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Sample records for morphology dependent stimulated

  1. Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation.

    Science.gov (United States)

    Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya

    2014-03-25

    Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticity-related morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders.

  2. Illicit stimulant use is associated with abnormal substantia nigra morphology in humans.

    Directory of Open Access Journals (Sweden)

    Gabrielle Todd

    Full Text Available Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed 'hyperechogenicity' when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs and cannabis users (n = 12; 25±7 yrs. Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm(2 than in the control (0.201±0.054 cm(2; P<0.001 and cannabis (0.202±0.045 cm(2; P<0.007 groups. 53% of stimulant users exhibited echogenicity that exceeded the 90(th percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson's disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system.

  3. 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

  4. Process depending morphology and resulting physical properties of TPU

    Energy Technology Data Exchange (ETDEWEB)

    Frick, Achim, E-mail: achim.frick@hs-aalen.de; Spadaro, Marcel, E-mail: marcel.spadaro@hs-aalen.de [Institute of Polymer Science and Processing (iPSP), Aalen University (Germany)

    2015-12-17

    Thermoplastic polyurethane (TPU) is a rubber like material with outstanding properties, e.g. for seal applications. TPU basically provides high strength, low frictional behavior and excellent wear resistance. Though, due to segmented structure of TPU, which is composed of hard segments (HSs) and soft segments (SSs), physical properties depend strongly on the morphological arrangement of the phase separated HSs at a certain ratio of HSs to SSs. It is obvious that the TPU deforms differently depending on its bulk morphology. Basically, the morphology can either consist of HSs segregated into small domains, which are well dispersed in the SS matrix or of few strongly phase separated large size HS domains embedded in the SS matrix. The morphology development is hardly ruled by the melt processing conditions of the TPU. Depending on the morphology, TPU provides quite different physical properties with respect to strength, deformation behavior, thermal stability, creep resistance and tribological performance. The paper deals with the influence of important melt processing parameters, such as temperature, pressure and shear conditions, on the resulting physical properties tested by tensile and relaxation experiments. Furthermore the morphology is studied employing differential scanning calorimeter (DSC), transmission light microscopy (TLM), scanning electron beam microscopy (SEM) and transmission electron beam microscopy (TEM) investigations. Correlations between processing conditions and resulting TPU material properties are elaborated. Flow and shear simulations contribute to the understanding of thermal and flow induced morphology development.

  5. The morphological and molecular changes of brain cells exposed to direct current electric field stimulation.

    Science.gov (United States)

    Pelletier, Simon J; Lagacé, Marie; St-Amour, Isabelle; Arsenault, Dany; Cisbani, Giulia; Chabrat, Audrey; Fecteau, Shirley; Lévesque, Martin; Cicchetti, Francesca

    2014-12-07

    The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  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. 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

  8. 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.

  9. Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis.

    Science.gov (United States)

    Madzak, Adnan; Olesen, Søren Schou; Haldorsen, Ingfrid Salvesen; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

    Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and healthy controls (HC) METHODS: Eighty-two patients with CP and 22 HC were enrolled in the study. Morphological imaging parameters included pancreatic main duct diameter, gland volume, fat signal fraction and apparent diffusion coefficient (ADC) values. Functional secretin-stimulated MRI (s-MRI) parameters included pancreatic secretion (bowel fluid volume) and changes in pancreatic ADC value before and after secretin stimulation. Patients were classified according to the modified Cambridge and M-ANNHEIM classification system and fecal elastase was collected. All imaging parameters differentiated CP patients from HC; however, correlations between morphological and functional parameters in CP were weak. Patients with alcoholic and non-alcoholic etiology had comparable s-MRI findings. Fecal elastase was positively correlated to pancreatic gland volume (r = 0.68, P = 0.0016) and negatively correlated to Cambridge classification (r = -0.35, P pancreatic gland volume was significantly decreased in the severe stages of CP (P = 0.001). S-MRI provides detailed information about pancreatic morphology and function and represents a promising non-invasive imaging method to characterize pancreatic pathophysiology and may enable monitoring of disease progression in patients with CP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  10. 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,

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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

  14. 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

  15. Cell Morphological Change and Caspase-3 Protein Expression on Epithelial Cells under Stimulation of Oral Bacterium Streptococcus sanguinis

    Directory of Open Access Journals (Sweden)

    Suryani Hutomo

    2015-07-01

    Full Text Available Oral commensal bacterium Streptococcus sanguinis may find in periodontal lesions, deep seated infection, and infective endocarditis that are usually dominated by anaerobes. This bacterium caused cell death on some cells but host responses to this species remained unclear. Objective: This study was aimed to detect cell morphologica change and role of caspase-3 in cell death mechanism induced by S. sanguinis. Methods: HeLa cells as representative model for oral epithelial cells were exposed to 107 cells/ml bacteria for 48 h. Morphological change was observed microscopically after hematoxyline-eosin staining. Expression of active caspase-3 was examined by immunocytochemical analysis after cell stimulation for 36 and 48 h with wild type supragingival S. sanguinis. Doxorubicin (0.5625 μg/ml was used as positive control for caspase-3 activation. Results: The results showed cell shrinkage of bacterial-treated cells; and active caspase-3 molecules were detected after 36 and 48 hours cell stimulation. Conclusion: This study would suggest cell shrinkage and caspase-3-dependent apoptotic cell death induced by S. sanguinis.DOI: 10.14693/jdi.v22i1.375

