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Sample records for excitable cells modulators

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

    Science.gov (United States)

    Varghese, Anthony

    2016-01-01

    The inwardly rectifying potassium current (IK1) and the fast inward sodium current (INa) are reciprocally modulated in mammalian ventricular myocytes. An increase in the expression of channels responsible for one of these two currents results in a corresponding increase in expression of the other. These currents are critical in the propagation of action potentials (AP) during the normal functioning of the heart. This study identifies a physiological role for IK1-INa reciprocal modulation in ventricular fiber activation thresholds and conduction. Simulations of action potentials in single cells and propagating APs in cardiac fibers were carried out using an existing model of electrical activity in cardiac ventricular myocytes. The conductances, GK1, of the inwardly rectifying potassium current, and GNa, of the fast inward sodium current were modified independently and in tandem to simulate reciprocal modulation. In single cells, independent modulation of GK1 alone resulted in changes in activation thresholds that were qualitatively similar to those for reciprocal GK1-GNa modulation and unlike those due to independent modulation of GNa alone, indicating that GK1 determines the cellular activation threshold. On the other hand, the variations in conduction velocity in cardiac cell fibers were similar for independent GNa modulation and for tandem changes in GK1-GNa, suggesting that GNa is primarily responsible for setting tissue AP conduction velocity. Conduction velocity dependence on GK1-GNa is significantly affected by the intercellular gap junction conductance. While the effects on the passive fiber space constant due to changes in both GK1 and the intercellular gap junction conductance, Ggj, were in line with linear cable theory predictions, both conductances had surprisingly large effects on fiber activation thresholds. Independent modulation of GK1 rendered cardiac fibers inexcitable at higher levels of GK1 whereas tandem GK1-GNa changes allowed fibers to remain

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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/...

  9. Evolution of Excited Convective Cells in Plasmas

    DEFF Research Database (Denmark)

    Pécseli, Hans; Juul Rasmussen, Jens; Sugai, H.

    1984-01-01

    Convective cells are excited externally in a fully ionized magnetized plasma and their space-time evolution is investigated by two-dimensional potential measurements. A positive cell is excited externally by control of the end losses in the 'scrape off' layer of a plasma column produced by surface...

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Lithium. Effects on excitable cell membranes

    NARCIS (Netherlands)

    Ploeger, Egbert Johan

    1974-01-01

    LITHIUM: Effects on excitable cell membranes. Lithium salts have been used in the treatment of manic-depressive psychosis for many years but their mechanism of action is not well understood. Many workers assume that the action of lithium on catecholamine metabolism and/or on electrolyte distribution

  17. 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.

  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. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Directory of Open Access Journals (Sweden)

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  20. 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

  1. 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

  2. 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.

  3. Module of solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Katsuaki; Ohira, Takeo

    1988-04-30

    It is proposed to apply transparent plastics film on the surface of solar cell module as the substitute of the transparent tempered glass. However, weather proof film made of polyester or polyvinyliden fluoride has a drawback of weak bonding with the filler made of ethylen-vinyl acetate copolymer. This invention relates to the improvement of the bonding characteristics without decreasing the transparency of the film, by covering the surface of it with Al or other metals, or inorganic material such as silicon dioxide, by applying sputtering or vapour deposition method. In addition, application of silan coupling agent is mentioned as an improving method of the bonding. (2 figs)

  4. 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.

  5. 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...

  6. Evolution of Externally Excited Convective Cells in Plasmas

    DEFF Research Database (Denmark)

    Sugai, H.; Juul Rasmussen, Jens; Thomsen, Kenneth

    1983-01-01

    Convective cells are excited externally in a fully ionized magnetized plasma, and their space-time evolution is investigated by two-dimensional potential measurements. A positive cell is excited externally in the `scrape-off' layer of a plasma column produced by surface ionization. Its interaction...

  7. 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...

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Photovoltaic cell module and method of forming

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Malinda; Juen, Donnie; Ketola, Barry; Tomalia, Mary Kay

    2017-12-12

    A photovoltaic cell module, a photovoltaic array including at least two modules, and a method of forming the module are provided. The module includes a first outermost layer and a photovoltaic cell disposed on the first outermost layer. The module also includes a second outermost layer disposed on the photovoltaic cell and sandwiching the photovoltaic cell between the second outermost layer and the first outermost layer. The method of forming the module includes the steps of disposing the photovoltaic cell on the first outermost layer, disposing a silicone composition on the photovoltaic cell, and compressing the first outermost layer, the photovoltaic cell, and the second layer to form the photovoltaic cell module.

  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. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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…

  1. Oncotripsy: Targeting cancer cells selectively via resonant harmonic excitation

    CERN Document Server

    Heyden, Stefanie

    2015-01-01

    We investigate a method of selectively targeting cancer cells by means of ultrasound harmonic excitation at their resonance frequency, which we refer to as oncotripsy. The geometric model of the cells takes into account the cytoplasm, nucleus and nucleolus, as well as the plasma membrane and nuclear envelope. Material properties are varied within a pathophysiologically-relevant range. A first modal analysis reveals the existence of a spectral gap between the natural frequencies and, most importantly, resonant growth rates of healthy and cancerous cells. The results of the modal analysis are verified by simulating the fully-nonlinear transient response of healthy and cancerous cells at resonance. The fully nonlinear analysis confirms that cancerous cells can be selectively taken to lysis by the application of carefully tuned ultrasound harmonic excitation while simultaneously leaving healthy cells intact.

  2. 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.

  3. 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.

  4. Development and Implementation of Biological Circuits Using Excitable and Non-Excitable Cells

    Energy Technology Data Exchange (ETDEWEB)

    Casasnovas-Orus, V.; Gomez-Cid, L.; Hernandez-Romero, I.; Fuentes, L.; Guillem, M.S.; Atienza, F.; Fernandez-Aviles, F.; Climent, A.M.

    2016-07-01

    Compared to conventional computation systems, living beings require reduced power and raw materials consumption, inviting to explore the concept of biological circuits. In this project, a proof-of-concept of logical biocircuits using cell patterns has been developed. These were based upon differential ionic communication between cells, being the cells types used excitable and non-excitable, modeled by cardiomyocytes and fibroblasts correspondingly. To begin, patterns for the basic logic computation blocks were designed, including the OR gate, AND gate and logic memory. The designs were evaluated with mathematical models and in vitro experiments. Results of mathematical modeling indicated that theoretical approval of the biocircuit function. Regarding in vitro biocircuit implementation, three different selective cell localization techniques proved useful for the pattern creation. Evaluation with optical mapping confirmed the operation of the OR gate and logic memory. More resolution in the cell placement strategy will be needed to observe the proper AND gate operation. Thus, fine-tuning of the implementation process will enable the construction of more complex biocircuits that will take on clinical applications relating to electric stimulation of tissues and programmed drug delivery. (Author)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Simulation and Theoretical Study of Spontaneous Excitation of Convective Cells by Kinetic Alfven Waves

    Science.gov (United States)

    Lin, Yu; Zonca, Fulvio; Chen, Liu

    2015-11-01

    It has been recently demonstrated that, generally, electrostatic (ES) and magnetostatic (MS) convective cells (CCs), or zonal flows, can be excited simultaneously by kinetic Alfven waves (KAWs). In this paper, spontaneous excitations of electrostatic as well as magnetostatic convective cells by KAWs are investigated through hybrid simulations, and the results are compared with the analytical theory based on the nonlinear gyrokinetic equations. In the hybrid simulation, ions are treated as fully kinetic particles, and electrons are treated as a massless fluid. It is found that finite ion-Larmor-radius (FILR) effects play a crucial. Furthermore, ES and MS convective cells are intrinsically coupled and must be treated on an equal footing. Excellent agreement is obtained for mode structure and generation rate of convective cells by KAW, demonstrating that ESCC and MSCC are indeed coupled, and that spontaneous CC excitation is suppressed at long wavelength, showing the crucial destabilizing role of FILR effects in the excitation via modulational instabilities. This work is supported by US DoE, NSF, ITER-CN, and NSFC grants.

  10. 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.

  11. Effects of cell cycle noise on excitable gene circuits

    CERN Document Server

    Veliz-Cuba, Alan; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2016-01-01

    We assess the impact of cell cycle noise on gene circuit dynamics. For bistable genetic switches and excitable circuits, we find that transitions between metastable states most likely occur just after cell division and that this concentration effect intensifies in the presence of transcriptional delay. We explain this concentration effect with a 3-states stochastic model. For genetic oscillators, we quantify the temporal correlations between daughter cells induced by cell division. Temporal correlations must be captured properly in order to accurately quantify noise sources within gene networks.

  12. 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...

  13. Snail modulates cell metabolism in MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Haraguchi, Misako, E-mail: haraguci@m3.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Indo, Hiroko P. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Iwasaki, Yasumasa [Health Care Center, Kochi University, Kochi 780-8520 (Japan); Iwashita, Yoichiro [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Fukushige, Tomoko [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Majima, Hideyuki J. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Izumo, Kimiko; Horiuchi, Masahisa [Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Kanekura, Takuro [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Furukawa, Tatsuhiko [Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Ozawa, Masayuki [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan)

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. PV Cell and Module Calibrations at NREL

    Energy Technology Data Exchange (ETDEWEB)

    Emery, Keith

    2012-10-22

    NREL has equipment to measure any conceivable cell or module technology. The lack of standards for low concentration modules complicates matters. Spectrally adjustable simulators are critical for more than three junctions. NREL's 10-channel fiber optic simulator has shown that the light can be set for each junction within 1% of what it would be under the reference spectrum for up to a five-junction cell. Uncertainty in module simulators dominated by spatial nonuniformity for calibration labs. Manufacturers can mitigate this error by using matched reference modules instead of cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

  3. 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

  4. Module level solutions to solar cell polarization

    Science.gov (United States)

    Xavier, Grace , Li; Bo, [San Jose, CA

    2012-05-29

    A solar cell module includes interconnected solar cells, a transparent cover over the front sides of the solar cells, and a backsheet on the backsides of the solar cells. The solar cell module includes an electrical insulator between the transparent cover and the front sides of the solar cells. An encapsulant protectively packages the solar cells. To prevent polarization, the insulator has resistance suitable to prevent charge from leaking from the front sides of the solar cells to other portions of the solar cell module by way of the transparent cover. The insulator may be attached (e.g., by coating) directly on an underside of the transparent cover or be a separate layer formed between layers of the encapsulant. The solar cells may be back junction solar cells.

  5. Infrared light excites cells by changing their electrical capacitance

    Science.gov (United States)

    Shapiro, Mikhail G.; Homma, Kazuaki; Villarreal, Sebastian; Richter, Claus-Peter; Bezanilla, Francisco

    2012-01-01

    Optical stimulation has enabled important advances in the study of brain function and other biological processes, and holds promise for medical applications ranging from hearing restoration to cardiac pace making. In particular, pulsed laser stimulation using infrared wavelengths >1.5 μm has therapeutic potential based on its ability to directly stimulate nerves and muscles without any genetic or chemical pre-treatment. However, the mechanism of infrared stimulation has been a mystery, hindering its path to the clinic. Here we show that infrared light excites cells through a novel, highly general electrostatic mechanism. Infrared pulses are absorbed by water, producing a rapid local increase in temperature. This heating reversibly alters the electrical capacitance of the plasma membrane, depolarizing the target cell. This mechanism is fully reversible and requires only the most basic properties of cell membranes. Our findings underscore the generality of pulsed infrared stimulation and its medical potential. PMID:22415827

  6. Infrared light excites cells by changing their electrical capacitance.

    Science.gov (United States)

    Shapiro, Mikhail G; Homma, Kazuaki; Villarreal, Sebastian; Richter, Claus-Peter; Bezanilla, Francisco

    2012-03-13

    Optical stimulation has enabled important advances in the study of brain function and other biological processes, and holds promise for medical applications ranging from hearing restoration to cardiac pace making. In particular, pulsed laser stimulation using infrared wavelengths >1.5 μm has therapeutic potential based on its ability to directly stimulate nerves and muscles without any genetic or chemical pre-treatment. However, the mechanism of infrared stimulation has been a mystery, hindering its path to the clinic. Here we show that infrared light excites cells through a novel, highly general electrostatic mechanism. Infrared pulses are absorbed by water, producing a rapid local increase in temperature. This heating reversibly alters the electrical capacitance of the plasma membrane, depolarizing the target cell. This mechanism is fully reversible and requires only the most basic properties of cell membranes. Our findings underscore the generality of pulsed infrared stimulation and its medical potential.

  7. Process of making solar cell module

    Science.gov (United States)

    Packer, M.; Coyle, P.J.

    1981-03-09

    A process is presented for the manufacture of solar cell modules. A solution comprising a highly plasticized polyvinyl butyral is applied to a solar cell array. The coated array is dried and sandwiched between at last two sheets of polyvinyl butyral and at least two sheets of a rigid transparent member. The sandwich is laminated by the application of heat and pressure to cause fusion and bonding of the solar cell array with the rigid transparent members to produce a solar cell module.

  8. Cytotoxicity of ZnO Nanowire Arrays on Excitable Cells

    Directory of Open Access Journals (Sweden)

    Yongchen Wang

    2017-04-01

    Full Text Available Zinc oxide (ZnO nanowires have been widely studied for their applications in electronics, optics, and catalysts. Their semiconducting, piezoelectric, fluorescent, and antibacterial properties have also attracted broad interest in their biomedical applications. Thus, it is imperative to evaluate the biosafety of ZnO nanowires and their biological effects. In this study, the cellular level biological effects of ZnO nanowire arrays are specifically tested on three types of excitable cells, including NG108-15 neuronal cell line, HL-1 cardiac muscle cell line, and neonatal rat cardiomyocytes. Vertically aligned and densely packed ZnO nanowire arrays are synthesized using a solution-based method and used as a substrate for cell culture. The metabolism levels of all three types of cells cultured on ZnO nanowire arrays are studied using the 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assays of a full factorial design. Under the studied settings, the results show statistically significant inhibitory effects of ZnO nanowire arrays on the metabolism of NG108-15 and HL-1 cells in comparison to gold, glass, and polystyrene substrates, and on the metabolism of cardiomyocytes in comparison to gold substrate.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. 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.

  14. Cell shunt resistance and photovoltaic module performance

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, T.J.; Basso, T.S.; Rummel, S.R. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    Shunt resistance of cells in photovoltaic modules can affect module power output and could indicate flawed manufacturing processes and reliability problems. The authors describe a two-terminal diagnostic method to directly measure the shunt resistance of individual cells in a series-connected module non-intrusively, without deencapsulation. Peak power efficiency vs. light intensity was measured on a 12-cell, series-connected, single crystalline module having relatively high cell shunt resistances. The module was remeasured with 0.5-, 1-, and 2-ohm resistors attached across each cell to simulate shunt resistances of several emerging technologies. Peak power efficiencies decreased dramatically at lower light levels. Using the PSpice circuit simulator, the authors verified that cell shunt and series resistances can indeed be responsible for the observed peak power efficiency vs. intensity behavior. The authors discuss the effect of basic cell diode parameters, i.e., shunt resistance, series resistance, and recombination losses, on PV module performance as a function of light intensity.

  15. Optical cell stimulation for neuronal excitation (Conference Presentation)

    Science.gov (United States)

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

    2017-02-01

    Optical manipulation of cellular functions represents a growing field in biomedical sciences. The possibility to modulate specific targets with high spatial and temporal precision in a contactless manner allows a broad range of applications. Here, we present a study on stimulation of neuronal cells by optical means. As a long-term objective, we seek to improve the performance of current electric neurostimulation, especially in the context of cochlear implants. Firstly, we tested a gold nanoparticle mediated approach to modulate transmembrane conductivity by irradiation using a picosecond pulsed Nd:YAG laser at 532 nm for 40 ms in a neuroblastoma cell line (N2A) and primary murine neurons. The light absorption leads to a rapid temperature increase of the gold nanoparticles, which can induce an increased permeabilisation of the cellular membrane. Calcium transients were recorded as an indicator of neuronal activity. Although calcium signals were reliably detected upon laser irradiation, the temporal behavior did not resemble action potentials. The origin of these signals was investigated by an inhibitor study. These results indicate calcium induced calcium release (CICR) as the major source of the calcium transients. Consecutively, we tested alternative approaches for cell stimulation, such as glutamate release and optogenetics, and evaluated the potential of these methods for the application in a cochlear implant. Compared to the gold nanoparticle approach, both techniques induce less cellular stress and reliably produce action potentials.

  16. 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 ...

  17. 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.

  18. Stochastic differential equation model for cerebellar granule cell excitability.

    Directory of Open Access Journals (Sweden)

    Antti Saarinen

    2008-02-01

    Full Text Available Neurons in the brain express intrinsic dynamic behavior which is known to be stochastic in nature. A crucial question in building models of neuronal excitability is how to be able to mimic the dynamic behavior of the biological counterpart accurately and how to perform simulations in the fastest possible way. The well-established Hodgkin-Huxley formalism has formed to a large extent the basis for building biophysically and anatomically detailed models of neurons. However, the deterministic Hodgkin-Huxley formalism does not take into account the stochastic behavior of voltage-dependent ion channels. Ion channel stochasticity is shown to be important in adjusting the transmembrane voltage dynamics at or close to the threshold of action potential firing, at the very least in small neurons. In order to achieve a better understanding of the dynamic behavior of a neuron, a new modeling and simulation approach based on stochastic differential equations and Brownian motion is developed. The basis of the work is a deterministic one-compartmental multi-conductance model of the cerebellar granule cell. This model includes six different types of voltage-dependent conductances described by Hodgkin-Huxley formalism and simple calcium dynamics. A new model for the granule cell is developed by incorporating stochasticity inherently present in the ion channel function into the gating variables of conductances. With the new stochastic model, the irregular electrophysiological activity of an in vitro granule cell is reproduced accurately, with the same parameter values for which the membrane potential of the original deterministic model exhibits regular behavior. The irregular electrophysiological activity includes experimentally observed random subthreshold oscillations, occasional spontaneous spikes, and clusters of action potentials. As a conclusion, the new stochastic differential equation model of the cerebellar granule cell excitability is found to expand

  19. 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.

  20. 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...

  1. 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 ...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Cell module and fuel conditioner

    Science.gov (United States)

    Hoover, D. Q., Jr.

    1980-01-01

    The computer code for the detailed analytical model of the MK-2 stacks is described. An ERC proprietary matrix is incorporated in the stacks. The mechanical behavior of the stack during thermal cycles under compression was determined. A 5 cell stack of the MK-2 design was fabricated and tested. Designs for the next three stacks were selected and component fabrication initiated. A 3 cell stack which verified the use of wet assembly and a new acid fill procedure were fabricated and tested. Components for the 2 kW test facility were received or fabricated and construction of the facility is underway. The definition of fuel and water is used in a study of the fuel conditioning subsystem. Kinetic data on several catalysts, both crushed and pellets, was obtained in the differential reactor. A preliminary definition of the equipment requirements for treating tap and recovered water was developed.

  12. Cell module and fuel conditioner

    Science.gov (United States)

    Hoover, D. Q., Jr.

    1980-07-01

    The computer code for the detailed analytical model of the MK-2 stacks is described. An ERC proprietary matrix is incorporated in the stacks. The mechanical behavior of the stack during thermal cycles under compression was determined. A 5 cell stack of the MK-2 design was fabricated and tested. Designs for the next three stacks were selected and component fabrication initiated. A 3 cell stack which verified the use of wet assembly and a new acid fill procedure were fabricated and tested. Components for the 2 kW test facility were received or fabricated and construction of the facility is underway. The definition of fuel and water is used in a study of the fuel conditioning subsystem. Kinetic data on several catalysts, both crushed and pellets, was obtained in the differential reactor. A preliminary definition of the equipment requirements for treating tap and recovered water was developed.

  13. 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.

  14. 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.

  15. An organic transistor-based system for reference-less electrophysiological monitoring of excitable cells

    Science.gov (United States)

    Spanu, A.; Lai, S.; Cosseddu, P.; Tedesco, M.; Martinoia, S.; Bonfiglio, A.

    2015-01-01

    In the last four decades, substantial advances have been done in the understanding of the electrical behavior of excitable cells. From the introduction in the early 70's of the Ion Sensitive Field Effect Transistor (ISFET), a lot of effort has been put in the development of more and more performing transistor-based devices to reliably interface electrogenic cells such as, for example, cardiac myocytes and neurons. However, depending on the type of application, the electronic devices used to this aim face several problems like the intrinsic rigidity of the materials (associated with foreign body rejection reactions), lack of transparency and the presence of a reference electrode. Here, an innovative system based on a novel kind of organic thin film transistor (OTFT), called organic charge modulated FET (OCMFET), is proposed as a flexible, transparent, reference-less transducer of the electrical activity of electrogenic cells. The exploitation of organic electronics in interfacing the living matters will open up new perspectives in the electrophysiological field allowing us to head toward a modern era of flexible, reference-less, and low cost probes with high-spatial and high-temporal resolution for a new generation of in-vitro and in-vivo monitoring platforms. PMID:25744085

  16. Genetic modulation of sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Steinberg, M.H. [Univ. of Mississippi School of Medicine, Jackson, MS (United States)

    1995-05-01

    Sickle cell anemia, a common disorder associated with reduced life span of the red blood cell and vasoocclusive events, is caused by a mutation in the {Beta}-hemoglobin gene. Yet, despite this genetic homogeneity, the phenotype of the disease is heterogeneous. This suggests the modulating influence of associated inherited traits. Some of these may influence the accumulation of fetal hemoglobin, a hemoglobin type that interferes with the polymerization of sickle hemoglobin. Another inherited trait determines the accumulation of {alpha}-globin chains. This review focuses on potential genetic regulators of the phenotype of sickle cell anemia. 125 refs., 6 figs., 3 tabs.

  17. Afferents originating from the dorsal penile nerve excite oxytocin cells in the hypothalamic paraventricular nucleus of the rat.

    Science.gov (United States)

    Yanagimoto, M; Honda, K; Goto, Y; Negoro, H

    1996-09-16

    Electrical stimulation of the dorsal penile nerve (DPN) produced orthodromic excitation in about half of oxytocin cells in the paraventricular nucleus (PVN). In contrast, less than 10% of vasopressin cells were excited. Tactile stimulation of the glans penis by a paintbrush produced excitation in 40% of oxytocin cells. Castration did not prevent activation of oxytocin cells. These results suggest that somatosensory information from the penis is transmitted to the PVN through the DPN and that such afferent input preferentially innervates oxytocin cells.

  18. 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

  19. 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.

  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. ZnO nanotube waveguide arrays on graphene films for local optical excitation on biological cells

    Science.gov (United States)

    Baek, Hyeonjun; Kwak, Hankyul; Song, Minho S.; Ha, Go Eun; Park, Jongwoo; Tchoe, Youngbin; Hyun, Jerome K.; Park, Hye Yoon; Cheong, Eunji; Yi, Gyu-Chul

    2017-04-01

    We report on scalable and position-controlled optical nanoprobe arrays using ZnO nanotube waveguides on graphene films for use in local optical excitation. For the waveguide fabrication, position-controlled and well-ordered ZnO nanotube arrays were grown on chemical vapor deposited graphene films with a submicron patterned mask layer and Au prepared between the interspace of nanotubes. Mammalian cells were cultured on the nanotube waveguide arrays and were locally excited by light illuminated through the nanotubes. Fluorescence and optogenetic signals could be excited through the optical nanoprobes. This method offers the ability to investigate cellular behavior with a high spatial resolution that surpasses the current limitation.

  2. 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....

  3. 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.

  4. Regulation of granule cell excitability by a low-threshold calcium spike in turtle olfactory bulb

    DEFF Research Database (Denmark)

    Pinato, Giulietta; Midtgaard, Jens

    2003-01-01

    Granule cells excitability in the turtle olfactory bulb was analyzed using whole cell recordings in current- and voltage-clamp mode. Low-threshold spikes (LTSs) were evoked at potentials that are subthreshold for Na spikes in normal medium. The LTSs were evoked from rest, but hyperpolarization...

  5. Deep Brain Stimulation: More Complex than the Inhibition of Cells and Excitation of Fibers.

    Science.gov (United States)

    Florence, Gerson; Sameshima, Koichi; Fonoff, Erich T; Hamani, Clement

    2016-08-01

    High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a "functional inhibition" of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation "local inhibition" and "distant excitation" is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS. © The Author(s) 2015.

  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. A Quantitative Analysis of Photovoltaic Modules Using Halved Cells

    Directory of Open Access Journals (Sweden)

    S. Guo

    2013-01-01

    Full Text Available In a silicon wafer-based photovoltaic (PV module, significant power is lost due to current transport through the ribbons interconnecting neighbour cells. Using halved cells in PV modules is an effective method to reduce the resistive power loss which has already been applied by some major PV manufacturers (Mitsubishi, BP Solar in their commercial available PV modules. As a consequence, quantitative analysis of PV modules using halved cells is needed. In this paper we investigate theoretically and experimentally the difference between modules made with halved and full-size solar cells. Theoretically, we find an improvement in fill factor of 1.8% absolute and output power of 90 mW for the halved cell minimodule. Experimentally, we find an improvement in fill factor of 1.3% absolute and output power of 60 mW for the halved cell module. Also, we investigate theoretically how this effect confers to the case of large-size modules. It is found that the performance increment of halved cell PV modules is even higher for high-efficiency solar cells. After that, the resistive loss of large-size modules with different interconnection schemes is analysed. Finally, factors influencing the performance and cost of industrial halved cell PV modules are discussed.

  8. Models of Excitation-Secretion Coupling in Pituitary Cells

    Science.gov (United States)

    1991-06-26

    using data from our own laboratory as well as data from studies of the interaction of nimodipine with calcium channels from GH4C3 cells (6) . Measurements...and nimodipine block of calcium channels were recently published(lO in Contract Related Publications). References 1. Dubinsky, J.M. and Oxford, G.S...Biometrics, 44:549-559. 1988. 6. Cohen, C.J. and McCarthy, R.T. Nimodipine block of calcium channels in rat anterior pituitary cells. J. Physiol (London

  9. Photoluminescence Excitation Spectroscopy Characterization of Cadmium Telluride Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Moore, James E.; Wang, Xufeng; Grubbs, Elizabeth K.; Drayton, Jennifer; Johnston, Steve; Levi, Dean; Lundstrom, Mark S.; Bermel, Peter

    2016-11-21

    The use of steady-state photoluminescence spectroscopy as a contactless characterization tool, suitable for inline optical characterization, has been previously demonstrated for high efficiency solar cells such as GaAs. In this paper, we demonstrate the use of PLE characterization on a thin film CdS/CdTe np heterojunction solar cell, and compare the results to measured EQE and I-V data. In contrast to previous work on high-quality GaAs, the PLE and EQE spectra do not match closely here. We still find, however, that reliable material parameters can be extracted from the PLE measurements. We also provide a physical explanation of the limits defining the cases when the PLE and EQE spectra may be expected to match.

  10. 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.

  11. 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

  12. 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

  13. Hydrodynamic modulation of pluripotent stem cells

    Science.gov (United States)

    2012-01-01

    Controlled expansion and differentiation of pluripotent stem cells (PSCs) using reproducible, high-throughput methods could accelerate stem cell research for clinical therapies. Hydrodynamic culture systems for PSCs are increasingly being used for high-throughput studies and scale-up purposes; however, hydrodynamic cultures expose PSCs to complex physical and chemical environments that include spatially and temporally modulated fluid shear stresses and heterogeneous mass transport. Furthermore, the effects of fluid flow on PSCs cannot easily be attributed to any single environmental parameter since the cellular processes regulating self-renewal and differentiation are interconnected and the complex physical and chemical parameters associated with fluid flow are thus difficult to independently isolate. Regardless of the challenges posed by characterizing fluid dynamic properties, hydrodynamic culture systems offer several advantages over traditional static culture, including increased mass transfer and reduced cell handling. This article discusses the challenges and opportunities of hydrodynamic culture environments for the expansion and differentiation of PSCs in microfluidic systems and larger-volume suspension bioreactors. Ultimately, an improved understanding of the effects of hydrodynamics on the self-renewal and differentiation of PSCs could yield improved bioprocessing technologies to attain scalable PSC culture strategies that will probably be requisite for the development of therapeutic and diagnostic applications. PMID:23168068

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

    Science.gov (United States)

    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

  15. Causes of excitation-induced muscle cell damage in isometric contractions: mechanical stress or calcium overload?

    DEFF Research Database (Denmark)

    Fredsted, Anne; Gissel, Hanne; Madsen, Klavs

    2007-01-01

    Prolonged or unaccustomed exercise leads to muscle cell membrane damage, detectable as release of the intracellular enzyme lactic acid dehydrogenase (LDH). This is correlated to excitation-induced influx of Ca2+, but it cannot be excluded that mechanical stress contributes to the damage. We here ...

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Altering the threshold of an excitable signal transduction network changes cell migratory modes.

    Science.gov (United States)

    Miao, Yuchuan; Bhattacharya, Sayak; Edwards, Marc; Cai, Huaqing; Inoue, Takanari; Iglesias, Pablo A; Devreotes, Peter N

    2017-04-01

    The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued. Conversely, innately keratocyte-like and oscillatory cells were promptly converted to amoeboid by inhibition of Ras effectors with restoration of directed migration. We use computational analysis to explain how thresholds control cell migration and discuss the architecture of the signal transduction network that gives rise to excitability.

  19. Quantifying Solar Cell Cracks in Photovoltaic Modules by Electroluminescence Imaging

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso

    2015-01-01

    This article proposes a method for quantifying the percentage of partially and totally disconnected solar cell cracks by analyzing electroluminescence images of the photovoltaic module taken under high- and low-current forward bias. The method is based on the analysis of the module......’s electroluminescence intensity distribution, applied at module and cell level. These concepts are demonstrated on a crystalline silicon photovoltaic module that was subjected to several rounds of mechanical loading and humidity-freeze cycling, causing increasing levels of solar cell cracks. The proposed method can...

  20. Simultaneous live cell imaging using dual FRET sensors with a single excitation light.

    Directory of Open Access Journals (Sweden)

    Yusuke Niino

    Full Text Available Fluorescence resonance energy transfer (FRET between fluorescent proteins is a powerful tool for visualization of signal transduction in living cells, and recently, some strategies for imaging of dual FRET pairs in a single cell have been reported. However, these necessitate alteration of excitation light between two different wavelengths to avoid the spectral overlap, resulting in sequential detection with a lag time. Thus, to follow fast signal dynamics or signal changes in highly motile cells, a single-excitation dual-FRET method should be required. Here we reported this by using four-color imaging with a single excitation light and subsequent linear unmixing to distinguish fluorescent proteins. We constructed new FRET sensors with Sapphire/RFP to combine with CFP/YFP, and accomplished simultaneous imaging of cAMP and cGMP in single cells. We confirmed that signal amplitude of our dual FRET measurement is comparable to of conventional single FRET measurement. Finally, we demonstrated to monitor both intracellular Ca(2+ and cAMP in highly motile cardiac myocytes. To cancel out artifacts caused by the movement of the cell, this method expands the applicability of the combined use of dual FRET sensors for cell samples with high motility.

  1. Toward Fourier interferometry fluorescence excitation/emission imaging of malignant cells combined with photoacoustic microscopy

    Science.gov (United States)

    Kohen, Elli; Hirschberg, Joseph G.; Berry, John P.; Ozkutuk, Nuri; Ornek, Ceren; Monti, Marco; Leblanc, Roger M.; Schachtschabel, Dietrich O.; Haroon, Sumaira

    2003-10-01

    Dual excitation fluorescence imaging has been used as a first step towards multi-wavelength excitation/emission fluorescence spectral imaging. Target cells are transformed keratinocytes, and other osteosarcoma, human breast and color cancer cells. Mitochondrial membrane potential probes, e.g. TMRM (tetramethylrhodamine methyl ester), Mitotracker Green (Molecular Probes, Inc., Eugene OR,USA; a recently synthesized mitochondrial oxygen probe, [PRE,P1"- pyrene butyl)-2-rhodamine ester] allow dual excitation in the UV plus in teh blue-green spectral regions. Also, using the natural endogenous probe NAD(P)H, preliminary results indicate mitochondrial responses to metabolic challenges (e.g. glucose addition), plus changes in mitochonrial distribution and morphology. In terms of application to biomedicine (for diagnostiscs, prognostsics and drug trials) three parameters have been selected in addition to the natural probe NAD(P)H, i.e. vital fluorescence probing of mitochondria, lysosomes and Golgi apparatus. It is hoped that such a multiparameter approach will allow malignant cell characterization and grading. A new area being introduced is the use of similar methodology for biotechnical applications such as the study of the hydrogen-producing alga Chlamydomonas Reinhardtii, and possible agricultural applications, such as Saccharomyces yeast for oenology. Complementation by Photoacoustic Microscopy is also contemplated, to study the internal conversion component which follows the excitation by photons.

  2. ZnO nanotube waveguide arrays on graphene films for local optical excitation on biological cells

    Directory of Open Access Journals (Sweden)

    Hyeonjun Baek

    2017-04-01

    Full Text Available We report on scalable and position-controlled optical nanoprobe arrays using ZnO nanotube waveguides on graphene films for use in local optical excitation. For the waveguide fabrication, position-controlled and well-ordered ZnO nanotube arrays were grown on chemical vapor deposited graphene films with a submicron patterned mask layer and Au prepared between the interspace of nanotubes. Mammalian cells were cultured on the nanotube waveguide arrays and were locally excited by light illuminated through the nanotubes. Fluorescence and optogenetic signals could be excited through the optical nanoprobes. This method offers the ability to investigate cellular behavior with a high spatial resolution that surpasses the current limitation.

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

    Science.gov (United States)

    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.

  4. 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

  5. Excitation of oxytocin cells in the hypothalamic supraoptic nucleus by electrical stimulation of the dorsal penile nerve and tactile stimulation of the penis in the rat.

    Science.gov (United States)

    Honda, K; Yanagimoto, M; Negoro, H; Narita, K; Murata, T; Higuchi, T

    1999-02-01

    In urethane-anaesthetized male rats, electrical stimulation of the dorsal penile nerve (DPN) excited 29 of 48 (60%) oxytocin cells in the contralateral supraoptic nucleus, whereas only 5 of 28 (18%) vasopressin cells were excited by the stimulation. The stimulus applied to the ipsilateral DPN to the recorded neurone also excited a similar proportion of oxytocin cells (25 of 43; 58%). Tactile stimulation of the glans penis excited 7 of 12 (58%) oxytocin cells, whereas the same stimulation excited only 3 of 16 (19%) vasopressin cells. The results suggest that sensory information arising from the penis preferentially excites oxytocin cells in the supraoptic nucleus.

  6. p-Type MWT. Integrated cell and module technology

    Energy Technology Data Exchange (ETDEWEB)

    Tool, C.J.J.; Kossen, E.J.; Bennett, I.J.

    2013-10-15

    A major issue of concern in MWT solar cells is the increased leakage current at reversed bias voltage through the vias compared. At ECN we have been working on reducing this leakage current to levels comparable to H-pattern cells. In this study we present the results of this work. We further show the benefit of a combined cell and module design for MWT solar cells. At the cell level, MWT production costs per wafer are comparable with H-pattern while the cell output increases. At the module level this design results in a further increase of the power output.

  7. The mechanism of abrupt transition between theta and hyper-excitable spiking activity in medial entorhinal cortex layer II stellate cells.

    Directory of Open Access Journals (Sweden)

    Tilman Kispersky

    2010-11-01

    Full Text Available Recent studies have shown that stellate cells (SCs of the medial entorhinal cortex become hyper-excitable in animal models of temporal lobe epilepsy. These studies have also demonstrated the existence of recurrent connections among SCs, reduced levels of recurrent inhibition in epileptic networks as compared to control ones, and comparable levels of recurrent excitation among SCs in both network types. In this work, we investigate the biophysical and dynamic mechanism of generation of the fast time scale corresponding to hyper-excitable firing and the transition between theta and fast firing frequency activity in SCs. We show that recurrently connected minimal networks of SCs exhibit abrupt, threshold-like transition between theta and hyper-excitable firing frequencies as the result of small changes in the maximal synaptic (AMPAergic conductance. The threshold required for this transition is modulated by synaptic inhibition. Similar abrupt transition between firing frequency regimes can be observed in single, self-coupled SCs, which represent a network of recurrently coupled neurons synchronized in phase, but not in synaptically isolated SCs as the result of changes in the levels of the tonic drive. Using dynamical systems tools (phase-space analysis, we explain the dynamic mechanism underlying the genesis of the fast time scale and the abrupt transition between firing frequency regimes, their dependence on the intrinsic SC's currents and synaptic excitation. This abrupt transition is mechanistically different from others observed in similar networks with different cell types. Most notably, there is no bistability involved. 'In vitro' experiments using single SCs self-coupled with dynamic clamp show the abrupt transition between firing frequency regimes, and demonstrate that our theoretical predictions are not an artifact of the model. In addition, these experiments show that high-frequency firing is burst-like with a duration modulated by an M-current.

  8. Temperature dependence of photovoltaic cells, modules, and systems

    Energy Technology Data Exchange (ETDEWEB)

    Emery, K.; Burdick, J.; Caiyem, Y. [National Renewable Energy Lab., Golden, CO (United States)] [and others

    1996-05-01

    Photovoltaic (PV) cells and modules are often rated in terms of a set of standard reporting conditions defined by a temperature, spectral irradiance, and total irradiance. Because PV devices operates over a wide range of temperatures and irradiances, the temperature and irradiance related behavior must be known. This paper surveys the temperature dependence of crystalline and thin-film, state-of-the-art, research-size cells, modules, and systems measured by a variety of methods. The various error sources and measurement methods that contribute to cause differences in the temperature coefficient for a given cell or module measured with various methods are discussed.

  9. Regulation of neuronal excitability by release of proteins from glial cells

    Science.gov (United States)

    Igelhorst, Birte A.; Niederkinkhaus, Vanessa; Karus, Claudia; Lange, Maren D.; Dietzel, Irmgard D.

    2015-01-01

    Effects of glial cells on electrical isolation and shaping of synaptic transmission between neurons have been extensively studied. Here we present evidence that the release of proteins from astrocytes as well as microglia may regulate voltage-activated Na+ currents in neurons, thereby increasing excitability and speed of transmission in neurons kept at distance from each other by specialized glial cells. As a first example, we show that basic fibroblast growth factor and neurotrophin-3, which are released from astrocytes by exposure to thyroid hormone, influence each other to enhance Na+ current density in cultured hippocampal neurons. As a second example, we show that the presence of microglia in hippocampal cultures can upregulate Na+ current density. The effect can be boosted by lipopolysaccharides, bacterial membrane-derived stimulators of microglial activation. Comparable effects are induced by the exposure of neuron-enriched hippocampal cultures to tumour necrosis factor-α, which is released from stimulated microglia. Taken together, our findings suggest that release of proteins from various types of glial cells can alter neuronal excitability over a time course of several days. This explains changes in neuronal excitability occurring in states of thyroid hormone imbalance and possibly also in seizures triggered by infectious diseases. PMID:26009773

  10. Potential of thin-film solar cell module technology

    Science.gov (United States)

    Shimada, K.; Ferber, R. R.; Costogue, E. N.

    1985-01-01

    During the past five years, thin-film cell technology has made remarkable progress as a potential alternative to crystalline silicon cell technology. The efficiency of a single-junction thin-film cell, which is the most promising for use in flat-plate modules, is now in the range of 11 percent with 1-sq cm cells consisting of amorphous silicon, CuInSe2 or CdTe materials. Cell efficiencies higher than 18 percent, suitable for 15 percent-efficient flat plate modules, would require a multijunction configuration such as the CdTe/CuInSe2 and tandem amorphous-silicon (a-Si) alloy cells. Assessments are presented of the technology status of thin-film-cell module research and the potential of achieving the higher efficiencies required for large-scale penetration into the photovoltaic (PV) energy market.

  11. Identifying gene expression modules that define human cell fates

    OpenAIRE

    Germanguz, I; Listgarten, J; Cinkornpumin, J.; Solomon, A; Gaeta, X.; Lowry, W. E.

    2016-01-01

    Using a compendium of cell-state-specific gene expression data, we identified genes that uniquely define cell states, including those thought to represent various developmental stages. Our analysis sheds light on human cell fate through the identification of core genes that are altered over several developmental milestones, and across regional specification. Here we present cell-type specific gene expression data for 17 distinct cell states and demonstrate that these modules of genes can in f...

  12. A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation

    Science.gov (United States)

    Xi, Xiaoyu; Yang, Fang; Chen, Di; Luo, Yi; Zhang, Dong; Gu, Ning; Wu, Junru

    2008-06-01

    In our previous work, it was found that acoustic cavitation might play a role in improving the cell permeability to microparticles when liposomes were used in an in vitro experiment. The purpose of this project is to expand our study and to learn other possible mechanisms by which cells may interact with liposomes under ultrasound (US) excitation and become transiently permeable to microparticles. It is further hypothesized that two possible scenarios may be involved in in vitro experiments: (1) drug-carrying liposomes transiently overcome the cell membrane barrier and enter into a cell while the cell is still viable; (2) the liposomes incorporate with a cell at its membrane through a fusing process. To prove this hypothesis, liposomes of two different structures were synthesized: one has fluorescent molecules encapsulated into liposomes and the other has fluorescent markers incorporated into the shells of liposomes. Liposomes of each kind were mixed with human breast cancer cells (MCF7-cell line) in a suspension at 5 (liposomes) : 1 (cell) ratio and were then exposed to a focused 1 MHz ultrasound beam at its focal region for 40 s. The US signal contained 20 cycles per tone-burst at a pulse-repetition-frequency of 10 kHz; the spatial peak acoustic pressure amplitude was 0.25 MPa. It was found that the possible mechanisms might include the acoustic cavitation, the endocytosis and cell-fusion. Acoustic radiation force might make liposomes collide with cells effectively and facilitate the delivery process.

  13. A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Xi Xiaoyu; Zhang Dong [Institute of Acoustics, Lab of Modern Acoustics, Nanjing University, Nanjing 210093 (China); Yang Fang; Gu Ning [State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Chen Di; Wu Junru [Department of Physics, The University of Vermont, Burlington, VT 05405 (United States); Luo Yi [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing 210093 (China)], E-mail: Jun-ru.wu@uvm.edu

    2008-06-21

    In our previous work, it was found that acoustic cavitation might play a role in improving the cell permeability to microparticles when liposomes were used in an in vitro experiment. The purpose of this project is to expand our study and to learn other possible mechanisms by which cells may interact with liposomes under ultrasound (US) excitation and become transiently permeable to microparticles. It is further hypothesized that two possible scenarios may be involved in in vitro experiments: (1) drug-carrying liposomes transiently overcome the cell membrane barrier and enter into a cell while the cell is still viable; (2) the liposomes incorporate with a cell at its membrane through a fusing process. To prove this hypothesis, liposomes of two different structures were synthesized: one has fluorescent molecules encapsulated into liposomes and the other has fluorescent markers incorporated into the shells of liposomes. Liposomes of each kind were mixed with human breast cancer cells (MCF7-cell line) in a suspension at 5 (liposomes) : 1 (cell) ratio and were then exposed to a focused 1 MHz ultrasound beam at its focal region for 40 s. The US signal contained 20 cycles per tone-burst at a pulse-repetition-frequency of 10 kHz; the spatial peak acoustic pressure amplitude was 0.25 MPa. It was found that the possible mechanisms might include the acoustic cavitation, the endocytosis and cell-fusion. Acoustic radiation force might make liposomes collide with cells effectively and facilitate the delivery process.

