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Sample records for basalis stimulation depends

  1. Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease - a two-case study.

    Science.gov (United States)

    Dürschmid, Stefan; Reichert, Christoph; Kuhn, Jens; Freund, Hans-Joachim; Hinrichs, Hermann; Heinze, Hans-Jochen

    2017-10-20

    Alzheimer's disease (AD) is associated with deterioration of memory and cognitive function and a degeneration of neurons of the nucleus basalis of Meynert (NBM). The NBM is the major input source of acetylcholine (ACh) to the cortex. The decreasing cholinergic innervation of the cortex due to degeneration of the NBM might be the cause of loss of memory function. NBM-Deep brain stimulation (NBM-DBS) is considered to serve as a potential therapeutic option for patients with AD by supporting residual cholinergic transmission to stabilize oscillatory activity in memory-relevant circuits. However, whether DBS could improve sensory memory functions in patients with AD is not clear. Here, in a passive auditory oddball paradigm, patients with AD (N = 2) listened to repetitive background tones (standard tones) randomly interrupted by frequency deviants in two blocks with NBM-DBS OFF and then NBM-DBS ON, while age-matched healthy controls (N = 6) repeated the experiment twice. The mismatch negativity in NBM-DBS OFF significantly differed from controls in both blocks, but not under NBM-DBS, which was likely due to a pronounced P50 increase overlapping with the N1 in NBM-DBS OFF. This early complex of EEG components recovered under stimulation to a normal level as defined by responses in controls. In this temporal interval, we found in patients with NBM-DBS ON (but not with NBM-DBS OFF) and in controls a strong repetition suppression effect to standard tones - with more attenuated responses to frequently repeated standard tones. This highlights the role of NBM-DBS for sensory gating of familiar auditory information into sensory memory. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Maternal Adaptive Immune Cells in Decidua Parietalis Display a More Activated and Coinhibitory Phenotype Compared to Decidua Basalis

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    Martin Solders

    2017-01-01

    Full Text Available The maternal part of the placenta, the decidua, consists of maternal immune cells, decidual stromal cells, and extravillous fetal trophoblasts. In a successful pregnancy, these cell compartments interact to provide an intricate balance between fetal tolerance and antimicrobial defense. These processes are still poorly characterized in the two anatomically different decidual tissues, basalis and parietalis. We examined immune cells from decidua basalis and parietalis from term placentas (n=15 with flow cytometry. By using multivariate discriminant analysis, we found a clear separation between the two decidual compartments based on the 81 investigated parameters. Decidua parietalis lymphocytes displayed a more activated phenotype with a higher expression of coinhibitory markers than those isolated from basalis and contained higher frequencies of T regulatory cells. Decidua basalis contained higher proportions of monocytes, B cells, and mucosal-associated invariant T (MAIT cells. The basalis B cells were more immature, and parietalis MAIT cells showed a more activated phenotype. Conventional T cells, NK cells, and MAIT cells from both compartments potently responded with the production of interferon-γ and/or cytotoxic molecules in response to stimulation. To conclude, leukocytes in decidua basalis and parietalis displayed remarkable phenotypic disparities, indicating that the corresponding stromal microenvironments provide different immunoregulatory signals.

  3. Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake

    Energy Technology Data Exchange (ETDEWEB)

    Metcalf, R.H.; Boegman, R.J.; Quirion, R.; Riopelle, R.J.; Ludwin, S.K.

    1987-08-01

    A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific (/sup 3/H)hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.

  4. The effect of age on sperm stock and egg laying in the parasitoid wasp, Dinarmus basalis

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    D. Damiens

    2003-07-01

    Full Text Available Sperm quantity and quality during storage may be constraints acting on female fecundity and hence fitness. In Hymenoptera, the importance of sperm quality has rarely been considered, despite its central role in reproductive strategies and especially in sex ratio control. In these insects, fertilized eggs develop into females and unfertilized eggs into males. Experiments were conducted on the female wasp, Dinarmus basalis, in the laboratory with and without egg-laying resources (hosts. The first point was to test if sperm age influenced sperm storage by measuring sperm count and viability using a sperm viability test (SYBR-14 : propidium iodide. The second point was the influence of prolonged storage in the female genital tract on the quantity, sex ratio and fitness of offspring produced. Results show that sperm viability in the spermatheca does not change significantly with maternal age, and that the sperm stock is not affected when females are deprived of hosts. Egg-laying is gradually restored after 21 days of host deprivation but remains at a low level after 115 days. The fitness of mated D. basalis females is therefore not constrained by sperm quantity or quality and seems to depend on host availability and female age.

  5. dependent/calmodulin- stimulated protein kinase from moss

    Indian Academy of Sciences (India)

    Unknown

    stimulated protein kinase; CDPK, calmodulin domain-like protein kinase; KM14, 14 amino acid synthetic peptide; .... used were obtained from Sigma Chemical Company, USA, ..... Plant chimeric Ca2+/Calmodulin-dependent protein kinase.

  6. Commonly used stimulants: Sleep problems, dependence and psychological distress.

    Science.gov (United States)

    Ogeil, Rowan P; Phillips, James G

    2015-08-01

    Caffeine and nicotine are commonly used stimulants that enhance alertness and mood. Discontinuation of both stimulants is associated with withdrawal symptoms including sleep and mood disturbances, which may differ in males and females. The present study examines changes in sleep quality, daytime sleepiness and psychological distress associated with use and dependence on caffeine and nicotine. An online survey comprising validated tools to assess sleep quality, excessive daytime sleepiness and psychological distress was completed by 166 participants (74 males, 96 females) with a mean age of 28 years. Participants completed the study in their own time, and were not offered any inducements to participate. Sleep quality was poorer in those dependent upon caffeine or nicotine, and there were also significant interaction effects with gender whereby females reported poorer sleep despite males reporting higher use of both stimulants. Caffeine dependence was associated with poorer sleep quality, increased daytime dysfunction, and increased levels of night time disturbance, while nicotine dependence was associated with poorer sleep quality and increased use of sleep medication and sleep disturbances. There were strong links between poor sleep and diminished affect, with psychological distress found to co-occur in the context of disturbed sleep. Stimulants are widely used to promote vigilance and mood; however, dependence on commonly used drugs including caffeine and nicotine is associated with decrements in sleep quality and increased psychological distress, which may be compounded in female dependent users. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. ApoE epsilon4 genotype is accompanied by lower metabolic activity in nucleus basalis of Meynert neurons in Alzheimer patients and controls as indicated by the size of the Golgi apparatus

    NARCIS (Netherlands)

    Dubelaar, E. J. G.; Verwer, R. W. H.; Hofman, M. A.; van Heerikhuize, J. J.; Ravid, R.; Swaab, D. F.

    2004-01-01

    We previously found apolipoprotein (apoE) epsilon4-dependent lower metabolic activity in nucleus basalis of Meynert (NBM) neurons in Alzheimer disease (AD). In the present study we examined the metabolic activity in the NBM of 39 mentally intact control subjects with different APOE genotype. The

  8. Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

    NARCIS (Netherlands)

    Crunelle, C.L.; Veltman, D.J.; Booij, J.; van Emmerik-van Oortmerssen, K.; van den Brink, W.

    2012-01-01

    Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence,

  9. Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

    Science.gov (United States)

    Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

    2017-09-15

    Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

  10. Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

    NARCIS (Netherlands)

    Crunelle, Cleo L.; Veltman, Dick J.; Booij, Jan; Emmerik-van Oortmerssen, Katelijne; den Brink, Wim

    2012-01-01

    Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys) function in stimulant dependence, including cocaine, (meth-) amphetamine, ecstasy and nicotine

  11. Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

    NARCIS (Netherlands)

    Harkany, Tibor; Varga, Csaba; Grosche, Jens; Mulder, Jan; Luiten, Paul G.M.; Hortobágyi, Tibor; Penke, Botond; Härtig, Wolfgang

    2002-01-01

    Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP

  12. Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

    2018-05-01

    Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

  13. Lethal and sublethal effects of four essential oils on the egg parasitoids Trissolcus basalis.

    Science.gov (United States)

    Werdin González, Jorge Omar; Laumann, Raúl Alberto; da Silveira, Samantha; Moraes, Maria Carolina Blassioli; Borges, Miguel; Ferrero, Adriana Alicia

    2013-07-01

    The essential oils from leaves of Schinus molle var. areira, Aloysia citriodora, Origanum vulgare and Thymus vulgaris have showed potential as phytoinsecticides against the green stink bug, Nezara viridula. In this work were evaluated their toxicological and behavioral effects on the parasitoid Trissolcus basalis, a biological control agent of this pest insect. Essential oils were obtained via hydrodestillation from fresh leaves. Insecticide activity in T. basalis females was evaluated in direct contact and fumigation bioassays. Behavioral effects were evaluated in olfactometer bioassays. To evaluate the residual toxicity, females of the parasitoids were exposed to oil residues; in these insects, the sublethal effects were evaluated (potential parasitism and survivorship of immature stages). The essential oils from O. vulgare and T. vulgaris proved to be highly selective when used as fumigant and did not change parasitoid behavior. After one week, the residues of these oils were harmless and did not show sublethal effects against T. basalis. According with these results, essential oils have potential applications for the integrated management of N. viridula. Published by Elsevier Ltd.

  14. Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation

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    Alireza eGharabaghi

    2014-03-01

    Full Text Available Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

  15. Age-dependent effects of brain stimulation on network centrality.

    Science.gov (United States)

    Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus; Prehn, Kristin; Thielscher, Axel; Ittermann, Bernd; Flöel, Agnes

    2018-04-18

    Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation were explained from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults. Copyright © 2018. Published by Elsevier Inc.

  16. Age-dependent effects of brain stimulation on network centrality

    DEFF Research Database (Denmark)

    Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus

    2018-01-01

    Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task......-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age associated differential neural tDCS effects. Three “online” tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30...... characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing...

  17. Probing phase- and frequency-dependent characteristics of cortical interneurons using combined transcranial alternating current stimulation and transcranial magnetic stimulation.

    Science.gov (United States)

    Hussain, Sara J; Thirugnanasambandam, Nivethida

    2017-06-01

    Paired-pulse transcranial magnetic stimulation (TMS) and peripheral stimulation combined with TMS can be used to study cortical interneuronal circuitry. By combining these procedures with concurrent transcranial alternating current stimulation (tACS), Guerra and colleagues recently showed that different cortical interneuronal populations are differentially modulated by the phase and frequency of tACS-imposed oscillations (Guerra A, Pogosyan A, Nowak M, Tan H, Ferreri F, Di Lazzaro V, Brown P. Cerebral Cortex 26: 3977-2990, 2016). This work suggests that different cortical interneuronal populations can be characterized by their phase and frequency dependency. Here we discuss how combining TMS and tACS can reveal the frequency at which cortical interneuronal populations oscillate, the neuronal origins of behaviorally relevant cortical oscillations, and how entraining cortical oscillations could potentially treat brain disorders. Copyright © 2017 the American Physiological Society.

  18. Size dependent emission stimulation in ZnO nanosheets

    International Nuclear Information System (INIS)

    Torchynska, T.V.; El Filali, B.

    2014-01-01

    Photoluminescence (PL), X ray diffraction (XRD) and Raman scattering have been studied in crystalline ZnO nanosheets (NSs) of different sizes, estimated by scanning electronic microscopy (SEM). ZnO NSs with the size from the range of 60–600 nm were created by the electrochemical (anodization) method and followed thermal annealing at 400 °C for 2 h in ambient air. XRD study confirms the wurtzite structure of ZnO NSs and has revealed that the lattice parameters increase monotonically with decreasing NS sizes. Simultaneously the intensity of a set of Raman peaks increases and Raman peaks shift into the low energy range. The surface phonon has been detected in smallest size ZnO NSs. Two types of PL bands deal with a set of phonon replicas of free excitons and the defect related emission have been detected in ZnO NSs. The intensity enhancement of exciton- and defect-related PL bands with decreasing ZnO NS sizes has been detected. The intensity stimulation of exciton-related PL bands is attributed to the realization of the week confinement and the exciton-light coupling with the formation of polariton in small size ZnO NSs of 67–170 nm. The intensity rising of defect-related PL bands is attributed to the concentration enlargement of surface defects when the surface to volume ration increases at decreasing ZnO NS sizes. Numerical simulations of radiative lifetimes and exciton radiative recombination rates in ZnO NSs for different emission wavelengths have been done using the exciton-light coupling model. Then the experimental and numerically simulated PL results have been compared and discussed. - Highlights: • Optical and structural investigations of the ZnO nanosheets with the sizes 60–600 nm. • The enlargement of interplanar distances in the wurtzite ZnO crystal lattice is detected. • The change of optic phonon energy and surface phonon appearing are reveled. • ZnO emission stimulation at the week confinement and electron-light coupling with the

  19. Temperature dependences in electron-stimulated desorption of neutral europium

    CERN Document Server

    Ageev, V N; Madey, T E

    2003-01-01

    The electron-stimulated desorption (ESD) yield for neutral europium (Eu) atoms from Eu layers adsorbed on oxygen-covered tungsten surfaces has been measured as a function of electron energy, europium coverage and degree of oxidation of tungsten, with an emphasis on effects of substrate temperature. The measurements have been carried out using a time-of-flight method and surface ionization detector. We expand on an earlier report, and compare ESD of multivalent Eu with ESD of monovalent alkali atoms, studied previously. The Eu atom ESD is a complicated function of Eu coverage, electron energy and substrate temperature. In the coverage range 0.05-0.35 monolayer (ML), overlapping resonant-like Eu atom yield peaks are observed at electron energies E sub e of 36 and 41 eV that might be associated with Eu or W shallow core level excitations. Additional resonant-like peaks are seen at E sub e of 54 and 84 eV that are associated with W 5p and 5s level excitations. The Eu atom yield peaks at 36 and 41 eV are seen only...

  20. Occurrence of Dinarmus basalis in Callosobruchus analis in stored soybean in São Paulo, Brazil Ocorrência de Dinarmus basalis (Rondani em Callosobruchus analis (F. em soja armazenada em São Paulo, Brasil

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    Valmir Antonio Costa

    2007-06-01

    Full Text Available Callosobruchus analis (F. is considered an important pest in several countries in Africa, Asia and Oceania. It has been observed infesting seeds belonging to 15 Leguminosae genera, including peanut, bean, chickpea, pea, cowpea, and soybean. One of its main natural enemies is the parasitoid Dinarmus basalis (Rondani (Hymenoptera: Pteromalidae, whose control efficiency has already been demonstrated in several studies. This paper records the occurrence of C. analis and its parasitoid, D. basalis, in stored soybean of the state of São Paulo, Brazil.Callosobruchus analis (F. é uma praga de expressão econômica em diversos países da África, Ásia e Oceania. Já foi observado infestando sementes de espécies de leguminosas pertencentes a 15 gêneros, incluindo-se culturas como amendoim, grão-de-bico, feijão, ervilha, caupi e soja. Um de seus inimigos naturais mais importantes é o parasitóide Dinarmus basalis (Rondani (Hymenoptera: Pteromalidae, cuja eficiência de controle já foi demonstrada em vários estudos. Neste trabalho registra-se a ocorrência de C. analis e de seu parasitóide, D. basalis, em grãos armazenados de soja no estado de São Paulo.

  1. Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

    Science.gov (United States)

    Ersche, Karen D; Bullmore, Edward T; Craig, Kevin J; Shabbir, Shaila S; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J; Merlo-Pich, Emilio V; Robbins, Trevor W

    2010-06-01

    There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges. Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18). Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation

  2. Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity.

    Science.gov (United States)

    Moran, Fidelma; Leonard, Tracey; Hawthorne, Stephanie; Hughes, Ciara M; McCrum-Gardner, Evie; Johnson, Mark I; Rakel, Barbara A; Sluka, Kathleen A; Walsh, Deirdre M

    2011-08-01

    Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18-64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups (P TENS and No Current Placebo TENS groups at the hand (P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r(2) = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Comparison of Experienced Violence in Women with Opiate-Dependent and Stimulant-Dependent Husbands

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    Neda Ahmadpour

    2013-01-01

    Full Text Available Objective: Opium and stimulants are two kinds of illegal substances which are different from each other in chemical structure, psychological and biological effects (material, and their potential adverse effects on consumers. The present study compares the effect of abuse of each of the two (opium and stimulants on violent behavior against wives. Materials & Methods: The present study was a non-experimental and comparative study. The study sample included 100 spouses of men addicted to opium and stimulants (50 opium and 50 stimulant addicts who attended governmental or non-governmental centers or camps in Tehran city (from October 2011 to January 2012, in order to receive professional assistances. (Both groups of subjects were selected by convenient sampling method to ensure the compatibility with input and output data. The “revised conflict tactics scale” was used to assess the rates of violence (psychological, sexual coercion, negotiation, injury and physical assault exerted by men. Results were analyzed using multi-variety analysis of variance and covariance. Results: Results showed that after controlling the age as a covariate, consumers of stimulants (especially methamphetamine were more violent toward their wives than were consumers of opium (P&le0.001. There were also significant differences between the two groups in the psychological, sexual coercion, injury and physical assault subscales, but not in the negotiation subscale (P&le0.05. Conclusion: It seems that the psychopharmacological effect of stimulants leads to more violent behaviors in its consumers (especially by methamphetamine than in consumers of opium.

  4. Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons: a PET study

    International Nuclear Information System (INIS)

    Kiyosawa, M.; Pappata, S.; Duverger, D.

    1987-01-01

    The cerebral metabolic rate for glucose was measured serially with positron emission tomography and [ 18 F]fluorodeoxyglucose in five baboons with stereotactic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days after lesion, a significant metabolic depression was present in the ipsilateral cerebral cortex, most marked in the frontotemporal region, and which recovered progressively within 6-13 weeks. These data demonstrate that adaptive mechanisms efficiently compensate for the cortical metabolic effects of NbM-lesion-induced cholinergic deafferentation. Moreover, unilateral NbM lesions also induced a transient reduction in contralateral cortical metabolic rate, the mechanisms of which are discussed. Explanation of these effects of cholinergic deafferentation in the primate could further our understanding of the metabolic deficits observed in dementia of the Alzheimer's type

  5. The Polarity-Dependent Effects of the Bilateral Brain Stimulation on Working Memory

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    Fatemeh Keshvari

    2013-08-01

    Full Text Available Introduction: Working memory plays a critical role in cognitive processes which are central to our daily life. Neuroimaging studies have shown that one of the most important areas corresponding to the working memory is the dorsolateral prefrontal cortex (DLFPC. This study was aimed to assess whether bilateral modulation of the DLPFC using a noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS, modi.es the working memory function in healthy adults.Methods: In a randomized sham-controlled cross-over study, 60 subjects (30 Males received sham and active tDCS in two subgroups (anode left/cathode right and anode right/cathode left of the DLPFC. Subjects were presented working memory n-back task while the reaction time and accuracy were recorded.Results: A repeated measures, mixed design ANOVA indicated a signi.cant difference between the type of stimulation (sham vs. active in anodal stimulation of the left DLPFC with cathodal stimulation of the right DLPFC [F(1,55= 5.29,  P=0.019], but not the inverse polarity worsened accuracy in the 2-back working memory task. There were also no statistically signi.cant changes in speed of working memory [F(1,55= 0.458 ,P=0.502] related to type or order of stimulation..Discussion: The results would imply to a polarity dependence of bilateral tDCS of working memory. Left anodal/ right cathodal stimulation of DLPFC could impair working memory, while the reverser stimulation had no effect. Meaning that bilateral stimulation of DLFC would not be a useful procedure to improve working memory. Further studies are required to understand subtle effects of different tDCS stimulation/inhibition electrode positioning on the working memory.

  6. Modulation of Corticospinal Excitability Depends on the Pattern of Mechanical Tactile Stimulation

    Directory of Open Access Journals (Sweden)

    Sho Kojima

    2018-01-01

    Full Text Available We investigated the effects of different patterns of mechanical tactile stimulation (MS on corticospinal excitability by measuring the motor-evoked potential (MEP. This was a single-blind study that included nineteen healthy subjects. MS was applied for 20 min to the right index finger. MS intervention was defined as simple, lateral, rubbing, vertical, or random. Simple intervention stimulated the entire finger pad at the same time. Lateral intervention stimulated with moving between left and right on the finger pad. Rubbing intervention stimulated with moving the stimulus probe, fixed by protrusion pins. Vertical intervention stimulated with moving in the forward and backward directions on the finger pad. Random intervention stimulated to finger pad with either row protrudes. MEPs were measured in the first dorsal interosseous muscle to transcranial magnetic stimulation of the left motor cortex before, immediately after, and 5–20 min after intervention. Following simple intervention, MEP amplitudes were significantly smaller than preintervention, indicating depression of corticospinal excitability. Following lateral, rubbing, and vertical intervention, MEP amplitudes were significantly larger than preintervention, indicating facilitation of corticospinal excitability. The modulation of corticospinal excitability depends on MS patterns. These results contribute to knowledge regarding the use of MS as a neurorehabilitation tool to neurological disorder.

  7. Modulation of Corticospinal Excitability Depends on the Pattern of Mechanical Tactile Stimulation.

    Science.gov (United States)

    Kojima, Sho; Onishi, Hideaki; Miyaguchi, Shota; Kotan, Shinichi; Sasaki, Ryoki; Nakagawa, Masaki; Kirimoto, Hikari; Tamaki, Hiroyuki

    2018-01-01

    We investigated the effects of different patterns of mechanical tactile stimulation (MS) on corticospinal excitability by measuring the motor-evoked potential (MEP). This was a single-blind study that included nineteen healthy subjects. MS was applied for 20 min to the right index finger. MS intervention was defined as simple, lateral, rubbing, vertical, or random. Simple intervention stimulated the entire finger pad at the same time. Lateral intervention stimulated with moving between left and right on the finger pad. Rubbing intervention stimulated with moving the stimulus probe, fixed by protrusion pins. Vertical intervention stimulated with moving in the forward and backward directions on the finger pad. Random intervention stimulated to finger pad with either row protrudes. MEPs were measured in the first dorsal interosseous muscle to transcranial magnetic stimulation of the left motor cortex before, immediately after, and 5-20 min after intervention. Following simple intervention, MEP amplitudes were significantly smaller than preintervention, indicating depression of corticospinal excitability. Following lateral, rubbing, and vertical intervention, MEP amplitudes were significantly larger than preintervention, indicating facilitation of corticospinal excitability. The modulation of corticospinal excitability depends on MS patterns. These results contribute to knowledge regarding the use of MS as a neurorehabilitation tool to neurological disorder.

  8. Yokukansan and Yokukansankachimpihange Ameliorate Aggressive Behaviors in Rats with Cholinergic Degeneration in the Nucleus Basalis of Meynert

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    Masahiro Tabuchi

    2017-04-01

    Full Text Available Yokukansan (YKS and yokukansankachimpihange (YKSCH are traditional Japanese Kampo medicines. The latter comprises YKS along with the medicinal herbs Citrus unshiu peel and Pinellia tuber. Both of these Kampo medicines are indicated for the treatment of night crying and irritability in children and for neurosis and insomnia in adults. In recent clinical trials, YKS exhibited ameliorative effects on the behavioral and psychological symptoms of dementia, such as aggressiveness, excitement, and irritability. In the present study, we aimed to clarify the involvement of cholinergic degeneration in the nucleus basalis of Meynert (NBM in the development of aggressiveness in rats. Subsequently, using this animal model, the effects of YKS and YKSCH on aggressiveness were compared and the mechanisms underlying these effects were investigated. L-Glutamic acid (Glu was injected into the right NBM of rats to induce deterioration of cholinergic neurons. On day 8 after Glu injection, aggressive behaviors were evaluated using resident–intruder tests. After the evaluation, YKS or YKSCH was administered to rats with aggressive behaviors daily for 7 days. In some groups, the 5-HT1A receptor antagonist WAY-100635 was coadministered with YKS or YKSCH over the same period. In other groups, locomotor activity was measured on days 12–14 after Glu injection. On day 15, immunohistochemistry was then performed to examine choline acetyltransferase (ChAT activities in the NBM. Aggressive behaviors had developed on day 8 after Glu injection and were maintained until day 15. YKS and YKSCH significantly ameliorated the aggressive behaviors. These suppressive effects were entirely abolished following coadministration of WAY-100635. Finally, the number of ChAT-positive cells in the right NBM was significantly reduced on day 15 after Glu injection, and treatment with YKS or YKSCH did not ameliorate these reduced cell numbers. Our results show that unilateral Glu injections

  9. Dependence of (anomalous) fading of infra-red stimulated luminescence on trap occupancy in feldspars

    DEFF Research Database (Denmark)

    Morthekai, P.; Jain, Mayank; Gach, Grzegorz

    2013-01-01

    Dose dependency of anomalous fading of infra-red stimulated luminescence (IRSL) from feldspars has been investigated using radiations of different ionisation qualities. The rate of fading of the IRSL signal after proton irradiation (9.4–30%/decade) is on an average almost twice compared...

  10. In situ hybridization of nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer disease

    International Nuclear Information System (INIS)

    Cohen, M.L.; Golde, T.E.; Usiak, M.F.; Younkin, L.H.; Younkin, S.G.

    1988-01-01

    To determine which cells within the brain produce β-amyloid mRNA and to assess expression of the β-amyloid gene in Alzheimer disease, the authors analyzed brain tissue from Alzheimer and control patients by in situ hybridization. The results demonstrate that β-amyloid mRNA is produced by neurons in the nucleus basalis of Meynert and cerebral cortex and that nuclues basalis perikarya from Alzheimer patients consistently hybridize more β-amyloid probe than those from controls. These observations support the hypothesis that increased expression of the β-amyloid gene plays an important role in the deposition of amyloid in the brains of patients with Alzheimer disease

  11. Transcranial electric stimulation for intraoperative motor evoked potential monitoring: dependence of required stimulation current on interstimulus interval value.

    Science.gov (United States)

    Joksimovic, Boban; Szelenyi, Andrea; Seifert, Volker; Damjanovic, Aleksandar; Damjanovic, Aleksandra; Rasulic, Lukas

    2015-05-01

    To evaluate the relationship between stimulus intensity by constant current transcranial electric stimulation and interstimulus interval (ISI) for eliciting muscle motor evoked potentials (MEPs) in three different hand muscles and the tibialis anterior muscles. We tested intraoperatively different monophasic constant current pulses and ISIs in 22 patients with clinically normal motor function. Motor thresholds of contralateral muscle MEPs were determined at 0.5 milliseconds (ms) pulse duration and ISIs of 1, 2, 3, 4, 5, and 10 ms using a train of 2, 3, and 5 monophasic constant current pulses of 62 to 104 mA before craniotomy and after closure of the dura mater. The lowest stimulation threshold to elicit MEPs in the examined muscles was achieved with a train of 5 pulses (ISI: 3 ms) before craniotomy, which was statistically significant compared with 2 pulses (ISI: 3 ms) as well as 3 pulses (ISIs: 3 and 10 ms). An ISI of 3 ms gave the lowest motor thresholds with statistical significance compared with the ISIs of 4 ms (2 pulses) and of 1 ms (3 pulses). All current intensity (mA) and ISI (ms) relationship graphs had a trend of the exponential function as y = a + bx + c ρ (x), where y is intensity (mA) and x is ISI (ms). The minimum of the function was determined for each patient and each muscle. The difference was statistically significant between 3 and 5 pulses before craniotomy and between 3 and 5 pulses and 2 and 5 pulses after closure of the dura mater. In adult neurosurgical patients with a normal motor status, a train of 5 pulses and an ISI of 3 ms provide the lowest motor thresholds. We provided evidence of the dependence of required stimulation current on ISI. Georg Thieme Verlag KG Stuttgart · New York.

  12. Luminol-dependent chemiluminescence in antibody-sensitized neutrophils stimulated with protein A-bearing staphylococci.

    Science.gov (United States)

    Nishihara, S; Seki, K; Ikigai, H; Masuda, S

    1988-01-01

    When mouse polymorphonuclear leukocytes (PMNs) sensitized with rabbit antibody to mouse Ehrlich ascites tumor cells were stimulated by Staphylococcus aureus Cowan I cells, a conspicuous luminol-dependent chemiluminescence was observed in the absence of opsonin. The profile of the chemiluminescence (CL) response evoked by staphylococcal cells from antibody-sensitized PMNs had two peaks. An initial peak, observed within 1 min after stimulation, was sharp and high and a second peak, observed about 5 min after stimulation, was low and extended. The CL response of antibody-sensitized PMNs stimulated by S. aureus Cowan I cells was dose-dependently blocked by preincubation with soluble SpA. Cells of a mutant derived from S. aureus Cowan I strain with trace amounts of cell-bound SpA failed to stimulate the antibody-sensitized PMNs to generate the CL response. The antibody-sensitized PMNs were found to phagocytize SpA-bearing S. aureus cells even in the absence of opsonic serum. These results suggest that the observation presented here might provide a useful tool for the investigation of CL response of PMNs.

  13. Nobiletin Stimulates Chloride Secretion in Human Bronchial Epithelia via a cAMP/PKA-Dependent Pathway

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    Yuan Hao

    2015-08-01

    Full Text Available Background/Aims: Nobiletin, a citrus flavonoid isolated from tangerines, alters ion transport functions in intestinal epithelia, and has antagonistic effects on eosinophilic airway inflammation of asthmatic rats. The present study examined the effects of nobiletin on basal short-circuit current (ISC in a human bronchial epithelial cell line (16HBE14o-, and characterized the signal transduction pathways that allowed nobiletin to regulate electrolyte transport. Methods: The ISC measurement technique was used for transepithelial electrical measurements. Intracellular calcium ([Ca2+]i and cAMP were also quantified. Results: Nobiletin stimulated a concentration-dependent increase in ISC, which was due to Cl- secretion. The increase in ISC was inhibited by a cystic fibrosis transmembrane conductance regulator inhibitor (CFTRinh-172, but not by 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS, Chromanol 293B, clotrimazole, or TRAM-34. Nobiletin-stimulated ISC was also sensitive to a protein kinase A (PKA inhibitor, H89, and an adenylate cyclase inhibitor, MDL-12330A. Nobiletin could not stimulate any increase in ISC in a cystic fibrosis (CF cell line, CFBE41o-, which lacked a functional CFTR. Nobiletin stimulated a real-time increase in cAMP, but not [Ca2+]i. Conclusion: Nobiletin stimulated transepithelial Cl- secretion across human bronchial epithelia. The mechanisms involved activation of adenylate cyclase- and cAMP/PKA-dependent pathways, leading to activation of apical CFTR Cl- channels.

  14. The Effect of Lamotrigine and Levetiracetam on TMS-Evoked EEG Responses Depends on Stimulation Intensity

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    Isabella Premoli

    2017-10-01

    Full Text Available The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG has uncovered underlying mechanisms of two anti-epileptic medications: levetiracetam and lamotrigine. Despite their different mechanism of action, both drugs modulated TMS-evoked EEG potentials (TEPs in a similar way. Since both medications increase resting motor threshold (RMT, the current aim was to examine the similarities and differences in post-drug TEPs, depending on whether stimulation intensity was adjusted to take account of post-drug RMT increase. The experiment followed a placebo controlled, double blind, crossover design, involving a single dose of either lamotrigine or levetiracetam. When a drug-induced increase of RMT occurred, post-drug measurements involved two blocks of stimulations, using unadjusted and adjusted stimulation intensity. A cluster based permutation analysis of differences in TEP amplitude between adjusted and unadjusted stimulation intensity showed that lamotrigine induced a stronger modulation of the N45 TEP component compared to levetiracetam. Results highlight the impact of adjusting stimulation intensity.

  15. DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.

    Science.gov (United States)

    Li, Wen; Yu, Min; Luo, Suhui; Liu, Huan; Gao, Yuxia; Wilson, John X; Huang, Guowei

    2013-07-01

    The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 μmol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Gene expression results in lipopolysaccharide-stimulated monocytes depend significantly on the choice of reference genes

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    Øvstebø Reidun

    2010-05-01

    Full Text Available Abstract Background Gene expression in lipopolysaccharide (LPS-stimulated monocytes is mainly studied by quantitative real-time reverse transcription PCR (RT-qPCR using GAPDH (glyceraldehyde 3-phosphate dehydrogenase or ACTB (beta-actin as reference gene for normalization. Expression of traditional reference genes has been shown to vary substantially under certain conditions leading to invalid results. To investigate whether traditional reference genes are stably expressed in LPS-stimulated monocytes or if RT-qPCR results are dependent on the choice of reference genes, we have assessed and evaluated gene expression stability of twelve candidate reference genes in this model system. Results Twelve candidate reference genes were quantified by RT-qPCR in LPS-stimulated, human monocytes and evaluated using the programs geNorm, Normfinder and BestKeeper. geNorm ranked PPIB (cyclophilin B, B2M (beta-2-microglobulin and PPIA (cyclophilin A as the best combination for gene expression normalization in LPS-stimulated monocytes. Normfinder suggested TBP (TATA-box binding protein and B2M as the best combination. Compared to these combinations, normalization using GAPDH alone resulted in significantly higher changes of TNF-α (tumor necrosis factor-alpha and IL10 (interleukin 10 expression. Moreover, a significant difference in TNF-α expression between monocytes stimulated with equimolar concentrations of LPS from N. meningitides and E. coli, respectively, was identified when using the suggested combinations of reference genes for normalization, but stayed unrecognized when employing a single reference gene, ACTB or GAPDH. Conclusions Gene expression levels in LPS-stimulated monocytes based on RT-qPCR results differ significantly when normalized to a single gene or a combination of stably expressed reference genes. Proper evaluation of reference gene stabiliy is therefore mandatory before reporting RT-qPCR results in LPS-stimulated monocytes.

  17. Time and frequency-dependent modulation of local field potential synchronization by deep brain stimulation.

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    Clinton B McCracken

    Full Text Available High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS, is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP, the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson's disease (PD. We performed simultaneous multi-site local field potential (LFP recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective, low-frequency (LF, 15 Hz; ineffective and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR, ventroanterior thalamus (VA, primary motor cortex (M1, and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic

  18. Storage of Pentatomid Eggs in Liquid Nitrogen and Dormancy of Trissolcus basalis (Wollaston) and Telenomus podisi Ashmead (Hymenoptera: Platygastridae) Adults as a Method of Mass Production.

    Science.gov (United States)

    Doetzer, A K; Foerster, L A

    2013-10-01

    The eggs of pentatomid species were evaluated to parasitism by Trissolcus basalis (Wollaston) and Telenomus podisi Ashmead after storage in liquid nitrogen. Adults which emerged from stored eggs were kept at 18°C for 120 and 180 days to investigate whether adult dormancy could be associated with host egg storage in liquid nitrogen as a method of mass production of these egg parasitoids. Eggs of Nezara viridula (L.) and Acrosternum pengue (Rolston) were successfully parasitized by T. basalis, as well as Piezodorus guildinii (Westwood) and Dichelops furcatus (F.) by T. podisi. The eggs of Edessa meditabunda (F.) were not parasitized by T. basalis. The emergence of T. podisi from eggs of Euschistus heros (F.) and Podisus nigrispinus (Dallas) stored for 6 months was lower than the control. Females of T. basalis and T. podisi that emerged from stored eggs were kept in dormancy at 18°C. Longevity of T. basalis was influenced by the storage time and sex, but not by the interaction of sex and storage time. For T. podisi, longevity was influenced by the storage time, sex, and by the interaction of sex and storage time. For T. basalis, storage in liquid nitrogen did not affect the fecundity of quiescent females, while the number of parasitized eggs by T. podisi decreased after storage. By the joint use of these techniques, it is possible to optimize mass production of T. basalis so that its life cycle can be monitored and synchronized with the life cycle and availability of hosts.

  19. Depolarization-stimulated 42K+ efflux in rat aorta is calcium- and cellular volume-dependent

    International Nuclear Information System (INIS)

    Magliola, L.; Jones, A.W.

    1987-01-01

    The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase 42 K+ efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium-stimulated 36 Cl- efflux. The addition of 25-150 mM KCl to normal physiologic solution stimulated 42 K+ efflux in a concentration-dependent manner. Diltiazem suppressed potassium-stimulated 42 K+ efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit 42 K+ efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium-stimulated 42 K+ efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the 42 K+ efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization-mediated 42 K+ efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists

  20. Stimulation of NADH-dependent microsomal DNA strand cleavage by rifamycin SV.

    Science.gov (United States)

    Kukiełka, E; Cederbaum, A I

    1995-04-15

    Rifamycin SV is an antibiotic anti-bacterial agent used in the treatment of tuberculosis. This drug can autoxidize, especially in the presence of metals, and generate reactive oxygen species. A previous study indicated that rifamycin SV can increase NADH-dependent microsomal production of reactive oxygen species. The current study evaluated the ability of rifamycin SV to interact with iron and increase microsomal production of hydroxyl radical, as detected by conversion of supercoiled plasmid DNA into the relaxed open circular state. The plasmid used was pBluescript II KS(-), and the forms of DNA were separated by agarose-gel electrophoresis. Incubation of rat liver microsomes with plasmid plus NADH plus ferric-ATP caused DNA strand cleavage. The addition of rifamycin SV produced a time- and concentration-dependent increase in DNA-strand cleavage. No stimulation by rifamycin SV occurred in the absence of microsomes, NADH or ferric-ATP. Stimulation occurred with other ferric complexes besides ferric-ATP, e.g. ferric-histidine, ferric-citrate, ferric-EDTA, and ferric-(NH4)2SO4. Rifamycin SV did not significantly increase the high rates of DNA strand cleavage found with NADPH as the microsomal reductant. The stimulation of NADH-dependent microsomal DNA strand cleavage was completely blocked by catalase, superoxide dismutase, GSH and a variety of hydroxyl-radical-scavenging agents, but not by anti-oxidants that prevent microsomal lipid peroxidation. Redox cycling agents, such as menadione and paraquat, in contrast with rifamycin SV, stimulated the NADPH-dependent reaction; menadione and rifamycin SV were superior to paraquat in stimulating the NADH-dependent reaction. These results indicate that rifamycin SV can, in the presence of an iron catalyst, increase microsomal production of reactive oxygen species which can cause DNA-strand cleavage. In contrast with other redox cycling agents, the stimulation by rifamycin SV is more pronounced with NADH than with NADPH as the

  1. Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

    Science.gov (United States)

    Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

    2014-09-01

    Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

  2. Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

    Science.gov (United States)

    Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

    2013-04-01

    Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

  3. Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

    Directory of Open Access Journals (Sweden)

    Marques-da-Silva A.C.

    1997-01-01

    Full Text Available The influence of Ca2+ on hepatic gluconeogenesis was measured in the isolated perfused rat liver at different cytosolic NAD+-NADH potentials. Lactate and pyruvate were the gluconeogenic substrates and the cytosolic NAD+-NADH potentials were changed by varying the lactate to pyruvate ratios from 0.01 to 100. The following results were obtained: a gluconeogenesis from lactate plus pyruvate was not affected by Ca2+-free perfusion (no Ca2+ in the perfusion fluid combined with previous depletion of the intracellular pools; gluconeogenesis was also poorly dependent on the lactate to pyruvate ratios in the range of 0.1 to 100; only for a ratio equal to 0.01 was a significantly smaller gluconeogenic activity observed in comparison to the other ratios. b In the presence of Ca2+, the increase in oxygen uptake caused by the infusion of lactate plus pyruvate at a ratio equal to 10 was the most pronounced one; in Ca2+-free perfusion the increase in oxygen uptake caused by lactate plus pyruvate infusion tended to be higher for all lactate to pyruvate ratios; the most pronounced difference was observed for a lactate/pyruvate ratio equal to 1. c In the presence of Ca2+ the effects of glucagon on gluconeogenesis showed a positive correlation with the lactate to pyruvate ratios; for a ratio equal to 0.01 no stimulation occurred, but in the 0.1 to 100 range stimulation increased progressively, producing a clear parabolic dependence between the effects of glucagon and the lactate to pyruvate ratio. d In the absence of Ca2+ the relationship between the changes caused by glucagon in gluconeogenesis and the lactate to pyruvate ratio was substantially changed; the dependence curve was no longer parabolic but sigmoidal in shape with a plateau beginning at a lactate/pyruvate ratio equal to 1; there was inhibition at the lactate to pyruvate ratios of 0.01 and 0.1 and a constant stimulation starting with a ratio equal to 1; for the lactate to pyruvate ratios of 10 and 100

  4. Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

    Directory of Open Access Journals (Sweden)

    Martina Reske

    Full Text Available Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate, which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.158 occasional stimulants users (OSU and 50 comparison subjects (CS performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions". The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42, or <50 lifetime marijuana uses (n = 32, were compared to CS with <50 lifetime uses (n = 46 to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring

  5. Personality Disorders, Narcotics, and Stimulants; Relationship in Iranian Male Substance Dependents Population.

    Science.gov (United States)

    Noorbakhsh, Simasadat; Zeinodini, Zahra; Khanjani, Zeynab; Poorsharifi, Hamid; Rajezi Esfahani, Sepideh

    2015-06-01

    Individuals with certain personality disorders, especially the antisocial and borderline personality disorders, are more prone to substance use disorders. Regarding the importance of substance use disorders, this study aimed to explore the association between personality disorders and types of used drugs (narcotics and stimulants) in Iranian male substance users. The current study was a correlation study. We evaluated 285 male substance users and excluded 25 according to exclusion criteria. A total of 130 narcotic users and 130 stimulant users were recruited randomly in several phases from January 2013 to October 2013. All participants were referred to Substance Dependency Treatment Clinics in Tehran, Iran. Data collection process was accomplished by means of clinical interview based on DSM-V criteria for substance use disorders, Iranian version of addiction severity index (ASI), and Millon clinical multi-axial inventory-III (MCMI-III). Data were analyzed by SPSS 21 using Pearson correlation coefficient and regression, the. There was a significant correlation between stimulant use and histrionic personality disorder (P personality disorders (P histrionic, and narcissistic personality disorders (P personality disorders (P personality disorders, and narcotic and stimulants consumption (P personality disorder and narcotics (P personality disorders and types of used drugs were in accordance with the previous studies results. It is necessary to design appropriate treatment plans for medical treatment of those with personality disorders.

  6. Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

    Science.gov (United States)

    Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

    2017-09-01

    Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

  7. Shared Neural Mechanisms for the Evaluation of Intense Sensory Stimulation and Economic Reward, Dependent on Stimulation-Seeking Behavior.

    Science.gov (United States)

    Norbury, Agnes; Valton, Vincent; Rees, Geraint; Roiser, Jonathan P; Husain, Masud

    2016-09-28

    Why are some people strongly motivated by intense sensory experiences? Here we investigated how people encode the value of an intense sensory experience compared with economic reward, and how this varies according to stimulation-seeking preference. Specifically, we used a novel behavioral task in combination with computational modeling to derive the value individuals assigned to the opportunity to experience an intense tactile stimulus (mild electric shock). We then examined functional imaging data recorded during task performance to see how the opportunity to experience the sensory stimulus was encoded in stimulation-seekers versus stimulation-avoiders. We found that for individuals who positively sought out this kind of sensory stimulation, there was common encoding of anticipated economic and sensory rewards in the ventromedial prefrontal cortex. Conversely, there was robust encoding of the modeled probability of receiving such stimulation in the insula only in stimulation-avoidant individuals. Finally, we found preliminary evidence that sensory prediction error signals may be positively signed for stimulation-seekers, but negatively signed for stimulation-avoiders, in the posterior cingulate cortex. These findings may help explain why high intensity sensory experiences are appetitive for some individuals, but not for others, and may have relevance for the increased vulnerability for some psychopathologies, but perhaps increased resilience for others, in high sensation-seeking individuals. People vary in their preference for intense sensory experiences. Here, we investigated how different individuals evaluate the prospect of an unusual sensory experience (electric shock), compared with the opportunity to gain a more traditional reward (money). We found that in a subset of individuals who sought out such unusual sensory stimulation, anticipation of the sensory outcome was encoded in the same way as that of monetary gain, in the ventromedial prefrontal cortex

  8. Intensity dependent waiting time for strong electron trapping events in speckle stimulated raman scatter

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Harvey [Los Alamos National Laboratory; Daughton, W [Los Alamos National Laboratory; Yin, L [Los Alamos National Laboratory

    2009-01-01

    The onset of Stimulated Raman scatter from an intense laser speckle is the simplest experimentally realizable laser-plasma-interaction environment. Despite this data and recent 3D particle simulations, the controlling mechanism at the onset of backscatter in the kinetic regime when strong electron trapping in the daughter Langmuir wave is a dominant nonlinearity is not understood. This paper explores the consequences of assuming that onset is controlled by large thermal fluctuations. A super exponential dependence of mean reflectivity on speckle intensity in the onset regime is predicted.

  9. Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells.

    Science.gov (United States)

    Huang, Jinghui; Ye, Zhengxu; Hu, Xueyu; Lu, Lei; Luo, Zhuojing

    2010-04-01

    Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1-fold increase in NGF release from cultured SCs. The ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering.

  10. Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

    Science.gov (United States)

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

    Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

    Science.gov (United States)

    Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

    2013-04-01

    Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI

  12. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

    International Nuclear Information System (INIS)

    Mu, Shumin; Tian, Xingsong; Ruan, Yongwei; Liu, Yuantao; Bian, Dezhi; Ma, Chunyan; Yu, Chunxiao; Feng, Mei; Wang, Furong; Gao, Ling; Zhao, Jia-jun

    2012-01-01

    Highlights: ► Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. ► Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. ► Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

  13. Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder.

    Science.gov (United States)

    Meunier, David; Ersche, Karen D; Craig, Kevin J; Fornito, Alex; Merlo-Pich, Emilio; Fineberg, Naomi A; Shabbir, Shaila S; Robbins, Trevor W; Bullmore, Edward T

    2012-01-16

    There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used permutation tests to identify i) brain regions where strength of connectivity was significantly different in both patient groups compared to healthy volunteers; and ii) brain regions and connections which had significantly different functional connectivity between patient groups. We found that functional connectivity of right inferior and superior orbitofrontal cortex (OFC) was abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients with higher scores on measures of compulsive symptom severity showed greater reductions of right orbitofrontal connectivity. Functional connections specifically between OFC and dorsal medial pre-motor and cingulate cortex were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. OCD and stimulant dependence are not identical at the level of brain functional systems but they have some important abnormalities in common compared with healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems biomarker for compulsivity across diagnostic categories. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    International Nuclear Information System (INIS)

    Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

    2011-01-01

    Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

  15. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

  16. Differentiation-Dependent Motility-Responses of Developing Neural Progenitors to Optogenetic Stimulation

    Directory of Open Access Journals (Sweden)

    Tímea Köhidi

    2017-12-01

    Full Text Available During neural tissue genesis, neural stem/progenitor cells are exposed to bioelectric stimuli well before synaptogenesis and neural circuit formation. Fluctuations in the electrochemical potential in the vicinity of developing cells influence the genesis, migration and maturation of neuronal precursors. The complexity of the in vivo environment and the coexistence of various progenitor populations hinder the understanding of the significance of ionic/bioelectric stimuli in the early phases of neuronal differentiation. Using optogenetic stimulation, we investigated the in vitro motility responses of radial glia-like neural stem/progenitor populations to ionic stimuli. Radial glia-like neural stem cells were isolated from CAGloxpStoploxpChR2(H134-eYFP transgenic mouse embryos. After transfection with Cre-recombinase, ChR2(channelrhodopsin-2-expressing and non-expressing cells were separated by eYFP fluorescence. Expression of light-gated ion channels were checked by patch clamp and fluorescence intensity assays. Neurogenesis by ChR2-expressing and non-expressing cells was induced by withdrawal of EGF from the medium. Cells in different (stem cell, migrating progenitor and maturing precursor stages of development were illuminated with laser light (λ = 488 nm; 1.3 mW/mm2; 300 ms in every 5 min for 12 h. The displacement of the cells was analyzed on images taken at the end of each light pulse. Results demonstrated that the migratory activity decreased with the advancement of neuronal differentiation regardless of stimulation. Light-sensitive cells, however, responded on a differentiation-dependent way. In non-differentiated ChR2-expressing stem cell populations, the motility did not change significantly in response to light-stimulation. The displacement activity of migrating progenitors was enhanced, while the motility of differentiating neuronal precursors was markedly reduced by illumination.

