and reduced afterhyperpolarization (AHP) amplitude of hippocampal CA1 neurons. This study explored the dose-dependent effect of dietary cholesterol on synaptic plasticity of rabbit hippocampal CA1 neurons and spine morphology, the postsynaptic structures responsible for synaptic plasticity. Field potential recordings revealed a low concentration of dietary cholesterol increased long-term potentiation (LTP) expression while high concentrations produced a pronounced reduction in LTP expression. Dietary cholesterol facilitated basal synaptic transmission but did not influence presynaptic function. DiI staining showed dietary cholesterol induced alterations in dendrite spine morphology characterized by increased mushroom spine density and decreased thin spine density, two kinds of dendritic spines that may be linked to memory consolidation and learning acquisition. Dietary cholesterol also modulated the geometric measures of mushroom spines. Therefore, dietary cholesterol dose-dependently modulated both synaptic plasticity and dendrite spine morphologies of hippocampal CA1 neurons that could mediate learning and memory changes previously seen to result from feeding a cholesterol diet. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Aminopeptidase N (CD13 Is Involved in Phagocytic Processes in Human Dendritic Cells and Macrophages

    Directory of Open Access Journals (Sweden)

    Mónica I. Villaseñor-Cardoso

    2013-01-01

    Full Text Available Aminopeptidase N (APN or CD13 is a membrane ectopeptidase expressed by many cell types, including myelomonocytic lineage cells: monocytes, macrophages, and dendritic cells. CD13 is known to regulate the biological activity of various peptides by proteolysis, and it has been proposed that CD13 also participates in several functions such as angiogenesis, cell adhesion, metastasis, and tumor invasion. We had previously reported that, in human monocytes and macrophages, CD13 modulates the phagocytosis mediated by receptors for the Fc portion of IgG antibodies (FcγRs. In this work, we analyzed the possible interaction of CD13 with other phagocytic receptors. We found out that the cross-linking of CD13 positively modulates the phagocytosis mediated by receptors of the innate immune system, since a significant increase in the phagocytosis of zymosan particles or heat-killed E. coli was observed when CD13 was cross-linked using anti-CD13 antibodies, in both macrophages and dendritic cells. Also, we observed that, during the phagocytosis of zymosan, CD13 redistributes and is internalized into the phagosome. These findings suggest that, besides its known functions, CD13 participates in phagocytic processes in dendritic cells and macrophages.

  8. Low cost solar array project production process and equipment task. A Module Experimental Process System Development Unit (MEPSDU)

    Science.gov (United States)

    1981-01-01

    Technical readiness for the production of photovoltaic modules using single crystal silicon dendritic web sheet material is demonstrated by: (1) selection, design and implementation of solar cell and photovoltaic module process sequence in a Module Experimental Process System Development Unit; (2) demonstration runs; (3) passing of acceptance and qualification tests; and (4) achievement of a cost effective module.

  9. Electrochromism and photocatalysis in dendrite structured Ti:WO3 thin films grown by sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Karuppasamy, A., E-mail: karuppasamy@psnacet.edu.in

    2015-12-30

    Graphical abstract: - Highlights: • Dendrite structured Ti doped WO{sub 3} (WTO) thin films are grown by co-sputtering. • Sputtering condition influences structure and surface morphology of WTO films. • Titanium doping and annealing lead to dendritic surface structures in WTO films. • Structural, optical, electrochromic and photocatalytic properties of WTO films. • Enhanced electrochromism and photocatalysis in dendrite structured WTO thin films. - Abstract: Titanium doped tungsten oxide (Ti:WO{sub 3}) thin films with dendrite surface structures were grown by co-sputtering titanium and tungsten in Ar + O{sub 2} atmosphere. Ti:WO{sub 3} thin films were deposited at oxygen flow rates corresponding to pressures in the range 1.0 × 10{sup −3}–5.0 × 10{sup −3} mbar. Argon flow rate and sputtering power densities for titanium (2 W/cm{sup 2}) and tungsten (3 W/cm{sup 2}) were kept constant. Ti:WO{sub 3} films deposited at an oxygen pressure of 5 × 10{sup −3} mbar are found to be better electrochromic and photocatalytic. They have high optical modulation (80% at λ = 550 nm), coloration efficiency (60 cm{sup 2}/C at λ = 550 nm), electron/ion storage and removal capacity (Qc: −22.01 mC/cm{sup 2}, Qa: 17.72 mC/cm{sup 2}), reversibility (80%) and methylene blue decomposition rate (−1.38 μmol/l d). The combined effects of titanium doping, dendrite surface structures and porosity leads to significant enhancement in the electrochromic and photocatalytic properties of Ti:WO{sub 3} films.

  10. Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages

    Science.gov (United States)

    Ling, Guang Sheng; Bennett, Jason; Woollard, Kevin J.; Szajna, Marta; Fossati-Jimack, Liliane; Taylor, Philip R.; Scott, Diane; Franzoso, Guido; Cook, H. Terence; Botto, Marina

    2014-01-01

    Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin αM (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS.

  11. Recruitment of Staufen2 Enhances Dendritic Localization of an Intron-Containing CaMKIIα mRNA

    Directory of Open Access Journals (Sweden)

    Raúl Ortiz

    2017-07-01

    Full Text Available Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain. This subpopulation of unspliced mRNA preferentially localizes to distal dendrites in a synaptic-activity-dependent manner. Staufen2, a well-established marker of RNA transport in dendrites, interacts with intron i16 sequences and enhances its distal dendritic localization, pointing to the existence of intron-mediated mechanisms in the molecular pathways that modulate dendritic transport and localization of synaptic mRNAs.

  12. Chronic cocaine treatment alters dendritic arborization in the adult motor cortex through a CB1 cannabinoid receptor-dependent mechanism.

    Science.gov (United States)

    Ballesteros-Yáñez, I; Valverde, O; Ledent, C; Maldonado, R; DeFelipe, J

    2007-06-08

    The CB1 cannabinoid receptors modulate the addictive processes associated with different drugs of abuse, including psychostimulants. Mice lacking CB1 receptors exhibit an important attenuation of the reinforcing responses produced by cocaine in an operant self-administration paradigm. We have investigated the effect of chronic cocaine treatment on dendrite structure and spine density of the principal cortical neuron, the pyramidal neuron, in CB1 knockout mice and wild type littermates. Layer III pyramidal cells of the motor cortex were injected intracellularly in fixed cortical slices and their morphometric parameters analyzed. Under basal conditions, the field area of the dendritic arbors was more extensive and dendritic spine density was higher in wild type mice than in CB1 knockout mice. Chronic treatment of cocaine diminished the size and length of the basal dendrites and spine density on pyramidal cells from wild type mice. However, the total number of spines in the pyramidal cells of CB1 knockout mice augmented slightly following chronic cocaine treatment, although no changes in the morphology of the dendritic arbor were observed. Our data demonstrate that microanatomy and synaptic connectivity are affected by cocaine, the magnitude and nature of these changes depend on the presence of CB1 receptors.

  13. Recruitment of Staufen2 Enhances Dendritic Localization of an Intron-Containing CaMKIIα mRNA.

    Science.gov (United States)

    Ortiz, Raúl; Georgieva, Maya V; Gutiérrez, Sara; Pedraza, Neus; Fernández-Moya, Sandra M; Gallego, Carme

    2017-07-05

    Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain. This subpopulation of unspliced mRNA preferentially localizes to distal dendrites in a synaptic-activity-dependent manner. Staufen2, a well-established marker of RNA transport in dendrites, interacts with intron i16 sequences and enhances its distal dendritic localization, pointing to the existence of intron-mediated mechanisms in the molecular pathways that modulate dendritic transport and localization of synaptic mRNAs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Dendritic mitochondria reach stable positions during circuit development.

    Science.gov (United States)

    Faits, Michelle C; Zhang, Chunmeng; Soto, Florentina; Kerschensteiner, Daniel

    2016-01-07

    Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca(2+)-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca(2+) transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites.

  15. Positron excitation of neon

    Science.gov (United States)

    Parcell, L. A.; Mceachran, R. P.; Stauffer, A. D.

    1990-01-01

    The differential and total cross section for the excitation of the 3s1P10 and 3p1P1 states of neon by positron impact were calculated using a distorted-wave approximation. The results agree well with experimental conclusions.

  16. Hardness and excitation energy

    Indian Academy of Sciences (India)

    It is shown that the first excitation energy can be given by the Kohn-Sham hardness (i.e. the energy difference of the ground-state lowest unoccupied and highest occupied levels) plus an extra term coming from the partial derivative of the ensemble exchange-correlation energy with respect to the weighting factor in the ...

  17. Excitation of Stellar Pulsations

    DEFF Research Database (Denmark)

    Houdek, G.

    2012-01-01

    In this review I present an overview of our current understanding of the physical mechanisms that are responsible for the excitation of pulsations in stars with surface convection zones. These are typically cooler stars such as the δ Scuti stars, and stars supporting solar-like oscillations....

  18. Stress and trauma: BDNF control of dendritic-spine formation and regression.

    Science.gov (United States)

    Bennett, M R; Lagopoulos, J

    2014-01-01

    Chronic restraint stress leads to increases in brain derived neurotrophic factor (BDNF) mRNA and protein in some regions of the brain, e.g. the basal lateral amygdala (BLA) but decreases in other regions such as the CA3 region of the hippocampus and dendritic spine density increases or decreases in line with these changes in BDNF. Given the powerful influence that BDNF has on dendritic spine growth, these observations suggest that the fundamental reason for the direction and extent of changes in dendritic spine density in a particular region of the brain under stress is due to the changes in BDNF there. The most likely cause of these changes is provided by the stress initiated release of steroids, which readily enter neurons and alter gene expression, for example that of BDNF. Of particular interest is how glucocorticoids and mineralocorticoids tend to have opposite effects on BDNF gene expression offering the possibility that differences in the distribution of their receptors and of their downstream effects might provide a basis for the differential transcription of the BDNF genes. Alternatively, differences in the extent of methylation and acetylation in the epigenetic control of BDNF transcription are possible in different parts of the brain following stress. Although present evidence points to changes in BDNF transcription being the major causal agent for the changes in spine density in different parts of the brain following stress, steroids have significant effects on downstream pathways from the TrkB receptor once it is acted upon by BDNF, including those that modulate the density of dendritic spines. Finally, although glucocorticoids play a canonical role in determining BDNF modulation of dendritic spines, recent studies have shown a role for corticotrophin releasing factor (CRF) in this regard. There is considerable improvement in the extent of changes in spine size and density in rodents with forebrain specific knockout of CRF receptor 1 (CRFR1) even when

  19. Dendritic cells derived from bone marrow cells fail to acquire and present major histocompatibility complex antigens from other dendritic cells

    Science.gov (United States)

    Bedford, Penelope A; Burke, Fiona; Stagg, Andrew J; Knight, Stella C

    2008-01-01

    Dendritic cells stimulate primary T-cell responses and a major activation route is via presentation of antigens pre-processed by other dendritic cells. This presentation of pre-processed antigens most likely proceeds through transfer of functional major histocompatibility complex (MHC) antigens through exosomes, ‘live nibbling’ or apoptotic vesicles. We hypothesized that not all dendritic cell populations may both donate MHC antigen to dendritic cells and present antigens acquired from other dendritic cells. All populations tested, including those derived from bone marrow precursor cells stimulated primary, allogeneic T-cell responses and acted as accessory cells for mitogen stimulation. Populations of responder type, splenic dendritic cells promoted allogeneic responses indirectly but those derived from bone marrow cells blocked rather than promoted T-cell proliferation. To identify mechanisms underlying this difference we studied transfer of I-A antigens between cells. Active, two-way transfer of allogeneic I-A occurred between splenic primary antigen presenting cells including CD8α+ lymphoid dendritic cells, CD8α− myeloid dendritic cells and B220+ cells; all these cell types donated as well as acquired MHC molecules. By contrast, the bone marrow-derived dendritic cells donated I-A antigens but acquired negligible amounts. Thus, dendritic cells derived directly from bone marrow cells may stimulate primary T-cell responses through transferring functional MHC to other dendritic cells but may not be able to acquire and present antigens from other dendritic cells. The evidence suggests that T-cell activation may be blocked by the presence of dendritic cells that have not matured through lymphoid tissues which are unable to acquire and present antigens pre-processed by other dendritic cells. PMID:18266716

  20. Different calcium sources control somatic versus dendritic SK channel activation during action potentials.

    Science.gov (United States)

    Jones, Scott L; Stuart, Greg J

    2013-12-11

    Small-conductance calcium-activated potassium (SK) channels play an important role in regulating neuronal excitability. While SK channels at the soma have long been known to contribute to the medium afterhyperpolarization (mAHP), recent evidence indicates they also regulate NMDA receptor activation in dendritic spines. Here we investigate the activation of SK channels in spines and dendrites of rat cortical pyramidal neurons during action potentials (APs), and compare this to SK channel activation at the soma. Using confocal calcium imaging, we demonstrate that the inhibition of SK channels with apamin results in a location-dependent increase in calcium influx into dendrites and spines during backpropagating APs (average increase, ~40%). This effect was occluded by block of R-type voltage-dependent calcium channels (VDCCs), but not by inhibition of N- or P/Q-type VDCCs, or block of calcium release from intracellular stores. During these experiments, we noticed that the calcium indicator (Oregon Green BAPTA-1) blocked the mAHP. Subsequent experiments using low concentrations of EGTA (1 mm) produced the same result, suggesting that somatic SK channels are not tightly colocalized with their calcium source. Consistent with this idea, all known subtypes of VDCCs except R-type were calcium sources for the apamin-sensitive mAHP at the soma. We conclude that SK channels in spines and dendrites of cortical pyramidal neurons regulate calcium influx during backpropagating APs in a distance-dependent manner, and are tightly coupled to R-type VDCCs. In contrast, SK channels activated by APs at the soma of these neurons are weakly coupled to a variety of VDCCs.

  1. Exotic nuclear excitations

    CERN Document Server

    Pancholi, S C

    2011-01-01

    By providing the reader with a foundational background in high spin nuclear structure physics and exploring exciting current discoveries in the field, this book presents new phenomena in a clear and compelling way. The quest for achieving the highest spin states has resulted in some remarkable successes which this monograph will address in comprehensive detail. The text covers an array of pertinent subject matter, including the rotational alignment and bandcrossings, magnetic rotation, triaxial strong deformation and wobbling motion and chirality in nuclei. Dr. Pancholi offers his readers a clearly-written and up-to-date treatment of the topics covered. The prerequisites for a proper appreciation are courses in nuclear physics and nuclear models and measurement techniques of observables like gamma-ray energies, intensities, multi-fold coincidences, angular correlations or distributions, linear polarization, internal conversion coefficients, short lifetime (pico-second range) of excited states etc. and instrum...

  2. Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle.

    Science.gov (United States)

    Meisel, Christian; Schulze-Bonhage, Andreas; Freestone, Dean; Cook, Mark James; Achermann, Peter; Plenz, Dietmar

    2015-11-24

    Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.

  3. Excitable scale free networks

    Science.gov (United States)

    Copelli, M.; Campos, P. R. A.

    2007-04-01

    When a simple excitable system is continuously stimulated by a Poissonian external source, the response function (mean activity versus stimulus rate) generally shows a linear saturating shape. This is experimentally verified in some classes of sensory neurons, which accordingly present a small dynamic range (defined as the interval of stimulus intensity which can be appropriately coded by the mean activity of the excitable element), usually about one or two decades only. The brain, on the other hand, can handle a significantly broader range of stimulus intensity, and a collective phenomenon involving the interaction among excitable neurons has been suggested to account for the enhancement of the dynamic range. Since the role of the pattern of such interactions is still unclear, here we investigate the performance of a scale-free (SF) network topology in this dynamic range problem. Specifically, we study the transfer function of disordered SF networks of excitable Greenberg-Hastings cellular automata. We observe that the dynamic range is maximum when the coupling among the elements is critical, corroborating a general reasoning recently proposed. Although the maximum dynamic range yielded by general SF networks is slightly worse than that of random networks, for special SF networks which lack loops the enhancement of the dynamic range can be dramatic, reaching nearly five decades. In order to understand the role of loops on the transfer function we propose a simple model in which the density of loops in the network can be gradually increased, and show that this is accompanied by a gradual decrease of dynamic range.

  4. Persistent Histamine Excitation of Glutamatergic Preoptic Neurons

    Science.gov (United States)

    Tabarean, Iustin V.

    2012-01-01

    Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca2+ concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca2+ concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca2+ elevation in glutamatergic MnPO neurons. PMID:23082195

  5. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Directory of Open Access Journals (Sweden)

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  6. Endoplasmic reticulum calcium stores in dendritic spines.

    Science.gov (United States)

    Segal, Menahem; Korkotian, Eduard

    2014-01-01

    Despite decades of research, the role of calcium stores in dendritic spines structure, function and plasticity is still debated. The reasons for this may have to do with the multitude of overlapping calcium handling machineries in the neuron, including stores, voltage and ligand gated channels, pumps and transporters. Also, different cells in the brain are endowed with calcium stores that are activated by different receptor types, and their differential compartmentalization in dendrites, spines and presynaptic terminals complicates their analysis. In the present review we address several key issues, including the role of calcium stores in synaptic plasticity, their role during development, in stress and in neurodegenerative diseases. Apparently, there is increasing evidence for a crucial role of calcium stores, especially of the ryanodine species, in synaptic plasticity and neuronal survival.

  7. Macrophages, Dendritic Cells, and Regression of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jonathan E. Feig

    2012-07-01

    Full Text Available Atherosclerosis is the number one cause of death in the Western world. It results from the interaction between modified lipoproteins and monocyte-derived cells such as macrophages, dendritic cells, T cells, and other cellular elements of the arterial wall. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, that protrude into the arterial lumen. Ultimately, plaque rupture and thrombosis can occur leading to the clinical complications of myocardial infarction or stroke. Although each of the cell types plays roles in the pathogenesis of atherosclerosis, in this review, the focus will be primarily on the monocyte derived cells- macrophages and dendritic cells. The roles of these cell types in atherogenesis will be highlighted. Finally, the mechanisms of atherosclerosis regression as it relates to these cells will be discussed.