  16. Temperature-dependent morphology of hybrid nanoflowers from elastin-like polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Koushik; Balog, Eva Rose M.; Sista, Prakash; Williams, Darrick J.; Martinez, Jennifer S., E-mail: jenm@lanl.gov, E-mail: rcrocha@lanl.gov; Rocha, Reginaldo C., E-mail: jenm@lanl.gov, E-mail: rcrocha@lanl.gov [Center for Integrated Nanotechnologies, Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Kelly, Daniel [Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2014-02-01

    We report a method for creating hybrid organic-inorganic “nanoflowers” using calcium or copper ions as the inorganic component and a recombinantly expressed elastin-like polypeptide (ELP) as the organic component. Polypeptides provide binding sites for the dynamic coordination with metal ions, and then such noncovalent complexes become nucleation sites for primary crystals of metal phosphates. We have shown that the interaction between the stimuli-responsive ELP and Ca{sup 2+} or Cu{sup 2+}, in the presence of phosphate, leads to the growth of micrometer-sized particles featuring nanoscale patterns shaped like flower petals. The morphology of these flower-like composite structures is dependent upon the temperature of growth and has been characterized by scanning electron microscopy. The composition of nanoflowers has also been analyzed by energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The temperature-dependent morphologies of these hybrid nanostructures, which arise from the controllable phase transition of ELPs, hold potential for morphological control of biomaterials in emerging applications such as tissue engineering and biocatalysis.

  17. Temperature-dependent morphology of hybrid nanoflowers from elastin-like polypeptides

    Directory of Open Access Journals (Sweden)

    Koushik Ghosh

    2014-02-01

    Full Text Available We report a method for creating hybrid organic-inorganic “nanoflowers” using calcium or copper ions as the inorganic component and a recombinantly expressed elastin-like polypeptide (ELP as the organic component. Polypeptides provide binding sites for the dynamic coordination with metal ions, and then such noncovalent complexes become nucleation sites for primary crystals of metal phosphates. We have shown that the interaction between the stimuli-responsive ELP and Ca2+ or Cu2+, in the presence of phosphate, leads to the growth of micrometer-sized particles featuring nanoscale patterns shaped like flower petals. The morphology of these flower-like composite structures is dependent upon the temperature of growth and has been characterized by scanning electron microscopy. The composition of nanoflowers has also been analyzed by energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The temperature-dependent morphologies of these hybrid nanostructures, which arise from the controllable phase transition of ELPs, hold potential for morphological control of biomaterials in emerging applications such as tissue engineering and biocatalysis.

  18. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Directory of Open Access Journals (Sweden)

    Anna Kubesova

    Full Text Available Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease. The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin, their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  19. 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.

  20. Glucagon Amyloid-like Fibril Morphology Is Selected via Morphology-Dependent Growth Inhibition

    DEFF Research Database (Denmark)

    Andersen, C.B.; Otzen, D.; Christiansen, Gunna

    2007-01-01

    Protein Structure and Biophysics, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Malov, Denmark, Centre for Insoluble Protein Structures (inSPIN), Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark, and Institute of Medical Microbiology and Immunology...... twisted fibril seeds cannot grow at high concentrations. We conclude that there exists a morphology-dependent mechanism for inhibition of glucagon fibril growth. Light scattering experiments indicate that glucagon is mainly monomeric below 1 mg/mL and increasingly trimeric above this concentration. We...

  1. Morphology-dependent photo-induced polarization recovery in ferroelectric thin films

    Science.gov (United States)

    Wang, J. Y.; Liu, G.; Sando, D.; Nagarajan, V.; Seidel, J.

    2017-08-01

    We investigate photo-induced ferroelectric domain switching in a series of Pb(Zr0.2Ti0.8)O3/La0.7Sr0.3MnO3 (PZT/LSMO) bilayer thin films with varying surface morphologies by piezoresponse force microscopy under light illumination. We demonstrate that reverse poled ferroelectric regions can be almost fully recovered under laser irradiation of the PZT layer and that the recovery process is dependent on the surface morphology on the nanometer scale. The recovery process is well described by the Kolmogorov-Avrami-Ishibashi model, and the evolution speed is controlled by light intensity, sample thickness, and initial write voltage. Our findings shed light on optical control of the domain structure in ferroelectric thin films with different surface morphologies.

  2. 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.

  3. Understanding morphology-mobility dependence in PEDOT:Tos

    Science.gov (United States)

    Rolland, Nicolas; Franco-Gonzalez, Juan Felipe; Volpi, Riccardo; Linares, Mathieu; Zozoulenko, Igor V.

    2018-04-01

    The potential of conjugated polymers to compete with inorganic materials in the field of semiconductor is conditional on fine-tuning of the charge carriers mobility. The latter is closely related to the material morphology, and various studies have shown that the bottleneck for charge transport is the connectivity between well-ordered crystallites, with a high degree of π -π stacking, dispersed into a disordered matrix. However, at this time there is a lack of theoretical descriptions accounting for this link between morphology and mobility, hindering the development of systematic material designs. Here we propose a computational model to predict charge carriers mobility in conducting polymer PEDOT depending on the physicochemical properties of the system. We start by calculating the morphology using molecular dynamics simulations. Based on the calculated morphology we perform quantum mechanical calculation of the transfer integrals between states in polymer chains and calculate corresponding hopping rates using the Miller-Abrahams formalism. We then construct a transport resistive network, calculate the mobility using a mean-field approach, and analyze the calculated mobility in terms of transfer integrals distributions and percolation thresholds. Our results provide theoretical support for the recent study [Noriega et al., Nat. Mater. 12, 1038 (2013), 10.1038/nmat3722] explaining why the mobility in polymers rapidly increases as the chain length is increased and then saturates for sufficiently long chains. Our study also provides the answer to the long-standing question whether the enhancement of the crystallinity is the key to designing high-mobility polymers. We demonstrate, that it is the effective π -π stacking, not the long-range order that is essential for the material design for the enhanced electrical performance. This generic model can compare the mobility of a polymer thin film with different solvent contents, solvent additives, dopant species or