  14. Parallel excitation-emission multiplexed fluorescence lifetime confocal microscopy for live cell imaging.

    Science.gov (United States)

    Zhao, Ming; Li, Yu; Peng, Leilei

    2014-05-05

    We present a novel excitation-emission multiplexed fluorescence lifetime microscopy (FLIM) method that surpasses current FLIM techniques in multiplexing capability. The method employs Fourier multiplexing to simultaneously acquire confocal fluorescence lifetime images of multiple excitation wavelength and emission color combinations at 44,000 pixels/sec. The system is built with low-cost CW laser sources and standard PMTs with versatile spectral configuration, which can be implemented as an add-on to commercial confocal microscopes. The Fourier lifetime confocal method allows fast multiplexed FLIM imaging, which makes it possible to monitor multiple biological processes in live cells. The low cost and compatibility with commercial systems could also make multiplexed FLIM more accessible to biological research community.

  15. 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

  16. PV modules, using color solar cells, designed for building

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, N.; Yamashita, H.; Goda, S. [Daido Hoxan Inc., Chitose, Hokkaido (Japan). Chitose Research Lab.] [and others

    1994-12-31

    The designs and structures of a photovoltaic module to be installed in a curtain wall were examined with the object of sharply reducing PV power generation costs. As for the design, solar cells of different colors were produced and an opinion survey of designers and other construction-related persons was conducted. Renderings based on color solar cells were prepared using computer graphics. In general, the output of cells decreases for colors other than shades of dark blue. However, there is a good possibility that greater importance will be put on design, including color and surface condition, than on output. In this case, the market share may expand and as a result, the cost may drop. As for the structure, various materials that can be used for a building-material-integrated-module were investigated and methods to install PV modules into building materials were examined. Moreover, experimental module samples fitted with stainless steel sheets and aluminum-sash frames were made.

  17. Enzyme-free cell detachment mediated by resonance vibration with temperature modulation.

    Science.gov (United States)

    Kurashina, Yuta; Hirano, Makoto; Imashiro, Chikahiro; Totani, Kiichiro; Komotori, Jun; Takemura, Kenjiro

    2017-10-01

    Cell detachment is an essential process in adherent cell culture. However, trypsinization, which is the most popular detachment technique used in culture, damages cellular membranes. Reducing cellular membrane damage during detachment should improve the quality of cell culture. In this article, we propose an enzyme-free cell detachment method based on resonance vibration with temperature modulation. We developed a culture device that can excite a resonance vibration and control temperature. We then evaluated the cell detachment ratio and the growth response, observed the morphology, and analyzed the cellular protein of the collected cells-mouse myoblast cell line (C2C12). With the temperature of 10°C and the maximum vibration amplitude of 2 μm, 77.9% of cells in number were successfully detached compared with traditional trypsinization. The 72-h proliferation ratio of the reseeded cells was similar to that with trypsinization, whereas the proliferation ratio of proposed method was 12.6% greater than that of trypsinization after freezing and thawing. Moreover, the cells can be collected relatively intact and both intracellular and cell surface proteins in the proposed method were less damaged than in trypsinization. These results show that this method has definite advantages over trypsinization, which indicates that it could be applied to subcultures of cells that are more susceptible to trypsin damage for mass culture of sustainable clinical use. Biotechnol. Bioeng. 2017;114: 2279-2288. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Plumbagin Modulates Leukemia Cell Redox Status

    Directory of Open Access Journals (Sweden)

    François Gaascht

    2014-07-01

    Full Text Available Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS. The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat.

  19. Adrenal steroids as modulators of nerve cell function

    NARCIS (Netherlands)

    Kloet, E.R. de

    1984-01-01

    Adrenal steroids modulate the function of nerve cells. Some, but not all actions of these steroids take place after binding to intracellular receptor systems and translocation of the steroid-receptor complex into the cell nucleus. Studies on the rat brain revealed heterogeneity of receptors. One

  20. 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 ...

  1. Applications of ``PV Optics`` for solar cell and module design

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B.L.; Madjdpour, J.; Chen, W. [National Renewable Energy Lab., Golden, CO (United States)

    1998-09-01

    This paper describes some applications of a new optics software package, PV Optics, developed for the optical design of solar cells and modules. PV Optics is suitable for the analysis and design of both thick and thin solar cells. It also includes a feature for calculation of metallic losses related to contacts and back reflectors.

  2. Thyroid hormone differentially modulates Warburg phenotype in breast cancer cells.

    Science.gov (United States)

    Suhane, Sonal; Ramanujan, V Krishnan

    2011-10-14

    Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Standing-wave-excited multiplanar fluorescence in a laser scanning microscope reveals 3D information on red blood cells

    CERN Document Server

    Amor, Rumelo; Amos, William Bradshaw; McConnell, Gail

    2014-01-01

    Standing-wave excitation of fluorescence is highly desirable in optical microscopy because it improves the axial resolution. We demonstrate here that multiplanar excitation of fluorescence by a standing wave can be produced in a single-spot laser scanning microscope by placing a plane reflector close to the specimen. We report that the relative intensities in each plane of excitation depend on the Stokes shift of the fluorochrome. We show by the use of dyes specific for the cell membrane how standing-wave excitation can be exploited to generate precise contour maps of the surface membrane of red blood cells, with an axial resolution of ~90 nm. The method, which requires only the addition of a plane mirror to an existing confocal laser scanning microscope, may well prove useful in studying diseases which involve the red cell membrane, such as malaria.

  4. Transparent electrode requirements for thin film solar cell modules

    KAUST Repository

    Rowell, Michael W.

    2011-01-01

    The transparent conductor (TC) layer in thin film solar cell modules has a significant impact on the power conversion efficiency. Reflection, absorption, resistive losses and lost active area either from the scribed interconnect region in monolithically integrated modules or from the shadow losses of a metal grid in standard modules typically reduce the efficiency by 10-25%. Here, we perform calculations to show that a competitive TC must have a transparency of at least 90% at a sheet resistance of less than 10 Ω/sq (conductivity/absorptivity ≥ 1 Ω -1) for monolithically integrated modules. For standard modules, losses are much lower and the performance of alternative lower cost TC materials may already be sufficient to replace conducting oxides in this geometry. © 2011 The Royal Society of Chemistry.

  5. Identifying gene expression modules that define human cell fates.

    Science.gov (United States)

    Germanguz, I; Listgarten, J; Cinkornpumin, J; Solomon, A; Gaeta, X; Lowry, W E

    2016-05-01

    Using a compendium of cell-state-specific gene expression data, we identified genes that uniquely define cell states, including those thought to represent various developmental stages. Our analysis sheds light on human cell fate through the identification of core genes that are altered over several developmental milestones, and across regional specification. Here we present cell-type specific gene expression data for 17 distinct cell states and demonstrate that these modules of genes can in fact define cell fate. Lastly, we introduce a web-based database to disseminate the results. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yu, E-mail: 1293363632@QQ.com [Faculty of Graduate Studies of Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region (China); Deng, Xin, E-mail: Hendly@163.com [Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, 10 East China Road, Nanning 530011, Guangxi Zhuang Autonomous Region (China); Liang, Jian, E-mail: lj99669@163.com [Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region (China)

    2017-03-15

    Hepatic fibrosis (HF) is the pathological component of a variety of chronic liver diseases. Hepatic stellate cells (HSC) are the main collagen-producing cells in the liver and their activation promotes HF. If HSC activation and proliferation can be inhibited, HF occurrence and development can theoretically be reduced and even reversed. Over the past ten years, a number of studies have addressed this process, and here we present a review of HSC modulation and HF reversal. - Highlights: • We present a review of the modulation of hepatic stellate cells (HSC) and reversibility of hepatic fibrosis (HF). • HSC are the foci of HF occurrence and development, HF could be prevented and treated by modulating HSC. • If HSC activation and proliferation can be inhibited, HF could theoretically be inhibited and even reversed. • Prevention or reversal of HSC activation, or promotion of HSC apoptosis, immune elimination, and senescence may prevent, inhibit or reverse HF.

  7. High Excitation Transfer Efficiency from Energy Relay Dyes in Dye-Sensitized Solar Cells

    KAUST Repository

    Hardin, Brian E.

    2010-08-11

    The energy relay dye, 4-(Dicyanomethylene)-2-methyl-6-(4- dimethylaminostyryl)-4H-pyran (DCM), was used with a near-infrared sensitizing dye, TT1, to increase the overall power conversion efficiency of a dye-sensitized solar cell (DSC) from 3.5% to 4.5%. The unattached DCM dyes exhibit an average excitation transfer efficiency (EÌ?TE) of 96% inside TT1-covered, mesostructured TiO2 films. Further performance increases were limited by the solubility of DCM in an acetonitrile based electrolyte. This demonstration shows that energy relay dyes can be efficiently implemented in optimized dye-sensitized solar cells, but also highlights the need to design highly soluble energy relay dyes with high molar extinction coefficients. © 2010 American Chemical Society.

  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. An electromagnetic compressive force by cell exciter stimulates chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Park, Sang-Hyug; Sim, Woo Young; Park, Sin Wook; Yang, Sang Sik; Choi, Byung Hyune; Park, So Ra; Park, Kwideok; Min, Byoung-Hyun

    2006-11-01

    In this study, we present a biological micro-electromechanical system and its application to the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (MSCs). Actuated by an electromagnetic force, the micro cell exciter was designed to deliver a cyclic compressive load (CCL) with various magnitudes. Two major parts in the system are an actuator and a cartridge-type chamber. The former has a permanent magnet and coil, and the latter is equipped with 7 sample dishes and 7 metal caps. Mixed with a 2.4% alginate solution, the alginate/MSC layers were positioned in the sample dishes; the caps contained chondrogenic defined medium without transforming growth factor-beta (TGF-beta). Once powered, the actuator coil-derived electromagnetic force pulled the metal caps down, compressing the samples. The cyclic load was given at 1-Hz frequency for 10 min twice a day. Samples in the dishes without a cap served as a control. The samples were analyzed at 3, 5, and 7 days after stimulation for cell viability, biochemical assays, histologic features, immunohistochemistry, and gene expression of the chondrogenic markers. Applied to the alginate/MSC layer, the CCL system enhanced the synthesis of cartilage-specific matrix proteins and the chondrogenic markers, such as aggrecan, type II collagen, and Sox9. We found that the micromechanically exerted CCL by the cell exciter was very effective in enhancing the chondrogenic differentiation of MSCs, even without using exogenous TGF-beta.

  10. In vivo spectral imaging of different cell types in the small intestine by two-photon excited autofluorescence

    Science.gov (United States)

    Orzekowsky-Schroeder, Regina; Klinger, Antje; Martensen, Björn; Blessenohl, Maike; Gebert, Andreas; Vogel, Alfred; Hüttmann, Gereon

    2011-11-01

    Spectrally resolved two-photon excited autofluorescence imaging is used to distinguish different cell types and functional areas during dynamic processes in the living gut. Excitation and emission spectra of mucosal tissue and tissue components are correlated to spectra of endogenous chromophores. We show that selective excitation with only two different wavelengths within the tuning range of a Ti:sapphire femtosecond laser system yields excellent discrimination between enterocytes, antigen presenting cells and lysosomes based on the excitation and emission properties of their autofluorescence. The method is employed for time-lapse microscopy over up to 8 h. Changes of the spectral signature with the onset of photodamage are demonstrated, and their origin is discussed.

  11. Charge-Transfer Dynamics in the Lowest Excited State of a Pentacene–Fullerene Complex: Implications for Organic Solar Cells

    KAUST Repository

    Joseph, Saju

    2017-10-02

    We characterize the dynamic nature of the lowest excited state in a pentacene/C60 complex on the femtosecond time scale, via a combination of ab initio molecular dynamics and time-dependent density functional theory. We analyze the correlations between the molecular vibrations of the complex and the oscillations in the electron-transfer character of its lowest excited state, which point to vibration-induced coherences between the (pentacene-based) local-excitation (LE) state and the complex charge-transfer (CT) state. We discuss the implications of our results on this model system for the exciton-dissociation process in organic solar cells.

  12. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  13. Cell module and fuel conditioner development

    Science.gov (United States)

    Feret, J. M.

    1982-01-01

    The efforts performed to develop a phosphoric acid fuel cell (PAFC) stack design having a 10 kW power rating for operation at higher than atmospheric pressure based on the existing Mark II design configuration are described. The work involves: (1) Performance of pertinent functional analysis, trade studies and thermodynamic cycle analysis for requirements definition and system operating parameter selection purposes, (2) characterization of fuel cell materials and components, and performance testing and evaluation of the repeating electrode components, (3) establishment of the state-of-the-art manufacturing technology for all fuel cell components at Westinghouse and the fabrication of short stacks of various sites, and (4) development of a 10 kW PAFC stack design for higher pressure operation utilizing the top down systems engineering approach.

  14. 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.

  15. 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.

  16. Solar cell junction temperature measurement of PV module

    KAUST Repository

    Huang, B.J.

    2011-02-01

    The present study develops a simple non-destructive method to measure the solar cell junction temperature of PV module. The PV module was put in the environmental chamber with precise temperature control to keep the solar PV module as well as the cell junction in thermal equilibrium with the chamber. The open-circuit voltage of PV module Voc is then measured using a short pulse of solar irradiation provided by a solar simulator. Repeating the measurements at different environment temperature (40-80°C) and solar irradiation S (200-1000W/m2), the correlation between the open-circuit voltage Voc, the junction temperature Tj, and solar irradiation S is derived.The fundamental correlation of the PV module is utilized for on-site monitoring of solar cell junction temperature using the measured Voc and S at a short time instant with open circuit. The junction temperature Tj is then determined using the measured S and Voc through the fundamental correlation. The outdoor test results show that the junction temperature measured using the present method, Tjo, is more accurate. The maximum error using the average surface temperature Tave as the junction temperature is 4.8 °C underestimation; while the maximum error using the present method is 1.3 °C underestimation. © 2010 Elsevier Ltd.

  17. Dual excitation multi-fluorescence flow cytometry for detailed analyses of viability and apoptotic cell transition

    Directory of Open Access Journals (Sweden)

    G Mazzini

    2009-06-01

    Full Text Available The discrimination of live/dead cells as well as the detection of apoptosis is a frequent need in many areas of experimental biology. Cell proliferation is linked to apoptosis and controlled by several genes. During the cell life, specific events can stimulate proliferation while others may trigger the apoptotic pathway. Very few methods (i.e. TUNEL are now available for studies aimed at correlation between apoptosis and proliferation. Therefore, there is interest in developing new methodological approaches that are able to correlate apoptosis to the cell cycle phases. Recently new approaches have been proposed to detect and enumerate apoptotic cells by flow cytometry. Among these, the most established and applied are those based on the cell membrane modifications induced in the early phases of the apoptotic process. The dye pair Hoechst 33342 (HO and Propidium Iodide (PI, thanks to their peculiar characteristics to be respectively permeable and impermeable to the intact cell membrane, seems to be very useful. Unfortunately the spectral interaction of these dyes generates a consistent “energy transfer” from HO to PI. The co-presence of the dyes in a nucleus results in a modification in the intensity of both the emitted fluorescences. In order to designate the damaged cells (red fluorescence to the specific cell cycle phases (blue fluorescence, we have tested different staining protocols aimed to minimize the interference of these dyes as much as possible. In cell culture models, we are able to detect serum-starved apoptotic cells as well as to designate their exact location in the cell cycle phases using a very low PI concentration. Using a Partec PAS flow cytometer equipped with HBO lamp and argon ion laser, a double UV/blue excitation has been performed. This analytical approach is able to discriminate live blue cells from the damaged (blue-red ones even at 0.05 ?g/mL PI. The same instrumental setting allows performing other multi

  18. Cell state switching factors and dynamical patterning modules ...

    Indian Academy of Sciences (India)

    2009-01-05

    Jan 5, 2009 ... Home; Journals; Journal of Biosciences; Volume 34; Issue 4. Cell state switching factors and dynamical patterning modules: complementary mediators of plasticity in development and evolution. Stuart A Newman Ramray Bhat Nadejda V Mezentseva. Articles Volume 34 Issue 4 October 2009 pp 553-572 ...

  19. Phosphatidylinositol 3 kinase modulation of trophoblast cell differentiation

    Directory of Open Access Journals (Sweden)

    Kent Lindsey N

    2010-09-01

    Full Text Available Abstract Background The trophoblast lineage arises as the first differentiation event during embryogenesis. Trophoblast giant cells are one of several end-stage products of trophoblast cell differentiation in rodents. These cells are located at the maternal-fetal interface and are capable of invasive and endocrine functions, which are necessary for successful pregnancy. Rcho-1 trophoblast stem cells can be effectively used as a model for investigating trophoblast cell differentiation. In this report, we evaluated the role of the phosphatidylinositol 3-kinase (PI3K signaling pathway in the regulation of trophoblast cell differentiation. Transcript profiles from trophoblast stem cells, differentiated trophoblast cells, and differentiated trophoblast cells following disruption of PI3K signaling were generated and characterized. Results Prominent changes in gene expression accompanied the differentiation of trophoblast stem cells. PI3K modulated the expression of a subset of trophoblast cell differentiation-dependent genes. Among the PI3K-responsive genes were those encoding proteins contributing to the invasive and endocrine phenotypes of trophoblast giant cells. Conclusions Genes have been identified with differential expression patterns associated with trophoblast stem cells and trophoblast cell differentiation; a subset of these genes are regulated by PI3K signaling, including those impacting the differentiated trophoblast giant cell phenotype.

  20. 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.

  1. Performance of Photovoltaic Modules of Different Solar Cells

    Directory of Open Access Journals (Sweden)

    Ankita Gaur

    2013-01-01

    Full Text Available In this paper, an attempt of performance evaluation of semitransparent and opaque photovoltaic (PV modules of different generation solar cells, having the maximum efficiencies reported in the literature at standard test conditions (STC, has been carried out particularly for the months of January and June. The outdoor performance is also evaluated for the commercially available semitransparent and opaque PV modules. Annual electrical energy, capitalized cost, annualized uniform cost (unacost, and cost per unit electrical energy for both types of solar modules, namely, semitransparent and opaque have also been computed along with their characteristics curves. Semitransparent PV modules have shown higher efficiencies compared to the opaque ones. Calculations show that for the PV modules made in laboratory, CdTe exhibits the maximum annual electrical energy generation resulting into minimum cost per unit electrical energy, whereas a-Si/nc-Si possesses the maximum annual electrical energy generation giving minimum cost per unit electrical energy when commercially available solar modules are concerned. CIGS has shown the lowest capitalized cost over all other PV technologies.

  2. 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.

  3. An excited-state intramolecular photon transfer fluorescence probe for localizable live cell imaging of cysteine

    Science.gov (United States)

    Liu, Wei; Chen, Wen; Liu, Si-Jia; Jiang, Jian-Hui

    2017-03-01

    Small molecule probes suitable for selective and specific fluorescence imaging of some important but low-concentration intracellular reactive sulfur species such as cysteine (Cys) pose a challenge in chemical biology. We present a readily available, fast-response fluorescence probe CHCQ-Ac, with 2-(5‧-chloro-2-hydroxyl-phenyl)-6-chloro-4(3 H)-quinazolinone (CHCQ) as the fluorophore and acrylate group as the functional moiety, that enables high-selectivity and high-sensitivity for detecting Cys in both solution and biological system. After specifically reacted with Cys, the probe undergoes a seven-membered intramolecular cyclization and released the fluorophore CHCQ with excited-state intramolecular photon transfer effect. A highly fluorescent, insoluble aggregate was then formed to facilitate high-sensitivity and high-resolution imaging. The results showed that probe CHCQ-Ac affords a remarkably large Stokes shift and can detect Cys under physiological pH condition with no interference from other analytes. Moreover, this probe was proved to have excellent chemical stability, low cytotoxicity and good cell permeability. Our design of this probe provides a novel potential tool to visualize and localize cysteine in bioimaging of live cells that would greatly help to explore various Cys-related physiological and pathological cellular processes in cell biology and diagnostics.

  4. Excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Kane, Christopher; Couch, Liam; Terracciano, Cesare M N

    2015-01-01

    Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold enormous potential in many fields of cardiovascular research. Overcoming many of the limitations of their embryonic counterparts, the application of iPSC-CMs ranges from facilitating investigation of familial cardiac disease and pharmacological toxicity screening to personalized medicine and autologous cardiac cell therapies. The main factor preventing the full realization of this potential is the limited maturity of iPSC-CMs, which display a number of substantial differences in comparison to adult cardiomyocytes. Excitation-contraction (EC) coupling, a fundamental property of cardiomyocytes, is often described in iPSC-CMs as being more analogous to neonatal than adult cardiomyocytes. With Ca(2+) handling linked, directly or indirectly, to almost all other properties of cardiomyocytes, a solid understanding of this process will be crucial to fully realizing the potential of this technology. Here, we discuss the implications of differences in EC coupling when considering the potential applications of human iPSC-CMs in a number of areas as well as detailing the current understanding of this fundamental process in these cells.

  5. Surface plasmon excitation using a Fourier-transform infrared spectrometer: Live cell and bacteria sensing

    Science.gov (United States)

    Lirtsman, Vladislav; Golosovsky, Michael; Davidov, Dan

    2017-10-01

    We report an accessory for beam collimation to be used as a plug-in for a conventional Fourier-Transform Infrared (FTIR) spectrometer. The beam collimator makes use of the built-in focusing mirror of the FTIR spectrometer which focuses the infrared beam onto the pinhole mounted in the place usually reserved for the sample. The beam is collimated by a small parabolic mirror and is redirected to the sample by a pair of plane mirrors. The reflected beam is conveyed by another pair of plane mirrors to the built-in detector of the FTIR spectrometer. This accessory is most useful for the surface plasmon excitation. We demonstrate how it can be employed for label-free and real-time sensing of dynamic processes in bacterial and live cell layers. In particular, by measuring the intensity of the CO2 absorption peak one can assess the cell layer metabolism, while by measuring the position of the surface plasmon resonance one assesses the cell layer morphology.

  6. Modulation of lens cell adhesion molecules by particle beams

    Science.gov (United States)

    McNamara, M. P.; Bjornstad, K. A.; Chang, P. Y.; Chou, W.; Lockett, S. J.; Blakely, E. A.

    2001-01-01

    Cell adhesion molecules (CAMs) are proteins which anchor cells to each other and to the extracellular matrix (ECM), but whose functions also include signal transduction, differentiation, and apoptosis. We are testing a hypothesis that particle radiations modulate CAM expression and this contributes to radiation-induced lens opacification. We observed dose-dependent changes in the expression of beta 1-integrin and ICAM-1 in exponentially-growing and confluent cells of a differentiating human lens epithelial cell model after exposure to particle beams. Human lens epithelial (HLE) cells, less than 10 passages after their initial culture from fetal tissue, were grown on bovine corneal endothelial cell-derived ECM in medium containing 15% fetal bovine serum and supplemented with 5 ng/ml basic fibroblast growth factor (FGF-2). Multiple cell populations at three different stages of differentiation were prepared for experiment: cells in exponential growth, and cells at 5 and 10 days post-confluence. The differentiation status of cells was characterized morphologically by digital image analysis, and biochemically by Western blotting using lens epithelial and fiber cell-specific markers. Cultures were irradiated with single doses (4, 8 or 12 Gy) of 55 MeV protons and, along with unirradiated control samples, were fixed using -20 degrees C methanol at 6 hours after exposure. Replicate experiments and similar experiments with helium ions are in progress. The intracellular localization of beta 1-integrin and ICAM-1 was detected by immunofluorescence using monoclonal antibodies specific for each CAM. Cells known to express each CAM were also processed as positive controls. Both exponentially-growing and confluent, differentiating cells demonstrated a dramatic proton-dose-dependent modulation (upregulation for exponential cells, downregulation for confluent cells) and a change in the intracellular distribution of the beta 1-integrin, compared to unirradiated controls. In contrast

  7. Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

    Directory of Open Access Journals (Sweden)

    Amy Llewellyn

    2017-10-01

    Full Text Available There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology.

  8. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation.

    Science.gov (United States)

    Burrello, Jacopo; Monticone, Silvia; Gai, Chiara; Gomez, Yonathan; Kholia, Sharad; Camussi, Giovanni

    2016-01-01

    Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.

  9. STEM CELL-DERIVED EXTRACELLULAR VESICLES AND IMMUNE-MODULATION

    Directory of Open Access Journals (Sweden)

    Jacopo Burrello

    2016-08-01

    Full Text Available Extra-cellular vesicles (EVs are bilayer membrane structures enriched with proteins, nucleic acids and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag-presenting cells for instance, have been involved in both innate and acquired (or adaptive immune responses, as Ag carriers or presenters, or as vehicles for delivering active signalling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response. Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review we will discuss how stem cell-derived EVs may contribute towards the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.

  10. 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.

  11. 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.

  12. Uremia modulates the phenotype of aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Madsen, Marie; Pedersen, Annemarie Aarup; Albinsson, Sebastian

    2017-01-01

    BACKGROUND AND AIMS: Chronic kidney disease leads to uremia and markedly accelerates atherosclerosis. Phenotypic modulation of smooth muscle cells (SMCs) in the arterial media plays a key role in accelerating atherogenesis. The aim of this study was to investigate whether uremia per se modulates...... the phenotype of aortic SMCs in vivo. METHODS: Moderate uremia was induced by 5/6 nephrectomy in apolipoprotein E knockout (ApoE(-/-)) and wildtype C57Bl/6 mice. Plasma analysis, gene expression, histology, and myography were used to determine uremia-mediated changes in the arterial wall. RESULTS: Induction...... in the aortic media. In the aortic arch, mRNA and miRNA expression patterns were consistent with a uremia-mediated phenotypic modulation of SMCs; e.g. downregulation of myocardin, α-smooth muscle actin, and transgelin; and upregulation of miR146a. Notably, these expression patterns were observed after acute (2...

  13. New test and characterization methods for PV modules and cells

    Energy Technology Data Exchange (ETDEWEB)

    Van Aken, B.; Sommeling, P. [ECN Solar Energy, Petten (Netherlands); Scholten, H. [Solland, Heerlen (Netherlands); Muller, J. [Moser-Baer, Eindhoven (Netherlands); Grossiord, N. [Holst Centre, Eindhoven (Netherlands); Smits, C.; Blanco Mantecon, M. [Holland Innovative, Eindhoven (Netherlands); Verheijen, M.; Van Berkum, J. [Philips Innovation Services, Eindhoven (Netherlands)

    2012-08-15

    The results of the project geZONd (shared facility for solar module analysis and reliability testing) are described. The project was set up by Philips, ECN, Holst, Solland, OM and T and Holland Innovative. The partners have shared most of their testing and analysis equipment for PV modules and cells, and together developed new or improved methods (including the necessary application know-how). This enables faster and more efficient innovation projects for each partner, and via commercial exploitation for other interested parties. The project has concentrated on five failure modes: corrosion, delamination, moisture ingress, UV irradiation, and mechanical bending. Test samples represented all main PV technologies: wafer based PV and rigid and flexible thin-film PV. Breakthroughs are in very early detection of corrosion, in quantitative characterization of adhesion, in-situ detection of humidity and oxygen inside modules, and ultra-fast screening of materials on UV stability.

  14. Enhanced multi-spectral imaging of live breast cancer cells using immunotargeted gold nanoshells and two-photon excitation microscopy

    Science.gov (United States)

    Bickford, Lissett; Sun, Jiantang; Fu, Kun; Lewinski, Nastassja; Nammalvar, Vengadesan; Chang, Joseph; Drezek, Rebekah

    2008-08-01

    We demonstrate the capability of using immunotargeted gold nanoshells as contrast agents for in vitro two-photon microscopy. The two-photon luminescence properties of different-sized gold nanoshells are first validated using near-infrared excitation at 780 nm. The utility of two-photon microscopy as a tool for imaging live HER2-overexpressing breast cancer cells labeled with anti-HER2-conjugated nanoshells is then explored and imaging results are compared to normal breast cells. Five different imaging channels are simultaneously examined within the emission wavelength range of 451-644 nm. Our results indicate that under near-infrared excitation, superior contrast of SK-BR-3 cancer cells labeled with immunotargeted nanoshells occurs at an emission wavelength ranging from 590 to 644 nm. Luminescence from labeled normal breast cells and autofluorescence from unlabeled cancer and normal cells remain imperceptible under the same conditions.

  15. Enhanced multi-spectral imaging of live breast cancer cells using immunotargeted gold nanoshells and two-photon excitation microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Bickford, Lissett; Sun Jiantang; Fu, Kun; Lewinski, Nastassja; Nammalvar, Vengadesan; Chang, Joseph; Drezek, Rebekah [Department of Bioengineering, Rice University, Houston, TX 77005 (United States)], E-mail: drezek@rice.edu

    2008-08-06

    We demonstrate the capability of using immunotargeted gold nanoshells as contrast agents for in vitro two-photon microscopy. The two-photon luminescence properties of different-sized gold nanoshells are first validated using near-infrared excitation at 780 nm. The utility of two-photon microscopy as a tool for imaging live HER2-overexpressing breast cancer cells labeled with anti-HER2-conjugated nanoshells is then explored and imaging results are compared to normal breast cells. Five different imaging channels are simultaneously examined within the emission wavelength range of 451-644 nm. Our results indicate that under near-infrared excitation, superior contrast of SK-BR-3 cancer cells labeled with immunotargeted nanoshells occurs at an emission wavelength ranging from 590 to 644 nm. Luminescence from labeled normal breast cells and autofluorescence from unlabeled cancer and normal cells remain imperceptible under the same conditions.

  16. Comparison of photovoltaic cell temperatures in modules operating with exposed and enclosed back surfaces

    Science.gov (United States)

    Namkoong, D.; Simon, F. F.

    1981-01-01

    Four different photovoltaic module designs were tested to determine the cell temperature of each design. The cell temperatures were compared to those obtained on identical design, using the same nominal operating cell temperature (NOCT) concept. The results showed that the NOCT procedure does not apply to the enclosed configurations due to continuous transient conditions. The enclosed modules had higher cell temperatures than the open modules, and insulated modules higher than the uninsulated. The severest performance loss - when translated from cell temperatures - 17.5 % for one enclosed, insulated module as a compared to that module mounted openly.

  17. A New Method To Evaluate Excited States Lifetimes Based on Green's Function: Application to Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Sulzer, David; Iuchi, Satoru; Yasuda, Koji

    2016-07-12

    Dye-sensitized solar cell (DSSCs) are the promising device for electricity generation. However, the initial stage in which an electron is injected from a dye to the semiconductor has not been precisely understood. Standard quantum chemistry methods cannot handle infinite number of orbitals coming from the band structure of the semiconductor, whereas solid state calculations cannot handle many excited states at a reasonable computational cost. In this regard, we propose a new method to evaluate lifetimes of many excited states of a molecule on a semi-infinite surface. On the basis of the theory of resonance state, the effect of the semi-infinite semiconductor is encoded into the complex self-energy from surface Green's function. The lifetimes of excited states are evaluated through the imaginary part of the self-energy, and the self-energy correction is included into excitation energies obtained from time-dependent density functional theory calculations. This new method is applied to a DSSC system composed of black dye attached to the TiO2 semiconductor, and the computed lifetimes are linked to the natures of excited states and to the surface properties. The present method provides the firm ground for analysis of interplay between many excited states of the dye and band structure of the semiconductor.

  18. Diagnosis of basal cell carcinoma by two photon excited fluorescence combined with lifetime imaging

    Science.gov (United States)

    Fan, Shunping; Peng, Xiao; Liu, Lixin; Liu, Shaoxiong; Lu, Yuan; Qu, Junle

    2014-02-01

    Basal cell carcinoma (BCC) is the most common type of human skin cancer. The traditional diagnostic procedure of BCC is histological examination with haematoxylin and eosin staining of the tissue biopsy. In order to reduce complexity of the diagnosis procedure, a number of noninvasive optical methods have been applied in skin examination, for example, multiphoton tomography (MPT) and fluorescence lifetime imaging microscopy (FLIM). In this study, we explored two-photon optical tomography of human skin specimens using two-photon excited autofluorescence imaging and FLIM. There are a number of naturally endogenous fluorophores in skin sample, such as keratin, melanin, collagen, elastin, flavin and porphyrin. Confocal microscopy was used to obtain structures of the sample. Properties of epidermic and cancer cells were characterized by fluorescence emission spectra, as well as fluorescence lifetime imaging. Our results show that two-photon autofluorescence lifetime imaging can provide accurate optical biopsies with subcellular resolution and is potentially a quantitative optical diagnostic method in skin cancer diagnosis.

  19. B cells as a target of immune modulation

    Directory of Open Access Journals (Sweden)

    Hawker Kathleen

    2009-01-01

    Full Text Available B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts. MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell-targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.

  20. CdTe Thin Film Solar Cells and Modules Tutorial; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Albin, David S.

    2015-06-13

    This is a tutorial presented at the 42nd IEEE Photovoltaics Specialists Conference to cover the introduction, background, and updates on CdTe cell and module technology, including CdTe cell and module structure and fabrication.

  1. Extracellular matrix type modulates cell migration on mechanical gradients.

    Science.gov (United States)

    Hartman, Christopher D; Isenberg, Brett C; Chua, Samantha G; Wong, Joyce Y

    2017-10-15

    Extracellular matrix composition and stiffness are known to be critical determinants of cell behavior, modulating processes including differentiation, traction generation, and migration. Recent studies have demonstrated that the ECM composition can modulate how cells migrate in response to gradients in environmental stiffness, altering a cell's ability to undergo durotaxis. These observations were limited to single varieties of extracellular matrix, but typically cells are exposed to environments containing complex mixtures of extracellular matrix proteins. Here, we investigate migration of NIH 3T3 fibroblasts on mechanical gradients coated with one or more type of extracellular matrix protein. Our results show that NIH 3T3 fibroblasts exhibit durotaxis on fibronectin-coated mechanical gradients but not on those coated with laminin, demonstrating that extracellular matrix type can act as a regulator of cell response to mechanical gradients. Interestingly, NIH 3T3 fibroblasts were also observed to migrate randomly on gradients coated with a mixture of both fibronectin and laminin, suggesting that there may be a complex interplay in the cellular response to mechanical gradients in the presence of multiple extracellular matrix signals. These findings indicate that specific composition of available adhesion ligands is a critical determinant of a cell's migratory response to mechanical gradients. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Multi-busbar solar cells and modules : high efficiencies and low silver consumption

    OpenAIRE

    Braun, Stefan; Hahn, Giso; Nissler, Robin; Pönisch, Christoph; Habermann, Dirk

    2013-01-01

    Ideally, future photovoltaic modules show higher power output without increasing costs during cell production or module interconnection. Today significant losses occur during stringing the cells in a module by using standard 3- busbar technology. In this paper an elegant approach for a front side design is discussed by using more busbars than the widely used 3-busbar design for the solar cell front electrode. Simulations demonstrated that the multi-busbar design allows higher cell and module ...

  3. Mesenchymal Stem Cell-Dependent Modulation of Liver Diseases.

    Science.gov (United States)

    Gazdic, Marina; Arsenijevic, Aleksandar; Markovic, Bojana Simovic; Volarevic, Ana; Dimova, Ivanka; Djonov, Valentin; Arsenijevic, Nebojsa; Stojkovic, Miodrag; Volarevic, Vladislav

    2017-01-01

    Acute liver failure and cirrhosis display sequential and overlapping severe pathogenic processes that include inflammation, hepatocyte necrosis, and fibrosis, carrying a high mortality rate. Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells with immunonodulatory characteristics. MSCs are considered to act through multiple mechanisms to coordinate a dynamic, integrated response to liver inflammation and fibrosis, which prevents the progressive distortion of hepatic architecture. Accordingly, MSCs as well as their products have been investigated as a novel therapeutic approach for the treatment of inflammatory and fibrotic liver diseases. In this review, we highlight the current findings on the MSC-based modulation of liver inflammation and fibrosis, and the possible use of MSCs in the therapy of immune-mediated liver pathology. We briefly describe the cellular and molecular mechanisms involved in MSC-dependent modulation of cytokine production, phenotype and function of liver infiltrated inflammatory cells and compare effects of engrafted MSCs versus MSC-generated conditioned medium (MSC-CM) in the therapy of acute liver injury. In order to elucidate therapeutic potential of MSCs and their products in modulation of chronic liver inflammation and fibrosis, we present the current findings regarding pathogenic role of immune cells in liver fibrosis and describe mechanisms involved in MSC-dependent modulation of chronic liver inflammation with the brief overview of on-going and already published clinical trials that used MSCs for the treatment of immune mediated chronic liver diseases. The accumulating evidence shows that MSCs had a significant beneficial effect in the treatment of immune-mediated liver diseases.

  4. Hepatocyte growth factor-modulated rat Leydig cell functions.

    Science.gov (United States)

    Del Bravo, Jessica; Catizone, Angela; Ricci, Giulia; Galdieri, Michela

    2007-01-01

    Hepatocyte growth factor (HGF) regulates many cellular functions acting through c-Met, its specific tyrosine kinase receptor. We previously reported that in prepuberal rats HGF is secreted by the peritubular myoid cells during the entire postnatal testicular development and by the Sertoli cells only at puberty. We have also demonstrated that germ cells at different stages of development express c-Met and that HGF modulates germ cell proliferation and apoptosis. In the present article, we extend our study to the interstitial compartment of the testis and demonstrate that the c-Met protein is present on Leydig cells. The receptor is functionally active as demonstrated by the detected effects of HGF. We report in this article that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The antiapoptotic effect of HGF is mediated by caspase-3 activity because the amount of the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However, treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. These data indicate that HGF regulates the functional activities of Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF in cultured explants of testicular tissues as well as the antiapoptotic effect of HGF. Therefore, our data indicate that HGF has a crucial role in the regulation of male fertility.

  5. Micropatterned Azopolymer Surfaces Modulate Cell Mechanics and Cytoskeleton Structure.

    Science.gov (United States)

    Rianna, Carmela; Ventre, Maurizio; Cavalli, Silvia; Radmacher, Manfred; Netti, Paolo A

    2015-09-30

    Physical and chemical characteristics of materials are important regulators of cell behavior. In particular, cell elasticity is a fundamental parameter that reflects the state of a cell. Surface topography finely modulates cell fate and function via adhesion mediated signaling and cytoskeleton generated forces. However, how topographies alter cell mechanics is still unclear. In this work we have analyzed the mechanical properties of peripheral and nuclear regions of NIH-3T3 cells on azopolymer substrates with different topographic patterns. Micrometer scale patterns in the form of parallel ridges or square lattices of surface elevations were encoded on light responsive azopolymer films by means of contactless optical methods. Cell mechanics was investigated by atomic force microscopy (AFM). Cells and consequently the cell cytoskeleton were oriented along the linear patterns affecting cytoskeletal structures, e.g., formation of actin stress fibers. Our data demonstrate that topographic substrate patterns are recognized by cells and mechanical information is transferred by the cytoskeleton. Furthermore, cytoskeleton generated forces deform the nucleus, changing its morphology that appears to be related to different mechanical properties in the nuclear region.

  6. History-dependent excitability as a single-cell substrate of transient memory for information discrimination.

    Directory of Open Access Journals (Sweden)

    Fabiano Baroni

    Full Text Available Neurons react differently to incoming stimuli depending upon their previous history of stimulation. This property can be considered as a single-cell substrate for transient memory, or context-dependent information processing: depending upon the current context that the neuron "sees" through the subset of the network impinging on it in the immediate past, the same synaptic event can evoke a postsynaptic spike or just a subthreshold depolarization. We propose a formal definition of History-Dependent Excitability (HDE as a measure of the propensity to firing in any moment in time, linking the subthreshold history-dependent dynamics with spike generation. This definition allows the quantitative assessment of the intrinsic memory for different single-neuron dynamics and input statistics. We illustrate the concept of HDE by considering two general dynamical mechanisms: the passive behavior of an Integrate and Fire (IF neuron, and the inductive behavior of a Generalized Integrate and Fire (GIF neuron with subthreshold damped oscillations. This framework allows us to characterize the sensitivity of different model neurons to the detailed temporal structure of incoming stimuli. While a neuron with intrinsic oscillations discriminates equally well between input trains with the same or different frequency, a passive neuron discriminates better between inputs with different frequencies. This suggests that passive neurons are better suited to rate-based computation, while neurons with subthreshold oscillations are advantageous in a temporal coding scheme. We also address the influence of intrinsic properties in single-cell processing as a function of input statistics, and show that intrinsic oscillations enhance discrimination sensitivity at high input rates. Finally, we discuss how the recognition of these cell-specific discrimination properties might further our understanding of neuronal network computations and their relationships to the distribution and

  7. 77 FR 14732 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-03-13

    ... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... of crystalline silicon photovoltaic cells, whether or not assembled into modules, from the People's.... \\1\\ See Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the...

  8. 77 FR 72884 - Crystalline Silicon Photovoltaic Cells and Modules From China

    Science.gov (United States)

    2012-12-06

    ... COMMISSION Crystalline Silicon Photovoltaic Cells and Modules From China Determinations On the basis of the... reason of imports of crystalline silicon photovoltaic cells and modules from China, provided for in... silicon photovoltaic cells and modules from China. Chairman Irving A. Williamson and Commissioner Dean A...

  9. 76 FR 81914 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2011-12-29

    ... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... photovoltaic cells, whether or not assembled into modules, from the People's Republic of China.\\1\\ Currently... Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's Republic of China: Initiation of...

  10. 77 FR 4764 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-01-31

    ... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... duty investigation of crystalline silicon photovoltaic cells, whether or not assembled into modules... Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's Republic of China: Postponement of...

  11. 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

  12. Immune modules shared by innate lymphoid cells and T cells.

    Science.gov (United States)

    Robinette, Michelle L; Colonna, Marco

    2016-11-01

    In recent years, innate lymphoid cells (ILCs) have emerged as innate correlates to T cells. The similarities between ILCs and T cells indicate that lymphocytes of fundamentally distinct lineages can share core "immune modules" that encompass transcriptional circuitry and effector functions while using nonredundant complementary mechanisms of pattern recognition to enact these functions. We review modules currently recognized to be shared between ILCs and T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Modulation of Cell-Cell Junctional Complexes by Matrix Metalloproteinases

    OpenAIRE

    Bartlett, J. D.; Smith, C. E.

    2013-01-01

    The ameloblast cell layer of the enamel organ is in contact with the forming enamel as it develops into the hardest substance in the body. Ameloblasts move in groups that slide by one another as the enamel layer thickens. Each ameloblast is responsible for the formation of one enamel rod, and the rods are the mineralized trail that moving ameloblasts leave behind. Matrix metalloproteinases (MMPs) facilitate cell movement in various tissues during development, and in this review we suggest tha...

  14. 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.