  8. A stepping stone in treating dendritic keratitis

    Directory of Open Access Journals (Sweden)

    Hosam Sheha, MD, PhD

    2017-09-01

    Conclusions and importance: Self-retained amniotic membrane after debridement appears effective in treating dendritic keratitis. While early debridement is crucial to remove the infected corneal epithelium, amniotic membrane was shown to enhance the healing without scarring or recurrence. Besides the known anti-inflammatory and anti-scarring effects of the amniotic membrane, it may have a potential topical antiviral effect that warrants further investigation.

  9. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  10. Nanodiamonds suppress the growth of lithium dendrites

    OpenAIRE

    Cheng, Xin-Bing; Zhao, Meng-Qiang; Chen, Chi; Pentecost, Amanda; Maleski, Kathleen; Mathis, Tyler; Zhang, Xue-Qiang; ZHANG, QIANG; Jiang, Jianjun; Gogotsi, Yury

    2017-01-01

    Lithium metal has been regarded as the future anode material for high-energy-density rechargeable batteries due to its favorable combination of negative electrochemical potential and high theoretical capacity. However, uncontrolled lithium deposition during lithium plating/stripping results in low Coulombic efficiency and severe safety hazards. Herein, we report that nanodiamonds work as an electrolyte additive to co-deposit with lithium ions and produce dendrite-free lithium deposits. First-...

  11. The Isothermal Dendritic Growth Experiment Archive

    Science.gov (United States)

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  12. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    Science.gov (United States)

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  13. Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3)

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Gad, Monika; Walter, Mark R

    2004-01-01

    Dendritic cells (DC) modulated to induce T cell hyporesponsiveness have promising potential in immunotherapy of autoimmune disorders and for the prevention of allograft rejection. While studying the effect of immunosuppressive agents on the maturation of DC we found that 1alpha,25-Dihydroxyvitami...... D(3) the active form of Vitamin D(3) (D(3)) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D(3) and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable...

  14. Modulation cancellation method (MOCAM) in modulation spectroscopy

    Science.gov (United States)

    Spagnolo, V.; Dong, L.; Kosterev, A. A.; Thomazy, D.; Doty, J. H.; Tittel, F. K.

    2011-05-01

    An innovative spectroscopic technique based on balancing and cancellation of modulated signals induced by two excitation sources. We used quartz enhanced photoacoustic spectroscopy (QEPAS) in a 2f wavelength modulation mode as an absorption sensing technique and employed a modulation cancelation approach for spectroscopic measurements of small temperature differences in a gas mixture and detection of broadband absorbers. We demonstrated measurement of small temperature differences in a C2H2/N2gas mixture with a sensitivity of 30 mK in 17 sec and detection of hydrazine, a broadband absorbing chemical species, down to concentration of 1 part per million in volume in 1 sec. In both cases we used near-infrared laser diodes and selected overtone transitions.nuscrip

  15. Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Víctor Casanova

    Full Text Available ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID. ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8, CCL3(MIP1-α, CCL4(MIP-1β and CCL5(RANTES cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.

  16. Differential protection of injured retinal ganglion cell dendrites by brimonidine.

    Science.gov (United States)

    Lindsey, James D; Duong-Polk, Karen X; Hammond, Dustin; Chindasub, Panida; Leung, Christopher Kai-Shun; Weinreb, Robert N

    2015-01-29

    To determine whether brimonidine protects against the retraction and loss of retinal ganglion cell (RGC) dendrites after optic nerve crush (ONC). Fluorescent RGCs of mice expressing yellow fluorescent protein (YFP) under the control of the Thy-1 promoter (Thy1-YFP mice) were imaged in vivo and assigned to one of six groups according to dendrite structure. The mice then received brimonidine every other day starting 2 days before, or 2 or 6 days after, unilateral ONC. Control animals received vehicle every other day starting 2 days before ONC. Control animals received vehicle every other day starting 2 days before ONC. Total dendrite length, dendrite branching complexity, and the time until complete loss of dendrites were assessed weekly for 4 weeks. Overall, brimonidine treatment significantly slowed the complete loss of RGC dendrites and significantly slowed the reduction of total dendrite length and branching complexity. Separate analysis of each RGC group showed brimonidine significantly delayed the time until complete loss of dendrites in four of the RGC groups. These delays generally were similar when treatment started either 2 days before or 2 days after ONC, but were smaller or absent when treatment started 6 days after ONC Protection against loss of total dendrite length and loss of branching complexity was observed in three of the RGC groups. In two of these RGC groups, protective effects persisted until the end of the study. Brimonidine protects many RGC types against dendrite retraction, loss of branching complexity, and complete loss of dendrites following ONC. However, the pattern and magnitude of this protection differs substantially among different RGC types. These results indicate that requirements for RGC-protective therapies following optic nerve injury may differ among RGC types. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  17. Ternary eutectic dendrites: Pattern formation and scaling properties

    Science.gov (United States)

    Rátkai, László; Szállás, Attila; Pusztai, Tamás; Mohri, Tetsuo; Gránásy, László

    2015-04-01

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.

  18. Theory of slow light excitation in 1D photonic crystals

    NARCIS (Netherlands)

    Yudistira, D.; Marpaung, D.A.I.; Handoyo, H.P.; Hoekstra, Hugo; Hammer, Manfred; Tjia, M.O.; Iskandar, A.A.P.; Iskandar, A.A.

    2004-01-01

    Slow light (SL) states corresponding to wavelength regions near the bandgap edge of grated structures are known to show strong eld enhancement. Such states may be excited efciently by well-optimised adiabatic transitions in grating structures, e.g., by slowly turning on the modulation depth. To

  19. Slow light excitation in tapered 1D photonic crystals: theory

    NARCIS (Netherlands)

    Yudistira, D.; Hoekstra, Hugo; Hammer, Manfred; Marpaung, D.A.I.

    2006-01-01

    Slow light (SL) states corresponding to wavelength regions near the bandgap edge of grated structures are known to show strong field enhancement. Such states may be excited efficiently by well-optimised adiabatic transitions in grated structures, e.g., by slowly turning on the modulation depth. To

  20. Excitability of Motor Cortices as a Function of Emotional Sounds

    NARCIS (Netherlands)

    Komeilipoor, N.; Pizzolato, F.; Daffertshofer, A.; Cesari, P.

    2013-01-01

    We used transcranial magnetic stimulation (TMS) to clarify how non-verbal emotionally-characterized sounds modulate the excitability of the corticospinal motor tract (CST). While subjects were listening to sounds (monaurally and binaurally), single TMS pulses were delivered to either left or right

  1. Periodic behavior for the parametrically excited Boussinesq equation

    Energy Technology Data Exchange (ETDEWEB)

    Maccari, Attilio E-mail: solitone@yahoo.it

    2004-10-01

    The asymptotic perturbation (AP) method is applied to the study of the parametrically excited and weakly damped Boussinesq equation in an infinite wall. Amplitude and phase modulation equations as well as external force-response and frequency-response curves are obtained. The presence of jump phenomena and bifurcations is demonstrated.

  2. Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Tobias Roider

    2016-12-01

    Full Text Available Antithymocyte globulin (ATG is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon® on human monocyte-derived dendritic cells (DC. ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

  3. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

    Science.gov (United States)

    Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail. PMID:26858719

  4. Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells.

    Science.gov (United States)

    Roider, Tobias; Katzfuß, Michael; Matos, Carina; Singer, Katrin; Renner, Kathrin; Oefner, Peter J; Dettmer-Wilde, Katja; Herr, Wolfgang; Holler, Ernst; Kreutz, Marina; Peter, Katrin

    2016-12-11

    Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon(®)) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

  5. Gliadin fragments promote migration of dendritic cells

    Czech Academy of Sciences Publication Activity Database

    Chládková, Barbara; Kamanová, Jana; Palová-Jelínková, Lenka; Cinová, Jana; Šebo, Peter; Tučková, Ludmila

    2011-01-01

    Roč. 15, č. 4 (2011), 938-948 ISSN 1582-1838 R&D Projects: GA ČR GA310/07/0414; GA ČR GD310/08/H077; GA ČR GA310/08/0447; GA AV ČR IAA500200801; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : celiac disease * gliadin * dendritic cell Subject RIV: EC - Immunology Impact factor: 4.125, year: 2011

  6. Viruses, dendritic cells and the lung

    Directory of Open Access Journals (Sweden)

    Graham Barney S

    2001-06-01

    Full Text Available Abstract The interaction between viruses and dendritic cells (DCs is varied and complex. DCs are key elements in the development of a host response to pathogens such as viruses, but viruses have developed survival tactics to either evade or diminish the immune system that functions to kill and eliminate these micro-organisms. In the present review we summarize current concepts regarding the function of DCs in the immune system, our understanding of how viruses alter DC function to attenuate both the virus-specific and global immune response, and how we may be able to exploit DC function to prevent or treat viral infections.

  7. Dendritic Cells as Danger-Recognizing Biosensors

    Directory of Open Access Journals (Sweden)

    Seokmann Hong

    2009-08-01

    Full Text Available Dendritic cells (DCs are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. DCs comprise several subsets with distinct phenotypes. After sensing any danger(s to the host via their innate immune receptors such as Toll-like receptors, DCs become mature and subsequently present antigens to CD4+ T cells. Since DCs possess the intrinsic capacity to polarize CD4+ helper cells, it is critical to understand the immunological roles of DCs for clinical applications. Here, we review the different DC subsets, their danger-sensing receptors and immunological functions. Furthermore, the cytokine reporter mouse model for studying DC activation is introduced.

  8. CINE: Comet INfrared Excitation

    Science.gov (United States)

    de Val-Borro, Miguel; Cordiner, Martin A.; Milam, Stefanie N.; Charnley, Steven B.

    2017-08-01

    CINE calculates infrared pumping efficiencies that can be applied to the most common molecules found in cometary comae such as water, hydrogen cyanide or methanol. One of the main mechanisms for molecular excitation in comets is the fluorescence by the solar radiation followed by radiative decay to the ground vibrational state. This command-line tool calculates the effective pumping rates for rotational levels in the ground vibrational state scaled by the heliocentric distance of the comet. Fluorescence coefficients are useful for modeling rotational emission lines observed in cometary spectra at sub-millimeter wavelengths. Combined with computational methods to solve the radiative transfer equations based, e.g., on the Monte Carlo algorithm, this model can retrieve production rates and rotational temperatures from the observed emission spectrum.

  9. Musical representation of dendritic spine distribution: a new exploratory tool.

    Science.gov (United States)

    Toharia, Pablo; Morales, Juan; de Juan, Octavio; Fernaud, Isabel; Rodríguez, Angel; DeFelipe, Javier

    2014-04-01

    Dendritic spines are small protrusions along the dendrites of many types of neurons in the central nervous system and represent the major target of excitatory synapses. For this reason, numerous anatomical, physiological and computational studies have focused on these structures. In the cerebral cortex the most abundant and characteristic neuronal type are pyramidal cells (about 85 % of all neurons) and their dendritic spines are the main postsynaptic target of excitatory glutamatergic synapses. Thus, our understanding of the synaptic organization of the cerebral cortex largely depends on the knowledge regarding synaptic inputs to dendritic spines of pyramidal cells. Much of the structural data on dendritic spines produced by modern neuroscience involves the quantitative analysis of image stacks from light and electron microscopy, using standard statistical and mathematical tools and software developed to this end. Here, we present a new method with musical feedback for exploring dendritic spine morphology and distribution patterns in pyramidal neurons. We demonstrate that audio analysis of spiny dendrites with apparently similar morphology may "sound" quite different, revealing anatomical substrates that are not apparent from simple visual inspection. These morphological/music translations may serve as a guide for further mathematical analysis of the design of the pyramidal neurons and of spiny dendrites in general.

  10. Blastic Plasmacytoid Dendritic Cell Leukemia in a Black Malian

    African Journals Online (AJOL)

    2017-06-28

    Jun 28, 2017 ... adhesion molecule 1) by blastic plasmacytoid dendritic cell neoplasms. JAMA Dermatology 2014;150:73‑6. 11. Goren Sahin D, Akay OM, Uskudar Teke H, Andic N, Gunduz E. Gulbas Z. Blastic plasmacytoid dendritic cell leukemia successfully treated by autologous hematopoietic stem cell transplantation ...

  11. Barriers in the brain : resolving dendritic spine morphology and compartmentalization

    NARCIS (Netherlands)

    Adrian, Max; Kusters, Remy; Wierenga, Corette J; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and

  12. Redefining the gonadotrophin-releasing hormone neurone dendrite.

    Science.gov (United States)

    Campbell, R E; Suter, K J

    2010-07-01

    Gonadotrophin-releasing hormone (GnRH) neurones are the final output neurones of the complex synaptic network responsible for the central control of fertility. This scattered population of neurones has been shown to have remarkably long dendritic processes by cell-filling of GnRH neurones in situ with low-molecular weight dyes. This review focuses on how the functional significance of these long dendritic extensions is being explored through dual somatic-dendritic electrophysiological recordings, computational modelling, immunolabelling for specific channels and multiple modes of microscopy and imaging. Remarkably, recent work has discovered that GnRH neurone dendrites not only actively propagate action potentials, but also comprise the primary site of action potential initiation. These findings, along with the discovery of regionalized expression of active conductances, highlight dendrites of single GnRH neurones as being central sites of signal integration. Moreover, imaging studies have shown that the long dendrites of GnRH neurones intertwine and bundle with one another. The presence of shared synaptic input to bundling dendrites, coupled with their active properties and the increased potency of distally placed synaptic inputs, is suggestive of a novel mechanism of GnRH neurone synchronisation, a feature critical for mammalian reproduction. Together, these discoveries of the GnRH neurone dendrite structure and function are changing the way that we view the central regulation of fertility.

  13. Differential expression of tetraspanin superfamily members in dendritic cell subsets

    NARCIS (Netherlands)

    M. Zuidscherwoude (Malou); K. Worah (Kuntal); A. Van Der Schaaf (Alie); S.I. Buschow (Sonja I.); A.B. Spriel (Annemiek )

    2017-01-01

    textabstractDendritic cells (DCs), which are essential for initiating immune responses, are comprised of different subsets. Tetraspanins organize dendritic cell membranes by facilitating protein-protein interactions within the so called tetraspanin web. In this study we analyzed expression of the

  14. Differential expression of tetraspanin superfamily members in dendritic cell subsets

    NARCIS (Netherlands)

    Zuidscherwoude, M.C.; Worah, K.; Schaaf, A. van der; Buschow, S.I.; Spriel, A.B. van

    2017-01-01

    Dendritic cells (DCs), which are essential for initiating immune responses, are comprised of different subsets. Tetraspanins organize dendritic cell membranes by facilitating protein-protein interactions within the so called tetraspanin web. In this study we analyzed expression of the complete

  15. Dendritic cell-based immunotherapy in ovarian cancer.

    Science.gov (United States)

    Coosemans, An; Vergote, Ignace; Van Gool, Stefaan W

    2013-12-01

    Worldwide, 80% of patients with ovarian cancer die of the disease. New treatments for this aggressive disease are therefore being intensively searched. Although dendritic cell-based vaccines against gynecological malignancies are in their infancy, this immunotherapeutic approach holds much promise. Here, we present our view on an optimal dendritic cell-based immunotherapeutic strategy against ovarian cancer.

  16. Self-Exciting Point Process Modeling of Conversation Event Sequences

    Science.gov (United States)

    Masuda, Naoki; Takaguchi, Taro; Sato, Nobuo; Yano, Kazuo

    Self-exciting processes of Hawkes type have been used to model various phenomena including earthquakes, neural activities, and views of online videos. Studies of temporal networks have revealed that sequences of social interevent times for individuals are highly bursty. We examine some basic properties of event sequences generated by the Hawkes self-exciting process to show that it generates bursty interevent times for a wide parameter range. Then, we fit the model to the data of conversation sequences recorded in company offices in Japan. In this way, we can estimate relative magnitudes of the self excitement, its temporal decay, and the base event rate independent of the self excitation. These variables highly depend on individuals. We also point out that the Hawkes model has an important limitation that the correlation in the interevent times and the burstiness cannot be independently modulated.

  17. Posture-Dependent Corticomotor Excitability Differs Between the Transferred Biceps in Individuals With Tetraplegia and the Biceps of Nonimpaired Individuals.

    Science.gov (United States)

    Peterson, Carrie L; Rogers, Lynn M; Bednar, Michael S; Bryden, Anne M; Keith, Michael W; Perreault, Eric J; Murray, Wendy M

    2017-04-01

    Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.

  18. Immune monitoring using mRNA-transfected dendritic cells

    DEFF Research Database (Denmark)

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by m......RNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate...... and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA....

  19. Excitation of plasmonic waveguide modes using principles of holography

    Science.gov (United States)

    Ignatov, Anton I.; Merzlikin, Alexander M.

    2017-08-01

    A method for development of gratings for effective excitation of surface plasmonic waves using holography principles has been proposed and theoretically analyzed. The case of excitation of a plasmonic wave in a dielectric layer on metal using volume holograms in the dielectric layer has been considered. For comparison, simple periodic gratings with refractive index of the dielectric layer modulated in the plane of the layer and invariable in the direction perpendicular to the layer plane have been considered. The efficiencies of the proposed holograms and gratings optimized for various incidence angles of exciting waves incident on the gratings/holograms from air have been analyzed. Based on this analysis, general enough conditions when holograms can be more efficient than simple gratings have been found out. In particular, a hologram is expected to be more efficient than the grating when the refractive index distribution in the hologram is considerably inhomogeneous (contrary to the gratings) in the direction perpendicular to the layer plane. For example, this may be the case if the exciting wave is incident on a hologram obliquely at a rather large angle or if phase fronts of either exciting wave or a wave being excited are curved. The proposed holographic method is quite universal. As expected, this can be extended for efficient excitation of different types of optical surface waves and modes of optical waveguides.

  20. Subsurface excitations in a metal

    DEFF Research Database (Denmark)

    Ray, M. P.; Lake, R. E.; Sosolik, C. E.

    2009-01-01

    We investigate internal hot carrier excitations in a Au thin film bombarded by hyperthermal and low energy alkali and noble gas ions. Excitations within the thin film of a metal-oxide-semiconductor device are measured revealing that ions whose velocities fall below the classical threshold given...... by the free-electron model of a metal still excite hot carriers. Excellent agreement between these results and a nonadiabatic model that accounts for the time-varying ion-surface interaction indicates that the measured excitations are due to semilocalized electrons near the metal surface....