  4. Micro-morphologic changes around biophysically-stimulated titanium implants in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Chang Ting-Ling

    2007-07-01

    Full Text Available Abstract Background Osteoporosis may present a risk factor in achievement of osseointegration because of its impact on bone remodeling properties of skeletal phsiology. The purpose of this study was to evaluate micro-morphological changes in bone around titanium implants exposed to mechanical and electrical-energy in osteoporotic rats. Methods Fifteen 12-week old sprague-dowley rats were ovariectomized to develop osteoporosis. After 8 weeks of healing period, two titanium implants were bilaterally placed in the proximal metaphyses of tibia. The animals were randomly divided into a control group and biophysically-stimulated two test groups with five animals in each group. In the first test group, a pulsed electromagnetic field (PEMF stimulation was administrated at a 0.2 mT 4 h/day, whereas the second group received low-magnitude high-frequency mechanical vibration (MECHVIB at 50 Hz 14 min/day. Following completion of two week treatment period, all animals were sacrificed. Bone sites including implants were sectioned, removed en bloc and analyzed using a microCT unit. Relative bone volume and bone micro-structural parameters were evaluated for 144 μm wide peri-implant volume of interest (VOI. Results Mean relative bone volume in the peri-implant VOI around implants PEMF and MECHVIB was significantly higher than of those in control (P P > .05 while the difference in trabecular-number among test and control groups was significant in all VOIs (P Conclusion Biophysical stimulation remarkably enhances bone volume around titanium implants placed in osteoporotic rats. Low-magnitude high-frequency MECHVIB is more effective than PEMF on bone healing in terms of relative bone volume.

  5. Thickness-dependent spontaneous dewetting morphology of ultrathin Ag films

    Energy Technology Data Exchange (ETDEWEB)

    Krishna, H; Favazza, C [Department of Physics, Washington University in St Louis, MO 63130 (United States); Sachan, R; Strader, J; Kalyanaraman, R [Department of Material Science and Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Khenner, M, E-mail: ramki@utk.edu [Department of Mathematics, Western Kentucky University, Bowling Green, KY 42101 (United States)

    2010-04-16

    We show here that the morphological pathway of spontaneous dewetting of ultrathin Ag films on SiO{sub 2} under nanosecond laser melting is dependent on film thickness. For films with thickness h of 2 nm {<=} h {<=} 9.5 nm, the morphology during the intermediate stages of dewetting consisted of bicontinuous structures. For films with 11.5 nm {<=} h {<=} 20 nm, the intermediate stages consisted of regularly sized holes. Measurement of the characteristic length scales for different stages of dewetting as a function of film thickness showed a systematic increase, which is consistent with the spinodal dewetting instability over the entire thickness range investigated. This change in morphology with thickness is consistent with observations made previously for polymer films (Sharma and Khanna 1998 Phys. Rev. Lett. 81 3463-6; Seemann et al 2001 J. Phys.: Condens. Matter 13 4925-38). Based on the behavior of free energy curvature that incorporates intermolecular forces, we have estimated the morphological transition thickness for the intermolecular forces for Ag on SiO{sub 2}. The theory predictions agree well with observations for Ag. These results show that it is possible to form a variety of complex Ag nanomorphologies in a consistent manner, which could be useful in optical applications of Ag surfaces, such as in surface enhanced Raman sensing.

  6. Effects of methamphetamine dependence and HIV infection on cerebral morphology

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Abthony C; Archibald, Sarah L.

    2005-01-01

    -dependent participants. CONCLUSIONS: These results suggest significant brain structure alterations associated with both HIV infection and methamphetamine dependence. The regional patterns of the changes associated with these factors were distinct but overlapping, and the effects on brain volumes were opposing. Although......OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age......- and education-matched comparison groups were analyzed. Main effects of age, HIV infection, methamphetamine dependence, and the interactions of these factors were examined in analyses of cerebral gray matter structure volumes. RESULTS: Independent of the effect of age, HIV infection was associated with reduced...