  15. Retinoid modulation of plasminogen activator production in rat Sertoli cells.

    Science.gov (United States)

    Canipari, R; Galdieri, M

    2000-08-01

    Tissue type (t) and urokinase type (u) plasminogen activators (PAs) have been shown to be secreted by Sertoli cells in the seminiferous tubules in a cyclic fashion and to be dependent upon FSH stimulation or upon the presence of adjacent spermatogenic cells. In the present study we have analyzed the production of PAs by retinoid-treated rat Sertoli cells. In addition, because retinoids modulate the response of Sertoli cells to FSH either potentiating or antagonizing its action, we have investigated a possible modulation of FSH-stimulated PA production. Under basal conditions, Sertoli cells, isolated from prepubertal rats, secrete predominantly uPA. A significant dose-dependent inhibition of uPA activity was observed after treatment with retinol, while no significant effect was detected upon tPA secretion. When Sertoli cells were cultured in the presence of 0.25 microM retinol, a significant inhibition of uPA activity was evident after 16 h of treatment and reached approximately 80% after 48 h of treatment. The analysis of the mRNA levels revealed that retinol induces an inhibition of the steady-state levels of uPA mRNA without affecting those of tPA. Moreover, retinol affected uPA mRNA levels by increasing mRNA turnover. The effect of retinoids on Sertoli cells isolated from older animals was less evident, possibly due to the reduced production of uPA with the increase of age of the donor animals. Our results on the effect of retinoids upon Sertoli cell uPA production reinforce the importance of retinoids in the control of postnatal testis development.

  16. Modulation of Cell-Cell Junctional Complexes by Matrix Metalloproteinases

    Science.gov (United States)

    Bartlett, J.D.; Smith, C.E.

    2013-01-01

    The ameloblast cell layer of the enamel organ is in contact with the forming enamel as it develops into the hardest substance in the body. Ameloblasts move in groups that slide by one another as the enamel layer thickens. Each ameloblast is responsible for the formation of one enamel rod, and the rods are the mineralized trail that moving ameloblasts leave behind. Matrix metalloproteinases (MMPs) facilitate cell movement in various tissues during development, and in this review we suggest that the tooth-specific MMP, enamelysin (MMP20), facilitates ameloblast movements during enamel development. Mmp20 null mice have thin brittle enamel with disrupted rod patterns that easily abrades from the underlying dentin. Strikingly, the Mmp20 null mouse enamel organ morphology is noticeably dysplastic during late-stage development, when MMP20 is no longer expressed. We suggest that in addition to its role of cleaving enamel matrix proteins, MMP20 also cleaves junctional complexes present on ameloblasts to foster the cell movement necessary for formation of the decussating enamel rod pattern. Therefore, inactivation of MMP20 would result in tight ameloblast cell-cell attachments that may cause maturation-stage enamel organ dysplasia. The tight ameloblast attachments would also preclude the ameloblast movement necessary to form decussating enamel rod patterns. PMID:23053846

  17. Frame-less solar cell module; Furemuresu taiyo denchi mojuru

    Energy Technology Data Exchange (ETDEWEB)

    Morishima, S.; Kasahara, A. [MSK Co. Ltd., Tokyo (Japan)

    1997-12-22

    The invented frame-less solar cell module is constructed in the following way: Thin film solar cell layer is formed on one side of the first transparent substrate, and the whole surface of the thin film solar cell layer is covered with insulator layer. The other side of the first transparent substrate faces to the insulator layer. The second transparent substrate which has the same size as the first transparent substrate adheres to the first substrate with synthetic resin adhesives. With this structure, even if water comes in the solar cell from the joint part of the two transparent substrates, it does not contact directly with the solar cell layer because the thin film solar cell layer is covered with the insulator layer. Since the light incidence side is the first transparent substrate side on which the thin film solar cell layer is formed, the electrode positioning on the insulator layer side makes the backside electrode. So that the electrode can be constructed with light shielding material like aluminum. Even when water comes into the cell from edge surface and penetrates into the clearance between the insulator layer and synthetic resin layer, or between the synthetic resin layer and the second transparent substrate, no change takes place in appearance and color on the light receiving side. 6 figs.

  18. Cancer Cell Metabolism and the Modulating Effects of Nitric Oxide

    Science.gov (United States)

    Chang, Ching-Fang; Diers, Anne R.; Hogg, Neil

    2016-01-01

    Altered metabolic phenotype has been recognized as a hallmark of tumor cells for many years, but this aspect of the cancer phenotype has come into greater focus in recent years. NOS2 (inducible nitric oxide synthase of iNOS) has been implicated as a component in many aggressive tumor phenotypes, including melanoma, glioblastoma and breast cancer. Nitric oxide has been well established as a modulator of cellular bioenergetics pathways, in many ways similar to the alteration of cellular metabolism observed in aggressive tumors. In this review we attempt to bring these concepts together with the general hypothesis that one function of NOS2 and NO in cancer is to modulate metabolic processes to facilitate increased tumor aggression. There are many mechanisms by which NO can modulate tumor metabolism, including direct inhibition of respiration, alterations in mitochondrial mass, oxidative inhibition of bioenergetic enzymes, and the stimulation of secondary signaling pathways. Here we review metabolic alterations in the context of cancer cells and discuss the role of NO as a potential mediator of these changes. PMID:25464273

  19. 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.

  20. 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.

  1. Solar cells and modules from dentritic web silicon

    Science.gov (United States)

    Campbell, R. B.; Rohatgi, A.; Seman, E. J.; Davis, J. R.; Rai-Choudhury, P.; Gallagher, B. D.

    1980-01-01

    Some of the noteworthy features of the processes developed in the fabrication of solar cell modules are the handling of long lengths of web, the use of cost effective dip coating of photoresist and antireflection coatings, selective electroplating of the grid pattern and ultrasonic bonding of the cell interconnect. Data on the cells is obtained by means of dark I-V analysis and deep level transient spectroscopy. A histogram of over 100 dentritic web solar cells fabricated in a number of runs using different web crystals shows an average efficiency of over 13%, with some efficiencies running above 15%. Lower cell efficiency is generally associated with low minority carrier time due to recombination centers sometimes present in the bulk silicon. A cost analysis of the process sequence using a 25 MW production line indicates a selling price of $0.75/peak watt in 1986. It is concluded that the efficiency of dentritic web cells approaches that of float zone silicon cells, reduced somewhat by the lower bulk lifetime of the former.

  2. 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

  3. THP-1 cell line: an in vitro cell model for immune-modulation approach : Review

    NARCIS (Netherlands)

    Chanput, W.; Mes, J.J.; Wichers, H.J.

    2014-01-01

    THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. This cell line has become a common model to estimate modulation of monocyte and macrophage activities. This review

  4. Endothelin-1 Activates MAPKs and Modulates Cell Cycle Proteins in OKP Cells

    Directory of Open Access Journals (Sweden)

    Tzong-Shinn Chu

    2007-01-01

    Conclusion: Binding of ET-1 to the ETB receptor of ETB-overexpressing OKP cells is proposed to signal proliferation of these cells through rapid activation of mitogen-activated protein kinases, increased c-jun expression, modulation of cyclin D1 activity, and increased RB phosphorylation. [J Formos Med Assoc 2007;106(4:273-280

  5. Modulation of Acupuncture on Cell Apoptosis and Autophagy

    Directory of Open Access Journals (Sweden)

    Dan Luo

    2017-01-01

    Full Text Available Acupuncture has been historically practiced to treat medical disorders by mechanically stimulating specific acupoints. Despite its well-documented efficacy, its biological basis largely remains elusive. Recent studies suggested that cell apoptosis and autophagy might play key roles in acupuncture therapy. Therefore, we searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI, aiming to find the potential relationship between acupuncture and cell apoptosis and autophagy. To provide readers with objective evidence, some problems regarding the design method, acupoints selection, acupuncture intervention measure, and related diseases existing in 40 related researches were shown in this review. These findings demonstrated that acupuncture has a potential role in modulating cell apoptosis and autophagy in animal models, suggesting it as a candidate mechanism in acupuncture therapy to maintain physiologic homeostasis.

  6. 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

  7. 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

  8. Tracking of mercury ions in living cells with a fluorescent chemodosimeter under single- or two-photon excitation

    Energy Technology Data Exchange (ETDEWEB)

    Lu Zhoujun [State Key Lab for Advanced Photonic Materials and Devices, Department of Optical Science and Engineering, Fudan University, Shanghai 200433 (China); Wang Peinan [State Key Lab for Advanced Photonic Materials and Devices, Department of Optical Science and Engineering, Fudan University, Shanghai 200433 (China)], E-mail: pnwang@fudan.edu.cn; Zhang Yu [State Key Lab for Advanced Photonic Materials and Devices, Department of Optical Science and Engineering, Fudan University, Shanghai 200433 (China); Chen Jiyao; Zhen Shen [Department of Physics, Fudan University, Shanghai 200433 (China); Leng Bing; Tian He [Labs for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237 (China)

    2007-08-10

    Tracking of Hg{sup 2+} in solutions as well as in living cells was conducted with a fluorescent chemodosimeter by measuring the spectral shift of its fluorescence under single- or two-photon excitation. The spectral hypsochromic shifts of this chemodosimeter when reacting with Hg{sup 2+} were found to be about 50 nm in acetonitrile/water solutions and 32 nm in Euglena gracilis 277 living cells. This chemodosimeter shows high sensitivity and selectivity, and is not influenced by the pH values. It can signal Hg{sup 2+} in solutions down to the ppb range under either single-photon excitation (SPE) at 405 nm or two-photon excitation (TPE) at 800 nm. However, with low cellular chemodosimeter concentrations, the SPE spectra were disturbed by the auto-fluorescence from the native fluorophore in the cell, while the TPE spectra were still of high quality since the two-photon absorption cross section of this chemodosimeter is much larger than that of the native fluorophores in the cell.

  9. Calcitriol Modulates the CD46 Pathway in T Cells

    Science.gov (United States)

    Kickler, Karoline; Ni Choileain, Siobhan; Williams, Anna; Richards, Anna; Astier, Anne L.

    2012-01-01

    The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D3 or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNγ ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS. PMID:23144765

  10. Display of Cell Surface Sites for Fibronectin Assembly Is Modulated by Cell Adherence to 1F3 and C-Terminal Modules of Fibronectin

    OpenAIRE

    Jielin Xu; Eunnyung Bae; Qinghong Zhang; Annis, Douglas S.; Erickson, Harold P.; Mosher, Deane F.

    2009-01-01

    BACKGROUND: Fibronectin-null cells assemble soluble fibronectin shortly after adherence to a substrate coated with intact fibronectin but not when adherent to the cell-binding domain of fibronectin (modules (7)F3-(10)F3). Interactions of adherent cells with regions of adsorbed fibronectin other than modules (7)F3-(10)F3, therefore, are required for early display of the cell surface sites that initiate and direct fibronectin assembly. METHODOLOGY/PRINCIPAL FINDINGS: To identify these regions, ...

  11. Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation.

    Science.gov (United States)

    Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

    2017-06-27

    Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram.

  12. Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation

    Science.gov (United States)

    Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

    2017-01-01

    Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram. PMID:28467792

  13. Hepatocyte growth factor (HGF) modulates Leydig cell extracellular matrix components.

    Science.gov (United States)

    Catizone, A; Ricci, G; Tufano, M A; Perfetto, B; Canipari, R; Galdieri, M

    2010-01-01

    Hepatocyte growth factor (HGF) is a pleiotropic factor that plays multiple roles during mammalian development. We previously demonstrated that in the postnatal testes, the HGF receptor, c-met, is expressed by Leydig cells and HGF increases the steroidogenetic activity of the cells. In the present article, we report that HGF modifies the composition of the extracellular matrix of cultured Leydig cells. We show that HGF increases the metabolic activity of isolated Leydig cells; in particular, the factor increases urokinase plasminogen activator and matrix metalloproteinase 2 secretion. We have also shown that the levels of active transforming growth factor beta are increased by HGF. On the contrary, using the Western blotting technique, a strong reduction in the amount of fibronectin present in the culture medium of cells cultured in the presence of HGF has been detected. The presented data demonstrate that HGF modulates several functional activities of Leydig cells, further supporting the hypothesis that this factor has a relevant role in the regulation of mammalian spermatogenesis.

  14. Methylene blue modulates adhesion molecule expression on microvascular endothelial cells.

    Science.gov (United States)

    Werner, Isabella; Guo, Fengwei; Stock, Ulrich A; Lupinski, Michèle; Meybohm, Patrick; Moritz, Anton; Beiras-Fernandez, Andres

    2014-08-01

    As methylene blue (MB) has been recently proposed to preserve blood pressure in case of vasoplegic syndrome and shock, an entity directly related to systemic inflammation, we aimed to elucidate the effect of MB on the expression of adhesion-molecules in endothelial-cells. Human microvascular endothelial-cells (HuMEC-1) were treated with 10, 30 or 60 µM MB for 30 min and 2 h each. Additionally, the treated HuMEC-1 were co-cultured with either human peripheral blood mononuclear cells (PBMCs) or Jurkat cells (human T-lymphocytes) for 2 h. HuMEC-1 were analyzed after MB treatment and after co-culture experiments for expression of different adhesion-molecules (ICAM-1, VCAM-1, L-selectin, E-selectin) via FACS measurement and western blot analysis. The supernatants of the experiments were analyzed with regard to the soluble forms of the adhesion molecules. We found that MB is able to modulate the expression of adhesion-molecules on EC. Administration of MB increases the expression of E-selectin and VCAM-1 depending on the dosage and time of exposure. ICAM-1 measurements provide evidence that different circulating blood cells can differently alter the adhesion-molecule expression on EC after MB exposure. Our results provide evidence regarding the immunomodulatory effect of MB upon endothelial-cells after inflammation.

  15. Below-Gap Excitation of π-Conjugated Polymer-Fullerene Blends: Implications for Bulk Organic Heterojunction Solar Cells

    Science.gov (United States)

    Drori, T.; Sheng, C.-X.; Ndobe, A.; Singh, S.; Holt, J.; Vardeny, Z. V.

    2008-07-01

    We used a variety of optoelectronic techniques such as broadband fs transient and cw photomodulation spectroscopies, electroabsorption, and short-circuit photocurrent in bulk heterojunctions organic solar cells for studying the photophysics in π-conjugated polymer-fullerene blends with below-gap excitation. In contrast to the traditional view, we found that below-gap excitation, which is incapable of generating intrachain excitons, nevertheless efficiently generates polarons on the polymer chains and fullerene molecules. The polaron action spectrum extends deep inside the gap as a result of a charge-transfer complex state formed between the polymer chain and fullerene molecule. With appropriate design engineering the long-lived polarons might be harvested in solar cell devices.

  16. Enhancing the power conversion efficiency of dye-sensitized solar cells via molecular plasmon-like excitations.

    Science.gov (United States)

    Li, Jian-Hao; Gryn'ova, Ganna; Prlj, Antonio; Corminboeuf, Clémence

    2017-02-21

    We introduce a tactic for employing molecular plasmon-like excitations to enhance solar-to-electric power conversion efficiency of dye-sensitized solar cells. We offer general design principles of dimeric dyes, in which a strong plasmonic interaction between two π-conjugated moieties is promoted. The π-stacked conformations of these dimeric dyes result in a desirable broadened absorption and a longer absorption onset wavelength.

  17. 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.

  18. NK cells and their ability to modulate T cells during virus infections.

    Science.gov (United States)

    Cook, Kevin D; Waggoner, Stephen N; Whitmire, Jason K

    2014-01-01

    Natural killer (NK) cells are important in protection against virus infections, and many viruses have evolved mechanisms to thwart NK cell activity. NK cells respond to inflammatory signals at an early stage of virus infection, resulting in proliferation, cytokine production, and cytolytic activity that can reduce virus loads. Moreover, the rapid kinetics of the NK cell response enables NK cells to influence other populations of innate immune cells, affect the inflammatory milieu, and guide adaptive immune responses to infection. Early NK cell interactions with other leukocytes can have long-lasting effects on the number and quality of memory T cells, as well as impact the exhaustion of T cells during chronic infections. The ability of NK cells to modulate T cell responses can be mediated through direct T-NK interactions, cytokine production, or indirectly through dendritic cells and other cell types. Herein, we summarize our current understanding of how NK cells interact with T cells, dendritic cells, B cells, and other cell types involved in adaptive immune responses to virus infection. We outline several mechanisms by which NK cells enhance or suppress adaptive immune response and long-lived immunological memory.

  19. Investigation of Cu-doping effects in CdTe solar cells by junction photoluminescence with various excitation wavelengths

    Science.gov (United States)

    Okamoto, Tamotsu; Shiina, Yasuyoshi; Okamoto, Shota

    2017-08-01

    Cu-doping effects and a CdS x Te1- x mixed crystal layer in CdS/CdTe solar cells were investigated on the basis of the photoluminescence (PL) of the CdS/CdTe junction using excitation lights incident on the glass substrate side (junction PL) with various excitation wavelengths. In the Cu-doped CdS/CdTe solar cells, broad emissions at 910-950 nm, which were probably caused by donor-acceptor pair (DAP) emission between CuCd acceptors and ClTe donors, were observed. The intensity of the junction PL markedly increased owing to the Cu doping. This result suggests that the intensity of junction PL is relevant to the conversion efficiency of CdTe solar cells. Furthermore, the PL peak energy increased with increasing excitation wavelength. This result indicates that the CdS x Te1- x mixed crystal layer is formed in the CdS/CdTe interface, and that the S composition decreased from the CdS/CdTe interface to the rear.

  20. From Cell to Module: Fabrication and Long-term Stability of Dye-sensitized Solar Cells

    Science.gov (United States)

    Nursam, N. M.; Hidayat, J.; Muliani, L.; Anggraeni, P. N.; Retnaningsih, L.; Idayanti, N.

    2017-07-01

    Dye-sensitized solar cell (DSSC), which has been firstly developed by Graetzel et al back in 1991, has attracted a considerable interest since its discovery. However, two of the main challenges that the DSSC technology will have to overcome towards commercialization involve device scale-up and long-term stability. In our group, the fabrication technology of DSSC has been developed from laboratory to module scale over the past few years, nevertheless, the long-term stability has still became a major concern. In this contribution, the long-term DSSC performance in relation to their scale-up from cell to module is investigated. The photoelectrode of the DSSCs were fabricated using nanocrystalline titanium dioxide materials that were subsequently sensitized using ruthenium-based dye. Additionally, TiCl4 pre- and post-treatment were carried out to enhance the overall device efficiency. When fabricated as cells, the DSSC prototypes showed relatively stable performance during repeated tests over three months. In order to increase the output power of the solar cells, the DSSCs were then connected in a Z-type series connection to obtain sub-module panels. The DSSC sub-modules exhibit poor stability, particularly as indicated by the significant decrease in the short circuit current (ISC ). Herein, the effect of photoelectrode and sealant materials as well as module design are investigated, highlighting their profound influence upon the DSSC efficiency and long-term stability.

  1. 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

  2. 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.

  3. 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

  4. Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging

    Science.gov (United States)

    Flusberg, Deborah A.; Sorger, Peter K.

    2013-06-01

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) holds promise as an anti-cancer therapeutic but efficiently induces apoptosis in only a subset of tumor cell lines. Moreover, even in clonal populations of responsive lines, only a fraction of cells dies in response to TRAIL and individual cells exhibit cell-to-cell variability in the timing of cell death. Fractional killing in these cell populations appears to arise not from genetic differences among cells but rather from differences in gene expression states, fluctuations in protein levels and the extent to which TRAIL-induced death or survival pathways become activated. In this study, we ask how cell-to-cell variability manifests in cell types with different sensitivities to TRAIL, as well as how it changes when cells are exposed to combinations of drugs. We show that individual cells that survive treatment with TRAIL can regenerate the sensitivity and death-time distribution of the parental population, demonstrating that fractional killing is a stable property of cell populations. We also show that cell-to-cell variability in the timing and probability of apoptosis in response to treatment can be tuned using combinations of drugs that together increase apoptotic sensitivity compared to treatment with one drug alone. In the case of TRAIL, modulation of cell-to-cell variability by co-drugging appears to involve a reduction in the threshold for mitochondrial outer membrane permeabilization.

  5. Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance.

    Science.gov (United States)

    Ene, Iuliana V; Walker, Louise A; Schiavone, Marion; Lee, Keunsook K; Martin-Yken, Hélène; Dague, Etienne; Gow, Neil A R; Munro, Carol A; Brown, Alistair J P

    2015-07-28

    The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock. The C. albicans cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antifungal therapy. Its tensile strength is conferred by

  6. Detachment variants of Chinese hamster cells. Hyaluronic acid as a modulator of cell detachment

    Energy Technology Data Exchange (ETDEWEB)

    Barnhart, B.J.; Cox, S.H.; Kraemer, P.M.

    1979-01-01

    Variants of the Chinese hamster cell line CHO have been isolated and characterized with respect to attachment and trypsin- or EGTA-mediated detachment kinetics, cell morphologies, and the complex carbohydrates (labeled with (/sup 3/H)glucosamine) of the cell surface. The variant which was more readily detached from the substratum exhibited a more rounded cell shape and had three times more label as hyaluronic acid on the cell surface than the parental cell. The slowly detaching variant had a morphology similar to the parental cell but only half the radioactivity ascribable to hyaluronic acid. Endogenous levels of cAMP were unaltered in the variants. Exogenous db-cAMP caused the cells to elongate and flatten but did not alter the characteristic detachment kinetics. The role of hyaluronic acid as a modulator of the cell substratum interface is discussed.

  7. Chemical modulation of the ultra-weak photon emission from Saccharomyces cerevisiae and differentiated HL-60 cells

    Science.gov (United States)

    Červinková, Kateřina; Nerudová, Michaela; Hašek, Jiří; Cifra, Michal

    2015-01-01

    The ultra-weak photon emission (UPE) is a universal phenomenon common to all cells with active oxidative metabolism. Generally accepted mechanism of the origin of the ultra-weak photon emission considers reactions of radical or nonradical reactive oxygen species (ROS) with biomolecules such as lipids and proteins which lead to the formation of electron excited species. During the transition to the ground state the excess energy is released as a photon with a wavelength in the visible range of the electromagnetic spectrum. Since the intensity of the light is very low it is possible to be measured only by highly sensitive devices. We used Hamamatsu Photonics PMT module H7360-01 mounted into a light-tight chamber for the purposes of this work. The goal of our research is to delineate an origin of UPE from two model organisms; differentiated HL-60 cells (human promyelocytic leukemia) and yeast cells Saccharomyces cerevisiae. While the UPE from the yeast cells arises spontaneously during the growth without any external stimuli, UPE from HL-60 is induced by phorbol 12-myristate, 13-acetate (PMA). It is possible to modulate the UPE production by certain antioxidants which scavenge ROS formed during the metabolism (yeast cells) or respiratory burst (HL-60 cells). The experiments are focused on the description of effects caused by antioxidants. Several kinds of antioxidants (ascorbic acid, mannitol, glutathione) with different concentration were used and we studied the changes in the UPE intensities of and the temporal developments of the optical signal.

  8. Simvastatin Modulates Mesenchymal Stromal Cell Proliferation and Gene Expression

    Science.gov (United States)

    Zanette, Dalila Lucíola; Lorenzi, Julio Cesar Cetrulo; Panepucci, Rodrigo Alexandre; Palma, Patricia Vianna Bonini; dos Santos, Daiane Fernanda; Prata, Karen Lima; Silva, Wilson Araújo

    2015-01-01

    Statins are widely used hypocholesterolemic drugs that block the mevalonate pathway, responsible for the biosysnthesis of cholesterol. However, statins also have pleiotropic effects that interfere with several signaling pathways. Mesenchymal stromal cells (MSC) are a heterogeneous mixture of cells that can be isolated from a variety of tissues and are identified by the expression of a panel of surface markers and by their ability to differentiate in vitro into osteocytes, adipocytes and chondrocytes. MSC were isolated from amniotic membranes and bone marrows and characterized based on ISCT (International Society for Cell Therapy) minimal criteria. Simvastatin-treated cells and controls were directly assayed by CFSE (Carboxyfluorescein diacetate succinimidyl ester) staining to assess their cell proliferation and their RNA was used for microarray analyses and quantitative PCR (qPCR). These MSC were also evaluated for their ability to inhibit PBMC (peripheral blood mononuclear cells) proliferation. We show here that simvastatin negatively modulates MSC proliferation in a dose-dependent way and regulates the expression of proliferation-related genes. Importantly, we observed that simvastatin increased the percentage of a subset of smaller MSC, which also were actively proliferating. The association of MSC decreased size with increased pluripotency and the accumulating evidence that statins may prevent cellular senescence led us to hypothesize that simvastatin induces a smaller subpopulation that may have increased ability to maintain the entire pool of MSC and also to protect them from cellular senescence induced by long-term cultures/passages in vitro. These results may be important to better understand the pleiotropic effects of statins and its effects on the biology of cells with regenerative potential. PMID:25874574

  9. Cell-specific modulation of surfactant proteins by ambroxol treatment.

    Science.gov (United States)

    Seifart, Carola; Clostermann, Ursula; Seifart, Ulf; Müller, Bernd; Vogelmeier, Claus; von Wichert, Peter; Fehrenbach, Heinz

    2005-02-15

    Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNA content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.

  10. Ground and excited state properties of high performance anthocyanidin dyes-sensitized solar cells in the basic solutions

    Energy Technology Data Exchange (ETDEWEB)

    Prima, Eka Cahya [Advanced Functional Material Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia); Computational Material Design and Quantum Engineering Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia); International Program on Science Education, Universitas Pendidikan Indonesia (Indonesia); Yuliarto, Brian; Suyatman, E-mail: yatman@tf.itb.ac.id [Advanced Functional Material Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia); Dipojono, Hermawan Kresno [Computational Material Design and Quantum Engineering Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia)

    2015-09-30

    The aglycones of anthocyanidin dyes were previously reported to form carbinol pseudobase, cis-chalcone, and trans-chalcone due to the basic levels. The further investigations of ground and excited state properties of the dyes were characterized using density functional theory with PCM(UFF)/B3LYP/6-31+G(d,p) level in the basic solutions. However, to the best of our knowledge, the theoretical investigation of their potential photosensitizers has never been reported before. In this paper, the theoretical photovoltaic properties sensitized by dyes have been successfully investigated including the electron injections, the ground and excited state oxidation potentials, the estimated open circuit voltages, and the light harvesting efficiencies. The results prove that the electronic properties represented by dyes’ LUMO-HOMO levels will affect to the photovoltaic performances. Cis-chalcone dye is the best anthocyanidin aglycone dye with the electron injection spontaneity of −1.208 eV, the theoretical open circuit voltage of 1.781 V, and light harvesting efficiency of 56.55% due to the best HOMO-LUMO levels. Moreover, the ethanol solvent slightly contributes to the better cell performance than the water solvent dye because of the better oxidation potential stabilization in the ground state as well as in the excited state. These results are in good agreement with the known experimental report that the aglycones of anthocyanidin dyes in basic solvent are the high potential photosensitizers for dye-sensitized solar cell.

  11. 77 FR 31309 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-05-25

    ... telluride (CdTe), or copper indium gallium selenide (CIGS). Also excluded from the scope of this... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... crystalline silicon photovoltaic cells, whether or not assembled into modules (``solar cells''), from the...

  12. 77 FR 63791 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled into Modules, from the People's...

    Science.gov (United States)

    2012-10-17

    ...-Si), cadmium telluride (CdTe), or copper indium gallium selenide (CIGS). ] Also excluded from the... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled into Modules... photovoltaic cells, whether or not assembled into modules (``solar cells''), from the People's Republic of...

  13. 77 FR 37877 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-06-25

    ... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... determination in the antidumping duty investigation of crystalline silicon photovoltaic cells, whether or not... Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's Republic of China: Preliminary...

  14. 76 FR 78313 - Crystalline Silicon Photovoltaic Cells and Modules From China

    Science.gov (United States)

    2011-12-16

    ... COMMISSION Crystalline Silicon Photovoltaic Cells and Modules From China Determinations On the basis of the... is materially injured by reason of imports from China of crystalline silicon photovoltaic cells and... crystalline silicon photovoltaic cells and modules from China. Accordingly, effective October 19, 2011, the...

  15. 77 FR 10478 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-02-22

    ... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... crystalline silicon photovoltaic cells, whether or not assembled into modules, from the People's Republic of..., 2012, which the Department granted.\\2\\ \\1\\ See Crystalline Silicon Photovoltaic Cells, Whether or Not...

  16. CD4 + T cells promote renal cell carcinoma proliferation via modulating YBX1.

    Science.gov (United States)

    Wang, Yong; Wang, Yiting; Xu, Liang; Lu, Xianqi; Fu, Donghe; Su, Jing; Geng, Hua; Qin, Guoxuan; Chen, Ruibing; Quan, Changyi; Niu, Yuanjie; Yue, Dan

    2018-02-01

    Renal cell carcinoma (RCC) is a common urologic tumor and the third leading cause of death among urological tumors. Recent studies demonstrate that RCC tumors are more heavily infiltrated by lymphocytes than other cancers. However, the exact roles played by CD4 + T cells in RCC proliferation remain unknown. In this study, we cocultured RCC cells with CD4 + T cells. Stable knockdown of YBX1 in RCC cells was constructed. The effects of CD4 + T cells, TGFβ1 and YBX1 on RCC cells were investigated using cell viability assays. In situ RCC nude mouse model was used to observe the tumor growth. The potential mechanisms of CD4 + T cells and YBX1 in RCC cells proliferation were explored by qRT-PCR and western blot. Expression of CD4, Foxp3 and TGFβ1 in RCC were quantified by immunohistochemical staining. The results indicated that CD4, Foxp3 and TGFβ1 were significantly up-regulated in RCC tissues. Human clinical sample and in vitro cell lines studies showed that RCC cells had better capacity than its surrounding normal kidney epithelial cells to recruit the CD4 + T cells. In vivo mouse model studies were consistent with the results by in vitro cell lines studies showing infiltrating T cells enhanced RCC cell proliferation. qRT-PCR and western blot exhibited that CD4 + T cells could enhance RCC cell proliferation via activating YBX1/HIF2α signaling pathway. Furthermore, CD4 + T cells functioned through inducing TGFβ1 expression. In a word, infiltrating CD4 + T cells promoted TGFβ1 expression in both RCC and T cells and regulated RCC cells proliferation via modulating TGFβ1/YBX1/ HIF2α signals. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Phenotypic and proliferative modulation of human mesenchymal stem cells via crosstalk with endothelial cells.

    Science.gov (United States)

    Bidarra, Sílvia J; Barrias, Cristina C; Barbosa, Mário A; Soares, Raquel; Amédée, Joelle; Granja, Pedro L

    2011-11-01

    The purpose of this work was to investigate if a coculture system of human mesenchymal stem cells (hMSC) with endothelial cells (human umbilical vein endothelial cells, HUVEC) could modulate the phenotype and proliferation of harvested MSCs. In addition to previous investigations on the crosstalk between these two cell types, in the present work different relative cell ratios were analyzed for long, therapeutically relevant, culture periods. Moreover, MSCs osteogenic commitment was assessed in a non-osteogenic medium and in the presence of HUVECs through magnetic cell separation, cell quantification by flow cytometry, morphology by fluorescent microscopy, metabolic activity and gene expression of osteogenic markers. Collectively, the present findings demonstrate that, by coculturing MSCs with HUVECs, there was not only the promotion of osteogenic differentiation (and its enhancement, depending on the relative cell ratios used), but also a significant increase on MSCs proliferation. This augmentation in cell proliferation occurred independently of relative cell ratios, but was favored by higher relative amounts of HUVECs. Taken together, this data suggests that HUVECs not only modulate MSC phenotype but also their proliferation rate. Therefore, a coculture system of MSCs and HUVECs can a have a broad impact on bone tissue engineering approaches. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling

    Science.gov (United States)

    Saegusa, Noriko; Garg, Vivek

    2013-01-01

    The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ∼50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate α-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from −80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells. PMID:23585132

  19. Steviol glycosides modulate glucose transport in different cell types.

    Science.gov (United States)

    Rizzo, Benedetta; Zambonin, Laura; Angeloni, Cristina; Leoncini, Emanuela; Dalla Sega, Francesco Vieceli; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

    2013-01-01

    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  20. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    Directory of Open Access Journals (Sweden)

    Benedetta Rizzo

    2013-01-01

    Full Text Available Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  1. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    Science.gov (United States)

    Rizzo, Benedetta; Zambonin, Laura; Leoncini, Emanuela; Vieceli Dalla Sega, Francesco; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

    2013-01-01

    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. PMID:24327825

  2. Distinct type I and type II toxin-antitoxin modules control Salmonella lifestyle inside eukaryotic cells

    National Research Council Canada - National Science Library

    Lobato-Márquez, Damián; Moreno-Córdoba, Inmaculada; Figueroa, Virginia; Díaz-Orejas, Ramón; García-del Portillo, Francisco

    2015-01-01

    .... Using the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as a model, here we show that a selected group of TA modules impact bacterial fitness inside eukaryotic cells...

  3. Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

    Science.gov (United States)

    Xu, Jianfeng; Lan, Yueheng

    2015-01-01

    Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

  4. The mycotoxin patulin, modulates tight junctions in caco-2 cells.

    Science.gov (United States)

    McLaughlin, John; Lambert, Daniel; Padfield, Philip J; Burt, Julian P H; O'Neill, Catherine A

    2009-02-01

    The mycotoxin patulin is a common contaminant of fruit. Here, we demonstrate that patulin reduces the barrier properties of the intestinal cell line, caco-2 by specific effects on tight junction components. Within 5h of exposure to 100 microM toxin, the transepithelial electrical resistance of caco-2 monolayers was reduced by approximately 95% and the monolayer became more permeable to FITC-labelled dextrans of 4-40 kDa. Immunoblotting revealed occludin proteolysis and a significant reduction in ZO-1 levels. Patulin had no influence on claudin levels but marked changes in their distribution were observed. These data indicate that patulin decreases the barrier properties of caco-2 monolayers by modulation of the tight junction.

  5. Integrating Optical Fiber Bridges in Microfluidic Devices to Create Multiple Excitation/Detection Points for Single Cell Analysis.

    Science.gov (United States)

    Patabadige, Damith E W; Sadeghi, Jalal; Kalubowilage, Madumali; Bossmann, Stefan H; Culbertson, Anne H; Latifi, Hamid; Culbertson, Christopher T

    2016-10-18

    A microfluidic device is reported that employs an out-of-plane optical fiber bridge to generate two excitation and two detection spots in a microfluidic channel using only one excitation source and one detector. This fiber optic bridge was integrated into a single cell analysis device to detect an intact cell just prior to lysis and the injected lysate 2, 5, 10, or 15 mm downstream of the injection point. Using this setup the absolute migration times for analytes from cells stochastically entering the lysis intersection could be determined for the first time in an automated fashion. This allowed the evaluation of several separation parameters, including analyte band velocity, migration time drift, diffusion coefficient, injection plug length, separation efficiency (N), and plate height (H), which previously could only be estimated. To demonstrate the utility of this system, a peptide substrate for protein kinase B (PKB) was designed, synthesized, and loaded into T-lymphocytes in order to measure PKB activity in individual cells. The optical fiber bridge is easy to implement, inexpensive, and flexible in terms of changing the distances between the two detection points.

  6. Cell-to-module optical loss/gain analysis for various photovoltaic module materials through systematic characterization

    Science.gov (United States)

    Hsian Saw, Min; Khoo, Yong Sheng; Singh, Jai Prakash; Wang, Yan

    2017-08-01

    Reducing levelized cost of electricity (LCOE) is important for solar photovoltaics to compete against other energy sources. Thus, the focus should not only be on improving the solar cell efficiency, but also on continuously reducing the losses (or achieving gain) in the cell-to-module process. This can be achieved by choosing the appropriate module material and design. This paper presents a detailed and systematic characterization of various photovoltaic (PV) module materials (encapsulants, tabbing ribbons, and backsheets) and an evaluation of their impact on the output power of silicon wafer-based PV modules. Various characterization tools/techniques, such as UV-vis (reflectance) measurement, external quantum efficiency (EQE) measurement and EQE line-scan are used. Based on the characterization results, we use module materials with the best-evaluated optical performance to build “optimized modules”. Compared to the standard mini-module, an optical gain of more than 5% is achievable for the “optimized module” with selected module materials.

  7. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells

    Science.gov (United States)

    Rhode, Jennifer; Fogoros, Sarah; Zick, Suzanna; Wahl, Heather; Griffith, Kent A; Huang, Jennifer; Liu, J Rebecca

    2007-01-01

    Background Ginger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro. Methods The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-κB and and production of VEGF and IL-8 was determined in the presence or absence of ginger. Results Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8. Conclusion Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer. PMID:18096028

  8. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Huang Jennifer

    2007-12-01

    Full Text Available Abstract Background Ginger (Zingiber officinale Rosc is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro. Methods The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-κB and and production of VEGF and IL-8 was determined in the presence or absence of ginger. Results Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8. Conclusion Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.

  9. Single-photon cesium Rydberg excitation spectroscopy using 3186-nm UV laser and room-temperature vapor cell

    Science.gov (United States)

    Wang, Jieying; Bai, Jiandong; He, Jun; Wang, Junmin

    2017-09-01

    We demonstrate a single-photon Rydberg excitation spectroscopy of cesium (Cs) atoms in a room-temperature vapor cell. Cs atoms are excited directly from 6S1/2 ground state to nP3/2 (n = 70 - 100) Rydberg states with a 318.6 nm ultraviolet (UV) laser,and Rydberg excitation spectra are obtained by transmission enhancement of a probe beam resonant to Cs 6S1/2, F = 4 - 6P3/2, F' = 5 transition as partial population on F = 4 ground state are transferred to Rydberg state .Analysis reveals that the observed spectra are velocity-selective spectroscopy of Rydberg state, from which the amplitude and linewidth influenced by lasers'Rabi frequency have been investigated. Fitting to energies of Cs nP3/2 (n = 70 -100) states, the determined quantum defect is 3.56671(42). The demodulated spectra can also be employed as frequency references to stabilize the UV laser frequency to specific Cs Rydberg transition.

  10. Leucine affects the fibroblastic Vero cells stimulating the cell proliferation and modulating the proteolysis process.

    Science.gov (United States)

    Gonçalves, Estela Maria; Gomes-Marcondes, Maria Cristina Cintra

    2010-01-01

    Branched-chain amino acids, especially leucine, exert regulatory influences on protein and carbohydrate metabolism, ribosome biogenesis and gene expression. This study investigated the effects of leucine in fibroblastic cells analysing viability, proliferation, morphology, proteolysis enzymes activities and protein turnover. After exposure to culture medium enriched with 25 or 50 microM leucine for 24, 48 and 72 h, Vero cells have no alterations on viability and morphology. Leucine-treated cells showed increase on alkaline phosphatase activity and proliferation. The protein synthesis was slightly increased, whereas the protein degradation showed a deep reduction after leucine incubation. The chymotrypsin-like, cathepsin B and H and calpain activities were decreased in leucine-treated cells. In conclusion, the proteolytic pathways and the total protein degradation were modulated by leucine in Vero cells. Our observations support the concept that Vero cells may represent a new model for protein turnover study.

  11. Environmental testing of Block II solar cell modules. Low-Cost Solar Array Project

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.S.

    1979-01-01

    The results of environmental tests of Block II solar modules are described. Block II was the second large scale procurement of silicon solar cell modules made by the JPL Low-Cost Solar Array Project with deliveries in 1977 and early 1978. The results of testing showed that the Block II modules were greatly improved over Block I modules. In several cases it was shown that design improvements were needed to reduce environmental test degradation. These improvements were incorporated during this production run.

  12. Multiplexing PKA and ERK1&2 kinases FRET biosensors in living cells using single excitation wavelength dual colour FLIM.

    Science.gov (United States)

    Demeautis, Claire; Sipieter, François; Roul, Julien; Chapuis, Catherine; Padilla-Parra, Sergi; Riquet, Franck B; Tramier, Marc

    2017-01-20

    Monitoring of different signalling enzymes in a single assay using multiplex biosensing provides a multidimensional workspace to elucidate biological processes, signalling pathway crosstalk, and determine precise sequence of events at the single living cell level. In this study, we interrogate the complexity in cAMP/PKA-MAPK/ERK1&2 crosstalk by using multi-parameter biosensing experiments to correlate biochemical activities simultaneously in time and space. Using a single excitation wavelength dual colour FLIM method we are able to detect fluorescence lifetime images of two donors to simultaneously measure PKA and ERK1&2 kinase activities in the same cellular localization by using FRET biosensors. To this end, we excite two FRET donors mTFP1 and LSSmOrange with a 440 nm wavelength and we alleviate spectral bleed-through associated limitations with the very dim-fluorescent acceptor ShadowG for mTFP1 and the red-shifted mKate2 for LSSmOrange. The simultaneous recording of PKA and ERK1&2 kinase activities reveals concomitant EGF-mediated activations of both kinases in HeLa cells. Under these conditions the subsequent Forskolin-induced cAMP release reverses the transient increase of EGF-mediated ERK1&2 kinase activity while reinforcing PKA activation. Here we propose a validated methodology for multiparametric kinase biosensing in living cells using FRET-FLIM.

  13. Multiplexing PKA and ERK1&2 kinases FRET biosensors in living cells using single excitation wavelength dual colour FLIM

    Science.gov (United States)

    Demeautis, Claire; Sipieter, François; Roul, Julien; Chapuis, Catherine; Padilla-Parra, Sergi; Riquet, Franck B.; Tramier, Marc

    2017-01-01

    Monitoring of different signalling enzymes in a single assay using multiplex biosensing provides a multidimensional workspace to elucidate biological processes, signalling pathway crosstalk, and determine precise sequence of events at the single living cell level. In this study, we interrogate the complexity in cAMP/PKA-MAPK/ERK1&2 crosstalk by using multi-parameter biosensing experiments to correlate biochemical activities simultaneously in time and space. Using a single excitation wavelength dual colour FLIM method we are able to detect fluorescence lifetime images of two donors to simultaneously measure PKA and ERK1&2 kinase activities in the same cellular localization by using FRET biosensors. To this end, we excite two FRET donors mTFP1 and LSSmOrange with a 440 nm wavelength and we alleviate spectral bleed-through associated limitations with the very dim-fluorescent acceptor ShadowG for mTFP1 and the red-shifted mKate2 for LSSmOrange. The simultaneous recording of PKA and ERK1&2 kinase activities reveals concomitant EGF-mediated activations of both kinases in HeLa cells. Under these conditions the subsequent Forskolin-induced cAMP release reverses the transient increase of EGF-mediated ERK1&2 kinase activity while reinforcing PKA activation. Here we propose a validated methodology for multiparametric kinase biosensing in living cells using FRET-FLIM. PMID:28106114

  14. Kinetic model of Nav1.5 channel provides a subtle insight into slow inactivation associated excitability in cardiac cells.