  1. Mapping extracellular excitability in an insect mechanoreceptor neuron.

    Science.gov (United States)

    Torkkeli, P H; French, A S

    1993-12-31

    The cockroach tactile spine contains a single bipolar mechanosensory neuron. Extracellular stimulation of the neuron is possible by cutting the spine and lowering a microelectrode into the lumen, where the neuron is located, but neither the microelectrode nor the neuron can be visualized during stimulation. The threshold for electrical stimulation of the neuron was measured as a function of spatial position in the lumen. The spine was then fixed and serially sectioned for computer-aided reconstruction. Alignment of threshold measurements with reconstructions produced maps of excitability around the neuron. The lowest threshold was always close to the sensory dendrite or the adjacent soma. These results are discussed in terms of models of action potential initiation in this class of sensory neurons.

  2. Dendrite coherency point: determination and significance

    Energy Technology Data Exchange (ETDEWEB)

    Veldman, N.L.M.; St John, D.H. [Queensland Univ., St. Lucia, QLD (Australia); Dahle, A.K.; Arnberg, L. [Norwegian University of Science and Technology, Trondheim (Norway)

    1996-09-01

    Measurements of the rheological properties of solidifying alloys have shown that the fraction solid at which dendrite coherency is reached varies systematically as a function of both alloy and solidification parameters. The coherency point of the alloys under investigation was determined in two different ways. Each method is based on indirect measurements of a physical property of the material which is assumed to undergo a significant liquid-solid transition at the dendrite coherency point. The coherency fraction solid for Al-Cu-Si alloys was found to decrease with increasing solute concentration. AA601 was found to have a higher coherency fraction solid than binary Al-7 wt%Si. Increasing the cooling rate was found to increase the coherency fraction solid of the alloys, as measured with the thermal analysis technique. Variation between the coherency fraction solids determined by rheological and thermal analysis methods are considered to be related to the different coherency criterion used in each experimental method. 15 refs., 6 figs.

  3. Dendritic growth model of multilevel marketing

    Science.gov (United States)

    Pang, James Christopher S.; Monterola, Christopher P.

    2017-02-01

    Biologically inspired dendritic network growth is utilized to model the evolving connections of a multilevel marketing (MLM) enterprise. Starting from agents at random spatial locations, a network is formed by minimizing a distance cost function controlled by a parameter, termed the balancing factor bf, that weighs the wiring and the path length costs of connection. The paradigm is compared to an actual MLM membership data and is shown to be successful in statistically capturing the membership distribution, better than the previously reported agent based preferential attachment or analytic branching process models. Moreover, it recovers the known empirical statistics of previously studied MLM, specifically: (i) a membership distribution characterized by the existence of peak levels indicating limited growth, and (ii) an income distribution obeying the 80 - 20 Pareto principle. Extensive types of income distributions from uniform to Pareto to a "winner-take-all" kind are also modeled by varying bf. Finally, the robustness of our dendritic growth paradigm to random agent removals is explored and its implications to MLM income distributions are discussed.

  4. Learning Enhances Intrinsic Excitability in a Subset of Lateral Amygdala Neurons

    Science.gov (United States)

    Sehgal, Megha; Ehlers, Vanessa L.; Moyer, James R., Jr.

    2014-01-01

    Learning-induced modulation of neuronal intrinsic excitability is a metaplasticity mechanism that can impact the acquisition of new memories. Although the amygdala is important for emotional learning and other behaviors, including fear and anxiety, whether learning alters intrinsic excitability within the amygdala has received very little…

  5. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    Directory of Open Access Journals (Sweden)

    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  6. Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.

    Science.gov (United States)

    Gray, Nora E; Zweig, Jonathan A; Murchison, Charles; Caruso, Maya; Matthews, Donald G; Kawamoto, Colleen; Harris, Christopher J; Quinn, Joseph F; Soumyanath, Amala

    2017-04-12

    The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer's disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Dendritic and Axonal L-Type Calcium Channels Cooperate to Enhance Motoneuron Firing Output duringDrosophilaLarval Locomotion.

    Science.gov (United States)

    Kadas, Dimitrios; Klein, Aylin; Krick, Niklas; Worrell, Jason W; Ryglewski, Stefanie; Duch, Carsten

    2017-11-08

    Behaviorally adequate neuronal firing patterns are critically dependent on the specific types of ion channel expressed and on their subcellular localization. This study combines in situ electrophysiology with genetic and pharmacological intervention in larval Drosophila melanogaster of both sexes to address localization and function of L-type like calcium channels in motoneurons. We demonstrate that Dmca1D (Ca v 1 homolog) L-type like calcium channels localize to both the somatodendritic and the axonal compartment of larval crawling motoneurons. In situ patch-clamp recordings in genetic mosaics reveal that Dmca1D channels increase burst duration and maximum intraburst firing frequencies during crawling-like motor patterns in semi-intact animals. Genetic and acute pharmacological manipulations suggest that prolonged burst durations are caused by dendritically localized Dmca1D channels, which activate upon cholinergic synaptic input and amplify EPSPs, thus indicating a conserved function of dendritic L-type channels from Drosophila to vertebrates. By contrast, maximum intraburst firing rates require axonal calcium influx through Dmca1D channels, likely to enhance sodium channel de-inactivation via a fast afterhyperpolarization through BK channel activation. Therefore, in unmyelinated Drosophila motoneurons different functions of axonal and dendritic L-type like calcium channels likely operate synergistically to maximize firing output during locomotion. SIGNIFICANCE STATEMENT Nervous system function depends on the specific excitabilities of different types of neurons. Excitability is largely shaped by different combinations of voltage-dependent ion channels. Despite a high degree of conservation, the huge diversity of ion channel types and their differential localization pose challenges in assigning distinct functions to specific channels across species. We find a conserved role, from fruit flies to mammals, for L-type calcium channels in augmenting motoneuron

  8. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  9. Astragalus root and elderberry fruit extracts enhance the IFN-ß stimulatory effects of Lactobacillus acidophilus in murine-derived dendritic cells

    DEFF Research Database (Denmark)

    Frøkiær, Hanne; Henningsen, Louise; Metzdorff, Stine Broeng

    2012-01-01

    cytokines, whereas gram-positive Lactobacillus acidophilus induces a robust interferon (IFN)-ß response. The immune-modulating effects of astragalus root and elderberry fruit extracts were examined in bone marrow-derived murine dendritic cells that were stimulated with L. acidophilus or E. coli. IFN......-ß and other cytokines were measured by ELISA and RT-PCR. Endocytosis of fluorescence-labeled dextran and L. acidophilus in the presence of elderberry fruit or astragalus root extract was evaluated in dendritic cells. Our results show that both extracts enhanced L. acidophilus-induced IFN-ß production...... influenced the viability of the cells. In conclusion, astragalus root and elderberry fruit extracts increase the IFN-ß inducing activity of L. acidophilus in dendritic cells, suggesting that they may exert antiviral and immune-enhancing activity....

  10. Inhibition of the differentiation of monocyte-derived dendritic cells by human gingival fibroblasts.

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    Sylvie Séguier

    Full Text Available We investigated whether gingival fibroblasts (GFs can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05 inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism.

  11. Inhibition of the differentiation of monocyte-derived dendritic cells by human gingival fibroblasts.

    Science.gov (United States)

    Séguier, Sylvie; Tartour, Eric; Guérin, Coralie; Couty, Ludovic; Lemitre, Mathilde; Lallement, Laetitia; Folliguet, Marysette; El Naderi, Samah; Terme, Magali; Badoual, Cécile; Lafont, Antoine; Coulomb, Bernard

    2013-01-01

    We investigated whether gingival fibroblasts (GFs) can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs) and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM) from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05) inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism.

  12. Immune System in the Brain: A Modulatory Role on Dendritic Spine Morphophysiology?

    Directory of Open Access Journals (Sweden)

    Oscar Kurt Bitzer-Quintero

    2012-01-01

    Full Text Available The central nervous system is closely linked to the immune system at several levels. The brain parenchyma is separated from the periphery by the blood brain barrier, which under normal conditions prevents the entry of mediators such as activated leukocytes, antibodies, complement factors, and cytokines. The myeloid cell lineage plays a crucial role in the development of immune responses at the central level, and it comprises two main subtypes: (1 resident microglia, distributed throughout the brain parenchyma; (2 perivascular macrophages located in the brain capillaries of the basal lamina and the choroid plexus. In addition, astrocytes, oligodendrocytes, endothelial cells, and, to a lesser extent, neurons are implicated in the immune response in the central nervous system. By modulating synaptogenesis, microglia are most specifically involved in restoring neuronal connectivity following injury. These cells release immune mediators, such as cytokines, that modulate synaptic transmission and that alter the morphology of dendritic spines during the inflammatory process following injury. Thus, the expression and release of immune mediators in the brain parenchyma are closely linked to plastic morphophysiological changes in neuronal dendritic spines. Based on these observations, it has been proposed that these immune mediators are also implicated in learning and memory processes.

  13. Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

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    Alma Zernecke

    2014-01-01

    Full Text Available Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis.

  14. Milk-derived GM3 and GD3 differentially inhibit dendritic cell maturation and effector functionalities

    DEFF Research Database (Denmark)

    Brønnum, H.; Seested, T.; Hellgren, Lars

    2005-01-01

    value of gangliosides in breast milk has yet to be elucidated but when milk is ingested, dietary gangliosides might conceptually affect immune cells, such as dendritic cells (DCs). In this study, we address the in vitro effect of GD(3) and GM(3) on DC effector functionalities. Treatment of bone marrow......Gangliosides are complex glycosphingolipids, which exert immune-modulating effects on various cell types. Ganglioside GD(3) and GM(3) are the predominant gangliosides of human breast milk but during the early phase of lactation, the content of GD(3) decreases while GM(3) increases. The biological...... by GM(3,) and the potency of DCs to activate CD4(+) cells in MLR was unaffected by GM(3). However, both gangliosides suppressed expression of CD40, CD80, CD86 and major histocompatibility complex class II on DCs. Because GD(3) overall inhibits DC functionalities more than GM(3), the immune modulating...

  15. Milk-derived GM(3) and GD(3) differentially inhibit dendritic cell maturation and effector functionalities

    DEFF Research Database (Denmark)

    Bronnum, H.; Seested, T.; Hellgren, Lars

    2005-01-01

    value of gangliosides in breast milk has yet to be elucidated but when milk is ingested, dietary gangliosides might conceptually affect immune cells, such as dendritic cells (DCs). In this study, we address the in vitro effect of GD(3) and GM(3) on DC effector functionalities. Treatment of bone marrow......Gangliosides are complex glycosphingolipids, which exert immune-modulating effects on various cell types. Ganglioside GD(3) and GM(3) are the predominant gangliosides of human breast milk but during the early phase of lactation, the content of GD(3) decreases while GM(3) increases. The biological...... by GM(3,) and the potency of DCs to activate CD4(+) cells in MLR was unaffected by GM(3). However, both gangliosides suppressed expression of CD40, CD80, CD86 and major histocompatibility complex class II on DCs. Because GD(3) overall inhibits DC functionalities more than GM(3), the immune modulating...

  16. Topological excitations in magnetic materials

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D., E-mail: bazeia@fisica.ufpb.br [Departamento de Física, Universidade Federal da Paraíba, 58051-970 João Pessoa, PB (Brazil); Doria, M.M. [Instituto de Física, Universidade Federal do Rio de Janeiro, Rio de Janeiro (Brazil); Dipartimento di Fisica, Università di Camerino, I-62032 Camerino (Italy); Rodrigues, E.I.B. [Departamento de Física, Universidade Federal da Paraíba, 58051-970 João Pessoa, PB (Brazil)

    2016-05-20

    In this work we propose a new route to describe topological excitations in magnetic systems through a single real scalar field. We show here that spherically symmetric structures in two spatial dimensions, which map helical excitations in magnetic materials, admit this formulation and can be used to model skyrmion-like structures in magnetic materials.

  17. Dendritic nonlinearities reduce network size requirements and mediate ON and OFF states of persistent activity in a PFC microcircuit model.

    Directory of Open Access Journals (Sweden)

    Athanasia Papoutsi

    2014-07-01

    Full Text Available Technological advances have unraveled the existence of small clusters of co-active neurons in the neocortex. The functional implications of these microcircuits are in large part unexplored. Using a heavily constrained biophysical model of a L5 PFC microcircuit, we recently showed that these structures act as tunable modules of persistent activity, the cellular correlate of working memory. Here, we investigate the mechanisms that underlie persistent activity emergence (ON and termination (OFF and search for the minimum network size required for expressing these states within physiological regimes. We show that (a NMDA-mediated dendritic spikes gate the induction of persistent firing in the microcircuit. (b The minimum network size required for persistent activity induction is inversely proportional to the synaptic drive of each excitatory neuron. (c Relaxation of connectivity and synaptic delay constraints eliminates the gating effect of NMDA spikes, albeit at a cost of much larger networks. (d Persistent activity termination by increased inhibition depends on the strength of the synaptic input and is negatively modulated by dADP. (e Slow synaptic mechanisms and network activity contain predictive information regarding the ability of a given stimulus to turn ON and/or OFF persistent firing in the microcircuit model. Overall, this study zooms out from dendrites to cell assemblies and suggests a tight interaction between dendritic non-linearities and network properties (size/connectivity that may facilitate the short-memory function of the PFC.

  18. Excitability of motor cortices as a function of emotional sounds.

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    Naeem Komeilipoor

    Full Text Available We used transcranial magnetic stimulation (TMS to clarify how non-verbal emotionally-characterized sounds modulate the excitability of the corticospinal motor tract (CST. While subjects were listening to sounds (monaurally and binaurally, single TMS pulses were delivered to either left or right primary motor cortex (M1, and electromyographic activities were recorded from the contralateral abductor pollicis brevis muscle. We found a significant increase in CST excitability in response to unpleasant as compared to neutral sounds. The increased excitability was lateralized as a function of stimulus valence: Unpleasant stimuli resulted in a significantly higher facilitation of motor potentials evoked in the left hemisphere, while pleasant stimuli yielded a greater CST excitability in the right one. Furthermore, TMS induced higher motor evoked potentials when listening to unpleasant sounds with the left than with the right ear. Taken together, our findings provide compelling evidence for an asymmetric modulation of CST excitability as a function of emotional sounds along with ear laterality.

  19. Dendritic mitochondria reach stable positions during circuit development

    Science.gov (United States)

    Faits, Michelle C; Zhang, Chunmeng; Soto, Florentina; Kerschensteiner, Daniel

    2016-01-01

    Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca2+-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca2+ transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites. DOI: http://dx.doi.org/10.7554/eLife.11583.001 PMID:26742087

  20. Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

    Directory of Open Access Journals (Sweden)

    Lauren M DePoy

    2014-10-01

    Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

  1. Dendritic cells and aging: consequences for autoimmunity.

    Science.gov (United States)

    Agrawal, Anshu; Sridharan, Aishwarya; Prakash, Sangeetha; Agrawal, Harsh

    2012-01-01

    The immune system has evolved to mount immune responses against foreign pathogens and to remain silent against self-antigens. A balance between immunity and tolerance is required as any disturbance may result in chronic inflammation or autoimmunity. Dendritic cells (DCs) actively participate in maintaining this balance. Under steady-state conditions, DCs remain in an immature state and do not mount an immune response against circulating self-antigens in the periphery, which maintains a state of tolerance. By contrast, foreign antigens result in DC maturation and DC-induced T-cell activation. Inappropriate maturation of DCs due to infections or tissue injury may cause alterations in the balance between the tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases. This article provides an overview of the effects of advancing age on DC functions and their implications in autoimmunity.

  2. Towards deep learning with segregated dendrites.

    Science.gov (United States)

    Guerguiev, Jordan; Lillicrap, Timothy P; Richards, Blake A

    2017-12-05

    Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the neocortex optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network learns to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful higher-order representations-the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the morphology of neocortical pyramidal neurons.

  3. Induction of RNA interference in dendritic cells.

    Science.gov (United States)

    Li, Mu; Qian, Hua; Ichim, Thomas E; Ge, Wei-Wen; Popov, Igor A; Rycerz, Katarzyna; Neu, John; White, David; Zhong, Robert; Min, Wei-Ping

    2004-01-01

    Dendritic cells (DC) reside at the center of the immunological universe, possessing the ability both to stimulate and inhibit various types of responses. Tolerogenic/regulatory DC with therapeutic properties can be generated through various means of manipulations in vitro and in vivo. Here we describe several attractive strategies for manipulation of DC using the novel technique of RNA interference (RNAi). Additionally, we overview some of our data regarding yet undescribed characteristics of RNAi in DC such as specific transfection strategies, persistence of gene silencing, and multi-gene silencing. The advantages of using RNAi for DC genetic manipulation gives rise to the promise of generating tailor-made DC that can be used effectively to treat a variety of immunologically mediated diseases.

  4. Killer dendritic cells: IKDC and the others.

    Science.gov (United States)

    Bonmort, Mathieu; Dalod, Marc; Mignot, Grégoire; Ullrich, Evelyn; Chaput, Nathalie; Zitvogel, Laurence

    2008-10-01

    Tumors can regress as a result of invading myeloid and lymphoid cells that act in concert. Although the myeloid cells are widely recognized as antigen presenters and lymphoid cells as classical effectors, recent evidence revealed the capacity of dendritic cells (DC) to kill tumor cells. The functional concept of 'natural killer (NK) myeloid DC' is supported by mouse and human in vitro data that may be clinically relevant because human killer DC can contribute to tumor shrinking during topical therapy with toll-like receptor (TLR) agonists. Whether tumor killing by DC is a 'catalyzing' step for efficient crosspresentation and/or a promoting step for an immunogenic cell death pathway remains an open question. We also discuss how interferon-producing killer DC (IKDC) may participate in the control of tumor progression.

  5. Maturation of dendritic cells by bacterial immunomodulators.

    Science.gov (United States)

    Spisek, Radek; Brazova, Jitka; Rozkova, Daniela; Zapletalova, Katerina; Sediva, Anna; Bartunkova, Jirina

    2004-07-29

    Dendritic cells (DC) become fully functional upon maturation by various stimuli. We tested whether an immunostimulatory effect of clinically used immunomodulators (Luivac, Biostim, Ribomunyl, Imudon, Bronchovaxom) is caused by direct DC activation. We found that Luivac, Biostim and Ribomunyl have a very high DC stimulatory potential in vitro. The level of DC activation was comparable or higher than DC maturation induced by standard maturation stimuli, Poly (I:C) or lipopolysaccharide. Treated DC had activated phenotype, reduced phagocytic activity and they induced the proliferation of allogeneic T lymphocytes. These results are important for understanding the physiology of action of these widely prescribed agents. Administration of bacterial immunomodulators should be considered with care to avoid the potential risk of inducing an autoimmune disease. They could also be used as well-defined maturating agents in the protocols used for the ex vivo production of DC-based vaccines for clinical trials.