  17. The role of the nucleus basalis of Meynert and reticular thalamic nucleus in pathogenesis of genetically determined absence epilepsy in rats : A lesion study

    NARCIS (Netherlands)

    Berdiev, R. K.; Chepurnov, S. A.; Veening, J. G.; Chepurnova, N. E.; van Luiftelaar, G.

    2007-01-01

    The role of cholinergic nucleus basalis (of Meynert) and the reticular thalamic nucleus in mechanisms of the generation spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. Selective lesions were affected by local unilateral intraparenchymal

  18. Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG

    International Nuclear Information System (INIS)

    Ryu, T.; Davis, J.M.; Schwartz, K.A.

    1990-01-01

    The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding

  19. Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

    Directory of Open Access Journals (Sweden)

    Guoshi Li

    2017-10-01

    Full Text Available The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh and norepinephrine (NE and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

  20. Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data

    Directory of Open Access Journals (Sweden)

    Tomasz Dzida

    2017-09-01

    Full Text Available We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα, RNA polymerase (Pol II and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.

  1. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

    Science.gov (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

    2014-01-01

    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  2. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Shumin [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Hospital Affiliated to Shandong Traditional Chinese Medicine University, Jinan 250011 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Tian, Xingsong; Ruan, Yongwei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Liu, Yuantao [The Second Hospital of Shandong University, Jinan 250033 (China); Bian, Dezhi [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Jining Medical College, Jining 272013 (China); Ma, Chunyan [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Yu, Chunxiao [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Feng, Mei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Wang, Furong [Shandong University of Traditional Chinese Medicine, Jinan 250011 (China); Gao, Ling [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Zhao, Jia-jun, E-mail: jjzhao@medmail.com.cn [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. Black-Right-Pointing-Pointer Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. Black-Right-Pointing-Pointer Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

  3. The beta-cell response to glucagon and mixed meal stimulation in non-insulin dependent diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Damsgaard, E M; Matzen, L E

    1988-01-01

    The aim of this study was to evaluate the correlations of the C-peptide and insulin responses after stimulation with glucagon intravenously as well as the 24-h urinary excretion of C-peptide to the C-peptide response to a standard mixed meal in 30 patients with non-insulin dependent diabetes...... plasma C-peptide (r = 0.55, p less than 0.01). The C-peptide and insulin responses after meal stimulation correlated modestly inversely with HbA1. In conclusion, measurement of C-peptide in fasting state, as well as measurements of C-peptide and insulin after glucagon stimulation, only modestly predict...... the C-peptide response to physiologic stimulation in NIDDM. Twenty-four-hour urinary C-peptide excretion does not predict this response. Patients with NIDDM seem to show a better metabolic control if they have a more pronounced beta-cell response to physiologic stimulation....

  4. Gravity dependence of the effect of optokinetic stimulation on the subjective visual vertical.

    Science.gov (United States)

    Ward, Bryan K; Bockisch, Christopher J; Caramia, Nicoletta; Bertolini, Giovanni; Tarnutzer, Alexander Andrea

    2017-05-01

    Accurate and precise estimates of direction of gravity are essential for spatial orientation. According to Bayesian theory, multisensory vestibular, visual, and proprioceptive input is centrally integrated in a weighted fashion based on the reliability of the component sensory signals. For otolithic input, a decreasing signal-to-noise ratio was demonstrated with increasing roll angle. We hypothesized that the weights of vestibular (otolithic) and extravestibular (visual/proprioceptive) sensors are roll-angle dependent and predicted an increased weight of extravestibular cues with increasing roll angle, potentially following the Bayesian hypothesis. To probe this concept, the subjective visual vertical (SVV) was assessed in different roll positions (≤ ± 120°, steps = 30°, n = 10) with/without presenting an optokinetic stimulus (velocity = ± 60°/s). The optokinetic stimulus biased the SVV toward the direction of stimulus rotation for roll angles ≥ ± 30° ( P stimulation. Variability and optokinetic bias were correlated ( R 2 = 0.71, slope = 0.71, 95% confidence interval = 0.57-0.86). An optimal-observer model combining an optokinetic bias with vestibular input reproduced measured errors closely. These findings support the hypothesis of a weighted multisensory integration when estimating direction of gravity with optokinetic stimulation. Visual input was weighted more when vestibular input became less reliable, i.e., at larger roll-tilt angles. However, according to Bayesian theory, the variability of combined cues is always lower than the variability of each source cue. If the observed increase in variability, although nonsignificant, is true, either it must depend on an additional source of variability, added after SVV computation, or it would conflict with the Bayesian hypothesis. NEW & NOTEWORTHY Applying a rotating optokinetic stimulus while recording the subjective visual vertical in different whole body roll angles, we noted the optokinetic

  5. NAD+-dependent HDAC inhibitor stimulates Monascus pigment production but inhibit citrinin.

    Science.gov (United States)

    Hu, Yan; Zhou, Youxiang; Mao, Zejing; Li, Huihui; Chen, Fusheng; Shao, Yanchun

    2017-08-23

    Monascus species are edible fungi due to the production of food colorant and other beneficial compounds. Hence, it has been an attractive thesis to improve their productivities. Increasing numbers of investigations revealed that regulating the activities of histone deacetylases can significantly perturb secondary metabolites (SM) production at a global level. In this study, dihydrocoumarin (DHC, an inhibitor of the Sirtuin family of NAD + -dependent deacetylases) was used to treat Monascus ruber for evaluating its effects on organism growth and SM production. The results revealed that the variation trends of colonial sizes, biomass and mycotoxin were in a dose-dependent manner. Generally, they decreased with the increased DHC concentrations in the designed range. But the variation trend of pigment was different. Comparison of SM profile, three new peaks occurred to the mycelia extractions from DHC-treated strain corresponding to molecular weights 402, 416 and 444, respectively. These three compounds were identified as Monasfluol B, Monascus azaphilone C and acetyl-monasfluol B (a new Monascus chemical pigment structure). In short, DHC can stimulate M. ruber strain to produce more pigment-like polyketides but inhibition of mycotoxin (citrinin).

  6. 2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter

    Directory of Open Access Journals (Sweden)

    Zhentao Yang

    2017-05-01

    Full Text Available 2-hydroxyglutarate-(2-HG-mediated inhibition of TET2 activity influences DNA hypermethylation in cells harboring mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2. Here, we show that 2-HG also regulates DNA methylation mediated by DNA methyltransferase 1 (DNMT1. DNMT1-dependent hypermethylation of the RIP3 promoter occurred in both IDH1 R132Q knockin mutant mouse embryonic fibroblast (MEFs and 2-HG-treated wild-type (WT MEFs. We found that 2-HG bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis. In human glioma samples, RIP3 protein levels correlated negatively with IDH1 R132H levels. Furthermore, ectopic expression of RIP3 in transformed IDH1-mutated MEFs inhibited the growth of tumors derived from these cells following transplantation into nude mice. Thus, our research sheds light on a mechanism of 2-HG-induced DNA hypermethylation and suggests that impaired necroptosis contributes to the tumorigenesis driven by IDH1/2 mutations.

  7. Lipopolysaccharide stimulates p62-dependent autophagy-like aggregate clearance in hepatocytes.

    Science.gov (United States)

    Chen, Christine; Deng, Meihong; Sun, Qian; Loughran, Patricia; Billiar, Timothy R; Scott, Melanie J

    2014-01-01

    Impairment of autophagy has been associated with liver injury. TLR4-stimulation by LPS upregulates autophagy in hepatocytes, although the signaling pathways involved remain elusive. The objective of this study was to determine the signaling pathway leading to LPS-stimulated autophagy in hepatocytes. Cell lysates from livers of wild type (WT; C57BL/6) mice given LPS (5 mg/kg-IP) and hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to 24 h were collected. LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined by immunoblot, immunofluorescence, and qPCR. Autophagy-like activation was measured by GFP-LC3-puncta formation and LC3II-expression. Beclin1, Nrf2, p62, MyD88, and TIRAP were knocked-down using siRNA. LC3II-expression increased in both liver and hepatocytes after LPS and was dependent on TLR4. Beclin1 expression did not increase after LPS in hepatocytes and beclin1-knockdown did not affect LC3II levels. In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPS-induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of both Nrf2 and NF κ B transcription factors to the nucleus to upregulate p62-expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1-mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress.

  8. Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

    Science.gov (United States)

    Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

    2018-05-01

    Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

  9. Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by Ca2+-dependent N-acyltransferase.

    Science.gov (United States)

    Hussain, Zahir; Uyama, Toru; Kawai, Katsuhisa; Binte Mustafiz, Smriti Sultana; Tsuboi, Kazuhito; Araki, Nobukazu; Ueda, Natsuo

    2018-05-01

    N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is produced in mammals through the transfer of an acyl chain from certain glycerophospholipids to phosphatidylethanolamine (PE) by Ca 2+ -dependent or -independent N-acyltransferases. The ε isoform of mouse cytosolic phospholipase A 2 (cPLA 2 ε) was recently identified as a Ca 2+ -dependent N-acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms of human cPLA 2 ε function as Ca-NAT. We next purified both mouse recombinant cPLA 2 ε and its two human orthologues to examine their catalytic properties. The enzyme absolutely required Ca 2+ for its activity and the activity was enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the presence of 1 mM CaCl 2 and lowered the EC 50 value of Ca 2+ >8-fold. Using a PS probe, we showed that cPLA 2 ε largely co-localizes with PS in plasma membrane and organelles involved in the endocytic pathway, further supporting the interaction of cPLA 2 ε with PS in living cells. Finally, we found that the Ca 2+ -ionophore ionomycin increased [ 14 C]NAPE levels >10-fold in [ 14 C]ethanolamine-labeled cPLA 2 ε-expressing cells while phospholipase A/acyltransferase-1, acting as a Ca 2+ -independent N-acyltransferase, was insensitive to ionomycin for full activity. In conclusion, PS potently stimulated the Ca 2+ -dependent activity and human cPLA 2 ε isoforms also functioned as Ca-NAT. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. An interferometer experiment to explore the aspect angle dependence of stimulated electromagnetic emission spectra

    Directory of Open Access Journals (Sweden)

    Isham

    2005-01-01

    Full Text Available When the Earth's ionosphere is irradiated by a radiofrequency (RF electromagnetic wave of sufficiently high power density and tuned to match a natural E- or F-region plasma frequency, ionospheric magnetoionic wave modes may be excited and may generate RF electromagnetic sideband waves via nonlinear interactions. These secondary emissions, which may then escape from the ionosphere, have been termed stimulated electromagnetic emission or SEE. The frequency spectra of this radiation has been studied extensively, and a number of characteristic spectral features have been identified and in some cases related to particular plasma processes. The separation in frequency between the RF pump and the harmonics of the local electron gyrofrequency is critical in determining the amount of anomalous absorption suffered by the pump wave and the spectral properties of the stimulated sidebands. The pump can excite electrostatic waves which do not propagate away but can in some cases be observed via radio-wave scattering from the electron density fluctuations associated with them. These enhanced density fluctuations are created by processes commonly referred to as upper-hybrid and Langmuir turbulence. Langmuir turbulence has been the subject of 930-MHz scattering observations with antenna scanning through several pre-selected angles between the geographic and geomagnetic zenith directions, and a preference for pointing angles between the Spitze angle and geomagnetic field-aligned was identified. Other phenomena, such as the generation of enhanced electron temperatures and artificial aurora, have more recently been shown to have special behavior at similar angles, near but apparently not quite at field-aligned. In view of this evidence for angular structure in several pump-induced effects, in light of the rich variety of SEE phenomena strongly dependent on the geomagnetic field via the frequency interval between the pump and the gyrofrequency harmonics, and in

  11. An interferometer experiment to explore the aspect angle dependence of stimulated electromagnetic emission spectra

    Directory of Open Access Journals (Sweden)

    Isham

    2005-01-01

    Full Text Available When the Earth's ionosphere is irradiated by a radiofrequency (RF electromagnetic wave of sufficiently high power density and tuned to match a natural E- or F-region plasma frequency, ionospheric magnetoionic wave modes may be excited and may generate RF electromagnetic sideband waves via nonlinear interactions. These secondary emissions, which may then escape from the ionosphere, have been termed stimulated electromagnetic emission or SEE. The frequency spectra of this radiation has been studied extensively, and a number of characteristic spectral features have been identified and in some cases related to particular plasma processes. The separation in frequency between the RF pump and the harmonics of the local electron gyrofrequency is critical in determining the amount of anomalous absorption suffered by the pump wave and the spectral properties of the stimulated sidebands. The pump can excite electrostatic waves which do not propagate away but can in some cases be observed via radio-wave scattering from the electron density fluctuations associated with them. These enhanced density fluctuations are created by processes commonly referred to as upper-hybrid and Langmuir turbulence. Langmuir turbulence has been the subject of 930-MHz scattering observations with antenna scanning through several pre-selected angles between the geographic and geomagnetic zenith directions, and a preference for pointing angles between the Spitze angle and geomagnetic field-aligned was identified. Other phenomena, such as the generation of enhanced electron temperatures and artificial aurora, have more recently been shown to have special behavior at similar angles, near but apparently not quite at field-aligned. In view of this evidence for angular structure in several pump-induced effects, in light of the rich variety of SEE phenomena strongly dependent on the geomagnetic field via the frequency interval between the pump and the gyrofrequency harmonics, and in view

  12. Global perception depends on coherent work of bilateral visual cortices: transcranial magnetic stimulation (TMS) studies.

    Science.gov (United States)

    Zhang, Xin; Han, ShiHui

    2007-08-01

    Previous research suggests that the right and left hemispheres dominate global and local perception of hierarchical patterns, respectively. The current work examined whether global perception of hierarchical stimuli requires coherent work of bilateral visual cortices using transcranial magnetic stimulation (TMS). Subjects discriminated global or local properties of compound letters in Experiment 1. Reaction times were recorded when single-pulse real TMS or sham TMS was delivered over the left or right visual cortex. While a global precedence effect (i.e., faster responses to global than local targets and stronger global-to-local interference than the reverse) was observed, TMS decreased global-to-local interference whereas increased local-to-global interference. Experiment 2 ruled out the possibility that the effects observed in Experiment 1 resulted from perceptual learning. Experiment 3 used compound shapes and observed TMS effect similar to that in Experiment 1. Moreover, TMS also slowed global RTs whereas speeded up local RTs in Experiment 3. Finally, the TMS effects observed in Experiments 1 and 3 did not differ between the conditions when TMS was applied over the left and right hemispheres. The results support a coherence hypothesis that global perception of compound stimuli depends upon the coherent work of bilateral visual cortices.

  13. Using brain-computer interfaces and brain-state dependent stimulation as tools in cognitive neuroscience

    Directory of Open Access Journals (Sweden)

    Ole eJensen

    2011-05-01

    Full Text Available Large efforts are currently being made to develop and improve online analysis of brain activity which can be used e.g. for brain-computer interfacing (BCI. A BCI allows a subject to control a device by willfully changing his/her own brain activity. BCI therefore holds the promise as a tool for aiding the disabled and for augmenting human performance. While technical developments obviously are important, we will here argue that new insight gained from cognitive neuroscience can be used to identify signatures of neural activation which reliably can be modulated by the subject at will. This review will focus mainly on oscillatory activity in the alpha band which is strongly modulated by changes in covert attention. Besides developing BCIs for their traditional purpose, they might also be used as a research tool for cognitive neuroscience. There is currently a strong interest in how brain state fluctuations impact cognition. These state fluctuations are partly reflected by ongoing oscillatory activity. The functional role of the brain state can be investigated by introducing stimuli in real time to subjects depending on the actual state of the brain. This principle of brain-state dependent stimulation may also be used as a practical tool for augmenting human behavior. In conclusion, new approaches based on online analysis of ongoing brain activity are currently in rapid development. These approaches are amongst others informed by new insight gained from EEG/MEG studies in cognitive neuroscience and hold the promise of providing new ways for investigating the brain at work.

  14. DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

    Science.gov (United States)

    Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

    2014-09-11

    We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  15. Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts.

    Science.gov (United States)

    Dafsari, Haidar Salimi; Petry-Schmelzer, Jan Niklas; Ray-Chaudhuri, K; Ashkan, Keyoumars; Weis, Luca; Dembek, Till A; Samuel, Michael; Rizos, Alexandra; Silverdale, Monty; Barbe, Michael T; Fink, Gereon R; Evans, Julian; Martinez-Martin, Pablo; Antonini, Angelo; Visser-Vandewalle, Veerle; Timmermann, Lars

    2018-03-16

    Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS. To investigate the impact of active contact location on NMS in STN-DBS in PD. In this prospective, open-label, multicenter study including 50 PD patients undergoing bilateral STN-DBS, we collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, motor complications, activities of daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and Bonferroni-correction for multiple comparisons. Although the STN was targeted visually, we employed an atlas-based approach to explore the relationship between active contact locations and DBS outcomes. Based on fused MRI/CT-images, we identified Cartesian coordinates of active contacts with patient-specific Mai-atlas standardization. We computed linear mixed-effects models with x-/y-/z-coordinates as independent, hemispheres as within-subject, and test change scores as dependent variables. NMSS, NMSQ, PDQ-8, motor examination, complications, and LEDD significantly improved at follow-up. Linear mixed-effect models showed that NMS and QoL improvement significantly depended on more medial (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ-8) neurostimulation. ADL improved more in posterior, LEDD in lateral neurostimulation locations. No relationship was observed for motor examination and complications scores. Our study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes. Copyright © 2018. Published by Elsevier Inc.

  16. Predictors and Neuropsychiatric Profile of Nucleus Basalis of Meynert Degeneration in Parkinson Disease

    Science.gov (United States)

    2017-10-01

    information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...region with deep brain stimulation as a potential symptomatic and neuroprotective therapy for psychosis in PD. 15. SUBJECT TERMS Parkinson disease...protein tau (MAPT); Deep brain stimulation . 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE

  17. IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

    Science.gov (United States)

    Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

    2017-10-01

    IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

  18. Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

    NARCIS (Netherlands)

    van Kempen, Anne A. M. W.; van der Crabben, Saskia N.; Ackermans, Mariëtte T.; Endert, Erik; Kok, Joke H.; Sauerwein, Hans P.

    2006-01-01

    In preterm infants, both hypo- and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis.

  19. Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

    DEFF Research Database (Denmark)

    Friis, P; Svehag, S E; Andersen, Ove

    1991-01-01

    . Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited...

  20. Sex differences in disinhibition and its relationship to physical abuse in a sample of stimulant-dependent patients.

    Science.gov (United States)

    Winhusen, Theresa; Lewis, Daniel

    2013-04-01

    Research suggests that impulsivity is a vulnerability factor for developing stimulant dependence, that women develop dependence more quickly than men, and that physical abuse can increase impulsivity and may have greater adverse health consequences in women. This study sought to tie these findings together by evaluating: (1) sex differences in disinhibition prior to lifetime initiation of stimulant abuse and (2) the relationship between physical abuse and disinhibition in stimulant-dependent patients. The Frontal Systems Behavior Scale (FrSBe) is a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses pre-morbid functioning and has a specific cutoff for defining clinically significant abnormalities. Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 118 methamphetamine- and/or cocaine-dependent participants. Lifetime physical abuse was measured by the Addiction Severity Index (ASI). The proportion reporting clinically significant disinhibition was significantly higher in women (64.9%) than in men (45.0%, p=0.04), with no significant difference on the other FrSBe scales. Physical abuse in women, but not men, was associated with worse functioning, with physically abused, relative to non-abused, women having a significantly greater proportion with clinically significant disinhibition (pabuse and that physical abuse in women is associated with greater disinhibition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age.

    Science.gov (United States)

    Dafsari, Haidar S; Reker, Paul; Stalinski, Lisa; Silverdale, Monty; Rizos, Alexandra; Ashkan, Keyoumars; Barbe, Michael T; Fink, Gereon R; Evans, Julian; Steffen, Julia; Samuel, Michael; Dembek, Till A; Visser-Vandewalle, Veerle; Antonini, Angelo; Ray-Chaudhuri, K; Martinez-Martin, Pablo; Timmermann, Lars

    2018-01-01

    The purpose of this study was to investigate how quality of life outcome after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) depends on age. In this prospective, open-label, multicenter study including 120 PD patients undergoing bilateral STN-DBS, we investigated the PDQuestionnaire-8 (PDQ-8), Unified PD Rating Scale-III, Scales for Outcomes in PD-motor examination, complications, activities of daily living, and levodopa equivalent daily dose preoperatively and at 5 months follow-up. Significant changes at follow-up were analyzed with Wilcoxon signed-rank test and Bonferroni correction for multiple comparisons. To explore the influence of age post hoc, the patients were classified into 3 age groups (≤59, 60-69, ≥70 years). Intragroup changes were analyzed with Wilcoxon signed-rank and intergroup differences with Kruskal-Wallis tests. The strength of clinical responses was evaluated using effect size. The PDQuestionnaire-8, Scales for Outcomes in PD-motor complications, activities of daily living, and levodopa equivalent daily dose significantly improved in the overall cohort and all age groups with no significant intergroup differences. However, PDQuestionnaire-8 effect sizes for age groups ≤59, 60 to 69, and ≥70 years, respectively, were strong, moderate, and small. Furthermore, PDQuestionnaire-8 domain analyses revealed that all domains except cognition and emotional well-being significantly improved in patients aged ≤59 years, whereas only communication, activities of daily living, and stigma improved in patients aged 60-69 years, and activities of daily living and stigma in patients aged ≥70 years. Although quality of life, motor complications, and activities of daily living significantly improved in all age groups after bilateral STN-DBS, the beneficial effect on overall quality of life was more pronounced and affected a wider range of quality of life domains in younger patients. © 2017 International

  2. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    International Nuclear Information System (INIS)

    Akter, Jesmin; Takatori, Atsushi; Islam, Md. Sazzadul; Nakazawa, Atsuko; Ozaki, Toshinori; Nagase, Hiroki; Nakagawara, Akira

    2014-01-01

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas

  3. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Akter, Jesmin [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Takatori, Atsushi, E-mail: atakatori@chiba-cc.jp [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Islam, Md. Sazzadul [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakazawa, Atsuko [Department of Pathology, National Center for Child Health and Development, Tokyo (Japan); Ozaki, Toshinori, E-mail: tozaki@chiba-cc.jp [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nagase, Hiroki [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakagawara, Akira [Saga Medical Centre, 840-8571 (Japan)

    2014-10-10

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

  4. Context-dependent effects of substantia nigra stimulation on eye movements.

    Science.gov (United States)

    Basso, Michele A; Liu, Ping

    2007-06-01

    In a series of now classic experiments, an output structure of the basal ganglia (BG)--the substantia nigra pars reticulata (SNr)--was shown to be involved in the generation of saccades made in particular behavioral contexts, such as when memory was required for guidance. Recent electrophysiological experiments, however, call this original hypothesis into question. Here we test the hypothesis that the SNr is involved preferentially in nonvisually guided saccades using electrical stimulation. Monkeys performed visually guided and memory-guided saccades to locations throughout the visual field. On 50% of the trials, electrical stimulation of the SNr occurred. Stimulation of the SNr altered the direction, amplitude, latency, and probability of saccades. Visually guided saccades tended to be rotated toward the field contralateral to the side of stimulation, whereas memory-guided saccades tended to be rotated toward the hemifield ipsilateral to the side of stimulation. Overall, the changes in saccade vector direction were larger for memory-guided than for visually guided saccades. Both memory- and visually guided saccades were hypometric during stimulation trials, but the stimulation preferentially affected the length of memory-guided saccades. Electrical stimulation of the SNr produced decreases in visually guided saccades bilaterally. In contrast, memory-guided saccades often had increases in saccade latency bilaterally. Finally, we found approximately 10% reduction in the probability of memory-guided saccades bilaterally. Visually guided saccade probability was unaltered. Taken together the results are consistent with the hypothesis that SNr primarily influences nonvisually guided saccades. The pattern of stimulation effects suggests that SNr influence is widespread, altering the pattern of activity bilaterally across the superior colliculus map of saccades.

  5. Perceived Intensity and Discrimination Ability for Lingual Electrotactile Stimulation Depends on Location and Orientation of Electrodes

    Directory of Open Access Journals (Sweden)

    Leslie M. Stone-Roy

    2017-04-01

    Full Text Available Malfunctioning sensory systems can severely impact quality of life and repair is not always possible. One solution, called sensory substitution, is to use another sensory system to bring lost information to the brain. This approach often involves the use of bioengineered devices that electrically stimulate somatosensory fibers. Interestingly, the tongue is an ideal location for electrotactile stimulation due to its dense innervation, moisture, and protected environment. Success with transmitting visual and vestibular information through the tongue indicates promise for future applications. However, sensitivity and discrimination ability varies between individuals and across the tongue surface complicating efforts to produce reliable and consistent sensations. The goals of the present study were to investigate these differences more precisely to better understand the mechanosensory innervation of the tongue so that future electrotactile devices can be designed more effectively. Specifically, we tested whether stimulation of certain regions of the tongue consistently result in better perception, whether the spacing of stimulating electrodes affects perceived intensity, and whether the orientation of electrodes affects perceived intensity and discrimination. To test these hypotheses, we built a custom tongue stimulation device, recruited 25 participants, and collected perceived intensity and discrimination data. We then subjected the data to thorough statistical analyses. Consistent with previous studies, we found that stimulation of the anterior medial tongue region was perceived as more intense than stimulation of lateral and posterior regions. This region also had the best discrimination ability for electrodes. Dividing the stimulated tongue area into 16 distinct regions allowed us to compare perception ability between anterior and posterior regions, medial and lateral regions, and the left and right sides of the tongue. Stimulation of the most

  6. Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

    Science.gov (United States)

    Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

    2016-01-01

    Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Ghrelin stimulates synaptic formation in cultured cortical networks in a dose-dependent manner

    NARCIS (Netherlands)

    Herzig, K.H.; Stoyanova, Irina; le Feber, Jakob; Rutten, Wim

    2013-01-01

    Ghrelin was initially related to appetite stimulation and growth hormone secretion. These findings suggest that ghrelin may provide a novel therapeutic strategy for the treatment of disorders related to synaptic impairment.

  8. Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease.

    Science.gov (United States)

    Ciampi de Andrade, Daniel; Lefaucheur, Jean-Pascal; Galhardoni, Ricardo; Ferreira, Karine S L; Brandão Paiva, Anderson Rodrigues; Bor-Seng-Shu, Edson; Alvarenga, Luciana; Myczkowski, Martin L; Marcolin, Marco Antonio; de Siqueira, Silvia R D T; Fonoff, Erich; Barbosa, Egberto Reis; Teixeira, Manoel Jacobsen

    2012-05-01

    The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P=.019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  9. Iron mediates N-methyl-D-aspartate receptor-dependent stimulation of calcium-induced pathways and hippocampal synaptic plasticity.

    Science.gov (United States)

    Muñoz, Pablo; Humeres, Alexis; Elgueta, Claudio; Kirkwood, Alfredo; Hidalgo, Cecilia; Núñez, Marco T

    2011-04-15

    Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist N-methyl-D-aspartate (NMDA), and the effects of iron addition/chelation on hippocampal basal synaptic transmission and long-term potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodine-reduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP.

  10. Task-dependent activity and connectivity predict episodic memory network-based responses to brain stimulation in healthy aging.

    Science.gov (United States)

    Vidal-Piñeiro, Dídac; Martin-Trias, Pablo; Arenaza-Urquijo, Eider M; Sala-Llonch, Roser; Clemente, Imma C; Mena-Sánchez, Isaias; Bargalló, Núria; Falcón, Carles; Pascual-Leone, Álvaro; Bartrés-Faz, David

    2014-01-01

    Transcranial magnetic stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. We applied a paradigm of repetitive TMS - intermittent theta-burst stimulation - over left inferior frontal gyrus in healthy elders (n = 24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. In the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. The results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

    Science.gov (United States)

    Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

    2016-03-22

    To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

  12. Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

    Science.gov (United States)

    Hanlon, C A; Dowdle, L T; Jones, J L

    2016-01-01

    Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). © 2016 Elsevier Inc. All rights reserved.

  13. The optimal stimulation pattern for skeletal muscle is dependent on muscle length

    NARCIS (Netherlands)

    Mela, P.; Veltink, Petrus H.; Huijing, P.A.J.B.M.; Salmons, S.; Jarvis, J.C.

    2002-01-01

    elicited muscle contraction. Such patterns, providing the desired force output with the minimum number of pulses, may reduce muscle fatigue, which has been shown to correlate to the number of pulses delivered. Applications of electrical stimulation to use muscle as a controllable biological actuator

  14. Is effect of transcranial direct current stimulation on visuomotor coordination dependent on task difficulty?

    Directory of Open Access Journals (Sweden)

    Yong Hyun Kwon

    2015-01-01

    Full Text Available Transcranial direct current stimulation (tDCS, an emerging technique for non-invasive brain stimulation, is increasingly used to induce changes in cortical excitability and modulate motor behavior, especially for upper limbs. The purpose of this study was to investigate the effects of tDCS of the primary motor cortex on visuomotor coordination based on three levels of task difficulty in healthy subjects. Thirty-eight healthy participants underwent real tDCS or sham tDCS. Using a single-blind, sham-controlled crossover design, tDCS was applied to the primary motor cortex. For real tDCS conditions, tDCS intensity was 1 mA while stimulation was applied for 15 minutes. For the sham tDCS, electrodes were placed in the same position, but the stimulator was turned off after 5 seconds. Visuomotor tracking task, consisting of three levels (levels 1, 2, 3 of difficulty with higher level indicating greater difficulty, was performed before and after tDCS application. At level 2, real tDCS of the primary motor cortex improved the accurate index compared to the sham tDCS. However, at levels 1 and 3, the accurate index was not significantly increased after real tDCS compared to the sham tDCS. These findings suggest that tasks of moderate difficulty may improve visuomotor coordination in healthy subjects when tDCS is applied compared with easier or more difficult tasks.

  15. Intensity dependent effects of transcranial direct current stimulation on corticospinal excitability in chronic spinal cord injury.

    Science.gov (United States)

    Murray, Lynda M; Edwards, Dylan J; Ruffini, Giulio; Labar, Douglas; Stampas, Argyrios; Pascual-Leone, Alvaro; Cortes, Mar

    2015-04-01

    To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). Single-blind, randomized, sham-controlled, crossover study. Medical research institute and rehabilitation hospital. Volunteers (N = 9) with chronic SCI and motor dysfunction in wrist extensor muscles. Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis [ECR] muscle representation on the left primary motor cortex, cathode over the right supraorbital area) using 1 mA, 2 mA, or sham stimulation, delivered at rest, with at least 1 week between sessions. Corticospinal excitability was assessed with motor-evoked potentials (MEPs) from the ECR muscle using surface electromyography after transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold, and muscle strength were also investigated. Mean MEP amplitude significantly increased by approximately 40% immediately after 2mA a-tDCS (pre: 0.36 ± 0.1 mV; post: 0.47 ± 0.11 mV; P = .001), but not with 1 mA or sham. Maximal voluntary contraction measures remained unaltered across all conditions. Sensory threshold significantly decreased over time after 1mA (P = .002) and 2mA (P = .039) a-tDCS and did not change with sham. F-wave persistence showed a nonsignificant trend for increase (pre: 32% ± 12%; post: 41% ± 10%; follow-up: 46% ± 12%) after 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. The a-tDCS can transiently raise corticospinal excitability to affected muscles in patients with chronic SCI after 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in patients with SCI and highlights the importance of stimulation intensity. Copyright © 2015 American Congress of Rehabilitation

  16. Dependence of the thermal influence on luminescence lifetimes from quartz on the duration of optical stimulation

    International Nuclear Information System (INIS)

    Chithambo, M.L.

    2003-01-01

    Time-resolved luminescence spectra may be measured from quartz at various stages of continuous optical stimulation in order to investigate properties of the spectra associated with the 'fast', 'medium', and 'slow' components of continuous optically stimulated luminescence (OSL). In this work, temperature related changes of luminescence lifetimes and luminescence intensity, both evaluated from time-resolved luminescence spectra recorded in the 'fast' 'medium' and 'slow' component regions of quartz OSL, have been investigated. The luminescence, stimulated at 525 nm, and measured at intervals between 20 deg. C and 200 deg. C reaches maximum intensity at 100 deg. C and decreases thereafter up to 200 deg. C, the maximum temperature of the investigations. Luminescence lifetimes, on the other hand, remain constant within 40±3 μs between 20 deg. C and 100 deg. C and then decrease down to about μs at 200 deg. C. The initial increase of luminescence intensity with temperature between 20 deg. C and 100 deg. C is discussed in terms of thermal assistance to luminescence stimulation. Beyond 100 deg. C, radiative recombination is affected by quenching of luminescence and reduction in luminescence lifetimes. The activation energy for thermal quenching was evaluated to be in the range 0.63±0.07 eV at all stimulation times and that of thermal assistance was evaluated to be about 0.06 eV for the 'fast' and 'medium' component regions and about 0.1 eV for the 'slow' component region of the OSL

  17. Atractylodes macrocephala Koidz stimulates intestinal epithelial cell migration through a polyamine dependent mechanism.

    Science.gov (United States)

    Song, Hou-Pan; Li, Ru-Liu; Zhou, Chi; Cai, Xiong; Huang, Hui-Yong

    2015-01-15

    decrease of cellular polyamines levels, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, thereby inhibiting IEC-6 cell migration. AMK not only reversed the inhibitory effects of DFMO on the polyamines content, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, but also restored cell migration to control levels. The results obtained from this study revealed that AMK significantly stimulates the migration of IEC-6 cells through a polyamine dependent mechanism, which could accelerate the healing of intestinal injury. These findings suggest the potential value of AMK in curing intestinal diseases characterized by injury and ineffective repair of the intestinal mucosa in clinical practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

    Directory of Open Access Journals (Sweden)

    Wai-Ping Fung-Leung

    Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

  19. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    Science.gov (United States)

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

  20. Personality Disorders, Narcotics, and Stimulants; Relationship in Iranian Male Substance Dependents Population

    OpenAIRE

    Noorbakhsh, Simasadat; Zeinodini, Zahra; Khanjani, Zeynab; Poorsharifi, Hamid; Rajezi Esfahani, Sepideh

    2015-01-01

    Background: Individuals with certain personality disorders, especially the antisocial and borderline personality disorders, are more prone to substance use disorders. Objectives: Regarding the importance of substance use disorders, this study aimed to explore the association between personality disorders and types of used drugs (narcotics and stimulants) in Iranian male substance users. Patients and Methods: The current study was a correlation study. We evaluated 285 male substance users and ...

  1. Prostaglandin E(2) stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells.

    Science.gov (United States)

    Sanzgiri, R P; Araque, A; Haydon, P G

    1999-11-05

    Recent Ca(2+) imaging studies in cell culture and in situ have shown that Ca(2+) elevations in astrocytes stimulate glutamate release and increase neuronal Ca(2+) levels, and that this astrocyte-neuron signaling can be stimulated by prostaglandin E(2) (PGE(2)). We investigated the electrophysiological consequences of the PGE(2)-mediated astrocyte-neuron signaling using whole-cell recordings on cultured rat hippocampal cells. Focal application of PGE(2) to astrocytes evoked a Ca(2+) elevation in the stimulated cell by mobilizing internal Ca(2+) stores, which further propagated as a Ca(2+) wave to neighboring astrocytes. Whole-cell recordings from neurons revealed that PGE(2) evoked a slow inward current in neurons adjacent to astrocytes. This neuronal response required the presence of an astrocyte Ca(2+) wave and was mediated through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Taken together with previous studies, these data demonstrate that PGE(2)-evoked Ca(2+) elevations in astrocyte cause the release of glutamate which activates neuronal ionotropic receptors. Copyright 1999 John Wiley & Sons, Inc.

  2. Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.

    Science.gov (United States)

    Heck, Julie A; Meng, Xiao; Frick, David N

    2009-04-01

    Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis.

  3. Deep brain stimulation for the treatment of Alzheimer disease and dementias.

    Science.gov (United States)

    Laxton, Adrian W; Lozano, Andres M

    2013-01-01

    To review the use of deep brain stimulation (DBS) for treatment of dementia. A PubMed literature search was conducted to identify all studies that have investigated the use of DBS for treatment of dementia. Three studies examined the use of DBS for dementia. One study involved fornix DBS for Alzheimer disease (AD), and two studies involved DBS of the nucleus basalis of Meynert, one to treat AD and one to treat Parkinson disease dementia. Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Pulse and integral optically stimulated luminescence (OSL). Similarities and dissimilarities to thermoluminescence (TL) dose dependence and dose-rate effects

    International Nuclear Information System (INIS)

    Chen, R.; Leung, P.L.

    2000-01-01

    Optically stimulated luminescence (OSL) and thermoluminescence (Tl) are two possible methods to monitor the absorbed radiation in solid samples, and therefore are utilized for dosimetry. For this application, two properties are desirable, namely, linear dose dependence of the measured quantity and dose-rate independence. For Tl, different kinds of super linear dose dependence have been reported in the literature in different materials, and in some cases, dose-rate dependence has also been found. These have been explained as being the result of competition. In OSL, some recent works reported on super linear dose dependence in annealed samples. In the present work, we explain the possible occurrence of these phenomena in OSL by solving numerically the relevant rate equations governing the process during irradiation, relaxation and read-out (heating or light stimulation). The results show that for short pulse OSL, quadratic dose dependence can be expected when only one trapping state and one kind of recombination center are involved and when the excitation starts with empty traps and centers. With the short pulse OSL, the calculation also reveals a possible dose-rate effect. Under the same circumstances, the area under the OSL curve depends linearly on the dose. The dependence of the whole area under the OSL curve on the dose is shown to be super linear when a disconnected trapping state or radiationless center take part in the process. Also, dose-rate effect can be expected in these cases, although no experimental effect of this sort has been reported so far. In pulse OSL, the analogy is made between the measured intensity and the initial rise range of non-first order Tl, whereas for the total area OSL, there is a nearly full analogy with the dose behavior of the Tl maximum. (Author)

  5. miR-375 induces human decidua basalis-derived stromal cells to become insulin-producing cells.

    Science.gov (United States)

    Shaer, Anahita; Azarpira, Negar; Vahdati, Akbar; Karimi, Mohammad Hosein; Shariati, Mehrdad

    2014-09-01

    This paper focuses on the development of renewable sources of isletreplacement tissue for the treatment of type I diabetes mellitus. Placental tissue-derived mesenchymal stem cells (MSCs) are a promising source for regenerative medicine due to their plasticity and easy availability. They have the potential to differentiate into insulin-producing cells. miR-375 is a micro RNA that is expressed in the pancreas and involved in islet development. Human placental decidua basalis MSCs (PDB-MSCs) were cultured from full-term human placenta. The immunophenotype of the isolated cells was checked for CD90, CD105, CD44, CD133 and CD34 markers. The MSCs (P3) were chemically transfected with hsa-miR-375. Total RNA was extracted 4 and 6 days after transfection. The expressions of insulin, NGN3, GLUT2, PAX4, PAX6, KIR6.2, NKX6.1, PDX1, and glucagon genes were evaluated using real-time qPCR. On day 6, we tested the potency of the clusters in response to the high glucose challenge and assessed the presence of insulin and NGN3 proteins via immunocytochemistry. Flow cytometry analysis confirmed that more than 90% of the cells were positive for CD90, CD105 and CD44 and negative for CD133 and CD34. Morphological changes were followed from day 2. Cell clusters formed during day 6. Insulin-producing clusters showed a deep red color with DTZ. The expression of pancreatic-specific transcription factors increased remarkably during the four days after transfection and significantly increased on day 7. The clusters were positive for insulin and NGN3 proteins, and C-peptide and insulin secretion increased in response to changes in the glucose concentration (2.8 mM and 16.7 mM). In conclusion, the MSCs could be programmed into functional insulin-producing cells by transfection of miR-375.

  6. Neomysin inhibits Ca2+-stimulated phosphatidylinositol hydrolysis and protects cultured rat cardiomyocytes from Ca2+-dependent cell injury

    International Nuclear Information System (INIS)

    Babson, J.R.; Dougherty, J.M.

    1991-01-01

    Exposure of cultured rat cardiomyocytes to ionomycin and extracellular Ca 2+ leads to a rapid, sustained increase in intracellular free Ca 2+ as monitored by Ca 2+ -dependent phosphorylase a activation and to a subsequent loss of cardiomyocyte viability as determined by lactate dehydrogenase (LDH) leakage. The intracellular free Ca 2+ increase coincided with a rapid hydrolysis of phosphatidylinositol that preceded cell death. Phosphatidylinositol hydrolysis was monitored by the release of radiolabeled phosphoinositides from cardiomyocytes prelabeled with [2- 3 H]-myo-inositol. Neomycin, a known inhibitor of phospholipase C, inhibited the phosphatidylinositol hydrolysis and markedly reduced the extent of cell injury. Inhibitors of other Ca 2+ -activated processes, including intracellular proteases and phospholipase A 2 , had no effect on ionomycin-mediated cell injury. These data suggest that ionomycin-induced Ca 2+ -dependent cell injury in cultured cardiomyocytes may be due in part to the stimulation of phosphatidylinositol hydrolysis, presumably catalyzed by a Ca 2+ -dependent phospholipase C

  7. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

    DEFF Research Database (Denmark)

    Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller

    2008-01-01

    AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho......-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of c......AMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response....

  8. Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

    DEFF Research Database (Denmark)

    Friis, P; Svehag, S E; Andersen, Ove

    1991-01-01

    . Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited......Conglutinin is a mammalian C-type lectin which shows anti-bacterial activity when tested in vivo and in vitro. This study concerns the effect of conglutinin on the respiratory burst of murine spleen cells, using a chemiluminescence assay for measurement of generated reactive oxygen metabolites...

  9. Dimension-dependent stimulated radiative interaction of a single electron quantum wavepacket

    Science.gov (United States)

    Gover, Avraham; Pan, Yiming

    2018-06-01

    In the foundation of quantum mechanics, the spatial dimensions of electron wavepacket are understood only in terms of an expectation value - the probability distribution of the particle location. One can still inquire how the quantum electron wavepacket size affects a physical process. Here we address the fundamental physics problem of particle-wave duality and the measurability of a free electron quantum wavepacket. Our analysis of stimulated radiative interaction of an electron wavepacket, accompanied by numerical computations, reveals two limits. In the quantum regime of long wavepacket size relative to radiation wavelength, one obtains only quantum-recoil multiphoton sidebands in the electron energy spectrum. In the opposite regime, the wavepacket interaction approaches the limit of classical point-particle acceleration. The wavepacket features can be revealed in experiments carried out in the intermediate regime of wavepacket size commensurate with the radiation wavelength.

  10. CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

    Science.gov (United States)

    Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

    2015-04-01

    The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

  11. Does Childhood Use of Stimulant Medication as a Treatment for ADHD Affect the Likelihood of Future Drug Abuse and Dependence? A Literature Review

    Science.gov (United States)

    Golden, Shawn M.

    2009-01-01

    This article describes the disparate research findings regarding the effects of stimulant medication in subsequent substance abuse and dependence. A minimum of 4 to 5% of children in the United States will be diagnosed with ADHD; thus it is important for parents to be informed when making decisions about the use of stimulant medication to treat…

  12. Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation.

    Science.gov (United States)

    Orellana, Renán A; Jeyapalan, Asumthia; Escobar, Jeffery; Frank, Jason W; Nguyen, Hanh V; Suryawan, Agus; Davis, Teresa A

    2007-11-01

    In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 microg.kg(-1).h(-1)), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis.

  13. The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

    Science.gov (United States)

    Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

    2016-03-01

    Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  14. Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

    Science.gov (United States)

    Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

    2016-11-01

    The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women.

    Science.gov (United States)

    Milivojevic, Verica; Fox, Helen C; Sofuoglu, Mehmet; Covault, Jonathan; Sinha, Rajita

    2016-03-01

    Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and drug craving in cocaine dependent subjects. Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M/8F) (400mg/day) or placebo (14M/9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5-7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. Progesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions, and reduced cocaine

  16. ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells.

    Science.gov (United States)

    Furumatsu, Takayuki; Maehara, Ami; Ozaki, Toshifumi

    2016-07-01

    Proper functioning of the meniscus depends on the composition and organization of its fibrocartilaginous extracellular matrix. We previously demonstrated that the avascular inner meniscus has a more chondrocytic phenotype compared with the outer meniscus. Inhibition of the Rho family GTPase ROCK, the major regulator of the actin cytoskeleton, stimulates the chondrogenic transcription factor Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. However, the crosstalk between ROCK inhibition, SOX9, and other transcription modulators on COL2A1 upregulation remains unclear in meniscus cells. The aim of this study was to investigate the role of SOX9-related transcriptional complex on COL2A1 expression under the inhibition of ROCK in human meniscus cells. Human inner and outer meniscus cells were prepared from macroscopically intact lateral menisci. Cells were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y27632). Gene expression, collagen synthesis, and nuclear translocation of SOX9 and Smad2/3 were analyzed. Treatment of ROCKi increased the ratio of type I/II collagen double positive cells derived from the inner meniscus. In real-time PCR analyses, expression of SOX9 and COL2A1 genes was stimulated by ROCKi treatment in inner meniscus cells. ROCKi treatment also induced nuclear translocation of SOX9 and phosphorylated Smad2/3 in immunohistological analyses. Complex formation between SOX9 and Smad3 was increased by ROCKi treatment in inner meniscus cells. Chromatin immunoprecipitation analyses revealed that association between SOX9/Smad3 transcriptional complex with the COL2A1 enhancer region was increased by ROCKi treatment. This study demonstrated that ROCK inhibition stimulated SOX9/Smad3-dependent COL2A1 expression through the immediate nuclear translocation of Smad3 in inner meniscus cells. Our results suggest that ROCK inhibition can stimulates type II collagen synthesis through the cooperative activation

  17. Inhibiting effects of fructanase on competence-stimulating peptide-dependent quorum sensing system in Streptococcus mutans.