  7. Magnetic resonance imaging of morphological and functional changes of the uterus induced by sacral surface electrical stimulation

    International Nuclear Information System (INIS)

    Ogura, Takahide; Murakami, Takashi; Ozawa, Yuka; Seki, Kazunori; Handa, Yasunobu

    2006-01-01

    The purpose of this study is to examine the morphological and kinematical changes of the uterus induced by electrical stimulation applied to the skin just above the second and fourth posterior sacral foramens (sacral surface electrical stimulation [ssES]) in 26 healthy subjects. Out of them, eight subjects who had severe pain subjectively during every menstruation received ssES just in menstruation. Morphological and functional changes of the uterus were examined by using T2-weighted magnetic resonance (MR) imaging and T1-weighted MR cinematography, respectively. Cyclic electrical stimulation for 15 min with 5 sec ON and 5 sec OFF was applied just before MR scanning. A decrease in thickness of the muscular layer of the uterus was observed in every subject after ssES for 15 min and was significant as compared with the thickness before ssES. Periodic uterine movement during menstruation was observed in the subjects with severe menstrual pain in MR cine and the power spectrum analysis of the movement showed a marked decrease in peak power and frequency after ssES treatment. We conclude that ssES causes a reduction of static muscle tension of the uterus in all menstrual cycle periods and suppression of uterine peristalsis during menstruation in the subjects with severe menstrual pain. Possible neural mechanisms for these static and dynamic effects of ssES on the uterus at spinal level are discussed. (author)

  8. Thickness-dependent spontaneous dewetting morphology of ultrathin Ag films.

    Science.gov (United States)

    Krishna, H; Sachan, R; Strader, J; Favazza, C; Khenner, M; Kalyanaraman, R

    2010-04-16

    We show here that the morphological pathway of spontaneous dewetting of ultrathin Ag films on SiO2 under nanosecond laser melting is dependent on film thickness. For films with thickness h of 2 nm < or = h < or = 9.5 nm, the morphology during the intermediate stages of dewetting consisted of bicontinuous structures. For films with 11.5 nm < or = h < or = 20 nm, the intermediate stages consisted of regularly sized holes. Measurement of the characteristic length scales for different stages of dewetting as a function of film thickness showed a systematic increase, which is consistent with the spinodal dewetting instability over the entire thickness range investigated. This change in morphology with thickness is consistent with observations made previously for polymer films (Sharma and Khanna 1998 Phys. Rev. Lett. 81 3463-6; Seemann et al 2001 J. Phys.: Condens. Matter 13 4925-38). Based on the behavior of free energy curvature that incorporates intermolecular forces, we have estimated the morphological transition thickness for the intermolecular forces for Ag on SiO2. The theory predictions agree well with observations for Ag. These results show that it is possible to form a variety of complex Ag nanomorphologies in a consistent manner, which could be useful in optical applications of Ag surfaces, such as in surface enhanced Raman sensing.

  9. Effects of methamphetamine dependence and HIV infection on cerebral morphology

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Abthony C; Archibald, Sarah L.

    2005-01-01

    OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age......- and education-matched comparison groups were analyzed. Main effects of age, HIV infection, methamphetamine dependence, and the interactions of these factors were examined in analyses of cerebral gray matter structure volumes. RESULTS: Independent of the effect of age, HIV infection was associated with reduced...... volumes of cortical, limbic, and striatal structures. There was also some evidence of an interaction between age and HIV infection such that older HIV-positive participants suffered disproportionate loss. Methamphetamine dependence was surprisingly associated with basal ganglia and parietal cortex volume...

  10. Morphology-dependent enhancement of the pseudocapacitance of template-guided tunable polyaniline nanostructures

    KAUST Repository

    Chen, Wei

    2013-07-25

    Polyaniline is one of the most investigated conducting polymers as supercapacitor material for energy storage applications. The preparation of nanostructured polyaniline with well-controlled morphology is crucial to obtaining good supercapacitor performance. We present here a facile chemical process to produce polyaniline nanostructures with three different morphologies (i.e., nanofibers, nanospheres, and nanotubes) by utilizing the corresponding tunable morphology of MnO2 reactive templates. A growth mechanism is proposed to explain the evolution of polyaniline morphology based on the reactive templates. The morphology-induced improvement in the electrochemical performance of polyaniline pseudocapacitors is as large as 51% due to the much enhanced surface area and the porous nature of the template-guided polyaniline nanostructures. In addition, and for the first time, a redox-active electrolyte is applied to the polyaniline pseudocapacitors to achieve significant enhancement of pseudocapacitance. Compared to the conventional electrolyte, the enhancement of pseudocapacitance in the redox-active electrolyte is 49%-78%, depending on the specific polyaniline morphology, reaching the highest reported capacitance of 896 F/g for polyaniline full cells so far. © 2013 American Chemical Society.

  11. Morphology-dependent enhancement of the pseudocapacitance of template-guided tunable polyaniline nanostructures

    KAUST Repository

    Chen, Wei; Baby, Rakhi Raghavan; Alshareef, Husam N.

    2013-01-01

    Polyaniline is one of the most investigated conducting polymers as supercapacitor material for energy storage applications. The preparation of nanostructured polyaniline with well-controlled morphology is crucial to obtaining good supercapacitor performance. We present here a facile chemical process to produce polyaniline nanostructures with three different morphologies (i.e., nanofibers, nanospheres, and nanotubes) by utilizing the corresponding tunable morphology of MnO2 reactive templates. A growth mechanism is proposed to explain the evolution of polyaniline morphology based on the reactive templates. The morphology-induced improvement in the electrochemical performance of polyaniline pseudocapacitors is as large as 51% due to the much enhanced surface area and the porous nature of the template-guided polyaniline nanostructures. In addition, and for the first time, a redox-active electrolyte is applied to the polyaniline pseudocapacitors to achieve significant enhancement of pseudocapacitance. Compared to the conventional electrolyte, the enhancement of pseudocapacitance in the redox-active electrolyte is 49%-78%, depending on the specific polyaniline morphology, reaching the highest reported capacitance of 896 F/g for polyaniline full cells so far. © 2013 American Chemical Society.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Morphology-dependent activity of Pt nanocatalysts for ethanol oxidation in acidic media: Nanowires versus nanoparticles

    International Nuclear Information System (INIS)

    Zhou Weiping; Li Meng; Koenigsmann, Christopher; Ma Chao; Wong, Stanislaus S.; Adzic, Radoslav R.