  6. Targeting dendritic cells--why bother?

    Science.gov (United States)

    Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

    2013-04-11

    Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

  7. Human dendritic cell culture and bacterial infection.

    Science.gov (United States)

    Jones, Hannah E; Klein, Nigel; Dixon, Garth L J

    2012-01-01

    Dendritic cells (DC) play a key role in the development of natural immunity to microbes. The DC form a bridge between the innate and adaptive immune system by providing key instructions particularly to antigen naïve T-cells. The interaction of DC with T lymphocytes involves three signals: (1) antigen processing and presentation in context of MHC Class I and/or II, (2) expression of T cell co-stimulatory molecules, and (3) cytokine production. Studying the interactions of DCs with specific pathogens allows for better understanding of how protective immunity is generated, and may be particularly useful for assessing vaccine components. In this chapter, we describe methods to generate human monocyte-derived DCs and assess their maturation, activation, and function, using interaction with the gram-negative bacterial pathogen Neisseria meningitidis as a model.

  8. Influence of dendritic cells on viral pathogenicity.

    Science.gov (United States)

    Freer, Giulia; Matteucci, Donatella

    2009-07-01

    Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.

  9. Influence of dendritic cells on viral pathogenicity.

    Directory of Open Access Journals (Sweden)

    Giulia Freer

    2009-07-01

    Full Text Available Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.

  10. Dendritic cell immunotherapy in uterine cancer.

    Science.gov (United States)

    Coosemans, An; Tuyaerts, Sandra; Vanderstraeten, Anke; Vergote, Ignace; Amant, Frédéric; Van Gool, Stefaan W

    2014-01-01

    Uterine cancer is the most common pelvic gynecological malignancy. Uterine sarcomas and relapsed uterine carcinomas have limited treatment options. The search for new therapies is urgent. Dendritic cell (DC) immunotherapy holds much promise, though has been poorly explored in uterine cancer. This commentary gives an insight in existing DC immunotherapy studies in uterine cancer and summarizes the possibilities and the importance of the loading of tumor antigens onto DC and their subsequent maturation. However, the sole application of DC immunotherapy to target uterine cancer will be insufficient because of tumor-induced immunosuppression, which will hamper the establishment of an effective anti-tumor immune response. The authors give an overview on the limited existing immunosuppressive data and propose a novel approach on DC immunotherapy in uterine cancer.

  11. Communications: Mechanical Deformation of Dendrites by Fluid Flow

    Science.gov (United States)

    Pilling, J.; Hellawell, A.

    1996-01-01

    It is generally accepted that liquid agitation during alloy solidification assists in crystal multiplication, as in dendrite fragmentation and the detachment of side arms in the mushy region of a casting. Even without deliberate stirring by electromagnetic or mechanical means, there is often vigorous interdendritic fluid flow promoted by natural thermosolutal convection. In this analysis, we shall estimate the stress at the root of a secondary dendrite arm of aluminum arising from the action of a flow of molten metal past the dendrite arm.

  12. Dendritic Growth of Hard-Sphere Crystals. Experiment 34

    Science.gov (United States)

    Russel, W. B.; Chaikin, P. M.; Zhu, Ji-Xiang; Meyer, W. V.; Rogers, R.

    1998-01-01

    Recent observations of the disorder-order transition for colloidal hard spheres under microgravity revealed dendritic crystallites roughly 1-2 mm in size for samples in the coexistence region of the phase diagram. Order-of-magnitude estimates rationalize the absence of large or dendritic crystals under normal gravity and their stability to annealing in microgravity. A linear stability analysis of the Ackerson and Schaetzel model for crystallization of hard spheres establishes the domain of instability for diffusion-limited growth at small supersaturations. The relationship between hard-sphere and molecular crystal growth is established and exploited to relate the predicted linear instability to the well-developed dendrites observed.

  13. Antibacterial activities of dendritic amphiphiles against nontuberculous mycobacteria.

    Science.gov (United States)

    Falkinham, Joseph O; Macri, Richard V; Maisuria, Bhadreshkumar B; Actis, Marcelo L; Sugandhi, Eko W; Williams, André A; Snyder, Alyson V; Jackson, Faunice R; Poppe, Michael A; Chen, Liang; Ganesh, Krithika; Gandour, Richard D

    2012-03-01

    The anti-mycobacterial activities of nine series of dicarboxyl and tricarboxyl dendritic amphiphiles with one alkyl, two alkyl, and cholestanyl tails against Mycobacterium abscessus, Mycobacterium avium, Mycobacterium chelonae, Mycobacterium marinum and Mycobacterium smegmatis have been measured. The dendritic amphiphiles overcame the limited aqueous solubility of natural long-chain fatty acids, alcohols, and amines to enable profiling the susceptibilities of the different mycobacterial species to the physicochemical properties of these amphiphiles. Several dendritic amphiphiles showed strong anti-mycobacterial activity with high critical micelle concentrations and low hemolytic activities thereby offering platforms for the development of antibiotics of higher activity against nontuberculous mycobacteria. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...... transcriptase polymerase chain reaction. The effect of glucocorticoid and phorbol ester stimulation on monocyte and dendritic cell CD163 and CD91 expression was investigated in cell culture of mononuclear cells using multicolor flow cytometry. We identified two CD163+ subsets in human blood with dendritic cell...

  15. Experimental Compaction in a Growing Dendritic Zone

    Science.gov (United States)

    Deguen, R.; Alboussière, T.; Brito, D.; La Rizza, P.; Masson, J.

    2007-12-01

    The Earth inner core is thought to be in a state of dynamical equilibrium between dendritic solidification and compaction of the resulting solid-liquid region (or 'mushy zone') (Sumita et al.,1996). One important question is how much liquid can be trapped in the inner core, or how efficient is compaction to squeeze out the liquid phase. While this can be estimated theoretically in the case of non-reacting liquid and solid phases, this problem is somewhat more complicated in the case of a crystallizing mushy zone, as it involves a continuous mass transfer between the two phases as the system evolves. Consequences on the evolution of the connectivity of the melt as solidification proceed are difficult to assess, making the dependence of the permeability on porosity difficult to predict theoretically, particularly when the liquid fraction becomes small. Other open questions includes how does compaction and convection compete in the mushy zone? What are the effects of compaction on the thickness of the convecting zone? on the interdendritic spacing? on the structure and dimensions of chimneys? We present here preliminary results of an experiment devoted to the study of compaction during the dendritic crystallization of a model material. In our experimental set-up, compaction is promoted by a high apparent gravity, which is imposed by putting the crystallizing sample in a standard lab centrifuge, where the centrifuge acceleration can reach a few thousand g. While solidification proceed, the sample is scanned in situ with ultrasounds, allowing us to follow the propagation of the solidification front and to investigate the variations of ultrasound velocity and attenuation in the liquid, mush and solid domains.

  16. A novel role of dendritic gap junction and mechanisms underlying its interaction with thalamocortical conductance in fast spiking inhibitory neurons

    Directory of Open Access Journals (Sweden)

    Sun Qian-Quan

    2009-10-01

    Full Text Available Abstract Background Little is known about the roles of dendritic gap junctions (GJs of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms. Results Under physiological conditions, excitatory post-junctional potentials (EPJPs interact with thalamocortical (TC inputs within an unprecedented few milliseconds (i.e. over 200 Hz to enhance the firing probability and synchrony of coupled fast-spiking (FS cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: 1 rapid capacitive current (Icap underlies the activation of voltage-gated sodium channels; 2 there was less than 2 milliseconds in which the Icap underlying TC input and EPJP was coupled effectively; 3 cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; 4 synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy. Conclusion Dendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz. Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances.

  17. Excited cooper pairs

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Arrietea, M. G.; Solis, M. A.; De Llano, M. [Universidad Nacional Autonoma de Mexico, Mexico, D.F (Mexico)

    2001-02-01

    Excited cooper pairs formed in a many-fermion system are those with nonzero total center-of mass momentum (CMM). They are normally neglected in the standard Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity for being too few compared with zero CMM pairs. However, a Bose-Einstein condensation picture requires both zero and nonzero CMM pairs. Assuming a BCS model interaction between fermions we determine the populations for all CMM values of Cooper pairs by actually calculating the number of nonzero-CMM pairs relative to that of zero-CMM ones in both 2D and 3D. Although this ratio decreases rapidly with CMM, the number of Cooper pairs for any specific CMM less than the maximum (or breakup of the pair) momentum turns out to be typically larger than about 95% of those with zero-CMM at zero temperature T. Even at T {approx}100 K this fraction en 2D is still as large as about 70% for typical quasi-2D cuprate superconductor parameters. [Spanish] Los pares de cooper excitados formados en un sistema de muchos electrones, son aquellos con momentos de centro de masa (CMM) diferente de cero. Normalmente estos no son tomados en cuenta en la teoria estandar de la superconductividad de Bardeen-Cooper-Schrieffer (BCS) al suponer que su numero es muy pequeno comparados con los pares de centro de masa igual a cero. Sin embargo, un esquema de condensacion Bose-Einstein requiere de ambos pares, con CMM cero y diferente de cero. Asumiendo una interaccion modelo BCS entre los fermiones, determinamos la poblacion de pares cooper con cada uno de todos los posibles valores del CMM calculando el numero de pares con momentos de centro de masa diferente de cero relativo a los pares de CMM igual a cero, en 2D y 3D. Aunque esta razon decrece rapidamente con el CMM, el numero de pares de cooper para cualquier CMM especifico menor que el momento maximo (o rompimiento de par) es tipicamente mas grande que el 95% de aquellos con CMM cero. Aun a T {approx}100 K esta fraccion en 2D es

  18. Uniform excitations in magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Steen Mørup

    2010-11-01

    Full Text Available We present a short review of the magnetic excitations in nanoparticles below the superparamagnetic blocking temperature. In this temperature regime, the magnetic dynamics in nanoparticles is dominated by uniform excitations, and this leads to a linear temperature dependence of the magnetization and the magnetic hyperfine field, in contrast to the Bloch T3/2 law in bulk materials. The temperature dependence of the average magnetization is conveniently studied by Mössbauer spectroscopy. The energy of the uniform excitations of magnetic nanoparticles can be studied by inelastic neutron scattering.

  19. Uniform excitations in magnetic nanoparticles

    DEFF Research Database (Denmark)

    Mørup, Steen; Frandsen, Cathrine; Hansen, Mikkel Fougt

    2010-01-01

    We present a short review of the magnetic excitations in nanoparticles below the superparamagnetic blocking temperature. In this temperature regime, the magnetic dynamics in nanoparticles is dominated by uniform excitations, and this leads to a linear temperature dependence of the magnetization...... and the magnetic hyperfine field, in contrast to the Bloch T3/2 law in bulk materials. The temperature dependence of the average magnetization is conveniently studied by Mössbauer spectroscopy. The energy of the uniform excitations of magnetic nanoparticles can be studied by inelastic neutron scattering....

  20. Emission of radiation by a resonance medium excited with a variable superluminal velocity

    Science.gov (United States)

    Arkhipov, R. M.; Pakhomov, A. V.

    2017-05-01

    Specific properties of the radiation emitted by a spatially modulated resonance medium excited by an ultrashort light pulse propagating through the medium at a variable superluminal velocity are analyzed. In so doing, frequencies different from that of the resonance transition of the medium may appear in the emission spectrum. It is demonstrated that, in contrast to an earlier studied case of medium excitation at constant velocity, variation of the excitation velocity leads to generation of a spectral continuum, the boundaries of which are determined by the range of variation of the medium-excitation velocity.

  1. Three-dimensional synaptic analyses of mitral cell and external tufted cell dendrites in rat olfactory bulb glomeruli.

    Science.gov (United States)

    Bourne, Jennifer N; Schoppa, Nathan E

    2017-02-15

    Recent studies have suggested that the two excitatory cell classes of the mammalian olfactory bulb, the mitral cells (MCs) and tufted cells (TCs), differ markedly in physiological responses. For example, TCs are more sensitive and broadly tuned to odors than MCs and also are much more sensitive to stimulation of olfactory sensory neurons (OSNs) in bulb slices. To examine the morphological bases for these differences, we performed quantitative ultrastructural analyses of glomeruli in rat olfactory bulb under conditions in which specific cells were labeled with biocytin and 3,3'-diaminobenzidine. Comparisons were made between MCs and external TCs (eTCs), which are a TC subtype in the glomerular layer with large, direct OSN signals and capable of mediating feedforward excitation of MCs. Three-dimensional analysis of labeled apical dendrites under an electron microscope revealed that MCs and eTCs in fact have similar densities of several chemical synapse types, including OSN inputs. OSN synapses also were distributed similarly, favoring a distal localization on both cells. Analysis of unlabeled putative MC dendrites further revealed gap junctions distributed uniformly along the apical dendrite and, on average, proximally with respect to OSN synapses. Our results suggest that the greater sensitivity of eTCs vs. MCs is due not to OSN synapse number or absolute location but rather to a conductance in the MC dendrite that is well positioned to attenuate excitatory signals passing to the cell soma. Functionally, such a mechanism could allow rapid and dynamic control of OSN-driven action potential firing in MCs through changes in gap junction properties. J. Comp. Neurol. 525:592-609, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Comparison of dendritic calcium transients in juvenile wild type and SOD1G93A mouse lumbar motoneurons

    Directory of Open Access Journals (Sweden)

    Katharina Ann Quinlan

    2015-04-01

    Full Text Available Previous studies of spinal motoneurons in the SOD1 mouse model of amyotrophic lateral sclerosis have shown alterations long before disease onset, including increased dendritic branching, increased persistent Na+ and Ca2+ currents, and impaired axonal transport. In this study dendritic Ca2+ entry was investigated using 2 photon excitation fluorescence microscopy and whole-cell patch-clamp of juvenile (P4-11 motoneurons. Neurons were filled with both Ca2+ Green-1 and Texas Red dextrans, and line scans performed throughout. Steps were taken to account for different sources of variability, including 1 dye filling and laser penetration, 2 dendritic anatomy, and 3 the time elapsed from the start of recording. First, Ca2+ Green-1 fluorescence was normalized by Texas Red; next, neurons were reconstructed so anatomy could be evaluated; finally, time was recorded. Customized software detected the largest Ca2+ transients (area under the curve from each line scan and matched it with parameters above. Overall, larger dendritic diameter and shorter path distance from the soma were significant predictors of larger transients, while time was not significant up to 2 hours (data thereafter was dropped. However, Ca2+ transients showed additional variability. Controlling for previous factors, significant variation was found between Ca2+ signals from different processes of the same neuron in 3/7 neurons. This could reflect differential expression of Ca2+ channels, local neuromodulation or other variations. Finally, Ca2+ transients in SOD1G93A motoneurons were significantly smaller than in non-transgenic motoneurons. In conclusion, motoneuron processes show highly variable Ca2+ transients, but these transients are smaller overall SOD1G93A motoneurons.

  3. Characterization of porcine dendritic cell response to Streptococcus suis

    Directory of Open Access Journals (Sweden)

    Lecours Marie-Pier

    2011-06-01

    Full Text Available Abstract Streptococcus suis is a major swine pathogen and important zoonotic agent causing mainly septicemia and meningitis. However, the mechanisms involved in host innate and adaptive immune responses toward S. suis as well as the mechanisms used by S. suis to subvert these responses are unknown. Here, and for the first time, the ability of S. suis to interact with bone marrow-derived swine dendritic cells (DCs was evaluated. In addition, the role of S. suis capsular polysaccharide in modulation of DC functions was also assessed. Well encapsulated S. suis was relatively resistant to phagocytosis, but it increased the relative expression of Toll-like receptors 2 and 6 and triggered the release of several cytokines by DCs, including IL-1β, IL-6, IL-8, IL-12p40 and TNF-α. The capsular polysaccharide was shown to interfere with DC phagocytosis; however, once internalized, S. suis was readily destroyed by DCs independently of the presence of the capsular polysaccharide. Cell wall components were mainly responsible for DC activation, since the capsular polysaccharide-negative mutant induced higher cytokine levels than the wild-type strain. The capsular polysaccharide also interfered with the expression of the co-stimulatory molecules CD80/86 and MHC-II on DCs. To conclude, our results show for the first time that S. suis interacts with swine origin DCs and suggest that these cells might play a role in the development of host innate and adaptive immunity during an infection with S. suis serotype 2.

  4. Enhanced immunological response by dendritic cells in male hypogonadism.

    Science.gov (United States)

    Corrales, Juan J; Almeida, María; Cordero, Mar; Martín-Martín, Lourdes; Méndez, Cristina; Miralles, José M; Orfao, Alberto

    2012-11-01

    The effect of male hypogonadism on the immune response is poorly understood, even though testosterone has both immunosuppressive and anti-inflammatory effects in men. In this study, we compared the distribution and functional status of peripheral blood (PB) monocytes, dendritic cells (DCs) [CD16(+) (monocytoid), CD33(+) (myeloid) and CD33(-) (plasmacytoid)] and CD4(+) CD25(+)CD127(-/lo) regulatory T cells from hypogonadic men and control subjects. Immunophenotypic studies were performed both on resting and in vitro-stimulated cells. Overall, no significant differences were detected on the number of monocytes, DCs and CD4(+) CD25(+) CD127(-/lo) regulatory T cells between both groups of subjects. However, hypogonadic men showed slightly higher numbers of circulating CD16(+) cells expressing the CD107b activation/degranulation-associated marker than controls, such differences reaching statistical significance after in vitro stimulation with CpG oligodeoxynucleotides. Interestingly, antigen-stimulated expression of CD107b on CD16(+) cells inversely correlated with the serum concentrations of total testosterone (r(2)=-0.45; P=0.01), free testosterone (r(2)=-0.48; P=0.005), calculated free testosterone (r(2)=-0.44; P=0.01) and bioavailable testosterone (r(2)=-0.46; P=0.008) among all cases studied, as well as with both the LH (r(2)=-0.53, P=0.04) and FSH (r(2)=-0.54, P=0.04) serum levels among hypogonadic men. These findings show an enhanced immunological response of circulating (activated) CD16(+) DCs to antigen stimulation, which was inversely related to testosterone and gonadotropin serum levels. Such findings suggest a modulation by the hypothalamic-hypophyseal-gonadal axis of the immune response and may have clinical implications for hypogonadic men, as regards susceptibility to autoimmune diseases and increased responses to antigenic stimuli. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical

  5. High-resolution in vivo imaging of regenerating dendrites of Drosophila sensory neurons during metamorphosis: local filopodial degeneration and heterotypic dendrite-dendrite contacts.