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    Full Text Available Voltage-gated sodium channel Nav1.5 has been linked to the cardiac cell excitability and a variety of arrhythmic syndromes including long QT, Brugada, and conduction abnormalities. Nav1.5 exhibits a slow inactivation, corresponding to a duration-dependent bi-exponential recovery, which is often associated with various arrhythmia syndromes. However, the gating mechanism of Nav1.5 and the physiological role of slow inactivation in cardiac cells remain elusive. Here a 12-state two-step inactivation Markov model was successfully developed to depict the gating kinetics of Nav1.5. This model can simulate the Nav1.5 channel in not only steady state processes, but also various transient processes. Compared with the simpler 8-state model, this 12-state model is well-behaved in simulating and explaining the processes of slow inactivation and slow recovery. This model provides a good framework for further studying the gating mechanism and physiological role of sodium channel in excitable cells.

  15. Display of cell surface sites for fibronectin assembly is modulated by cell adherence to (1)F3 and C-terminal modules of fibronectin.

    Science.gov (United States)

    Xu, Jielin; Bae, Eunnyung; Zhang, Qinghong; Annis, Douglas S; Erickson, Harold P; Mosher, Deane F

    2009-01-01

    Fibronectin-null cells assemble soluble fibronectin shortly after adherence to a substrate coated with intact fibronectin but not when adherent to the cell-binding domain of fibronectin (modules (7)F3-(10)F3). Interactions of adherent cells with regions of adsorbed fibronectin other than modules (7)F3-(10)F3, therefore, are required for early display of the cell surface sites that initiate and direct fibronectin assembly. To identify these regions, coatings of proteolytically derived or recombinant pieces of fibronectin containing modules in addition to (7)F3-(10)F3 were tested for effects on fibronectin assembly by adherent fibronectin-null fibroblasts. Pieces as large as one comprising modules (2)F3-(14)F3, which include the heparin-binding and cell adhesion domains, were not effective in supporting fibronectin assembly. Addition of module (1)F3 or the C-terminal modules to modules (2)F3-(14)F3 resulted in some activity, and addition of both (1)F3 and the C-terminal modules resulted in a construct, (1)F3-C, that best mimicked the activity of a coating of intact fibronectin. Constructs (1)F3-C V0, (1)F3-C V64, and (1)F3-C Delta(V(15)F3(10)F1) were all able to support fibronectin assembly, suggesting that (1)F3 through (11)F1 and/or (12)F1 were important for activity. Coatings in which the active parts of (1)F3-C were present in different proteins were much less active than intact (1)F3-C. These results suggest that (1)F3 acts together with C-terminal modules to induce display of fibronectin assembly sites on adherent cells.

  16. Principal cell spiking, postsynaptic excitation, and oxygen consumption in the rat cerebellar cortex

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Piilgaard, Henning; Gjedde, Albert

    2009-01-01

    One contention within the field of neuroimaging concerns the character of the depicted activity: Does it represent neuronal action potential generation (i.e., spiking) or postsynaptic excitation? This question is related to the metabolic costs of different aspects of neurosignaling. The cerebellar...... excitatory synaptic input. Subsequent inhibition of action potential propagation and neurotransmission by blocking voltage-gated Na+-channels eliminated the increases in CMRO2 due to PF stimulation and increased PC spiking, but left a large fraction of CMRO2, i.e., basal CMRO2, intact. In conclusion, whereas...

  17. Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells

    Directory of Open Access Journals (Sweden)

    Maria Magdalena eMontt-Guevara

    2015-07-01

    Full Text Available Estetrol (E4 is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO is a key player for vascular function and disease during pregnancy and throughout ageing in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS in cultured human umbilical vein endothelial cells (HUVEC. E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2 and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use.

  18. 77 FR 17439 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-03-26

    ... products produced from amorphous silicon (a-Si), cadmium telluride (CdTe), or copper indium gallium... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... into modules (solar cells) from the People's Republic of China (PRC). For information on the estimated...

  19. 77 FR 73018 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-12-07

    ... telluride (CdTe), or copper indium gallium selenide (CIGS). Also excluded from the scope of this order are... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... assembled into modules (``solar cells''), from the People's Republic of China (``PRC''). In addition, the...

  20. 77 FR 73017 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-12-07

    ... thin film photovoltaic products produced from amorphous silicon (a-Si), cadmium telluride (CdTe), or... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... into modules (solar cells), from the People's Republic of China (PRC). On November 30, 2012, the ITC...

  1. Insights into Host Cell Modulation and Induction of New Cells by the Corn Smut Ustilago maydis

    Directory of Open Access Journals (Sweden)

    Amey Redkar

    2017-05-01

    Full Text Available Many filamentous fungal pathogens induce drastic modulation of host cells causing abnormal infectious structures such as galls, or tumors that arise as a result of re-programming in the original developmental cell fate of a colonized host cell. Developmental consequences occur predominantly with biotrophic phytopathogens. This suggests that these host structures result as an outcome of efficient defense suppression and intimate fungal–host interaction to suit the pathogen’s needs for completion of its infection cycle. This mini-review mainly summarizes host cell re-programming that occurs in the Ustilago maydis – maize interaction, in which the pathogen deploys cell-type specific effector proteins with varying activities. The fungus senses the physiological status and identity of colonized host cells and re-directs the endogenous developmental program of its host. The disturbance of host cell physiology and cell fate leads to novel cell shapes, increased cell size, and/or the number of host cells. We particularly highlight the strategies of U. maydis to induce physiologically varied host organs to form the characteristic tumors in both vegetative and floral parts of maize.

  2. Insights into Host Cell Modulation and Induction of New Cells by the Corn Smut Ustilago maydis

    Science.gov (United States)

    Redkar, Amey; Matei, Alexandra; Doehlemann, Gunther

    2017-01-01

    Many filamentous fungal pathogens induce drastic modulation of host cells causing abnormal infectious structures such as galls, or tumors that arise as a result of re-programming in the original developmental cell fate of a colonized host cell. Developmental consequences occur predominantly with biotrophic phytopathogens. This suggests that these host structures result as an outcome of efficient defense suppression and intimate fungal–host interaction to suit the pathogen’s needs for completion of its infection cycle. This mini-review mainly summarizes host cell re-programming that occurs in the Ustilago maydis – maize interaction, in which the pathogen deploys cell-type specific effector proteins with varying activities. The fungus senses the physiological status and identity of colonized host cells and re-directs the endogenous developmental program of its host. The disturbance of host cell physiology and cell fate leads to novel cell shapes, increased cell size, and/or the number of host cells. We particularly highlight the strategies of U. maydis to induce physiologically varied host organs to form the characteristic tumors in both vegetative and floral parts of maize. PMID:28611813

  3. Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

    Science.gov (United States)

    Rego, António; Duarte, Ana M.; Azevedo, Flávio; Sousa, Maria J.; Côrte-Real, Manuela; Chaves, Susana R.

    2014-01-01

    Acetic acid triggers apoptotic cell death in Saccharomyces cerevisiae, similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria. PMID:28357256

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Altered excitability of cultured chromaffin cells following exposure to multi-walled carbon nanotubes.

    Science.gov (United States)

    Gavello, Daniela; Vandael, David H F; Cesa, Roberta; Premoselli, Federica; Marcantoni, Andrea; Cesano, Federico; Scarano, Domenica; Fubini, Bice; Carbone, Emilio; Fenoglio, Ivana; Carabelli, Valentina

    2012-02-01

    We studied the effects of multi-walled carbon nanotubes (MWCNTs) on the electrophysiological properties of cultured mouse chromaffin cells, a model of spontaneously firing cells. The exposure of chromaffin cells to MWCNTs at increasing concentrations (30-263 μg/ml) for 24 h reduced, in a dose-dependent way, both the cell membrane input resistance and the number of spontaneously active cells (from 80-52%). Active cells that survived from the toxic effects of MWCNTs exhibited more positive resting potentials, higher firing frequencies and unaltered voltage-gated Ca(2+), Na(+) and K+ current amplitudes. MWCNTs slowed down the inactivation kinetics of Ca(2+)-dependent BK channels. These electrophysiological effects were accompanied by MWCNTs internalization, as confirmed by transmission electron microscopy, indicating that most of the toxic effects derive from a dose-dependent MWCNTs-cell interaction that damages the spontaneous cell activity.

  6. Compatibility of copper-electroplated cells with Metal Wrap Through module materials

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, I.J.; Geerligs, L.J.; Olson, C.L.; Goris, M.J.A.A. [ECN Solar Energy, Petten (Netherlands)

    2013-10-16

    As part of the European FP7 RandD project 'Cu-PV', the compatibility of copper-electroplated metal wrapthrough (MWT) cells with conductive adhesives has been investigated. The objectives of this project include to reduce, by the use of copper plating, the amount of silver utilized in cell manufacturing, and to demonstrate the compatibility of high-power n-type back-contact module technology with copper-plated cells. The overall goal is to reduce the impact on the environment of cell and module manufacture. MWT module technology as developed by ECN uses conductive adhesive to make the interconnection between cells and a conductive backsheet foil. These adhesives have been proved to result in very reliable modules in the case of cells with fired silver metallization. To determine the compatibility of conductive adhesive with copper-plated cells, component tests were performed, followed by the manufacture of modules with copperplated cells and conductive adhesive interconnections. Climate chamber testing of these modules showed that the adhesive is compatible with the copper-plated cells. The next steps include further optimization of the plating process and additional testing at the module level.

  7. Simplified module assembly using back-contact crystalline-silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Gee, J.M.; Garrett, S.E.; Morgan, W.P.

    1997-11-01

    The authors are developing new module concepts that encapsulate and electrically connect all the crystalline-silicon (c-Si) photovoltaic (PV) cells in a module in a single step. The new assembly process (1) uses back-contact c-Si cells, (2) uses a module backplane that has both the electrical circuit, encapsulant, and backsheet in a single piece, and (3) uses a single-step process for assembly of these components into a module. This new process reduces module assembly cost by using planar processes that are easy to automate, by reducing the number of steps, and by eliminating low-throughput (e.g., individual cell tabbing, cell stringing, etc.) steps. The authors refer to this process as monolithic module assembly since it translates many of the advantages of monolithic module construction of thin-film PV modules to wafered c-Si PV modules. Preliminary development of the new module assembly process, and some estimations of the cost potential of the new process, are presented.

  8. The effect of noise and coupling on beta cell excitation dynamics

    DEFF Research Database (Denmark)

    system, but with a quantitative description of the effect of noise. This approach supports previous investigations of the channel sharing hypothesis. For beta cells coupled via gap junctions we briefly discuss the effects of the ATP driven potassium ion gate on reaction diffusion type waves. It is shown......Bursting electrical behavior is commonly observed in a variety of nerve and endocrine cells, including that in electrically coupled β-cells located in intact pancreatic islets. However, individual β-cells usually display either spiking or very fast bursting behavior, and the difference between...... isolated and coupled cells has been suggested to be due to stochastic fluctuations of the plasma membrane ion channels, which are supposed to have a stronger effect on single cells than on cells situated in clusters (the channel sharing hypothesis). This effect of noise has previously been studied using...

  9. Technical evaluation of Solar Cells, Inc., CdTe module and array at NREL

    Energy Technology Data Exchange (ETDEWEB)

    Kroposki, B.; Strand, T.; Hansen, R. [National Renewable Energy Lab., Golden, CO (United States); Powell, R.; Sasala, R. [Solar Cells, Inc., Toledo, OH (United States)

    1996-05-01

    The Engineering and Technology Validation Team at the National Renewable Energy Laboratory (NREL) conducts in-situ technical evaluations of polycrystalline thin-film photovoltaic (PV) modules and arrays. This paper focuses on the technical evaluation of Solar Cells, Inc., (SCI) cadmium telluride (CdTe) module and array performance by attempting to correlate individual module and array performance. This is done by examining the performance and stability of the modules and array over a period of more than one year. Temperature coefficients for module and array parameters (P{sub max}, V{sub oc}, V{sub max}, I{sub sc}, I{sub max}) are also calculated.

  10. High power n-type metal-wrap-through cells and modules using industrial processes

    Energy Technology Data Exchange (ETDEWEB)

    Guillevin, N.; Heurtault, B.J.B.; Geerligs, L.J.; Van Aken, B.B.; Bennett, I.J.; Jansen, M.J.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, P.O. Box 1, NL-1755 ZG Petten (Netherlands); Jianming, Wang; Ziqian, Wang; Jinye, Zhai; Zhiliang, Wan; Shuquan, Tian; Wenchao, Zhao; Zhiyan, Hu; Gaofei, Li; Bo, Yu; Jingfeng, Xiong [Yingli Green Energy Holding Co.,Ltd. 3399 North Chaoyang Avenue, Baoding (China)

    2013-10-15

    This paper reviews our recent progress in the development of metal wrap through (MWT) cells and modules, produced from n-type Czochralski silicon wafers. The use of n-type silicon as base material allows for high efficiencies: for front emitter-contacted industrial cells, efficiencies above 20% have been reported. N-type MWT (nMWT) cells produced by industrial process technologies allow even higher efficiency due to reduced front metal coverage. Based on the same industrial technology, the efficiency of the bifacial n-MWT cells exceeds the efficiency of the n-type front-and-rear contact and bifacial 'Pasha' technology (n-Pasha) by 0.1-0.2% absolute, with a maximum nMWT efficiency of 20.1% so far. Additionally, full back-contacting of the MWT cells in a module results in reduced cell to module (CTM) fill factor losses. In a direct 60-cell module performance comparison, the n-MWT module, based on integrated backfoil, produced 3% higher power output than the comparable tabbed front emitter-contacted n-Pasha module. Thanks to reduced resistive losses in copper circuitry on the backfoil compared to traditional tabs, the CTM FF loss of the MWT module was reduced by about 2.2%abs. compared to the tabbed front emitter contact module. A full-size module made using MWT cells of 19.6% average efficiency resulted in a power output close to 280W. Latest results of the development of the n-MWT technology at cell and module level are discussed in this paper, including a recent direct comparison run between n-MWT and n-Pasha cells and results of n-MWT cells from 140{mu}m thin mono-crystalline wafers, with only very slight loss (1% of Isc) for the thin cells. Also reverse characteristics and effects of reverse bias for extended time at cell and module level are reported, where we find a higher tolerance of MWT modules than tabbed front contact modules for hotspots.

  11. [Phenotypic modulation of corpus cavernous smooth musle cells and its influencing factors].

    Science.gov (United States)

    Chen, Gang; Lü, Bo-dong; Huang, Xiao-jun

    2010-03-01

    Corpus cavernous smooth muscle cells are the main functional component of the corpus cavernosum penis, whose phenotypic modulation is the key initial step in the proliferation and migration of smooth muscle cells. Therefore, an insight into the mechanism of the phenotypic modulation of smooth muscle cells and its influencing factors is important for the prevention and management of penis erectile dysfunction. Smooth muscle cells are generally divided into contracting (differentiated) and composing (undifferentiated, proliferated or dedifferentiated) types. It is found that TGF-beta, transcription factor E2F1, BTEB2 and insulin may affect the phenotypic modulation of smooth muscle cells. This paper presents an overview of the progress in the researches on the phenotypic modulation of corpus cavernous smooth muscle cells and its influencing factors.

  12. The Natural Killer Cell Cytotoxic Function Is Modulated by HIV-1 Accessory Proteins

    Directory of Open Access Journals (Sweden)

    Edward Barker

    2011-07-01

    Full Text Available Natural killer (NK cells’ major role in the control of viruses is to eliminate established infected cells. The capacity of NK cells to kill virus-infected cells is dependent on the interactions between ligands on the infected cell and receptors on the NK cell surface. Because of the importance of ligand-receptor interactions in modulating the NK cell cytotoxic response, HIV has developed strategies to regulate various NK cell ligands making the infected cell surprisingly refractory to NK cell lysis. This is perplexing because the HIV-1 accessory protein Vpr induces expression of ligands for the NK cell activating receptor, NKG2D. In addition, the accessory protein Nef removes the inhibitory ligands HLA-A and -B. The reason for the ineffective killing by NK cells despite the strong potential to eliminate infected cells is due to HIV-1 Vpu’s ability to down modulate the co-activation ligand, NTB-A, from the cell surface. Down modulation of NTB-A prevents efficient NK cell degranulation. This review will focus on the mechanisms through which the HIV-1 accessory proteins modulate their respective ligands, and its implication for NK cell killing of HIV-infected cells.

  13. Cells on the move: Modulation of guidance cues during germ cell migration.

    Science.gov (United States)

    Deshpande, Girish; Barr, Justinn; Gerlitz, Offer; Lebedeva, Lyubov; Shidlovskii, Yulii; Schedl, Paul

    2017-07-03

    In Drosophila melanogaster the progenitors of the germ-line stem cells, the primordial germ cells (PGCs) are formed on the outside surface of the early embryo, while the somatic gonadal precursor cells (SGPs) are specified during mid-embryogenesis. To form the primitive embryonic gonad, the PGCs travel from outside of the embryo, across the mid-gut and then migrate through the mesoderm to the SGPs. The migratory path of PGCs is dictated by a series of attractive and repulsive cues. Studies in our laboratory have shown that one of the key chemoattractants is the Hedgehog (Hh) ligand. Although, Hh is expressed in other cell types, the long-distance transmission of this ligand is specifically potentiated in the SGPs by the hmgcr isoprenoid biosynthetic pathway. The distant transmission of the Hh ligand is gated by restricting expression of hmgcr to the SGPs. This is particularly relevant in light of the recent findings that an ABC transporter, mdr49 also acts in a mesoderm specific manner to release the germ cell attractant. Our studies have demonstrated that mdr49 functions in hh signaling likely via its role in the transport of cholesterol. Given the importance of cholesterol in the processing and long distance transmission of the Hh ligand, this observation has opened up an exciting avenue concerning the possible role of components of the sterol transport machinery in PGC migration.

  14. Modulation of the homophilic interaction between the first and second Ig modules of neural cell adhesion molecule by heparin

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Rudenko, Olga; Kiselyov, V.

    2005-01-01

    The second Ig module (IgII) of the neural cell adhesion molecule (NCAM) is known to bind to the first Ig module (IgI) of NCAM (so-called homophilic binding) and to interact with heparan sulfate and chondroitin sulfate glycoconjugates. We here show by NMR that the heparin and chondroitin sulfate......II. Accordingly, we show that treatment of cerebellar granule neurons (CGNs) with heparin inhibits NCAM-mediated outgrowth. In contrast, treatment with heparinase III or chondroitinase ABC abrogates NCAM-mediated neurite outgrowth in CGNs emphasizing the importance of the presence of heparan/chondroitin sulfates...

  15. Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope

    Science.gov (United States)

    Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

    2015-01-01

    Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications. PMID:26525841

  16. Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope.

    Science.gov (United States)

    Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

    2015-11-03

    Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications.

  17. Melatonina: modulador de morte celular Melatonin: cell death modulator

    Directory of Open Access Journals (Sweden)

    Cecília da Silva Ferreira

    2010-01-01

    cells are eliminated after activation of a cell death program involving participation of pro-apoptotic molecules (Fas, Fas-L, Bax, caspases 2, 3, 6, 7, 8 and 9. Molecule activation causes typical morphological changes, such as cell shrinkage, loss of adhesion to the extracellular matrix and neighboring cells, chromatin condensation, DNA fragmentation and formation of apoptotic bodies. Anti-apoptotic molecules (Bcl-2, FLIP block the emergence and evolution of these cell changes and prevent cell death. The balance between molecules pro and anti-apoptotic ensures tissue homeostasis. When apoptosis is out of control, it contributes to the emergence of several neoplastic, autoimmune and neurodegenerative diseases. Several inducing and inhibitors of apoptosis agents are recognized as potential weapons in the fight against diseases related to proliferation and cell death disorders among which stand out hormones. Melatonin has been reported as important anti-apoptotic agent in various tissues by reducing cell calcium uptake, modulating expression of anti-oxidants and decreasing pro-apoptotic protein, such as Bax. The knowledge of new agents capable to act on the course pf apoptosis is important and of great value for developing further therapies against many diseases. Thus, the objective of this review was to elucidate the main aspects of cell death by apoptosis and the role of melatonin in this process.

  18. Cell encapsulation in sub-mm sized gel modules using replica molding.

    Directory of Open Access Journals (Sweden)

    Alison P McGuigan

    Full Text Available For many types of cells, behavior in two-dimensional (2D culture differs from that in three-dimensional (3D culture. Among biologists, 2D culture on treated plastic surfaces is currently the most popular method for cell culture. In 3D, no analogous standard method--one that is similarly convenient, flexible, and reproducible--exists. This paper describes a soft-lithographic method to encapsulate cells in 3D gel objects (modules in a variety of simple shapes (cylinders, crosses, rectangular prisms with lateral dimensions between 40 and 1000 microm, cell densities of 10(5-10(8 cells/cm(3, and total volumes between 1x10(-7 and 8x10(-4 cm(3. By varying (i the initial density of cells at seeding, and (ii the dimensions of the modules, the number of cells per module ranged from 1 to 2500 cells. Modules were formed from a range of standard biopolymers, including collagen, Matrigel, and agarose, without the complex equipment often used in encapsulation. The small dimensions of the modules allowed rapid transport of nutrients by diffusion to cells at any location in the module, and therefore allowed generation of modules with cell densities near to those of dense tissues (10(8-10(9 cells/cm(3. This modular method is based on soft lithography and requires little special equipment; the method is therefore accessible, flexible, and well suited to (i understanding the behavior of cells in 3D environments at high densities of cells, as in dense tissues, and (ii developing applications in tissue engineering.

  19. Studies of Frequency–Dependent Changes under Modulated Ultrasound Exposure on Cells in Suspension

    Directory of Open Access Journals (Sweden)

    Anna A. Oleshkevich

    2015-03-01

    Full Text Available Characteristics of the modulated ultrasound effect (range of modulation frequencies 10Hz–1000Hz intensity 0.2 W/cm2 on white blood cells (WBCs from different animals were studied. The quantitative ratio of WBCs was the most strongly altered by ultrasonic modulation frequency 1000 Hz. This frequency led to degenerative changes of cells. The presence of non-typeable or destroyed cells in smears was indicated. The results obtained demonstrated the possibility of directed impact on different WBC forms.

  20. Non-Flow Through Fuel Cell Power Module Demonstration on the SCARAB Rover

    Science.gov (United States)

    Jakupca, Ian; Guzik, Monica; Bennett, William R.; Edwards, Lawrence

    2017-01-01

    NASA demonstrated the Advanced Product Water Removal (APWR) Non-Flow-Through (NFT) PEM fuel cell technology by powering the Scarab rover over three-(3) days of field operations. The latest generation APWR NFT fuel cell stackwas packaged by the Advanced Exploration Systems (AES) Modular Power Systems (AMPS) team into a nominallyrated 1-kW fuel cell power module. This power module was functionally verified in a laboratory prior to field operations on the Scarab rover, which concluded on 2 September 2015. During this demonstration, the power module satisfied all required success criteria by supporting all electrical loads as the Scarab navigated the NASA Glenn Research Center.

  1. Dynamic flux of microvesicles modulate parasite-host cell interaction of Trypanosoma cruzi in eukaryotic cells.

    Science.gov (United States)

    Ramirez, M I; Deolindo, P; de Messias-Reason, I J; Arigi, Emma A; Choi, H; Almeida, I C; Evans-Osses, I

    2017-04-01

    Extracellular vesicles released from pathogens may alter host cell functions. We previously demonstrated the involvement of host cell-derived microvesicles (MVs) during early interaction between Trypanosoma cruzi metacyclic trypomastigote (META) stage and THP-1 cells. Here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. First, we observed that infective host cell-derived trypomastigote (tissue culture-derived trypomastigote [TCT]), META, and noninfective epimastigote (EPI) stages were able to induce different levels of MV release from THP-1 cells; however, only META and TCT could increase host cell invasion. Fluorescence resonance energy transfer microscopy revealed that THP-1-derived MVs can fuse with parasite-derived MVs. Furthermore, MVs derived from the TCT-THP-1 interaction showed a higher fusogenic capacity than those from META- or EPI-THP-1 interaction. However, a higher presence of proteins from META (25%) than TCT (12%) or EPI (5%) was observed in MVs from parasite-THP-1 interaction, as determined by proteomics. Finally, sera from patients with chronic Chagas disease at the indeterminate or cardiac phase differentially recognized antigens in THP-1-derived MVs resulting only from interaction with infective stages. The understanding of intracellular trafficking and the effect of MVs modulating the immune system may provide important clues about Chagas disease pathophysiology. © 2016 John Wiley & Sons Ltd.

  2. M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

    Directory of Open Access Journals (Sweden)

    Linda Cambier

    Full Text Available Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.

  3. Characterization of cell mismatch in a multi-crystalline silicon photovoltaic module

    Energy Technology Data Exchange (ETDEWEB)

    Crozier, J.L., E-mail: s207094248@live.nmmu.ac.za [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Dyk, E.E. van; Vorster, F.J. [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa)

    2012-05-15

    In this study the causes and effects of cell mismatch were identified in a multi-crystalline silicon photovoltaic module. Different techniques were used to identify the causes of the mismatch, including Electroluminescence (EL) imaging, Infrared (IR) imaging, current-voltage (I-V) characteristics, worst-case cell determination and Large Area Laser Beam Induced Current (LA-LBIC) scans. In EL images the cracked cells, broken fingers and material defects are visible. The presence of poorly contacted cells results in the formation of hot-spots. LA-LBIC line scans give the relative photoresponse of the cells in the module. However, this technique is limited due to the penetration depth of the laser beam. The worst case cell determination compares the I-V curves of the whole module with the I-V curve of the module with one cell covered, allowing the evaluation of the performance of each cell in a series-connected string. These methods allowed detection of the poorly performing cells in the module. Using all these techniques an overall view of the photoresponse in the cells and their performance is obtained.

  4. Ovarian Cancer Cell Adhesion/Migration Dynamics on Micro-Structured Laminin Gradients Fabricated by Multiphoton Excited Photochemistry

    Directory of Open Access Journals (Sweden)

    Ruei-Yu He

    2015-07-01

    Full Text Available Haptotaxis, i.e., cell migration in response to adhesive gradients, has been previously implicated in cancer metastasis. A better understanding of cell migration dynamics and their regulation could ultimately lead to new drug targets, especially for cancers with poor prognoses, such as ovarian cancer. Haptotaxis has not been well-studied due to the lack of biomimetic, biocompatible models, where, for example, microcontact printing and microfluidics approaches are primarily limited to 2D surfaces and cannot produce the 3D submicron features to which cells respond. Here we used multiphoton excited (MPE phototochemistry to fabricate nano/microstructured gradients of laminin (LN as 2.5D models of the ovarian basal lamina to study the haptotaxis dynamics of a series of ovarian cancer cells. Using these models, we found that increased LN concentration increased migration speed and also alignment of the overall cell morphology and their cytoskeleton along the linear axis of the gradients. Both these metrics were enhanced on LN compared to BSA gradients of the same design, demonstrating the importance of both topographic and ECM cues on the adhesion/migration dynamics. Using two different gradient designs, we addressed the question of the roles of local concentration and slope and found that the specific haptotactic response depends on the cell phenotype and not simply the gradient design. Moreover, small changes in concentration strongly affected the migration properties. This work is a necessary step in studying haptotaxis in more complete 3D models of the tumor microenvironment for ovarian and other cancers.

  5. Morphological modulation of human fibrosarcoma HT-1080 cells by hydroxybenzoate compounds during apoptosis

    Directory of Open Access Journals (Sweden)

    Jassem G Mahdi

    2015-10-01

    Full Text Available Hydroxybenzoate (HB compounds have shown to modulate the morphology in human fibrosarcoma HT-1080 cells. The changes in HT-1080 cells showed marker signs of apoptosis, which included the condensation of nucleus, cell round, blebbing and the formation of apoptotic bodies. The different stages of apoptosis were assessed microscopically using different staining and immunohistochemical techniques, as well as scanning electron microscopy. In addition, HB compounds increased the expression of caspase-3, which is closely associated with the development of the modulation in HT-1080 cells that are undergoing the programmed cell death. Both acetyl salicylic acid (ASA and HBZn compounds were dose and treatment duration dependent.

  6. Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity.

    Science.gov (United States)

    Nietz, Angela K; Vaden, Jada H; Coddington, Luke T; Overstreet-Wadiche, Linda; Wadiche, Jacques I

    2017-10-13

    Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.

  7. Excitation energy dependence of the photovoltaic behavior of InAs/GaAsSb quantum dot solar cells

    Science.gov (United States)

    Roeth, Alison; Cheng, Yang; Meleco, Anthony; Whiteside, Vincent; Debnath, Mukul; Santos, Michael; Sellers, Ian

    Intermediate band solar cells (IBSC) have been suggested as a potential route to achieve energy conversion efficiencies higher than that of single gap solar cells by harnessing lower energy light usually lost to transmission. Quantum dots have been proposed as a candidate system for the IB due to their localized nature. Here, InAs quantum dots inserted into the GaAsSb intrinsic region of a solar cell are investigated as a candidate system for IBSCs. The photovoltaic properties of this system will be presented under various conditions of optical excitation: both below (directly in the QDs) and above (in the matrix) the GaAsSb band gap to probe the physical properties of this system. The dependence of open-circuit voltage and short-circuit current as a function of temperature and power will be presented. By varying temperature and power, the effects of carrier confinement, escape, and transport, as well as intrinsic defects and the formation of a well localized intermediate band can all be evaluated. This research has been supported through the state of Oklahoma's Oklahoma Center for the Advancement of Science & Technology (ONAP 09-08, AR09.2-019, OARS AR12.2-043).

  8. 77 FR 63788 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-10-17

    ... crystalline silicon photovoltaic cells, not exceeding 10,000 mm\\2\\ in surface area, that are permanently... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... countervailable subsidies are being provided to producers and exporters of crystalline silicon photovoltaic cells...

  9. 77 FR 25400 - Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules, From the People's...

    Science.gov (United States)

    2012-04-30

    ... International Trade Administration Crystalline Silicon Photovoltaic Cells, Whether or Not Assembled Into Modules... in this countervailing duty (CVD) investigation of crystalline silicon photovoltaic cells, whether or... 19 CFR 351.210(b)(4)(i) and 210(i). \\1\\ See Crystalline Silicon Photovoltaic Cells, Whether or Not...

  10. Electrically-driven modulation of surface-grafted RGD peptides for manipulation of cell adhesion.

    Science.gov (United States)

    Lashkor, Minhaj; Rawson, Frankie J; Stephenson-Brown, Alex; Preece, Jon A; Mendes, Paula M

    2014-12-21

    Reported herein is a switchable surface that relies on electrically-induced conformational changes within surface-grafted arginine-glycine-aspartate (RGD) oligopeptides as the means of modulating cell adhesion.

  11. DIFFERENTIAL MODULATION OF CATECHOLAMINES BY CHLOROTRIAZINE HERBICIDES IN PHEOCHROMOCYTOMA (PC12) CELLS IN VITRO

    Science.gov (United States)

    Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.Das PC, McElroy WK, Cooper RL.Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.Epidemiological, wildlife, and lab...

  12. 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.

  13. Can Cell to Cell Thermal Runaway Propagation be Prevented in a Li-ion Battery Module?

    Science.gov (United States)

    Jeevarajan, Judith; Lopez, Carlos; Orieukwu, Josephat

    2014-01-01

    Increasing cell spacing decreased adjacent cell damage center dotElectrically connected adjacent cells drained more than physically adjacent cells center dotRadiant barrier prevents propagation when fully installed between BP cells center dotBP cells vent rapidly and expel contents at 100% SOC -Slower vent with flame/smoke at 50% -Thermal runaway event typically occurs at 160 degC center dotLG cells vent but do not expel contents -Thermal runaway event typically occurs at 200 degC center dotSKC LFP modules did not propagate; fuses on negative terminal of cell may provide a benefit in reducing cell to cell damage propagation. New requirement in NASA-Battery Safety Requirements document: JSC 20793 Rev C 5.1.5.1 Requirements - Thermal Runaway Propagation a. For battery designs greater than a 80-Wh energy employing high specific energy cells (greater than 80 watt-hours/kg, for example, lithium-ion chemistries) with catastrophic failure modes, the battery shall be evaluated to ascertain the severity of a worst-case single-cell thermal runaway event and the propensity of the design to demonstrate cell-to-cell propagation in the intended application and environment. NASA has traditionally addressed the threat of thermal runaway incidents in its battery deployments through comprehensive prevention protocols. This prevention-centered approach has included extensive screening for manufacturing defects, as well as robust battery management controls that prevent abuse-induced runaway even in the face of multiple system failures. This focused strategy has made the likelihood of occurrence of such an event highly improbable. b. The evaluation shall include all necessary analysis and test to quantify the severity (consequence) of the event in the intended application and environment as well as to identify design modifications to the battery or the system that could appreciably reduce that severity. In addition to prevention protocols, programs developing battery designs with

  14. Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Soares Fernando A

    2011-04-01

    Full Text Available Abstract Background Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+ and recurrent head and neck squamous cell carcinoma (HNSCC may increase our understanding of the complex biology of this disease. Methods Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative or tumor recurrence (recurrent or non-recurrent tumor after treatment (surgery with neck dissection followed by radiotherapy. Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results The most frequent alterations were the repression of modules in negative lymph node (N0 and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway

  15. 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

  16. Performance Analysis of a Hybrid Generation System of Wind Turbines, Photovoltaic Modules, and a Fuel Cell

    Directory of Open Access Journals (Sweden)

    Bartosz Ceran

    2015-06-01

    Full Text Available This paper presents the results of energy analysis of a generation system consisting of wind turbines, photovoltaic modules, a fuel cell with a polymer membrane, and an electrolyser. The analysis was carried out for three configurations of generating devices’ connections with consumer: I – wind turbines and photovoltaic modules supply electrolyser, II – paralel co-operation of fuel cell with renewables, III – renewables supply electrolyser, with the option of direct supply of the consumer.

  17. Performance Analysis of a Hybrid Generation System of Wind Turbines, Photovoltaic Modules, and a Fuel Cell

    OpenAIRE

    Bartosz Ceran; Krzysztof Sroka

    2015-01-01

    This paper presents the results of energy analysis of a generation system consisting of wind turbines, photovoltaic modules, a fuel cell with a polymer membrane, and an electrolyser. The analysis was carried out for three configurations of generating devices’ connections with consumer: I – wind turbines and photovoltaic modules supply electrolyser, II – paralel co-operation of fuel cell with renewables, III – renewables supply electrolyser, with the option of direct supply of the consumer....

  18. AII amacrine cells: quantitative reconstruction and morphometric analysis of electrophysiologically identified cells in live rat retinal slices imaged with multi-photon excitation microscopy.

    Science.gov (United States)

    Zandt, Bas-Jan; Liu, Jian Hao; Veruki, Margaret Lin; Hartveit, Espen

    2017-01-01

    AII amacrine cells have been found in all mammalian retinas examined and play an important role for visual processing under both scotopic and photopic conditions. Whereas ultrastructural investigations have provided a detailed understanding of synaptic connectivity, there is little information available with respect to quantitative properties and variation of cellular morphology. Here, we performed whole-cell recordings from AII amacrine cells in rat retinal slices and filled the cells with fluorescent dyes. Multi-photon excitation microscopy was used to acquire image stacks and after deconvolution, we performed quantitative morphological reconstruction by computer-aided manual tracing. We reconstructed and performed morphometric analysis on 43 AII amacrine cells, with a focus on branching pattern, dendritic lengths and diameters, surface area, and number and distribution of dendritic varicosities. Compared to previous descriptions, the most surprising result was the considerable extent of branching, with the maximum branch order ranging from approximately 10-40. We found that AII amacrine cells conform to a recently described general structural design principle for neural arbors, where arbor density decreases proportionally to increasing territory size. We confirmed and quantified the bi-stratified morphology of AII amacrine cells by analyzing the arborizations as a function of retinal localization or with Sholl spheres. Principal component and cluster analysis revealed no evidence for morphological subtypes of AII amacrines. These results establish a database of morphometric properties important for studies of development, regeneration, degeneration, and disease processes, as well as a workflow compatible with compartmental modeling.

  19. Climbing fibers mediate vestibular modulation of both "complex" and "simple spikes" in Purkinje cells.

    Science.gov (United States)

    Barmack, N H; Yakhnitsa, V

    2015-10-01

    Climbing and mossy fibers comprise two distinct afferent paths to the cerebellum. Climbing fibers directly evoke a large multispiked action potential in Purkinje cells termed a "complex spike" (CS). By logical exclusion, the other class of Purkinje cell action potential, termed "simple spike" (SS), has often been attributed to activity conveyed by mossy fibers and relayed to Purkinje cells through granule cells. Here, we investigate the relative importance of climbing and mossy fiber pathways in modulating neuronal activity by recording extracellularly from Purkinje cells, as well as from mossy fiber terminals and interneurons in folia 8-10. Sinusoidal roll-tilt vestibular stimulation vigorously modulates the discharge of climbing and mossy fiber afferents, Purkinje cells, and interneurons in folia 9-10 in anesthetized mice. Roll-tilt onto the side ipsilateral to the recording site increases the discharge of both climbing fibers (CSs) and mossy fibers. However, the discharges of SSs decrease during ipsilateral roll-tilt. Unilateral microlesions of the beta nucleus (β-nucleus) of the inferior olive blocks vestibular modulation of both CSs and SSs in contralateral Purkinje cells. The blockage of SSs occurs even though primary and secondary vestibular mossy fibers remain intact. When mossy fiber afferents are damaged by a unilateral labyrinthectomy (UL), vestibular modulation of SSs in Purkinje cells ipsilateral to the UL remains intact. Two inhibitory interneurons, Golgi and stellate cells, could potentially contribute to climbing fiber-induced modulation of SSs. However, during sinusoidal roll-tilt, only stellate cells discharge appropriately out of phase with the discharge of SSs. Golgi cells discharge in phase with SSs. When the vestibularly modulated discharge is blocked by a microlesion of the inferior olive, the modulated discharge of CSs and SSs is also blocked. When the vestibular mossy fiber pathway is destroyed, vestibular modulation of ipsilateral CSs and

  20. Low Doses of Curcuma longa Modulates Cell Migration and Cell-Cell Adhesion.

    Science.gov (United States)

    de Campos, Paloma Santos; Matte, Bibiana Franzen; Diel, Leonardo Francisco; Jesus, Luciano Henrique; Bernardi, Lisiane; Alves, Alessandro Menna; Rados, Pantelis Varvaki; Lamers, Marcelo Lazzaron

    2017-09-01

    Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. 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.

  2. The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Scheipers, Peter; Sørensen, Poul

    2003-01-01

    though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA) on primary T cells.......Histone deacetylase inhibitors (HDACIs) induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even...

  3. ICAM-3 activation modulates cell-cell contacts of human bone marrow endothelial cells

    NARCIS (Netherlands)

    van Buul, J. D.; Mul, F. P. J.; van der Schoot, C. E.; Hordijk, P. L.

    2004-01-01

    The Ig-like cell adhesion molecule ICAM-3 is mainly expressed on human leukocytes and is involved in cell-cell interactions. Its expression on endothelium is observed during disorders such as Crohn's disease and in solid tumors. We found low but detectable expression of ICAM-3 on VE-cadherin-

  4. PVSIM{copyright}: A simulation program for photovoltaic cells, modules, and arrays

    Energy Technology Data Exchange (ETDEWEB)

    King, D.L.; Dudley, J.K.; Boyson, W.E.

    1996-06-01

    An electrical simulation model for photovoltaic cells, modules, and arrays has been developed that will be useful to a wide range of analysts in the photovoltaic industry. The Microsoft{reg_sign} Windows{trademark} based program can be used to analyze individual cells, to analyze the effects of cell mismatch or reverse bias(`hot spot`) heating in modules and to analyze the performance of large arrays of modules including bypass and blocking diodes. User defined statistical variance can be applied to the fundamental parameters used to simulate the cells and diodes. The model is most appropriate for cells that can be accurately modeled using a two-diode equivalent circuit. This paper describes the simulation program and illustrates its versatility with examples.

  5. Nonlinear spectral imaging of human normal skin, basal cell carcinoma and squamous cell carcinoma based on two-photon excited fluorescence and second-harmonic generation

    Science.gov (United States)

    Xiong, S. Y.; Yang, J. G.; Zhuang, J.

    2011-10-01

    In this work, we use nonlinear spectral imaging based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) for analyzing the morphology of collagen and elastin and their biochemical variations in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin tissue. It was found in this work that there existed apparent differences among BCC, SCC and normal skin in terms of their thickness of the keratin and epithelial layers, their size of elastic fibers, as well as their distribution and spectral characteristics of collagen. These differences can potentially be used to distinguish BCC and SCC from normal skin, and to discriminate between BCC and SCC, as well as to evaluate treatment responses.

  6. 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.

  7. Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1.

    Science.gov (United States)

    Kiritoshi, Takaki; Sun, Hao; Ren, Wenjie; Stauffer, Shaun R; Lindsley, Craig W; Conn, P Jeffrey; Neugebauer, Volker

    2013-03-01

    The medial prefrontal cortex (mPFC) serves executive cognitive functions such as decision-making that are impaired in neuropsychiatric disorders and pain. We showed previously that amygdala-driven abnormal inhibition and decreased output of mPFC pyramidal cells contribute to pain-related impaired decision-making (Ji et al., 2010). Therefore, modulating pyramidal output is desirable therapeutic goal. Targeting metabotropic glutamate receptor subtype mGluR5 has emerged as a cognitive-enhancing strategy in neuropsychiatric disorders, but synaptic and cellular actions of mGluR5 in the mPFC remain to be determined. The present study determined synaptic and cellular actions of mGluR5 to test the hypothesis that increasing mGluR5 function can enhance pyramidal cell output. Whole-cell voltage- and current-clamp recordings were made from visually identified pyramidal neurons in layer V of the mPFC in rat brain slices. Both the prototypical mGluR5 agonist CHPG and a positive allosteric modulator (PAM) for mGluR5 (VU0360172) increased synaptically evoked spiking (E-S coupling) in mPFC pyramidal cells. The facilitatory effects of CHPG and VU0360172 were inhibited by an mGluR5 antagonist (MTEP). CHPG, but not VU0360172, increased neuronal excitability (frequency-current [F-I] function). VU0360172, but not CHPG, increased evoked excitatory synaptic currents (EPSCs) and amplitude, but not frequency, of miniature EPSCs, indicating a postsynaptic action. VU0360172, but not CHPG, decreased evoked inhibitory synaptic currents (IPSCs) through an action that involved cannabinoid receptor CB1, because a CB1 receptor antagonist (AM281) blocked the inhibitory effect of VU0360172 on synaptic inhibition. VU0360172 also increased and prolonged CB1-mediated depolarization-induced suppression of synaptic inhibition (DSI). Activation of CB1 with ACEA decreased inhibitory transmission through a presynaptic mechanism. The results show that increasing mGluR5 function enhances mPFC output. This

  8. Modulation of GLO1 Expression Affects Malignant Properties of Cells

    Directory of Open Access Journals (Sweden)

    Antje Hutschenreuther

    2016-12-01

    Full Text Available The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO. Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1 that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.

  9. Cellular Factors Targeting APCs to Modulate Adaptive T Cell Immunity

    Directory of Open Access Journals (Sweden)

    Anabelle Visperas

    2014-01-01

    Full Text Available The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity.

  10. Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions.