    Science.gov (United States)

    Suzuki, Yusuke; Nagasawa, Ryo; Senpuku, Hidenobu

    2017-09-01

    Streptococcus mutans produces glucosyltransferases encoded by the gtfB and gtfC genes, which synthesize insoluble glucan, and both insoluble and soluble glucans by conversion of sucrose, and are known as principal agents to provide strong biofilm formation and demineralization on tooth surfaces. S. mutans possess a Com-dependent quorum sensing (QS) system, which is important for survival in severe conditions. The QS system is stimulated by the interaction between ComD {Receptor to competence-stimulating peptide (CSP)} encoded by the comD and CSP encoded by the comC, and importantly associated with bacteriocin production and genetic competence. Previously, we found enzyme fructanase (FruA) as a new inhibitor for the glucan-dependent biofilm formation. In the present study, inhibiting effects by FruA on glucan-independent biofilm formation of S. mutans UA159, UA159.gtfB - , UA159.gtfC - , and UA159.gtfBC - were observed in sucrose and no sucrose sugars-supplemented conditions using the plate assay. The reduction of UA159.comC - and UA159.comD - biofilm formation were also observed as compared with UA159 in same conditions. These results suggested that inhibitions of glucan-independent and Com-dependent biofilm formation were involved in the inhibiting mechanism by FruA. To more thoroughly investigate effects by FruA on the QS system, we examined on CSP-stimulated and Com-dependent bacteriocin production and genetic transformation. FruA inhibited bacteriocin production in collaboration with CSP and genetic transformation in bacterial cell conditions treated with FruA. Our findings show that FruA has multiple effects that inhibit survival functions of S. mutans, including biofilm formation and CSP-dependent QS responses, indicating its potential use as an agent for prevention of dental caries. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase-Dependent Stimulation of Renal Klotho Expression by Spironolactone

    Directory of Open Access Journals (Sweden)

    Ioana Alesutan

    2013-11-01

    Full Text Available Background: Klotho, a transmembrane protein, protease and hormone mainly expressed in kidney, is required for the suppression of 1,25(OH2D3-generating 25-hydroxyvitamin D3 1-alpha-hydroxylase (Cyp27b1 by FGF23. Conversely, 1,25(OH2D3 stimulates, by activating the vitamin D3 receptor (Vdr, the expression of klotho, thus establishing a negative feedback loop. Klotho protects against renal and vascular injury. Klotho deficiency accelerates aging and early death, effects at least partially due to excessive formation of 1,25(OH2D3 and subsequent hyperphosphatemia. Klotho expression is inhibited by aldosterone. The present study explored the interaction of aldosterone and DOCA as well as the moderately selective mineralocorticoid receptor antagonist spironolactone on klotho expression. Methods: mRNA levels were determined utilizing quantitative RT-PCR in human embryonic kidney cells (HEK293 or in renal tissues from mice without or with prior mineralocorticoid (aldosterone or DOCA and/or spironolactone treatment. In HEK293 cells, protein levels were determined by western blotting. The experiments in HEK293 cells were performed without or with silencing of CYP27B1, of vitamin D3 receptor (VDR or of mineralocorticoid receptor (NR3C2. Results: In HEK293 cells aldosterone and in mice DOCA significantly decreased KLOTHO gene expression, effects opposed by spironolactone treatment. Spironolactone treatment alone significantly increased KLOTHO and CYP27B1 transcript levels in HEK293 cells (24 hours and mice (8 hours or 5 days. Moreover, spironolactone significantly increased klotho and CYP27B1 protein levels in HEK293 cells (48 hours. Reduced NR3C2 expression following silencing did not significantly affect KLOTHO and CYP27B1 transcript levels in presence or absence of spironolactone. Silencing of CYP27B1 and VDR significantly blunted the stimulating effect of spironolactone on KLOTHO mRNA levels in HEK293 cells. Conclusion: Besides blocking the effects of

  19. Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

    Science.gov (United States)

    Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

    2017-12-01

    Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

  20. The Effect of Cerebellar Transcranial Direct Current Stimulation on A Throwing Task Depends on Individual Level of Task Performance.

    Science.gov (United States)

    Mizuguchi, Nobuaki; Katayama, Takashi; Kanosue, Kazuyuki

    2018-02-10

    The effect of cerebellar transcranial direct current stimulation (tDCS) on motor performance remains controversial. Some studies suggest that the effect of tDCS depends upon task-difficulty and individual level of task performance. Here, we investigated whether the effect of cerebellar tDCS on the motor performance depends upon the individual's level of performance. Twenty-four naïve participants practiced dart throwing while receiving a 2-mA cerebellar tDCS for 20 min under three stimulus conditions (anodal-, cathodal-, and sham-tDCS) on separate days with a double-blind, counter-balanced cross-over design. Task performance was assessed by measuring the distance between the center of the bull's eye and the dart's position. Although task performance tended to improve throughout the practice under all stimulus conditions, improvement within a given day was not significant as compared to the first no-stimulus block. In addition, improvement did not differ among stimulation conditions. However, the magnitude of improvement was associated with an individual's level of task performance only under cathodal tDCS condition (p performance improvement only for the sub-group of participants with lower performance levels as compared to that with sham-tDCS (p task performance. Thus, cerebellar tDCS would facilitate learning of a complex motor skill task only in a subset of individuals. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Substrate dependence of electron-stimulated O - yields from dissociative electron attachment to physisorbed O2

    Science.gov (United States)

    Huels, M. A.; Parenteau, L.; Sanche, L.

    1994-03-01

    We present measurements of O- electron stimulated desorption yields obtained under identical experimental conditions from 0.15 monolayers (ML) of O2 deposited onto disordered substrates consisting of 4 ML of either Kr, Xe, C2H6, C2H4, N2O, CH3Cl, or H2O, all condensed on Pt (polycrystalline). The resulting O- yield functions, for incident electron energies below 20 eV, are compared to that obtained from the O2/Kr solid; this allows us to assess the order of magnitude effects of the local substrate environment on dissociative electron attachment (DEA) via the 2Πu and gas phase forbidden 2Σ+g,u resonances of O-2. We note that, in addition to electron energy losses in the substrate prior to DEA to O2 and post-dissociation interactions of the O- with the substrate molecules, charge or energy transfer from the O-2 transient anion to a substrate molecule, and capture of the incident electron into a dissociative anion resonance of the substrate molecule may contribute to a reduced O- yield from the physisorbed O2. In the case of O2 deposited on amorphous ice, we find that the O- signal from DEA to O2 is completely absent for electron energies below 14 eV; we attribute this to a complete quenching of the dissociative O-2(2Πu, 2Σ+) resonances by the adjacent water molecules.

  2. Change of central cholinergic receptors following lesions of nucleus basalis magnocellularis in rats: search for an imaging index suitable for the early detection of Alzheimer's disease

    International Nuclear Information System (INIS)

    Ogawa, Mikako; Iida, Yasuhiko; Nakagawa, Masaki; Kuge, Yugi; Kawashima, Hidekazu; Tominaga, Akiko; Ueda, Masashi; Magata, Yasuhiro; Saji, Hideo

    2006-01-01

    Cholinergic system in the central nervous system is involved in the memory function. Thus, because the dysfunction of cholinergic system that project to the cerebral cortex from nucleus basalis of Meynert (nbM) would be implicated in the memory function deficits in Alzheimer's disease (AD), evaluating cholinergic function may be useful for the early detection of AD. In this study, because the nucleus basalis magnocellularis (NBM) in rats is equivalent to nbM in human, we investigated the change in cholinergic receptors in the frontal cortex of rats with unilateral lesion to the NBM to find an appropriate index for the early detection of AD using techniques of nuclear medicine. The right NBM was injected with ibotenic acid. [ 18 F]FDG-PET images were obtained 3 days later. Some rats were sacrificed at 1 week, whereas others were subjected to a second [ 18 F]FDG-PET at 4 weeks then sacrificed for membrane preparation. The prepared membranes were subjected to radioreceptor assays to measure the density of nicotinic and muscarinic acetylcholine receptors. Glucose metabolism had decreased on the damaged side compared to the control side at 3 days, but at 4 weeks, there was no difference between the sides. Nicotinic acetylcholine receptors had significantly decreased in density compared to the control side at both 1 and 4 weeks. However, muscarinic receptors were not affected. These results suggested that neuronal dysfunction in AD could be diagnosed at an early stage by imaging nicotinic acetylcholine receptors

  3. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

    OpenAIRE

    Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

    2011-01-01

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess...

  4. TNF-alpha stimulates Akt by a distinct aPKC-dependent pathway in premalignant keratinocytes

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    , ERK1/2 and p38. The specific peptide blocking the activity of the atypical protein kinase C (aPKC) species zeta and iota/lambda abrogated the effects of TNF-alpha on Akt and ERK1/2 but increased the activation of p38. The TNF-alpha-dependent phosphorylation of Akt-ERK1/2 was slightly decreased by NF...

  5. Stimulation of NADH-dependent microsomal DNA strand cleavage by rifamycin SV.

    OpenAIRE

    Kukiełka, E; Cederbaum, A I

    1995-01-01

    Rifamycin SV is an antibiotic anti-bacterial agent used in the treatment of tuberculosis. This drug can autoxidize, especially in the presence of metals, and generate reactive oxygen species. A previous study indicated that rifamycin SV can increase NADH-dependent microsomal production of reactive oxygen species. The current study evaluated the ability of rifamycin SV to interact with iron and increase microsomal production of hydroxyl radical, as detected by conversion of supercoiled plasmid...

  6. 5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

    Directory of Open Access Journals (Sweden)

    Ricardo Alves Luz

    2014-01-01

    Full Text Available The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LTB4, a 5-lipoxygenase (5-LO metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1 were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

  7. Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

    Science.gov (United States)

    Lesage, Elise; Aronson, Sarah E; Sutherland, Matthew T; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A

    2017-06-01

    Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline

  8. Dose-dependent optically stimulated luminescence of synthetic quartz at room temperature

    International Nuclear Information System (INIS)

    Kale, Y.D.; Gandhi, Y.H.; Gartia, R.K.

    2008-01-01

    Physical conditions such as annealing temperature, duration of annealing, ionizing radiation, etc., play a significant role in the applications of optically stimulated luminescence (OSL) dating as well as OSL dosimetry. Many efforts are made to understand the effect of these physical parameters on quartz specimens owing to its use in such applications. Such factors induce changes in OSL decay pattern. The definite correlation between color centers and luminescence sensitivity can be established on account of such pre-treatments to the specimen. The purpose of present investigations is to study the effect of ionizing radiation under identical physical conditions on OSL properties measured at room temperature. The shapes of decay curve and dose-response data are considered for this purpose. This study can reveal the changes in color centers in response to the pre-conditions to the specimen. It was found that the OSL decay remains slow and OSL properties change systematically with the rise in beta dose up to a critical dose; however, it changes the pattern when the beta exposure to the specimen was increased higher than the critical dose. This critical dose was found to be different for different temperature of annealing. The shape of decay curve up to the critical dose was also studied by considering the difference of OSL intensities between two successive durations from the observed OSL decay data. The results are explained based on the changes in available shallow traps during OSL measurement at room temperature with changes in pre-conditions to the specimens. The results also have been confirmed with the corresponding changes in ESR signals

  9. Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on delta-opioid receptor stimulation.

    Science.gov (United States)

    Panneerselvam, Mathivadhani; Tsutsumi, Yasuo M; Bonds, Jacqueline A; Horikawa, Yousuke T; Saldana, Michelle; Dalton, Nancy D; Head, Brian P; Patel, Piyush M; Roth, David M; Patel, Hemal H

    2010-11-01

    Epicatechin, a flavonoid, is a well-known antioxidant linked to a variety of protective effects in both humans and animals. In particular, its role in protection against cardiovascular disease has been demonstrated by epidemiologic studies. Low-dose epicatechin, which does not have significant antioxidant activity, is also protective; however, the mechanism by which low-dose epicatechin induces this effect is unknown. Our laboratory tested the hypothesis that low-dose epicatechin mediates cardiac protection via opioid receptor activation. C57BL/6 mice were randomly assigned to 1 of 10 groups: control, epicatechin, naloxone (nonselective opioid receptor antagonist), epicatechin + naloxone, naltrindole (δ-specific opioid receptor antagonist), epicatechin + naltrindole, norbinaltorphimine (nor-BNI, κ-specific opioid receptor antagonist), epicatechin + nor-BNI, 5-hydroxydecanoic acid [5-HD, ATP-sensitive potassium channel antagonist], and epicatechin + 5-HD. Epicatechin (1 mg/kg) or other inhibitors (5 mg/kg) were administered by oral gavage or intraperitoneal injection, respectively, daily for 10 days. Mice were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion, and infarct size was determined via planimetry. Whole heart homogenates were assayed for downstream opioid receptor signaling targets. Infarct size was significantly reduced in epicatechin- and epicatechin + nor-BNI-treated mice compared with control mice. This protection was blocked by naloxone, naltrindole, and 5-HD. Epicatechin and epicatechin + nor-BNI increased the phosphorylation of Src, Akt, and IκBα, while simultaneously decreasing the expression of c-Jun NH(2)-terminal kinase and caspase-activated DNase. All signaling effects are consistent with opioid receptor stimulation and subsequent cardiac protection. Naloxone, naltrindole, and 5-HD attenuated these effects. In conclusion, epicatechin acts via opioid receptors and more specifically through the δ-opioid receptor to

  10. Calcium/calmodulin-dependent kinase II and nitric oxide synthase 1-dependent modulation of ryanodine receptors during β-adrenergic stimulation is restricted to the dyadic cleft.

    Science.gov (United States)

    Dries, Eef; Santiago, Demetrio J; Johnson, Daniel M; Gilbert, Guillaume; Holemans, Patricia; Korte, Sanne M; Roderick, H Llewelyn; Sipido, Karin R

    2016-10-15

    The dyadic cleft, where coupled ryanodine receptors (RyRs) reside, is thought to serve as a microdomain for local signalling, as supported by distinct modulation of coupled RyRs dependent on Ca 2+ /calmodulin-dependent kinase II (CaMKII) activation during high-frequency stimulation. Sympathetic stimulation through β-adrenergic receptors activates an integrated signalling cascade, enhancing Ca 2+ cycling and is at least partially mediated through CaMKII. Here we report that CaMKII activation during β-adrenergic signalling is restricted to the dyadic cleft, where it enhances activity of coupled RyRs thereby contributing to the increase in diastolic events. Nitric oxide synthase 1 equally participates in the local modulation of coupled RyRs. In contrast, the increase in the Ca 2+ content of the sarcoplasmic reticulum and related increase in the amplitude of the Ca 2+ transient are primarily protein kinase A-dependent. The present data extend the concept of microdomain signalling in the dyadic cleft and give perspectives for selective modulation of RyR subpopulations and diastolic events. In cardiac myocytes, β-adrenergic stimulation enhances Ca 2+ cycling through an integrated signalling cascade modulating L-type Ca 2+ channels (LTCCs), phospholamban and ryanodine receptors (RyRs). Ca 2+ /calmodulin-dependent kinase II (CaMKII) and nitric oxide synthase 1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca 2+ microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole-cell voltage-clamp and confocal line-scan imaging with Fluo-4 as a [Ca 2+ ] i indicator. Following conditioning depolarizing pulses, spontaneous RyR activity is recorded as Ca 2+ sparks, which are assigned to coupled and non-coupled RyR clusters. Isoproterenol (ISO) (10 nm) increases Ca 2+ spark frequency in both populations of RyRs. However, CaMKII inhibition reduces

  11. Mistletoe (Viscum album) infestation in the Scots pine stimulates drought-dependent oxidative damage in summer.

    Science.gov (United States)

    Mutlu, Salih; Ilhan, Veli; Turkoglu, Halil Ibrahim

    2016-04-01

    This study sought to contribute to the understanding of the detrimental effect of the mistletoe (Viscum albumL.), a hemiparasitic plant, on the mortality of the Scots pine (Pinus sylvestrisL.). Fieldwork was conducted in the town of Kelkit (Gumushane province, Turkey) from April to October in 2013. Pine needles of similar ages were removed from the branches of mistletoe-infested and noninfested Scots pine plants, then transported to the laboratory and used as research materials. The effects of the mistletoe on the Scots pine during infestation were evaluated by determining the levels of water, electrolyte leakage (EL), malondialdehyde (MDA, being a product of lipid peroxidation) and reactive oxygen species (ROS) such as superoxide anion (O2 (-•)), hydrogen peroxide (H2O2) and hydroxyl radical ((•)OH). In addition, the activities of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) were measured in the same samples. The highest level of drought stress was found in summer (especially in August) as a result of the lowest water content in the soil and the highest average temperature occurring in these months. The drought stress induced by mistletoe infestation caused a regular decrease in water content, while it increased the levels of EL, MDA and ROS (H2O2, O2 (-•)and(•)OH). The infestation also stimulated the activities of CAT and POX, with the exception of SOD. On the other hand, in August, when the drought conditions were the harshest, the levels of EL and MDA, which are two of the most important indicator parameters for oxidative stress, as well as the levels of H2O2and(•)OH, which are two of the ROS leading to oxidative stress, reached the highest values in both infested and noninfested needles, whereas the O2 (-•)level decreased. For the same period and needles, CAT activity increased, while SOD activity decreased. Peroxidase activity, however, did not exhibit a significant change. Our findings indicate

  12. Dependences of the geometrical parameters of cell community on stimulation voltage and frequency in chick embryonic cardiomyocytes

    Science.gov (United States)

    Fujii, Koki; Nomura, Fumimasa; Kaneko, Tomoyuki

    2018-03-01

    To investigate the optimal conditions for electrical stimulation, communities of lined-up chick embryonic cardiomyocytes were evaluated in terms of their threshold voltage for pacing (PVMin) and the half-maximum paced frequency (PF50), with a focus on the following factors: (1) the orientation of the major axis of cell communities to the electric field (EF) direction as the external factor; (2) the number of cells in a cell community, the length of the cell community, and the mean length of cells comprising the community as the internal factors. Firstly, PVMin decreased with increasing length of the cell network oriented parallel to the EF. PVMin was approximately 0.041 ± 0.025 V/mm when the community was sufficiently long. On the other hand, PVMin in the orthogonal orientation was constant at 1.7 ± 0.047 V/mm with no dependence on the length of the cell network. Secondly, we found that PF50 increased with increasing length of the cell network or the number of cells in the network; the PF50 values were 2.03 ± 0.05 and 3.39 ± 0.05 Hz when the respective cell network lengths were 100 µm (n = 43) and more than 300 µm (n = 6) and the cells were oriented parallel to the EF. These findings indicate that it is important to suppress ventricular fibrillation with minimal efficient stimulation by considering the EF direction with respect to the orientation of cardiomyocytes. Furthermore, expanded cells showed the loss of ability to respond to stimulation at higher frequencies. Cardiomyocytes combined with seeded fibroblasts as a cell network at a low density are a possible model of a ventricular remodeling heart.

  13. Regenerative Rehabilitation: Combining Stem Cell Therapies and Activity-Dependent Stimulation.

    Science.gov (United States)

    Moritz, Chet T; Ambrosio, Fabrisia

    2017-07-01

    The number of clinical trials in regenerative medicine is burgeoning, and stem cell/tissue engineering technologies hold the possibility of becoming the standard of care for a multitude of diseases and injuries. Advances in regenerative biology reveal novel molecular and cellular targets, with potential to optimize tissue healing and functional recovery, thereby refining rehabilitation clinical practice. The purpose of this review is to (1) highlight the potential for synergy between the fields of regenerative medicine and rehabilitation, a convergence of disciplines known as regenerative rehabilitation; (2) provide translational examples of regenerative rehabilitation within the context of neuromuscular injuries and diseases; and (3) offer recommendations for ways to leverage activity dependence via combined therapy and technology, with the goal of enhancing long-term recovery. The potential clinical benefits of regenerative rehabilitation will likely become a critical aspect in the standard of care for many neurological and musculoskeletal disorders.

  14. Haptic subjective vertical shows context dependence: task and vision play a role during dynamic tilt stimulation.

    Science.gov (United States)

    Wright, William Geoffrey; Glasauer, Stefan

    2003-10-01

    Perceiving one's vertical is an integral part of efficiently functioning in an environment physically polarized along that dimension. How one determines the direction of gravity is not a task left only to inertial sensors, such as the vestibular organs, rather as numerous studies have shown, this task is influenced visually and somatosensorily. In addition, there is evidence that higher order cognitive effects such as expectancies and context are critical in perception of the vertical. One's ability to integrate these various inputs during normal activity is not generally questioned, one's doubts being satisfied by observing a waiter navigating a crowded restaurant with a tray balanced on one hand, neither tripping or dropping an entree. But how these various sources are integrated is still debated. Most research focuses on subjective vertical perception used visual matching/alignment tasks, verbal reports, or saccadic eye movements as a dependent measure. Although a motor task involving a joystick or indicator to be aligned with gravity without visual feedback is used much less frequently, there is good evidence that individuals easily orient limbs to an external gravity-aligned coordinate axis while being statically tilted. By exposure to a dynamic situation, the central nervous system should be no more challenged by the task of determining the subjective vertical than during static conditions, because our spatial orientation systems were likely selected for just that. In addition, the sensitive calibration between visual and other sensory input also must have been key to its selection. This sensory interaction can be tested by changing the relation between the various sources. With the advent of virtual reality technology, a complex and "natural" visual stimulus is achievable and is easily manipulable. How one tests perception of verticality is also a pertinent question when researching spatial orientation systems. The system's performance may be better

  15. Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

    2014-01-01

    signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot......Background: Metformin-induced activation of AMPK has been associated with enhanced glucose uptake in skeletal muscle but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent upon AMPK...... analyzes. Results: Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (45%, P...

  16. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.

    Science.gov (United States)

    Licata, Stephanie C; Lowen, Steven B; Trksak, George H; Maclean, Robert R; Lukas, Scott E

    2011-08-15

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

    Science.gov (United States)

    Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

    2011-01-01

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782

  18. Characterization of gas-aerosol interaction kinetics using morphology dependent stimulated Raman scattering

    International Nuclear Information System (INIS)

    Aker, P.M.

    1993-01-01

    This study is aimed at characterizing the influence of aerosol surface structure on the kinetics of gas-aerosol interactions. Changes in gas phase chemical reaction rates as a function of exposure to a specific aerosol are measured with aerosols having different surface properties due to the composition and/or temperature of the material making up the aerosol. The kinetic data generated can be used directly in atmospheric modeling calculations. The surface structure of the aerosol is using morphology-dependent enhancement of simulated Raman scattering (MDSRS). Detailed dynamics of gas-aerosol interactions can be obtained by correlating the change in the reaction rate with change in surface structure and by monitoring the change in aerosol surface structure during, the course of the reaction. This dynamics information can be used to generate kinetic data for systems which are similar in nature to those studied, but are not amenable to laboratory investigation. We show here that increased MDSRS sensitivity is achieved by using an excitation laser source that has a narrow linewidth and we have been able to detect sulfate anion concentrations much lower than previously reported. We have shown that the linewidth of the MDSRS mode excited in a droplet is limited by the laser linewidth. This is a positive result for it eases our ability to quantify the MDSRS gain equation. This result also suggests that MDSRS signal size should be independent of droplet size, and preliminary experiments confirm this hypothesis

  19. Troglitazone stimulates β-arrestin-dependent cardiomyocyte contractility via the angiotensin II type 1A receptor

    International Nuclear Information System (INIS)

    Tilley, Douglas G.; Nguyen, Anny D.; Rockman, Howard A.

    2010-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPARγ-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPARγ activity, thus we hypothesized that a PPARγ agonist may exert physiologic effects via the angiotensin II type 1 A receptor (AT1 A R). In AT1 A R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPARγ agonist troglitazone (Trog) enhanced AT1 A R internalization and recruitment of endogenous β-arrestin1/2 (βarr1/2) to the AT1 A R. A fluorescence assay to measure diacylglycerol (DAG) accumulation showed that although Ang II induced AT1 A R-G q protein-mediated DAG accumulation, Trog had no impact on DAG generation. Trog-mediated recruitment of βarr1/2 was selective to AT1 A R as the response was prevented by an ARB- and Trog-mediated βarr1/2 recruitment to β1-adrenergic receptor (β1AR) was not observed. In isolated mouse cardiomyocytes, Trog increased both % and rate of cell shortening to a similar extent as Ang II, effects which were blocked with an ARB. Additionally, these effects were found to be βarr2-dependent, as cardiomyocytes isolated from βarr2-KO mice showed blunted contractile responses to Trog. These findings show for the first time that the PPARγ agonist Trog acts at the AT1 A R to simultaneously block G q protein activation and induce the recruitment of βarr1/2, which leads to an increase in cardiomyocyte contractility.

  20. Angular dependence of dose sensitivity of nanoDot optically stimulated luminescent dosimeters in different radiation geometries

    Energy Technology Data Exchange (ETDEWEB)

    Jursinic, Paul A., E-mail: pjursinic@wmcc.org [West Michigan Cancer Center, 200 North Park Street, Kalamazoo, Michigan 49007 (United States)

    2015-10-15

    Purpose: A type of in vivo dosimeter, an optically stimulated luminescent dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence of radiation. This work measures how angular dependence of a nanoDot changes with the geometry of the phantom in which irradiation occurs and with the intrinsic structure of the nanoDot. Methods: The OSLDs used in this work were nanoDot dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x-rays. NanoDots with various intrinsic sensitivities were irradiated in numerous phantoms that had geometric shapes of cylinders, rectangles, and a cube. Results: No angular dependence was seen in cylindrical phantoms, cubic phantoms, or rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular dependence of 1% was observed in rectangular phantoms with a thickness to width of 0.433–0.633. A group of nanoDots had sensitive layers with mass density of 2.42–2.58 g/cm{sup 3} and relative sensitivity of 0.92–1.09 and no difference in their angular dependence. Within experimental uncertainty, nanoDot measurements agree with a parallel-plate ion chamber at a depth of maximum dose. Conclusions: When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a maximum angular dependence of 1% or less at an incidence angle of 90°. For a sample of 78 new nanoDots, the range of their relative intrinsic sensitivity is 0.92–1.09. For a sample of ten nanoDots, on average, the mass in the sensitive layer is 73.1% Al{sub 2}O{sub 3}:C and 26.9% polyester. The mass density of the sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm{sup 3}. The angular dependence is not related to Al{sub 2}O{sub 3}:C loading of the nanoDot disc. The nanoDot at the depth of maximum dose has no more angular dependence than a parallel-plate ion chamber.

  1. Contact- and Protein Transfer-Dependent Stimulation of Assembly of the Gliding Motility Machinery in Myxococcus xanthus.

    Directory of Open Access Journals (Sweden)

    Beata Jakobczak

    2015-07-01

    Full Text Available Bacteria engage in contact-dependent activities to coordinate cellular activities that aid their survival. Cells of Myxococcus xanthus move over surfaces by means of type IV pili and gliding motility. Upon direct contact, cells physically exchange outer membrane (OM lipoproteins, and this transfer can rescue motility in mutants lacking lipoproteins required for motility. The mechanism of gliding motility and its stimulation by transferred OM lipoproteins remain poorly characterized. We investigated the function of CglC, GltB, GltA and GltC, all of which are required for gliding. We demonstrate that CglC is an OM lipoprotein, GltB and GltA are integral OM β-barrel proteins, and GltC is a soluble periplasmic protein. GltB and GltA are mutually stabilizing, and both are required to stabilize GltC, whereas CglC accumulate independently of GltB, GltA and GltC. Consistently, purified GltB, GltA and GltC proteins interact in all pair-wise combinations. Using active fluorescently-tagged fusion proteins, we demonstrate that GltB, GltA and GltC are integral components of the gliding motility complex. Incorporation of GltB and GltA into this complex depends on CglC and GltC as well as on the cytoplasmic AglZ protein and the inner membrane protein AglQ, both of which are components of the gliding motility complex. Conversely, incorporation of AglZ and AglQ into the gliding motility complex depends on CglC, GltB, GltA and GltC. Remarkably, physical transfer of the OM lipoprotein CglC to a ΔcglC recipient stimulates assembly of the gliding motility complex in the recipient likely by facilitating the OM integration of GltB and GltA. These data provide evidence that the gliding motility complex in M. xanthus includes OM proteins and suggest that this complex extends from the cytoplasm across the cell envelope to the OM. These data add assembly of gliding motility complexes in M. xanthus to the growing list of contact-dependent activities in bacteria.

  2. Synchrotron- and focal plane array-based Fourier-transform infrared spectroscopy differentiates the basalis and functionalis epithelial endometrial regions and identifies putative stem cell regions of human endometrial glands.

    Science.gov (United States)

    Theophilou, Georgios; Morais, Camilo L M; Halliwell, Diane E; Lima, Kássio M G; Drury, Josephine; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Hapangama, Dharani K; Martin, Francis L

    2018-05-09

    The cyclical process of regeneration of the endometrium suggests that it may contain a cell population that can provide daughter cells with high proliferative potential. These cell lineages are clinically significant as they may represent clonogenic cells that may also be involved in tumourigenesis as well as endometriotic lesion development. To determine whether the putative stem cell location within human uterine tissue can be derived using vibrational spectroscopy techniques, normal endometrial tissue was interrogated by two spectroscopic techniques. Paraffin-embedded uterine tissues containing endometrial glands were sectioned to 10-μm-thick parallel tissue sections and were floated onto BaF 2 slides for synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy and globar focal plane array-based FTIR spectroscopy. Different spectral characteristics were identified depending on the location of the glands examined. The resulting infrared spectra were subjected to multivariate analysis to determine associated biophysical differences along the length of longitudinal and crosscut gland sections. Comparison of the epithelial cellular layer of transverse gland sections revealed alterations indicating the presence of putative transient-amplifying-like cells in the basalis and mitotic cells in the functionalis. SR-FTIR microspectroscopy of the base of the endometrial glands identified the location where putative stem cells may reside at the same time pointing towards ν s PO 2 - in DNA and RNA, nucleic acids and amide I and II vibrations as major discriminating factors. This study supports the view that vibration spectroscopy technologies are a powerful adjunct to our understanding of the stem cell biology of endometrial tissue. Graphical abstract ᅟ.

  3. Sunlight Triggers Cutaneous Lupus through a Colony Stimulating Factor-1 (CSF-1) Dependent Mechanism in MRL-Faslpr mice

    Science.gov (United States)

    Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T.; Lucas, Julie A.; Rabacal, Whitney A.; Croker, Byron P.; Zong, Xiao-Hua; Stanley, E. Richard; Kelley, Vicki R.

    2008-01-01

    Sunlight (UVB) triggers cutaneous (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø) -mediated mechanism in MRL-Faslpr mice. By constructing mutant MRL-Faslpr strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex-vivo gene transfer to deliver CSF-1 intra-dermally, we determined that CSF-1 induces CLE in lupus-susceptible, MRL-Faslpr mice, but not in lupus-resistant, BALB/c mice. Notably, UVB incites an increase in Mø, apoptosis in the skin and CLE in MRL-Faslpr, but not in CSF-1-deficient MRL-Faslpr mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Mø that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Faslpr, but not lupus-resistant BALB/c mice. Taken together, we envision CSF-1 as the “match” and lupus-susceptibility as the “tinder” leading to CLE. PMID:18981160

  4. The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

    Directory of Open Access Journals (Sweden)

    Anna Sommansson

    Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

  5. Inhibiting effects of Streptococcus salivarius on competence-stimulating peptide-dependent biofilm formation by Streptococcus mutans.

    Science.gov (United States)

    Tamura, S; Yonezawa, H; Motegi, M; Nakao, R; Yoneda, S; Watanabe, H; Yamazaki, T; Senpuku, H

    2009-04-01

    The effects of Streptococcus salivarius on the competence-stimulating peptide (CSP)-dependent biofilm formation by Streptococcus mutans were investigated. Biofilms were grown on 96-well microtiter plates coated with salivary components in tryptic soy broth without dextrose supplemented with 0.25% sucrose. Biofilm formations were stained using safranin and quantification of stained biofilms was performed by measuring absorbance at 492 nm. S. mutans formed substantial biofilms, whereas biofilms of S. salivarius were formed poorly in the medium conditions used. Furthermore, in combination cultures, S. salivarius strongly inhibited biofilm formation when cultured with S. mutans. This inhibition occurred in the early phase of biofilm formation and was dependent on inactivation of the CSP of S. mutans, which is associated with competence, biofilm formation, and antimicrobial activity of the bacterium, and is induced by expression of the comC gene. Comparisons between the S. mutans clinical strains FSC-3 and FSC-3DeltaglrA in separate dual-species cultures with S. salivarius indicated that the presence of the bacitracin transport ATP-binding protein gene glrA caused susceptibility to inhibition of S. mutans biofilm formation by S. salivarius, and was also associated with the regulation of CSP production by com gene-dependent quorum sensing systems. It is considered that regulation of CSP by glrA in S. mutans and CSP inactivation by S. salivarius are important functions for cell-to-cell communication between biofilm bacteria and oral streptococci such as S. salivarius. Our results provide useful information for understanding the ecosystem of oral streptococcal biofilms, as well as the competition between and coexistence of multiple species in the oral cavity.

  6. Short-term quality of life after subthalamic stimulation depends on non-motor symptoms in Parkinson's disease.

    Science.gov (United States)

    Dafsari, Haidar Salimi; Weiß, Luisa; Silverdale, Monty; Rizos, Alexandra; Reddy, Prashanth; Ashkan, Keyoumars; Evans, Julian; Reker, Paul; Petry-Schmelzer, Jan Niklas; Samuel, Michael; Visser-Vandewalle, Veerle; Antonini, Angelo; Martinez-Martin, Pablo; Ray-Chaudhuri, K; Timmermann, Lars

    2018-02-24

    Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced Parkinson's disease (PD). However, considerable inter-individual variability has been observed for QoL outcome. We hypothesized that demographic and preoperative NMS characteristics can predict postoperative QoL outcome. In this ongoing, prospective, multicenter study (Cologne, Manchester, London) including 88 patients, we collected the following scales preoperatively and on follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS), NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, -complications, and -activities of daily living, levodopa equivalent daily dose. We dichotomized patients into "QoL responders"/"non-responders" and screened for factors associated with QoL improvement with (1) Spearman-correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions using aforementioned "responders/non-responders" as dependent variable. All outcomes improved significantly on follow-up. However, approximately 44% of patients were categorized as "QoL non-responders". Spearman-correlations, linear and logistic regression analyses were significant for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder voiding) as significant contributors to QoL outcome. Our results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS. Copyright © 2018. Published by Elsevier

  7. Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2.

    Science.gov (United States)

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

    2015-06-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production. This study investigated the mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. After stimulation with HNE to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production. Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. HIV-1 stimulates nuclear entry of amyloid beta via dynamin dependent EEA1 and TGF-β/Smad signaling

    International Nuclear Information System (INIS)

    András, Ibolya E.; Toborek, Michal

    2014-01-01

    Clinical evidence indicates increased amyloid deposition in HIV-1-infected brains, which contributes to neurocognitive dysfunction in infected patients. Here we show that HIV-1 exposure stimulates amyloid beta (Aβ) nuclear entry in human brain endothelial cells (HBMEC), the main component of the blood–brain barrier (BBB). Treatment with HIV-1 and/or Aβ resulted in concurrent increase in early endosomal antigen-1 (EEA1), Smad, and phosphorylated Smad (pSmad) in nuclear fraction of HBMEC. A series of inhibition and silencing studies indicated that Smad and EEA1 closely interact by influencing their own nuclear entry; the effect that was attenuated by dynasore, a blocker of GTP-ase activity of dynamin. Importantly, inhibition of dynamin, EEA1, or TGF-β/Smad effectively attenuated HIV-1-induced Aβ accumulation in the nuclei of HBMEC. The present study indicates that nuclear uptake of Aβ involves the dynamin-dependent EEA1 and TGF-β/Smad signaling pathways. These results identify potential novel targets to protect against HIV-1-associated dysregulation of amyloid processes at the BBB level. - Highlights: • HIV-1 induces nuclear accumulation of amyloid beta (Aβ) in brain endothelial cells. • EEA-1 and TGF-Β/Smad act in concert to regulate nuclear entry of Aβ. • Dynamin appropriates the EEA-1 and TGF-Β/Smad signaling. • Dynamin serves as a master regulator of HIV-1-induced nuclear accumulation of Aβ

  9. Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    Science.gov (United States)

    Kristensen, Jonas Møller; Treebak, Jonas T.; Schjerling, Peter; Goodyear, Laurie

    2014-01-01

    Metformin-induced activation of the 5′-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPKα2 mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (∼45%, P metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr308/Ser473 and TBC1D4 Thr642/Ser711 phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment. PMID:24644243

  10. HIV-1 stimulates nuclear entry of amyloid beta via dynamin dependent EEA1 and TGF-β/Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    András, Ibolya E., E-mail: iandras@med.miami; Toborek, Michal, E-mail: mtoborek@med.miami.edu

    2014-04-15

    Clinical evidence indicates increased amyloid deposition in HIV-1-infected brains, which contributes to neurocognitive dysfunction in infected patients. Here we show that HIV-1 exposure stimulates amyloid beta (Aβ) nuclear entry in human brain endothelial cells (HBMEC), the main component of the blood–brain barrier (BBB). Treatment with HIV-1 and/or Aβ resulted in concurrent increase in early endosomal antigen-1 (EEA1), Smad, and phosphorylated Smad (pSmad) in nuclear fraction of HBMEC. A series of inhibition and silencing studies indicated that Smad and EEA1 closely interact by influencing their own nuclear entry; the effect that was attenuated by dynasore, a blocker of GTP-ase activity of dynamin. Importantly, inhibition of dynamin, EEA1, or TGF-β/Smad effectively attenuated HIV-1-induced Aβ accumulation in the nuclei of HBMEC. The present study indicates that nuclear uptake of Aβ involves the dynamin-dependent EEA1 and TGF-β/Smad signaling pathways. These results identify potential novel targets to protect against HIV-1-associated dysregulation of amyloid processes at the BBB level. - Highlights: • HIV-1 induces nuclear accumulation of amyloid beta (Aβ) in brain endothelial cells. • EEA-1 and TGF-Β/Smad act in concert to regulate nuclear entry of Aβ. • Dynamin appropriates the EEA-1 and TGF-Β/Smad signaling. • Dynamin serves as a master regulator of HIV-1-induced nuclear accumulation of Aβ.

  11. G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1.

    Science.gov (United States)

    Zhang, Jie; Wang, Yafang; Shen, Yanyan; He, Pengxing; Ding, Jian; Chen, Yi

    2018-01-01

    Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Results: Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both in vitro and in vivo , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. Conclusions: These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.

  12. Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice.

    Science.gov (United States)

    Kawahara, Y; Nakase, Y; Isomoto, Y; Matsuda, N; Amagase, K; Kato, S; Takeuchi, K

    2011-08-01

    We examined the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice. Male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration. The numbers of macrophages and microvessels in the gastric mucosa were determined immunohistochemically with anti-CD68 and anti-CD31 antibodies, respectively. Expression of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) mRNA was determined via real-time reverse transcription-polymerase chain reaction (RT-PCR), and the mucosal content of prostaglandin (PG) E(2) was determined via enzyme immunoassay on day 10 after ulceration. The healing of gastric ulcers was significantly delayed in op/op mice compared with +/? mice. Further, significantly fewer macrophages were observed in the normal gastric mucosa of op/op mice than in +/? mice. Ulcer induction caused a marked accumulation of macrophages around the ulcer base in +/? mice, but this response was attenuated in op/op mice. The mucosal PGE(2) content as well as the expression of COX-2, VEGF, and TNF-α mRNA were all upregulated in the ulcerated area of +/? mice but significantly suppressed in op/op mice. The degree of vascularization in the ulcerated area was significantly lower in op/op mice than in +/? mice. Taken together, these results suggest that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production.

  13. TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

    Science.gov (United States)

    Zheng, Shasha; Hedl, Matija; Abraham, Clara

    2015-02-15

    Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

  14. Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

    Directory of Open Access Journals (Sweden)

    Terry B Huff

    2011-03-01

    Full Text Available High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

  15. LM-OSL signals from some insulators: an analysis of the dependency of the detrapping probability on stimulation light intensity

    DEFF Research Database (Denmark)

    Bulur, E.; Bøtter-Jensen, L.; Murray, A.S.

    2001-01-01

    Optically stimulated luminescence (OSL) signals from various insulators including quartz, Al2O3 : C, BeO and NaCl have been studied using the linear modulation OSL (LM-OSL) technique. LM-OSL is based on the linear increase of the stimulation light power from zero to a maximum during the measurement...... is not always correct. The initial decay rates of the blue (similar to 470 nm) light stimulated constant power OSL decay curves were examined to test the relation between the detrapping rates and the stimulation light intensity. In SiO2, Al2O3 : C and BeO a linear relation between the detrapping rates....... The resultant OSL curve initially increases and then decays after reaching a maximum, The analysis of LM-OSL data usually assumes a linear relationship between the detrapping rate and the stimulation light intensity. However, experiments carried out using various insulators have shown that this assumption...

  16. Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism

    Science.gov (United States)

    Joddar, Binata; Firstenberg, Michael S.; Reen, Rashmeet K.; Varadharaj, Saradhadevi; Khan, Mahmood; Childers, Rachel C.; Zweier, Jay L.; Gooch, Keith J.

    2015-01-01

    Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO2), which are much greater than what they experience in their native environment. The object of this study is to determine the impact of exposing human saphenous veins to arterial pO2. Saphenous veins and left internal mammary arteries from consenting patients undergoing coronary artery bypass grafting were cultured ex vivo for 2 weeks in the presence of arterial or venous pO2 using an established organ culture model. Saphenous veins cultured with arterial pO2 developed intimal hyperplasia as evidenced by 2.8-fold greater intimal area and 5.8-fold increase in cell proliferation compared to those freshly isolated. Saphenous veins cultured at venous pO2 or internal mammary arteries cultured at arterial pO2 did not develop intimal hyperplasia. Intimal hyperplasia was accompanied by two markers of elevated reactive oxygen species (ROS): increased dihydroethidium associated fluorescence (4-fold, ppO2 is suggested by the observation that chronic exposure to tiron, a ROS scavenger, during the two-week culture period, blocked intimal hyperplasia. Electron paramagnetic resonance based oximetry revealed that the pO2 in the wall of the vessel tracked that of the atmosphere with a ~30 mmHg offset, thus the cells in the vessel wall were directly exposed to variations in pO2. Monolayer cultures of smooth muscle cells isolated from saphenous veins exhibited increased proliferation when exposed to arterial pO2 relative to those cultured at venous pO2. This increased proliferation was blocked by tiron. Taken together, these data suggest that exposure of human SV to arterial pO2 stimulates IH via a ROS-dependent pathway. PMID:25799140

  17. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  18. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-01-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

  19. Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes.

    Science.gov (United States)

    Pabbidi, M R; Ji, X; Maxwell, J T; Mignery, G A; Samarel, A M; Lipsius, S L

    2016-01-01

    We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinterol (0.1 μM; zint-β2-AR) to stimulate ICa,L in atrial myocytes in the absence (+PKA) and presence (-PKA) of the PKA inhibitor (1 μM) KT5720 and compared these results with atrial myocytes attached to laminin (+LMN). Inhibition of Raf-1 (10 μM GW5074), phospholipase C (PLC; 0.5 μM edelfosine), PKC (4 μM chelerythrine) or IP3 receptor (IP3R) signaling (2 μM 2-APB) significantly inhibited zint-β2-AR stimulation of ICa,L in-PKA but not +PKA myocytes. Western blots showed that zint-β2-AR stimulation increased ERK1/2 phosphorylation in-PKA compared to +PKA myocytes. Adenoviral (Adv) expression of dominant negative (dn) -PKCα, dn-Raf-1 or an IP3 affinity trap, each inhibited zint-β2-AR stimulation of ICa,L in + LMN myocytes compared to control +LMN myocytes infected with Adv-βgal. In +LMN myocytes, zint-β2-AR stimulation of ICa,L was enhanced by adenoviral overexpression of wild-type cPLA2 and inhibited by double dn-cPLA2S505A/S515A mutant compared to control +LMN myocytes infected with Adv-βgal. In-PKA myocytes depletion of intracellular Ca2+ stores by 5 μM thapsigargin failed to inhibit zint-β2-AR stimulation of ICa,L via cPLA2. However, disruption of caveolae formation by 10 mM methyl-β-cyclodextrin inhibited zint-β2-AR stimulation of ICa,L in-PKA myocytes significantly more than in +PKA myocytes. We conclude that inhibition of PKA removes inhibition of Raf-1 and thereby allows β2-AR stimulation to act via PKCα/Raf-1/MEK/ERK1/2 and IP3-mediated Ca2+ signaling to stimulate cPLA2 signaling within caveolae. These findings may be relevant to the remodeling of

  20. Correction for the time dependent inner filter effect caused by transient absorption in femtosecond stimulated Raman experiment

    NARCIS (Netherlands)

    Kloz, M.; van Grondelle, R.; Kennis, J.T.M.

    2012-01-01

    Femtosecond stimulated Raman spectroscopy (FSRS) is a promising multiple-pulse ultrafast spectroscopic tool whose simplest form utilizes an actinic pump, a Raman pump and a continuum probe. Here, we report that the transient absorption generated by the actinic pulse modulates the overall magnitude

  1. Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism

    Science.gov (United States)

    The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of m...

  2. Imidazoline NNC77-0074 stimulates Ca2+-evoked exocytosis in INS-1E cells by a phospholipase A2-dependent mechanism

    DEFF Research Database (Denmark)

    Olsen, Hervør L; Nørby, Peder L; Høy, Marianne

    2003-01-01

    We have previously demonstrated that the novel imidazoline compound (+)-2-(2-(4,5-dihydro-1H-imidazol-2-yl)-thiopene-2-yl-ethyl)-pyridine (NNC77-0074) increases insulin secretion from pancreatic beta-cells by stimulation of Ca(2+)-dependent exocytosis. Using capacitance measurements, we now show...... that NNC77-0074 stimulates exocytosis in clonal INS-1E cells. NNC77-0074-stimulated exocytosis was antagonised by the cytoplasmic phospholipase A(2) (cPLA(2)) inhibitors ACA and AACOCF(3) and in cells treated with antisense oligonucleotide against cPLA(2)alpha. NNC77-0074-evoked insulin secretion...... was likewise inhibited by ACA, AACOCF(3), and cPLA(2)alpha antisense oligonucleotide treatment. In pancreatic islets NNC77-0074 stimulated PLA(2) activity. We propose that cPLA(2)alpha plays an important role in the regulation of NNC77-0074-evoked exocytosis in insulin secreting beta-cells....

  3. The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity

    DEFF Research Database (Denmark)

    Kelly, Karen R; Brooks, Latina M; Solomon, Thomas

    2009-01-01

    the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response......Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through...... to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults....

  4. Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

    Science.gov (United States)

    Santos-Pontelli, Taiza E G; Rimoli, Brunna P; Favoretto, Diandra B; Mazin, Suleimy C; Truong, Dennis Q; Leite, Joao P; Pontes-Neto, Octavio M; Babyar, Suzanne R; Reding, Michael; Bikson, Marom; Edwards, Dylan J

    2016-01-01

    Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.

  5. Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

    Directory of Open Access Journals (Sweden)

    Melissa eScheldrup

    2014-09-01

    Full Text Available There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine. Non-invasive brain stimulation – specifically transcranial Direct Current Stimulation (tDCS – has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks were seen with a right parietal (C4 to left shoulder montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008. No effects were seen with anodes over sites that stimulated only dorsal (C3 or only ventral (F10 attention networks. The speed subtask (update memory for symbols benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

  6. The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity.

    Science.gov (United States)

    Kelly, Karen R; Brooks, Latina M; Solomon, Thomas P J; Kashyap, Sangeeta R; O'Leary, Valerie B; Kirwan, John P

    2009-06-01

    Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P HYPO (-8.3 +/- 1.1 vs. -2.8 +/- 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

  7. Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

    Science.gov (United States)

    Scheldrup, Melissa; Greenwood, Pamela M; McKendrick, Ryan; Strohl, Jon; Bikson, Marom; Alam, Mahtab; McKinley, R Andy; Parasuraman, Raja

    2014-01-01

    There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation-specifically transcranial Direct Current Stimulation (tDCS)-has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

  8. Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

    International Nuclear Information System (INIS)

    Hepler, J.R.; Harden, T.K.