    Science.gov (United States)

    Satoh, Daisuke; Suyama, Ritsuko; Kimura, Ken-ichi; Uemura, Tadashi

    2012-12-01

    Neuronal circuits that are formed in early development are reorganized at later developmental stages to support a wide range of adult behaviors. At Drosophila pupal stages, one example of this reorganization is dendritic remodeling of multidendritic neurons, which is accomplished by pruning and subsequent regeneration of branches in environments quite distinct from those in larval life. Here, we used long-term in vivo time-lapse recordings at high spatiotemporal resolution and analyzed the dynamics of two adjacent cell types that remodel dendritic arbors, which eventually innervate the lateral plate of the adult abdomen. These neurons initially exhibited dynamic extension, withdrawal and local degeneration of filopodia that sprouted from all along the length of regenerating branches. At a midpupal stage, branches extending from the two cell types started fasciculating with each other, which prompted us to test the hypothesis that this heterotypic contact may serve as a guiding scaffold for shaping dendritic arbors. Unexpectedly, our cell ablation study gave only marginal effects on the branch length and the arbor shape. This result suggests that the arbor morphology of the adult neurons in this study can be specified mostly in the absence of the dendrite-dendrite contact. © 2012 The Authors Genes to Cells © 2012 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  6. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Wen Jing Sim

    2016-01-01

    Full Text Available Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

  7. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

    National Research Council Canada - National Science Library

    Mule, James

    1998-01-01

    The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene-modified fibroblasts with breast tumor-pulsed dendritic cells (DC...

  8. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

    National Research Council Canada - National Science Library

    Mule, James

    1997-01-01

    The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene modified fibroblasts with breast tumor pulsed dendritic cells (DC...

  9. Molecule Matters-Dendritic Architecture-A Clever Route to ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 1. Molecule Matters - Dendritic Architecture - A Clever Route to Monodispersed Macromolecules. N Jayaraman. Feature Article Volume 12 Issue 1 January 2007 pp 60-66 ...

  10. Use and abuse of dendritic cells by Toxoplasma gondii

    Science.gov (United States)

    Sanecka, Anna; Frickel, Eva-Maria

    2012-01-01

    The ubiquitous apicomplexan parasite Toxoplasma gondii stimulates its host’s immune response to achieve quiescent chronic infection. Central to this goal are host dendritic cells. The parasite exploits dendritic cells to disseminate through the body, produce pro-inflammatory cytokines, present its antigens to the immune system and yet at the same time subvert their signaling pathways in order to evade detection. This carefully struck balance by Toxoplasma makes it the most successful parasite on this planet. Recent progress has highlighted specific parasite and host molecules that mediate some of these processes particularly in dendritic cells and in other cells of the innate immune system. Critically, there are several important factors that need to be taken into consideration when concluding how the dendritic cells and the immune system deal with a Toxoplasma infection, including the route of administration, parasite strain and host genotype. PMID:23221473

  11. Simulation of dendritic growth of magnesium alloys with fluid flow

    Directory of Open Access Journals (Sweden)

    Meng-wu Wu

    2017-11-01

    Full Text Available Fluid flow has a significant impact on the microstructure evolution of alloys during solidification. Based on the previous work relating simulation of the dendritic growth of magnesium alloys with hcp (hexagonal close-packed structure, an extension was made to the formerly established CA (cellular automaton model with the purpose of studying the effect of fluid flow on the dendritic growth of magnesium alloys. The modified projection method was used to solve the transport equations of flow field. By coupling the flow field with the solute field, simulation results of equiaxed and columnar dendritic growth of magnesium alloys with fluid flow were achieved. The simulated results were quantitatively compared with those without fluid flow. Moreover, a comparison was also made between the present work and previous works conducted by others. It can be concluded that a deep understanding of the dendritic growth of magnesium alloys with fluid flow can be obtained by applying the present numerical model.

  12. Actin Remodeling and Polymerization Forces Control Dendritic Spine Morphology

    CERN Document Server

    Miermans, Karsten; Storm, Cornelis; Hoogenraad, Casper

    2015-01-01

    Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. This striking progression is coincident with the (re)configuration of the neuronal network during early development, learning and memory formation, and has been conjectured to be part of the machinery that encodes these processes at the scale of individual neuronal connections. It is well established that the structural plasticity of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present...

  13. Indirect excitation of ultrafast demagnetization

    National Research Council Canada - National Science Library

    Vodungbo, B; Tudu, B; Perron, J; Delaunay, R; Müller, L; Berntsen, M.H; Grübel, G; Malinowski, G; Weier, C; Gautier, J; Lambert, G; Zeitoun, P; Gutt, C; Jal, E; Reid, A.H; Granitzka, P.W; Jaouen, N; Dakovski, G.L; Moeller, S; Minitti, M.P; Mitra, A; Carron, S; Pfau, B; von Korff Schmising, C; Schneider, M; Eisebitt, S; Lüning, J

    2016-01-01

    .... Upon excitation with an intense femtosecond-short IR laser pulse, the film exhibits the classical ultrafast demagnetization phenomenon although only a negligible number of IR photons penetrate the aluminum layer...

  14. Transport waves as crystal excitations

    Science.gov (United States)

    Cepellotti, Andrea; Marzari, Nicola

    2017-09-01

    We introduce the concept of transport waves by showing that the linearized Boltzmann transport equation admits excitations in the form of waves that have well-defined dispersion relations and decay times. Crucially, these waves do not represent single-particle excitations, but are collective excitations of the equilibrium distribution functions. We study in detail the case of thermal transport, where relaxons are found in the long-wavelength limit, and second sound is reinterpreted as the excitation of one or several temperature waves at finite frequencies. Graphene is studied numerically, finding decay times of the order of microseconds. The derivation, obtained by a spectral representation of the Boltzmann equation, holds in principle for any crystal or semiclassical transport theory and is particularly relevant when transport takes place in the hydrodynamic regime.

  15. Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan fluorescence.

    Science.gov (United States)

    Koenig, S; Müller, L; Smith, D K

    2001-03-02

    Two series of dendritically modified tryptophan derivatives have been synthesised and their emission spectra measured in a range of different solvents. This paper presents the syntheses of these novel dendritic structures and discusses their emission spectra in terms of both solvent and dendritic effects. In the first series of dendrimers, the NH group of the indole ring is available for hydrogen bonding, whilst in the second series, the indole NH group has been converted to NMe. Direct comparison of the emission wavelengths of analogous NH and NMe derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter, which reflects the ability of the solvent to accept a hydrogen bond from the NH group, an effect not possible for the NMe series of dendrimers. For the NH dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads to a red shift in emission wavelength. This dendritic effect only operates in non-hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a dendritic shell has no effect on the emission spectra of the indole ring. This proves the importance of hydrogen bonding between the branched shell and the indole NH group in causing the dendritic effect. This is the first time a dendritic effect has been unambiguously assigned to individual hydrogen-bonding interactions and indicates that such intramolecular interactions are important in dendrimers, just as they are in proteins. Furthermore, this paper sheds light on the use of tryptophan residues as a probe of the microenvironment within proteins--in particular, it stresses the importance of hydrogen bonds formed by the indole NH group.

  16. Numerical Simulation of Three-Dimensional Dendritic Growth

    Energy Technology Data Exchange (ETDEWEB)

    Karma, A.; Rappel, W. [Department of Physics and Center for Interdisciplinary Research on Complex Systems, Northeastern University, Boston, Massachusetts 02115 (United States)

    1996-11-01

    Dendritic crystal growth in a pure undercooled melt is simulated quantitatively in three dimensions using a phase-field approach. The classic parameter {sigma}{sup *} that characterizes the dynamically selected operating state of the dendrite tip as well as the full nonaxisymmetric tip morphology are determined as a function of anisotropy for a crystal with a cubic symmetry. Results are compared to experiment and used to critically test solvability theory. {copyright} {ital 1996 The American Physical Society.}

  17. The dendritic spine story: an intriguing process of discovery

    OpenAIRE

    Javier eDeFelipe

    2015-01-01

    Dendritic spines are key components of a variety of microcircuits and they represent the majority of postsynaptic targets of glutamatergic axon terminals in the brain. The present article will focus on the discovery of dendritic spines, which was possible thanks to the application of the Golgi technique to the study of the nervous system, and will also explore the early interpretation of these elements. This discovery represents an interesting chapter in the history of neuroscience as it show...

  18. The dendritic cell niche in chronic obstructive pulmonary disease

    OpenAIRE

    Haczku, Angela

    2012-01-01

    Abstract The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathog...

  19. Indirect excitation of ultrafast demagnetization

    OpenAIRE

    Boris Vodungbo; Bahrati Tudu; Jonathan Perron; Renaud Delaunay; Leonard Müller; Berntsen, Magnus H.; Gerhard Grübel; Grégory Malinowski; Christian Weier; Julien Gautier; Guillaume Lambert; Philippe Zeitoun; Christian Gutt; Emmanuelle Jal; Reid, Alexander H.

    2016-01-01

    Does the excitation of ultrafast magnetization require direct interaction between the photons of the optical pump pulse and the magnetic layer? Here, we demonstrate unambiguously that this is not the case. For this we have studied the magnetization dynamics of a ferromagnetic cobalt/palladium multilayer capped by an IR-opaque aluminum layer. Upon excitation with an intense femtosecond-short IR laser pulse, the film exhibits the classical ultrafast demagnetization phenomenon although only a ne...

  20. Stochastic Hierarchical Systems: Excitable Dynamics

    OpenAIRE

    Leonhardt, Helmar; Zaks, Michael A.; Falcke, Martin; Schimansky-Geier, Lutz

    2008-01-01

    We present a discrete model of stochastic excitability by a low-dimensional set of delayed integral equations governing the probability in the rest state, the excited state, and the refractory state. The process is a random walk with discrete states and nonexponential waiting time distributions, which lead to the incorporation of memory kernels in the integral equations. We extend the equations of a single unit to the system of equations for an ensemble of globally coupled oscillators, derive...

  1. Autowaves in moving excitable media

    Directory of Open Access Journals (Sweden)

    V.A.Davydov

    2004-01-01

    Full Text Available Within the framework of kinematic theory of autowaves we suggest a method for analytic description of stationary autowave structures appearing at the boundary between the moving and fixed excitable media. The front breakdown phenomenon is predicted for such structures. Autowave refraction and, particulary, one-side "total reflection" at the boundary is considered. The obtained analytical results are confirmed by computer simulations. Prospects of the proposed method for further studies of autowave dynamics in the moving excitable media are discussed.

  2. Have Gluonic Excitations Been Found?

    OpenAIRE

    Page, Philip R.

    1996-01-01

    New experimental information on the non-exotic J^PC = 0^-+ isovector seen at 1.8 GeV by VES yields convincing evidence of its excited gluonic (hybrid) nature when a critical study of alternative quarkonium assignments is made in the context of ^3 P_0 decay by flux-tube breaking. Production of this gluonic excitation via meson exchange is promising, although its two photon production vanishes.

  3. The unfolded protein response is required for dendrite morphogenesis

    Science.gov (United States)

    Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

    2015-01-01

    Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

  4. Electron-excited molecule interactions

    Energy Technology Data Exchange (ETDEWEB)

    Christophorou, L.G. (Oak Ridge National Lab., TN (USA) Tennessee Univ., Knoxville, TN (USA). Dept. of Physics)

    1991-01-01

    In this paper the limited but significant knowledge to date on electron scattering from vibrationally/rotationally excited molecules and electron scattering from and electron impact ionization of electronically excited molecules is briefly summarized and discussed. The profound effects of the internal energy content of a molecule on its electron attachment properties are highlighted focusing in particular on electron attachment to vibrationally/rotationally and to electronically excited molecules. The limited knowledge to date on electron-excited molecule interactions clearly shows that the cross sections for certain electron-molecule collision processes can be very different from those involving ground state molecules. For example, optically enhanced electron attachment studies have shown that electron attachment to electronically excited molecules can occur with cross sections 10{sup 6} to 10{sup 7} times larger compared to ground state molecules. The study of electron-excited molecule interactions offers many experimental and theoretical challenges and opportunities and is both of fundamental and technological significance. 54 refs., 15 figs.

  5. Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

    NARCIS (Netherlands)

    van Gisbergen, Klaas P. J. M.; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2005-01-01

    Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal

  6. Collapsin response mediator protein 5 (CRMP5) induces mitophagy, thereby regulating mitochondrion numbers in dendrites.

    Science.gov (United States)

    Brot, Sébastien; Auger, Carole; Bentata, Rabia; Rogemond, Véronique; Ménigoz, Stéphane; Chounlamountri, Naura; Girard-Egrot, Agnès; Honnorat, Jérôme; Moradi-Améli, Mahnaz

    2014-01-24

    Degradation of damaged mitochondria by mitophagy is an essential process to ensure cell homeostasis. Because neurons, which have a high energy demand, are particularly dependent on the mitochondrial dynamics, mitophagy represents a key mechanism to ensure correct neuronal function. Collapsin response mediator proteins 5 (CRMP5) belongs to a family of cytosolic proteins involved in axon guidance and neurite outgrowth signaling during neural development. CRMP5, which is highly expressed during brain development, plays an important role in the regulation of neuronal polarity by inhibiting dendrite outgrowth at early developmental stages. Here, we demonstrated that CRMP5 was present in vivo in brain mitochondria and is targeted to the inner mitochondrial membrane. The mitochondrial localization of CRMP5 induced mitophagy. CRMP5 overexpression triggered a drastic change in mitochondrial morphology, increased the number of lysosomes and double membrane vesicles termed autophagosomes, and enhanced the occurrence of microtubule-associated protein 1 light chain 3 (LC3) at the mitochondrial level. Moreover, the lipidated form of LC3, LC3-II, which triggers autophagy by insertion into autophagosomes, enhanced mitophagy initiation. Lysosomal marker translocates at the mitochondrial level, suggesting autophagosome-lysosome fusion, and induced the reduction of mitochondrial content via lysosomal degradation. We show that during early developmental stages the strong expression of endogenous CRMP5, which inhibits dendrite growth, correlated with a decrease of mitochondrial content. In contrast, the knockdown or a decrease of CRMP5 expression at later stages enhanced mitochondrion numbers in cultured neurons, suggesting that CRMP5 modulated these numbers. Our study elucidates a novel regulatory mechanism that utilizes CRMP5-induced mitophagy to orchestrate proper dendrite outgrowth and neuronal function.

  7. Activation-induced cell death of dendritic cells is dependent on sphingosine kinase 1

    Directory of Open Access Journals (Sweden)

    Anja eSchwiebs

    2016-04-01

    Full Text Available Sphingosine 1-phosphate (S1P is an immune modulatory lipid mediator and has been implicated in numerous pathophysiological processes. S1P is produced by sphingosine kinase 1 (Sphk1 and Sphk2. Dendritic cells (DCs are central for the direction of immune responses and crucially involved in autoimmunity and cancerogenesis. In this study we examined the function and survival of bone marrow-derived DCs under long-term inflammatory stimulation. We observed that differentiated cells undergo activation-induced cell death upon LPS stimulation with an increased metabolic activity shortly after stimulation, followed by a rapid activation of caspase 3 and subsequent augmented apoptosis. Importantly, we highlight a profound role of Sphk1 in secretion of inflammatory cytokines and survival of dendritic cells that might be mediated by a change in sphingolipid levels as well as by a change in STAT3 expression. Cell growth during differentiation of Sphk1-deficient cells treated with the functional S1P receptor antagonist FTYP was reduced. Importantly, in dendritic cells we did not observe a compensatory regulation of Sphk2 mRNA in Sphk1-deficient cells. Instead, we discovered a massive increase in Sphk1 mRNA concentration upon long-term stimulation with LPS in wild type cells that might function as an attempt to rescue from inflammation-caused cell death. Taken together, in this investigation we describe details of a crucial involvement of sphingolipids and Sphk1 in activation-induced cell death during long-term immunogenic activity of DCs that might play an important role in autoimmunity and might explain the differences in immune response observed in in vivo studies of Sphk1 modulation.

  8. Activation-Induced Cell Death of Dendritic Cells Is Dependent on Sphingosine Kinase 1.

    Science.gov (United States)

    Schwiebs, Anja; Friesen, Olga; Katzy, Elisabeth; Ferreirós, Nerea; Pfeilschifter, Josef M; Radeke, Heinfried H

    2016-01-01

    Sphingosine 1-phosphate (S1P) is an immune modulatory lipid mediator and has been implicated in numerous pathophysiological processes. S1P is produced by sphingosine kinase 1 (Sphk1) and Sphk2. Dendritic cells (DCs) are central for the direction of immune responses and crucially involved in autoimmunity and cancerogenesis. In this study we examined the function and survival of bone marrow-derived DCs under long-term inflammatory stimulation. We observed that differentiated cells undergo activation-induced cell death (AICD) upon LPS stimulation with an increased metabolic activity shortly after stimulation, followed by a rapid activation of caspase 3 and subsequent augmented apoptosis. Importantly, we highlight a profound role of Sphk1 in secretion of inflammatory cytokines and survival of dendritic cells that might be mediated by a change in sphingolipid levels as well as by a change in STAT3 expression. Cell growth during differentiation of Sphk1-deficient cells treated with the functional S1P receptor antagonist FTYP was reduced. Importantly, in dendritic cells we did not observe a compensatory regulation of Sphk2 mRNA in Sphk1-deficient cells. Instead, we discovered a massive increase in Sphk1 mRNA concentration upon long-term stimulation with LPS in wild type cells that might function as an attempt to rescue from inflammation-caused cell death. Taken together, in this investigation we describe details of a crucial involvement of sphingolipids and Sphk1 in AICD during long-term immunogenic activity of DCs that might play an important role in autoimmunity and might explain the differences in immune response observed in in vivo studies of Sphk1 modulation.