    Science.gov (United States)

    Pan, Qunwen; Liu, Hua; Zheng, Chunyan; Zhao, Yuhui; Liao, Xiaorong; Wang, Yan; Chen, Yanfang; Zhao, Bin; Lazartigues, Eric; Yang, Yi; Ma, Xiaotang

    2016-01-01

    Purpose: Microvesicles (MV) can modulate the function of recipient cells by transferring their contents. Our previous study highlighted that MV released from tumor necrosis factor-α (TNF-α) plus serum deprivation (SD)-stimulated endothelial progenitor cells, induce detrimental effects on endothelial cells. In this study, we investigated the potential effects of endothelial MV (EMV) on proliferation, migration, and apoptosis of human brain vascular smooth cells (HBVSMC). Methods: EMV were prepared from human brain microvascular endothelial cells (HBMEC) cultured in a TNF-α plus SD medium. RNase-EMV were made by treating EMV with RNase A for RNA depletion. The proliferation, apoptosis and migration abilities of HBVSMC were determined after co-culture with EMV or RNase-EMV. The Mek1/2 inhibitor, PD0325901, was used for pathway analysis. Western blot was used for analyzing the proteins of Mek1/2, Erk1/2, phosphorylation Erk1/2, activated caspase-3 and Bcl-2. The level of miR-146a-5p was measured by qRT-PCR. Results: (1) EMV significantly promoted the proliferation and migration of HBVSMC. The effects were accompanied by an increase in Mek1/2 and p-Erk1/2, which could be abolished by PD0325901; (2) EMV decreased the apoptotic rate of HBVSMC by approximately 35%, which was accompanied by cleaved caspase-3 down-regulation and Bcl-2 up-regulation; (3) EMV increased miR-146a-5p level in HBVSMC by about 2-folds; (4) RNase-treated EMV were less effective than EMV on HBVSMC activities and miR-146a-5p expression. Conclusion: EMV generated under inflammation challenge can modulate HBVSMC function and fate via their carried RNA. This is associated with activation of theMek1/2/Erk1/2 pathway and caspase-3/Bcl-2 regulation, during which miR-146a-5p may play an important role. The data suggest that EMV derived from inflammation-challenged endothelial cells are detrimental to HBVSMC homeostatic functions, highlighting potential novel therapeutic targets for vascular diseases.

  11. Canonical Wnt signaling negatively modulates regulatory T cell function

    NARCIS (Netherlands)

    Loosdregt, J. van; Fleskens, V.; Mokry, M.; Boxtel, R. van; Meerding, J.M.; Pals, C.E.G.M.; Kurek, D.; Baert, M.R.; Delemarre, E.M.; Gröne, A.; Groot Koerkamp, M.J.A.; Sijts, E.J.A.M.; Nieuwenhuis, E.E.S.; Maurice, M.M.; Es, J.H. van; Berge, D. ten; Holstege, F.C.P.; Staal, F.J.T.; Zaiss, D.M.W.; Prakken, B.J.; Coffer, P.J

    2013-01-01

    Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active

  12. Canonical Wnt Signaling Negatively Modulates Regulatory T Cell Function

    NARCIS (Netherlands)

    Loosdregt, J. van; Fleskens, V.; Tiemessen, M.M.; Mokry, M.; Boxtel, R. van; Meerding, J.; Pals, C.E.G.M.; Kurek, D.; Baert, M.R.; Delemarre, E.M.; Gröne, A.; Groot Koerkamp, M.J.A.; Sijts, E.J.A.M.; Nieuwenhuis, E.E.S.; Maurice, M.M.; Es, J.H. van; Berge, D. ten; Holstege, F.C.; Staal, F.J.T.; Zaiss, D.M.W.; Prakken, A.B.J.; Coffer, P.J

    2013-01-01

    Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active

  13. 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.

  14. 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

  15. 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.

  16. Plasmonic excitation-assisted optical and electric enhancement in ultra-thin solar cells: the influence of nano-strip cross section

    Energy Technology Data Exchange (ETDEWEB)

    Sabaeian, Mohammad, E-mail: sabaiean@scu.ac.ir; Heydari, Mehdi; Ajamgard, Narges [Physics Department, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, 61357-43135 (Iran, Islamic Republic of)

    2015-08-15

    The effects of Ag nano-strips with triangle, rectangular and trapezoid cross sections on the optical absorption, generation rate, and short-circuit current density of ultra-thin solar cells were investigated. By putting the nano-strips as a grating structure on the top of the solar cells, the waveguide, surface plasmon polariton (SPP), and localized surface plasmon (LSP) modes, which are excited with the assistance of nano-strips, were evaluated in TE and TM polarizations. The results show, firstly, the TM modes are more influential than TE modes in optical and electrical properties enhancement of solar cell, because of plasmonic excitations in TM mode. Secondly, the trapezoid nano-strips reveal noticeable impact on the optical absorption, generation rate, and short-circuit current density enhancement than triangle and rectangular ones. In particular, the absorption of long wavelengths which is a challenge in ultra-thin solar cells is significantly improved by using Ag trapezoid nano-strips.

  17. Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module.

    Science.gov (United States)

    McIlrath, Victoria; Trye, Alice; Aguanno, Ann

    2015-06-18

    Undergraduate biology students are required to learn, understand and apply a variety of cellular and molecular biology concepts and techniques in preparation for biomedical, graduate and professional programs or careers in science. To address this, a simple laboratory module was devised to teach the concepts of cell division, cellular communication and cancer through the application of animal cell culture techniques. Here the mouse mammary tumor (MMT) cell line is used to model for breast cancer. Students learn to grow and characterize these animal cells in culture and test the effects of traditional and non-traditional chemotherapy agents on cell proliferation. Specifically, students determine the optimal cell concentration for plating and growing cells, learn how to prepare and dilute drug solutions, identify the best dosage and treatment time course of the antiproliferative agents, and ascertain the rate of cell death in response to various treatments. The module employs both a standard cell counting technique using a hemocytometer and a novel cell counting method using microscopy software. The experimental procedure lends to open-ended inquiry as students can modify critical steps of the protocol, including testing homeopathic agents and over-the-counter drugs. In short, this lab module requires students to use the scientific process to apply their knowledge of the cell cycle, cellular signaling pathways, cancer and modes of treatment, all while developing an array of laboratory skills including cell culture and analysis of experimental data not routinely taught in the undergraduate classroom.

  18. ROCK1 and LIM kinase modulate retrovirus particle release and cell-cell transmission events.

    Science.gov (United States)

    Wen, Xiaoyun; Ding, Lingmei; Wang, Jaang-Jiun; Qi, Mingli; Hammonds, Jason; Chu, Hin; Chen, Xuemin; Hunter, Eric; Spearman, Paul

    2014-06-01

    The assembly and release of retroviruses from the host cells require dynamic interactions between viral structural proteins and a variety of cellular factors. It has been long speculated that the actin cytoskeleton is involved in retrovirus production, and actin and actin-related proteins are enriched in HIV-1 virions. However, the specific role of actin in retrovirus assembly and release remains unknown. Here we identified LIM kinase 1 (LIMK1) as a cellular factor regulating HIV-1 and Mason-Pfizer monkey virus (M-PMV) particle release. Depletion of LIMK1 reduced not only particle output but also virus cell-cell transmission and was rescued by LIMK1 replenishment. Depletion of the upstream LIMK1 regulator ROCK1 inhibited particle release, as did a competitive peptide inhibitor of LIMK1 activity that prevented cofilin phosphorylation. Disruption of either ROCK1 or LIMK1 led to enhanced particle accumulation on the plasma membrane as revealed by total internal reflection fluorescence microscopy (TIRFM). Electron microscopy demonstrated a block to particle release, with clusters of fully mature particles on the surface of the cells. Our studies support a model in which ROCK1- and LIMK1-regulated phosphorylation of cofilin and subsequent local disruption of dynamic actin turnover play a role in retrovirus release from host cells and in cell-cell transmission events. Viruses often interact with the cellular cytoskeletal machinery in order to deliver their components to the site of assembly and budding. This study indicates that a key regulator of actin dynamics at the plasma membrane, LIM kinase, is important for the release of viral particles for HIV as well as for particle release by a distantly related retrovirus, Mason-Pfizer monkey virus. Moreover, disruption of LIM kinase greatly diminished the spread of HIV from cell to cell. These findings suggest that LIM kinase and its dynamic modulation of the actin cytoskeleton in the cell may be an important host factor for

  19. Rat peritubular cell secretory activity: modulation by vitamin A.

    Science.gov (United States)

    Galdieri, M; Provenzano, D

    1996-10-01

    Protein synthesis and secretion by rat peritubular cells cultured in the presence or in the absence of vitamin A were analyzed after labelling the cells with different amino acids. Vitamin A reduces the amount of proline incorporated into the newly-synthesized proteins secreted by the peritubular cells. By mono- and two-dimensional gel electrophoresis analysis, qualitative differences induced by retinol addition were detected in the proteins secreted by the proline-labelled cells. In particular we demonstrate that the amount of fibronectin secreted by the cells is reduced after retinol addition. Northern blot analysis indicates that fibronectin messenger RNA transcription is also reduced as a consequence of the vitamin addition.

  20. Gut microbiota modulate T cell trafficking into human colorectal cancer.

    Science.gov (United States)

    Cremonesi, Eleonora; Governa, Valeria; Garzon, Jesus Francisco Glaus; Mele, Valentina; Amicarella, Francesca; Muraro, Manuele Giuseppe; Trella, Emanuele; Galati-Fournier, Virginie; Oertli, Daniel; Däster, Silvio Raffael; Droeser, Raoul A; Weixler, Benjamin; Bolli, Martin; Rosso, Raffaele; Nitsche, Ulrich; Khanna, Nina; Egli, Adrian; Keck, Simone; Slotta-Huspenina, Julia; Terracciano, Luigi M; Zajac, Paul; Spagnoli, Giulio Cesare; Eppenberger-Castori, Serenella; Janssen, Klaus-Peter; Borsig, Lubor; Iezzi, Giandomenica

    2018-02-06

    Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Development and testing of shingle-type solar cell modules. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Shepard, N.F.

    1979-02-28

    The design, development, fabrication and testing of a shingle-type terrestrial solar cell module which produces 98 watts/m/sup 2/ of exposed module area at 1 kW/m/sup 2/ insolation and 61/sup 0/C are reported. These modules make it possible to easily incorporate photovoltaic power generation into the sloping roofs of residential or commercial buildings by simply nailing the modules to the plywood roof sheathing. This design consists of nineteen series-connected 53 mm diameter solar cells arranged in a closely packaged hexagon configuration. These cells are individually bonded to the embossed surface of a 3 mm thick thermally tempered hexagon-shaped piece of ASG SUNADEX glass. Monsanto SAFLEX polyvinyl butyral is used as the laminating adhesive. RTVII functions as the encapsulant between the underside of the glass superstrate and a rear protective sheet of 0.8 mm thick TEXTOLITE. The semi-flexible portion of each shingle module is a composite laminate construction consisting of outer layers of B.F. Goodrich FLEXSEAL and an epichlorohydrin closed cell foam core. The module design has satisfactorily survived the JPL-defined qualification testing program which includes 50 thermal cycles between -40 and +90/sup 0/C, a seven-day temperature-humidity exposure test and a mechanical integrity test consisting of a bidirectional cyclic loading at 2390 Pa (50 lb/ft/sup 2/) which is intended to simulate loads due to a 45 m/s (100 mph) wind.

  2. Modulation of immune cells and Th1/Th2 cytokines in insulin-treated ...

    African Journals Online (AJOL)

    Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus. Magloire Pandoua Nekoua1, Rufine Fachinan1, Amidou K Atchamou1, Odilon Nouatin2,. Daniel Amoussou-Guenou3, Marcellin K Amoussou-Guenou4, Kabirou Moutairou1, Akadiri Yessoufou1. 1. Laboratory of Cell Biology and ...

  3. Modulating the stem cell niche for tissue regeneration

    Science.gov (United States)

    Lane, Steven W; Williams, David A; Watt, Fiona M

    2015-01-01

    The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell–extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions. PMID:25093887

  4. Cadherin-11 modulates cell morphology and collagen synthesis in periodontal ligament cells under mechanical stress.

    Science.gov (United States)

    Feng, Lishu; Zhang, Yimei; Kou, Xiaoxing; Yang, Ruili; Liu, Dawei; Wang, Xuedong; Song, Yang; Cao, Haifeng; He, Danqing; Gan, Yehua; Zhou, Yanheng

    2017-03-01

    To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed β-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time- and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed β-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation.

  5. Single cell amperometry reveals curcuminoids modulate the release of neurotransmitters during exocytosis from PC12 cells.

    Science.gov (United States)

    Li, Xianchan; Mohammadi, Amir Saeid; Ewing, Andrew G

    2016-11-15

    We used single cell amperometry to examine whether curcumin and bisdemethoxycurcumin (BDMC), substances that are suggested to affect learning and memory, can modulate monoamine release from PC12 cells. Our results indicate both curcumin and BDMC need long-term treatment (72 h in this study) to influence exocytosis effectively. By analyzing the parameters calculated from single exocytosis events, it can be concluded that curcumin and BDMC affect exocytosis through different mechanisms. Curcumin accelerates the event dynamics with no significant change of the monoamine amount released from single exocytotic events, whereas BDMC attenuates the amount from single exocytotic event with no significant change of the event dynamics. This comparison of the effect of curcumin and BDMC on exocytosis at the single cell level brings insight into their different mechanisms, which might lead to different biological actions. The effect of curcumin and BDMC on the opening and closing of the exocytotic fusion pore were also investigated. These results might be helpful for understanding the improvement of learning and memory and the anti-depression properties of curcuminoids.

  6. Modulation of epithelial cell polarity by bacterial pathogens.

    Science.gov (United States)

    Tapia, Rocio; Kralicek, Sarah E; Hecht, Gail A

    2017-10-01

    Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and basolateral membrane domains separated by intercellular junctions, including tight junctions (TJs), which contribute to the maintenance of apical-basal polarity. Polarity complexes also contribute to the establishment of TJ formation. Several pathogens perturb epithelial TJ barrier function and structure in addition to causing a loss of apical-basal polarity. Here, we review the impact of pathogenic bacteria on the disruption of cell-cell junctions and epithelial polarity. © 2017 New York Academy of Sciences.

  7. Lactobacilli Modulate Natural Killer Cell Responses In Vitro

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    . The IFN-gamma concentration was measured by ELISA. Incubation of NK cells with a Lactobacillus acidophilus strain increased the proliferation of the NK cells and induced IFN-gamma production, both to levels comparable to PHA stimulation. The proliferative response was further enhanced with autologous...... monocytes present, probably because cytokines, secreted by monocytes having engulfed bacteria, stimulated the NK cells. In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. These results demonstrate that various strains of lactobacilli have...

  8. 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.

  9. Modulation of hepatocarcinoma cell morphology and activity by parylene-C coating on PDMS.

    Directory of Open Access Journals (Sweden)

    Nazaré Pereira-Rodrigues

    Full Text Available BACKGROUND: The ability to understand and locally control the morphogenesis of mammalian cells is a fundamental objective of cell and developmental biology as well as tissue engineering research. We present parylene-C (ParC deposited on polydimethylsiloxane (PDMS as a new substratum for in vitro advanced cell culture in the case of Human Hepatocarcinoma (HepG2 cells. PRINCIPAL FINDINGS: Our findings establish that the intrinsic properties of ParC-coated PDMS (ParC/PDMS influence and modulate initial extracellular matrix (ECM; here, type-I collagen surface architecture, as compared to non-coated PDMS substratum. Morphological changes induced by the presence of ParC on PDMS were shown to directly affect liver cell metabolic activity and the expression of transmembrane receptors implicated in cell adhesion and cell-cell interaction. These changes were characterized by atomic force microscopy (AFM, which elucidated differences in HepG2 cell adhesion, spreading, and reorganization into two- or three-dimensional structures by neosynthesis of ECM components. Local modulation of cell aggregation was successfully performed using ParC/PDMS micropatterns constructed by simple microfabrication. CONCLUSION/SIGNIFICANCE: We demonstrated for the first time the modulation of HepG2 cells' behavior in relation to the intrinsic physical properties of PDMS and ParC, enabling the local modulation of cell spreading in a 2D or 3D manner by simple microfabrication techniques. This work will provide promising insights into the development of cell-based platforms that have many applications in the field of in vitro liver tissue engineering, pharmacology and therapeutics.

  10. Resin material for solar cell module; Taiyo denchi mojuruyo jushi zairyo

    Energy Technology Data Exchange (ETDEWEB)

    Iwashiro, J.; Yoshikawa, H. [Tokai Rubber Co. Ltd., Aichi (Japan)

    1997-12-02

    The area of the solar cell module used for the solar car is as large as 8m{sup 2} as a maximum to cover the most part of the vehicle, and the conventional solar cell module for which glass sheets are used is too heavy. This invention relates to resin material for the solar cell module, which consists of non-yellowing type transparent thermoplastic polyurethane resin which has the hardness property of less than 90deg JIS A (H{sub s}) and can be used favorably as the resin for the solar cell module for the solar car. The solar cell module which uses synthetic resin harder than 90deg JIS A hardness (H{sub s}) is inferior in the impact resistance against splashing substances in high speed driving of the solar car. This special thermoplastic polyurethane resin is produced by the partial polymerization of polyisocyanate and polyol, and ether and ester system polyurethane resins are preferred. 7 figs., 2 tabs.

  11. Modulating Leukemia-Initiating Cell Quiescence to Improve Leukemia Treatment

    Science.gov (United States)

    2015-09-01

    pre-HSC stage (29), we found maternal B cells in the placenta at this time point whereas YS and P-Sp derived B-1 cells were confirmed to be embryonic...Ribera JM, Oriol A. Acute lymphoblastic leukemia in adolescents and young adults. Hematol Oncol Clin North Am 2009;23:1033-42; PMID:19825451; http

  12. Canonical Wnt signaling negatively modulates regulatory T cell function

    NARCIS (Netherlands)

    J. van Loosdregt (Jorg); V. Fleskens (Veerle); M.M. Tiemessen (Machteld); M. Mokry (Michal); R. van Boxtel (Ruben); J. Meerding (Jenny); C.E.G.M. Pals (Cornelieke); D. Kurek (Dorota); M.R.M. Baert (Miranda); E.M. Delemarre (Eveline); A. Gröne (Andrea); M.J.A. Groot Koerkamp (Marianne); A.J.A.M. Sijts (Alice ); E.E.S. Nieuwenhuis (Edward); M.M. Maurice (Madelon); J.H. van Es (Johan); D. ten Berge (Derk); F.C. Holstege (Frank); F.J.T. Staal (Frank); D.M.W. Zaiss (Dietmar); B.J. Prakken (Berent); P.J. Coffer (Paul)

    2013-01-01

    textabstractFoxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active

  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. Modulation of vesicular catecholamine release from rat PC12 cells

    NARCIS (Netherlands)

    Westerink, R.H.S.

    2002-01-01

    Intercellular communication is of vital importance for the nervous system, since the nervous system is the main coordinating system in animals. Nerve cell communication is initiated by the release of chemical messengers, neurotransmitters, from the presynaptic nerve cell. The neurotransmitters, such

  15. Adipose-Derived Stem Cell Modulation of T-Cell Regulation Correlates with Heme Oxgenase-1 Pathway Changes.

    Science.gov (United States)

    Chien, Ching-Ming; Chen, Yung-Wei; Chen, Chien-Chang; Wu, Yi-Chia; Huang, Shu-Hung; Lee, Su-Shin; Lai, Cheng-Sheng; Lin, Sin-Daw; Wang, Ching-Jen; Kuo, Yur-Ren

    2016-11-01

    The authors' previous proteome study revealed that haptoglobin was involved in adipose-derived stem cell modulation of allotransplant survival and T-cell regulation to induce immune tolerance. This study investigated whether adipose-derived stem cells could modulate T-cell regulation through haptoglobin and the downstream heme oxgenase-1 pathway in vitro. Splenocytes were isolated from Lewis rat spleens and then CD3 T cells were purified using anti-CD3 beads. Adipose-derived stem cells were harvested from Lewis rats and co-cultured with the T cells. After Transwell co-culture at different periods, the authors analyzed cell proliferation with a bromodeoxyuridine assay. Cell extractions and culture supernatants were collected for further analysis. Heme oxgenase-1 and related protein expression levels from the adipose-derived stem cells and T cells were detected using Western blotting. The related cytokine expression levels were analyzed with enzyme-linked immunosorbent assay kits. Flow cytometry was used to detect the regulatory T-cell proportion. The adipose-derived stem cells significantly suppressed T-cell proliferation. The regulatory T-cell percentages were significantly increased in the adipose-derived stem cells that were co-cultured with T cells compared with T cells alone without adipose-derived stem cell co-culture. Heme oxgenase-1 expression in concanavalin A-stimulated T cells that were co-cultured with adipose-derived stem cells revealed a significant increase compared with concanavalin A-stimulated T cells alone. Cytokine assays of the culture supernatants revealed that transforming growth factor-β and interleukin-10 were significantly increased and interferon-γ was statistically decreased in the adipose-derived stem cell-co-cultured T-cell group compared with other groups; however, blockade with a heme oxgenase-1 inhibitor (zinc protoporphyrin IX) protected against these changes. Adipose-derived stem cells modulate T-cell proliferation and enhance

  16. Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO.

    Science.gov (United States)

    Glazier, Kim S; Hake, Sandra B; Tobin, Helen M; Chadburn, Amy; Schattner, Elaine J; Denzin, Lisa K

    2002-04-15

    Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell-T cell interactions that are essential for B cells to survive positive selection in the GC.

  17. Mast cell function modulating IgE-mediated allergy

    Directory of Open Access Journals (Sweden)

    Ruby Pawankar

    1999-01-01

    Full Text Available Allergic diseases, such as atopic rhinitis, bronchial asthma and urticaria, are prevalent and increasing in frequency. Mast cells are known to play a central role in the immediate phase reaction of allergic diseases through the IgE-mediated release of a variety of chemical mediators, such as histamine, leukotrienes and prostaglandins. In contrast, T lymphocytes, basophils and eosinophils are thought to be responsible for inducing the late phase response. However, whether the mast cell can be simplistically assigned a role in the immediate phase allergic response and whether mast cells are necessary for the ongoing allergic response, including the development of hyperresponsiveness, remains to be completely studied. In the present article, the author will discuss the integrated roles of mast cells in IgE-mediated allergic inflammation, with specific emphasis on the roles of mast cell-derived cytokines in the late phase allergic response and chronic allergic inflammation.

  18. 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

  19. Lrp4 modulates extracellular integration of cell signaling pathways in development.

    Directory of Open Access Journals (Sweden)

    Atsushi Ohazama

    Full Text Available The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway.

  20. Lrp4 modulates extracellular integration of cell signaling pathways in development.

    Science.gov (United States)

    Ohazama, Atsushi; Johnson, Eric B; Ota, Masato S; Choi, Hong Y; Choi, Hong J; Porntaveetus, Thantrira; Oommen, Shelly; Itoh, Nobuyuki; Eto, Kazuhiro; Gritli-Linde, Amel; Herz, Joachim; Sharpe, Paul T

    2008-01-01

    The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway.

  1. Oct4 targets regulatory nodes to modulate stem cell function.

    Directory of Open Access Journals (Sweden)

    Pearl A Campbell

    2007-06-01

    Full Text Available Stem cells are characterized by two defining features, the ability to self-renew and to differentiate into highly specialized cell types. The POU homeodomain transcription factor Oct4 (Pou5f1 is an essential mediator of the embryonic stem cell state and has been implicated in lineage specific differentiation, adult stem cell identity, and cancer. Recent description of the regulatory networks which maintain 'ES' have highlighted a dual role for Oct4 in the transcriptional activation of genes required to maintain self-renewal and pluripotency while concomitantly repressing genes which facilitate lineage specific differentiation. However, the molecular mechanism by which Oct4 mediates differential activation or repression at these loci to either maintain stem cell identity or facilitate the emergence of alternate transcriptional programs required for the realization of lineage remains to be elucidated. To further investigate Oct4 function, we employed gene expression profiling together with a robust statistical analysis to identify genes highly correlated to Oct4. Gene Ontology analysis to categorize overrepresented genes has led to the identification of themes which may prove essential to stem cell identity, including chromatin structure, nuclear architecture, cell cycle control, DNA repair, and apoptosis. Our experiments have identified previously unappreciated roles for Oct4 for firstly, regulating chromatin structure in a state consistent with self-renewal and pluripotency, and secondly, facilitating the expression of genes that keeps the cell poised to respond to cues that lead to differentiation. Together, these data define the mechanism by which Oct4 orchestrates cellular regulatory pathways to enforce the stem cell state and provides important insight into stem cell function and cancer.

  2. NHERF-1: Modulator of Glioblastoma Cell Migration and Invasion

    Directory of Open Access Journals (Sweden)

    Kerri L. Kislin

    2009-04-01

    Full Text Available The invasive nature of malignant gliomas is a clinical problem rendering tumors incurable by conventional treatment modalities such as surgery, ionizing radiation, and temozolomide. Na+/H+ exchanger regulatory factor 1 (NHERF-1 is a multifunctional adaptor protein, recruiting cytoplasmic signaling proteins and membrane receptors/transporters into functional complexes. This study revealed that NHERF-1 expression is increased in highly invasive cells that reside in the rim of glioblastoma multiforme (GBM tumors and that NHERF-1 sustains glioma migration and invasion. Gene expression profiles were evaluated from laser capture-microdissected human GBM cells isolated from patient tumor cores and corresponding invaded white matter regions. The role of NHERF-1 in the migration and dispersion of GBM cell lines was examined by reducing its expression with small-interfering RNA followed by radial migration, three-dimensional collagen dispersion, immunofluorescence, and survival assays. The in situ expression of NHERF-1 protein was restricted to glioma cells and the vascular endothelium, with minimal to no detection in adjacent normal brain tissue. Depletion of NHERF-1 arrested migration and dispersion of glioma cell lines and caused an increase in cell-cell cohesiveness. Glioblastoma multiforme cells with depleted NHERF-1 evidenced a marked decrease in stress fibers, a larger cell size, and a more rounded shape with fewer cellular processes. When NHERF-1 expression was reduced, glioma cells became sensitized to temozolomide treatment resulting in increased apoptosis. Taken together, these results provide the first evidence for NHERF-1 as a participant in the highly invasive phenotype of malignant gliomas and implicate NHERF-1 as a possible therapeutic target for treatment of GBM.

  3. 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.

  4. 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.

  5. Promiscuous, non-catalytic, tandem carbohydrate-binding modules modulate the cell-wall structure and development of transgenic tobacco (Nicotiana tabacum) plants

    NARCIS (Netherlands)

    Olawole, O.; Jacobsen, E.; Timmers, J.F.P.; Gilbert, H.J.; Blake, W.; Knox, J.P.; Visser, R.G.F.; Vincken, J.P.

    2007-01-01

    We have compared heterologous expression of two types of carbohydrate binding module (CBM) in tobacco cell walls. These are the promiscuous CBM29 modules (a tandem CBM29-1-2 and its single derivative CBM29-2), derived from a non-catalytic protein1, NCP1, of the Piromyces equi cellulase/hemicellulase

  6. Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    L. Contreras-Ruiz

    2013-01-01

    Full Text Available Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice. We found that apoptosis of goblet cells was primarily induced by TNF-α and IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

  7. Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

    OpenAIRE

    Patel, Hiren; Bhartiya, Deepa; Parte, Seema; Gunjal, Pranesh; Yedurkar, Snehal; Bhatt, Mithun

    2013-01-01

    Background We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants ?progenitors? termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively spliced receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in literature of which FSH-R1 and FS...

  8. Five-cell superconducting RF module with a PBG coupler cell: design and cold testing of the copper prototype

    Energy Technology Data Exchange (ETDEWEB)

    Arsenyev, Sergey Andreyevich [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Simakov, Evgenya Ivanovna [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Shchegolkov, Dmitry [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Boulware, Chase [Niowave, Lansing, MI (United States); Grimm, Terry [Niowave, Lansing, MI (United States); Rogacki, Adam [Niowave, Lansing, MI (United States)

    2015-04-29

    We report the design and experimental data for a copper prototype of a superconducting radio-frequency (SRF) accelerator module. The five-cell module has an incorporated photonic band gap (PBG) cell with couplers. The purpose of the PBG cell is to achieve better higher order mode (HOM) damping, which is vital for preserving the quality of high-current electron beams. Better HOM damping raises the current threshold for beam instabilities in novel SRF accelerators. The PBG design also increases the real-estate gradient of the linac because both HOM damping and the fundamental power coupling can be done through the PBG cell instead of on the beam pipe via complicated end assemblies. First, we will discuss the design and accelerating properties of the structure. The five-cell module was optimized to provide good HOM damping while maintaining the same accelerating properties as conventional elliptical-cell modules. We will then discuss the process of tuning the structure to obtain the desired accelerating gradient profile. Finally, we will list measured quality factors for the accelerating mode and the most dangerous HOMs.

  9. Aptamers for CD Antigens: From Cell Profiling to Activity Modulation

    Directory of Open Access Journals (Sweden)

    Amin Nozari

    2017-03-01

    Full Text Available Nucleic acid-based aptamers are considered to be a promising alternative to antibodies because of their strong and specific binding to diverse targets, fast and inexpensive chemical synthesis, and easy labeling with a fluorescent dye or therapeutic agent. Cluster of differentiation (CD proteins are among the most popular antigens for aptamers on the cell surface. These anti-CD aptamers could be used in cell biology and biomedicine, from simple cell phenotyping by flow cytometry or fluorescent microscopy to diagnosis and treatment of HIV/AIDS to cancer and immune therapies. The unique feature of aptamers is that they can act simultaneously as an agonist and antagonist of CD receptors depending on a degree of aptamer oligomerization. Aptamers can also deliver small interfering RNA to silence vital genes in CD-positive cells. In this review, we summarize nucleic acid sequences of anti-CD aptamers and their use, which have been validated in multiple studies.

  10. Modulation of Acupuncture on Cell Apoptosis and Autophagy

    OpenAIRE

    Luo, Dan; Chen, Rui; Liang, Feng-xia

    2017-01-01

    Acupuncture has been historically practiced to treat medical disorders by mechanically stimulating specific acupoints. Despite its well-documented efficacy, its biological basis largely remains elusive. Recent studies suggested that cell apoptosis and autophagy might play key roles in acupuncture therapy. Therefore, we searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI), aiming to find the potential relationship between acupuncture and cell apoptosis an...

  11. Modulations of cell cycle checkpoints during HCV associated disease

    Directory of Open Access Journals (Sweden)

    Jafri Wasim

    2009-08-01

    Full Text Available Abstract Background Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC. This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. Methods Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1 with significant changes in mRNA levels (> 2-fold, p-value Results In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. Conclusion Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development.

  12. Keratin 8 modulates β-cell stress responses and normoglycaemia.

    Science.gov (United States)

    Alam, Catharina M; Silvander, Jonas S G; Daniel, Ebot N; Tao, Guo-Zhong; Kvarnström, Sofie M; Alam, Parvez; Omary, M Bishr; Hänninen, Arno; Toivola, Diana M

    2013-12-15

    Keratin intermediate filament (IF) proteins are epithelial cell cytoskeletal components that provide structural stability and protection from cell stress, among other cellular and tissue-specific functions. Numerous human diseases are associated with IF gene mutations, but the function of keratins in the endocrine pancreas and their potential significance for glycaemic control are unknown. The impact of keratins on β-cell organisation and systemic glucose control was assessed using keratin 8 (K8) wild-type (K8(+/+)) and K8 knockout (K8(-/-)) mice. Islet β-cell keratins were characterised under basal conditions, in streptozotocin (STZ)-induced diabetes and in non-obese diabetic (NOD) mice. STZ-induced diabetes incidence and islet damage was assessed in K8(+/+) and K8(-/-) mice. K8 and K18 were the predominant keratins in islet β-cells and K8(-/-) mice expressed only remnant K18 and K7. K8 deletion resulted in lower fasting glucose levels, increased glucose tolerance and insulin sensitivity, reduced glucose-stimulated insulin secretion and decreased pancreatic insulin content. GLUT2 localisation and insulin vesicle morphology were disrupted in K8(-/-) β-cells. The increased levels of cytoplasmic GLUT2 correlated with resistance to high-dose STZ-induced injury in K8(-/-) mice. However, K8 deletion conferred no long-term protection from STZ-induced diabetes and prolonged STZ-induced stress caused increased exocrine damage in K8(-/-) mice. β-cell keratin upregulation occurred 2 weeks after treatments with low-dose STZ in K8(+/+) mice and in diabetic NOD mice, suggesting a role for keratins, particularly in non-acute islet stress responses. These results demonstrate previously unrecognised functions for keratins in β-cell intracellular organisation, as well as for systemic blood glucose control under basal conditions and in diabetes-induced stress.

  13. 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.

  14. Carbon nanotube monolayer patterns for modulating stem cell behavior

    Science.gov (United States)

    Park, Sung Young; Lee, Ki-Bum; Hong, Seunghun

    2010-03-01

    Nanostructures and nanomaterials intrinsically can interact with biological systems at the fundamental molecular levels with high specificity, which has held great potential for developing methods of controlling cell behaviors such as adhesion, proliferation, and differentiation. For instance, carbon nanotubes (CNTs), as extracellular scaffolds, have been used to guide neural cell growth and regulate cell polarity. However, in order to harness the potential of nanomaterials as artificial scaffolds, there is a clear need to develop methods of patterning nanomaterials over large surfaces with high precision and maintaining biocompatibility of patterned nanostructures. Herein, we report a novel method to regulate stem cell behaviors by using of combinatorial CNT patterns with different shapes and sizes in an effective way. Importantly, the SCs exhibited preferential growth on CNT patterns, and the CNT monolayer patterns did not show cytotoxicity during the long-term cell culture. These results clearly show that CNT monolayer patterns have enormous potentials as a platform for basic research and applications in stem cell tissue-engineering.

  15. Solar concentrator modules with silicone-on-glass Fresnel lens panels and multijunction cells.

    Science.gov (United States)

    Rumyantsev, Valery D

    2010-04-26

    High-efficiency multijunction (MJ) solar cells, being very expensive to manufacture, should only be used in combination with solar concentrators in terrestrial applications. An essential cost reduction of electric power produced by photovoltaic (PV) installations with MJ cells, may be expected by the creation of highly-effective, but inexpensive, elements for optical concentration and sun tracking. This article is an overview of the corresponding approach under development at the Ioffe Physical Technical Institute. The approach to R&D of the solar PV modules is based on the concepts of sunlight concentration by small-aperture area Fresnel lenses and "all-glass" module design. The small-aperture area lenses are arranged as a panel with silicone-on-glass structure where the glass plate serves as the front surface of a module. In turn, high-efficiency InGaP/(In)GaAs/Ge cells are arranged on a rear module panel mounted on a glass plate which functions as a heat sink and integrated protective cover for the cells. The developed PV modules and sun trackers are characterized by simple design, and are regarded as the prototypes for further commercialization.

  16. Solar concentrator modules with silicone-onglass Fresnel lens panels and multijunction cells.

    Science.gov (United States)

    Rumyantsev, Valery D

    2010-04-26

    High-efficiency multijunction (MJ) solar cells, being very expensive to manufacture, should only be used in combination with solar concentrators in terrestrial applications. An essential cost reduction of electric power produced by photovoltaic (PV) installations with MJ cells, may be expected by the creation of highly-effective, but inexpensive, elements for optical concentration and sun tracking. This article is an overview of the corresponding approach under development at the Ioffe Physical Technical Institute. The approach to R&D of the solar PV modules is based on the concepts of sunlight concentration by small-aperture area Fresnel lenses and "all-glass" module design. The small-aperture area lenses are arranged as a panel with silicone-on-glass structure where the glass plate serves as the front surface of a module. In turn, high-efficiency InGaP/(In)GaAs/Ge cells are arranged on a rear module panel mounted on a glass plate which functions as a heat sink and integrated protective cover for the cells. The developed PV modules and sun trackers are characterized by simple design, and are regarded as the prototypes for further commercialization.

  17. Targeting cholesterol in a liquid-disordered environment by theonellamides modulates cell membrane order and cell shape.

    Science.gov (United States)

    Arita, Yuko; Nishimura, Shinichi; Ishitsuka, Reiko; Kishimoto, Takuma; Ikenouchi, Junichi; Ishii, Kumiko; Umeda, Masato; Matsunaga, Shigeki; Kobayashi, Toshihide; Yoshida, Minoru

    2015-05-21

    Roles of lipids in the cell membrane are poorly understood. This is partially due to the lack of methodologies, for example, tool chemicals that bind to specific membrane lipids and modulate membrane function. Theonellamides (TNMs), marine sponge-derived peptides, recognize 3β-hydroxysterols in lipid membranes and induce major morphological changes in cultured mammalian cells through as yet unknown mechanisms. Here, we show that TNMs recognize cholesterol-containing liquid-disordered domains and induce phase separation in model lipid membranes. Modulation of membrane order was also observed in living cells following treatment with TNM-A, in which cells shrank considerably in a cholesterol-, cytoskeleton-, and energy-dependent manner. These findings present a previously unrecognized mode of action of membrane-targeting natural products. Meanwhile, we demonstrated the importance of membrane order, which is maintained by cholesterol, for proper cell morphogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Multiphoton versus single-photon excitation of photosensitizers for laser-induced fluorescence diagnosis and photodynamic therapy of cancer cells

    Science.gov (United States)

    Roelofs, Theo A.; Graschew, Georgi; Schneider, Marc; Rakowsky, Stefan; Sinn, Hanns-joerg; Schlag, Peter M.

    2001-04-01

    In laser-induced fluorescence diagnosis and photodynamic therapy of cancer the applied photosensitizers (PS) are often covalently derivatized with macromolecules to improve their selective accumulation in the cancerous tissue, while maintaining its single-photon excited photophysical properties. In this contribution methoxy-polyethylene glycol (MPEG, MW ~5 kDa) and human serum albumin (HSA, MW ~60 kDa) are used as PS carriers. Multiphoton (MP) excitation of the PS is favorable as compared to single-photon excitation because the penetration depth of the laser light is improved (>5 mm) due to the longer wavelength of the ~200 fs laser pulses used in this case (700-1050 nm). In this study cotton fibers and silica gel beads (quinone) do not exhibit multiphoton-induced fluorescence. Some derivatized PS (sulforhodamine B, erythrosin B, purpurin) exhibit MP-induced fluorescence, although no single-photon absorption band exists in the spectral region around half the excitation wavelength

  19. Multi-crystalline II-VI based multijunction solar cells and modules

    Energy Technology Data Exchange (ETDEWEB)

    Hardin, Brian E.; Connor, Stephen T.; Groves, James R.; Peters, Craig H.

    2015-06-30

    Multi-crystalline group II-VI solar cells and methods for fabrication of same are disclosed herein. A multi-crystalline group II-VI solar cell includes a first photovoltaic sub-cell comprising silicon, a tunnel junction, and a multi-crystalline second photovoltaic sub-cell. A plurality of the multi-crystalline group II-VI solar cells can be interconnected to form low cost, high throughput flat panel, low light concentration, and/or medium light concentration photovoltaic modules or devices.

  20. Modulation of Osteoblastic Cell Efferocytosis by Bone Marrow Macrophages.

    Science.gov (United States)

    Michalski, Megan N; Koh, Amy J; Weidner, Savannah; Roca, Hernan; McCauley, Laurie K

    2016-12-01

    Apoptosis occurs at an extraordinary rate in the human body and the effective clearance of dead cells (efferocytosis) is necessary to maintain homeostasis and promote healing, yet the contribution and impact of this process in bone is unclear. Bone formation requires that bone marrow stromal cells (BMSCs) differentiate into osteoblasts which direct matrix formation and either become osteocytes, bone lining cells, or undergo apoptosis. A series of experiments were performed to identify the regulators and consequences of macrophage efferocytosis of apoptotic BMSCs (apBMSCs). Bone marrow derived macrophages treated with the anti-inflammatory cytokine interleukin-10 (IL-10) exhibited increased efferocytosis of apBMSCs compared to vehicle treated macrophages. Additionally, IL-10 increased anti-inflammatory M2-like macrophages (CD206(+) ), and further enhanced efferocytosis within the CD206(+) population. Stattic, an inhibitor of STAT3 phosphorylation, reduced the IL-10-mediated shift in M2 macrophage polarization and diminished IL-10-directed efferocytosis of apBMSCs by macrophages implicating the STAT3 signaling pathway. Cell culture supernatants and RNA from macrophages co-cultured with apoptotic bone cells showed increased secretion of monocyte chemotactic protein 1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) and transforming growth factor beta 1 (TGF-β1) and increased ccl2 gene expression. In conclusion, IL-10 increases M2 macrophage polarization and enhances macrophage-mediated engulfment of apBMSCs in a STAT3 phosphorylation-dependent manner. After engulfment of apoptotic bone cells, macrophages secrete TGF-β1 and MCP-1/CCL2, factors which fuel the remodeling process. A better understanding of the role of macrophage efferocytosis as it relates to normal and abnormal bone turnover will provide vital information for future therapeutic approaches to treat bone related diseases. J. Cell. Biochem. 117: 2697-2706, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

  1. Euphorbia tirucalli modulates gene expression in larynx squamous cell carcinoma.

    Science.gov (United States)

    Franco-Salla, Gabriela Bueno; Prates, Janesly; Cardin, Laila Toniol; Dos Santos, Anemari Ramos Dinarte; Silva, Wilson Araújo da; da Cunha, Bianca Rodrigues; Tajara, Eloiza Helena; Oliani, Sonia Maria; Rodrigues-Lisoni, Flávia Cristina

    2016-05-21

    Some plants had been used in the treatment of cancer and one of these has attracted scientific interest, the Euphorbia tirucalli (E. tirucalli), used in the treatment of asthma, ulcers, warts has active components with activities scientifically proven as antimutagenic, anti-inflammatory and anticancer. We evaluate the influence of the antitumoral fraction of the E. tirucalli latex in the larynx squamous cell carcinoma (Hep-2), on the morphology, cell proliferation and gene expression. The Hep-2 cells were cultivated in complete medium (MEM 10 %) and treated with E. tirucalli latex for 1, 3, 5 and 7 days. After statistically analyzing the proliferation of the tested cells, the cells were cultivated again for RNA extraction and the Rapid Subtractive Hybridization (RaSH) technique was used to identify genes with altered expression. The genes found using the RaSH technique were analyzed by Gene Ontology (GO) using Ingenuity Systems. The five genes found to have differential expression were validated by real-time quantitative PCR. Though treatment with E. tirucalli latex did not change the cell morphology in comparison to control samples, but the cell growth was significantly decreased. The RaSH showed change in the expression of some genes, including ANXA1, TCEA1, NGFRAP1, ITPR1 and CD55, which are associated with inflammatory response, transcriptional regulation, apoptosis, calcium ion transport regulation and complement system, respectively. The E. tirucalli latex treatment down-regulated ITPR1 and up-regulated ANXA1 and CD55 genes, and was validated by real-time quantitative PCR. The data indicate the involvement of E. tirucalli latex in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of larynx cancer.