    1986-01-01

    Formation of the inositol phosphates (InsP), InsP 3 , InsP 2 , and InsP 1 was increased in a concentration dependent manner (K/sub 0.5/ ∼ 5 μM) by GTPΣS in washed membranes prepared from 3 H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTPγS and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 μM GTPγS, carbachol stimulated (K/sub 0.5/ ∼ 10 μ M) the formation of InsP above the level achieved with GTPγS alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 μM carbachol was GTPγS > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTPγS or GTPγS plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTPγS in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells

  9. The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity

    OpenAIRE

    Kelly, Karen R.; Brooks, Latina M.; Solomon, Thomas P. J.; Kashyap, Sangeeta R.; O'Leary, Valerie B.; Kirwan, John P.

    2009-01-01

    Aging and obesity are characterized by decreased β-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% V̇o2 max) combined with a eucaloric (EX, n = 10) or ...

  10. Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

    DEFF Research Database (Denmark)

    Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj

    2003-01-01

    BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin....../or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow....... Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (Palpha...

  11. Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

    Science.gov (United States)

    Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

    2014-01-01

    Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is

  12. Current direction-dependent modulation of human hand motor function by intermittent theta burst stimulation (iTBS).

    Science.gov (United States)

    Shirota, Yuichiro; Dhaka, Suman; Paulus, Walter; Sommer, Martin

    2017-05-22

    Transcranial magnetic stimulation (TMS) with different current directions can activate different sets of neurons. Current direction can also affect the results of repetitive TMS. To test the influence of uni-directional intermittent theta burst stimulation (iTBS) using different current directions, namely posteroanterior (PA) and anteroposterior (AP), on motor behaviour. In a cross-over design, PA- and AP-iTBS was applied over the left primary motor cortex in 19 healthy, right-handed volunteers. Performance of a finger-tapping task was recorded before and 0, 10, 20, and 30min after the iTBS. The task was conducted with the right and left hands separately at each time point. As a control, AP-iTBS with reduced intensity was applied to 14 participants in a separate session (AP weak condition). The finger-tapping count with the left hand was decreased after PA-iTBS. Neither AP- nor AP weak -iTBS altered the performance. Current direction had a significant impact on the after-effects of iTBS. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Glucagon-like peptide-2, but not glucose-dependent insulinotropic polypeptide, stimulates glucagon release in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Knop, Filip K; Vilsbøll, Tina

    2010-01-01

    This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5 g...... intravenous arginine stimulation; on study days only treated with basal insulin substitution). On 3 study days, 180-minute two-step glucose clamps were performed. Plasma glucose (PG) was clamped at fasting values, with a mean of 7.4+/-0.5 mM in the first 90 min (period 1) and raised 1.5 times the fasting...

  14. Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking

    DEFF Research Database (Denmark)

    Andersen, Martin Nybo; Hefting, Louise Leth; Steffensen, Annette Buur

    2015-01-01

    The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the IKs current, which is enhanced by PKA mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.......1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not co-assemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin Darby Canine Kidney cells. While PKA inhibition...... reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition lead to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role...

  15. Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells

    International Nuclear Information System (INIS)

    Chung, Byung-Hee; Kim, Jong-Dai; Kim, Chun-Ki; Kim, Jung Huan; Won, Moo-Ho; Lee, Han-Soo; Dong, Mi-Sook; Ha, Kwon-Soo; Kwon, Young-Geun; Kim, Young-Myeong

    2008-01-01

    We investigated the molecular effect and signal pathway of icariin, a major flavonoid of Epimedium koreanum Nakai, on angiogenesis. Icariin stimulated in vitro endothelial cell proliferation, migration, and tubulogenesis, which are typical phenomena of angiogenesis, as well as increased in vivo angiogenesis. Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis. Icariin-induced ERK activation and angiogenic events were significantly inhibited by the MEK inhibitor PD98059, without affecting Akt and eNOS phosphorylation. The PI3K inhibitor Wortmannin suppressed icariin-mediated angiogenesis and Akt and eNOS activation without affecting ERK phosphorylation. Moreover, the NOS inhibitor NMA partially reduced the angiogenic activity of icariin. These results suggest that icariin stimulated angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways and may be a useful drug for angiogenic therapy

  16. Modulation of inhibitory activity markers by intermittent theta-burst stimulation in rat cortex is NMDA-receptor dependent.

    Science.gov (United States)

    Labedi, Adnan; Benali, Alia; Mix, Annika; Neubacher, Ute; Funke, Klaus

    2014-01-01

    Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition. Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors. In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis. iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects. Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Comparaison de quelques caractéristiques biologiques entre Dinarmus basalis Rond. (Hymenoptera: Pteromalidae élevé soit sur son hôte habituel Callosobruchus maculatus F. (Coleoptera: Bruchidae soit sur Acanthoscelides macrophthalmus Schaef. ou Bruchidius lineatopygus Pic. identifiés comme hôtes de substitution

    Directory of Open Access Journals (Sweden)

    Nuto, Y.

    2006-01-01

    Full Text Available Comparison of some Biological Characteristics between Dinarmus basalis Rond. (Hymenoptera: Pteromalidae Reared either on his Habitual Host Callosobruchus maculatus F. (Coleoptera: Bruchidae or on Acanthoscelides macrophthalmus Schaef. and Bruchidius lineatopygus Pic. Identified as Substitution Hosts. In this study, we have measured some biological parameters of Dinarmus basalis Rond. (Hymenoptera: Pteromalidae when this parasitoid grows on three hosts: Callosobruchus maculatus F. (usual host, Acanthoscelides macrophthalma Schaef. and Bruchidius lineatopygus Pic. (substitution hosts. The results of this comparative study in no choice situation show that, life duration and development duration of this parasitoid are identical in laboratory conditions. By contrast, the female fecundity, the sexual rate and the parasitism rate of D. basalis are different according to the hosts presented. Although such differences appear to be small between C. maculatus and A. macrophthalmus. In presence of these two species, the number of eggs laid by the female of D. basalis is respectively 61 ± 5.24 and 54 ± 5.60, the sexual rate 37.63 ± 2.13% and 41.73 ± 3.69% and the parasitism rate 85.46 ± 2.61% and 76.48 ± 5.90%. This indicates that these two Bruchids can be used as hosts to D. basalis for a mass production. In presence of B. lineatopygus, the fecundity and the parasitism rate of D. basalis female are very low and the sexual rate more favourable of the males. This situation is unfavourable for a parasitoid production. When D. basalis females are placed in choice situation with equal number of the hosts nowely C. maculatus and A. macrophthalmus, the parasitism rate obtained, is higher for C. maculatus that of A. macrophthalmus. This parasitism rate remains high for C. maculatus even when the other host A. macrophthalmus is twice the number of C. maculatus. Thus the parasitoid seems to have a preference for his natural host. However, A. macrophthalmus can

  18. Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation?

    Science.gov (United States)

    Sieg, Emily P; Payne, Russell A; Hazard, Sprague; Rizk, Elias

    2016-06-01

    Case reports, case series and case control studies have looked at the use of phrenic nerve stimulators in the setting of high spinal cord injuries and central hypoventilation syndromes dating back to the 1980s. We evaluated the evidence related to this topic by performing a systematic review of the published literature. Search terms "phrenic nerve stimulation," "phrenic nerve and spinal cord injury," and "phrenic nerve and central hypoventilation" were entered into standard search engines in a systematic fashion. Articles were reviewed by two study authors and graded independently for class of evidence according to published guidelines. The published evidence was reviewed, and the overall body of evidence was evaluated using the grading of recommendations, assesment, development and evaluations (GRADE) criteria Balshem et al. (J Clin Epidemiol 64:401-406, 2011). Our initial search yielded 420 articles. There were no class I, II, or III studies. There were 18 relevant class IV articles. There were no discrepancies among article ratings (i.e., kappa = 1). A meta-analysis could not be performed due to the low quality of the available evidence. The overall quality of the body of evidence was evaluated using GRADE criteria and fell within the "very poor" category. The quality of the published literature for phrenic nerve stimulation is poor. Our review of the literature suggests that phrenic nerve stimulation is a safe and effective option for decreasing ventilator dependence in high spinal cord injuries and central hypoventilation; however, we are left with critical questions that provide crucial directions for future studies.

  19. RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

    Energy Technology Data Exchange (ETDEWEB)

    Hahm, Jong Ryeal [Department of Internal Medicine, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Ahmed, Mahmoud [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Kim, Deok Ryong, E-mail: drkim@gnu.ac.kr [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of)

    2016-09-09

    3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-L-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-L-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity. - Highlights: • Overexpression of GFP-LC3 in 3T3-L1 cells produces intracellular lipid droplets. • SREBP2 is highly activated in preadipocytes transfected with adenoviral GFP-LC3. • RKIP phosphorylation at serine 153 is significantly increased during adipogenesis. • RKIP knockdown promotes ERK1 and PPARγ activation during adipogenesis. • RKIP-dependent ERK1 activation increases triacylglycerides in

  20. Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease.

    Science.gov (United States)

    Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

    2015-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson's disease (PD). However, some aspects of executive control are impaired with STN DBS. We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

  1. Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia.

    Science.gov (United States)

    Shah, Faraaz Ali; Singamsetty, Srikanth; Guo, Lanping; Chuan, Byron W; McDonald, Sherie; Cooper, Bryce A; O'Donnell, Brett J; Stefanovski, Darko; Wice, Burton; Zhang, Yingze; O'Donnell, Christopher P; McVerry, Bryan J

    2018-03-01

    Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice exposed to bacterial endotoxin and measured incretin hormone release, glucose disposal, and proinflammatory cytokine production. Compared with IV administration, enteral dextrose increased circulating levels of the incretin hormone glucose-dependent insulinotropic peptide (GIP) associated with increased insulin release and insulin sensitivity, improved mean arterial pressure, and decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued glucose metabolism, improved blood pressure, and increased insulin release in endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation of endogenous GIP secretion by early enteral dextrose maintains glucose homeostasis and attenuates the systemic inflammatory response in endotoxemic mice and may provide a therapeutic target for improving glycemic control and clinical outcomes in patients with sepsis. Published by Elsevier Inc.

  2. Glucose deprivation stimulates Cu(2+) toxicity in cultured cerebellar granule neurons and Cu(2+)-dependent zinc release.

    Science.gov (United States)

    Isaev, Nickolay K; Genrikhs, Elisaveta E; Aleksandrova, Olga P; Zelenova, Elena A; Stelmashook, Elena V

    2016-05-27

    Copper chloride (0.01mM, 2h) did not have significant influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution. However, CuCl2 caused severe neuronal damage by glucose deprivation (GD). The glutamate NMDA-receptors blocker MK-801 partially and antioxidant N-acetyl-l-cysteine (NAC) or Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) almost entirely protected CGNs from this toxic effect. Measurements of intracellular calcium ions using Fluo-4 AM, or zinc ions with FluoZin-3 AM demonstrated that 1 h-exposure to GD induced intensive increase of Fluo-4 but not FluoZin-3 fluorescence in neurons. The supplementation of solution with CuCl2 caused an increase of FluoZin-3, Fluo-4 and CellROX Green (reactive oxygen species probe) fluorescence by GD. The stimulation of Fluo-4 but not FluoZin-3 fluorescence by copper could be prevented partially by MK-801 and as well as CellROX Green fluorescence by NAC at GD. This data imply that during GD copper ions induce intense displacement zinc ions from intracellular stores, in addition free radical production, glutamate release and Ca(2+) overload of CGNs, that causes death of neurons as a result. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Discounting of money and sex: effects of commodity and temporal position in stimulant-dependent men and women.

    Science.gov (United States)

    Jarmolowicz, David P; Landes, Reid D; Christensen, Darren R; Jones, Bryan A; Jackson, Lisa; Yi, Richard; Bickel, Warren K

    2014-11-01

    Research on delay discounting has contributed to the understanding of numerous addiction-related phenomena. For example, studies have shown that substance dependent individuals discount their addictive substances (e.g., cocaine) more rapidly than they do other commodities (e.g., money). Recent research has shown that substance dependent individuals discount delayed sex more rapidly than delayed money, and their discounting rates for delayed sex were higher than those of non-addicted individuals. The particular reason that delay discounting rates for sex are higher than those for money, however, are unclear. Do individuals discount delayed sex rapidly because immediate sex is particularly appealing or because delayed sex does not retain its value? Moreover, do the same factors influence men and women's choices? The current study examined delay discounting in four conditions (money now versus money later; sex now versus sex later; money now, versus sex later; sex now versus money later) in cocaine dependent men and women. The procedures used isolated the role of the immediate versus delayed commodity. For men, the higher rates of delay discounting for sex were because delayed sex did not retain its value, whereas both the immediate and delayed commodity influenced the female participants' decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation.

    Science.gov (United States)

    Tsukamoto, Hiroki; Takeuchi, Shino; Kubota, Kanae; Kobayashi, Yohei; Kozakai, Sao; Ukai, Ippo; Shichiku, Ayumi; Okubo, Misaki; Numasaki, Muneo; Kanemitsu, Yoshitomi; Matsumoto, Yotaro; Nochi, Tomonori; Watanabe, Kouichi; Aso, Hisashi; Tomioka, Yoshihisa

    2018-05-14

    Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

  5. Nitric Oxide Synthase 1 Modulates Basal and β-Adrenergic-Stimulated Contractility by Rapid and Reversible Redox-Dependent S-Nitrosylation of the Heart

    Science.gov (United States)

    Vielma, Alejandra Z.; León, Luisa; Fernández, Ignacio C.; González, Daniel R.

    2016-01-01

    S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC. Selective NOS-1 blockade with S-methyl-L-thiocitrulline (SMTC) and Nω-propyl-l-arginine decreased basal contractility and relaxation (−25–30%) and basal S-nitrosylation of total proteins (−25–60%), RyR2, SERCA2 and LTCC (−60–75%). NOS-1 inhibition reduced (−25–40%) the inotropic response and protein S-nitrosylation induced by isoproterenol, particularly that of RyR2 (−85±7%). Tempol, a superoxide scavenger, mimicked the effects of NOS-1 inhibition on inotropism and protein S-nitrosylation; whereas selective NOS-3 inhibitor L-N5-(1-Iminoethyl)ornithine had no effect. Inhibition of NOS-1 did not affect phospholamban phosphorylation, but reduced its oligomerization. Attenuation of contractility was abolished by PKA blockade and unaffected by guanylate cyclase inhibition. Additionally, in isolated mouse cardiomyocytes, NOS-1 inhibition or removal reduced the Ca2+-transient amplitude and sarcomere shortening induced by isoproterenol or by direct PKA activation. We conclude that 1) normal cardiac performance requires basal NOS-1 activity and S-nitrosylation of the calcium-cycling machinery; 2) β-adrenergic stimulation induces rapid and reversible NOS-1 dependent, PKA and ROS-dependent, S-nitrosylation of RyR2 and other proteins, accounting for about one third of its

  6. Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner.

    Directory of Open Access Journals (Sweden)

    Tania J Fernandes

    Full Text Available In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and β-glycerophosphate these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM, and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2 actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells

  7. A calcium-dependent protein kinase can inhibit a calmodulin-stimulated Ca2+ pump (ACA2) located in the endoplasmic reticulum of Arabidopsis

    Science.gov (United States)

    Hwang, I.; Sze, H.; Harper, J. F.; Evans, M. L. (Principal Investigator)

    2000-01-01

    The magnitude and duration of a cytosolic Ca(2+) release can potentially be altered by changing the rate of Ca(2+) efflux. In plant cells, Ca(2+) efflux from the cytoplasm is mediated by H(+)/Ca(2+)-antiporters and two types of Ca(2+)-ATPases. ACA2 was recently identified as a calmodulin-regulated Ca(2+)-pump located in the endoplasmic reticulum. Here, we show that phosphorylation of its N-terminal regulatory domain by a Ca(2+)-dependent protein kinase (CDPK isoform CPK1), inhibits both basal activity ( approximately 10%) and calmodulin stimulation ( approximately 75%), as shown by Ca(2+)-transport assays with recombinant enzyme expressed in yeast. A CDPK phosphorylation site was mapped to Ser(45) near a calmodulin binding site, using a fusion protein containing the N-terminal domain as an in vitro substrate for a recombinant CPK1. In a full-length enzyme, an Ala substitution for Ser(45) (S45/A) completely blocked the observed CDPK inhibition of both basal and calmodulin-stimulated activities. An Asp substitution (S45/D) mimicked phosphoinhibition, indicating that a negative charge at this position is sufficient to account for phosphoinhibition. Interestingly, prior binding of calmodulin blocked phosphorylation. This suggests that, once ACA2 binds calmodulin, its activation state becomes resistant to phosphoinhibition. These results support the hypothesis that ACA2 activity is regulated as the balance between the initial kinetics of calmodulin stimulation and CDPK inhibition, providing an example in plants for a potential point of crosstalk between two different Ca(2+)-signaling pathways.

  8. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

    Directory of Open Access Journals (Sweden)

    Kathrin eHoppenrath

    2016-03-01

    Full Text Available Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV fast-spiking interneurons (FSIs, evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs of FSIs start to grow around postnatal day 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo – in vitro whole-cell patch clamp recordings from pre-labelled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28 and older animals (PD40-62. Slices of verum iTBS-treated rats further showed higher rates of spontaneous EPSCs. Based on these and previous findings we conclude that FSIs are particularly sensitive to theta-burst stimulation during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  9. Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells.

    Science.gov (United States)

    Wu, Ximei; Iguchi, Takuma; Itoh, Norio; Okamoto, Kousuke; Takagi, Tatsuya; Tanaka, Keiichi; Nakanishi, Tsuyoshi

    2008-01-01

    Reduced vitamin C [ascorbic acid (AA)], which is taken up into cells by sodium-dependent vitamin C transporter (SVCT) 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. To determine the steroidogenic effect of AA and the role of SVCT2 in AA-induced steroidogenesis, we tested the effects of AA treatment and SVCT2 knockdown on steroidogenesis in human choriocarcinoma cell lines. AA treatment of JEG-3, BeWo, and JAR cells for 48-h dose dependently increased progesterone and estradiol levels. In JEG-3 cells, AA increased the mRNA expression of P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase, key enzymes for steroidogenesis. Stable knockdown of SVCT2 in JEG-3 cells by retrovirally mediated RNA interference decreased the maximal velocity of AA uptake by approximately 50%, but apparent affinity values were not affected. SVCT2 knockdown in JEG-3 cells significantly suppressed the AA-induced mRNA expression of placental P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase. This suppression of the AA-induced mRNA expression of steroidogenic enzymes subsequently decreased progesterone and estradiol production. In addition, inhibition of MAPK kinase-ERK signaling, which is a major pathway for AA-regulated gene expression, failed to affect AA-induced steroidogenesis. Our observations indicate that SVCT2-mediated AA uptake into cells is necessary for AA-induced steroidogenesis in human choriocarcinoma cell, but MAPK kinase-ERK signaling is not involved in AA-induced steroidogenesis.

  10. Cyclic AMP-dependent protein kinase interferes with GTP γS stimulated IP3 formation in differentiated HL-60 cell membranes

    International Nuclear Information System (INIS)

    Misaki, Naoyuki; Imaizumi, Taro; Watanabe, Yashuiro

    1989-01-01

    The effects of addition of activated cyclic AMP-dependent protein kinase (PKA) on the function of islet-activating protein (IAP)-sensitive GTP-binding (G) protein were studied in the plasma membranes of 3 H-inositol-labeled differentiated human leukemic (HL-60) cells. Pretreatment of the membranes with activated PKA in the presence of MgATP for 15 min. at 37 degree C decreased GTP γS-stimulated inositol trisphosphate (IP 3 ) formation by about 30%, but had no influence on Ca 2+ -stimulated IP 3 formation. And autoradiography in the phosphorylation experiments of solubilized HL-60 cell membranes by PKA showed some 32 P incorporated bands, and among them one of the major bands showed the migration at 40 kDa supporting that the G protein coupling with PI response was phosphorylated by PKA. These results showed that pretreatment with activated PKA inhibited the mediating function of the G protein between the fMLP receptor and phospholipase C by its phosphorylation

  11. Crocin Suppresses LPS-Stimulated Expression of Inducible Nitric Oxide Synthase by Upregulation of Heme Oxygenase-1 via Calcium/Calmodulin-Dependent Protein Kinase 4

    Directory of Open Access Journals (Sweden)

    Ji-Hee Kim

    2014-01-01

    Full Text Available Crocin is a water-soluble carotenoid pigment that is primarily used in various cuisines as a seasoning and coloring agent, as well as in traditional medicines for the treatment of edema, fever, and hepatic disorder. In this study, we demonstrated that crocin markedly induces the expression of heme oxygenase-1 (HO-1 which leads to an anti-inflammatory response. Crocin inhibited inducible nitric oxide synthase (iNOS expression and nitric oxide production via downregulation of nuclear factor kappa B activity in lipopolysaccharide- (LPS- stimulated RAW 264.7 macrophages. These effects were abrogated by blocking of HO-1 expression or activity. Crocin also induced Ca2+ mobilization from intracellular pools and phosphorylation of Ca2+/calmodulin-dependent protein kinase 4 (CAMK4. CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling. Moreover, crocin-mediated suppression of iNOS expression was blocked by CAMK4 inhibition. Overall, these results suggest that crocin suppresses LPS-stimulated expression of iNOS by inducing HO-1 expression via Ca2+/calmodulin-CAMK4-PI3K/Akt-Nrf2 signaling cascades. Our findings provide a novel molecular mechanism for the inhibitory effects of crocin against endotoxin-mediated inflammation.

  12. Energy dependence measurement of small-type optically stimulated luminescence (OSL) dosimeter by means of characteristic X-rays induced with general diagnostic X-ray equipment.

    Science.gov (United States)

    Takegami, Kazuki; Hayashi, Hiroaki; Okino, Hiroki; Kimoto, Natsumi; Maehata, Itsumi; Kanazawa, Yuki; Okazaki, Tohru; Hashizume, Takuya; Kobayashi, Ikuo

    2016-01-01

    For X-ray inspections by way of general X-ray equipment, it is important to measure an entrance-skin dose. Recently, a small optically stimulated luminescence (OSL) dosimeter was made commercially available by Landauer, Inc. The dosimeter does not interfere with the medical images; therefore, it is expected to be a convenient detector for measuring personal exposure doses. In an actual clinical situation, it is assumed that X-rays of different energies will be detected by a dosimeter. For evaluation of the exposure dose measured by a dosimeter, it is necessary to know the energy dependence of the dosimeter. Our aim in this study was to measure the energy dependence of the OSL dosimeter experimentally in the diagnostic X-ray region. Metal samples weighing several grams were irradiated and, in this way, characteristic X-rays having energies ranging from 8 to 85 keV were generated. Using these mono-energetic X-rays, the dosimeter was irradiated. Simultaneously, the fluence of the X-rays was determined with a CdTe detector. The energy-dependent efficiency of the dosimeter was derived from the measured value of the dosimeter and the fluence. Moreover, the energy-dependent efficiency was calculated by Monte-Carlo simulation. The efficiency obtained in the experiment was in good agreement with that of the simulation. In conclusion, our proposed method, in which characteristic X-rays are used, is valuable for measurement of the energy dependence of a small OSL dosimeter in the diagnostic X-ray region.

  13. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease.

    Science.gov (United States)

    Thomas, Karen E; Sapone, Anna; Fasano, Alessio; Vogel, Stefanie N

    2006-02-15

    Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD.

  14. Dependence of fading patterns of photo-stimulated luminescence from imaging plates on radiation, energy, and image reader

    International Nuclear Information System (INIS)

    Ohuchi, H.; Yamadera, A.

    2002-01-01

    We have been investigating the fading characteristics of imaging plates (IPs) as integral type detectors. The dependence on alpha, beta, and gamma ray radiation and their energies of the fading effect was measured using three types of IPs (BAS-UR, BAS-TR, and BAS-MS). The functions to correct the fading were determined by using the method reported in a previous paper. In all types of IPs, we confirmed that the fading effect is independent of the energy of the incident particles of beta and gamma rays and also independent of radiation except for the first component, which fades out in a very short time after irradiation with alpha rays. These results are very useful in the utilization of IPs as integral detectors in practical radiation fields. Empirically, the fading pattern is known to change when the IP is scanned by different types of image readers. The differences in the fading patterns obtained with two types of image readers, the BAS-1000 and the BAS-5000 (Fuji Film Co.), is discussed. Development of an equation for correcting the effects of the differences in the image readers was attempted

  15. Effects of pregnane glycosides on food intake depend on stimulation of the melanocortin pathway and BDNF in an animal model.

    Science.gov (United States)

    Komarnytsky, Slavko; Esposito, Debora; Rathinasabapathy, Thirumurugan; Poulev, Alexander; Raskin, Ilya

    2013-02-27

    Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25-100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF.

  16. Host manipulation by the orange leafhopper Cicadulina bipunctata: gall induction on distant leaves by dose-dependent stimulation

    Science.gov (United States)

    Matsukura, Keiichiro; Matsumura, Masaya; Tokuda, Makoto

    2009-09-01

    The evolution of the gall-inducing ability in insects and the adaptive significance of the galling habit have been addressed by many studies. Cicadulina bipunctata, the maize orange leafhopper, is an ideal study organism for evaluating these topics because it can be mass-reared and it feeds on model plants such as rice ( Oryza sativa) and maize ( Zea mays). To reveal differences between gall inductions by C. bipunctata and other gall inducers, we conducted four experiments concerning (a) the relationship between the feeding site and gall-induction sites of C. bipunctata on maize, (b) the effects of leafhopper sex and density, (c) the effects of length of infestation on gall induction, and (d) the effects of continuous infestation. C. bipunctata did not induce galls on the leaves where it fed but induced galls on other leaves situated at more distal positions. The degree of gall induction was significantly correlated with infestation density and length. These results indicate that C. bipunctata induces galls in a dose-dependent manner on leaves distant from feeding sites, probably by injecting chemical(s) to the plant during feeding. We suggest that insect galls are induced by a chemical stimulus injected by gall inducers during feeding into the hosts.

  17. DREAM mediates cAMP-dependent, Ca2+-induced stimulation of GFAP gene expression and regulates cortical astrogliogenesis.

    Science.gov (United States)

    Cebolla, Beatriz; Fernández-Pérez, Antonio; Perea, Gertrudis; Araque, Alfonso; Vallejo, Mario

    2008-06-25

    In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to promote astrocyte differentiation of cortical precursors via activation of a cAMP-dependent pathway. Signals acting on progenitor cells of the developing cortex to generate astrocytes activate glial fibrillary acidic protein (GFAP) gene expression, but the transcriptional mechanisms that regulate this activation are unclear. Here, we identify the previously known transcriptional repressor downstream regulatory element antagonist modulator (DREAM) as an activator of GFAP gene expression. We found that DREAM occupies specific sites on the GFAP promoter before and after differentiation is initiated by exposure of cortical progenitor cells to PACAP. PACAP raises intracellular calcium concentration via a mechanism that requires cAMP, and DREAM-mediated transactivation of the GFAP gene requires the integrity of calcium-binding domains. Cortical progenitor cells from dream(-/-) mice fail to express GFAP in response to PACAP. Moreover, the neonatal cortex of dream(-/-) mice exhibits a reduced number of astrocytes and increased number of neurons. These results identify the PACAP-cAMP-Ca(2+)-DREAM cascade as a new pathway to activate GFAP gene expression during astrocyte differentiation.

  18. Protein kinase Cα phosphorylates a novel argininosuccinate synthase site at serine 328 during calcium-dependent stimulation of endothelial nitric-oxide synthase in vascular endothelial cells.

    Science.gov (United States)

    Haines, Ricci J; Corbin, Karen D; Pendleton, Laura C; Eichler, Duane C

    2012-07-27

    Endothelial nitric-oxide synthase (eNOS) utilizes l-arginine as its principal substrate, converting it to l-citrulline and nitric oxide (NO). l-Citrulline is recycled to l-arginine by two enzymes, argininosuccinate synthase (AS) and argininosuccinate lyase, providing the substrate arginine for eNOS and NO production in endothelial cells. Together, these three enzymes, eNOS, AS, and argininosuccinate lyase, make up the citrulline-NO cycle. Although AS catalyzes the rate-limiting step in NO production, little is known about the regulation of AS in endothelial cells beyond the level of transcription. In this study, we showed that AS Ser-328 phosphorylation was coordinately regulated with eNOS Ser-1179 phosphorylation when bovine aortic endothelial cells were stimulated by either a calcium ionophore or thapsigargin to produce NO. Furthermore, using in vitro kinase assay, kinase inhibition studies, as well as protein kinase Cα (PKCα) knockdown experiments, we demonstrate that the calcium-dependent phosphorylation of AS Ser-328 is mediated by PKCα. Collectively, these findings suggest that phosphorylation of AS at Ser-328 is regulated in accordance with the calcium-dependent regulation of eNOS under conditions that promote NO production and are in keeping with the rate-limiting role of AS in the citrulline-NO cycle of vascular endothelial cells.

  19. Stimulation and inhibition of bacterial growth by caffeine dependent on chloramphenicol and a phenolic uncoupler--a ternary toxicity study using microfluid segment technique.

    Science.gov (United States)

    Cao, Jialan; Kürsten, Dana; Schneider, Steffen; Köhler, J Michael

    2012-10-01

    A droplet-based microfluidic technique for the fast generation of three dimensional concentration spaces within nanoliter segments was introduced. The technique was applied for the evaluation of the effect of two selected antibiotic substances on the toxicity and activation of bacterial growth by caffeine. Therefore a three-dimensional concentration space was completely addressed by generating large sequences with about 1150 well separated microdroplets containing 216 different combinations of concentrations. To evaluate the toxicity of the ternary mixtures a time-resolved miniaturized optical double endpoint detection unit using a microflow-through fluorimeter and a two channel microflow-through photometer was used for the simultaneous analysis of changes on the endogenous cellular fluorescence signal and on the cell density of E. coli cultivated inside 500 nL microfluid segments. Both endpoints supplied similar results for the dose related cellular response. Strong non-linear combination effects, concentration dependent stimulation and the formation of activity summits on bolographic maps were determined. The results reflect a complex response of growing bacterial cultures in dependence on the combined effectors. A strong caffeine induced enhancement of bacterial growth was found at sublethal chloramphenicol and sublethal 2,4-dinitrophenol concentrations. The reliability of the method was proved by a high redundancy of fluidic experiments. The results indicate the importance of multi-parameter investigations for toxicological studies and prove the potential of the microsegmented flow technique for such requirements.

  20. Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Albino Villegas-Bastida

    2014-01-01

    Full Text Available Electrical vagus nerve (VN stimulation during sepsis attenuates tumor necrosis factor (TNF production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36 on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP. The septic rats were subsequently treated with EA-ST36 (CLP+ST36, and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P<0.05, and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.

  1. Insulin stimulates phospholipase D-dependent phosphatidylcholine hydrolysis, Rho translocation, de novo phospholipid synthesis, and diacylglycerol/protein kinase C signaling in L6 myotubes.

    Science.gov (United States)

    Standaert, M L; Bandyopadhyay, G; Zhou, X; Galloway, L; Farese, R V

    1996-07-01

    Previous studies have provided conflicting findings on whether insulin activates certain, potentially important, phospholipid signaling systems in skeletal muscle preparations. In particular, insulin effects on the hydrolysis of phosphatidylcholine (PC) and subsequent activation of protein kinase C (PKC) have not been apparent in some studies. Presently, we examined insulin effects on phospholipid signaling systems, diacylglycerol (DAG) production, and PKC translocation/activation in L6 myotubes. We found that insulin provoked rapid increases in phospholipase D (PLD)-dependent hydrolysis of PC, as evidenced by increases in choline release and phosphatidylethanol production in cells incubated in the presence of ethanol. In association with PC-PLD activation, Rho, a small G protein that is known to activate PC-PLD activation, translocated from the cytosol to the membrane fraction in response to insulin treatment. PC-PLD activation was also accompanied by increases in total DAG production and increases in the translocation of both PKC enzyme activity and DAG-sensitive PKC-alpha, -beta, -delta, and -epsilon from the cytosol to the membrane fraction. A potential role for PKC or a related protein kinase in insulin action was suggested by the finding that RO 31-8220 inhibited both PKC enzyme activity and insulin-stimulated [3H]2-deoxyglucose uptake. Our findings provide the first evidence that insulin stimulates Rho translocation and activates PC-PLD in L6 skeletal muscle cells. Moreover, this signaling system appears to lead to increases in DAG/PKC signaling, which, along with other related signaling factors, may regulate certain metabolic processes, such as glucose transport, in these cells.

  2. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion.

    Science.gov (United States)

    Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

    2016-01-01

    Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  3. Moringa olifeira Lam. Stimulates Activation of the Insulin-Dependent Akt Pathway. Antidiabetic Effect in a Diet-Induced Obesity (DIO) Mouse Model.

    Science.gov (United States)

    Attakpa, E S; Sangaré, M M; Béhanzin, G J; Ategbo, J-M; Seri, B; Khan, N A

    2017-01-01

    We investigated the antidiabetic effect of Moringa olifeira Lam. in a diet-induced obesity (DIO) mouse model. Six mice were randomly selected as normal controls. Moringa olifeira Lam. leaf extract at a dose of 200, 400 or 600 mg/kg body weight, glibenclamide (Glib) at the dose of 10 mg/kg (positive control) and distilled water at 10 ml/kg (control group) were administered orally by gastric intubation, and each group consisted of six mice. Insulinsensitive tissues (liver, skeletal muscle) were collected to investigate antidiabetic effects and examine the plant's molecular mechanisms. Moringa olifeira Lam. leaf extract prevented weight gain. It also reduced blood glucose in DIO mice. Glib and Moringa olifeira Lam. leaf extract, 400 mg/kg, treatments restored insulin levels towards normal values (P < 0.05 versus diabetic control group). Western immunoblot analysis of different tissues, collected at the end of the study, demonstrated that Moringa olifeira Lam. stimulated activation of the insulin-dependent Akt pathway and increased the protein content of Glut 4 in skeletal muscle. The improvement of hepatic steatosis observed in DIO-treated mice was associated with a decrease in the hepatic content of SREBP-1, a transcription factor involved in de novo lipogenesis. The hepatic PPARα protein content in the plant extract- treated mice remained significantly higher than those of the control group (P < 0.05). In conclusion, this study provides the first evidence for direct action of Moringa olifeira Lam. on pancreatic β-cells, enhancing glucose-stimulated insulin secretion. This correlated with hypoglycaemic effects in diabetic mice associated with restored levels of plasma insulin.

  4. Kaempferol stimulates large conductance Ca2+-activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway

    Science.gov (United States)

    Xu, Y C; Leung, G P H; Wong, P Y D; Vanhoutte, P M; Man, R Y K

    2008-01-01

    Background and purpose: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K+ channels in endothelial cells. Experimental approach: K+ channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. Key results: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca2+-activated K+ (BKCa) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca2+-activated K+ (SKCa) channel blocker, apamin, and the voltage-dependent K+ (KV) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of BkCa channels in HUVECs. Clamping intracellular Ca2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BKCa channels by kaempferol caused membrane hyperpolarization of HUVECs. Conclusion and implications: These results demonstrate that kaempferol activates the opening of BKCa channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol. PMID:18493242

  5. Stimulation of Pol III-dependent 5S rRNA and U6 snRNA gene expression by AP-1 transcription factors.

    Science.gov (United States)

    Ahuja, Richa; Kumar, Vijay

    2017-07-01

    RNA polymerase III transcribes structurally diverse group of essential noncoding RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth, and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by activator protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription. Our chromatin immunoprecipitation studies suggested that endogenous AP-1 factors bind to their cognate promoter elements during the G1/S transition of cell cycle apparently synchronous with Pol III transcriptional activity. Furthermore, the interaction of c-Jun with histone acetyltransferase p300 promoted the recruitment of p300/CBP complex on the promoters and facilitated the occupancy of Pol III transcriptional machinery via histone acetylation and chromatin remodeling. The findings of our study, together, suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6 snRNA expression with a potential role in cell proliferation. © 2017 Federation of European Biochemical Societies.

  6. Stimulation of apical sodium-dependent bile acid transporter expands the bile acid pool and generates bile acids with positive feedback properties.

    Science.gov (United States)

    Rudling, Mats; Bonde, Ylva

    2015-01-01

    Bile acid synthesis has been considered a prototype for how a physiological process is controlled by end product feedback inhibition. By this feedback inhibition, bile acid concentrations are kept within safe ranges. However, careful examination of published rodent data strongly suggests that bile acid synthesis is also under potent positive feedback control by hydrophilic bile acids. Current concepts on the regulation of bile acid synthesis are derived from mouse models. Recent data have shown that mice have farnesoid X receptor (FXR) antagonistic bile acids capable of quenching responses elicited by FXR agonistic bile acids. This is important to recognize to understand the regulation of bile acid synthesis in the mouse, and in particular to clarify if mouse model findings are valid also in the human situation. In addition to classic end product feedback inhibition, regulation of bile acid synthesis in the mouse largely appears also to be driven by changes in hepatic levels of murine bile acids such as α- and β-muricholic acids. This has not been previously recognized. Stimulated bile acid synthesis or induction of the apical sodium-dependent bile acid transporter in the intestine, increase the availability of chenodeoxycholic acid in the liver, thereby promoting hepatic conversion of this bile acid into muricholic acids. Recognition of these mechanisms is essential for understanding the regulation of bile acid synthesis in the mouse, and for our awareness of important species differences in the regulation of bile acid synthesis in mice and humans. 2015 S. Karger AG, Basel.

  7. Bidirectional interactions between neuronal and hemodynamic responses to transcranial direct current stimulation (tDCS: challenges for brain-state dependent tDCS

    Directory of Open Access Journals (Sweden)

    Anirban eDutta

    2015-08-01

    Full Text Available Transcranial direct current stimulation (tDCS has been shown to modulate cortical neural activity. During neural activity, the electric currents from excitable membranes of brain tissue superimpose in the extracellular medium and generate a potential at scalp, which is referred as the electroencephalogram (EEG. Respective neural activity (energy demand has been shown to be closely related, spatially and temporally, to cerebral blood flow (CBF that supplies glucose (energy supply via neurovascular coupling. The hemodynamic response can be captured by near-infrared spectroscopy (NIRS, which enables continuous monitoring of cerebral oxygenation and blood volume. This neurovascular coupling phenomenon led to the concept of neurovascular unit (NVU that consists of the endothelium, glia, neurons, pericytes, and the basal lamina. Here, recent works suggest NVU as an integrated system working in concert using feedback mechanisms to enable proper brain homeostasis and function where the challenge remains in capturing these mostly nonlinear spatiotemporal interactions within NVU during tDCS. Therefore, we propose EEG-NIRS-based whole-head monitoring of tDCS-induced neuronal and hemodynamic alterations for brain-state dependent tDCS.

  8. Mycobacterium tuberculosis UvrB Is a Robust DNA-Stimulated ATPase That Also Possesses Structure-Specific ATP-Dependent DNA Helicase Activity.

    Science.gov (United States)

    Thakur, Manoj; Kumar, Mohan B J; Muniyappa, K

    2016-10-18

    Much is known about the Escherichia coli nucleotide excision repair (NER) pathway; however, very little is understood about the proteins involved and the molecular mechanism of NER in mycobacteria. In this study, we show that Mycobacterium tuberculosis UvrB (MtUvrB), which exists in solution as a monomer, binds to DNA in a structure-dependent manner. A systematic examination of MtUvrB substrate specificity reveals that it associates preferentially with single-stranded DNA, duplexes with 3' or 5' overhangs, and linear duplex DNA with splayed arms. Whereas E. coli UvrB (EcUvrB) binds weakly to undamaged DNA and has no ATPase activity, MtUvrB possesses intrinsic ATPase activity that is greatly stimulated by both single- and double-stranded DNA. Strikingly, we found that MtUvrB, but not EcUvrB, possesses the DNA unwinding activity characteristic of an ATP-dependent DNA helicase. The helicase activity of MtUvrB proceeds in the 3' to 5' direction and is strongly modulated by a nontranslocating 5' single-stranded tail, indicating that in addition to the translocating strand it also interacts with the 5' end of the substrate. The fraction of DNA unwound by MtUvrB decreases significantly as the length of the duplex increases: it fails to unwind duplexes longer than 70 bp. These results, on one hand, reveal significant mechanistic differences between MtUvrB and EcUvrB and, on the other, support an alternative role for UvrB in the processing of key DNA replication intermediates. Altogether, our findings provide insights into the catalytic functions of UvrB and lay the foundation for further understanding of the NER pathway in M. tuberculosis.

  9. Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience-dependent plasticity.

    Science.gov (United States)

    Hannan, A J

    2014-02-01

    Environmental enrichment (EE) increases levels of novelty and complexity, inducing enhanced sensory, cognitive and motor stimulation. In wild-type rodents, EE has been found to have a range of effects, such as enhancing experience-dependent cellular plasticity and cognitive performance, relative to standard-housed controls. Whilst environmental enrichment is of course a relative term, dependent on the nature of control environmental conditions, epidemiological studies suggest that EE has direct clinical relevance to a range of neurological and psychiatric disorders. EE has been demonstrated to induce beneficial effects in animal models of a wide variety of brain disorders. The first evidence of beneficial effects of EE in a genetically targeted animal model was generated using Huntington's disease transgenic mice. Subsequent studies found that EE was also therapeutic in mouse models of Alzheimer's disease, consistent with epidemiological studies of relevant environmental modifiers. EE has also been found to ameliorate behavioural, cellular and molecular deficits in animal models of various neurological and psychiatric disorders, including Parkinson's disease, stroke, traumatic brain injury, epilepsy, multiple sclerosis, depression, schizophrenia and autism spectrum disorders. This review will focus on the effects of EE observed in animal models of neurodegenerative brain diseases, at molecular, cellular and behavioural levels. The proposal that EE may act synergistically with other approaches, such as drug and cell therapies, to facilitate brain repair will be discussed. I will also discuss the therapeutic potential of 'enviromimetics', drugs which mimic or enhance the therapeutic effects of cognitive activity and physical exercise, for both neuroprotection and brain repair. © 2013 British Neuropathological Society.

  10. Stimulation of Na+-alanine cotransport activates a voltage-dependent conductance in single proximal tubule cells isolated from frog kidney

    Science.gov (United States)

    Robson, L; Hunter, M

    1999-01-01

    The swelling induced by Na+-alanine cotransport in proximal tubule cells of the frog kidney is followed by regulatory volume decrease (RVD). This RVD is inhibited by gadolinium (Gd3+), an inhibitor of stretch-activated channels, but is independent of extracellular Ca2+. In this study, the whole cell patch clamp technique was utilized to examine the effect of Na+-alanine cotransport on two previously identified volume- and Gd3+-sensitive conductances. One conductance is voltage dependent and anion selective (GVD) whilst the other is voltage independent and cation selective (GVI). Addition of 5 mM L-alanine to the bathing solution increased the whole cell conductance and gave a positive (depolarizing) shift in the reversal potential (Vrev, equivalent to the membrane potential in current-clamped cells) consistent with activation of Na+-alanine cotransport. Vrev shifted from -36 ± 4·9 to +12·9 ± 4·2 mV (n= 15). In the presence of alanine, the total whole cell conductance had several components including the cotransporter conductance and GVD and GVI. These conductances were separated using Gd3+, which inhibits both GVD and GVI, and the time dependency of GVD. Of these two volume-sensitive conductances, L-alanine elicited a specific increase in GVD, whereas GVI was unaffected. The L-alanine-induced activation of GVD was significantly reduced when cells were incubated in a hypertonic bathing solution. In summary, in single proximal tubule cells isolated from frog kidney, on stimulation of Na+-alanine cotransport GVD is activated, while GVI is unaffected. Taken with other evidence, this suggests that GVD is activated by cell swelling, consequent upon alanine entry, and may play a role as an anion efflux pathway during alanine-induced volume regulation. PMID:10226159

  11. SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.

    Science.gov (United States)

    Kolodziej, Angela; Lippert, Michael; Angenstein, Frank; Neubert, Jenni; Pethe, Annette; Grosser, Oliver S; Amthauer, Holger; Schroeder, Ulrich H; Reymann, Klaus G; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

    2014-12-01

    Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography. Copyright © 2014 The Authors

  12. Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure.

    Science.gov (United States)

    Susick, Laura L; Lowing, Jennifer L; Bosse, Kelly E; Hildebrandt, Clara C; Chrumka, Alexandria C; Conti, Alana C

    2014-08-01

    Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the

  13. Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

    Science.gov (United States)

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-03-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism*

    Science.gov (United States)

    Ishii, Masakazu; Shibata, Rei; Kondo, Kazuhisa; Kambara, Takahiro; Shimizu, Yuuki; Tanigawa, Tohru; Bando, Yasuko K.; Nishimura, Masahiro; Ouchi, Noriyuki; Murohara, Toyoaki

    2014-01-01

    Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes in vitro and in vivo. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice in vivo. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes in vitro. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production. PMID:25100725

  15. Vildagliptin stimulates endothelial cell network formation and ischemia-induced revascularization via an endothelial nitric-oxide synthase-dependent mechanism.

    Science.gov (United States)

    Ishii, Masakazu; Shibata, Rei; Kondo, Kazuhisa; Kambara, Takahiro; Shimizu, Yuuki; Tanigawa, Tohru; Bando, Yasuko K; Nishimura, Masahiro; Ouchi, Noriyuki; Murohara, Toyoaki

    2014-09-26

    Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes in vitro and in vivo. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice in vivo. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes in vitro. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Urokinase-type plasminogen activator (uPA) stimulates triglyceride synthesis in Huh7 hepatoma cells via p38-dependent upregulation of DGAT2.

    Science.gov (United States)

    Paland, Nicole; Gamliel-Lazarovich, Aviva; Coleman, Raymond; Fuhrman, Bianca

    2014-11-01

    The liver is the central organ of fatty acid and triglyceride metabolism. Oxidation and synthesis of fatty acids and triglycerides is under the control of peroxisome-proliferator-activated receptors (PPAR) α. Impairment of these receptors' function contributes to the accumulation of triglycerides in the liver resulting in non-alcoholic fatty liver disease. Urokinase-type plasminogen activator (uPA) was shown to regulate gene expression in the liver involving PPARγ transcriptional activity. In this study we questioned whether uPA modulates triglyceride metabolism in the liver, and investigated the mechanisms involved in the observed processes. Huh7 hepatoma cells were incubated with increasing concentrations of uPA for 24 h uPA dose-dependently increased the cellular triglyceride mass, and this effect resulted from increased de novo triglyceride synthesis mediated by the enzyme diglyceride acyltransferase 2 (DGAT2). Also, the amount of free fatty acids was highly up regulated by uPA through activation of the transcription factor SREBP-1. Chemical activation of PPARα further increased uPA-stimulated triglyceride synthesis, whereas inhibition of p38, an upstream activator of PPARα, completely abolished the stimulatory effect of uPA on both triglyceride synthesis and DGAT2 upregulation. The effect of uPA on triglyceride synthesis in Huh7 cells was mediated via binding to its receptor, the uPAR. In vivo studies in uPAR(-/-) mice demonstrated that no lipid droplets were observed in their livers compared to C57BL/6 mice and the triglyceride levels were significantly lower. This study presents a new biological function of the uPA/uPAR system in the metabolism of triglycerides and might present a new target for an early therapeutic intervention for NAFLD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Effects of transcranial direct current stimulation over left dorsolateral pFC on the attentional blink depend on individual baseline performance

    NARCIS (Netherlands)

    London, R.E.; Slagter, H.A.