  9. The effects of Candida albicans cell wall protein fraction on dendritic cell maturation.

    Science.gov (United States)

    Roudbary, Maryam; Roudbar Mohammadi, Shahla; Bozorgmehr, Mahmood; Moazzeni, Seyed Mohammad

    2009-06-01

    Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are carbohydrates such as mannans, beta glucans and chitins, and proteins that partially modulate the host immune responses. Dendritic cells (DC), as the most important antigen-presenting cells of the immune system, play a critical role in inducing immune responses against different pathogens. We investigated the effect of the cell wall protein fraction (CPF) of C. albicans on DC maturation. The CPF of C. albicans cells was extracted by a lysis buffer containing sodium dodecyl sulphate, 2-mercaptoethanol and phosphate-buffered saline. The extract was dialyzed and its protein pattern was evaluated by electrophoresis. Dendritic cells were purified from Balb/c mice spleens through a three-step method including mononuclear cell separation, as well as 2-h and overnight cultures. The purified CPF was added at different concentrations to DC. The purity and maturation status of DC were determined by flow cytometry using monoclonal antibodies against CD11c, MHC-II, CD40 and CD86. Treatment of DC with 10 microg/ml of CPF increased the expression of maturation markers including MHC-II, CD86 and CD40 on DC compared to the control group. In this study we used C. albicans CPF with the molecular weight of 40-45 kDa for pulsing and maturation of dendritic cells. Since according to our results CPF significantly increased the expression of maturation markers on DC, we suggest that CPF may act as an efficient immunomodulator, or may be used as a potential adjuvant to boost the host immune system against infections.

  10. BAFF and APRIL from Activin A-Treated Dendritic Cells Upregulate the Antitumor Efficacy of Dendritic Cells In Vivo.

    Science.gov (United States)

    Shurin, Michael R; Ma, Yang; Keskinov, Anton A; Zhao, Ruijing; Lokshin, Anna; Agassandian, Marianna; Shurin, Galina V

    2016-09-01

    The members of the TGFβ superfamily play a key role in regulating developmental and homeostasis programs by controlling differentiation, proliferation, polarization, and survival of different cell types. Although the role of TGFβ1 in inflammation and immunity is well evident, the contribution of other TGFβ family cytokines in the modulation of the antitumor immune response remains less documented. Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI. In vivo, activin A-stimulated DCs demonstrate a significantly increased ability to induce tumor-specific CTLs and inhibit the growth of melanoma and lung carcinoma, which relies on DC-derived BAFF and APRIL, as knockdown of the BAFF and APRIL gene expression in activin A-treated DCs blocks augmentation of their antitumor potential. Although systemic administration of activin A, BAFF, or APRIL for the therapeutic purposes is not likely due to the pluripotent effects on malignant and nonmalignant cells, our data open a novel opportunity for improving the efficacy of DC vaccines. In fact, a significant augmentation of the antitumor activity of DC pretreated with activin A and the proven role of DC-derived BAFF and APRIL in the induction of antitumor immunity in vivo support this direction. Cancer Res; 76(17); 4959-69. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Regulatory multitasking of tolerogenic dendritic cells – lessons taken from Vitamin D3-treated tolerogenic dendritic cells

    Directory of Open Access Journals (Sweden)

    Tatjana eNikolic

    2013-05-01

    Full Text Available Tolerogenic dendritic cells (DCs work through silencing of differentiated antigen-specific T cells, activation and expansion of naturally occurring T regulatory cells (Tregs, transfer of regulatory properties to T cells and the differentiation of naïve T cells into Tregs. Due to an operational definition based on T cell activation assays, the identity of tolerogenic DCs has been a matter of debate and it need not represent a specialized DC subset. Human tolerogenic DCs generated in vitro using inhibitory cytokines, growth factors, natural immunomodulators or genetic manipulation have been effective and several of these tolerogenic DCs are currently being tested for clinical use. Ex vivo generated tolerogenic DCs reduce activation of naïve T cells using various means, promote a variety of regulatory T cells and most importantly, frequently show stable inhibitory phenotypes upon repetitive maturation with inflammatory factors. Yet, tolerogenic DCs differ with respect to the phenotype or the number of regulatory mechanisms they employ to modulate the immune system. In our experience, tolerogenic DCs generated using the biologically active form of vitamin D (VD3-DCs, alone or combined with dexamethasone are proficient in their immunoregulatory functions. These tolerogenic DCs show a stable maturation-resistant semi-mature phenotype with low expression of activating co-stimulatory molecules, no production of the IL-12 family of cytokines and high expression of inhibitory molecules and IL-10. VD3-DCs induce increased apoptosis of effector T cells and induce antigen-specific regulatory T cells, which work through linked suppression ensuring infectious tolerance. Lessons learned on VD3-DCs help understanding the contribution of different pattern recognition receptors (PRRs and secondary signals to the tolerogenic function and how a cross-talk between DCs and T cells translates into immune regulation.

  12. Electromagnons: Electrically active spin excitations in multiferroics

    Science.gov (United States)

    Kamba, Stanislav; Goian, Veronica; Kadlec, Filip; Kadlec, Christelle; Vanek, Premysl; Kempa, Martin; Gich, Marti; Academy of Sciences of the Czech Republic Team; Institut de Ciència de Materials de Barcelona Team

    2014-03-01

    In some multiferroics spin wave can be excited by electric component of elmg. radiation and such excitations activated by dynamic magnetoelectric coupling are called electromagnons. We will discuss mechanism of electromagnon activation in the THz spectra of three different compounds: In the multiferroic TbMnO3, the ferroelectricity is induced by inverse Dzyaloshinskii-Moriya interaction, but two electromagnons are activated by the magnetostriction. Second example is CaMn7O12, whose polarization is the highest among all spin-induced ferroelectrics. In this material we observed three electromagnons, whose frequencies correspond to maxima of magnon density of states, so they should correspond to magnons from Brillouin zone boundary. Finally we will demonstrate that electromagnons are not limited to spin-induced ferroelectrics. We have observed an electromagnon in nanograin ceramics of epsilon-Fe2O3. This material is below 490 K a pyroelectric ferrimagnet and the electromagnon activates in the THz spectra only below 110 K, when the magnetic structure becomes incommensurately modulated. We will show how by combining infrared, THz and inelastic neutron scattering experiments, the electromagnons can be discerned from magnons or phonons. Performed all measurements.

  13. Classical Dynamics of Excitations of Bose Condensates in Anisotropic Traps

    Science.gov (United States)

    Graham, Robert

    This lecture discusses some aspects of the dynamics of the collective and single-particle excitations at zero temperature of Bose-Einstein condensates of alkali-vapors in magnetic traps. We shall discuss those aspects which can be understood by taking the short-wavelength or 'eikonal' limit of the excitations. Trapped Bose-Einstein condensates can be excited experimentally either directly via periodic modulations of the trap potential or by scattering light off the condensate. My discussion here will closely follow some theoretical work published in [1-3] that has recently been done in collaboration with Andras Csordas and Peter Szepfalusy at the Research Institute for solid State Physics and Optics in Budapest, Hungary and with Martin Fliesser at the University of Essen, Germany.

  14. Active control of tensegrity structures under random excitation

    Science.gov (United States)

    Ganesh Raja, M.; Narayanan, S.

    2007-06-01

    In this paper we consider vibration control of tensegrity structures under stationary and nonstationary random excitations. These excitations may be representative of many physical loading conditions, such as earthquake, wind, aerodynamic and acoustic excitations. The optimal control theory based on H2 and \\mathrm {H}_{\\infty } controller with full state and limited state feedback is used for the control. The response of the tensegrity structure is represented by the zero lag covariance matrix and the same is obtained by solving the matrix Lyapunov equation. The force generated by the electro-mechanical coupling of the piezoelectric actuator is used in the formulation. A tensegrity structure of class-1 comprising of two modules, with 24 pretension cables and six struts with piezoelectric actuators, is considered.

  15. Probiotics, dendritic cells and bladder cancer.

    Science.gov (United States)

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  16. Measuring modulated luminescence using non-modulated stimulation: Ramping the sample period

    DEFF Research Database (Denmark)

    Poolton, N.R.J.; Bøtter-Jensen, L.; Andersen, C.E.

    2003-01-01

    Conventional methods of recording linearly modulated (LM) optically stimulated luminescence (OSL) require control over either the exciting light intensity, or the ability to pulse the source. For many light sources (e.g. constant-power CW lasers, arc lamps and synchrotrons) this can be problematic....... Directly analogous results to LM-OSL can, however, be achieved with non-modulated excitation sources, by ramping the sample period (RSP) of luminescence detection. RSP-OSL has the distinct advantage over LM-OSL in that, since the excitation remains at full power, data accumulation times (that can...

  17. A Novel Single-Excitation Capacitive Angular Position Sensor Design

    Science.gov (United States)

    Hou, Bo; Zhou, Bin; Song, Mingliang; Lin, Zhihui; Zhang, Rong

    2016-01-01

    This paper presents a high-precision capacitive angular position sensor (CAPS). The CAPS is designed to be excited by a single voltage to eliminate the matching errors of multi-excitations, and it is mainly composed of excitation electrodes, coupling electrodes, petal-form sensitive electrodes and a set of collection electrodes. A sinusoidal voltage is applied on the excitation electrodes, then the voltage couples to the coupling electrodes and sensitive electrodes without contact. The sensitive electrodes together with the set of collection electrodes encode the angular position to amplitude-modulated signals, and in order to increase the scale factor, the sensitive electrodes are patterned in the shape of petal-form sinusoidal circles. By utilizing a resolver demodulation method, the amplitude-modulated signals are digitally decoded to get the angular position. A prototype of the CAPS is fabricated and tested. The measurement results show that the accuracy of the sensor is 0.0036°, the resolution is 0.0009° and the nonlinearity over the full range is 0.008° (after compensation), indicating that the CAPS has great potential to be applied in high-precision applications with a low cost. PMID:27483278

  18. Stochastic hybrid model of spontaneous dendritic NMDA spikes.

    Science.gov (United States)

    Bressloff, Paul C; Newby, Jay M

    2014-02-01

    Following recent advances in imaging techniques and methods of dendritic stimulation, active voltage spikes have been observed in thin dendritic branches of excitatory pyramidal neurons, where the majority of synapses occur. The generation of these dendritic spikes involves both Na(+) ion channels and M-methyl-D-aspartate receptor (NMDAR) channels. During strong stimulation of a thin dendrite, the resulting high levels of glutamate, the main excitatory neurotransmitter in the central nervous system and an NMDA agonist, modify the current-voltage (I-V) characteristics of an NMDAR so that it behaves like a voltage-gated Na(+) channel. Hence, the NMDARs can fire a regenerative dendritic spike, just as Na(+) channels support the initiation of an action potential following membrane depolarization. However, the duration of the dendritic spike is of the order 100 ms rather than 1 ms, since it involves slow unbinding of glutamate from NMDARs rather than activation of hyperpolarizing K(+) channels. It has been suggested that dendritic NMDA spikes may play an important role in dendritic computations and provide a cellular substrate for short-term memory. In this paper, we consider a stochastic, conductance-based model of dendritic NMDA spikes, in which the noise originates from the stochastic opening and closing of a finite number of Na(+) and NMDA receptor ion channels. The resulting model takes the form of a stochastic hybrid system, in which membrane voltage evolves according to a piecewise deterministic dynamics that is coupled to a jump Markov process describing the opening and closing of the ion channels. We formulate the noise-induced initiation and termination of a dendritic spike in terms of a first-passage time problem, under the assumption that glutamate unbinding is negligible, which we then solve using a combination of WKB methods and singular perturbation theory. Using a stochastic phase-plane analysis we then extend our analysis to take proper account of the

  19. Synaptic input sequence discrimination on behavioral timescales mediated by reaction-diffusion chemistry in dendrites

    Science.gov (United States)

    Bhalla, Upinder Singh

    2017-01-01

    Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key computational operations, including pattern recognition, event prediction, and plasticity, involve neural discrimination of spatio-temporal sequences. Here, we show that synaptically-driven reaction-diffusion pathways on dendrites can perform sequence discrimination on behaviorally relevant time-scales. We used abstract signaling models to show that selectivity arises when inputs at successive locations are aligned with, and amplified by, propagating chemical waves triggered by previous inputs. We incorporated biological detail using sequential synaptic input onto spines in morphologically, electrically, and chemically detailed pyramidal neuronal models based on rat data. Again, sequences were recognized, and local channel modulation downstream of putative sequence-triggered signaling could elicit changes in neuronal firing. We predict that dendritic sequence-recognition zones occupy 5 to 30 microns and recognize time-intervals of 0.2 to 5 s. We suggest that this mechanism provides highly parallel and selective neural computation in a functionally important time range. DOI: http://dx.doi.org/10.7554/eLife.25827.001 PMID:28422010

  20. Dendritic Cell Interactions with Lymphatic Endothelium

    Science.gov (United States)

    Russo, Erica; Nitschké, Maximilian

    2013-01-01

    Abstract Afferent lymphatic vessels fulfill essential immune functions by transporting leukocytes and lymph-borne antigen to draining lymph nodes (dLNs). An important cell type migrating through lymphatic vessels are dendritic cells (DCs). DCs reside in peripheral tissues like the skin, where they take up antigen and transport it via the lymphatic vascular network to dLNs for subsequent presentation to T cells. As such, DCs play a key role in the induction of adaptive immune responses during infection and vaccination, but also for the maintenance of tolerance. Although the migratory pattern of DCs has been known for long time, interactions between DCs and lymphatic vessels are only now starting to be unraveled at the cellular level. In particular, new tools for visualizing lymphatic vessels in combination with time-lapse microscopy have recently generated valuable insights into the process of DC migration to dLNs. In this review we summarize and discuss current approaches for visualizing DCs and lymphatic vessels in tissues for imaging applications. Furthermore, we review the current state of knowledge about DC migration towards, into and within lymphatic vessels, particularly focusing on the cellular interactions that take place between DCs and the lymphatic endothelium. PMID:24044757

  1. The CD8+ dendritic cell subset.

    Science.gov (United States)

    Shortman, Ken; Heath, William R

    2010-03-01

    Mouse lymphoid tissues contain a subset of dendritic cells (DCs) expressing CD8 alpha together with a pattern of other surface molecules that distinguishes them from other DCs. These molecules include particular Toll-like receptor and C-type lectin pattern recognition receptors. A similar DC subset, although lacking CD8 expression, exists in humans. The mouse CD8(+) DCs are non-migrating resident DCs derived from a precursor, distinct from monocytes, that continuously seeds the lymphoid organs from bone marrow. They differ in several key functions from their CD8(-) DC neighbors. They efficiently cross-present exogenous cell-bound and soluble antigens on major histocompatibility complex class I. On activation, they are major producers of interleukin-12 and stimulate inflammatory responses. In steady state, they have immune regulatory properties and help maintain tolerance to self-tissues. During infection with intracellular pathogens, they become major presenters of pathogen antigens, promoting CD8(+) T-cell responses to the invading pathogens. Targeting vaccine antigens to the CD8(+) DCs has proved an effective way to induce cytotoxic T lymphocytes and antibody responses.

  2. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  3. Adhesion of dendritic cells to endothelia.

    Science.gov (United States)

    Alun Brown, K

    2001-01-01

    Many of the interdigitating dendritic cells (DC) that reside in lymph nodes arise from the migration of tissue interstitial DC such as Langerhans cells in the skin (1). Although this migration appears to be stimulated by cytokines (2), relatively little is known of the mechanisms underlying the maintenance and expansion of DC in the skin. Langerhans cells are bone-marrow derived (3), and their replacement in the epidermis following transportation of antigen to lymphoid tissue is likely to depend upon the tissue extravasation of circulating DC. Moreover, the continuous passage of DC across blood vessel walls could be responsible for the increase in DC numbers in tumors (4) and sites of chronic inflammation (5,6). Thus, germane to both homeostasis and pathological disturbance would be the interaction of circulating DC with blood vessel walls, and their subsequent entry into the surrounding tissue. The first stage in leukocyte migration across blood vessel walls is binding to vascular endothelium, and for lymphocytes, monocytes and neutrophils this event is governed by adhesion molecules on their surface recognizing corresponding endothelial ligands commonly referred to as vascular adhesion molecules (7). Despite the plethora of information concerning the molecular nature of the attachment of the major leukocyte subpopulations to endothelium, relatively few studies have been undertaken with DC. Understanding the controlling features of DC-endo-thelial cell interaction would be relevant to the clinical application of DC in immunodeficient disorders and malignancies (8,9) and to antagonizing their entry into sites of chronic inflammatory lesions.

  4. Brain dendritic cells: biology and pathology.

    Science.gov (United States)

    D'Agostino, Paul M; Gottfried-Blackmore, Andres; Anandasabapathy, Niroshana; Bulloch, Karen

    2012-11-01

    Dendritic cells (DC) are the professional antigen-presenting cells of the immune system. In their quiescent and mature form, the presentation of self-antigens by DC leads to tolerance; whereas, antigen presentation by mature DC, after stimulation by pathogen-associated molecular patterns, leads to the onset of antigen-specific immunity. DC have been found in many of the major organs in mammals (e.g. skin, heart, lungs, intestines and spleen); while the brain has long been considered devoid of DC in the absence of neuroinflammation. Consequently, microglia, the resident immune cell of the brain, have been charged with many functional attributes commonly ascribed to DC. Recent evidence has challenged the notion that DC are either absent or minimal players in brain immune surveillance. This review will discuss the recent literature examining DC involvement within both the young and aged steady-state brain. We will also examine DC contributions during various forms of neuroinflammation resulting from neurodegenerative autoimmune disease, injury, and CNS infections. This review also touches upon DC trafficking between the central nervous system and peripheral immune compartments during viral infections, the new molecular technologies that could be employed to enhance our current understanding of brain DC ontogeny, and some potential therapeutic uses of DC within the CNS.

  5. Dendritic spine changes associated with normal aging.

    Science.gov (United States)

    Dickstein, D L; Weaver, C M; Luebke, J I; Hof, P R

    2013-10-22

    Given the rapid rate of population aging and the increased incidence of cognitive decline and neurodegenerative diseases with advanced age, it is important to ascertain the determinants that result in cognitive impairment. It is also important to note that much of the aged population exhibit 'successful' cognitive aging, in which cognitive impairment is minimal. One main goal of normal aging studies is to distinguish the neural changes that occur in unsuccessful (functionally impaired) subjects from those of successful (functionally unimpaired) subjects. In this review, we present some of the structural adaptations that neurons and spines undergo throughout normal aging and discuss their likely contributions to electrophysiological properties and cognition. Structural changes of neurons and dendritic spines during aging, and the functional consequences of such changes, remain poorly understood. Elucidating the structural and functional synaptic age-related changes that lead to cognitive impairment may lead to the development of drug treatments that can restore or protect neural circuits and mediate cognition and successful aging. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Sodium pump organization in dendritic spines.