    2011-01-01

    Highlights: → We demonstrate the morphology effect of Pt catalysts in electrooxidation of ethanol and CO in an acidic solution. → Pt nanowires and nanoparticles were used as catalysts. → Pt nanowires display a higher catalytic activity by a factor of at least two relative to those nanoparticles for ethanol oxidation. → The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. - Abstract: The morphology of nanostructured Pt catalysts is known to affect significantly the kinetics of various reactions. Herein, we report on a pronounced morphology effect in the electrooxidation of ethanol and carbon monoxide (CO) on Pt nanowires and nanoparticles in an acidic solution. The high resolution transmission electron microscopy analysis showed the inherent morphology difference between these two nanostructured catalysts. Voltammetric and chronoamperometric studies of the ethanol electrooxidation revealed that these nanowires had a higher catalytic activity by a factor of two relative to these nanoparticles. The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. In situ infrared reflection-absorption spectroscopy measurements revealed a different trend for chemisorbed CO formation and CO 2 -to-acetic acid reaction product ratios on these two nanostructures. The morphology-induced change in catalytic activity and selectivity in ethanol electrocatalysis is discussed in detail.

  17. Morphology-dependent activity of Pt nanocatalysts for ethanol oxidation in acidic media: Nanowires versus nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Weiping, E-mail: wpzhou@bnl.gov [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Li Meng [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Koenigsmann, Christopher [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794 (United States); Ma Chao [Condensed Matter Physics and Materials Sciences Department, Brookhaven National Laboratory, Building 480, Upton, NY 11973 (United States); Wong, Stanislaus S. [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794 (United States); Condensed Matter Physics and Materials Sciences Department, Brookhaven National Laboratory, Building 480, Upton, NY 11973 (United States); Adzic, Radoslav R. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2011-11-30

    Highlights: > We demonstrate the morphology effect of Pt catalysts in electrooxidation of ethanol and CO in an acidic solution. > Pt nanowires and nanoparticles were used as catalysts. > Pt nanowires display a higher catalytic activity by a factor of at least two relative to those nanoparticles for ethanol oxidation. > The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. - Abstract: The morphology of nanostructured Pt catalysts is known to affect significantly the kinetics of various reactions. Herein, we report on a pronounced morphology effect in the electrooxidation of ethanol and carbon monoxide (CO) on Pt nanowires and nanoparticles in an acidic solution. The high resolution transmission electron microscopy analysis showed the inherent morphology difference between these two nanostructured catalysts. Voltammetric and chronoamperometric studies of the ethanol electrooxidation revealed that these nanowires had a higher catalytic activity by a factor of two relative to these nanoparticles. The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. In situ infrared reflection-absorption spectroscopy measurements revealed a different trend for chemisorbed CO formation and CO{sub 2}-to-acetic acid reaction product ratios on these two nanostructures. The morphology-induced change in catalytic activity and selectivity in ethanol electrocatalysis is discussed in detail.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. A CHROMATIN MODIFYING ENZYME, SDG8, IS REQUIRED FOR MORPHOLOGICAL, GENE EXPRESSION, AND EPIGENETIC RESPONSES TO MECHANICAL STIMULATION

    OpenAIRE

    Christopher Ian Cazzonelli; Nazia eNisar; Andrea C Roberts; Kevin eMurray; Justin O Borevitz; Barry James Pogson

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzy...

  1. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation

    OpenAIRE

    Cazzonelli, Christopher I.; Nisar, Nazia; Roberts, Andrea C.; Murray, Kevin D.; Borevitz, Justin O.; Pogson, Barry J.

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzym...

  2. Morphology Dependent Flow Stress in Nickel-Based Superalloys in the Multi-Scale Crystal Plasticity Framework

    Directory of Open Access Journals (Sweden)

    Shahriyar Keshavarz

    2017-11-01

    Full Text Available This paper develops a framework to obtain the flow stress of nickel-based superalloys as a function of γ-γ’ morphology. The yield strength is a major factor in the design of these alloys. This work provides additional effects of γ’ morphology in the design scope that has been adopted for the model developed by authors. In general, the two-phase γ-γ’ morphology in nickel-based superalloys can be divided into three variables including γ’ shape, γ’ volume fraction and γ’ size in the sub-grain microstructure. In order to obtain the flow stress, non-Schmid crystal plasticity constitutive models at two length scales are employed and bridged through a homogenized multi-scale framework. The multi-scale framework includes two sub-grain and homogenized grain scales. For the sub-grain scale, a size-dependent, dislocation-density-based finite element model (FEM of the representative volume element (RVE with explicit depiction of the γ-γ’ morphology is developed as a building block for the homogenization. For the next scale, an activation-energy-based crystal plasticity model is developed for the homogenized single crystal of Ni-based superalloys. The constitutive models address the thermo-mechanical behavior of nickel-based superalloys for a large temperature range and include orientation dependencies and tension-compression asymmetry. This homogenized model is used to obtain the morphology dependence on the flow stress in nickel-based superalloys and can significantly expedite crystal plasticity FE simulations in polycrystalline microstructures, as well as higher scale FE models in order to cast and design superalloys.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. Ultraviolet Stimulated Emission from Sol-Gel Spin Coated ZnO Thin Films