    2015-01-01

    Selection mechanisms that dynamically gate only relevant perceptual information for further processing and sustained representation in working memory are critical for goal-directed behavior. We examined whether this gating process can be modulated by anodal transcranial direct current stimulation

  18. Relative contribution of glycogenolysis and gluconeogenesis to basal, glucagon- and nerve stimulation-dependent glucose output in the perfused liver from fed and fasted rats

    NARCIS (Netherlands)

    Beuers, U.; JUNGERMANN, K.

    1990-01-01

    The relative contribution to basal, glucagon- and nerve stimulation-enhanced glucose output of glycogenolysis (glucose output in the presence of the gluconeogenic inhibitor mercaptopicolinate) and gluconeogenesis (difference in glucose output in the absence and presence of the inhibitor) was

  19. Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway

    International Nuclear Information System (INIS)

    Karam, Manale; Legay, Christine; Auclair, Christian; Ricort, Jean-Marc

    2012-01-01

    Protein kinase D1, PKD1, is a novel serine/threonine kinase whose altered expression and dysregulation in many tumors as well as its activation by several mitogens suggest that this protein could regulate proliferation and tumorigenesis. Nevertheless, the precise signaling pathways used are still unclear and the potential direct role of PKD1 in tumor development and progression has not been yet investigated. In order to clarify the role of PKD1 in cell proliferation and tumorigenesis, we studied the effects of PKD1 overexpression in a human adenocarcinoma breast cancer cell line, MCF-7 cells. We demonstrated that overexpression of PKD1 specifically promotes MCF-7 cell proliferation through accelerating G0/G1 to S phase transition of the cell cycle. Moreover, inhibition of endogenous PKD1 significantly reduced cell proliferation. Taken together, these results clearly strengthen the regulatory role of PKD1 in cell growth. We also demonstrated that overexpression of PKD1 specifically diminished serum- and anchorage-dependence for proliferation and survival in vitro and allowed MCF-7 cells to form tumors in vivo. Thus, all these data highlight the central role of PKD1 in biological processes which are hallmarks of malignant transformation. Analysis of two major signaling pathways implicated in MCF-7 cell proliferation showed that PKD1 overexpression significantly increased ERK1/2 phosphorylation state without affecting Akt phosphorylation. Moreover, PKD1 overexpression-stimulated cell proliferation and anchorage-independent growth were totally impaired by inhibition of the MEK/ERK kinase cascade. However, neither of these effects was affected by blocking the PI 3-kinase/Akt signaling pathway. Thus, the MEK/ERK signaling appears to be a determining pathway mediating the biological effects of PKD1 in MCF-7 cells. Taken together, all these data demonstrate that PKD1 overexpression increases the aggressiveness of MCF-7 breast cancer cells through enhancing their oncogenic

  20. Phosphorylation of rat kidney Na-K pump at Ser938 is required for rapid angiotensin II-dependent stimulation of activity and trafficking in proximal tubule cells.

    Science.gov (United States)

    Massey, Katherine J; Li, Quanwen; Rossi, Noreen F; Keezer, Susan M; Mattingly, Raymond R; Yingst, Douglas R

    2016-02-01

    How angiotensin (ANG) II acutely stimulates the Na-K pump in proximal tubules is only partially understood, limiting insight into how ANG II increases blood pressure. First, we tested whether ANG II increases the number of pumps in plasma membranes of native rat proximal tubules under conditions of rapid activation. We found that exposure to 100 pM ANG II for 2 min, which was previously shown to increase affinity of the Na-K pump for Na and stimulate activity threefold, increased the amount of the Na-K pump in plasma membranes of native tubules by 33%. Second, we tested whether previously observed increases in phosphorylation of the Na-K pump at Ser(938) were part of the stimulatory mechanism. These experiments were carried out in opossum kidney cells, cultured proximal tubules stably coexpressing the ANG type 1 (AT1) receptor, and either wild-type or a S938A mutant of rat kidney Na-K pump under conditions found by others to stimulate activity. We found that 10 min of incubation in 10 pM ANG II stimulated activity of wild-type pumps from 2.3 to 3.5 nmol K · mg protein(-1) · min(-1) and increased the amount of the pump in the plasma membrane by 80% but had no effect on cells expressing the S938A mutant. We conclude that acute stimulation of Na-K pump activity in native rat proximal tubules includes increased trafficking to the plasma membrane and that phosphorylation at Ser(938) is part of the mechanism by which ANG II directly stimulates activity and trafficking of the rat kidney Na-K pump in opossum kidney cells.

  1. Cerebral blood flow modulation by Basal forebrain or whisker stimulation can occur independently of large cytosolic Ca2+ signaling in astrocytes.

    Science.gov (United States)

    Takata, Norio; Nagai, Terumi; Ozawa, Katsuya; Oe, Yuki; Mikoshiba, Katsuhiko; Hirase, Hajime

    2013-01-01

    We report that a brief electrical stimulation of the nucleus basalis of Meynert (NBM), the primary source of cholinergic projection to the cerebral cortex, induces a biphasic cerebral cortical blood flow (CBF) response in the somatosensory cortex of C57BL/6J mice. This CBF response, measured by laser Doppler flowmetry, was attenuated by the muscarinic type acetylcholine receptor antagonist atropine, suggesting a possible involvement of astrocytes in this type of CBF modulation. However, we find that IP3R2 knockout mice, which lack cytosolic Ca2+ surges in astrocytes, show similar CBF changes. Moreover, whisker stimulation resulted in similar degrees of CBF increase in IP3R2 knockout mice and the background strain C57BL/6J. Our results show that neural activity-driven CBF modulation could occur without large cytosolic increases of Ca2+ in astrocytes.

  2. Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Bottelier, Marco A.; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G. H.; Bouziane, Cheima; Kooij, J. J. Sandra; de Ruiter, Michiel B.; Reneman, Liesbeth

    2017-01-01

    In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant

  3. The pathway to muscle fibrosis depends on myostatin stimulating the differentiation of fibro/adipogenic progenitor cells in chronic kidney disease.

    Science.gov (United States)

    Dong, Jiangling; Dong, Yanjun; Chen, Zihong; Mitch, William E; Zhang, Liping

    2017-01-01

    Fibrosis in skeletal muscle develops after injury or in response to chronic kidney disease (CKD), but the origin of cells becoming fibrous tissue and the initiating and sustaining mechanisms causing muscle fibrosis are unclear. We identified muscle fibro/adipogenic progenitor cells (FAPs) that potentially differentiate into adipose tissues or fibrosis. We also demonstrated that CKD stimulates myostatin production in muscle. Therefore, we tested whether CKD induces myostatin, which stimulates fibrotic differentiation of FAPs leading to fibrosis in skeletal muscles. We isolated FAPs from mouse muscles and found that myostatin stimulates their proliferation and conversion into fibrocytes. In vivo, FAPs isolated from EGFP-transgenic mice (FAPs-EGFP) were transplanted into muscles of mice with CKD or into mouse muscles that were treated with myostatin. CKD or myostatin stimulated FAPs-EGFP proliferation in muscle and increased α-smooth muscle actin expression in FAP-EGFP cells. When myostatin was inhibited with a neutralizing peptibody (a chimeric peptide-Fc fusion protein), the FAP proliferation and muscle fibrosis induced by CKD were both suppressed. Knocking down Smad3 in cultured FAPs interrupted their conversion into fibrocytes, indicating that myostatin directly converts FAPs into fibrocytes. Thus, counteracting myostatin may be a strategy for preventing the development of fibrosis in skeletal muscles of patients with CKD. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. TGF beta-1 dependent fast stimulation of ATM and p53 phosphorylation following exposure to ionizing radiation does not involve TGF beta-receptor I signalling

    NARCIS (Netherlands)

    Wiegman, Erwin M.; Blaese, Marcet A.; Loeffler, Heidi; Coppes, Rob P.; Rodemann, H. Peter

    Background and purpose: It has been proposed that radiation induced stimulation of ATM and downstream components involves activation of TGF beta-1 and that this may be due to TGF beta-1-receptor I-Smad signalling. Therefore, the aim of this study was to clarify the distinct role of TGF

  5. NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

    Directory of Open Access Journals (Sweden)

    Xinyan Gao

    2012-01-01

    Full Text Available Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs. Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-ylpropanoic-acid-(AMPA- receptor-(AMPAR- mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV. We also identified that suppression of presynaptic μ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A- containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

  6. Thermal dependence of time-resolved blue light stimulated luminescence in α-Al2O3:C

    DEFF Research Database (Denmark)

    Pagonis, Vasilis; Ankjærgaard, Christina; Jain, Mayank

    2013-01-01

    (activation energy, Eth=0.067±0.002 eV) and thermal quenching (activation energy W=(1.032+0.005) eV). Changes in the shape of the TR-OSL curves were analyzed at different stimulation temperatures using analytical expressions available in the literature. The TR-OSL signals contain a slower temperature...

  7. High density lipoprotein stimulated migration of macrophages depends on the scavenger receptor class B, type I, PDZK1 and Akt1 and is blocked by sphingosine 1 phosphate receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Aishah Al-Jarallah

    Full Text Available HDL carries biologically active lipids such as sphingosine-1-phosphate (S1P and stimulates a variety of cell signaling pathways in diverse cell types, which may contribute to its ability to protect against atherosclerosis. HDL and sphingosine-1-phosphate receptor agonists, FTY720 and SEW2871 triggered macrophage migration. HDL-, but not FTY720-stimulated migration was inhibited by an antibody against the HDL receptor, SR-BI, and an inhibitor of SR-BI mediated lipid transfer. HDL and FTY720-stimulated migration was also inhibited in macrophages lacking either SR-BI or PDZK1, an adaptor protein that binds to SR-BI's C-terminal cytoplasmic tail. Migration in response to HDL and S1P receptor agonists was inhibited by treatment of macrophages with sphingosine-1-phosphate receptor type 1 (S1PR1 antagonists and by pertussis toxin. S1PR1 activates signaling pathways including PI3K-Akt, PKC, p38 MAPK, ERK1/2 and Rho kinases. Using selective inhibitors or macrophages from gene targeted mice, we demonstrated the involvement of each of these pathways in HDL-dependent macrophage migration. These data suggest that HDL stimulates the migration of macrophages in a manner that requires the activities of the HDL receptor SR-BI as well as S1PR1 activity.

  8. Stimulation by ATP of proinsulin to insulin conversion in isolated rat pancreatic islet secretory granules. Association with the ATP-dependent proton pump

    International Nuclear Information System (INIS)

    Rhodes, C.J.; Lucas, C.A.; Mutkoski, R.L.; Orci, L.; Halban, P.A.

    1987-01-01

    Isolated rat pancreatic islets were pulse-labeled for 5 min with [ 3 H]leucine then chased for 25 min, during which time endogenously labeled [ 3 H]proinsulin becomes predominantly compartmented in immature secretory granules. The islets were then homogenized in isotonic sucrose (pH 7.4) and a beta-granule preparation obtained by differential centrifugation and discontinuous sucrose gradient ultracentrifugation. This preparation was enriched 8-fold in beta-granules. Aside from contamination with mitochondria and a limited number of lysosomes, the beta-granule preparation was essentially free of any other organelles involved in proinsulin synthesis and packaging (i.e. microsomal elements and, more particularly, Golgi complex). Conversion of endogenously labeled [ 3 H]proinsulin was followed in this beta-granule fraction for up to 2 h at 37 degrees C in a buffer (pH 7.3) that mimicked the cationic constituents of B-cell cytosol, during which time 92% of the beta-granules remained intact. Proinsulin conversion was analyzed by high performance liquid chromatography. The rate of proinsulin conversion to insulin was stimulated by 2.2 +/- 0.1-fold (n = 6) (at a 60-min incubation) in the presence of ATP (2 mM) and an ATP regenerating system compared to beta-granule preparations incubated without ATP. This ATP stimulation was abolished in the presence of beta-granule proton pump ATPase inhibitors (tributyltin, 2.5 microM, or 1,3-dicyclohexylcarbodiimide, 50 microM). Inhibitors of mitochondrial proton pump ATPases had no effect on the ATP stimulation of proinsulin conversion. When granules were incubated in a more acidic buffer, proinsulin conversion was increased relative to that at pH 7.3. At pH 5.5, ATP no longer stimulated conversion, and tributyltin and 1,3-dicyclohexylcarbodiimide had no effect

  9. Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism

    OpenAIRE

    Cawthorn, William P.; Bree, Adam J.; Yao, Yao; Du, Baowen; Hemati, Nahid; Martinez-Santibañez, Gabriel; MacDougald, Ormond A.

    2011-01-01

    Wnt10b is an established regulator of mesenchymal stem cell (MSC) fate that inhibits adipogenesis and stimulates osteoblastogenesis, thereby impacting bone mass in vivo. However, downstream mechanisms through which Wnt10b exerts these effects are poorly understood. Moreover, whether other endogenous Wnt ligands also modulate MSC fate remains to be fully addressed. In this study, we identify Wnt6 and Wnt10a as additional Wnt family members that, like Wnt10b, are downregulated during developmen...

  10. Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction.

    Science.gov (United States)

    Steiner, Jennifer L; Lang, Charles H

    2014-11-15

    Alcohol (EtOH) decreases protein synthesis and mammalian target of rapamycin (mTOR)-mediated signaling and blunts the anabolic response to growth factors in skeletal muscle. The purpose of the current investigation was to determine whether acute EtOH intoxication antagonizes the contraction-induced increase in protein synthesis and mTOR signaling in skeletal muscle. Fasted male mice were injected intraperitoneally with 3 g/kg EtOH or saline (control), and the right hindlimb was electrically stimulated (10 sets of 6 contractions). The gastrocnemius muscle complex was collected 30 min, 4 h, or 12 h after stimulation. EtOH decreased in vivo basal protein synthesis (PS) in the nonstimulated muscle compared with time-matched Controls at 30 min, 4 h, and 12 h. In Control, but not EtOH, PS was decreased 15% after 30 min. In contrast, PS was increased in Control 4 h poststimulation but remained unchanged in EtOH. Last, stimulation increased PS 10% in Control and EtOH at 12 h, even though the absolute rate remained reduced by EtOH. The stimulation-induced increase in the phosphorylation of S6K1 Thr(421)/Ser(424) (20-52%), S6K1 Thr(389) (45-57%), and its substrate rpS6 Ser(240/244) (37-72%) was blunted by EtOH at 30 min, 4 h, and 12 h. Phosphorylation of 4E-BP1 Ser(65) was also attenuated by EtOH (61%) at 4 h. Conversely, phosphorylation of extracellular signal-regulated kinase Thr(202)/Tyr(204) was increased by stimulation in Control and EtOH mice at 30 min but only in Control at 4 h. Our data indicate that acute EtOH intoxication suppresses muscle protein synthesis for at least 12 h and greatly impairs contraction-induced changes in synthesis and mTOR signaling. Copyright © 2014 the American Physiological Society.

  11. Analyzing the experiences of adolescent control rats: Effects of the absence of physical or social stimulation on anxiety-like behaviour are dependent on the test.

    Science.gov (United States)

    Joshi, Namrata; Leslie, Ronald A; Perrot, Tara S

    2017-10-01

    The present study was designed to systematically assess the control experience routinely used in our laboratory as part of studies on predator odour stress. Specifically, we examined effects of the physical and social components of this control experience on measures of anxiety-like behaviour in adolescent rats. Adolescent animals are at increased susceptibility to environmental perturbations and have been used for such studies much less often. Long-Evans rats of both sexes were subjected to physical stimulation (Exposed or Unexposed) and social stimulation (Single-Housed or Pair-Housed), resulting in four groups. Exposed rats received six 30-min exposures to an enclosed arena containing an unscented piece of cat collar occurring between adolescence and early adulthood, while Unexposed remained in the home cage. Groups of Exposed and Unexposed animals were housed singly (Single-Housed) from early adolescence to early adulthood or Pair-Housed during this time. Experimental procedures began in adolescence and involved repeated assessment of startle amplitude (measure of anxiety-like behaviour) and prepulse inhibition (PPI; a measure of sensorimotor gating) to gauge the short-term impact of social and/or physical stimulation. All animals were re-paired in adulthood prior to a final startle/PPI session to assess if isolation limited to adolescence could impose long-term effects that were not reversible. We also measured anxiety-like behaviour in adulthood using an extended open field test (EOFT; addition of novel objects to the open field on later days), and the elevated plus maze task (EPM), as well as a sucrose preference test (SPT) to measure anhedonia. An absence of social or physical stimulation resulted in increased startle amplitude and some measures of anxiety-like behaviour in the EOFT, but a reduction in such anxiety-like behaviour in the EPM task. These results suggest common neural substrates for the physical and social experiences. Performance in the SPT

  12. Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Møller, Jens

    1994-01-01

    . CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused......Abstract OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose...... without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P

  13. Formation of PI 3-kinase products in platelets by thrombin, but not collagen, is dependent on synergistic autocrine stimulation, particularly through secreted ADP.

    Science.gov (United States)

    Selheim, F; Idsøe, R; Fukami, M H; Holmsen, H; Vassbotn, F S

    1999-10-05

    Platelet activation by thrombin or collagen results in secretion and synthesis of several platelet agonists that enhance the responses to the primary agonists (autocrine stimulation). To disclose the effects of thrombin and collagen on the phosphorylation of 3-phosphoinositides per se we incubated platelets with five inhibitors of platelet autocrine stimulation (IAS) that act extracellularly. We found that IAS almost totally blocked thrombin-induced production of phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)]. In contrast, collagen induced massive production of PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) in the presence of IAS. When testing the effect of each inhibitor individually we found the strongest inhibition of thrombin-induced PtdIns(3,4)P(2) production with the ADP scavenger system CP/CPK. Furthermore, we found a strong synergistic effect between exogenously added ADP and thrombin on production of PtdIns(3,4)P(2). In contrast to the results from 3-phosphorylated phosphoinositides, CP/CPK had little effect on thrombin-induced protein tyrosine phosphorylation. Our results show the importance of autocrine stimulation in thrombin-induced accumulation of 3-phosphorylated phosphoinositides and raise the question as to whether thrombin by itself is capable of inducing PI 3-K activation. In marked contrast to thrombin, collagen per se appears to be able to trigger increased production of PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3). Copyright 1999 Academic Press.

  14. Tetanic stimulation leads to increased accumulation of Ca2+ calmodulin-dependent protein kinase II via dendritic protein synthesis in hippocampal neurons

    OpenAIRE

    Rosenstein, Alan; Kreiman, Gabriel; Schuman, Erin M; Kennedy, Mary

    1999-01-01

    mRNA for the alpha-subunit of CaMKII is abundant in dendrites of neurons in the forebrain (Steward, 1997). Here we show that tetanic stimulation of the Schaffer collateral pathway causes an increase in the concentration of alpha-CaMKII in the dendrites of postsynaptic neurons. The increase is blocked by anisomycin and is detected by both quantitative immunoblot and semiquantitative immunocytochemistry. The increase in dendritic alpha-CaMKII can be measured 100-200 micrometer away from the neu...

  15. Monitoring the distributed impact wave on a concrete slab due to the traffic based on polarization dependence on stimulated Brillouin scattering

    International Nuclear Information System (INIS)

    Bao Xiaoyi; Zhang Chunshu; Li Wenhai; Eisa, M; El-Gamal, S; Benmokrane, B

    2008-01-01

    For the first time to our knowledge, distributed impact waves due to the highway traffic on concrete slabs reinforced with FRP bars are monitored in real time using stimulated Brillouin scattering. The impact wave is caused by the traffic passing on the highway pavement at high speed (>100 km h −1 ), which induced pressure on the concrete slabs, and in turn created a local birefringence change, leading to variation of the local state of polarization change (SOP). The pump and probe waves of the stimulated Brillouin scattering 'see' the SOP change and react with a decrease of the Brillouin gain or loss signal, when the pump and probe waves have the same input polarization state. The frequency difference between the pump and probe waves are locked at the static-strain-related Brillouin frequency. Optical fiber was embedded throughout the concrete pavement continuously reinforced with FRP bars in Highway 40 East, Montréal, Quebec to detect impact waves caused by cars and trucks passing on these pavements at a sampling rate of 10 kHz. A spatial resolution of 2 m was used over a sensing length of 300 m

  16. Human interleukin 1. beta. stimulates islet insulin release by a mechanism not dependent on changes in phospholipase C and protein kinase C activities or Ca sup 2+ handling

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, N.; Nilsson, T.; Hallberg, A.; Arkhammar, P.; Berggren, P.-O.; Sandler, S.

    1989-01-01

    Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1{beta} in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca{sup 2+} handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In shortterm incubations (<1 min) interleukin 1{beta} did not affect the production of inositoltrisphosphate. Addition of interleukin 1{beta} affected neither the cytoplasmic free Ca{sup 2+} concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a {sup 32}P-labelled substrate for this enzyme, was not altered by interleukin 1{beta}. Separation of {sup 32}P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1{beta} are not caused by acute activation of phospholipase C and protein kinase C or by an alternation of islet Ca{sup 2+} handling of the B-cells. (author).

  17. Human interleukin 1β stimulates islet insulin release by a mechanism not dependent on changes in phospholipase C and protein kinase C activities or Ca2+ handling

    International Nuclear Information System (INIS)

    Welsh, N.; Nilsson, T.; Hallberg, A.; Arkhammar, P.; Berggren, P.-O.; Sandler, S.

    1989-01-01

    Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1β in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca 2+ handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In shortterm incubations ( 2+ concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a 32 P-labelled substrate for this enzyme, was not altered by interleukin 1β. Separation of 32 P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1β are not caused by acute activation of phospholipase C and protein kinase C or by an alternation of islet Ca 2+ handling of the B-cells. (author)

  18. growth stimulant

    African Journals Online (AJOL)

    Effects of timing and duration of supplementation of LIVFIT VET ® (growth stimulant) as substitute for fish meal on the growth performance, haematology and clinical enzymes concentration of growing pigs.

  19. Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway

    DEFF Research Database (Denmark)

    Kolkova, K; Novitskaya, V; Pedersen, N

    2000-01-01

    , inhibitors of the nonreceptor tyrosine kinase p59(fyn), PLC, PKC and MEK and an activator of PKC, phorbol-12-myristate-13-acetate (PMA). MEK2 transfection rescued cells treated with all inhibitors. The same was found for PMA treatment, except when cells concomitantly were treated with the MEK inhibitor....... Arachidonic acid rescued cells treated with antibodies to the FGF receptor or the PLC inhibitor, but not cells in which the activity of PKC, p59(fyn), FAK, Ras, or MEK was inhibited. Interaction of NCAM with a synthetic NCAM peptide ligand, known to induce neurite outgrowth, was shown to stimulate...... phosphorylation of the MAP kinases extracellular signal-regulated kinases ERK1 and ERK2. The MAP kinase activation was sustained, because ERK1 and ERK2 were phosphorylated in PC12-E2 cells and primary hippocampal neurons even after 24 hr of cultivation on NCAM-expressing fibroblasts. Based on these results, we...

  20. High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

    Directory of Open Access Journals (Sweden)

    Ji Young Oh

    2018-04-01

    Full Text Available Background/Aims: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC migration, and analyze the mechanism accompanied by this effect. Methods: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. Results: High concentration glucose (25 mM elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS promotes two signaling; JNK which regulates γ–secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. Conclusion: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.

  1. Glucose-Dependent Insulin Secretion in Pancreatic β-Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptors.

    Directory of Open Access Journals (Sweden)

    Paola Llanos

    Full Text Available Glucose-stimulated insulin secretion (GSIS from pancreatic β-cells requires an increase in intracellular free Ca2+ concentration ([Ca2+]. Glucose uptake into β-cells promotes Ca2+ influx and reactive oxygen species (ROS generation. In other cell types, Ca2+ and ROS jointly induce Ca2+ release mediated by ryanodine receptor (RyR channels. Therefore, we explored here if RyR-mediated Ca2+ release contributes to GSIS in β-cell islets isolated from male rats. Stimulatory glucose increased islet insulin secretion, and promoted ROS generation in islets and dissociated β-cells. Conventional PCR assays and immunostaining confirmed that β-cells express RyR2, the cardiac RyR isoform. Extended incubation of β-cell islets with inhibitory ryanodine suppressed GSIS; so did the antioxidant N-acetyl cysteine (NAC, which also decreased insulin secretion induced by glucose plus caffeine. Inhibitory ryanodine or NAC did not affect insulin secretion induced by glucose plus carbachol, which engages inositol 1,4,5-trisphosphate receptors. Incubation of islets with H2O2 in basal glucose increased insulin secretion 2-fold. Inhibitory ryanodine significantly decreased H2O2-stimulated insulin secretion and prevented the 4.5-fold increase of cytoplasmic [Ca2+] produced by incubation of dissociated β-cells with H2O2. Addition of stimulatory glucose or H2O2 (in basal glucose to β-cells disaggregated from islets increased RyR2 S-glutathionylation to similar levels, measured by a proximity ligation assay; in contrast, NAC significantly reduced the RyR2 S-glutathionylation increase produced by stimulatory glucose. We propose that RyR2-mediated Ca2+ release, induced by the concomitant increases in [Ca2+] and ROS produced by stimulatory glucose, is an essential step in GSIS.

  2. Computational Flux Balance Analysis Predicts that Stimulation of Energy Metabolism in Astrocytes and their Metabolic Interactions with Neurons Depend on Uptake of K+ Rather than Glutamate.

    Science.gov (United States)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2017-01-01

    Brain activity involves essential functional and metabolic interactions between neurons and astrocytes. The importance of astrocytic functions to neuronal signaling is supported by many experiments reporting high rates of energy consumption and oxidative metabolism in these glial cells. In the brain, almost all energy is consumed by the Na + /K + ATPase, which hydrolyzes 1 ATP to move 3 Na + outside and 2 K + inside the cells. Astrocytes are commonly thought to be primarily involved in transmitter glutamate cycling, a mechanism that however only accounts for few % of brain energy utilization. In order to examine the participation of astrocytic energy metabolism in brain ion homeostasis, here we attempted to devise a simple stoichiometric relation linking glutamatergic neurotransmission to Na + and K + ionic currents. To this end, we took into account ion pumps and voltage/ligand-gated channels using the stoichiometry derived from available energy budget for neocortical signaling and incorporated this stoichiometric relation into a computational metabolic model of neuron-astrocyte interactions. We aimed at reproducing the experimental observations about rates of metabolic pathways obtained by 13 C-NMR spectroscopy in rodent brain. When simulated data matched experiments as well as biophysical calculations, the stoichiometry for voltage/ligand-gated Na + and K + fluxes generated by neuronal activity was close to a 1:1 relationship, and specifically 63/58 Na + /K + ions per glutamate released. We found that astrocytes are stimulated by the extracellular K + exiting neurons in excess of the 3/2 Na + /K + ratio underlying Na + /K + ATPase-catalyzed reaction. Analysis of correlations between neuronal and astrocytic processes indicated that astrocytic K + uptake, but not astrocytic Na + -coupled glutamate uptake, is instrumental for the establishment of neuron-astrocytic metabolic partnership. Our results emphasize the importance of K + in stimulating the activation of

  3. On the nanotoxicity of PAMAM dendrimers: Superfect® stimulates the EGFR-ERK1/2 signal transduction pathway via an oxidative stress-dependent mechanism in HEK 293 cells.

    Science.gov (United States)

    Akhtar, Saghir; Chandrasekhar, Bindu; Attur, Sreeja; Yousif, Mariam H M; Benter, Ibrahim F

    2013-05-01

    Polyamidoamine (PAMAM) dendrimers are cationic branch-like macromolecules that may serve as drug delivery systems for gene-based therapies such as RNA interference. For their safe use in the clinic, they should ideally only enhance drug delivery to target tissues and exhibit no adverse effects. However, little is known about their toxicological profiles in terms of their interactions with cellular signal transduction pathways such as the epidermal growth factor receptor (EGFR). The EGFR is an important signaling cascade that regulates cell growth, differentiation, migration, survival and apoptosis. Here, we investigated the impact of naked, unmodified Superfect (SF), a commercially available generation 6 PAMAM dendrimer, on the epidermal growth factor receptor (EGFR) tyrosine kinase-extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway in human embryonic kidney (HEK 293) cells. At concentrations routinely used for transfection, SF exhibited time and dose-dependent stimulation of EGFR and ERK1/2 phosphorylation whereas AG1478, a selective EGFR tyrosine kinase antagonist, inhibited EGFR-ERK1/2 signaling. SF-induced phosphorylation of EGFR for 1h was partly reversible upon removal of the dendrimer and examination of cells 24 later. Co-treatment of SF with epidermal growth factor (EGF) ligand resulted in greater EGFR stimulation than either agent alone implying that the stimulatory effects of SF and the ligand are synergistic. Dendrimer-induced stimulation of EGFR-ERK1/2 signaling could be attenuated by the antioxidants apocynin, catalase and tempol implying that an oxidative stress dependent mechanism was involved. These results show for the first time that PAMAM dendrimers, aside from their ability to improve drug delivery, can modulate the important EGFR-ERK1/2 cellular signal transduction pathway - a novel finding that may have a bearing on their safe application as drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients.

    Directory of Open Access Journals (Sweden)

    Sarah C Herremans

    Full Text Available In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has been suggested that high-frequency (HF repetitive transcranial magnetic stimulation (rTMS may have beneficial effects. However, exactly how this application exerts its effect on the underlying craving neurocircuit is currently unclear. In an effort to induce alcohol craving and to maximize detection of HF-rTMS effects to cue-induced alcohol craving, patients were exposed to a block and event-related alcohol cue-reactivity paradigm while being scanned with fMRI. Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC stimulation on cue-induced and general alcohol craving, and the related craving neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were included. First, we evaluated the impact of one sham-controlled stimulation session. Second, we examined the effect of accelerated right DLPFC HF-rTMS treatment: here patients received 15 sessions in an open label accelerated design, spread over 4 consecutive days. General craving significantly decreased after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not altered. Our brain imaging results did not show that the cue-exposure affected the underlying craving neurocircuit after both one and fifteen active HF-rTMS sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions, respectively, were observed in regions associated with the extended reward system and the default mode network, but only during the presentation of the event-related paradigm. Our findings indicate that accelerated HF-rTMS applied to the right DLPFC does not manifestly affect the craving neurocircuit during an alcohol-related cue-exposure, but instead it may influence the attentional network.

  5. Phosphorylated intermediate of (Ca2+ + K+)-stimulated Mg2+-dependent transport ATPase in endoplasmic reticulum from rat pancreatic acinar cells

    International Nuclear Information System (INIS)

    Imamura, K.; Schulz, I.

    1985-01-01

    Formation and decomposition of the phosphorylated intermediate of endoplasmic reticulum (Ca 2+ + Mg 2+ )-ATPase from pancreatic acinar cells have been studied using lithium dodecyl sulfate- and tetradecyltrimethylammonium bromide-polyacrylamide gel electrophoresis. Incorporation of 32 P from [gamma- 32 P]ATP is Ca 2+ -dependent (approximate Km for free [Ca 2+ ] = 2-3 x 10(-8) mol/liter). Formation of the 100-kDa phosphoprotein is rapid, reaching maximal 32 P incorporation within 1 s at room temperature. At 4 degrees C, phosphorylation is slower and dephosphorylation is drastically decreased. For dephosphorylation, Mg 2+ and monovalent cations such as K + or Na + are necessary. Vanadate inhibits both 32 P incorporation and 32 P liberation dose dependently (Km = 3 x 10(-6) mol/liter), whereas mitochondrial inhibitors and ouabain have no effect. The phosphoprotein is stable at pH 2 and destabilizes with increasing pH being completely decomposed at pH 9. Reduction of 32 P incorporation in the presence of high concentrations of cold ATP and hydroxylamine suggests formation of acylphosphate present in the ATPase intermediate. The characteristics of Ca 2+ , cation, and pH dependencies of the ATPase activity are similar to those previously described for MgATP-dependent Ca 2+ transport into rough endoplasmic reticulum from pancreatic acinar cells. The data suggest that the 100-kDa phosphoprotein as described in this study is the intermediate of this Ca2+ transport ATPase

  6. Thyroid hormone stimulated glucose uptake in human mononuclear blood cells from normal persons and from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1989-01-01

    Thyroxine and T3 induced oxygen consumption and glucose uptake were studied in vitro in mononuclear blood cells isolated from patients with non-insulin-dependent diabetes mellitus (NIDDM) and from non-diabetic control persons. Cellular oxygen consumption and glucose uptake were promptly increased...

  7. Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

    DEFF Research Database (Denmark)

    Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

    2008-01-01

    The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

  8. AS160 associates with the Na+,K+-ATPase and mediates the adenosine monophosphate-stimulated protein kinase-dependent regulation of sodium pump surface expression.

    Science.gov (United States)

    Alves, Daiane S; Farr, Glen A; Seo-Mayer, Patricia; Caplan, Michael J

    2010-12-01

    The Na(+),K(+)-ATPase is the major active transport protein found in the plasma membranes of most epithelial cell types. The regulation of Na(+),K(+)-ATPase activity involves a variety of mechanisms, including regulated endocytosis and recycling. Our efforts to identify novel Na(+),K(+)-ATPase binding partners revealed a direct association between the Na(+),K(+)-ATPase and AS160, a Rab-GTPase-activating protein. In COS cells, coexpression of AS160 and Na(+),K(+)-ATPase led to the intracellular retention of the sodium pump. We find that AS160 interacts with the large cytoplasmic NP domain of the α-subunit of the Na(+),K(+)-ATPase. Inhibition of the activity of the adenosine monophosphate-stimulated protein kinase (AMPK) in Madin-Darby canine kidney cells through treatment with Compound C induces Na(+),K(+)-ATPase endocytosis. This effect of Compound C is prevented through the short hairpin RNA-mediated knockdown of AS160, demonstrating that AMPK and AS160 participate in a common pathway to modulate the cell surface expression of the Na(+),K(+)-ATPase.

  9. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

  10. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

  11. Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Bottelier, Marco A; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G H; Bouziane, Cheima; Kooij, J J Sandra; de Ruiter, Michiel B; Reneman, Liesbeth

    2017-11-30

    In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0.5mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Visual spatial attention enhances the amplitude of positive and negative fMRI responses to visual stimulation in an eccentricity-dependent manner

    Science.gov (United States)

    Bressler, David W.; Fortenbaugh, Francesca C.; Robertson, Lynn C.; Silver, Michael A.

    2013-01-01

    Endogenous visual spatial attention improves perception and enhances neural responses to visual stimuli at attended locations. Although many aspects of visual processing differ significantly between central and peripheral vision, little is known regarding the neural substrates of the eccentricity dependence of spatial attention effects. We measured amplitudes of positive and negative fMRI responses to visual stimuli as a function of eccentricity in a large number of topographically-organized cortical areas. Responses to each stimulus were obtained when the stimulus was attended and when spatial attention was directed to a stimulus in the opposite visual hemifield. Attending to the stimulus increased both positive and negative response amplitudes in all cortical areas we studied: V1, V2, V3, hV4, VO1, LO1, LO2, V3A/B, IPS0, TO1, and TO2. However, the eccentricity dependence of these effects differed considerably across cortical areas. In early visual, ventral, and lateral occipital cortex, attentional enhancement of positive responses was greater for central compared to peripheral eccentricities. The opposite pattern was observed in dorsal stream areas IPS0 and putative MT homolog TO1, where attentional enhancement of positive responses was greater in the periphery. Both the magnitude and the eccentricity dependence of attentional modulation of negative fMRI responses closely mirrored that of positive responses across cortical areas. PMID:23562388

  13. The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients

    Directory of Open Access Journals (Sweden)

    Qiao J

    2016-09-01

    Full Text Available Jun Qiao,1,2 Guixing Jin,1,2 Licun Lei,3 Lan Wang,1,2 Yaqiang Du,3 Xueyi Wang1,2 1Institute of Mental Health, The First Hospital of Hebei Medical University, 2Brain Ageing and Cognitive Neuroscience Laboratory, Hebei Medical University, 3Department of Radiology, The First Hospital of Hebei Medical University, Hebei, People’s Republic of China Objective: To explore the effect of right dorsolateral prefrontal cortex (DLPFC repetitive transcranial magnetic stimulation (rTMS on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy (1H-MRS in recently detoxified alcohol-dependent patients. Materials and methods: In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions and the control group (sham stimulation. Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R and Brief Visuospatial Memory Test-Revised (BVMT-R before and after treatment. 1H-MRS was used to detect the levels of N-acetyl aspartic acid (NAA, choline (Cho, and creatine (Cr in bilateral hippocampi before and after treatment. Results: Thirty-eight patients (18 in the experimental group and 20 in the control group were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. Conclusion: High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified alcohol-dependent patients. Keywords: alcohol dependence, memory, repetitive transcranial magnetic stimulation, MR spectroscopy

  14. The radioprotector O-phospho-tyrosine stimulates DNA-repair via epidermal growth factor receptor- and DNA-dependent kinase phosphorylation

    International Nuclear Information System (INIS)

    Dittmann, Klaus; Mayer, Claus; Wanner, Gabriele; Kehlbach, Rainer; Rodemann, H. Peter

    2007-01-01

    Background and purpose: Purpose of the study was to elucidate the underlying molecular mechanism of the radioprotector O-phospho-tyrosine (P-Tyr). Methods: Molecular effects of P-Tyr at the level of EGFR responses were investigated in vitro with bronchial carcinoma cell line A549. Nuclear EGFR transport and DNA-PK activation were quantified after Western blotting. Residual DNA-damages were quantified by help of γH 2 AX focus assay. Results: As determined by dose-response curves, treatment of cells with P-Tyr for 16 h before irradiation results in radioprotection. Simultaneous treatment with EGFR blocking antibody Cetuximab abolished P-Tyr associated radioprotection. At the molecular level P-Tyr mediated a general phosphorylation of EGFR and a pronounced phosphorylation of nuclear EGFR at residue Thr No. 654, also observed after treatment with ionizing radiation. This phosphorylation was associated with nuclear EGFR accumulation. Moreover, P-Tyr-triggered EGFR nuclear accumulation was associated with phosphorylation of DNA-PK at Thr 2609. This activated form of DNA-PK was not DNA associated, but after radiation, DNA binding increased, particularly after P-Tyr pre-treatment. These molecular effects of P-Tyr resulted in a reduction of residual DNA-damage after irradiation. Conclusions: Radioprotection by P-Tyr is mediated through its stimulation of nuclear EGFR transport and concurrent, but DNA-damage independent, activation of DNA-PK. Thus, subsequent irradiation results in increased binding of DNA-PK to DNA, improved DNA-repair and increased cell survival

  15. Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism

    Science.gov (United States)

    Hamdi, M M; Mutungi, G

    2011-01-01

    Abstract Dihydrotestosterone (DHT) has acute/non-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acute/non-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and α-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acute/non-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression. PMID:21606113

  16. The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients.

    Science.gov (United States)

    Qiao, Jun; Jin, Guixing; Lei, Licun; Wang, Lan; Du, Yaqiang; Wang, Xueyi

    2016-01-01

    To explore the effect of right dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy ( 1 H-MRS) in recently detoxified alcohol-dependent patients. In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions) and the control group (sham stimulation). Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) before and after treatment. 1 H-MRS was used to detect the levels of N -acetyl aspartic acid (NAA), choline (Cho), and creatine (Cr) in bilateral hippocampi before and after treatment. Thirty-eight patients (18 in the experimental group and 20 in the control group) were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1 H-MRS in recently detoxified alcohol-dependent patients.

  17. Pacemaker, implanted cardiac defibrillator and irradiation: Management proposal in 2010 depending on the type of cardiac stimulator and prognosis and location of cancer

    International Nuclear Information System (INIS)

    Lambert, P.; Da Costa, A.; Marcy, P.Y.; Kreps, S.; Angellier, G.; Marcie, S.; Bondiau, P.Y.; Briand-Amoros, C.; Thariat, J.

    2011-01-01

    Ionizing radiation may interfere with electric components of pacemakers or implantable cardioverter defibrillators. The type, severity and extent of radiation damage to pacemakers, have previously been shown to depend on the total dose and dose rate. Over 300,000 new cancer cases are treated yearly in France, among which 60% are irradiated in the course of their disease. One among 400 of these patients has an implanted pacemaker or defibrillator. The incidence of pacemaker and implanted cardioverter defibrillator increases in an ageing population. The oncologic prognosis must be weighted against the cardiologic prognosis in a multidisciplinary and transversal setting. Innovative irradiation techniques and technological sophistications of pacemakers and implantable cardioverter-defibrillators (with the introduction of more radiosensitive complementary metal-oxide-semiconductors since 1970) have potentially changed the tolerance profiles. This review of the literature studied the geometric, dosimetric and radiobiological characteristics of the radiation beams for high energy photons, stereotactic irradiation, proton-therapy. Standardized protocols and radiotherapy optimization (particle, treatment fields, energy) are advisable in order to improve patient management during radiotherapy and prolonged monitoring is necessary following radiation therapy. The dose received at the pacemaker/heart should be calculated. The threshold for the cumulated dose to the pacemaker/implantable cardioverter-defibrillator (2 to 5 Gy depending on the brand), the necessity to remove/displace the device based on the dose-volume histogram on dosimetry, as well as the use of lead shielding and magnet are discussed. (authors)

  18. Airborne signals from Trichoderma fungi stimulate iron uptake responses in roots resulting in priming of jasmonic acid-dependent defences in shoots of Arabidopsis thaliana and Solanum lycopersicum.

    Science.gov (United States)

    Martínez-Medina, Ainhoa; Van Wees, Saskia C M; Pieterse, Corné M J

    2017-11-01

    Root colonization by Trichoderma fungi can trigger induced systemic resistance (ISR). In Arabidopsis, Trichoderma-ISR relies on the transcription factor MYB72, which plays a dual role in the onset of ISR and the activation of Fe uptake responses. Volatile compounds (VCs) from rhizobacteria are important elicitors of MYB72 in Arabidopsis roots. Here, we investigated the mode of action of VCs from Trichoderma fungi in the onset of ISR and Fe uptake responses. VCs from Trichoderma asperellum and Trichoderma harzianum were applied in an in vitro split-plate system with Arabidopsis or tomato seedlings. Locally, Trichoderma-VCs triggered MYB72 expression and molecular, physiological and morphological Fe uptake mechanisms in Arabidopsis roots. In leaves, Trichoderma-VCs primed jasmonic acid-dependent defences, leading to an enhanced resistance against Botrytis cinerea. By using Arabidopsis micrografts of VCs-exposed rootstocks and non-exposed scions, we demonstrated that perception of Trichoderma-VCs by the roots leads to a systemic signal that primes shoots for enhanced defences. Trichoderma-VCs also elicited Fe deficiency responses and shoot immunity in tomato, suggesting that this phenomenon is expressed in different plant species. Our results indicate that Trichoderma-VCs trigger locally a readjustment of Fe homeostasis in roots, which links to systemic elicitation of ISR by priming of jasmonic acid-dependent defences. © 2017 John Wiley & Sons Ltd.

  19. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  20. [In vitro release of [5Met]- and [5Leu]-enkephalins from the rat brain crude synaptosomal (P2) fraction: Ca2+-dependency of K+-stimulation and effects of various drugs].

    Science.gov (United States)

    Koida, M; Takahashi, M; Takenaga, K

    1983-01-01

    The rat brain P2 fraction was suspended in Krebs Ringer bicarbonate buffer containing 20 microM bacitracin and incubated at 37 degrees C for 10 min under an atmosphere of 95% O2-5% CO2. Incubation was terminated by centrifugation at 4 degrees C and 10,000 X g for 10 min. The supernatant was designated as the S1 fraction, and from the pellet, the S2 to S4 fractions were collected by repeated suspension, incubation, and centrifugation. The radioimmunoassays of each S fraction revealed the spontaneous release of [5Met]- and [5Leu]-enkephalins at the ratio of 2 to 1. The peptide contents gradually decreased from S1 to S4, but the release tended to become constant in S3 and S4. Thus, the effects of some ions and drugs on the release were compared at the stage of obtaining the S3 fraction. The release of both peptides were significantly stimulated in 50 mM KCl buffer, and the stimulatory effect appears to be dependent on Ca2+ concentration. Veratrine and A23187 were also effective stimulants of the release. On the other hand, neither spontaneous nor K+-stimulated release of enkephalins was affected by morphine (1 microM), naloxone (1 microM), kyotorphin (1 or 10 microM), and Li+ (50 mM). Similar results were obtained with the release of 3H-noradrenaline taken up in vitro by the P2 fraction. The usability of the P2 fraction as an in vitro model for the study of stimulus-coupled release of enkephalins was discussed with some limitations found herein.

  1. miR-214-Dependent Increase of PHLPP2 Levels Mediates the Impairment of Insulin-Stimulated Akt Activation in Mouse Aortic Endothelial Cells Exposed to Methylglyoxal

    Directory of Open Access Journals (Sweden)

    Cecilia Nigro

    2018-02-01

    Full Text Available Evidence has been provided linking microRNAs (miRNAs and diabetic complications, by the regulation of molecular pathways, including insulin-signaling, involved in the pathophysiology of vascular dysfunction. Methylglyoxal (MGO accumulates in diabetes and is associated with cardiovascular complications. This study aims to analyze the contribution of miRNAs in the MGO-induced damaging effect on insulin responsiveness in mouse aortic endothelial cells (MAECs. miRNA modulation was performed by transfection of specific miRNA mimics and inhibitors in MAECs, treated or not with MGO. miRNA-target protein levels were evaluated by Western blot. PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2 regulation by miR-214 was tested by luciferase assays and by the use of a target protector specific for miR-214 on PHLPP2-3′UTR. This study reveals a 4-fold increase of PHLPP2 in MGO-treated MAECs. PHLPP2 levels inversely correlate with miR-214 modulation. Moreover, miR-214 overexpression is able to reduce PHLPP2 levels in MGO-treated MAECs. Interestingly, a direct regulation of PHLPP2 is proved to be dependent by miR-214. Finally, the inhibition of miR-214 impairs the insulin-dependent Akt activation, while its overexpression rescues the insulin effect on Akt activation in MGO-treated MAECs. In conclusion, this study shows that PHLPP2 is a target of miR-214 in MAECs, and identifies miR-214 downregulation as a contributing factor to MGO-induced endothelial insulin-resistance.

  2. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  3. Dual Stimulus-Dependent Effect of Oenothera paradoxa Extract on the Respiratory Burst in Human Leukocytes: Suppressing for Escherichia coli and Phorbol Myristate Acetate and Stimulating for Formyl-Methionyl-Leucyl-Phenylalanine

    Directory of Open Access Journals (Sweden)

    Izabela Burzynska-Pedziwiatr

    2014-01-01

    Full Text Available Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA, and formyl-methionyl-leucyl-phenylalanine (fMLP. Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05 and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05. Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D-glucose (PGG, the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

  4. Dual stimulus-dependent effect of Oenothera paradoxa extract on the respiratory burst in human leukocytes: suppressing for Escherichia coli and phorbol myristate acetate and stimulating for formyl-methionyl-leucyl-phenylalanine.

    Science.gov (United States)

    Burzynska-Pedziwiatr, Izabela; Bukowiecka-Matusiak, Malgorzata; Wojcik, Marzena; Machala, Waldemar; Bienkiewicz, Malgorzata; Spolnik, Grzegorz; Danikiewicz, Witold; Wozniak, Lucyna Alicja

    2014-01-01

    Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

  5. Surface expression of anti-CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A-engineered human umbilical cord mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Qing; Yuan, Xiang-Fei; Lu, Yang; Li, Zhen-Zhen; Bao, Shi-Qi; Zhang, Xiao-Long; Yang, Yuan-Yuan; Fan, Dong-Mei; Zhang, Yi-Zhi; Wu, Chen-Xuan; Guo, Hong-Xing; Zhang, Yan-Jun; Ye, Zhou; Xiong, Dong-Sheng

    2017-10-01

    Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy. © 2017 UICC.