    Science.gov (United States)

    Blom, Hans; Bernhem, Kristoffer; Brismar, Hjalmar

    2016-10-01

    Advancement in fluorescence imaging with the invention of several super-resolution microscopy modalities (e.g., PALM/STORM and STED) has opened up the possibility of deciphering molecular distributions on the nanoscale. In our quest to better elucidate postsynaptic protein distribution in dendritic spines, we have applied these nanoscopy methods, where generated results could help improve our understanding of neuronal functions. In particular, we have investigated the principal energy transformer in the brain, i.e., the [Formula: see text]-ATPase (or sodium pump), an essential protein responsible for maintaining resting membrane potential and a major controller of intracellular ion homeostasis. In these investigations, we have focused on estimates of protein amount, giving assessments of how variations may depend on labeling strategies, sample analysis, and choice of nanoscopic imaging method, concluding that all can be critical factors for quantification. We present a comparison of these results and discuss the influences this may have for homeostatic sodium regulation in neurons and energy consumption.

  7. Sadomasochism, sexual excitement, and perversion.

    Science.gov (United States)

    Kernberg, O F

    1991-01-01

    Sadomasochism, an ingredient of infantile sexuality, is an essential part of normal sexual functioning and love relations, and of the very nature of sexual excitement. Sadomasochistic elements are also present in all sexual perversions. Sadomasochism starts out as the potential for erotic masochism in both sexes, and represents a very early capacity to link aggression with the libidinal elements of sexual excitement. Sexual excitement may be considered a basic affect that overcomes primitive splitting of love and hatred. Erotic desire is a more mature form of sexual excitement. Psychoanalytic exploration makes it possible to uncover the unconscious components of sexual excitement: wishes for symbiotic fusion and for aggressive penetration and intermingling; bisexual identifications; the desire to transgress oedipal prohibitions and the secretiveness of the primal scene, and to violate the boundaries of a teasing and withholding object. The relation between these wishes and the development of erotic idealization processes in both sexes is explored in the context of a critical review of the pertinent psychoanalytic literature.

  8. Coulomb excitation of (31)Mg

    CERN Document Server

    Seidlitz, M; Reiter, P; Bildstein, V; Blazhev, A; Bree, N; Bruyneel, B; Cederkall, J; Clement, E; Davinson, T; van Duppen, P; Ekstrom, A; Finke, F; Fraile, L M; Geibel, K; Gernhauser, R; Hess, H; Holler, A; Huyse, M; Ivanov, O; Jolie, J; Kalkuhler, M; Kotthaus, T; Krucken, R; Lutter, R; Piselli, E; Scheit, H; Stefanescu, I; van de Walle, J; Voulot, D; Warr, N; Wenander, F; Wiens, A

    2011-01-01

    The ground state properties of ^3^1Mg indicate a change of nuclear shape at N=19 with a deformed J^@p=1/2^+ intruder state as a ground state, implying that ^3^1Mg is part of the ''island of inversion''. The collective properties of excited states were the subject of a Coulomb excitation experiment at REX-ISOLDE, CERN, employing a radioactive ^3^1Mg beam. De-excitation @c-rays were detected by the MINIBALL @c-spectrometer in coincidence with scattered particles in a segmented Si-detector. The level scheme of ^3^1Mg was extended. Spin and parity assignment of the 945 keV state yielded 5/2^+ and its de-excitation is dominated by a strong collective M1 transition. Comparison of the transition probabilities of ^3^0^,^3^1^,^3^2Mg establishes that for th e N=19 magnesium isotope not only the ground state but also excited states are largely dominated by a deformed pf intruder configuration.

  9. Photochemistry-based immune modulation in the treatment of cutaneous leishmaniasis

    Science.gov (United States)

    Akilov, Oleg E.; Kosaka, Sachiko; Hasan, Tayyaba

    2009-06-01

    The destruction of infectious pathogens by photodynamic therapy (PDT) is an emerging modality. We demonstrated the efficacy of PDT for the management of cutaneous leishmaniasis in our previous studies. However, much remains to be done for the improvement of PDT regimens. The modulation of the immune response by photochemistry is an exciting but under-explored area of PDT research. The goal of this study is to understand the mechanisms of the augmentation of the host immune response after PDT of cutaneous leishmaniasis (CL). We found that PDT with phenoxiazine analogues was capable for induction of Th1 immune response due to stimulation of IL- 12 production by dendritic cells. Single PDT treatment facilitated fast healing of the CL lesions due to effective parasite eradication and augmentation of the immune system. Comparative study with different photosensitizers (PS) (porphyrins, pehnoxiazines) demonstrated different immunomodulating properties of PDT depending on chemical class of PS. Knowing the particular profiles and immunomodulating properties of the pertinent PSs allows us to select the optimal PS with regards to both the photodestructive and immunostimulating potential.

  10. BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Wei Cao

    2007-09-01

    Full Text Available Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs uniquely express blood dendritic cell antigen 2 (BDCA2 protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon RI gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR, which is distinct from the system involved in T cell receptor (TCR signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.

  11. Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons.

    Directory of Open Access Journals (Sweden)

    Sangdeuk Ha

    Full Text Available Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC and agouti-related peptide (AgRP/Neuropeptide Y (NPY/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb. Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM, confocal-laser scanning microscopy (CLSM, and electron microscopy (EM to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb (+/+ mice and in Leprb (db/db mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms.

  12. Photothermal excitation setup for a modified commercial atomic force microscope

    Energy Technology Data Exchange (ETDEWEB)

    Adam, Holger; Rode, Sebastian; Schreiber, Martin; Kühnle, Angelika, E-mail: kuehnle@uni-mainz.de [Institute of Physical Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55099 Mainz (Germany); Kobayashi, Kei; Yamada, Hirofumi [Department of Electronic Science and Engineering, Kyoto University, Katsura, Nishikyo, Kyoto 615-8510 (Japan)

    2014-02-15

    High-resolution imaging in liquids using frequency modulation atomic force microscopy is known to suffer from additional peaks in the resonance spectrum that are unrelated to the cantilever resonance. These unwanted peaks are caused by acoustic modes of the liquid and the setup arising from the indirect oscillation excitation by a piezoelectric transducer. Photothermal excitation has been identified as a suitable method for exciting the cantilever in a direct manner. Here, we present a simple design for implementing photothermal excitation in a modified Multimode scan head from Bruker. Our approach is based on adding a few components only to keep the modifications as simple as possible and to maintain the low noise level of the original setup with a typical deflection noise density of about 15 fm/√(Hz) measured in aqueous solution. The success of the modification is illustrated by a comparison of the resonance spectra obtained with piezoelectric and photothermal excitation. The performance of the systems is demonstrated by presenting high-resolution images on bare calcite in liquid as well as organic adsorbates (Alizarin Red S) on calcite with simultaneous atomic resolution of the underlying calcite substrate.

  13. Higher Order Parametric Excitation Modes for Spaceborne Quadrupole Mass Spectrometers

    Science.gov (United States)

    Gershman, D. J.; Block, B. P.; Rubin, M.; Benna, M.; Mahaffy, P. R.; Zurbuchen, T. H.

    2011-01-01

    This paper describes a technique to significantly improve upon the mass peak shape and mass resolution of spaceborne quadrupole mass spectrometers (QMSs) through higher order auxiliary excitation of the quadrupole field. Using a novel multiresonant tank circuit, additional frequency components can be used to drive modulating voltages on the quadrupole rods in a practical manner, suitable for both improved commercial applications and spaceflight instruments. Auxiliary excitation at frequencies near twice that of the fundamental quadrupole RF frequency provides the advantages of previously studied parametric excitation techniques, but with the added benefit of increased sensed excitation amplitude dynamic range and the ability to operate voltage scan lines through the center of upper stability islands. Using a field programmable gate array, the amplitudes and frequencies of all QMS signals are digitally generated and managed, providing a robust and stable voltage control system. These techniques are experimentally verified through an interface with a commercial Pfeiffer QMG422 quadrupole rod system.When operating through the center of a stability island formed from higher order auxiliary excitation, approximately 50% and 400% improvements in 1% mass resolution and peak stability were measured, respectively, when compared with traditional QMS operation. Although tested with a circular rod system, the presented techniques have the potential to improve the performance of both circular and hyperbolic rod geometry QMS sensors.

  14. Semiconductor Spatial Light Modulators.

    Science.gov (United States)

    1982-06-01

    68 29 Experimental time-expansion of modulated C02 laser beam for three levels of punp energies. CalcJlaten time-aependent solution is super... Gallium -Arsenide sample. Tre photo-excited carriers decay i Ga~s in a shorter distance because of their lower diffusion lengths as co’,nared to InSb...electron populations and producing large changes in te Far3day Dotation of another beam tined to a frequency close to tie absorption line. It has been shown

  15. Efficient primary and parametric resonance excitation of bistable resonators

    KAUST Repository

    Ramini, Abdallah

    2016-09-12

    We experimentally demonstrate an efficient approach to excite primary and parametric (up to the 4th) resonance of Microelectromechanical system MEMS arch resonators with large vibrational amplitudes. A single crystal silicon in-plane arch microbeam is fabricated such that it can be excited axially from one of its ends by a parallel-plate electrode. Its micro/nano scale vibrations are transduced using a high speed camera. Through the parallel-plate electrode, a time varying electrostatic force is applied, which is converted into a time varying axial force that modulates dynamically the stiffness of the arch resonator. Due to the initial curvature of the structure, not only parametric excitation is induced, but also primary resonance. Experimental investigation is conducted comparing the response of the arch near primary resonance using the axial excitation to that of a classical parallel-plate actuation where the arch itself forms an electrode. The results show that the axial excitation can be more efficient and requires less power for primary resonance excitation. Moreover, unlike the classical method where the structure is vulnerable to the dynamic pull-in instability, the axial excitation technique can provide large amplitude motion while protecting the structure from pull-in. In addition to primary resonance, parametrical resonances are demonstrated at twice, one-half, and two-thirds the primary resonance frequency. The ability to actuate primary and/or parametric resonances can serve various applications, such as for resonator based logic and memory devices. (C) 2016 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license

  16. Indirect excitation of ultrafast demagnetization

    Science.gov (United States)

    Vodungbo, Boris; Tudu, Bahrati; Perron, Jonathan; Delaunay, Renaud; Müller, Leonard; Berntsen, Magnus H.; Grübel, Gerhard; Malinowski, Grégory; Weier, Christian; Gautier, Julien; Lambert, Guillaume; Zeitoun, Philippe; Gutt, Christian; Jal, Emmanuelle; Reid, Alexander H.; Granitzka, Patrick W.; Jaouen, Nicolas; Dakovski, Georgi L.; Moeller, Stefan; Minitti, Michael P.; Mitra, Ankush; Carron, Sebastian; Pfau, Bastian; von Korff Schmising, Clemens; Schneider, Michael; Eisebitt, Stefan; Lüning, Jan

    2016-01-01

    Does the excitation of ultrafast magnetization require direct interaction between the photons of the optical pump pulse and the magnetic layer? Here, we demonstrate unambiguously that this is not the case. For this we have studied the magnetization dynamics of a ferromagnetic cobalt/palladium multilayer capped by an IR-opaque aluminum layer. Upon excitation with an intense femtosecond-short IR laser pulse, the film exhibits the classical ultrafast demagnetization phenomenon although only a negligible number of IR photons penetrate the aluminum layer. In comparison with an uncapped cobalt/palladium reference film, the initial demagnetization of the capped film occurs with a delayed onset and at a slower rate. Both observations are qualitatively in line with energy transport from the aluminum layer into the underlying magnetic film by the excited, hot electrons of the aluminum film. Our data thus confirm recent theoretical predictions.

  17. Magnetic excitations in deformed nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Nojarov, R. [Tuebingen Univ. (Germany). Inst. fuer Theoretische Physik

    1995-08-01

    Cross sections for inelastic electron scattering and energy distributions of M1 and E2 strengths of K{sup {pi}} - 1{sup +} excitations in titanium, rare-earth, and actinide nuclei are studied microscopically within QRPA. The spin M1 strength has two peaks, isoscalar and isovector, residing between the low-and high-energy orbital M1 strength. The latter is strongly fragmented and lies in the region of the IVGQR, where the (e,e`) cross sections are almost one order of magnitude larger for E2 than for M1 excitations. Comparison with the quantized isovector rotor allows the interpretation of all the orbital M1 excitations at both low and high energies as manifestation of the collective scissors mode. (author).

  18. Excitation optimization for damage detection

    Energy Technology Data Exchange (ETDEWEB)

    Bement, Matthew T [Los Alamos National Laboratory; Bewley, Thomas R [UCSD

    2009-01-01

    A technique is developed to answer the important question: 'Given limited system response measurements and ever-present physical limits on the level of excitation, what excitation should be provided to a system to make damage most detectable?' Specifically, a method is presented for optimizing excitations that maximize the sensitivity of output measurements to perturbations in damage-related parameters estimated with an extended Kalman filter. This optimization is carried out in a computationally efficient manner using adjoint-based optimization and causes the innovations term in the extended Kalman filter to be larger in the presence of estimation errors, which leads to a better estimate of the damage-related parameters in question. The technique is demonstrated numerically on a nonlinear 2 DOF system, where a significant improvement in the damage-related parameter estimation is observed.

  19. Indirect excitation of ultrafast demagnetization.

    Science.gov (United States)

    Vodungbo, Boris; Tudu, Bharati; Tudu, Bahrati; Perron, Jonathan; Delaunay, Renaud; Müller, Leonard; Berntsen, Magnus H; Grübel, Gerhard; Malinowski, Grégory; Weier, Christian; Gautier, Julien; Lambert, Guillaume; Zeitoun, Philippe; Gutt, Christian; Jal, Emmanuelle; Reid, Alexander H; Granitzka, Patrick W; Jaouen, Nicolas; Dakovski, Georgi L; Moeller, Stefan; Minitti, Michael P; Mitra, Ankush; Carron, Sebastian; Pfau, Bastian; von Korff Schmising, Clemens; Schneider, Michael; Eisebitt, Stefan; Lüning, Jan

    2016-01-06

    Does the excitation of ultrafast magnetization require direct interaction between the photons of the optical pump pulse and the magnetic layer? Here, we demonstrate unambiguously that this is not the case. For this we have studied the magnetization dynamics of a ferromagnetic cobalt/palladium multilayer capped by an IR-opaque aluminum layer. Upon excitation with an intense femtosecond-short IR laser pulse, the film exhibits the classical ultrafast demagnetization phenomenon although only a negligible number of IR photons penetrate the aluminum layer. In comparison with an uncapped cobalt/palladium reference film, the initial demagnetization of the capped film occurs with a delayed onset and at a slower rate. Both observations are qualitatively in line with energy transport from the aluminum layer into the underlying magnetic film by the excited, hot electrons of the aluminum film. Our data thus confirm recent theoretical predictions.

  20. Autoresonant Excitation of Antiproton Plasmas

    CERN Document Server

    Andresen, Gorm B; Baquero-Ruiz, Marcelo; Bertsche, William; Bowe, Paul D; Butler, Eoin; Carpenter, P T; Cesar, Claudio L; Chapman, Steven; Charlton, Michael; Fajans, Joel; Friesen, Tim; Fujiwara, Makoto C; Gill, David R; Hangst, Jeffrey S; Hardy, Walter N; Hayden, Michael E; Humphries, Andrew J; Hurt, J L; Hydomako, Richard; Jonsell, Svante; Madsen, Niels; Menary, Scott; Nolan, Paul; Olchanski, Konstantin; Olin, Art; Povilus, Alexander; Pusa, Petteri; Robicheaux, Francis; Sarid, Eli; Silveira, Daniel M; So, Chukman; Storey, James W; Thompson, Robert I; van der Werf, Dirk P; Wurtele, Jonathan S; Yamazaki, Yasunori

    2011-01-01

    We demonstrate controllable excitation of the center-of-mass longitudinal motion of a thermal antiproton plasma using a swept-frequency autoresonant drive. When the plasma is cold, dense, and highly collective in nature, we observe that the entire system behaves as a single-particle nonlinear oscillator, as predicted by a recent theory. In contrast, only a fraction of the antiprotons in a warm plasma can be similarly excited. Antihydrogen was produced and trapped by using this technique to drive antiprotons into a positron plasma, thereby initiating atomic recombination.

  1. The Drosophila transcription factor Adf-1 (nalyot) regulates dendrite growth by controlling FasII and Staufen expression downstream of CaMKII and neural activity.

    Science.gov (United States)

    Timmerman, Christina; Suppiah, Somu; Gurudatta, Baraka V; Yang, Jingping; Banerjee, Christopher; Sandstrom, David J; Corces, Victor G; Sanyal, Subhabrata

    2013-07-17

    Memory deficits in Drosophila nalyot mutants suggest that the Myb family transcription factor Adf-1 is an important regulator of developmental plasticity in the brain. However, the cellular functions for this transcription factor in neurons or molecular mechanisms by which it regulates plasticity remain unknown. Here, we use in vivo 3D reconstruction of identifiable larval motor neuron dendrites to show that Adf-1 is required cell autonomously for dendritic development and activity-dependent plasticity of motor neurons downstream of CaMKII. Adf-1 inhibition reduces dendrite growth and neuronal excitability, and results in motor deficits and altered transcriptional profiles. Surprisingly, analysis by comparative chromatin immunoprecipitation followed by sequencing (ChIP-Seq) of Adf-1, RNA Polymerase II (Pol II), and histone modifications in Kc cells shows that Adf-1 binding correlates positively with high Pol II-pausing indices and negatively with active chromatin marks such as H3K4me3 and H3K27ac. Consistently, the expression of Adf-1 targets Staufen and Fasciclin II (FasII), identified through larval brain ChIP-Seq for Adf-1, is negatively regulated by Adf-1, and manipulations of these genes predictably modify dendrite growth. Our results imply mechanistic interactions between transcriptional and local translational machinery in neurons as well as conserved neuronal growth mechanisms mediated by cell adhesion molecules, and suggest that CaMKII, Adf-1, FasII, and Staufen influence crucial aspects of dendrite development and plasticity with potential implications for memory formation. Further, our experiments reveal molecular details underlying transcriptional regulation by Adf-1, and indicate active interaction between Adf-1 and epigenetic regulators of gene expression during activity-dependent neuronal plasticity.