    Directory of Open Access Journals (Sweden)

    Ahmed S. Razeen

    2017-01-01

    Full Text Available Low cost ultraviolet stimulated emission has been generated using optical excitation of ZnO thin films deposited by sol-gel spin coating on n+ As-doped 100 Si-substrate. The number of deposited layers and the heat treatment have been investigated to obtain a film that can generate stimulated emission under optical excitation. The optimum condition for preparation of the film has been presented. X-ray diffraction and scanning electron microscope have been used for structural and morphological investigations. Input-output intensity dependence and spectral width, peak emission wavelength, and the quantum efficiency versus the pump intensity have been presented. A quantum efficiency of about 24.2% has been reported, a power exponent higher than 8 has been obtained in input-output intensity dependence, and a threshold of about 23 Mw/cm2 has been evaluated for the samples. The mechanism by which stimulated emission occurs has been discussed. The results show that sol-gel spin coating is a promising method for generating ultraviolet stimulated emission from ZnO thin films.

  8. 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....

  9. 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.

  10. 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.

  11. Morphology effects on spin-dependent transport and recombination in polyfluorene thin films

    Science.gov (United States)

    Miller, Richards; van Schooten, K. J.; Malissa, H.; Joshi, G.; Jamali, S.; Lupton, J. M.; Boehme, C.

    2016-12-01

    We have studied the role of spin-dependent processes on conductivity in polyfluorene (PFO) thin films by preforming continuous wave (cw) electrically detected magnetic resonance (EDMR) spectroscopy at temperatures between 10 K and room temperature using microwave frequencies between about 1 GHz and 20 GHz, as well as pulsed EDMR at the X band (10 GHz). Variable frequency EDMR allows us to establish the role of spin-orbit coupling in spin-dependent processes whereas pulsed EDMR allows for the observation of coherent spin motion effects. We used PFO for this study in order to allow for the investigation of the effects of microscopic morphological ordering since this material can adopt two distinct intrachain morphologies: an amorphous (glassy) phase, in which monomer units are twisted with respect to each other, and an ordered (β) phase, where all monomers lie within one plane. In thin films of organic light-emitting diodes, the appearance of a particular phase can be controlled by deposition parameters and solvent vapor annealing, and is verified by electroluminescence spectroscopy. Under bipolar charge-carrier injection conditions, we conducted multifrequency cw EDMR, electrically detected Rabi spin-beat experiments, and Hahn echo and inversion-recovery measurements. Coherent echo spectroscopy reveals electrically detected electron-spin-echo envelope modulation due to the coupling of the carrier spins to nearby nuclear spins. Our results demonstrate that, while conformational disorder can influence the observed EDMR signals, including the sign of the current changes on resonance as well as the magnitudes of local hyperfine fields and charge-carrier spin-orbit interactions, it does not qualitatively affect the nature of spin-dependent transitions in this material. In both morphologies, we observe the presence of at least two different spin-dependent recombination processes. At room temperature and 10 K, polaron-pair recombination through weakly spin-spin coupled

  12. 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.

  13. 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...

  14. Morphology-dependent resonances of a microsphere-optical fiber system

    Science.gov (United States)

    Griffel, Giora; Arnold, Stephen; Taskent, Dogan; Serpengüzel, Ali; Connolly, John; Morris, Nancy

    1996-05-01

    Morphology-dependent resonances of microspheres sitting upon an index-matched single-mode fiber half-coupler are excited by a tunable 753-nm distributed-feedback laser. Resonance peaks in the scattering spectra and associated dips in the transmission spectra for the TE and TM modes are observed. We present a new model that describes this interaction in terms of the fiber-sphere coupling coefficient and the microsphere's intrinsic quality factor Q0 . This model enables us to obtain expressions for the finesse and the Q factor of the composite particle-fiber system, the resonance width, and the depth of the dips measured in the transmission spectra. Our model shows that index matching improves the coupling efficiency by more than a factor of 2 compared with that of a non-index-matched system.

  15. 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.

  16. 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

  17. Physical and morphological properties of z ~ 3 Lyman break galaxies: dependence on Lyα line emission

    Science.gov (United States)

    Pentericci, L.; Grazian, A.; Scarlata, C.; Fontana, A.; Castellano, M.; Giallongo, E.; Vanzella, E.

    2010-05-01

    Aims: We investigate the physical and morphological properties of Lyman break galaxies (LBGs) at redshift ~2.5 to ~3.5, to determine if and how they depend on the nature and strength of the Lyα emission. Methods: We selected U-dropout galaxies from the z-detected GOODS-MUSIC catalog by adapting the classical Lyman break criteria on the GOODS filter set. We kept only those galaxies with spectroscopic confirmation, mainly from VIMOS and FORS public observations. Using the full multi-wavelength 14-bands information (U to IRAC), we determined the physical properties of the galaxies through a standard spectral energy distribution fitting procedure with the updated Charlot & Bruzual (2009) templates. We also added other relevant observations of the GOODS field, i.e. the 24 μm observations from Spitzer/MIPS and the 2 MSec Chandra X-ray observations. Finally, using non parametric diagnostics (Gini, Concentration, Asymmetry, M20 and ellipticity), we characterized the rest-frame UV morphologies of the galaxies. We then analyzed how these physical and morphological properties correlate with the presence of the Lyα emission line in the optical spectra. Results: We find that unlike at higher redshift, the dependence of physical properties on the Lyα line is milder: galaxies without Lyα in emission tend to be more massive and dustier than the rest of the sample, but all other parameters, ages, star formation rates (SFR), X-ray emission and UV morphology do not depend strongly on the presence of the Lyα emission. A simple scenario where all LBGs have intrinsically high Lyα emission, but where the dust and neutral hydrogen content (which shapes the final appearance of the Lyα) depend on the mass of the galaxies, is able to reproduce the majority of the observed properties at z˜3. Some modification might be needed to account for the observed evolution of these properties with cosmic epoch, which is also discussed.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. The stimulating effects of polyphenol and protein fractions from jelly fig (Ficus awkeotsang Makino achenes against proliferation of leukemia cells