  6. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

  7. Anti-Inflammatory Action of an Antimicrobial Model Peptide That Suppresses the TRIF-Dependent Signaling Pathway via Inhibition of Toll-Like Receptor 4 Endocytosis in Lipopolysaccharide-Stimulated Macrophages.

    Directory of Open Access Journals (Sweden)

    Do-Wan Shim

    Full Text Available Antimicrobial peptides (AMPs, also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1β, IL-6, INF-β, and TNF-α. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation.

  8. Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

    Directory of Open Access Journals (Sweden)

    Rong Jin

    Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better

  9. Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice.

    Science.gov (United States)

    Hotta, Harumi; Uchida, Sae; Kagitani, Fusako; Maruyama, Naoki

    2011-05-01

    We examined whether activity of the nucleus basalis of Meynert (NBM) regulates regional cerebral cortical blood flow (rCBF) in mice, using laser speckle and laser Doppler flowmetry. In anesthetized mice, unilateral focal stimulation, either electrical or chemical, of the NBM increased rCBF of the ipsilateral cerebral cortex in the frontal, parietal and occipital lobes, independent of changes in systemic blood pressure. Most of vasodilative responses to low intensity stimuli (2 times threshold intensity: 2T) were abolished by atropine (a muscarinic cholinergic blocker), whereas responses to higher intensity stimuli (3T) were abolished by atropine and mecamylamine (a nicotinic cholinergic blocker). Blood flow changes were largest when the tip of the electrode was located within the area containing cholinergic neurons shown by choline acetyltransferase-immunocytochemistry. These results suggest that cholinergic projections from basal forebrain neurons in mice cause vasodilation in the ipsilateral cerebral cortex by a combination of muscarinic and nicotinic mechanisms, as previously found in rats and cats.

  10. [Caffeine dependence].

    Science.gov (United States)

    Ogawa, Naoshi; Ueki, Hirofumi

    2010-08-01

    Caffeine is the most widely consumed psychoactive substance in the world and is a legal stimulant that is readily available to children. The potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Although in recent studies, a subset of the general population was found to demonstrate caffeine dependence. It is valuable for psychiatrists and primary care physicians to recognize caffeine dependence as a clinical syndrome, since some people are distressed by their caffeine use and feel they can not control or stop their problematic use.

  11. Mean-field dynamics of a Bose-Einstein condensate in a time-dependent triple-well trap: Nonlinear eigenstates, Landau-Zener models, and stimulated Raman adiabatic passage

    International Nuclear Information System (INIS)

    Graefe, E. M.; Korsch, H. J.; Witthaut, D.

    2006-01-01

    We investigate the dynamics of a Bose-Einstein condensate in a triple-well trap in a three-level approximation. The interatomic interactions are taken into account in a mean-field approximation (Gross-Pitaevskii equation), leading to a nonlinear three-level model. Additional eigenstates emerge due to the nonlinearity, depending on the system parameters. Adiabaticity breaks down if such a nonlinear eigenstate disappears when the parameters are varied. The dynamical implications of this loss of adiabaticity are analyzed for two important special cases: A three-level Landau-Zener model and the stimulated Raman adiabatic passage (STIRAP) scheme. We discuss the emergence of looped levels for an equal-slope Landau-Zener model. The Zener tunneling probability does not tend to zero in the adiabatic limit and shows pronounced oscillations as a function of the velocity of the parameter variation. Furthermore we generalize the STIRAP scheme for adiabatic coherent population transfer between atomic states to the nonlinear case. It is shown that STIRAP breaks down if the nonlinearity exceeds the detuning

  12. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

    International Nuclear Information System (INIS)

    Aceves, J.; Young, J.M.; Arias-Montano, J.A.; Floran, B.; Garcia, M.

    1997-01-01

    The release of [ 3 H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K + from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D 1 receptor activation. The histamine H 3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [ 3 H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H 3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [ 3 H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [ 3 H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [ 3 H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H 3 receptors leads to the selective inhibition of the component of depolarization-induced [ 3 H]GABA release in substantia nigra pars reticulata slices which is dependent upon D 1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [ 3 H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  13. Dopamine D1/D5, but not D2/D3, receptor dependency of synaptic plasticity at hippocampal mossy fiber synapses that is enabled by patterned afferent stimulation, or spatial learning

    Directory of Open Access Journals (Sweden)

    Hardy Hagena

    2016-09-01

    Full Text Available Although the mossy fiber (MF synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24h synaptic plasticity that is akin to that observed at the Schaffer collateral (SCH-CA1 and perforant path (PP-dentate gyrus (DG synapses of freely behaving rats. In addition, they also respond to novel spatial learning with very enduring forms of long-term potentiation (LTP and long-term depression (LTD. These latter forms of synaptic plasticity are directly related to the learning behavior: novel exploration of generalized changes in space facilitates the expression of LTP at MF-CA3 synapses, whereas exploration of novel configurations of large environmental features facilitates the expression of LTD. In the absence of spatial novelty, synaptic plasticity is not expressed. Motivation is a potent determinant of whether learning about spatial experience effectively occurs and the neuromodulator dopamine plays a key role in motivation-based learning. Prior research on the regulation by dopamine receptors of long-term synaptic plasticity in CA1 and dentate gyrus synapses in vivo suggests that whereas D2/D3 receptors may modulate a general predisposition toward expressing plasticity, D1/D5 receptors may directly regulate the direction of change in synaptic strength that occurs during learning. Although the CA3 region is believed to play a pivotal role in many forms of learning, the role of these receptors in persistent (>24h forms of synaptic plasticity at MF-CA3 synapses is unknown. Here, we report that whereas pharmacological antagonism of D2/D3 receptors had no impact on LTP or LTD, antagonism of D1/D5 receptors significantly impaired LTP and LTD that were induced by solely by means of patterned afferent stimulation, or LTP/LTD that are typically enhanced by the conjunction of afferent stimulation and novel spatial learning. These data

  14. Particle trapping in stimulated scattering processes

    International Nuclear Information System (INIS)

    Karttunen, S.J.; Heikkinen, J.A.

    1981-01-01

    Particle trapping effects on stimulated Brillouin and Raman scattering are investigated. A time and space dependent model assumes a Maxwellian plasma which is taken to be homogeneous in the interaction region. Ion trapping has a rather weak effect on stimulated Brillouin scattering and large reflectivities are obtained even in strong trapping regime. Stimulated Raman scattering is considerably reduced by electron trapping. Typically 15-20 times larger laser intensities are required to obtain same reflectivity levels than without trapping. (author)

  15. Effects of polycationic compounds on mitogen stimulation

    DEFF Research Database (Denmark)

    Heron, I; Larsen, B; Hokland, M

    1981-01-01

    The effects of polycations added to phytomitogen stimulated human lymphocyte cultures have been studied. Within certain dose ranges all polycations tested gave rise to augmented thymidine uptake in mitogen stimulated cultures. The optimum enhancing concentrations of polycations was depending on t...

  16. Temperature-dependent luminescence and temperature-stimulated NIR-to-VIS up-conversion in Nd3+-doped La2O3-Na2O-ZnO-TeO2 glasses

    Science.gov (United States)

    Sobczyk, Marcin

    2013-04-01

    Telluride glasses of the composition xNd2O3-(7-x)La2O3-3Na2O-25ZnO-65TeO2, where (0≤x≤7) were prepared by the melt quench technique. Some physical and optical properties of the glasses were evaluated. The thermal behavior i.e. glass transition and crystallization temperatures were studied by using TGA-DTA technique. Optical properties of Nd3+-doped telluride glasses were investigated between 298 and 700 K. Basing on the obtained values of J-O parameter values (×10-20 cm2: Ω2=4.49±0.84, Ω4=5.03±0.61, Ω6=4.31±0.73), the radiative transition probabilities (AT), radiative lifetimes (τR), fluorescence branching ratios (β) and emission cross-sections (σem) were calculated for the 4F3/2→4IJ/2 (where J=9, 11 and 13) transitions of Nd3+ ions. The τR value of the 4F3/2 level amount to 164 μs and is slightly higher than the measured decay time of 162 μs. With the increasing of Nd2O3 concentration from 0.5 to 7.0 mol% the experimental lifetime of the fluorescent level decreases from 162 to 5.6 μs. The estimated quantum efficiency amount to 100%, based on a comparison of τR and the experimental decay time of a slightly doped Nd3+ telluride glass. An analysis of the non-radiative decay was based on the cross-relaxation mechanisms. The 4F3/2→4I9/2 and 4F5/2→4I9/2 transitions were analyzed with respect to the fluorescence intensity ratio (FIR) and were found to be temperature dependent. Infrared-to-visible up-conversion emissions with a maximum at 603.0 and 635.3 nm were observed at high temperatures using the 804 nm excitation and are due to the 4G5/2→4I9/2 and 4G5/2→4I11/2 transitions of Nd3+ ions, respectively. The near quadratic dependence of fluorescence on excitation laser power confirms that two photons contribute to up-conversion of the orange emissions. The temperature-stimulated up-conversion excitation processes have been analyzed in detail. The optical results indicate that the investigated glasses are potentially applicable as a 1063 nm

  17. Stimulation of phagocytosis by sulforaphane

    International Nuclear Information System (INIS)

    Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

    2011-01-01

    Research highlights: → Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. → This effect does not require Nrf2-dependent induction of phase 2 genes. → Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-μm diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2 -/- mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  18. Stimulation of phagocytosis by sulforaphane

    Energy Technology Data Exchange (ETDEWEB)

    Suganuma, Hiroyuki, E-mail: hsuganu1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Fahey, Jed W., E-mail: jfahey@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Bryan, Kelley E., E-mail: kbryanm1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Healy, Zachary R., E-mail: zhealy1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Talalay, Paul, E-mail: ptalalay@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States)

    2011-02-04

    Research highlights: {yields} Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. {yields} This effect does not require Nrf2-dependent induction of phase 2 genes. {yields} Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-{mu}m diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2{sup -/-} mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  19. Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine. Predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies

    International Nuclear Information System (INIS)

    Hartung-Knemeyer, V.; Nagarajah, J.; Jentzen, W.; Ruhlmann, M.; Freudenberg, L.S.; Stahl, A.R.; Bockisch, A.; Rosenbaum-Krumme, S.J.

    2012-01-01

    Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using 124 I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed. 198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using 124 I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT. There was no high-grade bone marrow toxicity (id est (i.e.) ≥grade 3) in patients receiving less than 2 Gy blood dose-independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman's correlation coefficient >-0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered 131 I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq). The range of BDpA among DTC patients is rather wide. Our

  20. Spinal cord stimulation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

  1. Feldspar, Infrared Stimulated Luminescence

    DEFF Research Database (Denmark)

    Jain, Mayank

    2014-01-01

    This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars.......This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars....

  2. Growth hormone stimulation test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of ...

  3. Stimulation of a Cd-binding protein, and inhibition of the vitamin D-dependent calcium-binding protein, by zinc or cadmium in organ-cultured embryonic chick duodenum

    International Nuclear Information System (INIS)

    Corradino, R.A.; Fullmer, C.S.

    1980-01-01

    Embryonic chick duodenum maintained in organ culture responds to 1 α,25-dihydroxy vitamin D 3 in the culture medium by de novo synthesis of a specific calcium-binding protein (CaBP). The addition of Cd 2+ (3-5 x 10 -5 M) or Zn 2+ (10 -5 -10 -4 M) to the medium inhibited CaBP, but stimulated biosynthesis of a Cd-binding protein (CdBP). CdBP in duodenal homogenate supernatants was assessed in two ways: first, by its 109 Cd-binding activity ( 109 CdBA) using a competitive ion exchange procedure; and, second, by the extent of [ 35 S]-cystine incorporation into a specific peak or band after gel filtration or analytical polyacrylamide disc gel electrophoresis, respectively. Regardless of whether cadmium- or zinc-stimulated, the 35 S-labeled CdBP - the only protein significantly labeled under the conditions employed - migrated identically upon gel filtration and electrophoresis, and comigrated with purified chick liver Cd-metallothionein. Neither actinomycin D nor α-amanitin, in concentrations sufficient to severely inhibit CaBP, significantly reduced CdBP production. However, cycloheximide did inhibit either Cd 2+ - or Zn 2+ -stimulated CdBP by about 50% at an inhibitor concentration which abolished CaBP. The inhibitor studies, coupled with the observations of extensive incorporation of [ 35 S]cystine into CdBP, suggest that the metals stimulated biosynthesis by a mechanism operating at the translational level. The organ-cultured duodenum seems well suited for studies of the regulation of CdBP biosynthesis especially since it responds predictably to the steroid hormone, 1α,25-dihydroxy vitamin D 3 , in the induction of another specific protein, CaBP, at the transcriptional level. The biosynthesis of CaBP thus may serve as a convenient control in studies of CdBP production under various experimental conditions

  4. Optimal number of stimulation contacts for coordinated reset neuromodulation

    Science.gov (United States)

    Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

    2013-01-01

    In this computational study we investigate coordinated reset (CR) neuromodulation designed for an effective control of synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchrony characteristic for several neurological disorders. We study how many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sites may significantly prolong the post-stimulation desynchronized transient after the stimulation is completely switched off. This can, in turn, reduce the amount of the administered stimulation current for the intermittent ON–OFF CR stimulation protocol, where time intervals with stimulation ON are recurrently followed by time intervals with stimulation OFF. In addition, we found that the optimal number of stimulation sites essentially depends on how strongly the administered current decays within the neuronal tissue with increasing distance from the stimulation site. In particular, for a broad spatial stimulation profile, i.e., for a weak spatial decay rate of the stimulation current, CR stimulation can optimally be delivered via a small number of stimulation sites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation. PMID:23885239

  5. Femtosecond Broadband Stimulated Raman Spectroscopy

    International Nuclear Information System (INIS)

    Lee, Soo-Y; Yoon, Sagwoon; Mathies, Richard A

    2006-01-01

    Femtosecond broadband stimulated Raman spectroscopy (FSRS) is a new technique where a narrow bandwidth picosecond Raman pump pulse and a red-shifted broadband femtosecond Stokes probe pulse (with or without time delay between the pulses) act on a sample to produce a high resolution Raman gain spectrum with high efficiency and speed, free from fluorescence background interference. It can reveal vibrational structural information and dynamics of stationary or transient states. Here, the quantum picture for femtosecond broadband stimulated Raman spectroscopy (FSRS) is used to develop the semiclassical coupled wave theory of the phenomenon and to derive an expression for the measurable Raman gain in FSRS. The semiclassical theory is applied to study the dependence of lineshapes in FSRS on the pump-probe time delay and to deduce vibrational dephasing times in cyclohexane in the ground state

  6. [Transcranial magnetic stimulation].

    Science.gov (United States)

    Tormos, J M; Catalá, M D; Pascual-Leone, A

    Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS. The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans. In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.

  7. Stimulating at the right time: phase-specific deep brain stimulation.

    Science.gov (United States)

    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  8. Adrenergic influence on pentagastrin and bethanechol stimulated gastric acid secretion in dogs with gastric fistula

    DEFF Research Database (Denmark)

    Hovendal, C; Bech, K; Gottrup, F

    1984-01-01

    . The inhibitory effect of isoprenaline on pentagastrin stimulated acid secretion showed the characteristics of competitive type and on bethanechol stimulated acid secretion of non competitive type. An increasing and dose-dependent stimulation of bethanechol stimulated gastric acid secretion was found for dopamine...

  9. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

    Science.gov (United States)

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  10. Music acupuncture stimulation method.

    Science.gov (United States)

    Brătilă, F; Moldovan, C

    2007-01-01

    Harmonic Medicine is the model using the theory that the body rhythms synchronize to an outer rhythm applied for therapeutic purpose, can restores the energy balance in acupuncture channels and organs and the condition of well-being. The purpose of this scientific work was to demonstrate the role played by harmonic sounds in the stimulation of the Lung (LU) Meridian (Shoutaiyin Feijing) and of the Kidney (KI) Meridian (Zushaoyin Shenjing). It was used an original method that included: measurement and electronic sound stimulation of the Meridian Entry Point, measurement of Meridian Exit Point, computer data processing, bio feed-back adjustment of the music stimulation parameters. After data processing, it was found that the sound stimulation of the Lung Meridian Frequency is optimal between 122 Hz and 128 Hz, with an average of 124 Hz (87% of the subjects) and for Kidney Meridian from 118 Hz to 121 Hz, with an average of 120 Hz (67% of the subjects). The acupuncture stimulation was more intense for female subjects (> 7%) than for the male ones. We preliminarily consider that an informational resonance phenomenon can be developed between the acupuncture music stimulation frequency and the cellular dipole frequency, being a really "resonant frequency signature" of an acupoint. The harmonic generation and the electronic excitation or low-excitation status of an acupuncture point may be considered as a resonance mechanism. By this kind of acupunctural stimulation, a symphony may act and play a healer role.

  11. Anal sphincter responses after perianal electrical stimulation

    DEFF Research Database (Denmark)

    Pedersen, Ejnar; Klemar, B; Schrøder, H D

    1982-01-01

    By perianal electrical stimulation and EMG recording from the external anal sphincter three responses were found with latencies of 2-8, 13-18 and 30-60 ms, respectively. The two first responses were recorded in most cases. They were characterised by constant latency and uniform pattern, were...... not fatigued by repeated stimulation, were most dependent on placement of stimulating and recording electrodes, and always had a higher threshold than the third response. The third response was constantly present in normal subjects. It had the longest EMG response and the latency decreased with increasing...... stimulation to a minimum of 30-60 ms. This response represented the clinical observable spinal reflex, "the classical anal reflex". The latencies of the two first responses were so short that they probably do not represent spinal reflexes. This was further supported by the effect of epidural anaesthesia which...

  12. Transcranial alternating current stimulation (tACS

    Directory of Open Access Journals (Sweden)

    Andrea eAntal

    2013-06-01

    Full Text Available Transcranial alternating current stimulation (tACS seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency or desynchronize (e.g. by the application of several frequencies cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the ripple range induces intensity dependent inhibition or excitation in the motor cortex most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in the 200 kHz range may have a potential in oncology.

  13. Closing the loop of deep brain stimulation.

    Science.gov (United States)

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-12-20

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

  14. Closing the loop of deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Romain eCARRON

    2013-12-01

    Full Text Available High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfils these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

  15. Closing the loop of deep brain stimulation

    Science.gov (United States)

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-01-01

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

  16. Albumin stimulates the activity of the human UDP-glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the effects are enzyme and substrate dependent.

    Science.gov (United States)

    Manevski, Nenad; Troberg, Johanna; Svaluto-Moreolo, Paolo; Dziedzic, Klaudyna; Yli-Kauhaluoma, Jari; Finel, Moshe

    2013-01-01

    Human UDP-glucuronosyltransferases (UGTs) are important enzymes in metabolic elimination of endo- and xenobiotics. It was recently shown that addition of fatty acid free bovine serum albumin (BSA) significantly enhances in vitro activities of UGTs, a limiting factor in in vitro-in vivo extrapolation. Nevertheless, since only few human UGT enzymes were tested for this phenomenon, we have now performed detailed enzyme kinetic analysis on the BSA effects in six previously untested UGTs, using 2-4 suitable substrates for each enzyme. We also examined some of the previously tested UGTs, but using additional substrates and a lower BSA concentration, only 0.1%. The latter concentration allows the use of important but more lipophilic substrates, such as estradiol and 17-epiestradiol. In five newly tested UGTs, 1A7, 1A8, 1A10, 2A1, and 2B15, the addition of BSA enhanced, to a different degree, the in vitro activity by either decreasing reaction's K(m), increasing its V(max), or both. In contrast, the activities of UGT2B17, another previously untested enzyme, were almost unaffected. The results of the assays with the previously tested UGTs, 1A1, 1A6, 2B4, and 2B7, were similar to the published BSA only as far as the BSA effects on the reactions' K(m) are concerned. In the cases of V(max) values, however, our results differ significantly from the previously published ones, at least with some of the substrates. Hence, the magnitude of the BSA effects appears to be substrate dependent, especially with respect to V(max) increases. Additionally, the BSA effects may be UGT subfamily dependent since K(m) decreases were observed in members of subfamilies 1A, 2A and 2B, whereas large V(max) increases were only found in several UGT1A members. The results shed new light on the complexity of the BSA effects on the activity and enzyme kinetics of the human UGTs.

  17. Albumin stimulates the activity of the human UDP-glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the effects are enzyme and substrate dependent.

    Directory of Open Access Journals (Sweden)

    Nenad Manevski

    Full Text Available Human UDP-glucuronosyltransferases (UGTs are important enzymes in metabolic elimination of endo- and xenobiotics. It was recently shown that addition of fatty acid free bovine serum albumin (BSA significantly enhances in vitro activities of UGTs, a limiting factor in in vitro-in vivo extrapolation. Nevertheless, since only few human UGT enzymes were tested for this phenomenon, we have now performed detailed enzyme kinetic analysis on the BSA effects in six previously untested UGTs, using 2-4 suitable substrates for each enzyme. We also examined some of the previously tested UGTs, but using additional substrates and a lower BSA concentration, only 0.1%. The latter concentration allows the use of important but more lipophilic substrates, such as estradiol and 17-epiestradiol. In five newly tested UGTs, 1A7, 1A8, 1A10, 2A1, and 2B15, the addition of BSA enhanced, to a different degree, the in vitro activity by either decreasing reaction's K(m, increasing its V(max, or both. In contrast, the activities of UGT2B17, another previously untested enzyme, were almost unaffected. The results of the assays with the previously tested UGTs, 1A1, 1A6, 2B4, and 2B7, were similar to the published BSA only as far as the BSA effects on the reactions' K(m are concerned. In the cases of V(max values, however, our results differ significantly from the previously published ones, at least with some of the substrates. Hence, the magnitude of the BSA effects appears to be substrate dependent, especially with respect to V(max increases. Additionally, the BSA effects may be UGT subfamily dependent since K(m decreases were observed in members of subfamilies 1A, 2A and 2B, whereas large V(max increases were only found in several UGT1A members. The results shed new light on the complexity of the BSA effects on the activity and enzyme kinetics of the human UGTs.

  18. Optimal number of stimulation contacts for coordinated reset neuromodulation

    Directory of Open Access Journals (Sweden)

    Borys eLysyansky

    2013-07-01

    Full Text Available In this computational study we investigatecoordinated reset (CR neuromodulation designed for an effective controlof synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchronycharacteristic for several neurological disorders. We studyhow many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sitesmay significantly prolong the post-stimulation desynchronized transientafter the stimulation is completely switched off. This can, in turn,reduce the amount of the administered stimulation current for theintermittent ON-OFF CR stimulation protocol, where time intervalswith stimulation ON are recurrently followed by time intervals withstimulation OFF. In addition, we found that the optimal number ofstimulation sites essentially depends on how strongly the administeredcurrent decays within the neuronal tissue with increasing distancefrom the stimulation site. In particular, for a broad spatial stimulationprofile, i.e., for a weak spatial decay rate of the stimulation current,CR stimulation can optimally be delivered via a small number of stimulationsites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation.

  19. Dose-dependent stimulation of hepatic retinoic acid hydroxylation/oxidation and glucuronidation in brook trout, Salvelinus fontinalis, after exposure to 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl

    Energy Technology Data Exchange (ETDEWEB)

    Boyer, P.M.; Ndayibagira, A.; Spear, P.A.

    2000-03-01

    Extremely low stores of vitamin A have been reported in fish and birds inhabiting regions contaminated by coplanar polychlorinated biphenyls (PCBs) and other organochlorines, suggesting many possible effects on retinoid biochemical pathways. Metabolic imbalances associated with biologically active retinoids (e.g., retinoic acid) could be associated with tetratogenesis, edema, growth inhibition, reproductive impairment, immunosuppression, and susceptibility to cancer. Sexually mature brook trout were injected imtraperitoneally with the coplanar PCB 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl (TCBP) and again 4 weeks later. At 8 weeks, retinoic acid metabolism was measured in liver microsomes. To the authors' knowledge, retinoic acid conjugation by UDP-glucuronyltransferase is described here for the first time in fish. A substantial rate of glucuronidation was detected in the microsomes from control brook trout, which tended to increase over the dose range of TCBP. Glucuronidation was significantly greater in fish receiving the 10 {micro}g/g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, resulting in significantly greater production of 4-hydroxyretinoic acid at the 10 {micro}g/g dose level. In contrast, subsequent oxidation to 4-oxo-retinoic acid was greatest at the 1 {micro}g/g dose level and did not increase further at higher doses. Liver stores of dehydroretinyl palmitate/oleate were significantly decreased at the 5 and 10 {micro}g/g dose levels.

  20. Internal jugular vein: Peripheral vein adrenocorticotropic hormone ratio in patients with adrenocorticotropic hormone-dependent Cushing′s syndrome: Ratio calculated from one adrenocorticotropic hormone sample each from right and left internal jugular vein during corticotrophin releasing hormone stimulation test

    Directory of Open Access Journals (Sweden)

    Sachin Chittawar

    2013-01-01

    Full Text Available Background: Demonstration of central: Peripheral adrenocorticotropic hormone (ACTH gradient is important for diagnosis of Cushing′s disease. Aim: The aim was to assess the utility of internal jugular vein (IJV: Peripheral vein ACTH ratio for diagnosis of Cushing′s disease. Materials and Methods: Patients with ACTH-dependent Cushing′s syndrome (CS patients were the subjects for this study. One blood sample each was collected from right and left IJV following intravenous hCRH at 3 and 5 min, respectively. A simultaneous peripheral vein sample was also collected with each IJV sample for calculation of IJV: Peripheral vein ACTH ratio. IJV sample collection was done under ultrasound guidance. ACTH was assayed using electrochemiluminescence immunoassay (ECLIA. Results: Thirty-two patients participated in this study. The IJV: Peripheral vein ACTH ratio ranged from 1.07 to 6.99 ( n = 32. It was more than 1.6 in 23 patients. Cushing′s disease could be confirmed in 20 of the 23 cases with IJV: Peripheral vein ratio more than 1.6. Four patients with Cushing′s disease and 2 patients with ectopic ACTH syndrome had IJV: Peripheral vein ACTH ratio less than 1.6. Six cases with unknown ACTH source were excluded for calculation of sensitivity and specificity of the test. Conclusion: IJV: Peripheral vein ACTH ratio calculated from a single sample from each IJV obtained after hCRH had 83% sensitivity and 100% specificity for diagnosis of CD.

  1. New York Canyon Stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Raemy, Bernard

    2012-06-21

    The New York Canyon Stimulation Project was to demonstrate the commercial application of Enhanced Geothermal System techniques in Buena Vista Valley area of Pershing County, Nevada. From October 2009 to early 2012, TGP Development Company aggressively implemented Phase I of Pre-Stimulation and Site/Wellbore readiness. This included: geological studies; water studies and analyses and procurement of initial permits for drilling. Oversubscription of water rights and lack of water needed for implementation of EGS were identified and remained primary obstacles. Despite extended efforts to find alternative solutions, the water supply circumstances could not be overcome and led TGP to determine a "No Go" decision and initiate project termination in April 2012.

  2. Relaxation oscillations in stimulated Raman scattering

    International Nuclear Information System (INIS)

    Kachen, G.I.; Lowdermilk, W.H.

    1977-01-01

    Light pulses created by stimulated Raman scattering having been found to exhibit a complex time dependence which resembles relaxation oscillations. A focused laser pulse generated both forward and backward Raman emissions which appeared as a series of pulses with durations much shorter than the incident laser pulse. Time dependence of the Raman emission was observed directly by use of a streak camera. The number of observed pulses increased with the intensity of the incident pulse, while separation of the pulses in time depended on the length of the focal region. Beam focusing was incorporated in the coupled wave equations for stimulated Raman scattering. These rate equations were then solved numerically, and the results are in good qualitative agreement with the experimental observations. The short Raman pulses are created by a process associated with depletion of the incident laser pulse. This process occurs under a broad range of conditions

  3. Understanding the True Stimulated Reservoir Volume in Shale Reservoirs

    KAUST Repository

    Hussain, Maaruf; Saad, Bilal; Negara, Ardiansyah; Sun, Shuyu

    2017-01-01

    Successful exploitation of shale reservoirs largely depends on the effectiveness of hydraulic fracturing stimulation program. Favorable results have been attributed to intersection and reactivation of pre-existing fractures by hydraulically

  4. Alanine administration does not stimulate gluconeogenesis in preterm infants

    NARCIS (Netherlands)

    van Kempen, Anne A. M. W.; Romijn, Johannes A.; Ruiter, An F. C.; Endert, Erik; Weverling, Gerrit Jan; Kok, Johanna H.; Sauerwein, Hans P.

    2003-01-01

    Gluconeogenesis partially depends on sufficient precursor supply, and plasma alanine concentrations are generally low in preterm infants. Stimulation of gluconeogenesis may contribute to the prevention of hypoglycemia, an important clinical problem in these infants. In this study we evaluated the

  5. The Underlying Mechanism of Preventing Facial Nerve Stimulation by Triphasic Pulse Stimulation in Cochlear Implant Users Assessed With Objective Measure.

    Science.gov (United States)

    Bahmer, Andreas; Baumann, Uwe

    2016-10-01

    Triphasic pulse stimulation prevents from facial nerve stimulation (FNS) because of a different electromyographic input-output function compared with biphasic pulse stimulation. FNS is sometimes observed in cochlear implant users as an unwanted side effect of electrical stimulation of the auditory nerve. The common stimulation applied in current cochlear implant consists of biphasic pulse patterns. Two common clinical remedies to prevent unpleasant FNS caused by activation of certain electrodes are to expand their pulse phase duration or simply deactivate them. Unfortunately, in some patients these methods do not provide sufficient FNS prevention. In these patients triphasic pulse can prevent from FNS. The underlying mechanism is yet unclear. Electromyographic (EMG) recordings of muscles innervated by the facial nerve (musculi orbicularis ori and oculi) were applied to quantitatively assess the effects on FNS. Triphasic and biphasic fitting maps were compared in four subjects with severe FNS. Based on the recordings, a model is presented which intends to explain the beneficial effects of triphasic pulse application. Triphasic stimulation provided by fitting of an OPUS 2 speech processor device. For three patients, EMG was successfully recorded depending on stimulation level up to uncomfortable and intolerable FNS stimulation as upper boarder. The obtained EMG recordings demonstrated high individual variability. However, a difference between the input-output function for biphasic and triphasic pulse stimulation was visually observable. Compared with standard biphasic stimulation, triphasic pulses require higher stimulation levels to elicit an equal amount of FNS, as reflected by EMG amplitudes. In addition, we assume a steeper slope of the input-output function for biphasic pulse stimulation compared with triphasic pulse stimulation. Triphasic pulse stimulation prevents from FNS because of a smaller gradient of EMG input-output function compared with biphasic pulse

  6. IDEA: Stimulating Oral Production.

    Science.gov (United States)

    Easley, Jacob J.

    1995-01-01

    Presents daily activities that facilitate complete sentence response, promote oral production, and aid the learning of vocabulary in foreign-language classes. Because speech is the primary form of communication in the foreign-language classroom, it is important to stimulate students to converse as soon as possible. (Author/CK)

  7. stimulated BV2 Microglial

    African Journals Online (AJOL)

    2012-03-26

    Mar 26, 2012 ... 2), in LPS-stimulated BV2 microglial cells. The level of NO production was analyzed using Griess reaction. The release of PGE2 was determined using sandwich enzyme-linked immunosorbent assay. The DNA-binding activity of nuclear factor-κB (NF-κB) was measured by electrophoretic mobility shift assay ...

  8. Brain stimulation in migraine.

    Science.gov (United States)

    Brighina, Filippo; Cosentino, Giuseppe; Fierro, Brigida

    2013-01-01

    Migraine is a very prevalent disease with great individual disability and socioeconomic burden. Despite intensive research effort in recent years, the etiopathogenesis of the disease remains to be elucidated. Recently, much importance has been given to mechanisms underlying the cortical excitability that has been suggested to be dysfunctional in migraine. In recent years, noninvasive brain stimulation techniques based on magnetic fields (transcranial magnetic stimulation, TMS) and on direct electrical currents (transcranial direct current stimulation, tDCS) have been shown to be safe and effective tools to explore the issue of cortical excitability, activation, and plasticity in migraine. Moreover, TMS, repetitive TMS (rTMS), and tDCS, thanks to their ability to interfere with and/or modulate cortical activity inducing plastic, persistent effects, have been also explored as potential therapeutic approaches, opening an interesting perspective for noninvasive neurostimulation for both symptomatic and preventive treatment of migraine and other types of headache. In this chapter we critically review evidence regarding the role of noninvasive brain stimulation in the pathophysiology and treatment of migraine, delineating the advantages and limits of these techniques together with potential development and future application. © 2013 Elsevier B.V. All rights reserved.

  9. Metallic taste from electrical and chemical stimulation.

    Science.gov (United States)

    Lawless, Harry T; Stevens, David A; Chapman, Kathryn W; Kurtz, Anne

    2005-03-01

    A series of three experiments investigated the nature of metallic taste reports after stimulation with solutions of metal salts and after stimulation with metals and electric currents. To stimulate with electricity, a device was fabricated consisting of a small battery affixed to a plastic handle with the anode side exposed for placement on the tongue or oral tissues. Intensity of taste from metals and batteries was dependent upon the voltage and was more robust in areas dense in fungiform papillae. Metallic taste was reported from stimulation with ferrous sulfate solutions, from metals and from electric stimuli. However, reports of metallic taste were more frequent when the word 'metallic' was presented embedded in a list of choices, as opposed to simple free-choice labeling. Intensity decreased for ferrous sulfate when the nose was occluded, consistent with a decrease in retronasal smell, as previously reported. Intensity of taste evoked by copper metal, bimetallic stimuli (zinc/copper) or small batteries (1.5-3 V) was not affected by nasal occlusion. This difference suggests two distinct mechanisms for evocation of metallic taste reports, one dependent upon retronasal smell and a second mediated by oral chemoreceptors.

  10. A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

    Science.gov (United States)

    Dong, Xiaoxi; Liu, Tianjun; Wang, Han; Yang, Jichun; Chen, Zhuying; Hu, Yong; Li, Yingxin

    2017-07-01

    This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order

  11. [Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

    Science.gov (United States)

    Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

    2012-12-01

    Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

  12. Grating stimulated echo

    International Nuclear Information System (INIS)

    Dubetsky, B.; Berman, P.R.; Sleator, T.

    1992-01-01

    A theory of a grating simulated echo (GTE) is developed. The GSE involves the sequential excitation of atoms by two counterpropagating traveling waves, a standing wave, and a third traveling wave. It is shown that the echo signal is very sensitive to small changes in atomic velocity, much more sensitive than the normal stimulated echo. Use of the GSE as a collisional probe or accelerometer is discussed

  13. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  14. Path Dependency

    OpenAIRE

    Mark Setterfield

    2015-01-01

    Path dependency is defined, and three different specific concepts of path dependency – cumulative causation, lock in, and hysteresis – are analyzed. The relationships between path dependency and equilibrium, and path dependency and fundamental uncertainty are also discussed. Finally, a typology of dynamical systems is developed to clarify these relationships.

  15. Low intensity transcranial electric stimulation

    DEFF Research Database (Denmark)

    Antal, Andrea; Alekseichuk, I; Bikson, M

    2017-01-01

    Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears...

  16. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  17. Non-invasive neural stimulation

    Science.gov (United States)

    Tyler, William J.; Sanguinetti, Joseph L.; Fini, Maria; Hool, Nicholas

    2017-05-01

    Neurotechnologies for non-invasively interfacing with neural circuits have been evolving from those capable of sensing neural activity to those capable of restoring and enhancing human brain function. Generally referred to as non-invasive neural stimulation (NINS) methods, these neuromodulation approaches rely on electrical, magnetic, photonic, and acoustic or ultrasonic energy to influence nervous system activity, brain function, and behavior. Evidence that has been surmounting for decades shows that advanced neural engineering of NINS technologies will indeed transform the way humans treat diseases, interact with information, communicate, and learn. The physics underlying the ability of various NINS methods to modulate nervous system activity can be quite different from one another depending on the energy modality used as we briefly discuss. For members of commercial and defense industry sectors that have not traditionally engaged in neuroscience research and development, the science, engineering and technology required to advance NINS methods beyond the state-of-the-art presents tremendous opportunities. Within the past few years alone there have been large increases in global investments made by federal agencies, foundations, private investors and multinational corporations to develop advanced applications of NINS technologies. Driven by these efforts NINS methods and devices have recently been introduced to mass markets via the consumer electronics industry. Further, NINS continues to be explored in a growing number of defense applications focused on enhancing human dimensions. The present paper provides a brief introduction to the field of non-invasive neural stimulation by highlighting some of the more common methods in use or under current development today.

  18. Spinal Cord Stimulation

    DEFF Research Database (Denmark)

    Meier, Kaare

    2014-01-01

    Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain that is refractory to other treatment. Originally described by Shealy et al. in 1967(1), it is used to treat a range of conditions such as complex regional pain syndrome (CRPS I)(2), angina pectoris(3), radicular...... pain after failed back surgery syndrome (FBSS)(4), pain due to peripheral nerve injury, stump pain(5), peripheral vascular disease(6) and diabetic neuropathy(7,8); whereas phantom pain(9), postherpetic neuralgia(10), chronic visceral pain(11), and pain after partial spinal cord injury(12) remain more...

  19. Effect of sevoflurane on neuronal activity during deep brain stimulation surgery for epilepsy: A case report

    OpenAIRE

    Michaël J. Bos, MD; Linda Ackermans, MD, PhD; Frédéric L.W.V.J. Schaper, MD; Rob P.W. Rouhl, MD, PhD; Vivianne H.J.M. van Kranen-Mastenbroek, MD, PhD; Wolfgang F. Buhre, MD, PhD; Marcus L.F. Janssen, MD, PhD

    2018-01-01

    Deep brain stimulation of the anterior nucleus of the thalamus is an effective treatment for patients with refractory epilepsy who do not respond sufficiently to medical therapy. Optimal therapeutic effects of deep brain stimulation probably depend on accurate positioning of the stimulating electrodes. Microelectrode recordings show bursty firing neurons in the anterior nucleus of the thalamus region, which confirms the anatomical target determined by the surgeon. Deep brain stimulation elect...

  20. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

    Science.gov (United States)

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-01-01

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation. PMID:25624815

  1. Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

    Science.gov (United States)

    Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

    2016-01-01

    Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use.

  2. Theory of feedback controlled brain stimulations for Parkinson's disease

    Science.gov (United States)

    Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

    2016-01-01

    Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

  3. Ipsilateral masking between acoustic and electric stimulations.

    Science.gov (United States)

    Lin, Payton; Turner, Christopher W; Gantz, Bruce J; Djalilian, Hamid R; Zeng, Fan-Gang

    2011-08-01

    Residual acoustic hearing can be preserved in the same ear following cochlear implantation with minimally traumatic surgical techniques and short-electrode arrays. The combined electric-acoustic stimulation significantly improves cochlear implant performance, particularly speech recognition in noise. The present study measures simultaneous masking by electric pulses on acoustic pure tones, or vice versa, to investigate electric-acoustic interactions and their underlying psychophysical mechanisms. Six subjects, with acoustic hearing preserved at low frequencies in their implanted ear, participated in the study. One subject had a fully inserted 24 mm Nucleus Freedom array and five subjects had Iowa/Nucleus hybrid implants that were only 10 mm in length. Electric masking data of the long-electrode subject showed that stimulation from the most apical electrodes produced threshold elevations over 10 dB for 500, 625, and 750 Hz probe tones, but no elevation for 125 and 250 Hz tones. On the contrary, electric stimulation did not produce any electric masking in the short-electrode subjects. In the acoustic masking experiment, 125-750 Hz pure tones were used to acoustically mask electric stimulation. The acoustic masking results showed that, independent of pure tone frequency, both long- and short-electrode subjects showed threshold elevations at apical and basal electrodes. The present results can be interpreted in terms of underlying physiological mechanisms related to either place-dependent peripheral masking or place-independent central masking.

  4. A distributed current stimulator ASIC for high density neural stimulation.

    Science.gov (United States)

    Jeong Hoan Park; Chaebin Kim; Seung-Hee Ahn; Tae Mok Gwon; Joonsoo Jeong; Sang Beom Jun; Sung June Kim

    2016-08-01

    This paper presents a novel distributed neural stimulator scheme. Instead of a single stimulator ASIC in the package, multiple ASICs are embedded at each electrode site for stimulation with a high density electrode array. This distributed architecture enables the simplification of wiring between electrodes and stimulator ASIC that otherwise could become too complex as the number of electrode increases. The individual ASIC chip is designed to have a shared data bus that independently controls multiple stimulating channels. Therefore, the number of metal lines is determined by the distributed ASICs, not by the channel number. The function of current steering is also implemented within each ASIC in order to increase the effective number of channels via pseudo channel stimulation. Therefore, the chip area can be used more efficiently. The designed chip was fabricated with area of 0.3 mm2 using 0.18 μm BCDMOS process, and the bench-top test was also conducted to validate chip performance.

  5. Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

    Directory of Open Access Journals (Sweden)

    Magteld Zeitler

    2018-05-01

    Full Text Available A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on

  6. Impact of Behavioral Control on the Processing of Nociceptive Stimulation

    Science.gov (United States)

    Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

    2012-01-01

    How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

  7. Impact of behavioral control on the processing of nociceptive stimulation

    Directory of Open Access Journals (Sweden)

    James W Grau

    2012-08-01

    Full Text Available How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation, it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation. These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: Controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit. Uncontrollable stimulation also enhances mechanical reactivity (allodynia. We review evidence that training with controllable stimulation engages a BDNF-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin. A model is proposed that assumes nociceptive input is gated at an early stage, within the dorsal horn. his gate is sensitive to current environmental relations (between proprioceptive and nociceptive input, allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain.

  8. Dependent Classes

    DEFF Research Database (Denmark)

    Gasiunas, Vaidas; Mezini, Mira; Ostermann, Klaus

    2007-01-01

    of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types. [29] T.Nipkow, L.C. Poulson, and M. Wenzel. Isabelle/HOL -- A Proof Assistant for Higher-Order Logic, volume 2283 of LNCS, Springer, 2002......Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot...... be modeled and a class must know all classes that depend on its objects. This paper presents dependent classes, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility...

  9. Exercise Dependence

    Directory of Open Access Journals (Sweden)

    Erdal Vardar

    2012-06-01

    Full Text Available Exercise dependence define a condition in which a person performs excessive exercise resulting in deterioration of his or her physical and mental health wellness. Despite many clinical research studies on exercise dependence, exact diagnostic criteria has not been developed yet. Clinical evidences concerning etiology, epidemiology, underlying mechanisms and treatment of exercise dependence are still not sufficient. Moreover, evaluation of this clinical disorder within dependency perspective is a fairly new concept. Recent studies have shown that exercise dependence has similar features like chemical substance dependence with regards to withdrawal and tolerance symptoms. The aim of this review was to briefly evaluate diagnostic and clinical features of exercise dependence. [Archives Medical Review Journal 2012; 21(3.000: 163-173

  10. Testosterone Suppression of CRH-stimulated Cortisol in Men

    OpenAIRE

    Rubinow, David R.; Roca, Catherine A.; Schmidt, Peter J.; Danaceau, Merry A.; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

    2005-01-01

    Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in ten men (ages 18–45) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower ...

  11. Stimulated Thomson scattering

    International Nuclear Information System (INIS)

    Spencer, R.L.

    1979-03-01

    The theory of stimulated Thomson scattering is investigated both quantum mechanically and classically. Two monochromatic electromagnetic waves of like polarization travelling in opposite directions are allowed to interact for a time tau with the electrons in a collisionless plasma. The electromagnetic waves have frequencies well above the plasma frequency, and their difference frequency is allowed to range upward from the plasma frequency. With the difference frequency well above the plasma frequency, the rate at which energy is transferred from one wave to the other is calculated quantum mechanically, classically from a fluid theory, and classically from an independent electron theory. The rate is calculated in both the homogeneously broadened limit, and in the inhomogeneously broadened limit

  12. Engagement sensitive visual stimulation

    Directory of Open Access Journals (Sweden)

    Deepesh Kumar

    2016-06-01

    Full Text Available Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one’s performance.

  13. Stimulated coherent transition radiation

    International Nuclear Information System (INIS)

    Hung-chi Lihn.

    1996-03-01

    Coherent radiation emitted from a relativistic electron bunch consists of wavelengths longer than or comparable to the bunch length. The intensity of this radiation out-numbers that of its incoherent counterpart, which extends to wavelengths shorter than the bunch length, by a factor equal to the number of electrons in the bunch. In typical accelerators, this factor is about 8 to 11 orders of magnitude. The spectrum of the coherent radiation is determined by the Fourier transform of the electron bunch distribution and, therefore, contains information of the bunch distribution. Coherent transition radiation emitted from subpicosecond electron bunches at the Stanford SUNSHINE facility is observed in the far-infrared regime through a room-temperature pyroelectric bolometer and characterized through the electron bunch-length study. To measure the bunch length, a new frequency-resolved subpicosecond bunch-length measuring system is developed. This system uses a far-infrared Michelson interferometer to measure the spectrum of coherent transition radiation through optical autocorrelation with resolution far better than existing time-resolved methods. Hence, the radiation spectrum and the bunch length are deduced from the autocorrelation measurement. To study the stimulation of coherent transition radiation, a special cavity named BRAICER is invented. Far-infrared light pulses of coherent transition radiation emitted from electron bunches are delayed and circulated in the cavity to coincide with subsequent incoming electron bunches. This coincidence of light pulses with electron bunches enables the light to do work on electrons, and thus stimulates more radiated energy. The possibilities of extending the bunch-length measuring system to measure the three-dimensional bunch distribution and making the BRAICER cavity a broadband, high-intensity, coherent, far-infrared light source are also discussed

  14. Effect of Parkinson's Disease in Transcranial Magnetic Stimulation Treatment

    Science.gov (United States)

    Syeda, Farheen; Magsood, Hamzah; Lee, Erik; El-Gendy, Ahmed; Jiles, David; Hadimani, Ravi

    Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

  15. Dependency Parsing

    CERN Document Server

    Kubler, Sandra; Nivre, Joakim

    2009-01-01

    Dependency-based methods for syntactic parsing have become increasingly popular in natural language processing in recent years. This book gives a thorough introduction to the methods that are most widely used today. After an introduction to dependency grammar and dependency parsing, followed by a formal characterization of the dependency parsing problem, the book surveys the three major classes of parsing models that are in current use: transition-based, graph-based, and grammar-based models. It continues with a chapter on evaluation and one on the comparison of different methods, and it close

  16. Ultrasound stimulation on bone healing. The optimization of stimulation time

    International Nuclear Information System (INIS)

    Rosim, R.C.; Paulin, J.B.P.; Goncalves, R.P.