  2. In vitro interaction of Stenotrophomonas maltophilia with human monocyte-derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Emanuela eRoscetto

    2015-07-01

    Full Text Available Stenotrophomonas maltophilia is increasingly identified as an opportunistic pathogen in immunocompromised, cancer and cystic fibrosis (CF patients. Knowledge on innate immune responses to S. maltophilia and its potential modulation is poor. The present work investigated the ability of 12 clinical S. maltophilia strains (5 from CF patients, 7 from non-CF patients and one environmental strain to survive inside human monocyte-derived dendritic cells (DCs. The effects of the bacteria on maturation of and cytokine secretion by DCs were also measured. S. maltophilia strains presented a high degree of heterogeneity in internalization and intracellular replication efficiencies as well as in the ability of S. maltophilia to interfere with normal DCs maturation. By contrast, all S. maltophilia strains were able to activate DCs, as measured by increase in the expression of surface maturation markers and proinflammatory cytokines secretion.

  3. Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

    Science.gov (United States)

    Reihl, Alec M.

    2016-01-01

    Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965

  4. Depletion of cutaneous macrophages and dendritic cells promotes growth of basal cell carcinoma in mice.

    Science.gov (United States)

    König, Simone; Nitzki, Frauke; Uhmann, Anja; Dittmann, Kai; Theiss-Suennemann, Jennifer; Herrmann, Markus; Reichardt, Holger M; Schwendener, Reto; Pukrop, Tobias; Schulz-Schaeffer, Walter; Hahn, Heidi

    2014-01-01

    Basal cell carcinoma (BCC) belongs to the group of non-melanoma skin tumors and is the most common tumor in the western world. BCC arises due to mutations in the tumor suppressor gene Patched1 (Ptch). Analysis of the conditional Ptch knockout mouse model for BCC reveals that macrophages and dendritic cells (DC) of the skin play an important role in BCC growth restraining processes. This is based on the observation that a clodronate-liposome mediated depletion of these cells in the tumor-bearing skin results in significant BCC enlargement. The depletion of these cells does not modulate Ki67 or K10 expression, but is accompanied by a decrease in collagen-producing cells in the tumor stroma. Together, the data suggest that cutaneous macrophages and DC in the tumor microenvironment exert an antitumor effect on BCC.

  5. The dendritic cell niche in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Haczku Angela

    2012-09-01

    Full Text Available Abstract The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD. The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung.

  6. Study of the twinned dendrite tip shape II: Experimental assessment

    Energy Technology Data Exchange (ETDEWEB)

    Salgado-Ordorica, M.A., E-mail: mario.salgado@novelis.com [Laboratoire de Simulation des Materiaux LSMX, Ecole Polytechnique Federale de Lausanne, Station 12, 1015 Lausanne (Switzerland); Burdet, P.; Cantoni, M. [Centre Interdisciplinaire de Microscopie Electronique CIME, Ecole Polytechnique Federale de Lausanne, Station 12, 1015 Lausanne (Switzerland); Rappaz, M. [Laboratoire de Simulation des Materiaux LSMX, Ecole Polytechnique Federale de Lausanne, Station 12, 1015 Lausanne (Switzerland)

    2011-08-15

    The favorable growth kinetics of twinned dendrites can be explained by their complex morphology, multiple side branching mechanisms, growth undercooling and tip morphology. Three models were proposed for the twinned dendrite tip shape: (i) a grooved tip satisfying the Smith condition at the triple line; (ii) a doublon , i.e. a double-tip dendrite that grows with a narrow and deep liquid channel in its center; and (iii) a pointed (or edgy) tip, with consideration of the solid-liquid interfacial energy anisotropy. In the first part of this work, phase field simulations of half a twinned dendrite with an appropriate boundary condition to reproduce the Smith condition supported the doublon conjecture, with a narrow liquid channel ending its solidification with the formation of small liquid droplets. In this part, experimental observations of twinned dendrite tips reveal the presence of a small, but well-defined, groove, thus definitely eliminating the edged tip hypothesis. Focused ion beam nanotomography and energy-dispersive spectroscopy chemical analysis in a transmission electron microscope reveal the existence of a positive solute gradient in a region localized within 2 {mu}m around the twin plane. In Al-Zn specimens, small particles aligned within the twin plane further support the doublon conjecture and the predicted formation of small liquid droplets below the doublon root.

  7. Noise tolerant dendritic lattice associative memories

    Science.gov (United States)

    Ritter, Gerhard X.; Schmalz, Mark S.; Hayden, Eric; Tucker, Marc

    2011-09-01

    Linear classifiers based on computation over the real numbers R (e.g., with operations of addition and multiplication) denoted by (R, +, x), have been represented extensively in the literature of pattern recognition. However, a different approach to pattern classification involves the use of addition, maximum, and minimum operations over the reals in the algebra (R, +, maximum, minimum) These pattern classifiers, based on lattice algebra, have been shown to exhibit superior information storage capacity, fast training and short convergence times, high pattern classification accuracy, and low computational cost. Such attributes are not always found, for example, in classical neural nets based on the linear inner product. In a special type of lattice associative memory (LAM), called a dendritic LAM or DLAM, it is possible to achieve noise-tolerant pattern classification by varying the design of noise or error acceptance bounds. This paper presents theory and algorithmic approaches for the computation of noise-tolerant lattice associative memories (LAMs) under a variety of input constraints. Of particular interest are the classification of nonergodic data in noise regimes with time-varying statistics. DLAMs, which are a specialization of LAMs derived from concepts of biological neural networks, have successfully been applied to pattern classification from hyperspectral remote sensing data, as well as spatial object recognition from digital imagery. The authors' recent research in the development of DLAMs is overviewed, with experimental results that show utility for a wide variety of pattern classification applications. Performance results are presented in terms of measured computational cost, noise tolerance, classification accuracy, and throughput for a variety of input data and noise levels.

  8. Rheumatoid arthritis synovium contains plasmacytoid dendritic cells

    Science.gov (United States)

    Cavanagh, Lois L; Boyce, Amanda; Smith, Louise; Padmanabha, Jagadish; Filgueira, Luis; Pietschmann, Peter; Thomas, Ranjeny

    2005-01-01

    We have previously described enrichment of antigen-presenting HLA-DR+ nuclear RelB+ dendritic cells (DCs) in rheumatoid arthritis (RA) synovium. CD123+HLA-DR+ plasmacytoid DCs (pDCs) and their precursors have been identified in human peripheral blood (PB), lymphoid tissue, and some inflamed tissues. We hypothesized recruitment of pDCs into the inflamed RA synovial environment and their contribution as antigen-presenting cells (APCs) and inflammatory cells in RA. CD11c+ myeloid DCs and CD123+ pDCs were compared in normal and RA PB, synovial fluid (SF), and synovial tissue by flow cytometry, immunohistochemistry, and electron microscopy and were sorted for functional studies. Nuclear RelB-CD123+ DCs were located in perivascular regions of RA, in a similar frequency to nuclear RelB+CD123- DCs, but not normal synovial tissue sublining. Apart from higher expression of HLA-DR, the numbers and phenotypes of SF pDCs were similar to those of normal PB pDCs. While the APC function of PB pDCs was less efficient than that of PB myeloid DCs, RA SF pDCs efficiently activated resting allogeneic PB T cells, and high levels of IFN-γ, IL-10, and tumor necrosis factor α were produced in response to incubation of allogeneic T cells with either type of SF DCs. Thus, pDCs are recruited to RA synovial tissue and comprise an APC population distinct from the previously described nuclear RelB+ synovial DCs. pDCs may contribute significantly to the local inflammatory environment. PMID:15743469

  9. Sulforaphane Epigenetically Regulates Innate Immune Responses of Porcine Monocyte-Derived Dendritic Cells Induced with Lipopolysaccharide

    Science.gov (United States)

    Qu, Xueqi; Pröll, Maren; Neuhoff, Christiane; Zhang, Rui; Cinar, Mehmet Ulas; Hossain, Md. Munir; Tesfaye, Dawit; Große-Brinkhaus, Christine; Salilew-Wondim, Dessie; Tholen, Ernst; Looft, Christian; Hölker, Michael; Schellander, Karl; Uddin, Muhammad Jasim

    2015-01-01

    Histone acetylation, regulated by histone deacetylases (HDACs) is a key epigenetic mechanism controlling gene expressions. Although dendritic cells (DCs) are playing pivotal roles in host immune responses, the effect of epigenetic modulation of DCs immune responses remains unknown. Sulforaphane (SFN) as a HDAC inhibitor has anti-inflammatory properties, which is used to investigate the epigenetic regulation of LPS-induced immune gene and HDAC family gene expressions in porcine monocyte-derived dendritic cells (moDCs). SFN was found to inhibit the lipopolysaccharide LPS induced HDAC6, HDAC10 and DNA methyltransferase (DNMT3a) gene expression, whereas up-regulated the expression of DNMT1 gene. Additionally, SFN was observed to inhibit the global HDAC activity, and suppressed moDCs differentiation from immature to mature DCs through down-regulating the CD40, CD80 and CD86 expression and led further to enhanced phagocytosis of moDCs. The SFN pre-treated of moDCs directly altered the LPS-induced TLR4 and MD2 gene expression and dynamically regulated the TLR4-induced activity of transcription factor NF-κB and TBP. SFN showed a protective role in LPS induced cell apoptosis through suppressing the IRF6 and TGF-ß1 production. SFN impaired the pro-inflammatory cytokine TNF-α and IL-1ß secretion into the cell culture supernatants that were induced in moDCs by LPS stimulation, whereas SFN increased the cellular-resident TNF-α accumulation. This study demonstrates that through the epigenetic mechanism the HDAC inhibitor SFN could modulate the LPS induced innate immune responses of porcine moDCs. PMID:25793534

  10. Effects of decreased inhibition on synaptic plasticity and dendritic morphology in the juvenile prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Xanthippi Konstantoudaki

    2014-03-01

    Full Text Available Excitation-inhibition balance is critical for maintaining proper functioning of the cerebral cortex, as evident from electrophysiological and modeling studies, and it is also important for animal behavior (Yizhar et al., 2011. In the cerebral cortex, excitation is provided by glutamate release from pyramidal neurons, while inhibition is provided by GABA release from several types of interneurons. Many neuropsychiatric disorders, such as epilepsy, anxiety, schizophrenia and autism exhibit an imbalance between the excitatory and inhibitory mechanisms of cortical circuits within key brain regions as prefrontal cortex or hippocampus, primarily through dysfunctions in the inhibitory system (Lewis, Volk, & Hashimoto, 2003; Marín, 2012 Given the significant role of GABAergic inhibition in shaping proper function of the cerebral cortex, we used a mouse model of developmentally decreased GABAergic inhibition in order to examine its effects in network properties, namely basal synaptic transmission, synaptic plasticity and dendritic morphology of pyramidal neurons. For our study, we used mice (postnatal day 20-30 in which the Rac1 protein was deleted from Nkx2.1-expressing neurons (Vidaki et al., 2012, (Rac1fl/flNkx2.1 +/cre referred as Rac1 KO mice, and heterozygous (Rac1+/flNkx2.1 +/cre or control (Rac1+/flNkx2.1 +/+ mice. The specific ablation of Rac1 protein from NKx2.1-expressing MGE-derived progenitors leads to a perturbation of their cell cycle exit resulting in decreased number of interneurons in the cortex(Vidaki et al, 2012. We prepared brain slices from the prefrontal cortex and recorded field excitatory postsynaptic potentials (fEPSPs from layer II neurons while stimulating axons in layer II. We find that the evoked fEPSPs are decreased in Rac1 KO mice compared to Rac1 heterozygous or control mice. This could suggest that the decreased GABAergic inhibition causes network alterations that result in reduced glutamatergic function. Furthermore

  11. Excitation of a biconical line

    Science.gov (United States)

    Goshin, G. G.

    1985-01-01

    The Kontorovich-Lebedev integral transformation is used to obtain in an analytic form a rigorous solution to the quasi-three-dimensional problem involving the excitation of a biconical surface with ideally conducting boundaries by slotted ring sources that are phased according to the traveling-wave law. The results can be used in the design of elliptical-polarization biconical antennas.

  12. Performance of thermally excited resonators

    NARCIS (Netherlands)

    Lammerink, Theodorus S.J.; Elwenspoek, Michael Curt; van Ouwerkerk, R.H.; Bouwstra, S.; Bouwstra, S.; Fluitman, J.H.J.

    A study of electrothermal excitation of micro-machined silicon beams is reported. The temperature distribution is calculated as a function of the position of the transducer, resulting in stress in the structure which reduces the resonance frequency. Test samples are realized and measurements or

  13. Indirect excitation of ultrafast demagnetization

    NARCIS (Netherlands)

    Vodungbo, B.; Tudu, B.; Perron, J.; Delaunay, R.; Müller, L.; Berntsen, M.H.; Grübel, G.; Malinowski, G.; Weier, C.; Gautier, J.; Lambert, G.; Zeitoun, P.; Gutt, C.; Jal, E.; Reid, A.H.; Granitzka, P.W.; Jaouen, N,; Dakovski, G.L.; Moeller, S.; Minitti, M.P.; Mitra, A.; Carron, S.; Pfau, B.; von Korff Schmising, C.; Schneider, M.; Eisebitt, S.; Lüning, J.

    2016-01-01

    Does the excitation of ultrafast magnetization require direct interaction between the photons of the optical pump pulse and the magnetic layer? Here, we demonstrate unambiguously that this is not the case. For this we have studied the magnetization dynamics of a ferromagnetic cobalt/palladium

  14. Predictions for Excited Strange Baryons

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, Ishara P.; Goity, Jose L. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2016-04-01

    An assessment is made of predictions for excited hyperon masses which follow from flavor symmetry and consistency with a 1/N c expansion of QCD. Such predictions are based on presently established baryonic resonances. Low lying hyperon resonances which do not seem to fit into the proposed scheme are discussed.

  15. Complete response of metastatic renal cancer with dendritic cell vaccine

    Directory of Open Access Journals (Sweden)

    Dall'Oglio Marcos

    2003-01-01

    Full Text Available INTRODUCTION: We report a case of metastatic renal cell carcinoma that presented involution following therapy with dendritic cells. CASE REPORT: Male, 51-year old patient underwent left radical nephrectomy in September 1999 due to renal cell carcinoma, evolved with recurrence of the neoplasia in January 2002, confirmed by resection of the lesion. A vaccine therapy based on dendritic cells was then performed during 5 months (4 applications. After this period, there was occurrence of new lesions, whose resection revealed areas of necrosis and inflammatory infiltrate. DISCUSSION: The outcome of renal cell carcinoma is influenced by prognostic factors that confer more aggressive tumor characteristics. However, in cases of recurrence, the systemic therapy with dendritic cells-based vaccine can be associated with a better outcome with regression of disease.

  16. Analytical model for the dynamics of semiflexible dendritic polymers

    Science.gov (United States)

    Fürstenberg, Florian; Dolgushev, Maxim; Blumen, Alexander

    2012-04-01

    We study the dynamics of semiflexible dendritic polymers following the method of Dolgushev and Blumen [J. Chem. Phys. 131, 044905 (2009), 10.1063/1.3184797]. The scheme allows to formulate in analytical form the corresponding Langevin equations. We determine the eigenvalues by first block-diagonalizing the problem, which allows to treat even very large dendritic objects. A basic ingredient of the procedure is the observation that a set of eigenmodes in the semiflexible case is similar to that chosen by Cai and Chen [Macromolecules 30, 5104 (1997), 10.1021/ma970059z] for fully flexible dendritic structures. Varying the flexibility of the macromolecules allows us to better understand their mechanical loss moduli G″(ω) based on their eigenvalue spectra. We present the G″(ω) for a series of stiffness parameters and for different functionalities of the branching points.

  17. Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Julio Aliberti

    2016-01-01

    Full Text Available Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn’s disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

  18. A Model of Dendritic Cell Therapy for Melanoma

    Directory of Open Access Journals (Sweden)

    Ami eRadunskaya

    2013-03-01

    Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

  19. Involvement of dendritic cells in autoimmune diseases in children

    Directory of Open Access Journals (Sweden)

    Reed Ann M

    2007-07-01

    Full Text Available Abstract Dendritic cells (DCs are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood.

  20. Miro's N-Terminal GTPase Domain Is Required for Transport of Mitochondria into Axons and Dendrites

    Science.gov (United States)

    Babic, Milos; Russo, Gary J.; Wellington, Andrea J.; Sangston, Ryan M.; Gonzalez, Migdalia

    2015-01-01

    Mitochondria are dynamically transported in and out of neuronal processes to maintain neuronal excitability and synaptic function. In higher eukaryotes, the mitochondrial GTPase Miro binds Milton/TRAK adaptor proteins linking microtubule motors to mitochondria. Here we show that Drosophila Miro (dMiro), which has previously been shown to be required for kinesin-driven axonal transport, is also critically required for the dynein-driven distribution of mitochondria into dendrites. In addition, we used the loss-of-function mutations dMiroT25N and dMiroT460N to determine the significance of dMiro's N-terminal and C-terminal GTPase domains, respectively. Expression of dMiroT25N in the absence of endogenous dMiro caused premature lethality and arrested development at a pupal stage. dMiroT25N accumulated mitochondria in the soma of larval motor and sensory neurons, and prevented their kinesin-dependent and dynein-dependent distribution into axons and dendrites, respectively. dMiroT25N mutant mitochondria also were severely fragmented and exhibited reduced kinesin and dynein motility in axons. In contrast, dMiroT460N did not impair viability, mitochondrial size, or the distribution of mitochondria. However, dMiroT460N reduced dynein motility during retrograde mitochondrial transport in axons. Finally, we show that substitutions analogous to the constitutively active Ras-G12V mutation in dMiro's N-terminal and C-terminal GTPase domains cause neomorphic phenotypic effects that are likely unrelated to the normal function of each GTPase domain. Overall, our analysis indicates that dMiro's N-terminal GTPase domain is critically required for viability, mitochondrial size, and the distribution of mitochondria out of the neuronal soma regardless of the employed motor, likely by promoting the transition from a stationary to a motile state. PMID:25855186