  2. Dihydropyridine Derivatives as Cell Growth Modulators In Vitro

    Science.gov (United States)

    Bruvere, Imanta; Bisenieks, Egils; Uldrikis, Janis; Plotniece, Aiva; Pajuste, Karlis; Rucins, Martins; Vigante, Brigita; Kalme, Zenta; Gosteva, Marina; Domracheva, Ilona; Vukovic, Tea; Milkovic, Lidija

    2017-01-01

    The effects of eleven 1,4-dihydropyridine derivatives (DHPs) used alone or together with prooxidant anticancer drug doxorubicin were examined on two cancer (HOS, HeLa) and two nonmalignant cell lines (HMEC, L929). Their effects on the cell growth (3H-thymidine incorporation) were compared with their antiradical activities (DPPH assay), using well-known DHP antioxidant diludine as a reference. Thus, tested DHPs belong to three groups: (1) antioxidant diludine; (2) derivatives with pyridinium moieties at position 4 of the 1,4-DHP ring; (3) DHPs containing cationic methylene onium (pyridinium, trialkylammonium) moieties at positions 2 and 6 of the 1,4-DHP ring. Diludine and DHPs of group 3 exerted antiradical activities, unlike compounds of group 2. However, novel DHPs had cell type and concentration dependent effects on 3H-thymidine incorporation, while diludine did not. Hence, IB-32 (group 2) suppressed the growth of HOS and HeLa, enhancing growth of L929 cells, while K-2-11 (group 3) enhanced growth of every cell line tested, even in the presence of doxorubicin. Therefore, growth regulating and antiradical activity principles of novel DHPs should be further studied to find if DHPs of group 2 could selectively suppress cancer growth and if those of group 3 promote wound healing. PMID:28473879

  3. Survivin Selectively Modulates Genes Deregulated in Human Leukemia Stem Cells

    Directory of Open Access Journals (Sweden)

    Seiji Fukuda

    2011-01-01

    Full Text Available ITD-Flt3 mutations are detected in leukemia stem cells (LSCs in acute myeloid leukemia (AML patients. While antagonizing Survivin normalizes ITD-Flt3-induced acute leukemia, it also impairs hematopoietic stem cell (HSC function, indicating that identification of differences in signaling pathways downstream of Survivin between LSC and HSC are crucial to develop selective Survivin-based therapeutic strategies for AML. Using a Survivin-deletion model, we identified 1,096 genes regulated by Survivin in ITD-Flt3-transformed c-kit+, Sca-1+, and lineageneg (KSL cells, of which 137 are deregulated in human LSC. Of the 137, 124 genes were regulated by Survivin exclusively in ITD-Flt3+ KSL cells but not in normal CD34neg KSL cells. Survivin-regulated genes in LSC connect through a network associated with the epidermal growth factor receptor signaling pathway and falls into various functional categories independent of effects on apoptosis. Pathways downstream of Survivin in LSC that are distinct from HSC can be potentially targeted for selective anti-LSC therapy.

  4. Structural defects and recombination behavior of excited carriers in Cu(In,GaSe2 solar cells

    Directory of Open Access Journals (Sweden)

    J. Yang

    2016-08-01

    Full Text Available The carriers’ behavior in neutral region (NTR and space charged region (SCR of Cu(In,GaSe2 thin film based solar cells has been investigated by temperature dependent photoluminescence (PL-T, electroluminescence (EL-T and current-voltage (IV-T from 10 to 300 K. PL-T spectra show that three kinds of defects, namely VSe, InCu and (InCu+VCu, are localized within the band gap of NTR and SCR of CIGS layer, corresponding to the energy levels of EC-0.08, EC-0.20 and EC-0.25 eV, respectively. The InCu and (InCu+VCu deep level defects are non-radiative recombination centers at room temperature. The IV-T and EL-T analysis reveals that the injection modes of electrons from ZnO conduction band into Cu(In,GaSe2 layer are tunneling, thermally-excited tunneling and thermionic emission under 10-40, 60-160, and 180-300 K, respectively. At 10-160 K, the electrons tunnel into (InCu+VCu and Vse defect levels in band gap of SCR and the drifting is involved in the emission bands at 0.96 and 1.07 eV, which is the direct evidence for a tunneling assisted recombination. At 180-300 K, the electrons are directly injected into the Cu(In,GaSe2 conduction band, and the emission of 1.13 eV are ascribed to the transitions from the conduction band to the valence band.

  5. Ribosome Mediated Quinary Interactions Modulate In-Cell Protein Activities.

    Science.gov (United States)

    DeMott, Christopher M; Majumder, Subhabrata; Burz, David S; Reverdatto, Sergey; Shekhtman, Alexander

    2017-08-15

    Ribosomes are present inside bacterial cells at micromolar concentrations and occupy up to 20% of the cell volume. Under these conditions, even weak quinary interactions between ribosomes and cytosolic proteins can affect protein activity. By using in-cell and in vitro NMR spectroscopy, and biophysical techniques, we show that the enzymes, adenylate kinase and dihydrofolate reductase, and the respective coenzymes, ATP and NADPH, bind to ribosomes with micromolar affinity, and that this interaction suppresses the enzymatic activities of both enzymes. Conversely, thymidylate synthase, which works together with dihydrofolate reductase in the thymidylate synthetic pathway, is activated by ribosomes. We also show that ribosomes impede diffusion of green fluorescent protein in vitro and contribute to the decrease in diffusion in vivo. These results strongly suggest that ribosome-mediated quinary interactions contribute to the differences between in vitro and in vivo protein activities and that ribosomes play a previously under-appreciated nontranslational role in regulating cellular biochemistry.

  6. Indole prevents Escherichia coli cell division by modulating membrane potential

    Science.gov (United States)

    Chimerel, Catalin; Field, Christopher M.; Piñero-Fernandez, Silvia; Keyser, Ulrich F.; Summers, David K.

    2012-01-01

    Indole is a bacterial signalling molecule that blocks E. coli cell division at concentrations of 3–5 mM. We have shown that indole is a proton ionophore and that this activity is key to the inhibition of division. By reducing the electrochemical potential across the cytoplasmic membrane of E. coli, indole deactivates MinCD oscillation and prevents formation of the FtsZ ring that is a prerequisite for division. This is the first example of a natural ionophore regulating a key biological process. Our findings have implications for our understanding of membrane biology, bacterial cell cycle control and potentially for the design of antibiotics that target the cell membrane. PMID:22387460

  7. Dexverapamil to modulate vinblastine resistance in metastatic renal cell carcinoma

    NARCIS (Netherlands)

    G.H.J. Mickisch; M.A. Noordzij (Marinus); A.v.d. Gaast (A. v d); P. Gebreamlack (P.); K.U. Köhrmann (K.); E. Mogler-Drautz (E.); N. Kupper (Nina); F.H. Schröder (Fritz)

    1995-01-01

    textabstractMultidrug resistance (MDR) in a variety of human tumours such as renal cell carcinoma (RCC) is thought to be caused by expression of the MDR1 gene and may be reversed by applying modern chemosensitisers such as dexverapamil, which inhibit the MDR1 gene product P-glycoprotein. This

  8. Cell state switching factors and dynamical patterning modules ...

    Indian Academy of Sciences (India)

    Prakash

    of endoderm and mesoderm in the sea urchin (Smith et al. 2007). The emergence of a multicellular aggregate composed of cells in more than one state would have represented an evolutionary novelty: a primitive “body plan.” As with the. DPMs described earlier, the generation of morphological variation by MOR is tied to ...

  9. Towards the scaling up of perovskite solar cells and modules

    NARCIS (Netherlands)

    Galagan, Y.; Coenen, E.W.C.; Verhees, W.J.H.; Andriessen, R.

    2016-01-01

    A direct current (DC) simulation for perovskite solar cells with different dimensions was performed. The theoretical results demonstrate a good agreement with experimental data, indicating the reliability of the performed simulation. A theoretical model was applied for the investigation of large

  10. Hybrid Modulation Scheme for Cascaded H-Bridge Inverter Cells ...

    African Journals Online (AJOL)

    This work proposes a switching technique for cascaded H-Bridge (CHB) cells. Single carrier Sinusoidal PWM (SCSPWM) scheme is employed in the generation of the gating signals. A sequential switching and base PWM circulation schemes are presented for this fundamental cascaded multilevel inverter topology.

  11. Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Alan M. [School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH (United Kingdom); Paxton, Jennifer Z.; Hung, Yi-Pei; Hadley, Martin J.; Bowen, James; Williams, Richard L. [School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT (United Kingdom); Grover, Liam M., E-mail: l.m.grover@bham.ac.uk [School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT (United Kingdom)

    2015-03-01

    Calcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40 years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macro-scale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation. - Highlights: • Crystallinity of HA at the nano-scale was dominant over macro-scale topography. • Lower crystallinity caused rapid cell attachment and proliferation rate. • Crystallinity could be easily adjusted by without compromising coating purity.

  12. 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 ...

  13. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Science.gov (United States)

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate tha...

  14. Parameter study for polymer solar modules based on various cell lengths and light intensities

    Energy Technology Data Exchange (ETDEWEB)

    Slooff, L.H.; Burgers, A.R.; Bende, E.E.; Kroon, J.M. [ECN Solar Energy, P.O. Box 1, 1755 ZG Petten (Netherlands); Veenstra, S.C. [ECN Solar Energy, Solliance, High Tech Campus 5, P63, 5656AE Eindhoven (Netherlands)

    2013-10-15

    Polymer solar cells may be applied in portable electronic devices, where light intensity and spectral distribution of the illuminating source can be very different compared to outdoor applications. As the power output of solar cells depends on temperature, light intensity and spectrum, the design of the module must be optimized for the specific illumination conditions in the different applications. The interconnection area between cells in a module must be as narrow as possible to maximize the active area, also called geometrical fill factor, of the module. Laser scribing has the potential to realize this. The optimal width of the interconnection zone depends both on technological limitations, e.g. laser scribe width and the minimal distance between scribes, and electrical limitations like resistive losses. The latter depends on the generated current in the cell and thus also on illumination intensity. Besides that, also the type of junction, i.e. a single or tandem junction, will influence the optimal geometry. In this paper a calculation model is presented that can be used for electrical modeling of polymer cells and modules in order to optimize the performance for the specific illumination conditions.

  15. 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.

  16. 14th Workshop on Crystalline Silicon Solar Cells& Modules: Materials and Processes; Extended Abstracts and Papers

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B. L.

    2004-08-01

    The 14th Workshop will provide a forum for an informal exchange of technical and scientific information between international researchers in the photovoltaic and relevant non-photovoltaic fields. It will offer an excellent opportunity for researchers in private industry and at universities to prioritize mutual needs for future collaborative research. The workshop is intended to address the fundamental properties of PV silicon, new solar cell designs, advanced solar cell processing techniques, and cell-related module issues. A combination of oral presentations by invited speakers, poster sessions, and discussion sessions will review recent advances in crystal growth, new cell designs, new processes and process characterization techniques, cell fabrication approaches suitable for future manufacturing demands, and solar cell encapsulation. This year's theme, ''Crystalline Si Solar Cells: Leapfrogging the Barriers,'' reflects the continued success of crystalline Si PV in overcoming technological barriers to improve solar cell performance and lower the cost of Si PV. The workshop will consist of presentations by invited speakers, followed by discussion sessions. In addition, there will be two poster sessions presenting the latest research and development results. Some presentations will address recent technologies in the microelectronics field that may have a direct bearing on PV. The sessions will include: Advances in crystal growth and material issues; Impurities and defects; Dynamics during device processing; Passivation; High-efficiency Si solar cells; Advanced processing; Thin Si solar cells; and Solar cell reliability and module issues.

  17. Label-free distinguishing between neurons and glial cells based on two-photon excited fluorescence signal of neuron perinuclear granules

    Science.gov (United States)

    Du, Huiping; Jiang, Liwei; Wang, Xingfu; Liu, Gaoqiang; Wang, Shu; Zheng, Liqin; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin

    2016-08-01

    Neurons and glial cells are two critical cell types of brain tissue. Their accurate identification is important for the diagnosis of psychiatric disorders such as depression and schizophrenia. In this paper, distinguishing between neurons and glial cells by using the two-photon excited fluorescence (TPEF) signals of intracellular intrinsic sources was performed. TPEF microscopy combined with TUJ-1 and GFAP immunostaining and quantitative image analysis demonstrated that the perinuclear granules of neurons in the TPEF images of brain tissue and the primary cultured cortical cells were a unique characteristic of neurons compared to glial cells which can become a quantitative feature to distinguish neurons from glial cells. With the development of miniaturized TPEF microscope (‘two-photon fiberscopes’) imaging devices, TPEF microscopy can be developed into an effective diagnostic and monitoring tool for psychiatric disorders such as depression and schizophrenia.

  18. A visible-light-excited europium(III) complex-based luminescent probe for visualizing copper ions and hydrogen sulfide in living cells

    Science.gov (United States)

    Wang, Yiren; Wang, Huan; Yang, Mei; Yuan, Jingli; Wu, Jing

    2018-01-01

    Development of visible-light-excited lanthanide (III) complex-based luminescent probes is highly appealing due to their superiority of less damage to the living biosystems over the conventional UV-light-excited ones. In this work, a visible-light-excited europium (III) complex-based luminescent probe, BPED-BHHCT-Eu3+-BPT, has been designed and synthesized by conjugating the Cu2+-binding N,N-bis(2-pyridylmethyl)ethanediamine (BPED) to a tetradentate β-diketone ligand 4,4‧-bis(1″,1″,1″,2″,2″,3″,3″-heptafluoro-4″,6″-hexanedione-6″-yl)chlorosulfo-o-terphenyl (BHHCT) and coordinating with a coligand 2-(N,N-diethylanilin-4-yl)-4,6-bis(pyrazol-1-yl)-1,3,5-triazine) (BPT) for the time-gated luminescence detection of Cu2+ ions and hydrogen sulfide (H2S) in living cells. BPED-BHHCT-Eu3+-BPT exhibited a sharp excitation peak at 407 nm and a wide excitation window extending to beyond 460 nm. Upon its reaction with Cu2+ ions, the luminescence of BPED-BHHCT-Eu3+-BPT was efficiently quenched, which could be reversibly restored by the addition of H2S due to the strong affinity between Cu2+ ions and H2S. The "on-off-on" type luminescence behavior of BPED-BHHCT-Eu3+-BPT towards Cu2+ ions and H2S enabled the sensing of the two species with high sensitivity and selectivity. The performances of BPED-BHHCT-Eu3+-BPT for visualizing intracellular Cu2+ ions and H2S were investigated, and the results have demonstrated the practical applicability of the probe for molecular imaging of cells.

  19. Improved film morphology reduces charge carrier recombination into the triplet excited state in a small bandgap polymer-fullerene photovoltaic cell

    Energy Technology Data Exchange (ETDEWEB)

    Di Nuzzo, Daniele; Shahid, Munazza; Gevaerts, Veronique S. [Molecular Materials and Nanosystems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven (Netherlands); Dutch Polymer Institute (DPI), P.O. Box 902, 5600 AX Eindhoven (Netherlands); Aguirre, Aranzazu; Meskers, Stefan C.J.; Janssen, Rene A.J. [Molecular Materials and Nanosystems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven (Netherlands)

    2010-10-08

    The use of diiodooctane as processing additive for construction of PCPDTBT:PCBM solar cells results in a profound change in photophysical behavior of this blend. In the improved morphology obtained with the additive, recombination of charge carriers to the lowest triplet excited state is suppressed. This contributes to the boost in solar power conversion efficiency induced by the use of the processing agent. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  20. Placental Kisspeptins Differentially Modulate Vital Parameters of Estrogen Receptor-Positive and -Negative Breast Cancer Cells

    Science.gov (United States)

    Rasoulzadeh, Zahra; Ghods, Roya; Kazemi, Tohid; Mirzadegan, Ebrahim; Ghaffari-Tabrizi-Wizsy, Nassim; Rezania, Simin; Kazemnejad, Somaieh; Arefi, Soheila; Ghasemi, Jamileh; Vafaei, Sedigheh; Mahmoudi, Ahmad-Reza; Zarnani, Amir-Hassan

    2016-01-01

    Kisspeptins (KPs) are major regulators of trophoblast and cancer invasion. Thus far, limited and conflicting data are available on KP-mediated modulation of breast cancer (BC) metastasis; mostly based on synthetic KP-10, the most active fragment of KP. Here, we report for the first time comprehensive functional effects of term placental KPs on proliferation, adhesion, Matrigel invasion, motility, MMP activity and pro-inflammatory cytokine production in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). KPs were expressed at high level by term placental syncytiotrophoblasts and released in soluble form. Placental explant conditioned medium containing KPs (CM) significantly reduced proliferation of both cell types compared to CM without (w/o) KP (CM-w/o KP) in a dose- and time-dependent manner. In MDA-MB-231 cells, placental KPs significantly reduced adhesive properties, while increased MMP9 and MMP2 activity and stimulated invasion. Increased invasiveness of MDA-MB-231 cells after CM treatment was inhibited by KP receptor antagonist, P-234. CM significantly reduced motility of MCF-7 cells at all time points (2–30 hr), while it stimulated motility of MDA-MB-231 cells. These effects were reversed by P-234. Co-treatment with selective ER modulators, Tamoxifen and Raloxifene, inhibited the effect of CM on motility of MCF-7 cells. The level of IL-6 in supernatant of MCF-7 cells treated with CM was higher compared to those treated with CM-w/o KP. Both cell types produced more IL-8 after treatment with CM compared to those treated with CM-w/o KP. Taken together, our observations suggest that placental KPs differentially modulate vital parameters of estrogen receptor-positive and -negative BC cells possibly through modulation of pro-inflammatory cytokine production. PMID:27101408

  1. Placental Kisspeptins Differentially Modulate Vital Parameters of Estrogen Receptor-Positive and -Negative Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Zahra Rasoulzadeh

    Full Text Available Kisspeptins (KPs are major regulators of trophoblast and cancer invasion. Thus far, limited and conflicting data are available on KP-mediated modulation of breast cancer (BC metastasis; mostly based on synthetic KP-10, the most active fragment of KP. Here, we report for the first time comprehensive functional effects of term placental KPs on proliferation, adhesion, Matrigel invasion, motility, MMP activity and pro-inflammatory cytokine production in MDA-MB-231 (estrogen receptor-negative and MCF-7 (estrogen receptor-positive. KPs were expressed at high level by term placental syncytiotrophoblasts and released in soluble form. Placental explant conditioned medium containing KPs (CM significantly reduced proliferation of both cell types compared to CM without (w/o KP (CM-w/o KP in a dose- and time-dependent manner. In MDA-MB-231 cells, placental KPs significantly reduced adhesive properties, while increased MMP9 and MMP2 activity and stimulated invasion. Increased invasiveness of MDA-MB-231 cells after CM treatment was inhibited by KP receptor antagonist, P-234. CM significantly reduced motility of MCF-7 cells at all time points (2-30 hr, while it stimulated motility of MDA-MB-231 cells. These effects were reversed by P-234. Co-treatment with selective ER modulators, Tamoxifen and Raloxifene, inhibited the effect of CM on motility of MCF-7 cells. The level of IL-6 in supernatant of MCF-7 cells treated with CM was higher compared to those treated with CM-w/o KP. Both cell types produced more IL-8 after treatment with CM compared to those treated with CM-w/o KP. Taken together, our observations suggest that placental KPs differentially modulate vital parameters of estrogen receptor-positive and -negative BC cells possibly through modulation of pro-inflammatory cytokine production.

  2. Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity.

    Directory of Open Access Journals (Sweden)

    Ulf Schulze-Topphoff

    Full Text Available Laquinimod is a novel oral drug that is currently being evaluated for the treatment of relapsing-remitting (RR multiple sclerosis (MS. Using the animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE, we examined how laquinimod promotes immune modulation. Oral laquinimod treatment reversed established RR-EAE and was associated with reduced central nervous system (CNS inflammation, decreased Th1 and Th17 responses, and an increase in regulatory T cells (Treg. In vivo laquinimod treatment inhibited donor myelin-specific T cells from transferring EAE to naive recipient mice. In vivo laquinimod treatment altered subpopulations of myeloid antigen presenting cells (APC that included a decrease in CD11c(+CD11b(+CD4(+ dendritic cells (DC and an elevation of CD11b(hiGr1(hi monocytes. CD11b(+ cells from these mice exhibited an anti-inflammatory type II phenotype characterized by reduced STAT1 phosphorylation, decreased production of IL-6, IL-12/23 and TNF, and increased IL-10. In adoptive transfer, donor type II monocytes from laquinimod-treated mice suppressed clinical and histologic disease in recipients with established EAE. As effects were observed in both APC and T cell compartments, we examined whether T cell immune modulation occurred as a direct effect of laquinimod on T cells, or as a consequence of altered APC function. Inhibition of Th1 and Th17 differentiation was observed only when type II monocytes or DC from laquinimod-treated mice were used as APC, regardless of whether myelin-specific T cells were obtained from laquinimod-treated or untreated mice. Thus, laquinimod modulates adaptive T cell immune responses via its effects on cells of the innate immune system, and may not influence T cells directly.

  3. Incorporation of Biomaterials in Multicellular Aggregates Modulates Pluripotent Stem Cell Differentiation

    Science.gov (United States)

    Bratt-Leal, Andrés M.; Carpenedo, Richard L.; Ungrin, Mark; Zandstra, Peter W.; McDevitt, Todd C.

    2010-01-01

    Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell-biomaterial interactions have largely been studied by introducing stem cells into artificial environments, such as 2D cell culture on biomaterial surfaces, encapsulation of cell suspensions within hydrogel materials, or cell seeding on 3D polymeric scaffolds. In this study, microparticles fabricated from different materials, such as agarose, PLGA and gelatin, were stably integrated, in a dose-dependent manner, within aggregates of pluripotent stem cells (PSCs) prior to differentiation as a means to directly examine stem cell-biomaterial interactions in 3D. Interestingly, the presence of the materials within the stem cell aggregates differentially modulated the gene and protein expression patterns of several differentiation markers without adversely affecting cell viability. Microparticle incorporation within 3D stem cell aggregates can control the spatial presentation of extracellular environmental cues (i.e. soluble factors, extracellular matrix and intercellular adhesion molecules) as a means to direct the differentiation of stem cells for tissue engineering and regenerative medicine applications. In addition, these results suggest that the physical presence of microparticles within stem cell aggregates does not compromise PSC differentiation, but in fact the choice of biomaterials can impact the propensity of stem cells to adopt particular differentiated cell phenotypes. PMID:20864164

  4. Human saliva exposure modulates bone cell performance in vitro.

    Science.gov (United States)

    Proksch, Susanne; Steinberg, Thorsten; Keller, Constantin; Wolkewitz, Martin; Wiedmann-Al-Ahmad, Margit; Finkenzeller, Guenter; Hannig, Christian; Hellwig, Elmar; Al-Ahmad, Ali

    2012-02-01

    Various situations encountered by a clinician during the daily routine including surgical periodontitis therapy, dental implant insertion, or tooth extraction involve the contact of saliva with the jaw bone. However, there are only sparse data concerning the influence of saliva on bone cells. Saliva specimens were incorporated within culture medium and administered to murine MC3T3 osteoblasts, of which the morphology (REM), proliferation (EZ4U), and differentiation (qRT-PCR, alkaline phosphatase activity, extracellular matrix calcification) were assessed. Simultaneously, the composition of saliva media was analyzed with respect to the content of lactoferrin, activities of classical salivary enzymes, and the ability to provoke inflammatory cytokine production (enzyme-linked immunosorbent assay) in MC3T3 osteoblasts. The morphology, proliferation, and expression of differentiation-associated genes were seriously handicapped by saliva contact. Saliva-touched cells exhibited less alkaline phosphatase but normal levels of extracellular matrix mineralization. Saliva-containing culture media featured physiological activities of salivary enzymes and considerable amounts of lactoferrin but almost completely lacked salivary alkaline phosphatase and unspecific proteases. Upon saliva incubation, MC3T3 osteoblasts did not release noteworthy levels of interleukin-1 beta or tumor necrosis factor alpha. Although saliva is generally considered to vitalize oral tissues, this study reveals that it harms osteoblast-like cells more due to the presence of salivary enzymes than by triggering of inflammation. This issue is clinically relevant because it broadens the understanding of the bone cell fate within the rather complex cosmos of the oral cavity thereby providing a basis for clinical decision making and treatment guidelines. It seems to be reasonable to restrict the contact period between saliva and bone.

  5. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  6. Cell density modulates intracellular mass transport in neural networks.

    Science.gov (United States)

    Cintora, Patricia; Arikkath, Jyothi; Kandel, Mikhail; Popescu, Gabriel; Best-Popescu, Catherine

    2017-05-01

    In order to fully understand brain connectivity and elucidate the mechanisms involved in central nervous system disease, the field of neuroscience depends on quantitative studies of neuronal structure and function. Cell morphology and neurite (axonal and dendritic) arborization are typically studied by immunohistochemical and fluorescence techniques. However, dry mass content and intracellular mass transport rates have largely been under-investigated given the inherent difficulties in their measurement. Here, spatial light interference microscopy (SLIM) and dispersion-relation phase spectroscopy (DPS) were used to measure pathlength fluctuations that report on the dry mass and transport within cultured primary neurons across low, medium, and high cell density conditions. It was found that cell density (confluence) affects significantly both the growth rate and mass transport. The analysis method is label-free and does not require neuronal tracing, particle tracking, or neuron reconstruction. Since SLIM can upgrade any existing phase contrast microscope and the imaging and analysis are high-throughput, we anticipate that this approach will be embraced by neuroscientists for broad scale studies. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  7. Photo-thermal hybrid module with photovoltaic cells and thermoelectric devices for space application

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Moriaki; Hayashibara, Mitsuo

    1988-11-30

    Based upon the assumption that higher efficeint thermoelectric device will come in practice, a feasibility study was carried out to investigate the performance of photo-thermal hybrid module for space application. The photo-thermal hybrid modules consist of laminate of photovoltaic cells, thermoelectric devices and radiators. Solar energies collected are converted to the power generation by the photovoltaic cells and to heat them to the moderate temperature level, and then the thermoelectric devices generate the electric power, utilizing the temperature difference of thermoelectric devices between the junction surface with the photovoltaic cells (high temperature side) and one with the radiators (low temperature side). As an experimental result on the photo-thermal hybrid module which was constituted of the combination of a GaAs photovoltaic cell and a BiTe thermoelectric device, the hybrid module was able to have higher efficiency than a concentration type GaAs system. The photo-thermal arrays for space application with higher efficiency and lower specific weight might be realized, when a high performance thermoelectric device, such as a FeSi thermoelectric device, the performance of which is able to expect to be one digit higher than a BiTe thermoelectric device, is developed. 4 references, 10 figures, 1 table.

  8. Bovine colostrum modulates immune activation cascades in human peripheral blood mononuclear cells in vitro

    DEFF Research Database (Denmark)

    Jenny, Marcel; Pedersen, Ninfa R; Hidayat, Budi J

    2010-01-01

    factors and has a long history of use in traditional medicine. In an approach to evaluate the effects of bovine colostrum (BC) on the T-cell/macrophage interplay, we investigated and compared the capacity of BC containing low and high amounts of lactose and lactoferrin to modulate tryptophan degradation...

  9. Edge sealing for low cost stability enhancement of roll-to-roll processed flexible polymer solar cell modules

    DEFF Research Database (Denmark)

    Tanenbaum, David M.; Dam, Henrik Friis; Rösch, R.

    2012-01-01

    Fully roll-to-roll processed polymer solar cell modules were prepared, characterized, and laminated. Cell modules were cut from the roll and matched pairs were selected, one module with exposed cut edges, the other laminated again with the same materials and adhesive sealing fully around the cut...... edges. The edge sealing rim was 10 mm wide. Cell modules were characterized by periodic measurements of IV curves over extended periods in a variety of conditions, as well as by a variety of spatial imaging techniques. Data show significant stability benefits of the edge sealing process. The results...

  10. Calcium Signalling through Ligand-Gated Ion Channels such as P2X1 Receptors in the Platelet and other Non-Excitable Cells.

    Science.gov (United States)

    Mahaut-Smith, Martyn P; Taylor, Kirk A; Evans, Richard J

    2016-01-01

    Ligand-gated ion channels on the cell surface are directly activated by the binding of an agonist to their extracellular domain and often referred to as ionotropic receptors. P2X receptors are ligand-gated non-selective cation channels with significant permeability to Ca(2+) whose principal physiological agonist is ATP. This chapter focuses on the mechanisms by which P2X1 receptors, a ubiquitously expressed member of the family of ATP-gated channels, can contribute to cellular responses in non-excitable cells. Much of the detailed information on the contribution of P2X1 to Ca(2+) signalling and downstream functional events has been derived from the platelet. The underlying primary P2X1-generated signalling event in non-excitable cells is principally due to Ca(2+) influx, although Na(+) entry will also occur along with membrane depolarization. P2X1 receptor stimulation can lead to additional Ca(2+) mobilization via a range of routes such as amplification of G-protein-coupled receptor-dependent Ca(2+) responses. This chapter also considers the mechanism by which cells generate extracellular ATP for autocrine or paracrine activation of P2X1 receptors. For example cytosolic ATP efflux can result from opening of pannexin anion-permeable channels or following damage to the cell membrane. Alternatively, ATP stored in specialised secretory vesicles can undergo quantal release via the process of exocytosis. Examples of physiological or pathophysiological roles of P2X1-dependent signalling in non-excitable cells are also discussed, such as thrombosis and immune responses.

  11. Modulating cancer cell survival by targeting intracellular cholesterol transport.

    Science.gov (United States)

    Kuzu, Omer F; Gowda, Raghavendra; Noory, Mohammad A; Robertson, Gavin P

    2017-08-08

    Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. Here, the chemotherapeutic utility of ASM inhibition was investigated. The effect of FIASMAs on intracellular cholesterol levels, cholesterol homoeostasis, cellular endocytosis and signalling cascades were investigated. The in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and a nanoparticle formulation was developed to overcome dose-limiting CNS-associated side effects of certain FIASMAs. Functional ASM inhibitors inhibited intracellular cholesterol transport leading to disruption of autophagic flux, cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major oncogenic signalling cascades on which cancer cells were reliant for survival were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are also clinically used as antipsychotics, were effective in inhibiting xenografted tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its chemotherapeutic efficacy while decreasing CNS-associated side effects. This study suggests that disruption of intracellular cholesterol transport by targeting ASM could be utilised as a potential chemotherapeutic approach for treating cancer.

  12. Generator module architecture for a large solid oxide fuel cell power plant

    Science.gov (United States)

    Gillett, James E.; Zafred, Paolo R.; Riggle, Matthew W.; Litzinger, Kevin P.

    2013-06-11

    A solid oxide fuel cell module contains a plurality of integral bundle assemblies, the module containing a top portion with an inlet fuel plenum and a bottom portion receiving air inlet feed and containing a base support, the base supports dense, ceramic exhaust manifolds which are below and connect to air feed tubes located in a recuperator zone, the air feed tubes passing into the center of inverted, tubular, elongated, hollow electrically connected solid oxide fuel cells having an open end above a combustion zone into which the air feed tubes pass and a closed end near the inlet fuel plenum, where the fuel cells comprise a fuel cell stack bundle all surrounded within an outer module enclosure having top power leads to provide electrical output from the stack bundle, where the fuel cells operate in the fuel cell mode and where the base support and bottom ceramic air exhaust manifolds carry from 85% to all 100% of the weight of the stack, and each bundle assembly has its own control for vertical and horizontal thermal expansion control.

  13. The sneaking ligand approach for cell type-specific modulation of intracellular signalling pathways.

    Science.gov (United States)

    Sehnert, Bettina; Burkhardt, Harald; Finzel, Stephanie; Dübel, Stefan; Voll, Reinhard E

    2017-09-01

    Small molecules interfering with intracellular signalling pathways are used in the treatment of multiple diseases including RA. However, small molecules usually affect signalling in most cell types, not only in those which need to be targeted. This general inhibition of signalling pathways causes often adverse effects, which could be avoided by cell type-specific inhibitors. For cell-type specific modulation of signal transduction, we developed the sneaking ligand fusion proteins (SLFPs). SLFPs contain three domains: (1) the binding domain mediating cell type-specific targeting and endocytosis; (2) the endosomal release sequence releasing the effector domain into the cytoplasm; (3) the effector domain modulating signalling. Using our SLFP NF-kappaB inhibitor termed SLC1 we demonstrated that cell-type-specific modulation of intracellular signalling pathways is feasible, that endothelial NF-kappaB activation is critical for arthritis and peritonitis and that SLFPs help to identify disease-relevant pathways in defined cell types. Hence, SLFPs may improve risk-benefit ratios of therapeutic interventions. Copyright © 2017. Published by Elsevier Inc.

  14. Widefield Two-Photon Excitation without Scanning: Live Cell Microscopy with High Time Resolution and Low Photo-Bleaching.

    Directory of Open Access Journals (Sweden)

    Rumelo Amor

    Full Text Available We demonstrate fluorescence imaging by two-photon excitation without scanning in biological specimens as previously described by Hwang and co-workers, but with an increased field size and with framing rates of up to 100 Hz. During recordings of synaptically-driven Ca(2+ events in primary rat hippocampal neurone cultures loaded with the fluorescent Ca(2+ indicator Fluo-4 AM, we have observed greatly reduced photo-bleaching in comparison with single-photon excitation. This method, which requires no costly additions to the microscope, promises to be useful for work where high time-resolution is required.

  15. Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells

    Directory of Open Access Journals (Sweden)

    Sunyoung Joo

    2014-02-01

    Full Text Available Cell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, thus making them suitable for allogeneic applications. However, it is unclear whether allogeneic and myogenic-induced mesenchymal stem cells retain their immunomodulatory characteristics. Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro. We investigated the immunologic properties of mesenchymal stem cells after myogenic induction. Mesenchymal stem cells were obtained from C57BL/6 mice and the C3H/10T1/2 murine mesenchymal stem cell line. Two different 5-aza-2′-deoxycytidine doses (0.5 and 3 µM were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions. Using a mixed lymphocytic reaction, we determined the optimal splenocyte proliferation inhibition dose. The induction of regulatory T cells was markedly increased by the addition of 3 µM 5-aza-2′-deoxycytidine–treated mesenchymal stem cells. Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses. These findings support the hypothesis that myogenic-induced mesenchymal stem cells may be transplantable across allogeneic barriers.

  16. 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.

  17. 77 FR 35425 - Crystalline Silicon Photovoltaic Cells and Modules From China; Scheduling of the Final Phase of...

    Science.gov (United States)

    2012-06-13

    ... amorphous silicon (a-Si), cadmium telluride (CdTe), or copper indium gallium selenide (CIGS). Also excluded... COMMISSION Crystalline Silicon Photovoltaic Cells and Modules From China; Scheduling of the Final Phase of... crystalline silicon photovoltaic cells and modules, provided for in subheadings 8501.31.80, 8501.61.00, 8507...

  18. Neurally released pituitary adenylate cyclase-activating polypeptide enhances guinea pig intrinsic cardiac neurone excitability.

    Science.gov (United States)

    Tompkins, John D; Ardell, Jeffrey L; Hoover, Donald B; Parsons, Rodney L

    2007-07-01

    Intracellular recordings were made in vitro from guinea-pig cardiac ganglia to determine whether endogenous neuropeptides such as pituitary adenylate cyclase-activating polypeptide (PACAP) or substance P released during tetanic neural stimulation modulate cardiac neurone excitability and/or contribute to slow excitatory postsynaptic potentials (sEPSPs). When nicotinic and muscarinic receptors were blocked by hexamethonium and atropine, 20 Hz stimulation for 10 s initiated a sEPSP in all innervated neurones. In 40% of the cells, excitability was enhanced after termination of the sEPSP. This suggested that non-cholinergic receptor-mediated mechanisms contributed to the sEPSP and modulated neuronal excitability. Exogenous PACAP and substance P initiated a slow depolarization in the neurones whereas neuronal excitability was only increased by PACAP. When ganglia were treated with the PAC1 antagonist PACAP6-38 (500 nM), the sEPSP evoked by 20 Hz stimulation was reduced by approximately 50% and an enhanced excitability occurred in only 10% of the cells. These observations suggested that PACAP released from preganglionic nerve terminals during tetanic stimulation enhanced neuronal excitability and evoked sEPSPs. After addition of 1 nM PACAP to the bath, 7 of 9 neurones exhibited a tonic firing pattern whereas in untreated preparations, the neurons had a phasic firing pattern. PACAP6-38 (500 nM) diminished the increase in excitability caused by 1 nM PACAP so that only 4 of 13 neurones exhibited a tonic firing pattern and the other 9 cells retained a phasic firing pattern. These findings indicate that PACAP can be released by tetanic neural stimulation in vitro and increase the excitability of intrinsic cardiac neurones. We hypothesize that in vivo PACAP released during preganglionic firing may modulate neurotransmission within the intrinsic cardiac ganglia.

  19. Solar-cell interconnect design for terrestrial photovoltaic modules

    Science.gov (United States)

    Mon, G. R.; Moore, D. M.; Ross, R. G., Jr.

    1984-01-01

    Useful solar cell interconnect reliability design and life prediction algorithms are presented, together with experimental data indicating that the classical strain cycle (fatigue) curve for the interconnect material does not account for the statistical scatter that is required in reliability predictions. This shortcoming is presently addressed by fitting a functional form to experimental cumulative interconnect failure rate data, which thereby yields statistical fatigue curves enabling not only the prediction of cumulative interconnect failures during the design life of an array field, but also the quantitative interpretation of data from accelerated thermal cycling tests. Optimal interconnect cost reliability design algorithms are also derived which may allow the minimization of energy cost over the design life of the array field.

  20. Modulation of phosphoinositide metabolism in aortic smooth muscle cells by allylamine

    Energy Technology Data Exchange (ETDEWEB)

    Cox, L.R.; Murphy, S.K.; Ramos, K. (Philadelphia College of Pharmacy and Science, PA (USA))

    1990-08-01

    Aortic smooth muscle cells (SMC) modulate from a contractile to a proliferative phenotype upon subchronic exposure to allylamine. The present studies were designed to determine if this phenotypic modulation is associated with alterations in the metabolism of membrane phosphoinositides. 32P incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) was lower by 31, 35, and 22%, respectively, in SMC from allylamine-treated animals relative to controls. In contrast, incorporation of (3H)myoinositol into inositol phosphates did not differ in allylamine cells relative to control cells. Exposure to dibutyryl (db) cAMP (0.2 mM) and theophylline (0.1 mM) reduced 32P incorporation into PIP and PIP2 in SMC from both experimental groups. Under these conditions, a decrease in (3H)myoinositol incorporation into inositol 1-phosphate was only observed in allylamine cells. The effects of db cAMP and theophylline in allylamine and control SMC correlated with a marked decrease in cellular proliferation. These results suggest that alterations in phosphoinositide synthesis and/or degradation contribute to the enhanced proliferation of SMC induced by allylamine. To further examine this concept, the effects of agents which modulate protein kinase C (PKC) activity were evaluated. Sphingosine (125-500 ng/ml), a PKC inhibitor, decreased SMC proliferation in allylamine, but not control cells. 12-O-Tetradecanoylphorbol-13-acetate (1-100 ng/ml), a PKC agonist, stimulated proliferation in control cells, but inhibited proliferation in cells from allylamine-treated animals. We conclude that allylamine-induced phenotypic modulation of SMC is associated with alterations in phosphoinositide metabolism.

  1. The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses

    Directory of Open Access Journals (Sweden)

    Moreira José

    2003-11-01

    Full Text Available Abstract Background Histone deacetylase inhibitors (HDACIs induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA on primary T cells. Methods To ascertain the effect of TSA on resting and activated T cells we used a model system where an enriched cell population consisting of primary T-cells was stimulated in vitro with immobilized anti-CD3/anti-CD28 antibodies whilst exposed to pharmacological concentrations of Trichostatin A. Results We found that this drug causes a rapid decline in cytokine expression, accumulation of cells in the G1 phase of the cell cycle, and induces apoptotic cell death. The mitochondrial respiratory chain (MRC plays a critical role in the apoptotic response to TSA, as dissipation of mitochondrial membrane potential and reactive oxygen species (ROS scavengers block TSA-induced T-cell death. Treatment of T cells with TSA results in the altered expression of a subset of genes involved in T cell responses, as assessed by microarray gene expression profiling. We also observed up- as well as down-regulation of various costimulatory/adhesion molecules, such as CD28 and CD154, important for T-cell function. Conclusions Taken together, our findings indicate that HDAC inhibitors have an immunomodulatory potential that may contribute to the potency and specificity of these antineoplastic compounds and might be useful in the treatment of autoimmune disorders.

  2. Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.

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    Bahareh Pezeshkian

    Full Text Available In acute myeloid leukemia (AML, the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

  3. Correlating excited state and charge carrier dynamics with photovoltaic parameters of perylene dye sensitized solar cells: influences of an alkylated carbazole ancillary electron-donor.

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    Li, Yang; Wang, Junting; Yuan, Yi; Zhang, Min; Dong, Xiandui; Wang, Peng

    2017-01-18

    Two perylene dyes characteristic of electron-donors phenanthrocarbazole (PC) and carbazyl functionalized PC are selected to study the complicated dynamics of excited states and charge carriers, which underlie the photovoltaic parameters of dye-sensitized solar cells (DSCs). We have combined femtosecond fluorescence up-conversion and time-resolved single-photon counting techniques to probe the wavelength-dependent photoluminescence dynamics of dye molecules not only dissolved in THF but also grafted on the surface of oxide nanoparticles. Excited state relaxation and electron injection both occur on a similar timescale, resulting in a very distributive kinetics of electron injection. It is also found that the carbazyl ancillary electron-donor causes a faster electron injection, which over-compensates the adverse impact of a slightly shorter lifetime of the equilibrium excited state. Nanosecond transient absorption and transient photovoltage decay measurements have shown that conjugating carbazyl to PC can effectively slow down the kinetics of charge recombination of electrons in titania with both photo-oxidized dye molecules and triiodide anions, improving the cell photovoltage.

  4. Modulation of RANTES expression by HCV core protein in liver derived cell lines

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    Rapicetta Maria

    2007-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is associated with high percentage of chronicity which implies the ability of the virus to evade or modulate host cell immune system. Modulation of chemokines, such as RANTES may be part of the virus induced pathogenicity. We examined the effect of core and structural proteins of HCV on RANTES expression in two liver derived cell lines, HepG2 and Chang Liver (CHL. Methods HepG2 and Chang Liver (CHL cell lines were established and selected for constitutive expression of HCV core and structural genes. Flow cytometry and quantitative RT-PCR analysis were performed to examine the effect of HCV core protein on RANTES expression. Luciferase analysis after RANTES-Luc-promoter transfection of established cell lines was assayed by luminometer measurements (RLU of RANTES promoter activity. IRF-1 and IRF-7 expression was then examined by immunoblotting analysis. Results Results of flow cytometry and RT-PCR analysis indicated that RANTES is differentially regulated by HCV core protein in the two cell lines examined as its expression was inhibited in HepG2 cells, by a reduction of RANTES promoter activity. Conversely, RANTES protein and mRNA were induced by the core protein in CHL cells, through the induction of the promoter. Since HCV genome modulates IRF-1 and IRF-7 in replicon system and IRF-1, IRF-3 and IRF-7 have been reported to regulate RANTES promoter in various cell systems, analysis of the mechanism underlying RANTES modulation by the core protein revealed that IRF-1 expression was induced in HepG2 cells by the core protein, whereas in CHL cells it was expressed at a very low level that was not influenced by transfection with the core protein construct. This suggested that IRF-1 level may mediate the expression of RANTES in cell lines of liver origin. The effect of the core protein on RANTES promoter was countered by co-transfection with NF90, a double-stranded-RNA binding protein that activates

  5. 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.