    1990-01-01

    Previous works in ultrasonic simulation of bone healing dealt with parameters optimization. Albertin (1983) studied the stimulation time and found forty minutes as ideal. However, this stimulation time was the largest one employed and remained some doubt about the most appropriated value. 30, 40, 50 and 60 minutes of stimulation time were selected, while others parameters were held constant with: pulse width in 200 μs, repetition rate in 1000 pulses per second and amplitude in 30 V. Partial incomplete transverse osteotomies were done in the middle third of radio in the right forearm of rabbits. Twenty four animals divided in four subgroups, with 6 animals each were stimulated. The daily stimulation time for each subgroup was 30, 40, 50 and minutes respectively, during 15 consecutive days. The stimulation procedure started 24 hours after surgery. After the stimulation period, radiological, histological and morphometric evaluations were done and greater bone healing was found for the 50 minutes stimulation subgroup, in them new bone was also prominent. (author)

  17. Rationale for Using Exercise in the Treatment of Stimulant Use Disorders

    Science.gov (United States)

    Greer, Tracy L.; Ring, Kolette M.; Warden, Diane; Grannemann, Bruce D.; Church, Timothy S.; Somoza, Eugene; Blair, Steven N.; Szapocznik, Jose; Stoutenberg, Mark; Rethorst, Chad; Walker, Robrina; Morris, David W.; Kosinski, Andrzej S.; Kyle, Tiffany; Marcus, Bess; Crowell, Becca; Oden, Neal; Nunes, Edward; Trivedi, Madhukar H.

    2013-01-01

    Novel approaches to the treatment of stimulant abuse and dependence are needed. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse. In addition, exercise has been associated with improvements in many other health-related areas that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight, quality of life, and anhedonia. Neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes in stimulant abuse. The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. If effective, exercise may provide an additional approach to the treatment of stimulant use disorders. PMID:25364477

  18. Transcranial brain stimulation: closing the loop between brain and stimulation

    DEFF Research Database (Denmark)

    Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

    2016-01-01

    -related and state-related variability. Fluctuations in brain-states can be traced online with functional brain imaging and inform the timing or other settings of transcranial brain stimulation. State-informed open-loop stimulation is aligned to the expression of a predefined brain state, according to prespecified......PURPOSE OF REVIEW: To discuss recent strategies for boosting the efficacy of noninvasive transcranial brain stimulation to improve human brain function. RECENT FINDINGS: Recent research exposed substantial intra- and inter-individual variability in response to plasticity-inducing transcranial brain...... stimulation. Trait-related and state-related determinants contribute to this variability, challenging the standard approach to apply stimulation in a rigid, one-size-fits-all fashion. Several strategies have been identified to reduce variability and maximize the plasticity-inducing effects of noninvasive...

  19. Temporal evolution of stimulated Brillouin backscatter

    International Nuclear Information System (INIS)

    Hinkel, D.E.; Williams, E.A.; Berger, R.L.

    1994-01-01

    A qualitative understanding of the time dependence of stimulated Brillouin scattering (SBS) provides estimates of the amount of temporal growth that occurs in current inertial confinement fusion and short laser pulse interaction experiments when the growth is limited by the length of the experiment or by motion of the ''hot spots'' of the laser intensity pattern induced by beam smoothing. In the weak coupling limit, the instantaneous growth rate depends upon the plasma initial conditions early in time, is proportional to t -1/2 later in time, and asymptotically approaches the absolute growth rate (in the absence of damping). When the instability is strongly coupled, the growth rate depends upon the plasma initial conditions early in time but is proportional to t -1/3 later in time. When the growth rate drops to a value comparable to that of the ion acoustic frequency, the instability becomes effectively weakly coupled. The effects of damping are also discussed

  20. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  1. EOR by stimulated microflora

    Energy Technology Data Exchange (ETDEWEB)

    Svarovskaya, L.I.; Altunina, L.K.; Rozhenkova, Z.A.; Bulavin, V.D. [Institute of Petroleum Chemistry, Tomsk (Russian Federation)

    1995-12-31

    A combined microbiological and physico-chemical method for EOR has been developed for flooded West Siberia oil fields with formation temperature of 45{degrees}-95{degrees}C (318-365K). Formation water includes rich and various biocenoses numbering up to 2 x 10{sup 7} cells per ml. Representatives of genera, i.e, Pseudomonas, Bacillus, Actinomyces, Micrococcus, Mycobacterium, Sarcina, etc. were found to be the most widely distributed microorganisms. The method is based on injection of systems exhibiting high oil displacing capacity and at the same time being an additional nitrous nutrient for endemic populations of microorganisms. Their injection into formation water favors biomass growth by 4-6 orders and promotes syntheses of biosurfactants, biopolymers, acids, etc., and gaseous products. The features of residual oil displacement have been studied on laboratory models using a combined microbiological and physico-chemical method. A curve for the yield of residual oil is presented by two peaks. The first peak is stipulated by the washing action of oil displacement system, and the second one by the effect of metabolites produced at stimulation of biogenic processes. Oil displacement index increases by 15%-30%.

  2. Subliminal Stimulation: Hoax or Reality?

    Science.gov (United States)

    Trank, Douglas M.

    Subliminal stimulation is defined as that which is perceived by an individual below the threshold of awareness or cognizance. This article traces the history of research in subliminal stimulation to illustrate that under certain circumstances and conditions, this behavioral phenomenon does occur. Although subliminal stimuli do affect human…

  3. Stimulating Language: Insights from TMS

    Science.gov (United States)

    Devlin, Joseph T.; Watkins, Kate E.

    2007-01-01

    Fifteen years ago, Pascual-Leone and colleagues used transcranial magnetic stimulation (TMS) to investigate speech production in pre-surgical epilepsy patients and in doing so, introduced a novel tool into language research. TMS can be used to non-invasively stimulate a specific cortical region and transiently disrupt information processing. These…

  4. Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

    Science.gov (United States)

    Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

    2014-01-01

    Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

  5. Ab initio simulation of stimulated bremsstrahlung in an intense laser field

    International Nuclear Information System (INIS)

    Volkova, E.A.; Popov, A.M.; Popovicheva, O.B.

    1992-01-01

    Numerical solution of the time-dependent Schroedinger equation for a quantum system in the field of an electromagnetic wave is used to study a one-dimensional model of stimulated bremsstrahlung (absorption or emission of photons by a field in connection with Coulomb scattering of an electron). The time dependence of the stimulated bremsstrahlung effect is analyzed for various laser radiation intensities. The process of stimulated photorecombination is examined. The results of the calculation are compared with the analytical theory of the stimulated bremsstrahlung effect. 14 refs., 6 figs

  6. Colony stimulating factors and their clinical implication

    International Nuclear Information System (INIS)

    Asano, Shigetaka

    1989-01-01

    Granulocytes and macrophage are dependent for their production and/or functional activation in vitro on the presence of a family of glycoproteins. They are generally called colony-stimulating factors (CSFs) because of their capacity to stimulate colony formation in semi-solid cultures, and are currently classified into four distinct subtypes, that is, Multi-CSF, GM-CSF, G-CSF and M-CSF, according to the cell type of colonies formed under their stimulation or their target cell specificity. All of the murine and human CSF subtypes and the genes for them have become available in a purified form and in a large scale, and now allow us to investigate their interactions, the mechanisms for their actions, the cell-cell interactions leading to their production and secretion, and their actions in vivo. Furthermore, the preclinical and/or clinical studies which were carried out using the purified CSFs strongly indicate that human CSFs will be effective strategies for preventing and treating opportunistic bacterial and fungal infection as a major cause of death in granulocytopenic patients. (author)

  7. Vagal nerve stimulation therapy: what is being stimulated?

    Science.gov (United States)

    Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

    2014-01-01

    Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

  8. Vagal nerve stimulation therapy: what is being stimulated?

    Directory of Open Access Journals (Sweden)

    Guy Kember

    Full Text Available Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

  9. Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A Computational Modeling Analysis.

    Science.gov (United States)

    Kent, Alexander R; Min, Xiaoyi; Hogan, Quinn H; Kramer, Jeffery M

    2018-04-01

    The mechanisms of dorsal root ganglion (DRG) stimulation for chronic pain remain unclear. The objective of this work was to explore the neurophysiological effects of DRG stimulation using computational modeling. Electrical fields produced during DRG stimulation were calculated with finite element models, and were coupled to a validated biophysical model of a C-type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz afferent signal or somatic ectopic firing. The transmembrane potential was measured along the neuron to determine the effect of stimulation on intrinsic activity across stimulation parameters, cell location/orientation, and membrane properties. The model was validated by showing close correspondence in action potential (AP) characteristics and firing patterns when compared to experimental measurements. Subsequently, the model output demonstrated that T-junction filtering was amplified with DRG stimulation, thereby blocking afferent signaling, with cathodic stimulation at amplitudes of 2.8-5.5 × stimulation threshold and frequencies above 2 Hz. This amplified filtering was dependent on the presence of calcium and calcium-dependent small-conductance potassium channels, which produced a hyperpolarization offset in the soma, stem, and T-junction with repeated somatic APs during stimulation. Additionally, DRG stimulation suppressed somatic ectopic activity by hyperpolarizing the soma with cathodic or anodic stimulation at amplitudes of 3-11 × threshold and frequencies above 2 Hz. These effects were dependent on the stem axon being relatively close to and oriented toward a stimulating contact. These results align with the working hypotheses on the mechanisms of DRG stimulation, and indicate the importance of stimulation amplitude, polarity, and cell location/orientation on neuronal responses. © 2018 International Neuromodulation Society.

  10. Anti-kindling induced by two-stage coordinated reset stimulation with weak onset intensity

    Directory of Open Access Journals (Sweden)

    Magteld eZeitler

    2016-05-01

    Full Text Available Abnormal neuronal synchrony plays an important role in a number of brain diseases. To specifically counteract abnormal neuronal synchrony by desynchronization, Coordinated Reset (CR stimulation, a spatiotemporally patterned stimulation technique, was designed with computational means. In neuronal networks with spike timing–dependent plasticity CR stimulation causes a decrease of synaptic weights and finally anti-kindling, i.e. unlearning of abnormally strong synaptic connectivity and abnormal neuronal synchrony. Long-lasting desynchronizing aftereffects of CR stimulation have been verified in pre-clinical and clinical proof of concept studies. In general, for different neuromodulation approaches, both invasive and non-invasive, it is desirable to enable effective stimulation at reduced stimulation intensities, thereby avoiding side effects. For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity. Numerical simulations show that a two-stage CR stimulation can induce the same degree of anti-kindling as a single-stage CR stimulation with intermediate stimulation intensity. This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects. This might, e.g., be relevant in the context of acoustic CR stimulation in tinnitus patients with hyperacusis or in the case of electrical deep brain CR stimulation with sub-optimally positioned leads or side effects caused by stimulation of the target itself. We discuss how to apply our method in first in man and proof of concept studies.

  11. Electrical stimulation in exercise training

    Science.gov (United States)

    Kroll, Walter

    1994-01-01

    Electrical stimulation has a long history of use in medicine dating back to 46 A.D. when the Roman physician Largus found the electrical discharge of torpedo fishes useful in the treatment of pain produced by headache and gout. A rival Greek physician, Dioscorides, discounted the value of the torpedo fish for headache relief but did recommend its use in the treatment of hemorrhoids. In 1745, the Leyden jar and various sized electrostatic generators were used to treat angina pectoris, epilepsy, hemiplegia, kidney stones, and sciatica. Benjamin Franklin used an electrical device to treat successfully a young woman suffering from convulsive fits. In the late 1800's battery powered hydroelectric baths were used to treat chronic inflammation of the uterus while electrified athletic supporters were advertised for the treatment of male problems. Fortunately, such an amusing early history of the simple beginnings of electrical stimulation did not prevent eventual development of a variety of useful therapeutic and rehabilitative applications of electrical stimulation. Over the centuries electrical stimulation has survived as a modality in the treatment of various medical disorders with its primary application being in the rehabilitation area. Recently, a surge of new interest in electrical stimulation has been kindled by the work of a Russian sport scientist who reported remarkable muscle strength and endurance improvements in elite athletes. Yakov Kots reported his research on electric stimulation and strength improvements in 1977 at a Canadian-Soviet Exchange Symposium held at Concordia University in Montreal. Since then an explosion of new studies has been seen in both sport science and in medicine. Based upon the reported works of Kots and the present surge of new investigations, one could be misled as to the origin of electrical stimulation as a technique to increase muscle strength. As a matter of fact, electric stimulation has been used as a technique to improve

  12. Toward stimulated interaction of surface phonon polaritons

    Energy Technology Data Exchange (ETDEWEB)

    Kong, B. D.; Trew, R. J.; Kim, K. W., E-mail: kwk@ncsu.edu [Department of Electrical and Computer Engineering, North Carolina State University, Raleigh, North Carolina 27695-7911 (United States)

    2013-12-21

    Thermal emission spectra mediated by surface phonon polariton are examined by using a theoretical model that accounts for generation processes. Specifically, the acoustic phonon fusion mechanism is introduced to remedy theoretical deficiencies of the near thermal equilibrium treatments. The model clarifies the thermal excitation mechanism of surface phonon polaritons and the energy transfer path under non-zero energy flow. When applied to GaAs and SiC semi-infinite surfaces, the nonequilibrium model predicts that the temperature dependence of the quasi-monochromatic peak can exhibit distinctly different characteristics of either sharp increase or slow saturation depending on the materials, which is in direct contrast with the estimate made by the near-equilibrium model. The proposed theoretical tool can accurately analyze the nonequilibrium steady states, potentially paving a pathway to demonstrate stimulated interaction/emission of thermally excited surface phonon polaritons.

  13. Path Dependence

    DEFF Research Database (Denmark)

    Madsen, Mogens Ove

    Begrebet Path Dependence blev oprindelig udviklet inden for New Institutionel Economics af bl.a. David, Arthur og North. Begrebet har spredt sig vidt i samfundsvidenskaberne og undergået en udvikling. Dette paper propagerer for at der er sket så en så omfattende udvikling af begrebet, at man nu kan...... tale om 1. og 2. generation af Path Dependence begrebet. Den nyeste udvikling af begrebet har relevans for metodologi-diskusionerne i relation til Keynes...

  14. Multielectrode intrafascicular and extraneural stimulation

    NARCIS (Netherlands)

    Veltink, Petrus H.; van Alste, Jan A.; Boom, H.B.K.

    1989-01-01

    The relationship between nerve stimulation, pulse amplitude and isometric muscle force was measured to investigate recruitment of motor units. Force addition experiments were performed to obtain insight in the intersection of motor unit groups recruited by different electrodes. Intrafascicular and

  15. Noninvasive Stimulation of the Human Brain

    DEFF Research Database (Denmark)

    Di Lazzaro, Vincenzo; Rothwell, John; Capogna, Marco

    2017-01-01

    Noninvasive brain stimulation methods, such as transcranial electric stimulation and transcranial magnetic stimulation are widely used tools for both basic research and clinical applications. However, the cortical circuits underlying their effects are poorly defined. Here we review the current...

  16. Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

    Science.gov (United States)

    Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Bouchard, Caroline; Ardell, Jeffrey L; Foreman, Robert D; Armour, J Andrew

    2006-11-01

    Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

  17. Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps stimulation.

    Science.gov (United States)

    Rodriguez-Falces, Javier; Place, Nicolas

    2013-12-01

    To investigate potential differences in the recruitment order of motor units (MUs) in the quadriceps femoris when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using femoral nerve stimulation and direct quadriceps stimulation of gradually increasing intensity from 20 young, healthy subjects. Recruitment order was investigated by analysing the time-to-peak twitch and the time interval from the stimulus artefact to the M-wave positive peak (M-wave latency) for the vastus medialis (VM) and vastus lateralis (VL) muscles. During femoral nerve stimulation, time-to-peak twitch and M-wave latency decreased consistently (P  0.05). For the VM muscle, M-wave latency decreased with increasing stimulation level for both femoral nerve and direct quadriceps stimulation, whereas, for the VL muscle, the variation of M-wave latency with stimulus intensity was different for the two stimulation geometries (P recruitment order during direct quadriceps stimulation was more complex, depending ultimately on the architecture of the peripheral nerve and its terminal branches below the stimulating electrodes for each muscle. For the VM, MUs were orderly recruited for both stimulation geometries, whereas, for the VL muscle, MUs were orderly recruited for femoral nerve stimulation, but followed no particular order for direct quadriceps stimulation.

  18. Economics of nuclear gas stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Frank, G W [Austral Oil Company Incorporated, Houston, TX (United States); Coffer, H F; Luetkehans, G R [CER Geonuclear Corporation, Las Vegas, NV (United States)

    1970-05-01

    Nuclear stimulation of the Mesaverde Formation in the Piceance Basin appears to be the only available method that can release the contained gas economically. In the Rulison Field alone estimates show six to eight trillion cubic feet of gas may be made available by nuclear means, and possibly one hundred trillion cubic feet could be released in the Piceance Basin. Several problems remain to be solved before this tremendous gas reserve can be tapped. Among these are (1) rates of production following nuclear stimulation; (2) costs of nuclear stimulation; (3) radioactivity of the chimney gas; and (4) development of the ideal type of device to carry out the stimulations. Each of these problems is discussed in detail with possible solutions suggested. First and foremost is the rate at which gas can be delivered following nuclear stimulation. Calculations have been made for expected production behavior following a 5-kiloton device and a 40-kiloton device with different permeabilities. These are shown, along with conventional production history. The calculations show that rates of production will be sufficient if costs can be controlled. Costs of nuclear stimulation must be drastically reduced for a commercial process. Project Rulison will cost approximately $3.7 million, excluding lease costs, preliminary tests, and well costs. At such prices, nothing can possibly be commercial; however, these costs can come down in a logical step-wise fashion. Radiation contamination of the gas remains a problem. Three possible solutions to this problem are included. (author)

  19. Economics of nuclear gas stimulation

    International Nuclear Information System (INIS)

    Frank, G.W.; Coffer, H.F.; Luetkehans, G.R.

    1970-01-01

    Nuclear stimulation of the Mesaverde Formation in the Piceance Basin appears to be the only available method that can release the contained gas economically. In the Rulison Field alone estimates show six to eight trillion cubic feet of gas may be made available by nuclear means, and possibly one hundred trillion cubic feet could be released in the Piceance Basin. Several problems remain to be solved before this tremendous gas reserve can be tapped. Among these are (1) rates of production following nuclear stimulation; (2) costs of nuclear stimulation; (3) radioactivity of the chimney gas; and (4) development of the ideal type of device to carry out the stimulations. Each of these problems is discussed in detail with possible solutions suggested. First and foremost is the rate at which gas can be delivered following nuclear stimulation. Calculations have been made for expected production behavior following a 5-kiloton device and a 40-kiloton device with different permeabilities. These are shown, along with conventional production history. The calculations show that rates of production will be sufficient if costs can be controlled. Costs of nuclear stimulation must be drastically reduced for a commercial process. Project Rulison will cost approximately $3.7 million, excluding lease costs, preliminary tests, and well costs. At such prices, nothing can possibly be commercial; however, these costs can come down in a logical step-wise fashion. Radiation contamination of the gas remains a problem. Three possible solutions to this problem are included. (author)

  20. Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Kimberly B. Hoang

    2017-10-01

    Full Text Available The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs, and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs, and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.

  1. A monoenergetic electron source generated by nuclear stimulated desorption

    International Nuclear Information System (INIS)

    Kelson, I.; Levy, Y.; Nir, D.; Haustein, P.E.

    1994-01-01

    A series of measurements of nuclear stimulated desorption was performed for 103 Ru, using thin ruthenium films irradiated by thermal neutrons. The magnitude, time dependence and electric charge state of the outgoing 103m Rh flux was investigated. The utilization of monoenergetic electrons accompanying the 103 Rh decay for thin film thickness measurement is considered. (Author)

  2. Photon distribution function for stocks wave for stimulated Raman scattering

    International Nuclear Information System (INIS)

    Man'ko, O.V.; Tcherniega, N.V.

    1997-04-01

    New time-dependent integrals of motion are found for stimulated Raman scattering. Explicit formula for the photon-number probability distribution as a function of the laser-field intensity and the medium parameters is obtained in terms of Hermite polynomials of two variables. (author). 29 refs

  3. Intermittent stimulation delays adaptation to electrocutaneous sensory feedback

    NARCIS (Netherlands)

    Buma, D.G.; Buma, Dorindo G.; Buitenweg, Jan R.; Veltink, Petrus H.

    Electrotactile displays deliver information to the user by means of electrocutaneous stimulation. If such displays are used in prostheses, the functionality depends on long term stability of this information channel. The perceived sensation, however, decays within 15 min due to central adaptation if

  4. Pharyngeal Electrical Stimulation for Treatment of Dysphagia in Subacute Stroke

    DEFF Research Database (Denmark)

    Bath, Philip M W; Scutt, Polly; Love, Jo

    2016-01-01

    BACKGROUND AND PURPOSE: Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. METHODS...

  5. Nonlinear joint angle control for artificially stimulated muscle

    NARCIS (Netherlands)

    Veltink, Petrus H.; Chizeck, Howard J.; Crago, Patrick E.; El-Bialy, Ahmed

    1992-01-01

    Designs of both open- and closed-loop controllers of electrically stimulated muscle that explicitly depend on a nonlinear mathematical model of muscle input-output properties are presented and evaluated. The muscle model consists of three factors: a muscle activation dynamics factor, an angle-torque

  6. Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

    Science.gov (United States)

    Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R

    2016-01-01

    A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Biophysical Model of Cortical Network Activity and the Influence of Electrical Stimulation

    Science.gov (United States)

    2015-11-13

    model, multicompartment model, subdural cortical stimulation, anode, cathode, epilepsy REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S...and axon orientation in respect to the electrode position. 4) A single stimulation pulse causes a sequence of action potentials ectopically generated...Bergey, P.J. Franaszczuk. Phase-dependent stimulation effects on bursting activity in a neural network cortical simulation, Epilepsy Research (07 2008

  8. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation: A functional MRI study.

    Science.gov (United States)

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-08-25

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.

  9. Electrical stimulation and motor recovery.

    Science.gov (United States)

    Young, Wise

    2015-01-01

    In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical

  10. Improved discrimination of visual stimuli following repetitive transcranial magnetic stimulation.

    Directory of Open Access Journals (Sweden)

    Michael L Waterston

    Full Text Available BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a "virtual lesion" in stimulated brain regions, with correspondingly diminished behavioral performance. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of rTMS to visual cortex on subjects' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task. CONCLUSIONS/SIGNIFICANCE: Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.

  11. Evoked Electromyographically Controlled Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Hayashibe

    2016-07-01

    Full Text Available Time-variant muscle responses under electrical stimulation (ES are often problematic for all the applications of neuroprosthetic muscle control. This situation limits the range of ES usage in relevant areas, mainly due to muscle fatigue and also to changes in stimulation electrode contact conditions, especially in transcutaneous ES. Surface electrodes are still the most widely used in noninvasive applications.Electrical field variations caused by changes in the stimulation contact condition markedly affect the resulting total muscle activation levels. Fatigue phenomena under functional electrical stimulation (FES are also well known source of time-varying characteristics coming from muscle response under ES. Therefore it is essential to monitor the actual muscle state and assess the expected muscle response by ES so as to improve the current ES system in favour of adaptive muscle-response-aware FES control. To deal with this issue, we have been studying a novel control technique using evoked electromyography (eEMG signals to compensate for these muscle time-variances under ES for stable neuroprosthetic muscle control. In this perspective article, I overview the background of this topic and highlight important points to be aware of when using ES to induce the desired muscle activation regardless of the time-variance. I also demonstrate how to deal with the common critical problem of ES to move toward robust neuroprosthetic muscle control with the Evoked Electromyographically Controlled Electrical Stimulation paradigm.

  12. Glycogen depletion and resynthesis during 14 days of chronic low-frequency stimulation of rabbit muscle

    DEFF Research Database (Denmark)

    Prats, C; Bernal, C; Cadefau, J A

    2002-01-01

    Electro-stimulation alters muscle metabolism and the extent of this change depends on application intensity and duration. The effect of 14 days of chronic electro-stimulation on glycogen turnover and on the regulation of glycogen synthase in fast-twitch muscle was studied. The results showed that...

  13. Resveratrol stimulates AMP kinase activity in neurons.

    Science.gov (United States)

    Dasgupta, Biplab; Milbrandt, Jeffrey

    2007-04-24

    Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction (CR), such as increased life span and delay in the onset of diseases associated with aging. CR improves neuronal health, and the global beneficial effects of CR have been postulated to be mediated by the nervous system. One key enzyme thought to be activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular energy levels. AMPK is activated by increases in the cellular AMP:ATP ratio, whereupon it functions to help preserve cellular energy. In this regard, the regulation of dietary food intake by hypothalamic neurons is mediated by AMPK. The suppression of nonessential energy expenditure by activated AMPK along with the CR mimetic and neuroprotective properties of resveratrol led us to hypothesize that neuronal activation of AMPK could be an important component of resveratrol activity. Here, we show that resveratrol activated AMPK in Neuro2a cells and primary neurons in vitro as well as in the brain. Resveratrol and the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) promoted robust neurite outgrowth in Neuro2a cells, which was blocked by genetic and pharmacologic inhibition of AMPK. Resveratrol also stimulated mitochondrial biogenesis in an AMPK-dependent manner. Resveratrol-stimulated AMPK activity in neurons depended on LKB1 activity but did not require the NAD-dependent protein deacetylase SIRT1 during this time frame. These findings suggest that neuronal activation of AMPK by resveratrol could affect neuronal energy homeostasis and contribute to the neuroprotective effects of resveratrol.

  14. MOTORIC STIMULATION RELATED TO FINE MOTORIC DEVELOPMENT ON CHILD

    Directory of Open Access Journals (Sweden)

    Mira Triharini

    2017-07-01

    Full Text Available Introduction: Motor developmental stimulation is an activity undertaken to stimulate the children basic skills and so they can grow and develop optimally. Children who obtain a direct stimulus will grow faster than who get less stimulus. Mother’s behavior of stimulation is very important for children, it is considering as the basic needs of children and it must be fulfilled. Providing good stimulation could optimize fine motor development in children. The purpose of this study was to analyze mother’s behavior about motor stimulation with fine motor development in toddler age 4-5 years old. Method: Design have been  used in this study was cross sectional. Population were mothers and their toddler in Group A of Dharma Wanita Persatuan Driyorejo Gresik Preschool. Sample were 51 respondents recruited by using purposive sampling technique according to inclusion and exclusion criteria. The independent variable was mother’s behavior about motor stimulation whereas dependent variable was fine motor development in toddler. The data were collected using questionnaire and conducting observation on fine motor development based on Denver Development Screening Test (DDST. Data then analyzed using Spearman Rho (r test to find relation between mother’s behaviors about stimulation motor on their toddler fine motor development. Result: Results  of this study showed that there were correlations between mother’s knowledge and fine motor development in toddler (p=0.000, between mother’s attitude and fine motor development in toddler (p=0.000, and between mother’s actions and fine motor development in toddler (p=0.000. Analysis: In sort study found that there were relation between fine motor development and mother’s behavior. Discussion: Therefore mother’s behavior needed to be improved. Further research about stimulation motor and fine motor development aspects in toddler is required.

  15. Spectral characteristics of light sources for S-cone stimulation.

    Science.gov (United States)

    Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

    2002-11-01

    Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

  16. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

    Directory of Open Access Journals (Sweden)

    Thanos Manos

    2018-04-01

    Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

  17. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

    Science.gov (United States)

    Manos, Thanos; Zeitler, Magteld; Tass, Peter A

    2018-01-01

    In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long

  18. Stimulation of Suicidal Erythrocyte Death by Garcinol

    Directory of Open Access Journals (Sweden)

    Antonella Fazio

    2015-09-01

    Full Text Available Background/Aims: The benzophenone garcinol from dried fruit rind of Garcinia indica counteracts malignancy, an effect at least in part due to stimulation of apoptosis. The proapototic effect of garcinol is attributed in part to inhibition of histone acetyltransferases and thus modification of gene expression. Moreover, garcinol triggers mitochondrial depolarisation. Erythrocytes lack gene expression and mitochondria but are nevertheless able to enter apoptosis-like suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, energy depletion and Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i. The present study explored, whether and how garcinol induces eryptosis. Methods: To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and cytosolic ATP levels utilizing a luciferin-luciferase-based assay. Results: A 24 hours exposure of human erythrocytes to garcinol (2.5 or 5 µM significantly increased the percentage of annexin-V-binding cells. Garcinol decreased (at 1 µM and 2.5 µM or increased (at 5 µM forward scatter. Garcinol (5 µM further increased Fluo3-fluorescence, increased DCFDA fluorescence, and decreased cytosolic ATP levels. The effect of garcinol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Garcinol triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of ROS formation, energy depletion and Ca2+ entry.

  19. Electrical stimulation superimposed onto voluntary muscular contraction.

    Science.gov (United States)

    Paillard, Thierry; Noé, Frédéric; Passelergue, Philippe; Dupui, Philippe

    2005-01-01

    Electrical stimulation (ES) reverses the order of recruitment of motor units (MU) observed with voluntary muscular contraction (VOL) since under ES, large MU are recruited before small MU. The superimposition of ES onto VOL (superimposed technique: application of an electrical stimulus during a voluntary muscle action) can theoretically activate more motor units than VOL performed alone, which can engender an increase of the contraction force. Two superimposed techniques can be used: (i) the twitch interpolation technique (ITT), which consists of interjecting an electrical stimulus onto the muscle nerve; and (ii) the percutaneous superimposed electrical stimulation technique (PST), where the stimulation is applied to the muscle belly. These two superimposed techniques can be used to evaluate the ability to fully activate a muscle. They can thus be employed to distinguish the central or peripheral nature of fatigue after exhausting exercise. In general, whatever the technique employed, the superimposition of ES onto volitional exercise does not recruit more MU than VOL, except with eccentric actions. Nevertheless, the neuromuscular response associated with the use of the superimposed technique (ITT and PST) depends on the parameter of the superimposed current. The sex and the training level of the subjects can also modify the physiological impact of the superimposed technique. Although the motor control differs drastically between training with ES and VOL, the integration of the superimposed technique in training programmes with healthy subjects does not reveal significant benefits compared with programmes performed only with voluntary exercises. Nevertheless, in a therapeutic context, training programmes using ES superimposition compensate volume and muscle strength deficit with more efficiency than programmes using VOL or ES separately.

  20. Noninvasive Transcranial Brain Stimulation and Pain

    OpenAIRE

    Rosen, Allyson C.; Ramkumar, Mukund; Nguyen, Tam; Hoeft, Fumiko

    2009-01-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the tre...

  1. Stimulating effects of ionizing radiation

    International Nuclear Information System (INIS)

    Jaworowski, Z.

    1995-01-01

    The influence of low doses on human organism is not definite known up to now. The worldwide discussion on this topic has been presented. A lot of analysed statistical data proved that the stimulating effect of low doses of ionizing radiation really exists and can have a beneficial influence on human health. 43 refs, 4 figs, 6 tabs

  2. Ovarian stimulation and embryo quality

    NARCIS (Netherlands)

    Baart, Esther; Macklon, Nick S.; Fauser, Bart J. C. M.

    To Study the effects of different ovarian stimulation approaches on oocyte and embryo quality, it is imperative to assess embryo quality with a reliable and objective method. Embryos rated as high quality by standardized morphological assessment are associated with higher implantation and pregnancy

  3. Enteral feeding without pancreatic stimulation

    DEFF Research Database (Denmark)

    Kaushik, Neeraj; Pietraszewski, Marie; Holst, Jens Juul

    2005-01-01

    OBJECTIVE: All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result...

  4. Transcranial magnetic stimulation in schizophrenia.

    Science.gov (United States)

    Zaman, Rashid; Thind, Dilraj; Kocmur, Marga

    2008-11-01

    Transcranial magnetic stimulation (TMS) is a non-invasive and painless way of stimulating the neural tissue (cerebral cortex, spinal roots, and cranial and peripheral nerves). The first attempts at stimulating the neural tissue date back to 1896 by d'Arsonval; however, it was successfully carried out by Barker and colleagues in Sheffield, UK, in 1985. It soon became a useful tool in neuroscience for neurophysiologists and neurologists and psychiatrists. The original single-pulse TMS, largely used as an investigative tool, was further refined and developed in the early 1990s into what is known as repetitive TMS (rTMS), having a frequency range of 1-60 Hz. The stimulation by both TMS and rTMS of various cortical regions displayed alteration of movement, mood, and behavior, leading researchers to investigate a number of psychiatric and neuropsychiatric disorders, as well as to explore its therapeutic potential. There is now a large amount of literature on the use of TMS/rTMS in depression; however, its use in schizophrenia, both as an investigative and certainly as a therapeutic tool is relatively recent with a limited but increasing number of publications. In this article, we will outline the principles of TMS/rTMS and critically review their use in schizophrenia both as investigative and potential therapeutic tools.

  5. Aversive Stimulation -- Criteria for Application.

    Science.gov (United States)

    O'Donnell, Patrick A.; Ohlson, Glenn A.

    Criteria for applying aversive stimulation with severely handicapped children are examined, and practical and ethical issues are considered. Factors seen to influence punishment outcomes include timing, intensity, and schedule of reinforcement. Suggested is the need for further research on the comparative effectiveness of positive and negative…

  6. Thalamic stimulation in absence epilepsy

    NARCIS (Netherlands)

    Luttjohann, A.K.; Luijtelaar, E.L.J.M. van

    2013-01-01

    Purpose The site specific effects of two different types of electrical stimulation of the thalamus on electroencephalic epileptic activity as generated in the cortico-thalamo-cortical system were investigated in genetic epileptic WAG/Rij rats, a well characterized and validated absence

  7. Dosimetry of typical transcranial magnetic stimulation devices

    Science.gov (United States)

    Lu, Mai; Ueno, Shoogo

    2010-05-01

    The therapeutic staff using transcranial magnetic stimulation (TMS) devices could be exposed to magnetic pulses. In this paper, dependence of induced currents in real human man model on different coil shapes, distance between the coil and man model as well as the rotation of the coil in space have been investigated by employing impedance method. It was found that the figure-of-eight coil has less leakage magnetic field and low current density induced in the body compared with the round coil. The TMS power supply cables play an important role in the induced current density in human body. The induced current density in TMS operator decreased as the coil rotates from parallel position to perpendicular position. Our present study shows that TMS operator should stand at least 110 cm apart from the coil.

  8. Ripplon laser through stimulated emission mediated by water waves

    Science.gov (United States)

    Kaminski, Samuel; Martin, Leopoldo L.; Maayani, Shai; Carmon, Tal

    2016-12-01

    Lasers rely on stimulated electronic transition, a quantum phenomenon in the form of population inversion. In contrast, phonon masers depend on stimulated Raman scattering and are entirely classical. Here we extend Raman lasers to rely on capillary waves, which are unique to the liquid phase of matter and relate to the attraction between intimate fluid particles. We fabricate resonators that co-host capillary and optical modes, control them to operate at their non-resolved sideband and observe stimulated capillary scattering and the coherent excitation of capillary resonances at kilohertz rates (which can be heard in audio files recorded by us). By exchanging energy between electromagnetic and capillary waves, we bridge the interfacial tension phenomena at the liquid phase boundary to optics. This approach may impact optofluidics by allowing optical control, interrogation and cooling of water waves.

  9. Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.

    Directory of Open Access Journals (Sweden)

    José Luis Vargas Luna

    Full Text Available Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.

  10. Nanosecond laser pulse stimulation of spiral ganglion neurons and model cells.

    Science.gov (United States)

    Rettenmaier, Alexander; Lenarz, Thomas; Reuter, Günter

    2014-04-01

    Optical stimulation of the inner ear has recently attracted attention, suggesting a higher frequency resolution compared to electrical cochlear implants due to its high spatial stimulation selectivity. Although the feasibility of the effect is shown in multiple in vivo experiments, the stimulation mechanism remains open to discussion. Here we investigate in single-cell measurements the reaction of spiral ganglion neurons and model cells to irradiation with a nanosecond-pulsed laser beam over a broad wavelength range from 420 nm up to 1950 nm using the patch clamp technique. Cell reactions were wavelength- and pulse-energy-dependent but too small to elicit action potentials in the investigated spiral ganglion neurons. As the applied radiant exposure was much higher than the reported threshold for in vivo experiments in the same laser regime, we conclude that in a stimulation paradigm with nanosecond-pulses, direct neuronal stimulation is not the main cause of optical cochlea stimulation.

  11. Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender.

    Science.gov (United States)

    Meiron, Oded; Lavidor, Michal

    2013-05-01

    Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory representations in interference-rich conditions, and is highly dependent on DLPFC function. We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined "online" WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Optical stimulation of the facial nerve: a surgical tool?

    Science.gov (United States)

    Richter, Claus-Peter; Teudt, Ingo Ulrik; Nevel, Adam E.; Izzo, Agnella D.; Walsh, Joseph T., Jr.

    2008-02-01

    One sequela of skull base surgery is the iatrogenic damage to cranial nerves. Devices that stimulate nerves with electric current can assist in the nerve identification. Contemporary devices have two main limitations: (1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue. Stimulation and screening of the nerve is possible without making physical contact. The gerbil facial nerve was irradiated with 250-μs-long pulses of 2.12 μm radiation delivered via a 600-μm-diameter optical fiber at a repetition rate of 2 Hz. Muscle action potentials were recorded with intradermal electrodes. Nerve samples were examined for possible tissue damage. Eight facial nerves were stimulated with radiant exposures between 0.71-1.77 J/cm2, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3-0.4 mV, 0.15-1.4 mV and 0.3-2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm2, but no apparent damage at radiant exposures of 2.0 J/cm2.

  13. Electrical stimulation of transplanted motoneurons improves motor unit formation

    Science.gov (United States)

    Liu, Yang; Grumbles, Robert M.

    2014-01-01

    Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

  14. A Novel In Vitro System for Comparative Analyses of Bone Cells and Bacteria under Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Thomas Josef Dauben

    2016-01-01

    Full Text Available Electrical stimulation is a promising approach to enhance bone regeneration while having potential to inhibit bacterial growth. To investigate effects of alternating electric field stimulation on both human osteoblasts and bacteria, a novel in vitro system was designed. Electric field distribution was simulated numerically and proved by experimental validation. Cells were stimulated on Ti6Al4V electrodes and in short distance to electrodes. Bacterial growth was enumerated in supernatant and on the electrode surface and biofilm formation was quantified. Electrical stimulation modulated gene expression of osteoblastic differentiation markers in a voltage-dependent manner, resulting in significantly enhanced osteocalcin mRNA synthesis rate on electrodes after stimulation with 1.4VRMS. While collagen type I synthesis increased when stimulated with 0.2VRMS, it decreased after stimulation with 1.4VRMS. Only slight and infrequent influence on bacterial growth was observed following stimulations with 0.2VRMS and 1.4VRMS after 48 and 72 h, respectively. In summary this novel test system is applicable for extended in vitro studies concerning definition of appropriate stimulation parameters for bone cell growth and differentiation, bacterial growth suppression, and investigation of general effects of electrical stimulation.

  15. Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.

    Science.gov (United States)

    Tsuji, Kojun; Tsujimura, Takanori; Magara, Jin; Sakai, Shogo; Nakamura, Yuki; Inoue, Makoto

    2015-02-01

    The aim of the present study was to investigate the adaptation of the swallowing reflex in terms of reduced swallowing reflex initiation following continuous superior laryngeal nerve stimulation. Forty-four male Sprague Dawley rats were anesthetized with urethane. To identify swallowing, electromyographic activity of the left mylohyoid and thyrohyoid muscles was recorded. To evoke the swallowing response, the superior laryngeal nerve (SLN), recurrent laryngeal nerve, or cortical swallowing area was electrically stimulated. Repetitive swallowing evoked by continuous SLN stimulation was gradually reduced, and this reduction was dependent on the resting time duration between stimulations. Prior SLN stimulation also suppressed subsequent swallowing initiation. The reduction in evoked swallows induced by recurrent laryngeal nerve or cortical swallowing area stimulation was less than that following superior laryngeal nerve stimulation. Decerebration had no effect on the reduction in evoked swallows. Prior subthreshold stimulation reduced subsequent initiation of swallowing, suggesting that there was no relationship between swallowing movement evoked by prior stimulation and the subsequent reduction in swallowing initiation. Overall, these data suggest that reduced sensory afferent nerve firing and/or trans-synaptic responses, as well as part of the brainstem central pattern generator, are involved in adaptation of the swallowing reflex following continuous stimulation of swallow-inducing peripheral nerves and cortical areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    Science.gov (United States)

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes

    International Nuclear Information System (INIS)

    Freemark, M.; D'Ercole, A.J.; Handwerger, S.

    1985-01-01

    The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [ 14 C]glucose incorporation into glycogen (14.4-72.9% and total cell glycogen content (10.6-34.3%. Maximal stimulation of glycogen synthesis by Sm-C occurred at 2-4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [ 14 C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm-C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism

  18. Uncovering the mechanism(s) of deep brain stimulation

    International Nuclear Information System (INIS)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y

    2005-01-01

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS

  19. Dosimetry based on thermally and optically stimulated luminescence

    International Nuclear Information System (INIS)

    Agersnap Larsen, Niels

    1999-01-01

    Thermally Stimulated Luminescence (TL) and Optically Stimulated Luminescence (OSL) properties of quartz and α-Al 2 O 3 have been investigated. Anneling-induced OSL and TL sensitivity changes in quartz has been investigated by experiments and modelling. This study does not support a pre-dose effect to account for the observed annealing-induced sensitivity change. The experimental data indicates a more simple mechanism that involves alteration of the concentration of the defect centers. Results from modelling of removal or creation of defect centers comparing well with experimentally obtained data. Thermal quenching of luminescence for the main emission center, the F-center, in α-Al 2 O 3 :C has been investigated by analysing TL curves obtained at different heating rates. The thermal quenching dependence of luminescence is found to follow the classical Mott-Seitz expression. Basic investigations of OSL properties of αAl 2 O 3 :C, including: the thermal depth of the OSL traps, the temperature dependence of OSL, and the OSL stimulation spectra. Simultaneous measurements of TL and thermally stimulated conductivity (TSC) are presented for γ-irradiated αAl 2 O 3 :C. Activation energy analysis of the data reveals a superposition of several first-order TL and TSC peaks caused by release of charge carriers from a distribution of trapping states. Furthermore a description of an experimental method developed to determine the sign of the thermally released charge carriers has been presented. (au)

  20. How to personalize ovarian stimulation in clinical practice.

    Science.gov (United States)

    Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

    2017-09-01

    Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

  1. Somato stimulation and acupuncture therapy.

    Science.gov (United States)

    Zhao, Jing-Jun; Rong, Pei-Jing; Shi, Li; Ben, Hui; Zhu, Bing

    2016-05-01

    Acupuncture is an oldest somato stimulus medical technique. As the most representative peripheral nerve stimulation therapy, it has a complete system of theory and application and is applicable to a large population. This paper expounds the bionic origins of acupuncture and analyzes the physiological mechanism by which acupuncture works. For living creatures, functionally sound viscera and effective endurance of pain are essential for survival. This paper discusses the way in which acupuncture increases the pain threshold of living creatures and the underlying mechanism from the perspective of bionics. Acupuncture can also help to adjust visceral functions and works most effectively in facilitating the process of digestion and restraining visceral pain. This paper makes an in-depth overview of peripheral nerve stimulation therapy represented by acupuncture. We look forward to the revival of acupuncture, a long-standing somato stimulus medicine, in the modern medical systems.

  2. Vagal stimulation in heart failure.

    Science.gov (United States)

    De Ferrari, Gaetano M

    2014-04-01

    Heart failure (HF) is accompanied by an autonomic imbalance that is almost always characterized by both increased sympathetic activity and withdrawal of vagal activity. Experimentally, vagal stimulation has been shown to exert profound antiarrhythmic activity and to improve cardiac function and survival in HF models. A open-label pilot clinical study in 32 patients with chronic HF has shown safety and tolerability of chronic vagal stimulation associated with subjective (improved quality of life and 6-min walk test) and objective improvements (reduced left ventricular systolic volumes and improved left ventricular ejection fraction). Three larger clinical studies, including a phase III trial are currently ongoing and will evaluate the clinical role of this new approach.

  3. Tactile Stimulation and Consumer Response.

    OpenAIRE

    Hornik, Jacob

    1992-01-01

    Tactile behavior is a basic communication form as well as an expression of interpersonal involvement. This article presents three studies offering evidence for the positive role of casual interpersonal touch on consumer behavior. More specifically, it provides initial support for the view that tactile stimulation in various consumer behavior situations enhances the positive feeling for and evaluation of both the external stimuli and the touching source. Further, customers touched by a request...

  4. Resonant Impulsive Stimulated Raman Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Mokhtari, A; Chesnoy, J

    1988-03-15

    Using a femtosecond dye laser, we observe in real-time vibrational oscillations excited by impulsive stimulated Raman scattering (ISRS) close to an electronic resonance. We perform single-beam Raman excitation and probe the driven coherence by a polarization-sensitive detection. We demonstrate for the first time impulsively Raman-induced dichroism, birefringence as well as frequency and time delay shifts. We analyse the characteristics of resonant ISRS on a vibrational mode of a dye molecule (malachite green) in solution.

  5. Transcranial Magnetic Stimulation in Children

    OpenAIRE

    Garvey, Marjorie A.; Mall, Volker

    2008-01-01

    Developmental disabilities (e.g. attention deficit disorder; cerebral palsy) are frequently associated with deviations of the typical pattern of motor skill maturation. Neurophysiologic tools, such as transcranial magnetic stimulation (TMS), which probe motor cortex function, can potentially provide insights into both typical neuromotor maturation and the mechanisms underlying the motor skill deficits in children with developmental disabilities. These insights may set the stage for finding ef...

  6. Resonant Impulsive Stimulated Raman Scattering

    International Nuclear Information System (INIS)

    Mokhtari, A.; Chesnoy, J.

    1988-01-01

    Using a femtosecond dye laser, we observe in real-time vibrational oscillations excited by impulsive stimulated Raman scattering (ISRS) close to an electronic resonance. We perform single-beam Raman excitation and probe the driven coherence by a polarization-sensitive detection. We demonstrate for the first time impulsively Raman-induced dichroism, birefringence as well as frequency and time delay shifts. We analyse the characteristics of resonant ISRS on a vibrational mode of a dye molecule (malachite green) in solution

  7. Optical stimulated luminescence (OSL) dating

    International Nuclear Information System (INIS)

    Banerjee, D.