    Directory of Open Access Journals (Sweden)

    Yi-Zhen Shih

    2017-10-01

    Full Text Available This study aimed to investigate the direct and immune-stimulated antiproliferative activities of jelly fig achenes fractions including pectinesterase inhibitors, crude polyphenols extract, and purified polyphenols extract (PP. Beside the measurement of cell viability of U937, the quantity of cytokines in conditioned medium and morphologic changes in leukemia were observed. After surveying all fractions in jelly fig, the obtained fractions of polyphenol exhibited the highest stimulating effects and directly cytotoxic effects against leukemia with the lowest effect found in protein fractions. The leukemia treated by our PP fraction showed dose-dependent response between the concentration and G2/M cell numbers of the U937 cells. The PP fraction had more pronounced effect on immune-stimulated than direct antiproliferative activities. The finding was also supported by morphological analysis by showing the formation of apoptotic bodies and differentiation from immature U937 cells into mature monocytes/macrophages on cells cultured with PP-conditioned medium. In conclusion, polyphenol fraction of pectinesterase inhibitors from jelly fig showed the immune-stimulated antiproliferative activities against U937 cell.

  20. Morphology Dependent Assessment of Resilience for Urban Areas

    Directory of Open Access Journals (Sweden)

    Kai Fischer

    2018-05-01

    Full Text Available The formation of new threats and the increasing complexity of urban built infrastructures underline the need for more robust and sustainable systems, which are able to cope with adverse events. Achieving sustainability requires the strengthening of resilience. Currently, a comprehensive approach for the quantification of resilience of urban infrastructure is missing. Within this paper, a new generalized mathematical framework is presented. A clear definition of terms and their interaction builds the basis of this resilience assessment scheme. Classical risk-based as well as additional components are aligned along the timeline before, during and after disruptive events, to quantify the susceptibility, the vulnerability and the response and recovery behavior of complex systems for multiple threat scenarios. The approach allows the evaluation of complete urban surroundings and enables a quantitative comparison with other development plans or cities. A comprehensive resilience framework should cover at least preparation, prevention, protection, response and recovery. The presented approach determines respective indicators and provides decision support, which enhancement measures are more effective. Hence, the framework quantifies for instance, if it is better to avoid a hazardous event or to tolerate an event with an increased robustness. An application example is given to assess different urban forms, i.e., morphologies, with consideration of multiple adverse events, like terrorist attacks or earthquakes, and multiple buildings. Each urban object includes a certain number of attributes, like the object use, the construction type, the time-dependent number of persons and the value, to derive different performance targets. The assessment results in the identification of weak spots with respect to single resilience indicators. Based on the generalized mathematical formulation and suitable combination of indicators, this approach can quantify the

  1. [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.

  2. 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.

  3. 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.

  4. Relationship Between Genotype Variants Follicle-stimulating Hormone Receptor Gene Polymorphisms (FSHR) and Morphology of Oocytes Prior to ICSI Procedures

    Science.gov (United States)

    Gashi, Zafer; Elezaj, Shkelzen; Zeqiraj, Afrim; Grabanica, Driton; Shabani, Isak; Gruda, Bujar; Gashi, Fitore

    2016-01-01

    Introduction: This study investigated association of Asn680Ser FSHR polymorphism with the ovarian response in 104 women of Albanian ethnic population enrolled in ICSI program. The reason of infertility in all cases has been identified as male factor. Methods: Analysis of the Asn680Ser polymorphism was performed using TaqMan® SNP Genotyping Assay. Clinical and endocrinologic parameters were analyzed based on the genotype, age, BMI, oocyte yield, number of transferred embryos and pregnancy rate. Results: The frequencies of the Asn680 Ser genotype variants were as follows: Asn/Asn 22.1%, Asn/Ser 47.1%, and Ser/Ser 30.8%, respectively. BMI was significantly higher in the Ser/Ser group as compared to those from the Asn/Ser or the Asn/Asn group (p= 0.0010). The genotype variants Ser/Ser indicates a higher rate of oocyte retrieval (25.9%) in the immature form, metaphase I (MI) as opposed to the other two groups (Asn/Asn 23.7 % vs. Asn/Ser 21.9%), which was statistically significant (p = 0.3020). Conclusions: FSH receptor polymorphism is associated with different ovarian response to controlled ovarian stimulation (COS), but is not an important factor in increasing the degree of pregnancy. Polymorphisms of the FSH receptor is associated with normal morphology and genetic maturation (metaphase II) oocytes in dependence of genotypic variation polymorphisms. PMID:27994298

  5. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

    Science.gov (United States)

    Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

    2018-03-01

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

  6. 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.