  6. Electrical synapses between AII amacrine cells in the retina: Function and modulation.

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    Hartveit, Espen; Veruki, Margaret Lin

    2012-12-03

    Adaptation enables the visual system to operate across a large range of background light intensities. There is evidence that one component of this adaptation is mediated by modulation of gap junctions functioning as electrical synapses, thereby tuning and functionally optimizing specific retinal microcircuits and pathways. The AII amacrine cell is an interneuron found in most mammalian retinas and plays a crucial role for processing visual signals in starlight, twilight and daylight. AII amacrine cells are connected to each other by gap junctions, potentially serving as a substrate for signal averaging and noise reduction, and there is evidence that the strength of electrical coupling is modulated by the level of background light. Whereas there is extensive knowledge concerning the retinal microcircuits that involve the AII amacrine cell, it is less clear which signaling pathways and intracellular transduction mechanisms are involved in modulating the junctional conductance between electrically coupled AII amacrine cells. Here we review the current state of knowledge, with a focus on the recent evidence that suggests that the modulatory control involves activity-dependent changes in the phosphorylation of the gap junction channels between AII amacrine cells, potentially linked to their intracellular Ca(2+) dynamics. This article is part of a Special Issue entitled Electrical Synapses. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Thin Film CIGS Solar Cells, Photovoltaic Modules, and the Problems of Modeling

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    Antonino Parisi

    2013-01-01

    Full Text Available Starting from the results regarding a nonvacuum technique to fabricate CIGS thin films for solar cells by means of single-step electrodeposition, we focus on the methodological problems of modeling at cell structure and photovoltaic module levels. As a matter of fact, electrodeposition is known as a practical alternative to costly vacuum-based technologies for semiconductor processing in the photovoltaic device sector, but it can lead to quite different structural and electrical properties. For this reason, a greater effort is required to ensure that the perspectives of the electrical engineer and the material scientist are given an opportunity for a closer comparison and a common language. Derived parameters from ongoing experiments have been used for simulation with the different approaches, in order to develop a set of tools which can be used to put together modeling both at single cell structure and complete module levels.

  8. Prospects of Nanostructure-Based Solar Cells for Manufacturing Future Generations of Photovoltaic Modules

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    N. Gupta

    2009-01-01

    Full Text Available We present a comprehensive review on prospects for one-, two-, or three-dimensional nanostructure-based solar cells for manufacturing the future generation of photovoltaic (PV modules. Reducing heat dissipation and utilizing the unabsorbed part of the solar spectrum are the key driving forces for the development of nanostructure-based solar cells. Unrealistic assumptions involved in theoretical work and the tendency of stretching observed experimental results are the primary reasons why quantum phenomena-based nanostructures solar cells are unlikely to play a significant role in the manufacturing of future generations of PV modules. Similar to the invention of phase shift masks (to beat the conventional diffraction limit of optical lithography clever design concepts need to be invented to take advantage of quantum-based nanostructures. Silicon-based PV manufacturing will continue to provide sustained growth of the PV industry.

  9. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling.

    Science.gov (United States)

    Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M Ruth; Irving, Andrew J; Lluís, Carme; Canela, Enric I; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J; Sánchez, Cristina

    2014-08-08

    The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Apoptosis induced by ultraviolet radiation is enhanced by amplitude modulated radiofrequency radiation in mutant yeast cells.

    Science.gov (United States)

    Markkanen, Ari; Penttinen, Piia; Naarala, Jonne; Pelkonen, Jukka; Sihvonen, Ari-Pekka; Juutilainen, Jukka

    2004-02-01

    The aim of this study was to investigate whether radiofrequency (RF) electromagnetic field (EMF) exposure affects cell death processes of yeast cells. Saccharomyces cerevisiae yeast cells of the strains KFy417 (wild-type) and KFy437 (cdc48-mutant) were exposed to 900 or 872 MHz RF fields, with or without exposure to ultraviolet (UV) radiation, and incubated simultaneously with elevated temperature (+37 degrees C) to induce apoptosis in the cdc48-mutated strain. The RF exposure was carried out in a special waveguide exposure chamber where the temperature of the cell cultures can be precisely controlled. Apoptosis was analyzed using the annexin V-FITC method utilizing flow cytometry. Amplitude modulated (217 pulses per second) RF exposure significantly enhanced UV induced apoptosis in cdc48-mutated cells, but no effect was observed in cells exposed to unmodulated fields at identical time-average specfic absorption rates (SAR, 0.4 or 3.0 W/kg). The findings suggest that amplitude modulated RF fields, together with known damaging agents, can affect the cell death process in mutated yeast cells. Bioelectromagnetics 25:127-133, 2004. Copyright 2004 Wiley-Liss, Inc.

  11. Murine brain endothelial cells differently modulate interferon-γ and interleukin-17 production in vitro

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    Momčilović Miljana

    2009-01-01

    Full Text Available Brain endothelial cells (BEC are the major constituents of the blood-brain barrier (BBB, the structure that controls entrance of immune cells into CNS parenchyma. Our aim was to investigate the influence of BEC on production of IL-17 and IFN-γ-cytokines that are important for CNS inflammation. To that end, co-cultivations of the bEnd.3 brain endothelial cell line and lymph node cells (LNC were performed, and gene expression and production of IL-17 and IFN-γ were determined. It was found that bEnd.3 cells inhibited expression and production of IFN-γ, but not of IL-17. Additionally, bEnd.3 cells also reduced production of the major IFN-γ-promoting cytokine - IL-12 - in LNC. The observed variation in modulation of pro-inflammatory cytokines by BEC could be of importance for the understanding of CNS inflammation.

  12. Integrated modulation of phorbol ester-induced Raf activation in EL4 lymphoma cells.

    Science.gov (United States)

    Han, Shujie; Meier, Kathryn E

    2009-05-01

    The EL4 murine lymphoma cell line exists in variant phenotypes that differ with respect to responses to the tumor promoter phorbol 12-myristate 13-acetate (PMA1). Previous work showed that "PMA-sensitive" cells, characterized by a high magnitude of PMA-induced Erk activation, express RasGRP, a phorbol ester receptor that directly activates Ras. In "PMA-resistant" and "intermediate" EL4 cell lines, PMA induces Erk activation to lesser extents, but with a greater response in intermediate cells. In the current study, these cell lines were used to examine mechanisms of Raf-1 modulation. Phospho-specific antibodies were utilized to define patterns and kinetics of Raf-1 phosphorylation on several sites. Further studies showed that Akt is constitutively activated to a greater extent in PMA-resistant than in PMA-sensitive cells, and also to a greater extent in resistant than intermediate cells. Akt negatively regulates Raf-1 activation (Ser259), partially explaining the difference between resistant and intermediate cells. Erk activation exerts negative feedback on Raf-1 (Ser289/296/301), thus resulting in earlier termination of the signal in cells with a higher level of Erk activation. RKIP, a Raf inhibitory protein, is expressed at higher levels in resistant cells than in sensitive or intermediate cells. Knockdown of RKIP increases Erk activation and also negative feedback. In conclusion, this study delineates Raf-1 phosphorylation events occurring in response to PMA in cell lines with different extents of Erk activation. Variations in the levels of expression and activation of multiple signaling proteins work in an integrated fashion to modulate the extent and duration of Erk activation.

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

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    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.

  14. 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.

  15. Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling.

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    Kaur, Sukhbir; Roberts, David D

    2016-12-01

    Thrombospondin-1 is a secreted matricellular protein that regulates the differentiation and function of many cell types. Thrombospondin-1 is not required for embryonic development, but studies using lineage-committed adult stem cells have identified positive and negative effects of thrombospondin-1 on stem cell differentiation and self-renewal and identified several thrombospondin-1 receptors that mediate these responses. Genetic studies in mice reveal a broad inhibitory role of thrombospondin-1 mediated by its receptor CD47. Cells and tissues lacking thrombospondin-1 or CD47 exhibit an increased capacity for self-renewal associated with increased expression of the stem cell transcription factors c-Myc, Sox2, Klf4, and Oct4. Thrombospondin-1 inhibits expression of these transcription factors in a CD47-dependent manner. However, this regulation differs in some neoplastic cells. Tumor initiating/cancer stem cells express high levels of CD47, but in contrast to nontransformed stem cells CD47 signaling supports cancer stem cells. Suppression of CD47 expression in cancer stem cells or ligation of CD47 by function blocking antibodies or thrombospondin-1 results in loss of self-renewal. Therefore, the therapeutic CD47 antagonists that are in clinical development for stimulating innate anti-tumor immunity may also inhibit tumor growth by suppressing cancer stem cells. These and other therapeutic modulators of thrombospondin-1 and CD47 signaling may also have applications in regenerative medicine to enhance the function of normal stem cells. Published by Elsevier Ltd.

  16. Plasmonic excitation-assisted optical and electric enhancement in ultra-thin solar cells: the influence of nano-strip cross section

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    Mohammad Sabaeian

    2015-08-01

    Full Text Available The effects of Ag nano-strips with triangle, rectangular and trapezoid cross sections on the optical absorption, generation rate, and short-circuit current density of ultra-thin solar cells were investigated. By putting the nano-strips as a grating structure on the top of the solar cells, the waveguide, surface plasmon polariton (SPP, and localized surface plasmon (LSP modes, which are excited with the assistance of nano-strips, were evaluated in TE and TM polarizations. The results show, firstly, the TM modes are more influential than TE modes in optical and electrical properties enhancement of solar cell, because of plasmonic excitations in TM mode. Secondly, the trapezoid nano-strips reveal noticeable impact on the optical absorption, generation rate, and short-circuit current density enhancement than triangle and rectangular ones. In particular, the absorption of long wavelengths which is a challenge in ultra-thin solar cells is significantly improved by using Ag trapezoid nano-strips.

  17. Targeting metabolic plasticity in breast cancer cells via mitochondrial complex I modulation.

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    Xu, Qijin; Biener-Ramanujan, Eva; Yang, Wei; Ramanujan, V Krishnan

    2015-02-01

    Heterogeneity commonly observed in clinical tumors stems both from the genetic diversity as well as from the differential metabolic adaptation of multiple cancer types during their struggle to maintain uncontrolled proliferation and invasion in vivo. This study aims to identify a potential metabolic window of such adaptation in aggressive human breast cancer cell lines. With a multidisciplinary approach using high-resolution imaging, cell metabolism assays, proteomic profiling and animal models of human tumor xenografts and via clinically-relevant pharmacological approach for modulating mitochondrial complex I function in human breast cancer cell lines, we report a novel route to target metabolic plasticity in human breast cancer cells. By a systematic modulation of mitochondrial function and by mitigating metabolic switch phenotype in aggressive human breast cancer cells, we demonstrate that the resulting metabolic adaptation signatures can predictably decrease tumorigenic potential in vivo. Proteomic profiling of the metabolic adaptation in these cells further revealed novel protein-pathway interactograms highlighting the importance of antioxidant machinery in the observed metabolic adaptation. Improved metabolic adaptation potential in aggressive human breast cancer cells contribute to improving mitochondrial function and reducing metabolic switch phenotype-which may be vital for targeting primary tumor growth in vivo.

  18. Dickkopf-3, a tissue-derived modulator of local T cell responses

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    Michael eMeister

    2015-02-01

    Full Text Available The adaptive immune system protects organisms from harmful environmental insults. In parallel, regulatory mechanisms control immune responses in order to assure preservation of organ integrity. Yet, molecules involved in the control of T cell responses in peripheral tissues are poorly characterized. Here, we investigated the function of Dickkopf-3 in the modulation of local T cell reactivity. Dkk3 is a secreted, mainly tissue derived protein with highest expression in organs considered as immune privileged such as the eye, embryo, placenta and brain. While T cell development and activation status in naïve Dkk3 deficient mice was comparable to littermate controls, we found that Dkk3 contributes to the immunosuppressive microenvironment that protects transplanted, class-I mismatched embryoid bodies from T cell mediated rejection. Moreover, genetic deletion or antibody mediated neutralization of Dkk3 led to an exacerbated experimental autoimmune encephalomyelitis (EAE. This phenotype was accompanied by a change of T cell polarization displayed by an increase of IFNγ producing T cells within in the CNS. In the wild type situation, Dkk3 expression in the brain was up-regulated during the course of EAE in an IFNγ dependent manner. In turn, Dkk3 decreased IFNγ activity and served as part of a negative feedback mechanism. Thus, our findings suggest that Dkk3 functions as a tissue-derived modulator of local CD4+ and CD8+ T cell responses.

  19. Ubiquitous [Na+]i/[K+]i-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca2+i-Independent Excitation-Transcription Coupling

    Science.gov (United States)

    Koltsova, Svetlana V.; Trushina, Yulia; Haloui, Mounsif; Akimova, Olga A.; Tremblay, Johanne; Hamet, Pavel; Orlov, Sergei N.

    2012-01-01

    Stimulus-dependent elevation of intracellular Ca2+ ([Ca2+]i) affects the expression of numerous genes – a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na+]i trigger c-Fos expression via a novel Ca2+i-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na+]i/[K+]i-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na+]i and reduce [K+]i, cells were treated for 3 hrs with the Na+,K+-ATPase inhibitor ouabain or placed for the same time in the K+-free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p0.62). Among these Na+i/K+i-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca2+]i, we performed identical experiments in Ca2+-free media supplemented with extracellular and intracellular Ca2+ chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell-type specific Na+i/K+i-sensitive genes. Among the ubiquitous Na+i/K+i-sensitive genes whose expression was regulated independently of the presence of Ca2+ chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca2+-depleted cells. Overall, our findings indicate that Ca2+i-independent mechanisms of excitation-transcription coupling are involved in

  20. H-1 and N-15 resonance assignment of the second fibronectin type III module of the neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Kiselyov, Vladislav V; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    We report here the NMR assignment of the second fibronectin type III module of the neural cell adhesion molecule (NCAM). This module has previously been shown to interact with the fibroblast growth factor receptor (FGFR), and the FGFR-binding site was mapped by NMR to the FG-loop region of the mo......We report here the NMR assignment of the second fibronectin type III module of the neural cell adhesion molecule (NCAM). This module has previously been shown to interact with the fibroblast growth factor receptor (FGFR), and the FGFR-binding site was mapped by NMR to the FG-loop region...

  1. Modulating autophagy in cancer therapy: advancements and challenges for cancer cell death sensitization.

    Science.gov (United States)

    Bhat, Punya; Kriel, Jurgen; Shubha Priya, Babu; Salundi, Basappa; Shivananju, Nanjunda Swamy; Loos, Ben

    2017-12-01

    Autophagy is a major protein degradation pathway capable of upholding cellular metabolism under nutrient limiting conditions, making it a valuable resource to highly proliferating tumour cells. Although the regulatory machinery of the autophagic pathway has been well characterized, accurate modulation of this pathway remains complex in the context of clinical translatability for improved cancer therapies. In particular, the dynamic relationship between the rate of protein degradation through autophagy, i.e. autophagic flux, and the susceptibility of tumours to undergo apoptosis remains largely unclear. Adding to inefficient clinical translation is the lack of measurement techniques that accurately depict autophagic flux. Paradoxically, both increased autophagic flux as well as autophagy inhibition have been shown to sensitize cancer cells to undergo cell death, indicating the highly context dependent nature of this pathway. In this article, we aim to disentangle the role of autophagy modulation in tumour suppression by assessing existing literature in the context of autophagic flux and cellular metabolism at the interface of mitochondrial function. We highlight the urgency to not only assess autophagic flux more accurately, but also to center autophagy manipulation within the unique and inherent metabolic properties of cancer cells. Lastly, we discuss the challenges faced when targeting autophagy in the clinical setting. In doing so, it is hoped that a better understanding of autophagy in cancer therapy is revealed in order to overcome tumour chemoresistance through more controlled autophagy modulation in the future. Copyright © 2017. Published by Elsevier Inc.

  2. Talin Modulation by a Synthetic N-Acylurea Derivative Reduces Angiogenesis in Human Endothelial Cells

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    I-Rang Lim

    2017-01-01

    Full Text Available Talin is a focal adhesion protein that activates integrins and recruits other focal adhesion proteins. Talin regulates the interactions between integrins and the extracellular matrix, which are critical for endothelial cells during angiogenesis. In this study, we successfully synthesized a novel talin modulator, N-((2-(1H-indol-3-ylethylcarbamoyl-2-(benzo[d][1,3]dioxol-5-yloxyacetamide, referred to as KCH-1521. KCH-1521 was determined to bind talin and modulate downstream signaling molecules of talin. After 24 h of treatment, KCH-1521 changed the cell morphology of human umbilical vein endothelial cells (HUVECs and reduced focal adhesion protein expression including vinculin and paxillin. Talin downstream signaling is regulated via focal adhesion kinase (FAK, kinase B (AKT, and extracellular signal-regulated kinase (ERK pathways, however, treatment with KCH-1521 decreased phosphorylation of FAK, AKT, and ERK, leading to reduction of cell proliferation, survival, and angiogenesis. Interestingly, the expression of various angiogenic genes was significantly decreased after treatment with KCH-1521. Also, in vitro tube forming assay revealed that KCH-1521 reduced angiogenic networks in a time-dependent manner. To investigate the reversibility of its effects, KCH-1521 was removed after treatment. HUVECs recovered their morphology through rearrangement of the cytoskeleton and the expression of angiogenic genes was also recovered. By further optimization and in vivo studies of KCH-1521, a novel drug of talin modulation could be used to achieve therapeutic anti-angiogenesis for vascular diseases and cancers.

  3. Mechanisms and modulation of microvesicle uptake in a model of alveolar cell communication.

    Science.gov (United States)

    Schneider, Daniel J; Speth, Jennifer M; Penke, Loka R; Wettlaufer, Scott H; Swanson, Joel A; Peters-Golden, Marc

    2017-11-03

    Extracellular vesicles (EVs), including exosomes and shed microvesicles (MVs), can be internalized by recipient cells to modulate function. Although the mechanism by which EVs are internalized is incompletely characterized, it is generally regarded to involve endocytosis and an initial surface binding event. Furthermore, modulation of uptake by microenvironmental factors is largely unstudied. Here we used flow cytometry, confocal microscopy, and pharmacologic and molecular targeting to address these gaps in knowledge in a model of pulmonary alveolar cell-cell communication. Alveolar macrophage-derived MVs were fully internalized by alveolar epithelial cells in a time-, dose-, and temperature-dependent manner. Uptake was dependent on dynamin and actin polymerization. However, it was neither saturable nor dependent on clathrin or receptor binding. Internalization was enhanced by extracellular proteins, but was inhibited by cigarette smoke extract via oxidative disruption of actin polymerization. We conclude that MV internalization occurs via a pathway more consistent with fluid-phase than receptordependent endocytosis, and is subject to bidirectional modulation by relevant pathologic perturbations. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  4. ADAR1-Mediated RNA Editing, A Novel Mechanism Controlling Phenotypic Modulation of Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Fei, Jia; Cui, Xiao-Bing; Wang, Jia-Ning; Dong, Kun; Chen, Shi-You

    2016-07-22

    Vascular smooth muscle cell (SMC) phenotypic modulation is characterized by the downregulation of SMC contractile genes. Platelet-derived growth factor-BB, a well-known stimulator of SMC phenotypic modulation, downregulates SMC genes via posttranscriptional regulation. The underlying mechanisms, however, remain largely unknown. To establish RNA editing as a novel mechanism controlling SMC phenotypic modulation. Precursor mRNAs (pre-mRNA) of SMC myosin heavy chain and smooth muscle α-actin were accumulated while their mature mRNAs were downregulated during SMC phenotypic modulation, suggesting an abnormal splicing of the pre-mRNAs. The abnormal splicing resulted from SMC marker pre-mRNA editing that was facilitated by adenosine deaminase acting on RNA 1 (ADAR1), an enzyme converting adenosines to inosines (A→I editing) in RNA sequences. ADAR1 expression inversely correlated with SMC myosin heavy chain and smooth muscle α-actin levels; knockdown of ADAR1 restored SMC myosin heavy chain and smooth muscle α-actin expression in phenotypically modulated SMC, and editase domain mutation diminished the ADAR1-mediated abnormal splicing of SMC marker pre-mRNAs. Moreover, the abnormal splicing/editing of SMC myosin heavy chain and smooth muscle α-actin pre-mRNAs occurred during injury-induced vascular remodeling. Importantly, heterozygous knockout of ADAR1 dramatically inhibited injury-induced neointima formation and restored SMC marker expression, demonstrating a critical role of ADAR1 in SMC phenotypic modulation and vascular remodeling in vivo. Our results unraveled a novel molecular mechanism, that is, pre-mRNA editing, governing SMC phenotypic modulation. © 2016 American Heart Association, Inc.

  5. Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior.

    Science.gov (United States)

    Heinke, J; Kerber, M; Rahner, S; Mnich, L; Lassmann, S; Helbing, T; Werner, M; Patterson, C; Bode, C; Moser, M

    2012-06-14

    Bone morphogenetic proteins (BMPs) are growth factors that exert important functions in cell proliferation, migration and differentiation. Till date, multiple human tumors have been reported to display a dysregulation of several members of the BMP pathway that is associated with enhanced malignant tumor growth and metastasis. BMPER (BMP endothelial cell precursor-derived regulator) is a direct BMP modulator that is necessary for BMPs to exert their full-range signaling activity. Moreover, BMPER is expressed by endothelial cells and their progenitors, and has pro-angiogenic features in these cells. Here, we describe the expression of BMPER in human specimens of lung, colon and cervix carcinomas and cell lines derived from such carcinomas. In contrast to healthy tissues, BMPER is highly expressed upon malignant deterioration. Functionally, loss of BMPER in the lung tumor cell line A549 impairs proliferation, migration, invasion as well as tumor cell-induced endothelial cell sprout formation. In contrast, stimulation of A549 cells with exogenous BMPER had no further effect. We found that the BMPER effect may be transduced by regulation of the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 9 and 2. These facilitators of cell migration are downregulated when BMPER is absent. To prove the relevance of our in vitro results in vivo, we generated Lewis lung carcinoma cells with impaired BMPER expression and implanted them into the lungs of C57BL/6 mice. In this model, the absence of BMPER resulted in severely reduced tumor growth and tumor angiogenesis. Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER.

  6. Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection

    Science.gov (United States)

    Goff, Eric E.; Reindl, Katie M.; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G.; Schroeder, Noah L.; White, Alan R.

    2017-01-01

    Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend greatly on how well the student prepares before class. As a possible preparatory resource, we test the efficacy of a learning module developed for the Virtual Cell Animation Collection. This module presents the concepts of meiosis in an interactive, dynamic environment that has previously been shown to facilitate learning in introductory biology students. Participants (n = 534) were enrolled in an introductory biology course and were presented the concepts of meiosis in one of two treatments: the interactive-learning module or a traditional lecture session. Analysis of student achievement shows that students who viewed the learning module as their only means of conceptual presentation scored significantly higher (d = 0.40, p students who only attended a traditional lecture on the topic. Our results show the animation-based learning module effectively conveyed meiosis conceptual understanding, which suggests that it may facilitate student learning outside the classroom. Moreover, these results have implications for instructors seeking to expand their arsenal of tools for “flipping” undergraduate biology courses. PMID:28188282

  7. Aging-Associated Changes to Intrinsic Neuronal Excitability in the Bed Nucleus of the Stria Terminalis Is Cell Type-Dependent

    Directory of Open Access Journals (Sweden)

    Hannah E. Smithers

    2017-12-01

    Full Text Available Intrinsic neuronal excitability has been reported to change during normal aging. The bed nucleus of the stria terminalis (BNST, a limbic forebrain structure, is involved in fear, stress and anxiety; behavioral features that exhibit age-dependent properties. To examine the effect of aging on intrinsic neuronal properties in BNST we compared patch clamp recordings from cohorts of female mice at two ages, 3–4 months (Young and 29–30 months (Aged focusing on 2 types of BNST neurons. Aged Type I neurons exhibited a hyperpolarized resting membrane potential (RMP of circa -80 mV compared to circa -70 mV in the Young. A key finding in this study is a hyper-excitability of Type II neurons with age reflected in an increase in firing frequency in response to depolarizing current injections; activation of Type II neurons is believed to dampen anxiety like responses. Such age-related changes in intrinsic neurophysiological function are likely to modulate how the limbic system, acting via BNST, shapes function in the HPA-axis.

  8. Islet microenvironment, modulated by vascular endothelial growth factor-A signaling, promotes β cell regeneration

    Science.gov (United States)

    Brissova, Marcela; Aamodt, Kristie; Brahmachary, Priyanka; Prasad, Nripesh; Hong, Ji-Young; Dai, Chunhua; Mellati, Mahnaz; Shostak, Alena; Poffenberger, Greg; Aramandla, Radhika; Levy, Shawn E.; Powers, Alvin C.

    2014-01-01

    SUMMARY Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature, islet microenvironment, and β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to β cell loss. After withdrawal of the VEGF-A stimulus, β cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing β cells. Bone marrow-derived macrophages (MΦs) recruited to the site of β cell injury were crucial for the β cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated β cells will improve strategies aimed at β cell regeneration and expansion. PMID:24561261

  9. Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

    Science.gov (United States)

    Salem, Heba F; Ahmed, Sayed M; Hassaballah, Ashraf E; Omar, Mahmoud M

    2015-01-01

    Background The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results The size of glutathione-modulated nanoliposomes was glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections. PMID:26229435

  10. Co-incubation of PMN and CaCo-2 cells modulates inflammatory potential.

    Science.gov (United States)

    Schaefer, M B; Schaefer, C A; Hecker, M; Morty, R E; Witzenrath, M; Seeger, W; Mayer, K

    2017-05-20

    Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only. Human neutrophil elastase (HNE) and respiratory Burst were measured. To evaluate the modulation of inflammatory crosstalk we applied inhibitors of COX (acetyl salicylic acid; ASA), NO-synthase (N-monomethyl-L-arginin; L-NMMA), and the PAF-receptor (WEB2086). Unstimulated, co-incubation of CaCo-2 cells and PMN led to significantly reduced Burst and elevated HNE as compared to PMN. After stimulation with A23187, co-incubation resulted in an inhibition of Burst and HNE. Using fMLP co-incubation failed to modulate Burst but increased HNE. Without stimulation, all three inhibitors abolished the effect of co-incubation on Burst but did not change HNE.  ASA partly prevented modulation of Burst L-NMMA and WEB2086 did not change Burst but abolished mitigation of HNE. Without stimulation, co-incubation reduced Burst and elevated HNE. Activation of PMN and CaCo-2 cells by fMLP as compared to A23187 resulted in a completely different pattern of Burst and HNE, possibly due to single vs. dual cell activation. Anti-inflammatory effect of co-incubation might in part be due to due to COX-signalling governing Burst whereas NO- and PAF-dependent signalling seemed to control HNE release.

  11. Coxiella burnetii Nine Mile II proteins modulate gene expression of monocytic host cells during infection

    Directory of Open Access Journals (Sweden)

    Shaw Edward I

    2010-09-01

    Full Text Available Abstract Background Coxiella burnetii is an intracellular bacterial pathogen that causes acute and chronic disease in humans. Bacterial replication occurs within enlarged parasitophorous vacuoles (PV of eukaryotic cells, the biogenesis and maintenance of which is dependent on C. burnetii protein synthesis. These observations suggest that C. burnetii actively subverts host cell processes, however little is known about the cellular biology mechanisms manipulated by the pathogen during infection. Here, we examined host cell gene expression changes specifically induced by C. burnetii proteins during infection. Results We have identified 36 host cell genes that are specifically regulated when de novo C. burnetii protein synthesis occurs during infection using comparative microarray analysis. Two parallel sets of infected and uninfected THP-1 cells were grown for 48 h followed by the addition of chloramphenicol (CAM to 10 μg/ml in one set. Total RNA was harvested at 72 hpi from all conditions, and microarrays performed using Phalanx Human OneArray™ slides. A total of 784 (mock treated and 901 (CAM treated THP-1 genes were up or down regulated ≥2 fold in the C. burnetii infected vs. uninfected cell sets, respectively. Comparisons between the complementary data sets (using >0 fold, eliminated the common gene expression changes. A stringent comparison (≥2 fold between the separate microarrays revealed 36 host cell genes modulated by C. burnetii protein synthesis. Ontological analysis of these genes identified the innate immune response, cell death and proliferation, vesicle trafficking and development, lipid homeostasis, and cytoskeletal organization as predominant cellular functions modulated by C. burnetii protein synthesis. Conclusions Collectively, these data indicate that C. burnetii proteins actively regulate the expression of specific host cell genes and pathways. This is in addition to host cell genes that respond to the presence of the

  12. Neuropeptide Substance-P-Conjugated Chitosan Nanofibers as an Active Modulator of Stem Cell Recruiting

    Directory of Open Access Journals (Sweden)

    Min Sup Kim

    2016-01-01

    Full Text Available The goal to successful wound healing is essentially to immobilize and recruit appropriate numbers of host stem or progenitor cells to the wound area. In this study, we developed a chitosan nanofiber-immobilized neuropeptide substance-P (SP, which mediates stem cell mobilization and migration, onto the surfaces of nanofibers using a peptide-coupling agent, and evaluated its biological effects on stem cells. The amount of immobilized SP on chitosan nanofibers was modulated over the range of 5.89 ± 3.27 to 75.29 ± 24.31 ng when reacted with 10 to 500 ng SP. In vitro migration assays showed that SP-incorporated nanofibers induced more rapid migration of human mesenchymal stem cells on nanofibers compared to pristine samples. Finally, the conjugated SP evoked a minimal foreign body reaction and recruited a larger number of CD29- and CD44-positive stem cells into nanofibers in a mouse subcutaneous pocket model.

  13. Dietary lutein modulates growth and survival genes in prostate cancer cells.

    Science.gov (United States)

    Rafi, Mohamed M; Kanakasabai, Saravanan; Gokarn, Sarita V; Krueger, Eric G; Bright, John J

    2015-02-01

    Lutein is a carotenoid pigment present in fruits and vegetables that has anti-inflammatory and antitumor properties. In this study, we examined the effect of lutein on proliferation and survival-associated genes in prostate cancer (PC-3) cells. We found that in vitro culture of PC-3 cells with lutein induced mild decrease in proliferation that improved in combination treatment with peroxisome proliferator-activated receptor gamma (PPARγ) agonists and other chemotherapeutic agents. Flow cytometry analyses showed that lutein improved drug-induced cell cycle arrest and apoptosis in prostate cancer. Gene array and quantitative reverse transcription-polymerase chain reaction analyses showed that lutein altered the expression of growth and apoptosis-associated biomarker genes in PC-3 cells. These findings highlight that lutein modulates the expression of growth and survival-associated genes in prostate cancer cells.

  14. Implementation of a Service-Learning Module in Medical Microbiology and Cell Biology Classes at an Undergraduate Liberal Arts University

    Directory of Open Access Journals (Sweden)

    Maia Larios-Sanz

    2011-03-01

    Full Text Available Here we discuss the implementation of a service-learning module in two upper-division biology classes, Medical Microbiology and Cell Biology. This exciting hands-on learning experience provided our students with an opportunity to extend their learning of in-class topics to a real-life scenario. Students were required to volunteer their time (a minimum of 10 hours in a semester at an under-served clinic in Houston, Texas. As they interacted with the personnel at the clinic, they were asked to identify the most prevalent disease (infectious for Medical Microbiology, and cellular-based for Cell seen at the clinic and, working in groups, come up with educational material in the form of a display or brochure to be distributed to patients. The material was meant to educate patients about the disease in general terms, as well as how to recognize (symptoms, prevent and treat it. Students were required to keep a reflective journal in the form of a blog throughout the semester, and present their final materials to the class orally. Students were surveyed about their opinion of the experience at the end of the semester. The vast majority of student participants felt that the project was a positive experience and that it helped them develop additional skills beyond what they learn in the classroom and understand how lecture topics relate to every day life. Here we discuss the implementation of a service-learning module in two upper division biology classes, Medical Microbiology and Cell Biology. This exciting hands-on learning experience provided our students with an opportunity to extend their learning of in-class topics into a real life scenario. Students were required to volunteer their time (a minimum of 10 hours in a semester at an under-served clinic in Houston, Texas. As they interacted with the personnel at the clinic, they were asked to identify the most prevalent disease (infectious for Medical Microbiology, and cellular-based for Cell seen at the

  15. All solution processing of ITO-free organic solar cell modules directly on barrier foil

    DEFF Research Database (Denmark)

    Angmo, Dechan; Hösel, Markus; Krebs, Frederik C

    2012-01-01

    In this study, we demonstrate fully solution processed semi-transparent silver electrodes on flexible substrates having a sheet resistance as low as 5Ω/□ and transmittance of ∼30% at 550nm. We demonstrate the use of this electrode as a substitute for ITO in an inverted organic solar cell (OSC...... and processing cost and is a cost-effective alternative to ITO for low-cost organic solar cells.......-transparent Ag electrode fabrication in a roll-to-roll (R2R) process using slot-die coating. This electrode is further utilized in R2R processing of large area modules (active area 35.5cm2) where all layers in the modules are R2R processed with solution-based materials in ambient conditions without any use...

  16. Process development for automated solar cell and module production. Task 4: automated array assembly

    Energy Technology Data Exchange (ETDEWEB)

    Hagerty, J.J.

    1980-06-30

    The scope of work under this contract involves specifying a process sequence which can be used in conjunction with automated equipment for the mass production of solar cell modules for terrestrial use. This process sequence is then critically analyzed from a technical and economic standpoint to determine the technological readiness of each process step for implementation. The process steps are ranked according to the degree of development effort required and according to their significance to the overall process. Under this contract the steps receiving analysis were: back contact metallization, automated cell array layup/interconnect, and module edge sealing. For automated layup/interconnect both hard automation and programmable automation (using an industrial robot) were studied. The programmable automation system was then selected for actual hardware development. Economic analysis using the SAMICS system has been performed during these studies to assure that development efforts have been directed towards the ultimate goal of price reduction. Details are given. (WHK)

  17. NK Cells and Their Ability to Modulate T Cells during Virus Infections

    OpenAIRE

    Cook, Kevin D.; Waggoner, Stephen N.; Jason K. Whitmire

    2014-01-01

    Natural killer (NK) cells are important in protection against virus infections, and many viruses have evolved mechanisms to thwart NK cell activity. NK cells respond to inflammatory signals at an early stage of virus infection, resulting in proliferation, cytokine production, and cytolytic activity that can reduce virus loads. Moreover, the rapid kinetics of the NK cell response enables NK cells to influence other populations of innate immune cells, affect the inflammatory milieu, and guide a...

  18. 17th Workshop on Crystalline Silicon Solar Cells and Modules: Materials and Processes; Workshop Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B. L.

    2007-08-01

    The National Center for Photovoltaics sponsored the 17th Workshop on Crystalline Silicon Solar Cells & Modules: Materials and Processes, held in Vail, CO, August 5-8, 2007. This meeting provided a forum for an informal exchange of technical and scientific information between international researchers in the photovoltaic and relevant non-photovoltaic fields. The theme of this year's meeting was 'Expanding Technology for a Future Powered by Si Photovoltaics.'

  19. Vitamin D modulates different IL-17-secreting T cell subsets in multiple sclerosis patients.

    Science.gov (United States)

    da Costa, Denise S M Medrado; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Monteiro, Clarice; Oliveira, Aleida; Tavares, Felipe; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-10-15

    Vitamin D deficiency is an environmental risk factor for MS, a Th17 cell-mediated autoimmune disease that results in demyelination in the CNS. Therefore, we aimed to evaluate the ability of in vitro 1,25(OH)2D in modulating different Th17 cell subsets in MS patients in remission phase. In the present study, the production of Th17-related cytokines (IL-1β, IL-6, IL-17, IL-22), as well as GM-CSF, was significantly higher in cell cultures from MS patients than in healthy subjects (HS). The 1,25(OH)2D reduced all pro-inflammatory cytokines essayed, mainly those released from HS cell cultures. The proportion of both IL-17+IFN-γ+ (CD4+ and CD8+) T cells and IL-17+IFN-γ-CD8+ T cells was positively related with neurological disorders, determined by EDSS score. The addition of 1,25(OH)2D reduced not only these pathogenic T cell subsets but elevated the percentage of IL-10-secreting conventional (FoxP3+CD25+CD127-CD4+) and non-conventional (IL-17+) regulatory-like T cells. Taken together, the results indicate that the active form of vitamin D should benefit MS patients by attenuating the percentage of pathogenic T cells. This effect could be direct and/or indirect, by enhancing classical and non-classical regulatory T cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. 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.

  1. Crosslinking of extracellular matrix scaffolds derived from pluripotent stem cell aggregates modulates neural differentiation.

    Science.gov (United States)

    Sart, Sébastien; Yan, Yuanwei; Li, Yan; Lochner, Eric; Zeng, Changchun; Ma, Teng; Li, Yan

    2016-01-01

    At various developmental stages, pluripotent stem cells (PSCs) and their progeny secrete a large amount of extracellular matrices (ECMs) which could interact with regulatory growth factors to modulate stem cell lineage commitment. ECMs derived from PSC can be used as unique scaffolds that provide broad signaling capacities to mediate cellular differentiation. However, the rapid degradation of ECMs can impact their applications as the scaffolds for in vitro cell expansion and in vivo transplantation. To address this issue, this study investigated the effects of crosslinking on the ECMs derived from embryonic stem cells (ESCs) and the regulatory capacity of the crosslinked ECMs on the proliferation and differentiation of reseeded ESC-derived neural progenitor cells (NPCs). To create different biological cues, undifferentiated aggregates, spontaneous embryoid bodies, and ESC-derived NPC aggregates were decellularized. The derived ECMs were crosslinked using genipin or glutaraldehyde to enhance the scaffold stability. ESC-derived NPC aggregates were reseeded on different ECM scaffolds and differential cellular compositions of neural progenitors, neurons, and glial cells were observed. The results indicate that ESC-derived ECM scaffolds affect neural differentiation through intrinsic biological cues and biophysical properties. These scaffolds have potential for in vitro cell culture and in vivo tissue regeneration study. Dynamic interactions of acellular extracellular matrices and stem cells are critical for lineage-specific commitment and tissue regeneration. Understanding the synergistic effects of biochemical, biological, and biophysical properties of acellular matrices would facilitate scaffold design and the functional regulation of stem cells. The present study assessed the influence of crosslinked embryonic stem cell-derived extracellular matrix on neural differentiation and revealed the synergistic interactions of various matrix properties. While embryonic stem

  2. Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3.

    Science.gov (United States)

    Patel, Hiren; Bhartiya, Deepa; Parte, Seema; Gunjal, Pranesh; Yedurkar, Snehal; Bhatt, Mithun

    2013-01-01

    We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants 'progenitors' termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively spliced receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in literature of which FSH-R1 and FSH-R3 have biological activity. Present study was undertaken to identify FSHR isoforms mediating FSH action on ovarian stem cells, using sheep OSE cells culture as the study model. Cultures of sheep OSE cells (a mix of epithelial cells, VSELs, OGSCs and few contaminating red blood cells) were established with and without FSH 5IU/ml treatment. Effect of FSH treatment on self-renewal of VSELs and their differentiation into OGSCs was studied after 15 hrs by qRT-PCR using markers specific for VSELs (Oct-4A, Sox-2) and OGSCs (Oct-4). FSH receptors and its specific transcripts (R1 and R3) were studied after 3 and 15 hrs of FSH treatment by immunolocalization, in situ hybridization and qRT-PCR. FSHR and OCT-4 were also immuno-localized on sheep ovarian sections, in vitro matured follicles and early embryos. FSH treatment resulted in increased stem cells self-renewal and clonal expansion evident by the appearance of stem cell clusters. FSH receptors were expressed on ovarian stem cells whereas the epithelial cells were distinctly negative. An increase in R3 mRNA transcripts was noted after 3 hrs of FSH treatment and was reduced to basal levels by 15 hrs, whereas R1 transcript expression remained unaffected. Both FSHR and OCT-4 were immuno-localized in nuclei of stem cells, showed nuclear or ooplasmic localization in oocytes of primordial follicles and in cytoplasm of granulosa cells in growing follicles. FSH modulates ovarian stem cells via FSH-R3 to undergo potential self-renewal, clonal

  3. Upscaling from single cells to modules – fabrication of vacuum- and ITO-free polymer solar cells on flexible substrates with long lifetime

    DEFF Research Database (Denmark)

    Carlé, Jon Eggert; Helgesen, Martin; Madsen, Morten Vesterager

    2014-01-01

    Fabrication of polymer solar cell (PSC) modules was done on a previously reported compact coating/printing machine and tested in a readily scalable roll process on flexible substrates without applying vacuum, ITO or spin coating. Our aim was to establish loss upon scaling from cells to small...... modules. We studied from single cells (1 cm2) to modules comprising four serially connected devices with a total active area of 8 cm2. Four different polymers (P3HT, PV-D4610, PDTSTTz-4 and PBDTTTz-4) were applied in the preparation of the modules and efficiencies of more than 3% were achieved which...... is comparable to single cell devices prepared using the same process. This proves that it is possible to scale up new materials in an ITO free device context to modules without having an efficiency drop, due to reliable and consistent processing. The main loss observed was due to the packaging using barrier...

  4. Mast cells modulate acute ozone-induced inflammation of the murine lung

    Energy Technology Data Exchange (ETDEWEB)

    Kleeberger, S.R.; Seiden, J.E.; Levitt, R.C.; Zhang, L.Y. (Johns Hopkins School of Public Health, Baltimore, MD (United States))

    1993-11-01

    We hypothesized that mast cells modulate lung inflammation that develops after acute ozone (O3) exposure. Two tests were done: (1) genetically mast-cell-deficient (WBB6F1-W/Wv, WCB6F1-SI/SId) and bone-marrow-transplanted W/Wv mice were exposed to O3 or filtered air, and the inflammatory responses were compared with those of mast-cell-sufficient congenic mice (WBB6F1-(+)/+, WCB6F1-(+)/+); (2) genetically O3-susceptible C57BL/6J mice were treated pharmacologically with putative mast-cell modulators or vehicle, and the O3-induced inflammatory responses were compared. Mice were exposed to 1.75 ppm O3 or air for 3 h, and lung inflammation was assessed by bronchoalveolar lavage (BAL) 6 and 24 h after exposure. Relative to O3-exposed W/Wv and SI/SId mice, the mean numbers of lavageable polymorphonuclear leukocytes (PMNs) and total BAL protein concentration (a marker of permeability) were significantly greater in the respective O3-exposed normal congenic +/+ mice (p < 0.05). Mast cells were reconstituted in W/Wv mice by transplantation of bone marrow cells from congenic +/+ mice, and O3-induced lung inflammation was assessed in the mast-cell-replete W/Wv mice. After O3 exposure, the changes in lavageable PMNs and total protein of mast-cell-replete W/Wv mice were not different from age-matched normal +/+ control mice, and they were significantly greater than those of sham-transplanted W/Wv mice (p < 0.05). Genetically susceptible C57BL/6J mice were pretreated with a mast-cell stabilizer (nedocromil sodium), secretagogue (compound 48/80), or vehicle, and the mice were exposed to O3.