    1999-01-01

    Since the pioneering work by Huntley et al. (1985), optical dating is being increasingly recognised as an important technique for establishing a time frame of deposition of sediments (Aitken, 1998). Optical dating differs from thermoluminescence (TL) dating in that visible/infrared light from lasers or LEDs (light-emitting-diodes) is used as a means of stimulation, in contrast to thermal stimulation. It has several advantages over TL dating: (i) the resetting of the OSL (optically stimulated luminescence) clock is more effective than that of TL clock; for sediments transported under water or in other situations where the sediment grains have undergone inhomogeneous bleaching, this property ensures that ages based on optical dating are generally more reliable than TL ages, (ii) the optical dating technique is non-destructive, and multiple readouts of the optical signal is possible; this feature has resulted in the development of single-aliquot and single-grain protocols (Murray and Wintle, 1999; Banerjee et al. 1999), (iii) the sample is not heated as in TL; thus, spurious luminescence is avoided and there is a significant reduction in blackbody radiation. Dating of materials which change phase on heating is also practical, and finally, (iv) thermal quenching of luminescence is negligible, allowing accurate estimation of kinetic parameters using standard techniques and providing access to deep OSL traps. This characteristic may be helpful in extending the limits of optical dating beyond the last 150 ka from a global point of view

  8. Performance Enhancement by Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Parisa Gazerani

    2017-09-01

    Full Text Available Number of substances and strategies are available to increase performance in sport (Catlin and Murray, 1996. Since 2004, the World Anti-Doping Agency (WADA posts an updated list of substances and methods prohibited to athletes. Drugs (e.g., steroids, stimulants are a major part of this list; however, technologies and methods (e.g., gene doping are increasingly being identified and added (WADA, 2017. Among technologies and methods that might exert a potential effect on athletic performance, brain stimulation has recently been subjected to extensive discussion. Neuro-enhancement for doping purposes has been termed “neurodoping” in the literature (Davis, 2013; however, this concept needs further documentation before the term “neurodoping” can be used properly. Two major non-invasive techniques of brain stimulations are transcranial magnetic stimulation (TMS (Hallett, 2007; Rossi et al., 2009, and transcranial direct current stimulation (tDCS (Stagg and Nitsche, 2011. In TMS, an electric coil held over the head applies magnetic pulses to create currents in the brain. In tDCS, a low, continuous electrical current is delivered to the brain by using surface electrodes attached on the scalp. TMS and tDCS have been used in both research and clinic (Shin and Pelled, 2017 for example to examine alterations in cognitive function or motor skills or to assist in recovering motor function after a stroke (Gomez Palacio Schjetnan et al., 2013 or reducing fatigue in patients with multiple sclerosis (Saiote et al., 2014. In an opinion paper, it was proposed that use of emerging brain stimulation techniques might also enhance physical and mental performance in sports (Davis, 2013. The assumption was based on several reports. For example some studies have shown that TMS could shorten reaction times to visual, auditory and touch stimuli, reduce tremor, and enhance the acquisition of complex motor skills. Based on the current evidence, a recent review (Colzato

  9. Cortical stimulation and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Cristiane Cagnoni Ramos

    2015-02-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2015v28n2p1 This paper is a review of physiological and behavioral data on motor cortex stimulation (MCS and its role in persistent neuropathic pain. MCS has been widely used in clinical medicine as a tool for the management of pain that does not respond satisfactorily to any kind of conventional analgesia. Some important mechanisms involved in nociceptive modulation still remains unclear. The aim of this study was to describe the mechanisms involved in neuropathic pain and introduce the effectiveness of electrical stimulation of the motor cortex used in the treatment of this disease. The ascending pain pathways are activated by peripheral receptors, in which there is the transduction of a chemical, physical or mechanical stimulus as a nerve impulse, where this impulse is transmitted to the dorsal horn of the spinal cord, which connects with second-order neurons and ascends to different locations in the central nervous system where the stimulus is perceived as pain. Because MCS has been proved to modulate this pathway in the motor cortex, it has been studied to mimic its effects in clinical practice and improve the treatments used for chronic pain. MCS has gained much attention in recent years due to its action in reversing chronic neuropathic pain, this being more effective than electrical stimulation at different locations and related pain nuclei.

  10. Cortical stimulation and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Cristiane Cagnoni Ramos

    2015-05-01

    Full Text Available This paper is a review of physiological and behavioral data on motor cortex stimulation (MCS and its role in persistent neuropathic pain. MCS has been widely used in clinical medicine as a tool for the management of pain that does not respond satisfactorily to any kind of conventional analgesia. Some important mechanisms involved in nociceptive modulation still remains unclear. The aim of this study was to describe the mechanisms involved in neuropathic pain and introduce the effectiveness of electrical stimulation of the motor cortex used in the treatment of this disease. The ascending pain pathways are activated by peripheral receptors, in which there is the transduction of a chemical, physical or mechanical stimulus as a nerve impulse, where this impulse is transmitted to the dorsal horn of the spinal cord, which connects with second-order neurons and ascends to different locations in the central nervous system where the stimulus is perceived as pain. Because MCS has been proved to modulate this pathway in the motor cortex, it has been studied to mimic its effects in clinical practice and improve the treatments used for chronic pain. MCS has gained much attention in recent years due to its action in reversing chronic neuropathic pain, this being more effective than electrical stimulation at different locations and related pain nuclei.

  11. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

    Science.gov (United States)

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-05-14

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

  12. Contributions to muscle force and EMG by combined neural excitation and electrical stimulation

    Science.gov (United States)

    Crago, Patrick E.; Makowski, Nathaniel S.; Cole, Natalie M.

    2014-10-01

    Objective. Stimulation of muscle for research or clinical interventions is often superimposed on ongoing physiological activity without a quantitative understanding of the impact of the stimulation on the net muscle activity and the physiological response. Experimental studies show that total force during stimulation is less than the sum of the isolated voluntary and stimulated forces, but the occlusion mechanism is not understood. Approach. We develop a model of efferent motor activity elicited by superimposing stimulation during a physiologically activated contraction. The model combines action potential interactions due to collision block, source resetting, and refractory periods with previously published models of physiological motor unit recruitment, rate modulation, force production, and EMG generation in human first dorsal interosseous muscle to investigate the mechanisms and effectiveness of stimulation on the net muscle force and EMG. Main results. Stimulation during a physiological contraction demonstrates partial occlusion of force and the neural component of the EMG, due to action potential interactions in motor units activated by both sources. Depending on neural and stimulation firing rates as well as on force-frequency properties, individual motor unit forces can be greater, smaller, or unchanged by the stimulation. In contrast, voluntary motor unit EMG potentials in simultaneously stimulated motor units show progressive occlusion with increasing stimulus rate. The simulations predict that occlusion would be decreased by a reverse stimulation recruitment order. Significance. The results are consistent with and provide a mechanistic interpretation of previously published experimental evidence of force occlusion. The models also predict two effects that have not been reported previously—voluntary EMG occlusion and the advantages of a proximal stimulation site. This study provides a basis for the rational design of both future experiments and clinical

  13. Follicle-stimulating hormone (FSH) blood test

    Science.gov (United States)

    ... ency/article/003710.htm Follicle-stimulating hormone (FSH) blood test To use the sharing features on this page, please enable JavaScript. The follicle stimulating hormone (FSH) blood test measures the level of FSH in blood. FSH ...

  14. Vagus Nerve Stimulation for Treating Epilepsy

    Science.gov (United States)

    ... and their FAMILIES VAGUS NERVE STIMULATION FOR TREATING EPILEPSY This information sheet is provided to help you ... how vagus nerve stimulation (VNS) may help treat epilepsy. The American Academy of Neurology (AAN) is the ...

  15. 3D stroke rehabilitation using electrical stimulation and robotics

    OpenAIRE

    Tong, Daisy; Cai, Zhonglun; Meadmore, Katie; Hughes, Anne-Marie; Freeman, Christopher; Burridge, Jane; Rogers, E

    2011-01-01

    Stroke is the third leading cause of death and foremost cause of adult disability in the UK. A third of the surviving patients suffer from some degree of motor disability and depend on others to undertake daily activities. Conventional rehabilitation can mitigate this disability, but only 5% of the severely paralysed patients regain full upper limb function. Past studies have shown evidence of more effective technologies such as rehabilitation robotics and functional electrical stimulation (F...

  16. A Chip for an Implantable Neural Stimulator

    DEFF Research Database (Denmark)

    Gudnason, Gunnar; Bruun, Erik; Haugland, Morten

    2000-01-01

    This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation (FES). The purpose of FES is to restore muscular control in disabled patients. The chip performs all the signal processing required in an implanted neural stimulator. The power and digital data...

  17. Frequency shifts in stimulated Raman scattering

    International Nuclear Information System (INIS)

    Zinth, W.; Kaiser, W.

    1980-01-01

    The nonresonant contributions to the nonlinear susceptibility chisup(()3) produce a frequency chirp during stimulated Raman scattering. In the case of transient stimulated Raman scattering, the spectrum of the generated Stokes pulse is found at higher frequencies than expected from spontaneous Raman data. The frequency difference can be calculated from the theory of stimulated Raman scattering. (orig.)

  18. Geothermal Reservoir Well Stimulation Program: technology transfer

    Energy Technology Data Exchange (ETDEWEB)

    1980-05-01

    Each of the following types of well stimulation techniques are summarized and explained: hydraulic fracturing; thermal; mechanical, jetting, and drainhole drilling; explosive and implosive; and injection methods. Current stimulation techniques, stimulation techniques for geothermal wells, areas of needed investigation, and engineering calculations for various techniques. (MHR)

  19. Optical stimulator for vision-based sensors

    DEFF Research Database (Denmark)

    Rössler, Dirk; Pedersen, David Arge Klevang; Benn, Mathias

    2014-01-01

    We have developed an optical stimulator system for vision-based sensors. The stimulator is an efficient tool for stimulating a camera during on-ground testing with scenes representative of spacecraft flights. Such scenes include starry sky, planetary objects, and other spacecraft. The optical...

  20. Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Damián Hernández

    2016-01-01

    Full Text Available Background. Human induced pluripotent stem cells (iPSCs are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

  1. Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening

    Directory of Open Access Journals (Sweden)

    Silvia ePicazio

    2015-03-01

    Full Text Available Non-invasive brain stimulation modulates cortical excitability depending on the initial activation state of the structure being stimulated. Combination of cognitive with neurophysiological stimulations has been successfully employed to modulate responses of specific brain regions. The present research combined a neurophysiological pre-conditioning with a cognitive conditioning stimulation to modulate behavior. We applied this new state-dependency approach to investigate the cerebellar role in musical and spatial information processing, given that a link between musical perception and visuo-spatial abilities and a clear cerebellar involvement in music perception and visuo-spatial tasks have been reported. Cathodal, anodal or sham transcranial cerebellar Direct Current Stimulation (tcDCS pre-conditioning was applied on the left cerebellar hemisphere followed by conditioning stimulation through music or white noise listening in a sample of healthy subjects performing a Line Bisection Task (LBT. The combination of the cathodal stimulation with music listening resulted in a marked attentional shift toward the right hemispace, compensating thus the natural leftward bias of the baseline condition (pseudoneglect. Conversely, the anodal or sham pre-conditioning stimulations combined with either music and white noise conditioning listening did not modulate spatial attention. The efficacy of the combined stimulation (cathodal pre-conditioning and music conditioning and the absence of any effect of the single stimulations provide a strong support to the state-dependency theory. They propose that tcDCS in combination with music listening could act as a rehabilitative tool to improve cognitive functions in the presence of neglect or other spatial disorders.

  2. Bayesian neural adjustment of inhibitory control predicts emergence of problem stimulant use.

    Science.gov (United States)

    Harlé, Katia M; Stewart, Jennifer L; Zhang, Shunan; Tapert, Susan F; Yu, Angela J; Paulus, Martin P

    2015-11-01

    Bayesian ideal observer models quantify individuals' context- and experience-dependent beliefs and expectations about their environment, which provides a powerful approach (i) to link basic behavioural mechanisms to neural processing; and (ii) to generate clinical predictors for patient populations. Here, we focus on (ii) and determine whether individual differences in the neural representation of the need to stop in an inhibitory task can predict the development of problem use (i.e. abuse or dependence) in individuals experimenting with stimulants. One hundred and fifty-seven non-dependent occasional stimulant users, aged 18-24, completed a stop-signal task while undergoing functional magnetic resonance imaging. These individuals were prospectively followed for 3 years and evaluated for stimulant use and abuse/dependence symptoms. At follow-up, 38 occasional stimulant users met criteria for a stimulant use disorder (problem stimulant users), while 50 had discontinued use (desisted stimulant users). We found that those individuals who showed greater neural responses associated with Bayesian prediction errors, i.e. the difference between actual and expected need to stop on a given trial, in right medial prefrontal cortex/anterior cingulate cortex, caudate, anterior insula, and thalamus were more likely to exhibit problem use 3 years later. Importantly, these computationally based neural predictors outperformed clinical measures and non-model based neural variables in predicting clinical status. In conclusion, young adults who show exaggerated brain processing underlying whether to 'stop' or to 'go' are more likely to develop stimulant abuse. Thus, Bayesian cognitive models provide both a computational explanation and potential predictive biomarkers of belief processing deficits in individuals at risk for stimulant addiction. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please

  3. Stimulation of the sensory pudendal nerve increases bladder capacity in the rat.

    Science.gov (United States)

    Hokanson, James A; Langdale, Christopher L; Sridhar, Arun; Grill, Warren M

    2018-04-01

    Pudendal nerve stimulation is a promising treatment approach for lower urinary tract dysfunction, including symptoms of overactive bladder. Despite some promising clinical studies, there remain many unknowns as to how best to stimulate the pudendal nerve to maximize therapeutic efficacy. We quantified changes in bladder capacity and voiding efficiency during single-fill cystometry in response to electrical stimulation of the sensory branch of the pudendal nerve in urethane-anesthetized female Wistar rats. Increases in bladder capacity were dependent on both stimulation amplitude and rate. Stimulation that produced increases in bladder capacity also led to reductions in voiding efficiency. Also, there was a stimulation carryover effect, and increases in bladder capacity persisted during several nonstimulated trials following stimulated trials. Intravesically administered PGE 2 reduced bladder capacity, producing a model of overactive bladder (OAB), and sensory pudendal nerve stimulation again increased bladder capacity but also reduced voiding efficiency. This study serves as a basis for future studies that seek to maximize the therapeutic efficacy of sensory pudendal nerve stimulation for the symptoms of OAB.

  4. Technical review of the high energy gas stimulation technique

    Energy Technology Data Exchange (ETDEWEB)

    Haney, B.; Cuthill, D. [Computalog Ltd., Calgary, AB (Canada)

    1997-08-01

    High Energy Gas Stimulation (HEGS) or propellant stimulation is a process that enhances production of oil wells by decreasing wellbore damage and increasing near wellbore permeability. The technique has been used on about 7,000 wells with varying results. The HEGS tool is a cast cylinder of solid rocket propellant with a central ignition system. The propellant is fired and as it burns it produces a pressure load on the formation, increasing fracture volume which enhances the flow channels. Background information on the development and application of this stimulation technique was provided. The introduction of fractures around a wellbore is dependent on the pressure loading rate and the dynamic response of the rock. Propellant stimulation relies on controlling the pressure-time behaviour to maximize fracture growth by fluid pressurization. The process is composed of 3 sequential phases: (1) wellbore pressurization, (2) fracture initiation, and (3) fracture extension. A full description of each of these phases was provided. Geologic and well-tool factors that have a significant influence on the fracturing process such as in-situ stress, natural fractures and flaws, formation mechanical properties, formation fluid and flow properties, formation thermal properties, and wellbore, tool, and tamp configuration, were also reviewed. The many applications for HEGS were presented. It was emphasized that the success of HEGS is dependent on pre-stimulation problem evaluation and on proper charge design. Since HEGS will decrease near-wellbore restrictions and initiate formation breakdown, it should only be used in cases where this will be beneficial to the well. Careful attention to engineering will optimize results. 21 refs., 13 figs.

  5. Stimulated-emission effects in particle creation near black holes

    International Nuclear Information System (INIS)

    Wald, R.M.

    1976-01-01

    It has recently been shown that if a black hole is formed by gravitational collapse, spontaneous particle creation will occur and a thermal spectrum of all species of particles will be emitted to infinity if the quantum matter was initially in the vacuum state. In this paper we investigate the stimulated-emission effects which occur if particles are present initially. We show in general that for a Hermitian scalar field in an external potential or in curved, asymptotically flat spacetime, stimulated-emission effects can occur precisely in those modes for which there is spontaneous particle creation from the vacuum. For the case of a Schwarzschild black hole, this result appears paradoxical, since spontaneous emission occurs at late times but there is no classical analog of stimulated emission at late times. The resolution of this paradox is that in order to induce emission of particles which emerge at late times one must send in particles at early times, so that they reach the black hole very near the instant of its formation. However, enormous energy is required of these incoming particles in order to stimulate emission of particles which emerge at late times. Thus, for a Schwarzschild black hole, even if particles are initially present (with limited energy) they will induce emission only at early times; at late times one will see only the spontaneously emitted blackbody thermal radiation. For the case of a Kerr black hole stimulated emission can be induced by particles sent in at late times with the appropriate frequencies and angular dependence. If the number of incoming particles is large, this quantum stimulated emission just gives the classical superradiant scattering

  6. Stimulation of hair cells with ultraviolet light

    Science.gov (United States)

    Azimzadeh, Julien B.; Fabella, Brian A.; Hudspeth, A. J.

    2018-05-01

    Hair bundles are specialized organelles that transduce mechanical inputs into electrical outputs. To activate hair cells, physiologists have resorted to mechanical methods of hair-bundle stimulation. Here we describe a new method of hair-bundle stimulation, irradiation with ultraviolet light. A hair bundle illuminated by ultraviolet light rapidly moves towards its tall edge, a motion typically associated with excitatory stimulation. The motion disappears upon tip-link rupture and is associated with the opening of mechanotransduction channels. Hair bundles can be induced to move sinusoidally with oscillatory modulation of the stimulation power. We discuss the implications of ultraviolet stimulation as a novel hair-bundle stimulus.

  7. Thermally stimulated scattering in plasmas

    DEFF Research Database (Denmark)

    Dysthe, K. B.; Mjølhus, E.; Pécseli, H. L.

    1985-01-01

    this experiment local heat conduction is of little importance and the dynamic evolution for the electron temperature is dominated by heating and energy exchange with the ion component. These features are incorporated in the analysis. The resulting set of equations gives a growth rate and characteristic scale size......A theory for stimulated scattering of a laser beam is formulated where the dominant nonlinearity is the ohmic heating of the plasma. The analysis is carried out with particular reference to experimental investigations of CO2 laser heating of linear discharge plasma. In the conditions characterizing...

  8. Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

    Science.gov (United States)

    Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

    2010-04-01

    The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

  9. Evaluation of different types of rooting stimulators

    Directory of Open Access Journals (Sweden)

    Petr Salaš

    2012-01-01

    Full Text Available This paper focuses on the assessment of selected stimulators, especially from Rhizopon product line, which are used for rooting and root system enhancement in various ornamental woody species. Two available methods of cuttings stimulation were selected from the available range of rooting stimulators: stimulation by long-term immersion in solutions or treatment of cuttings with powder stimulators. The experiment involved stimulators with two active components, currently the most commonly used phytohormones for this purpose – IBA and NAA – that were applied in different concentrations. The experiment took place in three propagation terms with twelve coniferous and deciduous shrub varieties. The results of the experiment show the different reactions of the individual species as well as varieties on the respective term of propagation and used form of stimulator.

  10. Femtosecond stimulated Raman evidence for charge-transfer character in pentacene singlet fission† †Electronic supplementary information (ESI) available: Actinic pump spectrum, discussion on ground state addition process, peak fitting procedure, transient absorption data, power dependence measurements, etalon pulse shaping, TIPS-pentacene FSRS data, and optimized geometry and frequency calculation results. See DOI: 10.1039/c7sc03496b

    Science.gov (United States)

    Hart, Stephanie M.; Silva, W. Ruchira

    2017-01-01

    Singlet fission is a spin-allowed process in which an excited singlet state evolves into two triplet states. We use femtosecond stimulated Raman spectroscopy, an ultrafast vibrational technique, to follow the molecular structural evolution during singlet fission in order to determine the mechanism of this process. In crystalline pentacene, we observe the formation of an intermediate characterized by pairs of excited state peaks that are red- and blue-shifted relative to the ground state features. We hypothesize that these features arise from the formation of cationic and anionic species due to partial transfer of electron density from one pentacene molecule to a neighboring molecule. These observations provide experimental evidence for the role of states with significant charge-transfer character which facilitate the singlet fission process in pentacene. Our work both provides new insight into the singlet fission mechanism in pentacene and demonstrates the utility of structurally-sensitive time-resolved spectroscopic techniques in monitoring ultrafast processes. PMID:29675170

  11. Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder

    NARCIS (Netherlands)

    Groenman, A.P.; Oosterlaan, J.; Rommelse, N.N.J.; Franke, B.; Greven, C.U.; Hoekstra, P.J.; Hartman, C.A.; Luman, M.; Roeyers, H.; Oades, R.D.; Sergeant, J.A.; Buitelaar, J.K.; Faraone, S.V.

    2013-01-01

    BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. AIMS: To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD

  12. Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder

    NARCIS (Netherlands)

    Groenman, Annabeth P.; Oosterlaan, Jaap; Rommelse, Nanda N. J.; Franke, Barbara; Greven, Corina U.; Hoekstra, Pieter J.; Hartman, Catharina A.; Luman, Marjolein; Roeyers, Herbert; Oades, Robert D.; Sergeant, Joseph A.; Buitelaar, Jan K.; Faraone, Stephen V.

    Background Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. Aims To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD

  13. Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder.

    NARCIS (Netherlands)

    Groenman, A.P.; Oosterlaan, J.; Rommelse, N.; Franke, B.; Greven, C.U.; Hoekstra, P.J.; Hartman, C.A.; Luman, M.; Roeyers, H.; Oades, R.D.; Sergeant, J.A.; Buitelaar, J.K.; Faraone, S.V.

    2013-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. Aims: To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD

  14. Braille line using electrical stimulation

    International Nuclear Information System (INIS)

    Puertas, A; Pures, P; Echenique, A M; Ensinck, J P Graffigna y G

    2007-01-01

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards

  15. Braille line using electrical stimulation

    Science.gov (United States)

    Puertas, A.; Purés, P.; Echenique, A. M.; Ensinck, J. P. Graffigna y. G.

    2007-11-01

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards.

  16. Transcranial magnetic stimulation: language function.

    Science.gov (United States)

    Epstein, C M

    1998-07-01

    Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

  17. Braille line using electrical stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Puertas, A; Pures, P; Echenique, A M; Ensinck, J P Graffigna y G [Gabinete de TecnologIa Medica. Universidad N. de San Juan (Argentina)

    2007-11-15

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards.

  18. Stimulation of mitochondrial respiration induced by laser irradiation in the presence of rhodamine dyes

    International Nuclear Information System (INIS)

    Krasnikov, B.F.; Zorov, D.B.

    1996-01-01

    The effect of micromolar concentration of rhodamine 123 (methylrhodamine) and ethyl and amyl esters of unsubstituted rhodamine on oxygen consumption by rat liver mitochondria was studied under irradiation by an argon laser (488 and 514 nm). Irradiation of mitochondria in the presence of rhodamine stimulates their respiration. Light-induced stimulation of respiration is not inhibited by free radical scavenger ionol and by inhibitor of the permeability transition pore cyclosporine A. Stimulation of respiration by moderate doses of radiation is reversed in the dark. Increase in radiation dose resulted in only partial reversal of stimulated respiration in the dark. Rhodamine efficacy in stimulation of mitochondrial respiration depends on its structure (amyl > ethyl > methylrhodamine). 22 refs.; 4 figs

  19. Experimental study on stimulated scattering of ZnO nanospheres dispersed in water

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Jiulin, E-mail: hyq1304@126.com; Wu, Haopeng [Nanchang Hangkong University, Jiangxi Engineering Laboratory for Optoelectronics Testing Technology (China); Yan, Feng; Yang, Junjie [Nanchang Hangkong University, School of Measuring and Optical Engineering (China); He, Xingdao, E-mail: xingdaohe@126.com [Nanchang Hangkong University, Jiangxi Engineering Laboratory for Optoelectronics Testing Technology (China)

    2016-01-15

    The backward stimulated scattering (BSS) from ZnO nanospheres dispersed in water has been investigated experimentally by employing a Nd:YAG pulse laser with ∼532 nm wavelength and ∼8 ns pulse width as the pump laser source. The present results show that the BSS effect is uniquely and unequivocally different compared to other known stimulated scattering, such as stimulated Rayleigh scattering, stimulated Brillouin scattering, and stimulated Raman scattering, and it displays the characteristics of no frequency shift and threshold dependence on initial spontaneous Mie scattering seed source. These can be understood by means of the Mie scattering theory and a laser-induced stationary Bragg grating model.

  20. Unilateral phrenic nerve stimulation for neurogenic hypoventilation in Arnold Chiari malformation

    Directory of Open Access Journals (Sweden)

    Nitin Garg

    2013-01-01

    Full Text Available Long- term ventilator dependence in patients with neurogenic hypoventilation is associated with significant morbidity and restricts mobility. Diaphragmatic pacing by phrenic nerve stimulation (PNS is a viable alternative. This is a case report of patient with Arnold-Chiari malformation with extensive syrinx who had neurogenic hypoventilation during sleep even after foramen magnum decompression and resolution of the syrinx. Unilateral PNS was done using spinal cord stimulator. With intermittent stimulation for 8 h while asleep, patient could be weaned off the ventilator completely. At 2 years follow- up, patient is ambulant and has returned to his routine activities. PNS is a good treatment tool in patients with neurogenic hypoventilation. Spinal cord stimulator can be used with optimal results. This is first such reported case of using spinal cord stimulator for PNS from India.

  1. Role of spontaneous and stimulated emission in photon correlations

    International Nuclear Information System (INIS)

    Chopra, S.; Bohidar, H.; Harwalkar, V.

    1984-01-01

    Photon correlations have been alternately attributed to either spontaneous or stimulated emission by various authors. In this paper, the authors interpret, on the basis of available experimental data, the contribution of each emission form to the evolution of photon statistics. The laser is used as an example of a source which exhibits different statistical characteristics depending on the level of excitation, which is governed by the pump parameter a. From the data, it is evident that the transition from below to above threshold is accompanied by a significant drop in the magnitude of correlation and an increase in decay time. It may be noted that this transition causes a substantial increase in the coherent output which emphasizes the predominance of stimulated emission. In the case of a laser below threshold, however, photon correlations arise due to superposition of the more dominant spontaneously emitted wavetrains. Exact solutions of quantized systems do not exist in the presence of saturation effects. This implies that factorization and identification of terms with spontaneous or stimulated emission has not yet been done. This does not preculde a physical and intuitive interpretation of photon statistics within the framework of a standard model, and it is therefore argued that spontaneous emission is responsible for photon correlations while stimulated emission shows up in the dynamics as the coherence time

  2. Photovoltaic Pixels for Neural Stimulation: Circuit Models and Performance.

    Science.gov (United States)

    Boinagrov, David; Lei, Xin; Goetz, Georges; Kamins, Theodore I; Mathieson, Keith; Galambos, Ludwig; Harris, James S; Palanker, Daniel

    2016-02-01

    Photovoltaic conversion of pulsed light into pulsed electric current enables optically-activated neural stimulation with miniature wireless implants. In photovoltaic retinal prostheses, patterns of near-infrared light projected from video goggles onto subretinal arrays of photovoltaic pixels are converted into patterns of current to stimulate the inner retinal neurons. We describe a model of these devices and evaluate the performance of photovoltaic circuits, including the electrode-electrolyte interface. Characteristics of the electrodes measured in saline with various voltages, pulse durations, and polarities were modeled as voltage-dependent capacitances and Faradaic resistances. The resulting mathematical model of the circuit yielded dynamics of the electric current generated by the photovoltaic pixels illuminated by pulsed light. Voltages measured in saline with a pipette electrode above the pixel closely matched results of the model. Using the circuit model, our pixel design was optimized for maximum charge injection under various lighting conditions and for different stimulation thresholds. To speed discharge of the electrodes between the pulses of light, a shunt resistor was introduced and optimized for high frequency stimulation.

  3. Testosterone suppression of CRH-stimulated cortisol in men.

    Science.gov (United States)

    Rubinow, David R; Roca, Catherine A; Schmidt, Peter J; Danaceau, Merry A; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

    2005-10-01

    Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (pcortisol area under the curve was lower at a trend level (pcortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (pcortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

  4. Transcranial focused ultrasound stimulation of human primary visual cortex

    Science.gov (United States)

    Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

    2016-09-01

    Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

  5. Quantitative EEG findings associated with chronic stimulant and cannabis abuse and ADHD in an adult male substance use disorder population.

    Science.gov (United States)

    Trudeau, D L; Thuras, P; Stockley, H

    1999-10-01

    QEEG was studied in a population of chronic male PSUD/ADHD (psychoactive substance use disorder/attention deficit hyperactivity disorder) subjects vs. a matched sample of non-ADHD subjects with PSUD. Our first interest in conducting this study was to determine if the Thatcher University of Maryland database and complex demodulation method could replicate the specific QEEG findings reported for cocaine and cannabis using the John-NYU database and Fourier Transform method. The effects of cannabis and stimulants were also studied both separately and together to see if there were interactions and to see if the QEEG changes associated with chronic stimulant dependence were predicted by childhood ADHD status. Eyes-closed QEEGs were obtained and two independent artifacted 60 second samples were compared for reliability. The Thatcher database was used to analyze QEEG data from 56 subjects with mixed substance use disorder. Results showed that the Thatcher database replicates the John database for chronic stimulant dependence findings. Because of confounding variables of alcohol and polysubstance abuse, the findings related to cannabis and stimulant interaction were difficult to assess. Cannabis and stimulant dependence together produced more QEEG changes than either alone. More right temporal abnormalities were observed with stimulant dependence. In the absence of stimulant use, the QEEG effects of cannabis were relatively small; however, sample selection and methods used precluded comparison to previous studies. The persistent QEEG abnormalities associated with chronic stimulant dependence were independent of ADHD status in this sample using the methods of this study. Further research is needed to clarify the relationship of stimulant dependence with QEEG changes and ADHD status, and to clarify the interactions of chronic stimulant and cannabis abuse on QEEG.

  6. Further investigations into pulsed optically stimulated luminescence from feldspars using blue and green light

    International Nuclear Information System (INIS)

    Ankjaergaard, C.; Jain, M.; Kalchgruber, R.; Lapp, T.; Klein, D.; McKeever, S.W.S.; Murray, A.S.; Morthekai, P.

    2009-01-01

    The purpose of this paper is to investigate characteristics of luminescence signals resulting from pulsed optical stimulation of feldspars and thereby to understand the underlying processes giving rise to the signal. Fourteen different feldspar specimens were investigated using time-resolved optically stimulated luminescence (TR-OSL), and these signals can be mathematically described as a sum of 4 exponential components (a, b, c, d). The slowest component, d, increases with the duration of the light pulse as expected from the exponential model. The stimulation temperature dependence experiment suggests that the TR-OSL signal decay is governed by the recombination process and not by the excited state lifetime. Furthermore data from the TR-OSL signal dependence on stimulation time and preheat temperature suggest that the recombination process may not be a sum of exponentials, although the model cannot be rejected definitively.

  7. Sweet Taste Receptor Activation in the Gut Is of Limited Importance for Glucose-Stimulated GLP-1 and GIP Secretion

    DEFF Research Database (Denmark)

    Saltiel, Monika Yosifova; Kuhre, Rune Ehrenreich; Christiansen, Charlotte Bayer

    2017-01-01

    Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated whether the sweet taste receptor (STR) triggers this secretion. We investigated the role of STR activation for glucose-stimulated incretin...

  8. Introducing transcranial magnetic stimulation (TMS) and its property of causal inference in investigating brain-function relationships

    NARCIS (Netherlands)

    Schutter, D.J.L.G.; Honk, E.J. van; Panksepp, J.

    2004-01-01

    Transcranial magnetic stimulation (TMS) is a method capable of transiently modulating neural excitability. Depending on the stimulation parameters information processing in the brain can be either enhanced or disrupted. This way the contribution of different brain areas involved in mental processes

  9. Luminescence lifetimes in quartz: dependence on annealing temperature prior to beta irradiation

    International Nuclear Information System (INIS)

    Galloway, R.B.

    2002-01-01

    It is well known that the thermal history of a quartz sample influences the optically stimulated luminescence sensitivity of the quartz. It is found that the optically stimulated luminescence lifetime, determined from time resolved spectra obtained with pulsed stimulation, also depends on past thermal treatment. For samples at 20 deg. C during stimulation, the lifetime depends on beta dose and on duration of preheating at 220 deg. C prior to stimulation for quartz annealed at 600 deg. C and above, but is independent of these factors for quartz annealed at 500 deg. C and below. For stimulation at higher temperatures, the lifetime becomes shorter if the sample is held at temperatures above 125 deg. C during stimulation, in a manner consistent with thermal quenching. A single exponential decay is all that is required to fit the time resolved spectra for un-annealed quartz regardless of the temperature during stimulation (20-175 deg. C), or to fit the time resolved spectra from all samples held at 20 deg. C during stimulation, regardless of annealing temperature (20-1000 deg. C). An additional shorter lifetime is found for some combinations of annealing temperature and temperature during stimulation. The results are discussed in terms of a model previously used to explain thermal sensitisation. The luminescence lifetime data are best explained by the presence of two principal luminescence centres, their relative importance depending on the annealing temperature, with a third centre involved for limited combinations of annealing temperature and temperature during stimulation

  10. Calmodulin stimulation of calcium transport in carrot microsomal vesicles

    International Nuclear Information System (INIS)

    Pierce, W.S.; Sze, H.

    1987-01-01

    ATP-dependent 45 Ca 2+ uptake into microsomal vesicles isolated from cultured carrot cells (Daucus carota Danvers) was stimulated 2-3 fold by 5 ug/ml calmodulin (CaM). Microsomal vesicles separated with a linear sucrose gradient showed two peaks with CaM-stimulated Ca 2+ uptake activities. One peak (at 1.12 g/cc) comigrated with the activity of the antimycin A-insensitive NADH-dependent cytochrome c reductase. This transport activity was enhanced 10-20 fold by 10 mM oxalate and appeared to be associates with vesicles derived primarily from the ER. The other peak of CaM-stimulated Ca 2+ uptake (at 1.17 g/cc) was not affected by oxalate. These vesicles are probably derived from the plasma membrane. Preliminary experiments with the low-density vesicles (ER) vesicles, indicate that inositol-1,4,5-trisphosphate caused a transient reduction in intravesicular Ca 2+ . These results are consistent with the ER being an important site of intracellular Ca 2+ regulation

  11. Augmented brain function by coordinated reset stimulation with slowly varying sequences

    OpenAIRE

    Magteld eZeitler; Peter A. Tass; Peter A. Tass; Peter A. Tass

    2015-01-01

    Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e. an unlearning of abnormal synaptic connectivity and abnormal sync...

  12. Augmented brain function by coordinated reset stimulation with slowly varying sequences

    OpenAIRE

    Zeitler, Magteld; Tass, Peter A.

    2015-01-01

    Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and abnormal syn...

  13. Chemical dependence - resources

    Science.gov (United States)

    Substance use - resources, Drug abuse - resources; Resources - chemical dependence ... are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd. ...

  14. Multisensory stimulation in stroke rehabilitation

    Directory of Open Access Journals (Sweden)

    Barbro Birgitta Johansson

    2012-04-01

    Full Text Available The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, or various kinds of music therapy. Several studies have shown positive effects been reported but to give general recommendation more studies are needed. Patient heterogeneity and the interactions of age, gender, genes and environment are discussed. Randomized controlled longitudinal trials starting earlier post stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation.

  15. Consensus paper: combining transcranial stimulation with neuroimaging

    DEFF Research Database (Denmark)

    Siebner, Hartwig R; Bergmann, Til O; Bestmann, Sven

    2009-01-01

    neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce...... information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need......In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during...

  16. Bursting behaviours in cascaded stimulated Brillouin scattering

    International Nuclear Information System (INIS)

    Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

    2012-01-01

    Stimulated Brillouin scattering is studied by numerically solving the Vlasov—Maxwell system. A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave—wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light. (physics of gases, plasmas, and electric discharges)

  17. Mimicking muscle activity with electrical stimulation

    Science.gov (United States)

    Johnson, Lise A.; Fuglevand, Andrew J.

    2011-02-01

    Functional electrical stimulation is a rehabilitation technology that can restore some degree of motor function in individuals who have sustained a spinal cord injury or stroke. One way to identify the spatio-temporal patterns of muscle stimulation needed to elicit complex upper limb movements is to use electromyographic (EMG) activity recorded from able-bodied subjects as a template for electrical stimulation. However, this requires a transfer function to convert the recorded (or predicted) EMG signals into an appropriate pattern of electrical stimulation. Here we develop a generalized transfer function that maps EMG activity into a stimulation pattern that modulates muscle output by varying both the pulse frequency and the pulse amplitude. We show that the stimulation patterns produced by this transfer function mimic the active state measured by EMG insofar as they reproduce with good fidelity the complex patterns of joint torque and joint displacement.

  18. Noninvasive transcranial brain stimulation and pain.

    Science.gov (United States)

    Rosen, Allyson C; Ramkumar, Mukund; Nguyen, Tam; Hoeft, Fumiko

    2009-02-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the treatment of chronic pain. Furthermore, TMS and tDCS can be applied with other techniques, such as event-related potentials and pharmacologic manipulation, to illuminate the underlying physiologic mechanisms of normal and pathological pain. This review presents a description and overview of the uses of two major brain stimulation techniques and a listing of useful references for further study.

  19. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  20. Presenilin dependence of phospholipase C and protein kinase C signaling

    DEFF Research Database (Denmark)

    Dehvari, Nodi; Cedazo-Minguez, Angel; Isacsson, Ola

    2007-01-01

    -stimulated phospholipase C (PLC) activity which was gamma-secretase dependent. To further evaluate the dependence of PLC on PSs we measured PLC activity and the activation of variant protein kinase C (PKC) isoforms in mouse embryonic fibroblasts (MEFs) lacking either PS1, PS2, or both. PLC activity and PKCalpha...

  1. Frequency dependent changes in NMDAR-dependent synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Arvind eKumar

    2011-09-01

    Full Text Available The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or LTD depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ~5-15Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike-timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process.

  2. Plasmon-enhanced optically stimulated luminescence

    Energy Technology Data Exchange (ETDEWEB)

    Guidelli, E. J.; Baffa, O. [Universidade de Sao Paulo, Faculdade de Filosofia, Ciencias e Letras de Ribeirao Preto, Departamento de Fisica, Av. Bandeirantes 3900, 14040-901 Ribeirao Preto, Sao Paulo (Brazil); Ramos, A. P., E-mail: ederguidelli@gmail.com [Universidade de Sao Paulo, Faculdade de Filosofia, Ciencias e Letras de Ribeirao Preto, Departamento de Quimica, Av. Bandeirantes 3900, 14040-901 Ribeirao Preto, Sao Paulo (Brazil)

    2015-10-15

    Full text: Optically Stimulated Luminescence dosimeters (OSLD) have been largely used for personal, medical, and industrial radiation dosimetry. Developing highly sensitive and small-sized radiation detectors and dosimeters is essential for improving spatial resolution and consequently diagnosis quality and treatment efficacy in the case of applications in radiodiagnosis and radiation therapy, for instance. Conventional methods to improve the OSLD sensitivity consist of doping and co-doping the host materials with atoms of other elements, thereby increasing the amount of trapping and/or luminescent centers. Our group is researching on the use of the plasmon properties of noble metal nanoparticles to increase OSL intensity. Upon incidence of a light beam with appropriate resonant wavelengths, the oscillation of the free electrons at the nanoparticle surface originates the Localized Surface Plasmons (LSP) and the consequent plasmon resonance band. The interaction between the LSP and the surrounding luminescent material leads to new optical properties largely employed for enhancing several luminescent processes. Here we will show our results regarding the use of LSP to increase OSLD sensitivity. The interaction between the traps/luminescent centers and the plasmons depends on the distance between them, on the plasmon resonance band intensity and position, as well as on the surrounding medium. Therefore, the plasmon-enhanced luminescence is a promising tool to develop more sensitive and miniaturized OSLD. (Author)

  3. Plasmon-enhanced optically stimulated luminescence

    International Nuclear Information System (INIS)

    Guidelli, E. J.; Baffa, O.; Ramos, A. P.

    2015-10-01

    Full text: Optically Stimulated Luminescence dosimeters (OSLD) have been largely used for personal, medical, and industrial radiation dosimetry. Developing highly sensitive and small-sized radiation detectors and dosimeters is essential for improving spatial resolution and consequently diagnosis quality and treatment efficacy in the case of applications in radiodiagnosis and radiation therapy, for instance. Conventional methods to improve the OSLD sensitivity consist of doping and co-doping the host materials with atoms of other elements, thereby increasing the amount of trapping and/or luminescent centers. Our group is researching on the use of the plasmon properties of noble metal nanoparticles to increase OSL intensity. Upon incidence of a light beam with appropriate resonant wavelengths, the oscillation of the free electrons at the nanoparticle surface originates the Localized Surface Plasmons (LSP) and the consequent plasmon resonance band. The interaction between the LSP and the surrounding luminescent material leads to new optical properties largely employed for enhancing several luminescent processes. Here we will show our results regarding the use of LSP to increase OSLD sensitivity. The interaction between the traps/luminescent centers and the plasmons depends on the distance between them, on the plasmon resonance band intensity and position, as well as on the surrounding medium. Therefore, the plasmon-enhanced luminescence is a promising tool to develop more sensitive and miniaturized OSLD. (Author)

  4. Optogenetic stimulation: Understanding memory and treating deficits.

    Science.gov (United States)

    Barnett, S C; Perry, B A L; Dalrymple-Alford, J C; Parr-Brownlie, L C

    2018-05-09

    Technology allowing genetically targeted cells to be modulated by light has revolutionised neuroscience in the past decade, and given rise to the field of optogenetic stimulation. For this, non-native, light activated proteins (e.g. channelrhodopsin) are expressed in a specific cell phenotype (e.g. glutamatergic neurons) in a subset of central nervous system nuclei, and short pulses of light of a narrow wavelength (e.g. blue, 473 nm) are used to modulate cell activity. Cell activity can be increased or decreased depending on which light activated protein is used. We review how the greater precision provided by optogenetics has transformed the study of neural circuits, in terms of cognition and behaviour, with a focus on learning and memory. We also explain how optogenetic modulation is facilitating a better understanding of the mechanistic underpinnings of some neurological and psychiatric conditions. Based on this research, we suggest that optogenetics may provide tools to improve memory in neurological conditions, particularly diencephalic amnesia and Alzheimer's disease. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  5. Step-wise stimulated martensitic transformations

    International Nuclear Information System (INIS)

    Airoldi, G.; Riva, G.

    1991-01-01

    NiTi alloys, widely known both for their shape memory properties and for unusual pseudoelastic behaviour, are now on the forefront attention for step-wise induced memory processes, thermal or stress stimulated. Literature results related to step-wise stimulated martensite (direct transformation) are examined and contrasted with step-wise thermal stimulated parent phase (reverse transformation). Hypothesis are given to explain the key characters of both transformations, a thermodynamic model from first principles being till now lacking

  6. Analysis of Facial Expression by Taste Stimulation

    Science.gov (United States)

    Tobitani, Kensuke; Kato, Kunihito; Yamamoto, Kazuhiko

    In this study, we focused on the basic taste stimulation for the analysis of real facial expressions. We considered that the expressions caused by taste stimulation were unaffected by individuality or emotion, that is, such expressions were involuntary. We analyzed the movement of facial muscles by taste stimulation and compared real expressions with artificial expressions. From the result, we identified an obvious difference between real and artificial expressions. Thus, our method would be a new approach for facial expression recognition.

  7. Effects of Dual-Channel Functional Electrical Stimulation on Gait Performance in Patients with Hemiparesis

    Science.gov (United States)

    Springer, Shmuel; Vatine, Jean-Jacques; Lipson, Ronit; Wolf, Alon; Laufer, Yocheved

    2012-01-01

    The study objective was to assess the effect of functional electrical stimulation (FES) applied to the peroneal nerve and thigh muscles on gait performance in subjects with hemiparesis. Participants were 45 subjects (age 57.8 ± 14.8 years) with hemiparesis (5.37 ± 5.43 years since diagnosis) demonstrating a foot-drop and impaired knee control. Thigh stimulation was applied either to the quadriceps or hamstrings muscles, depending on the dysfunction most affecting gait. Gait was assessed during a two-minute walk test with/without stimulation and with peroneal stimulation alone. A second assessment was conducted after six weeks of daily use. The addition of thigh muscles stimulation to peroneal stimulation significantly enhanced gait velocity measures at the initial and second evaluation. Gait symmetry was enhanced by the dual-channel stimulation only at the initial evaluation, and single-limb stance percentage only at the second assessment. For example, after six weeks, the two-minute gait speed with peroneal stimulation and with the dual channel was 0.66 ± 0.30 m/sec and 0.70 ± 0.31 m/sec, respectively (P hemiparesis more than peroneal FES alone. PMID:23097635

  8. Augmented brain function by coordinated reset stimulation with slowly varying sequences

    Directory of Open Access Journals (Sweden)

    Magteld eZeitler

    2015-03-01

    Full Text Available Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e. an unlearning of abnormal synaptic connectivity and abnormal synchrony. The spatiotemporal sequence by which all stimulation sites are stimulated exactly once is called the stimulation site sequence, or briefly sequence. So far, in simulations, pre-clinical and clinical applications CR was applied either with fixed sequences or rapidly varying sequences (RVS. In this computational study we show that appropriate repetition of the sequence with occasional random switching to the next sequence may significantly improve the anti-kindling effect of CR. To this end, a sequence is applied many times before randomly switching to the next sequence. This new method is called SVS CR stimulation, i.e. CR with slowly varying sequences. In a neuronal network with strong short-range excitatory and weak long-range inhibitory dynamic couplings SVS CR stimulation turns out to be superior to CR stimulation with fixed sequences or RVS.

  9. Augmented brain function by coordinated reset stimulation with slowly varying sequences.

    Science.gov (United States)

    Zeitler, Magteld; Tass, Peter A

    2015-01-01

    Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and abnormal synchrony. The spatiotemporal sequence by which all stimulation sites are stimulated exactly once is called the stimulation site sequence, or briefly sequence. So far, in simulations, pre-clinical and clinical applications CR was applied either with fixed sequences or rapidly varying sequences (RVS). In this computational study we show that appropriate repetition of the sequence with occasional random switching to the next sequence may significantly improve the anti-kindling effect of CR. To this end, a sequence is applied many times before randomly switching to the next sequence. This new method is called SVS CR stimulation, i.e., CR with slowly varying sequences. In a neuronal network with strong short-range excitatory and weak long-range inhibitory dynamic couplings SVS CR stimulation turns out to be superior to CR stimulation with fixed sequences or RVS.

  10. Effects of Dual-Channel Functional Electrical Stimulation on Gait Performance in Patients with Hemiparesis

    Directory of Open Access Journals (Sweden)

    Shmuel Springer

    2012-01-01

    Full Text Available The study objective was to assess the effect of functional electrical stimulation (FES applied to the peroneal nerve and thigh muscles on gait performance in subjects with hemiparesis. Participants were 45 subjects (age 57.8 ± 14.8 years with hemiparesis (5.37 ± 5.43 years since diagnosis demonstrating a foot-drop and impaired knee control. Thigh stimulation was applied either to the quadriceps or hamstrings muscles, depending on the dysfunction most affecting gait. Gait was assessed during a two-minute walk test with/without stimulation and with peroneal stimulation alone. A second assessment was conducted after six weeks of daily use. The addition of thigh muscles stimulation to peroneal stimulation significantly enhanced gait velocity measures at the initial and second evaluation. Gait symmetry was enhanced by the dual-channel stimulation only at the initial evaluation, and single-limb stance percentage only at the second assessment. For example, after six weeks, the two-minute gait speed with peroneal stimulation and with the dual channel was 0.66 ± 0.30 m/sec and 0.70 ± 0.31 m/sec, respectively (. In conclusion, dual-channel FES may enhance gait performance in subjects with hemiparesis more than peroneal FES alone.

  11. Effect of anatomical variability in brain on transcranial magnetic stimulation treatment

    Science.gov (United States)

    Syeda, F.; Magsood, H.; Lee, E. G.; El-Gendy, A. A.; Jiles, D. C.; Hadimani, R. L.

    2017-05-01

    Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. S