  5. NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Haiwen Ni

    Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

  6. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  7. Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

    Science.gov (United States)

    Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

    2018-01-01

    Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

  8. Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.

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    Valeria Gabriela Antico Arciuch

    2009-10-01

    Full Text Available Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473 by mTORC2 and Thr(308 by PDK1. On these bases, we investigated the mechanistic connection of H(2O(2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H(2O(2 entails the entrance of cytosolic P-Akt1 Ser(473 to mitochondria, where it is further phosphorylated at Thr(308 by constitutive PDK1. Phosphorylation of Thr(308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H(2O(2, Akt1-PDK1 association is disrupted and P-Akt1 Ser(473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H(2O(2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys(310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.

  9. CCR1 plays a critical role in modulating pain through hematopoietic and non-hematopoietic cells.

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    Nuruddeen D Lewis

    Full Text Available Inflammation is associated with immune cells infiltrating into the inflammatory site and pain. CC chemokine receptor 1 (CCR1 mediates trafficking of leukocytes to sites of inflammation. However, the contribution of CCR1 to pain is incompletely understood. Here we report an unexpected discovery that CCR1-mediated trafficking of neutrophils and CCR1 activity on non-hematopoietic cells both modulate pain. Using a genetic approach (CCR1-/- animals and pharmacological inhibition of CCR1 with selective inhibitors, we show significant reductions in pain responses using the acetic acid-induced writhing and complete Freund's adjuvant-induced mechanical hyperalgesia models. Reductions in writhing correlated with reduced trafficking of myeloid cells into the peritoneal cavity. We show that CCR1 is highly expressed on circulating neutrophils and their depletion decreases acetic acid-induced writhing. However, administration of neutrophils into the peritoneal cavity did not enhance acetic acid-induced writhing in wild-type (WT or CCR1-/- mice. Additionally, selective knockout of CCR1 in either the hematopoietic or non-hematopoietic compartments also reduced writhing. Together these data suggest that CCR1 functions to significantly modulate pain by controlling neutrophil trafficking to the inflammatory site and having an unexpected role on non-hematopoietic cells. As inflammatory diseases are often accompanied with infiltrating immune cells at the inflammatory site and pain, CCR1 antagonism may provide a dual benefit by restricting leukocyte trafficking and reducing pain.

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

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    Martin H Schaefer

    2014-06-01

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

  11. Raloxifene and anti-estrogenic Gonadorelin inhibits intestinal tumorigenesis by modulating immune cells and decreasing stem like cells

    Science.gov (United States)

    Janakiram, Naveena B.; Mohammed, Altaf; Brewer, Misty; Bryant, Taylor; Biddick, Laura; Lightfoot, Stan; Pathuri, Gopal; Gali, Hariprasad; Rao, Chinthalapally V.

    2014-01-01

    Studies suggest that estrogen plays a contributing role in colorectal cancer (CRC). This project examined the preventive effects of raloxifene, a selective estrogen receptor modulator (SERM), and gonadorelin, an anti-estrogenic drug, in female ApcMin/+ mouse intestinal tumorigenesis. Six-week-old ApcMin/+ mice were fed diet containing 1 ppm raloxifene or control diet. Gonadorelin (150ng/mouse) was injected subcutaneously into one treatment group. Intestinal tumors were evaluated for tumor multiplicity and size. Mice treated with raloxifene and gonadorelin showed colon tumor inhibition of 80% and 75% respectively. Both drugs significantly inhibited small intestinal tumor multiplicity and size (75 – 65%, PRaloxifene and gonadorelin showed significant tumor inhibition with 98% and 94% inhibition of polyps >2 mm in size. In mice fed with raloxifene or injected with gonadorelin, tumors showed significantly reduced proliferating cell nuclear antigen expression (58-65%, PRaloxifene treatment decreased β-catenin, cyclin D1, laminin 1β, Ccl6 and stem like cells (Lgr 5, EpCAM, CD44/CD24), as well as suppressed inflammatory genes (COX-2, mPGES-1, 5-LOX,). Gonadorelin showed significant decrease in COX-2, mPGES-1, iNOS, and stem like cells or increased NK cells and chemokines required for NK cells. Both drugs were effective in suppressing tumor growth albeit with different mechanisms. These observations show that either suppression of estrogen levels or modulation of estrogen receptor dramatically suppresses small intestinal and colonic tumor formation in female ApcMin/+ mice. These results support the concept of chemoprevention by these agents in reducing endogenous levels of estrogen or modulating ER signaling. PMID:24431404

  12. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1.

    Science.gov (United States)

    Apps, Richard; Gardner, Lucy; Sharkey, Andrew M; Holmes, Nick; Moffett, Ashley

    2007-07-01

    In healthy individuals, the non-classical MHC molecule HLA-G is only expressed on fetal trophoblast cells that invade the decidua during placentation. We show that a significant proportion of HLA-G at the surface of normal human trophoblast cells is present as a disulphide-linked homodimer of the conventional beta(2)m-associated HLA-I complex. HLA-G is a ligand for leukocyte immunoglobulin-like receptors (LILR), which bind much more efficiently to dimeric HLA-G than to conventional HLA-I molecules. We find that a LILRB1-Fc fusion protein preferentially binds the dimeric form of HLA-G on trophoblast cells. We detect LILRB1 expression on decidual myelomonocytic cells; therefore, trophoblast HLA-G may modulate the function of these cells. Co-culture with HLA-G(+) cells does not inhibit monocyte-derived dendritic cell up-regulation of HLA-DR and costimulatory molecules on maturation, but did increase production of IL-6 and IL-10. Furthermore, proliferation of allogeneic lymphocytes was inhibited by HLA-G binding to LILRB1/2 on responding antigen-presenting cells (APC). As HLA-G is the only HLA-I molecule that forms beta(2)m-associated dimers with increased avidity for LILRB1, this interaction could represent a placental-specific signal to decidual APC. We suggest that the placenta is modulating maternal immune responses locally in the uterus through HLA-G, a trophoblast-specific, monomorphic signal present in almost every pregnancy. See accompanying commentary: (http://dx.doi.org/10.1002/eji.200737515).

  13. Heme oxygenase-1 (HO-1 expression in prostate cancer cells modulates the oxidative response in bone cells.

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    Mercedes Ferrando

    Full Text Available Prostate cancer (PCa is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1 counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs, we demonstrated that HO-1 pharmacological induction (hemin treatment abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3 Hem with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1 cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis.

  14. The modulation of stem cell behaviors by functionalized nanoceramic coatings on Ti-based implants

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    Xiangmei Liu

    2016-09-01

    Full Text Available Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery. Stem cells have been found to have osteogenic capabilities. It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo. In this paper, we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings, including surface chemistry, surface roughness and microporosity. In addition, mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals. In the final part, the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.

  15. Connecting the dots: artificial antigen presenting cell-mediated modulation of natural killer T cells.

    Science.gov (United States)

    Sun, Wenji; Subrahmanyam, Priyanka B; East, James E; Webb, Tonya J

    2012-11-01

    Natural killer T (NKT) cells constitute an important subset of T cells that can both directly and indirectly mediate antitumor immunity. However, we and others have reported that cancer patients have a reduction in both NKT cell number and function. NKT cells can be stimulated and expanded with α-GalCer and cytokines and these expanded NKT cells retain their phenotype, remain responsive to antigenic stimulation, and display cytotoxic function against tumor cell lines. These data strongly favor the use of ex vivo expanded NKT cells in adoptive immunotherapy. NKT cell based-immunotherapy has been limited by the use of autologous antigen-presenting cells, which can vary substantially in their quantity and quality. A standardized system that relies on artificial antigen-presenting cells (aAPCs) could produce the stimulating effects of dendritic cell (DC) without the pitfalls of allo- or xenogeneic cells. In this review, we discuss the progress that has been made using CD1d-based aAPC and how this acellular antigen presenting system can be used in the future to enhance our understanding of NKT cell biology and to develop NKT cell-specific adoptive immunotherapeutic strategies.

  16. Modulation of Heterotypic and Homotypic Cell-Cell Interactions via Zwitterionic Lipid Masks.

    Science.gov (United States)

    Park, Matthew; Youn, Wongu; Kim, Doyeon; Ko, Eun Hyea; Kim, Beom Jin; Kang, Sung Min; Kang, Kyungtae; Choi, Insung S

    2017-08-01

    Since the pioneering work by Whitesides, innumerable platforms that aim to spatio-selectively seed cells and control the degree of cell-cell interactions in vitro have been developed. These methods, however, have generally been technically and methodologically complex, or demanded stringent materials and conditions. In this work, we introduce zwitterionic lipids as patternable, cell-repellant masks for selectively seeding cells. The lipid masks are easily removed with a routine washing step under physiological conditions (37 °C, pH 7.4), and are used to create patterned cocultures, as well as to conduct cell migration studies. We demonstrate, via patterned cocultures of NIH 3T3 fibroblasts and HeLa cells, that HeLa cells proliferate far more aggressively than NIH 3T3 cells, regardless of initial population sizes. We also show that fibronectin-coated substrates induce cell movement akin to collective migration in NIH 3T3 fibroblasts, while the cells cultured on unmodified substrates migrate independently. Our lipid mask platform offers a rapid and highly biocompatible means of selectively seeding cells, and acts as a versatile tool for the study of cell-cell interactions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Pericyte actomyosin-mediated contraction at the cell-material interface can modulate the microvascular niche

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    Lee, Sunyoung; Zeiger, Adam; Maloney, John M; Van Vliet, Krystyn J [Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Kotecki, Maciej; Herman, Ira M, E-mail: krystyn@mit.ed, E-mail: ira.herman@tufts.ed [Department of Physiology, Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111 (United States)

    2010-05-19

    Pericytes physically surround the capillary endothelium, contacting and communicating with associated vascular endothelial cells via cell-cell and cell-matrix contacts. Pericyte-endothelial cell interactions thus have the potential to modulate growth and function of the microvasculature. Here we employ the experimental finding that pericytes can buckle a freestanding, underlying membrane via actin-mediated contraction. Pericytes were cultured on deformable silicone substrata, and pericyte-generated wrinkles were imaged via both optical and atomic force microscopy (AFM). The local stiffness of subcellular domains both near and far from these wrinkles was investigated by using AFM-enabled nanoindentation to quantify effective elastic moduli. Substratum buckling contraction was quantified by the normalized change in length of initially flat regions of the substrata (corresponding to wrinkle contour lengths), and a model was used to relate local strain energies to pericyte contractile forces. The nature of pericyte-generated wrinkling and contractile protein-generated force transduction was further explored by the addition of pharmacological cytoskeletal inhibitors that affected contractile forces and the effective elastic moduli of pericyte domains. Actin-mediated forces are sufficient for pericytes to exert an average buckling contraction of 38% on the elastomeric substrata employed in these in vitro studies. Actomyosin-mediated contractile forces also act in vivo on the compliant environment of the microvasculature, including the basement membrane and other cells. Pericyte-generated substratum deformation can thus serve as a direct mechanical stimulus to adjacent vascular endothelial cells, and potentially alter the effective mechanical stiffness of nonlinear elastic extracellular matrices, to modulate pericyte-endothelial cell interactions that directly influence both physiologic and pathologic angiogenesis.

  18. Epigenetic modulations in early endothelial cells and DNA hypermethylation in human skin after sulfur mustard exposure.

    Science.gov (United States)

    Steinritz, Dirk; Schmidt, Annette; Balszuweit, Frank; Thiermann, Horst; Simons, Thilo; Striepling, Enno; Bölck, Birgit; Bloch, Wilhelm

    2016-02-26

    Victims that were exposed to the chemical warfare agent sulfur mustard (SM) suffer from chronic dermal and ocular lesions, severe pulmonary problems and cancer development. It has been proposed that epigenetic perturbations might be involved in that process but this has not been investigated so far. In this study, we investigated epigenetic modulations in vitro using early endothelial cells (EEC) that were exposed to different SM concentrations (0.5, 1.0, 23.5 and 50μM). A comprehensive analysis of 78 genes related to epigenetic pathways (i.e., DNA-methylation and post-translational histone modifications) was performed. Moreover, we analyzed global DNA methylation in vitro in EEC after SM exposure as a maker for epigenetic modulations and in vivo using human skin samples that were obtained from a patient 1 year after an accidently exposure to pure SM. SM exposure resulted in a complex regulation pattern of epigenetic modulators which was accompanied by a global increase of DNA methylation in vitro. Examination of the SM exposed human skin samples also revealed a significant increase of global DNA methylation in vivo, underlining the biological relevance of our findings. Thus, we demonstrated for the first time that SM affects epigenetic pathways and causes epigenetic modulations both in vivo and in vitro. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. [Intensity-modulated radiation therapy in non-small cell lung cancers].

    Science.gov (United States)

    Ayadi, M; Zahra, N; Thariat, J; Bouilhol, G; Boissard, P; Van Houtte, P; Claude, L; Mornex, F

    2014-10-01

    Intensity modulated radiotherapy is increasingly used in non-small-cell lung cancers despite a low level of evidence. A literature review was conducted. Several critical physical and dosimetric uncertainties are however unsolved. Methods to circumvent these limitations are being developed. In several retrospective studies, survival rates were at least similar with intensity-modulated radiotherapy as those reported with three-dimensional irradiation. To date, intensity modulated radiotherapy might be authorized in complex anatomical situations such as tumours close to the spinal cord (such as Pancoast Tobias, paraspinal and paracardiac tumours) or with limited motion amplitudes. Dosimetric benefits should also account for 4D dose distribution issues. The reduction of intermediate and high doses in the organs at risk with intensity modulated radiotherapy is advantageous. However, the effect of low doses in large volumes (lung, bone, unspecified tissues along beam paths) and the effect of increasing integral dose are still poorly known. In conclusion, dose-volume correlations need to be better documented and prospective randomized trials should be encouraged. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  20. Epithelial to mesenchymal transition of a primary prostate cell line with switches of cell adhesion modules but without malignant transformation.

    Directory of Open Access Journals (Sweden)

    Xi-Song Ke

    Full Text Available BACKGROUND: Epithelial to mesenchymal transition (EMT has been connected with cancer progression in vivo and the generation of more aggressive cancer cell lines in vitro. EMT has been induced in prostate cancer cell lines, but has previously not been shown in primary prostate cells. The role of EMT in malignant transformation has not been clarified. METHODOLOGY/PRINCIPAL FINDINGS: In a transformation experiment when selecting for cells with loss of contact inhibition, the immortalized prostate primary epithelial cell line, EP156T, was observed to undergo EMT accompanied by loss of contact inhibition after about 12 weeks in continuous culture. The changed new cells were named EPT1. EMT of EPT1 was characterized by striking morphological changes and increased invasion and migration compared with the original EP156T cells. Gene expression profiling showed extensively decreased epithelial markers and increased mesenchymal markers in EPT1 cells, as well as pronounced switches of gene expression modules involved in cell adhesion and attachment. Transformation assays showed that EPT1 cells were sensitive to serum or growth factor withdrawal. Most importantly, EPT1 cells were not able to grow in an anchorage-independent way in soft agar, which is considered a critical feature of malignant transformation. CONCLUSIONS/SIGNIFICANCE: This work for the first time established an EMT model from primary prostate cells. The results show that EMT can be activated as a coordinated gene expression program in association with early steps of transformation. The model allows a clearer identification of the molecular mechanisms of EMT and its potential role in malignant transformation.

  1. Modulation of CXCL-8 expression in human melanoma cells regulates tumor growth, angiogenesis, invasion, and metastasis.

    Science.gov (United States)

    Wu, Sheng; Singh, Seema; Varney, Michelle L; Kindle, Scott; Singh, Rakesh K

    2012-12-01

    CXCL-8, a chemokine secreted by melanoma and stromal cells, serves as a growth and angiogenic factor for melanoma progression. This study evaluated how modulation of CXCL-8 levels in melanoma cell lines with different tumorigenic and metastatic potentials affected multiple tumor phenotypes. A375P cells (CXCL-8 low expressor) were stably transfected with a CXCL-8 mammalian expression vector to overexpress CXCL-8, whereas A375SM cells (CXCL-8 high expressor) were transfected with a CXCL-8 antisense expression vector to suppress CXCL-8 expression. Subsequent cell proliferation, migration, invasion, and soft-agar colony formation were analyzed, and in vivo tumor growth and metastasis were evaluated using mouse xenograft models. Our data demonstrate that overexpression of CXCL-8 significantly enhanced primary tumor growth and lung metastasis, accompanied by increased microvessel density in vivo, as compared with vector control-transfected cells. We also observed increased clonogenic ability, growth, and invasive potential of CXCL-8 overexpressing cells in vitro. Knockdown of CXCL-8 using an antisense vector resulted in increased cell death and reduced tumor growth relative to control. Taken together, these data confirm that CXCL-8 expression plays a critical role in regulating multiple cellular phenotypes associated with melanoma growth and metastasis.

  2. Effects of epigenetic modulation on reporter gene expression: implications for stem cell imaging.

    Science.gov (United States)

    Krishnan, Manickam; Park, Jinha M; Cao, Feng; Wang, Dongxu; Paulmurugan, Ramasay; Tseng, Jeffrey R; Gonzalgo, Mark L; Gambhir, Sanjiv S; Wu, Joseph C

    2006-01-01

    Tracking stem cell localization, survival, differentiation, and proliferation after transplantation in living subjects is essential for understanding stem cell biology and physiology. In this study, we investigated the long-term stability of reporter gene expression in an embryonic rat cardiomyoblast cell line and the role of epigenetic modulation on reversing reporter gene silencing. Cells were stably transfected with plasmids carrying cytomegalovirus promoter driving firefly luciferase reporter gene (CMV-Fluc) and passaged repeatedly for 3-8 months. Within the highest expressor clone, the firefly luciferase activity decreased progressively from passage 1 (843+/-28) to passage 20 (250+/-10) to passage 40 (44+/-3) to passage 60 (3+/-1 RLU/microg; P<0.05 vs. passage 1). Firefly luciferase activity was maximally rescued by treatment with 5-azacytidine (DNA methyltransferase inhibitor) compared with trichostatin A (histone deacetylase inhibitor) and retinoic acid (transcriptional activator; P<0.05). Increasing dosages of 5-azacytidine treatment led to higher levels of firefly luciferase mRNA (RT-PCR) and protein (Western blots) and inversely lower levels of methylation in the CMV promoter (DNA nucleotide sequence). These in vitro results were extended to in vivo bioluminescence imaging (BLI) of cell transplant in living animals. Cells treated with 5-azacytidine were monitored for 2 wk compared with 1 wk for untreated cells (P<0.05). These findings should have important implications for reporter gene-based imaging of stem cell transplantation.

  3. Mast Cell Subsets and Their Functional Modulation by the Acanthocheilonema viteae Product ES-62

    Directory of Open Access Journals (Sweden)

    Dimity H. Ball

    2013-01-01

    Full Text Available ES-62, an immunomodulator secreted by filarial nematodes, exhibits therapeutic potential in mouse models of allergic inflammation, at least in part by inducing the desensitisation of FcεRI-mediated mast cell responses. However, in addition to their pathogenic roles in allergic and autoimmune diseases, mast cells are important in fighting infection, wound healing, and resolving inflammation, reflecting that mast cells exhibit a phenotypic and functional plasticity. We have therefore characterised the differential functional responses to antigen (via FcεRI and LPS and their modulation by ES-62 of the mature peritoneal-derived mast cells (PDMC; serosal and those of the connective tissue-like mast cells (CTMC and the mucosal-like mast cells derived from bone marrow progenitors (BMMC as a first step to produce disease tissue-targeted therapeutics based on ES-62 action. All three mast cell populations were rendered hyporesponsive by ES-62 and whilst the mechanisms underlying such desensitisation have not been fully delineated, they reflect a downregulation of calcium and PKCα signalling. ES-62 also downregulated MyD88 and PKCδ in mucosal-type BMMC but not PDMC, the additional signals targeted in mucosal-type BMMC likely reflecting that these cells respond to antigen and LPS by degranulation and cytokine secretion whereas PDMC predominantly respond in a degranulation-based manner.

  4. Resistin modulates glucose uptake and glucose transporter-1 (GLUT-1) expression in trophoblast cells

    Science.gov (United States)

    Di Simone, Nicoletta; Di Nicuolo, Fiorella; Marzioni, Daniela; Castellucci, Mario; Sanguinetti, Maurizio; D’lppolito, Silvia; Caruso, Alessandro

    2009-01-01

    Abstract The adipocytokine resistin impairs glucose tolerance and insulin sensitivity. Here, we examine the effect of resistin on glucose uptake in human trophoblast cells and we demonstrate that transplacental glucose transport is mediated by glucose transporter (GLUT)-1. Furthermore, we evaluate the type of signal transduction induced by resistin in GLUT-1 regulation. BeWo choriocarcinoma cells and primary cytotrophoblast cells were cultured with increasing resistin concentrations for 24 hrs. The main outcome measures include glucose transport assay using [3H]-2-deoxy glucose, GLUT-1 protein expression by Western blot analysis and GLUT-1 mRNA detection by quantitative real-time RT-PCR. Quantitative determination of phospho(p)-ERK1/2 in cell lysates was performed by an Enzyme Immunometric Assay and Western blot analysis. Our data demonstrate a direct effect of resistin on normal cytotrophoblastic and on BeWo cells: resistin modulates glucose uptake, GLUT-1 messenger ribonucleic acid (mRNA) and protein expression in placental cells. We suggest that ERK1/2 phosphorylation is involved in the GLUT-1 regulation induced by resistin. In conclusion, resistin causes activation of both the ERK1 and 2 pathway in trophoblast cells. ERK1 and 2 activation stimulated GLUT-1 synthesis and resulted in increase of placental glucose uptake. High resistin levels (50–100 ng/ml) seem able to affect glucose-uptake, presumably by decreasing the cell surface glucose transporter. PMID:18410529

  5. Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

    Directory of Open Access Journals (Sweden)

    Itsuro Kazama

    2013-04-01

    Full Text Available Background/Aims: Salicylate and chlorpromazine exert differential effects on the chemokine release from mast cells. Since these drugs are amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membranes, they would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate and chlorpromazine on the membrane capacitance (Cm during exocytosis in rat peritoneal mast cells. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on plasma membrane deformation of the cells. Results: Salicylate dramatically accelerated the GTP-γ-S-induced increase in the Cm immediately after its application, whereas chlorpromazine significantly suppressed the increase. Treatment with salicylate increased the trapping of the dye on the cell surface, while treatment with chlorpromazine completely washed it out, indicating that both drugs induced membrane surface deformation in mast cells. Conclusion: This study demonstrated for the first time that membrane amphipaths, such as salicylate and chlorpromazine, may oppositely modulate the process of exocytosis in mast cells, as detected by the changes in the Cm. The plasma membrane deformation induced by the drugs was thought to be responsible for their differential effects.

  6. Resveratrol protects RPE cells from sodium iodate by modulating PPARα and PPARδ.

    Science.gov (United States)

    Qin, Suofu; Lu, Yimin; Rodrigues, Gerard A

    2014-01-01

    Selective killing of RPE cells in vivo by sodium iodate develops cardinal phenotypes of atrophic age-related macular degeneration. However, the molecular mechanisms are elusive. We tried to search for small cyto-protective molecules against sodium iodate and explore their mechanisms of action. Sodium iodate-mediated RPE cell death was associated with increased levels of reactive oxygen species (ROS) and IL-8. Resveratrol, a natural occurring polyphenol compound, was found to strongly protect RPE cells from sodium iodate with inhibition of production of ROS and IL-8. Resveratrol activated all isoforms of PPARs. Treatment with PPARα and PPARδ agonists inhibited sodium iodate-induced ROS production and protected RPE cells from sodium iodate. A PPARα antagonist significantly reduced resveratrol's protection of RPE cells from sodium iodate. Paradoxically, knocking down PPARδ also rendered RPE cells resistant to sodium iodate. Moreover, PPAR agonists reversed sodium iodate-induced production of IL-8. However, neutralizing extracellular IL-8 failed to protect RPE cells from sodium iodate. Taken together, these observations show that resveratrol protects RPE cells from sodium iodate injury through the activation of PPARα and alteration of PPARδ conformation. PPARα and δ modulators might ameliorate stress-induced RPE degeneration in vivo. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Salmonella Modulates B Cell Biology to Evade CD8+ T Cell-Mediated Immune Responses

    Science.gov (United States)

    Lopez-Medina, Marcela; Perez-Lopez, Araceli; Alpuche-Aranda, Celia; Ortiz-Navarrete, Vianney

    2014-01-01

    Although B cells and antibodies are the central effectors of humoral immunity, B cells can also produce and secrete cytokines and present antigen to helper T cells. The uptake of antigen is mainly mediated by endocytosis; thus, antigens are often presented by MHC-II molecules. However, it is unclear if B cells can present these same antigens via MHC-I molecules. Recently, Salmonella bacteria were found to infect B cells, allowing possible antigen cross-processing that could generate bacterial peptides for antigen presentation via MHC-I molecules. Here, we will discuss available knowledge regarding Salmonella antigen presentation by infected B cell MHC-I molecules and subsequent inhibitory effects on CD8+ T cells for bacterial evasion of cell-mediated immunity. PMID:25484884

  8. Hepatocyte growth factor modulates in vitro survival and proliferation of germ cells during postnatal testis development.

    Science.gov (United States)

    Catizone, A; Ricci, G; Del Bravo, J; Galdieri, M

    2006-04-01

    The hepatocyte growth factor (HGF) is a pleiotropic cytokine that influences mitogenesis, motility and differentiation of many different cell types by its tyrosine kinase receptor c-Met. We previously demonstrated that the c-Met/HGF system is present and functionally active during postnatal testis development. We found also that spermatozoa express c-Met and that HGF has a positive effect on the maintenance of sperm motility. In the present paper, we extend our study on the germ cells at different stages of differentiation during the postnatal development of the testis. We demonstrate that c-met is present in rat spermatogonia, pachytene spermatocytes and round spermatids and that HGF significantly increases spermatogonial proliferation in 8- to 10-day-old pre-pubertal rats. At this age HGF does not affect Sertoli cells and peritubular myoid cells proliferation. In addition, we studied the effect of the factor on germ cell apoptosis and we show that HGF prevents the germ cell apoptotic process. We also studied the effect of HGF on 18- to 20-day-old and 28- to 30-day-old rat testes. At these ages also the factor significantly increases germ cell duplication and decreases the number of apoptotic cells. However, the effect on programmed cell death is higher in the 8- to 10-day-old rats and declines in the older animals. In conclusion, we report that rat germ cells (spermatogonia, pachytene spermatocytes and round spermatids) express c-met and that HGF modulates germ cell proliferating activity and apoptosis in vitro. These data indicate that the c-Met/HGF system is involved in male germ cell homeostasis and, consequently, has a role in male fertility.

  9. Interleukin-21 induces proliferation and modulates receptor expression and effector function in canine natural killer cells.

    Science.gov (United States)

    Shin, Dong-Jun; Lee, Soo-Hyeon; Park, Ji-Yun; Kim, Ju-Sun; Lee, Je-Jung; Suh, Guk-Hyun; Lee, Youn-Kyung; Cho, Duck; Kim, Sang-Ki

    2015-05-15

    Interleukin (IL)-21 is an important modulator of natural killer (NK) cell function. However, little is known about IL-21 function in canine NK cells because the phenotype of these cells remains undefined. In this study, we selectively expanded non-B and non-T large granular NK lymphocytes (CD3(-)CD21(-)CD5(-)CD4(-)TCRαβ(-)TCRγδ(-)) ex vivo from the peripheral blood mononuclear cells (PBMCs) of healthy dogs using a combination of IL-2, IL-15, and IL-21 in the presence of 100 Gy-irradiated K562 cells. We investigated the effects of varying the duration and timing of IL-21 treatment on stimulation of proliferation, expression of NK-related receptors, anti-tumor activity and production of interferon (IFN)-γ. The expanded NK cells in each treatment group became enlarged and highly granular after 21 days in culture. NK cells proliferated rapidly in response to activation by IL-21 for 3 weeks, and IL-21 was able to induce changes in the mRNA expression of NK cell-related receptors and enhance the effector function of NK cells in perforin- and granzyme-B-dependent manners. The duration, frequency and timing of IL-21 stimulation during culture affected the rate of proliferation, patterns of receptor expression, cytokine production, and anti-tumor activity. The optimal conditions for maximizing the IL-21-induced proliferation and effector function of NK cells in the presence of IL-2 and IL-15 were seen in cells treated with IL-21 for the first 7 days of culture but without any further IL-21 stimulation other than an additional 2-day treatment prior to harvesting on day 21. The results of this study suggest that synergistic interactions of IL-21 with IL-2 and IL-15 play an important role in the proliferation, receptor expression, and effector function of canine NK cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Analysis of ribosome biogenesis factor-modules in yeast cells depleted from pre-ribosomes.

    Science.gov (United States)

    Merl, Juliane; Jakob, Steffen; Ridinger, Katrin; Hierlmeier, Thomas; Deutzmann, Rainer; Milkereit, Philipp; Tschochner, Herbert

    2010-05-01

    Formation of eukaryotic ribosomes requires more than 150 biogenesis factors which transiently interact with the nascent ribosomal subunits. Previously, many pre-ribosomal intermediates could be distinguished by their protein composition and rRNA precursor (pre-rRNA) content. We purified complexes of ribosome biogenesis factors from yeast cells in which de novo synthesis of rRNA precursors was down-regulated by genetic means. We compared the protein composition of these largely pre-rRNA free assemblies with the one of analogous pre-ribosomal preparations by semi-quantitative mass spectrometry. The experimental setup minimizes the possibility that the analysed pre-rRNA free protein modules were derived from (partially) disrupted pre-ribosomal particles and provides thereby strong evidence for their pre-ribosome independent existence. In support of the validity of this approach (i) the predicted composition of the analysed protein modules was in agreement with previously described rRNA-free complexes and (ii) in most of the cases we could identify new candidate members of reported protein modules. An unexpected outcome of these analyses was that free large ribosomal subunits are associated with a specific set of ribosome biogenesis factors in cells where neo-production of nascent ribosomes was blocked. The data presented strengthen the idea that assembly of eukaryotic pre-ribosomal particles can result from transient association of distinct building blocks.

  11. Development of the PedsQL™ Sickle Cell Disease Module items: qualitative methods.

    Science.gov (United States)

    Panepinto, Julie A; Torres, Sylvia; Varni, James W

    2012-03-01

    The objective of this qualitative study was to develop the items and support the content validity of the PedsQL™ Sickle Cell Disease Module for pediatric patients with sickle cell disease (SCD). The iterative process included multiphase qualitative methodology. A literature review on SCD was conducted to generate domains of interest for the individual in-depth interviews. Ten healthcare experts with clinical experience in SCD participated in the development of the conceptual framework. A total of 13 pediatric patients with SCD ages 5-18 and 18 parents of patients ages 2-18 participated in the individual in-depth interviews. A total of 33 pediatric patients with SCD ages 5-18 and 39 parents of patients ages 2-18 participated in individually conducted cognitive interviews that included both think aloud and cognitive debriefing techniques to assess the interpretability and readability of the item stems. Six domains were derived from the qualitative methods involving patient/parent interviews and expert opinion, with content saturation achieved, resulting in 48 items. The six domains consisted of items measuring Pain Intensity/Location (9 items), Pain Interference (11 items), Worry (7 items), Emotions (3 items), Disease Symptoms/Treatment, (12 items), and Communication (6 items). Qualitative methods involving pediatric patients and parents in the item development process support the content validity for the PedsQL™ SCD Module. The PedsQL™ SCD Module is now undergoing national multisite field testing for the psychometric validation phase of instrument development.

  12. [Salidroside inhibits hypoxia-induced phenotypic modulation of corpus cavernosum smooth muscle cells in vitro].

    Science.gov (United States)

    Chen, Gang; Huang, Xiao-Jun; Lü, Bo-Dong; Chen, Shi-Tao; Zhang, Shi-Geng; Yang, Ke-Bing

    2013-08-01

    To explore the effects of salidroside on the phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMC) in hypoxic SD rats. CCSMCs were cultured in vitro and identified by immunohistochemistry. The cells were divided into six groups: normal control (21% O2), hypoxia (1% O2), hypoxia + salidroside 1 mg/L, hypoxia + salidroside 3 mg/L, hypoxia + salidroside 5 mg/L and hypoxia + PGE1 0.4 microg/L, and then cultured for 48 hours. The relative expressions of alpha-actin and osteopontin (OPN) in each group were determined by RT-PCR. The in vitro cultured CCSMCs grew well, with anti-alpha-smooth muscle actin monoclonal antibodies immunohistochemically positive. The relative expression of alpha-actin was markedly decreased while that of OPN remarkably increased in the hypoxia group as compared with the normal control group (P salidroside 5 mg/L group showed a significantly higher expression of alpha-actin and lower expression of OPN than the hypoxia group (P 0.05). Hypoxia can reduce the relative expression level of alpha-actin and increase that of OPN in the CCSMCs of SD rats, namely, induce their phenotypic modulation from the contraction to the non-contraction type. Salidroside can restrain hypoxia-induced phenotypic modulation of CCSMCs, and its inhibitory effect at 5 mg/L is similar to that of PGE1.

  13. Human Intestinal Cells Modulate Conjugational Transfer of Multidrug Resistance Plasmids between Clinical Escherichia coli Isolates

    Science.gov (United States)

    Machado, Ana Manuel Dantas; Sommer, Morten O. A.

    2014-01-01

    Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co-cultured with human intestinal cells. We show that filtered media from co-cultures contain a factor that reduces conjugation efficiency. Protease treatment of the filtered media eliminates this inhibition of conjugation. This data suggests that a peptide or protein based factor is secreted on the apical side of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut. PMID:24955767

  14. Human intestinal cells modulate conjugational transfer of multidrug resistance plasmids between clinical Escherichia coli isolates.

    Directory of Open Access Journals (Sweden)

    Ana Manuel Dantas Machado

    Full Text Available Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co-cultured with human intestinal cells. We show that filtered media from co-cultures contain a factor that reduces conjugation efficiency. Protease treatment of the filtered media eliminates this inhibition of conjugation. This data suggests that a peptide or protein based factor is secreted on the apical side of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut.

  15. Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions.

    Directory of Open Access Journals (Sweden)

    Yuval Ramot

    Full Text Available BACKGROUND: Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle (HF is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown. METHODS AND FINDINGS: We have studied the effects of the prototypic polyamine, spermidine (0.1-1 µM, on human scalp HFs and human HF epithelial stem cells in serum-free organ culture. Under these conditions, spermidine promoted hair shaft elongation and prolonged hair growth (anagen. Spermidine also upregulated expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity in situ and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells in vitro. Inhibiting the rate-limiting enzyme of polyamine synthesis, ornithine decarboyxlase (ODC, downregulated intrafollicular K15 expression. In primary human epidermal keratinocytes, spermidine slightly promoted entry into the S/G2-M phases of the cell cycle. By microarray analysis of human HF mRNA extracts, spermidine upregulated several key target genes implicated e.g. in the control of cell adherence and migration (POP3, or endoplasmic reticulum and mitochondrial functions (SYVN1, NACA and SLC25A3. Excess spermidine may restrict further intrafollicular polyamine synthesis by inhibiting ODC gene and protein expression in the HF's companion layer in situ. CONCLUSIONS: These physiologically and clinically relevant data provide the first direct evidence that spermidine is a potent stimulator of human hair growth and a previously unknown modulator of human epithelial stem cell biology.

  16. Modulation of gastrin processing by vesicular monoamine transporter type 1 (VMAT1) in rat gastrin cells

    Science.gov (United States)

    Hussain, I; Bate, G W; Henry, J; Djali, P; Dimaline, R; Dockray, G J; Varro, A

    1999-01-01

    Gastrointestinal endocrine cells produce biogenic amines which are transported into secretory vesicles by one of two proton-amine exchangers, vesicular monoamine transporters type 1 and 2 (VMAT1 and 2). We report here the presence of VMAT1 in rat gastrin (G) cells and the relevance of VMAT1 function for the modulation of progastrin processing by biogenic and dietary amines. In immunocytochemical studies VMAT1, but not VMAT2, was localized to subpopulations of G cells and enterochromaffin (EC) cells; neither was found in antral D cells. The expression of VMAT1 in antral mucosa was confirmed by Northern blot analysis, which revealed an mRNA band of approximately 3.2 kb, and by Western blot analysis, which revealed a major protein of 55 kDa. In pulse-chase labelling experiments, the conversion of the amidated gastrin G34 to G17 was inhibited by biogenic amine precursors (L-DOPA and 5-hydroxytryptophan). This inhibition was stereospecific and sensitive to reserpine (50 nM), which blocks VMAT1 and VMAT2, but resistant to tetrabenazine, which is a selective inhibitor of VMAT2. Dietary amines such as tyramine and tryptamine also inhibited G34 cleavage. This effect was associated with a loss of the electron-dense core of G cell secretory vesicles. It was not stereospecific or reserpine sensitive, but was correlated with hydrophobicity. Thus rat antral G cells can express VMAT1; transport of biogenic amines into secretory vesicles by VMAT1 is associated with inhibition of G34 cleavage, perhaps by raising intravesicular pH. Dietary amines also modulate cleavage of progastrin-derived peptides, but do so by a VMAT1-independent mechanism; they may act as weak bases that passively permeate secretory vesicle membranes and raise intravesicular pH. PMID:10332097

  17. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Directory of Open Access Journals (Sweden)

    Hui Xu

    Full Text Available MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  18. Development of measurement device for evaluation of solar cell module output. 2; Taiyo denchi module shutsuryoku hyokayo sokuteiki no kaihatsu. 2

    Energy Technology Data Exchange (ETDEWEB)

    Minoda, M.; Itsumi, J. [Kumamoto Institute of Technology, Kumamoto (Japan)

    1996-10-27

    Enhancement in design efficiency may be attained as well as utilization in maintenance if on-the-spot data is made available, for the purpose of flexibly dealing with changes in design or matching with a house structure, in calculating the power generation output of a solar cell (PV) module. Under the circumstances, a small-sized compound measuring device was produced as a prototype which, using an I-V curve tracer, measured output and condition of a roof at the time of installation, compared with the optimum operation and predicted the power generation. The device was structured with the main body consisting of a computing part, measurement controller and power supply and with various sensor modules. The electron load control method was employed in order to measure I-V characteristics of the PV module, since it was desirable to use a variable load and to cover the range from the release voltage of a solar cell to the short-circuit state through the maximum output point. The reference module method was used for the system evaluation. The device was presumably applicable to a PV system design by incorporating a sensor module for measuring design environment data, which was essential at the time of a system design, in addition to those for measuring output. 9 refs., 4 figs., 3 tabs.

  19. Flow perfusion rate modulates cell deposition onto scaffold substrate during cell seeding.

    Science.gov (United States)

    Campos Marín, A; Brunelli, M; Lacroix, D

    2017-11-29

    The combination of perfusion bioreactors with porous scaffolds is beneficial for the transport of cells during cell seeding. Nonetheless, the fact that cells penetrate into the scaffold pores does not necessarily imply the interception of cells with scaffold substrate and cell attachment. An in vitro perfusion system was built to relate the selected flow rate with seeding efficiency. However, the in vitro model does not elucidate how the flow rate affects the transport and deposition of cells onto the scaffold. Thus, a computational model was developed mimicking in vitro conditions to identify the mechanisms that bring cells to the scaffold from suspension flow. Static and dynamic cell seeding configurations were investigated. In static seeding, cells sediment due to gravity until they encounter the first obstacle. In dynamic seeding, 12, 120 and 600 [Formula: see text] flow rates were explored under the presence or the absence of gravity. Gravity and secondary flow were found to be key factors for cell deposition. In vitro and in silico seeding efficiencies are in the same order of magnitude and follow the same trend with the effect of fluid flow; static seeding results in higher efficiency than dynamic perfusion although irregular spatial distribution of cells was found. In dynamic seeding, 120 [Formula: see text] provided the best seeding results. Nevertheless, the perfusion approach reports low efficiencies for the scaffold used in this study which leads to cell waste and low density of cells inside the scaffold. This study suggests gravity and secondary flow as the driving mechanisms for cell-scaffold deposition. In addition, the present in silico model can help to optimize hydrodynamic-based seeding strategies prior to experiments and enhance cell seeding efficiency.

  20. Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Richard Francis

    Full Text Available Knockout mice deficient in the gap junction gene connexin43 exhibit developmental anomalies associated with abnormal neural crest, primordial germ cell, and proepicardial cell migration. These migration defects are due to a loss of directional cell movement, and are associated with abnormal actin stress fiber organization and a loss of polarized cell morphology. To elucidate the mechanism by which Cx43 regulates cell polarity, we used a wound closure assays with mouse embryonic fibroblasts (MEFs to examine polarized cell morphology and directional cell movement. Studies using embryonic fibroblasts from Cx43 knockout (Cx43KO mice showed Cx43 deficiency caused cell polarity defects as characterized by a failure of the Golgi apparatus and the microtubule organizing center to reorient with the direction of wound closure. Actin stress fibers at the wound edge also failed to appropriately align, and stabilized microtubule (Glu-tubulin levels were markedly reduced. Forced expression of Cx43 with deletion of its tubulin-binding domain (Cx43dT in both wildtype MEFs and neural crest cell explants recapitulated the cell migration defects seen in Cx43KO cells. However, forced expression of Cx43 with point mutation causing gap junction channel closure had no effect on cell motility. TIRF imaging revealed increased microtubule instability in Cx43KO cells, and microtubule targeting of membrane localized Cx43 was reduced with expression of Cx43dT construct in wildtype cells. Together, these findings suggest the essential role of Cx43 gap junctions in development is mediated by regulation of the tubulin cytoskeleton and cell polarity by Cx43 via a nonchannel function.

  1. Electroluminescence of thin-film CdTe solar cells and modules

    Science.gov (United States)

    Raguse, John Michael

    Thin-film photovoltaics has the potential to be a major source of world electricity. Mitigation of non-uniformities in thin-film solar cells and modules may help improve photovoltaic conversion efficiencies. In this manuscript, a measurement technique is discussed in detail which has the capability of detecting such non-uniformities in a form useful for analysis. Thin-film solar cells emit radiation while operating at forward electrical bias, analogous to an LED, a phenomena known as electroluminescence (EL). This process relatively is inefficient for polycrystalline CdTe devices, on the order of 10-4%, as most of the energy is converted into heat, but still strong enough for many valuable measurements. A EL sy