  7. 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...

  8. A CHROMATIN MODIFYING ENZYME, SDG8, IS REQUIRED FOR MORPHOLOGICAL, GENE EXPRESSION, AND EPIGENETIC RESPONSES TO MECHANICAL STIMULATION

    Directory of Open Access Journals (Sweden)

    Christopher Ian Cazzonelli

    2014-10-01

    Full Text Available Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many touch responsive genes identified in Arabidopsis. SDG8 is required for the permissive expression of touch induced genes; and the loss of function of sdg8 perturbs the maximum levels of induction on selected touch gene targets. SDG8 is required to maintain permissive H3K4 trimethylation marks surrounding the Arabidopsis touch-inducible gene TOUCH 3 (TCH3, which encodes a calmodulin-like protein (CML12. The gene neighbouring was also slightly down regulated, revealing a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show perturbed morphological response to wind-agitated mechanical stimuli, implicating an epigenetic memory-forming process in the acclimation response of thigmomorphogenesis.

  9. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation.

    Science.gov (United States)

    Cazzonelli, Christopher I; Nisar, Nazia; Roberts, Andrea C; Murray, Kevin D; Borevitz, Justin O; Pogson, Barry J

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many touch responsive genes identified in Arabidopsis. SDG8 is required for the permissive expression of touch induced genes; and the loss of function of sdg8 perturbs the maximum levels of induction on selected touch gene targets. SDG8 is required to maintain permissive H3K4 trimethylation marks surrounding the Arabidopsis touch-inducible gene TOUCH 3 (TCH3), which encodes a calmodulin-like protein (CML12). The gene neighboring was also slightly down regulated, revealing a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show perturbed morphological response to wind-agitated mechanical stimuli, implicating an epigenetic memory-forming process in the acclimation response of thigmomorphogenesis.

  10. 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

  11. 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

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

    Directory of Open Access Journals (Sweden)

    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

  13. Rheology and Morphology of PP/ionomer/clay Nancomposites Depending on Selective Dispersion of Organoclays

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Doohyun; Ock, Hyun Geun; Ahn, Kyung Hyun; Lee, Seung Jong [Seoul National University, Seoul (Korea, Republic of)

    2015-12-15

    In this study, structural developments of polypropylene / ionomer / clay ternary composites were investigated depending on the dispersion and localization of clay. The changes in physical properties were observed adding organoclays 1-10wt% to 90% polypropylene and 10% ionomer blends. The organoclays were localized inside of the dispersed phase under the composition of 3wt%, however, over that composition, clay particles formed stiff network structure in the dispersed phase and additional clays were localized at the interface between two phases. According to the developments of microstructure, the interaction of ternary composites changed from polypropylene-ionomer to polypropylene- ionomer and ionomer-clay which affected rheological properties. The storage modulus (G') of the composites was similar to the blends when clays were localized inside of dispersed phase but increased when clays were localized at interface. Also, the fractured morphology of the composites showed phase boundary and growing radius of dispersed phase depending on addition of fillers when clays were found inside. However, when fillers found at the interface between blends, the radius of the dispersed phase decreased and compatibilized morphology were observed. The interfacial interaction of the ternary composite was quantified depending on the structural development of dispersed phase and localization of clay particles by the rheological properties. The interaction of composites at solid state which was measured through peel adhesion strength increased by growth of interfacial interaction of each component. Furthermore, the crystallinity of the composites was decreased when the clay particles were localized at the interface.

  14. Rheology and Morphology of PP/ionomer/clay Nancomposites Depending on Selective Dispersion of Organoclays

    International Nuclear Information System (INIS)

    Kim, Doohyun; Ock, Hyun Geun; Ahn, Kyung Hyun; Lee, Seung Jong

    2015-01-01

    In this study, structural developments of polypropylene / ionomer / clay ternary composites were investigated depending on the dispersion and localization of clay. The changes in physical properties were observed adding organoclays 1-10wt% to 90% polypropylene and 10% ionomer blends. The organoclays were localized inside of the dispersed phase under the composition of 3wt%, however, over that composition, clay particles formed stiff network structure in the dispersed phase and additional clays were localized at the interface between two phases. According to the developments of microstructure, the interaction of ternary composites changed from polypropylene-ionomer to polypropylene- ionomer and ionomer-clay which affected rheological properties. The storage modulus (G') of the composites was similar to the blends when clays were localized inside of dispersed phase but increased when clays were localized at interface. Also, the fractured morphology of the composites showed phase boundary and growing radius of dispersed phase depending on addition of fillers when clays were found inside. However, when fillers found at the interface between blends, the radius of the dispersed phase decreased and compatibilized morphology were observed. The interfacial interaction of the ternary composite was quantified depending on the structural development of dispersed phase and localization of clay particles by the rheological properties. The interaction of composites at solid state which was measured through peel adhesion strength increased by growth of interfacial interaction of each component. Furthermore, the crystallinity of the composites was decreased when the clay particles were localized at the interface.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  18. 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.

  19. 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.

  20. 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.

  1. [MORPHOLOGICAL CHANGES OF THE LIVER IN OBTURATION JAUNDICE, CAUSED BY CHOLEDOCHOLITHIASIS, DEPENDING ON ITS DURATION].

    Science.gov (United States)

    Sipliviy, V A; Yevtushenko, D V; Naumova, O V; Andreyeshchev, S A; Yevtushenko, A V

    2016-02-01

    Abstract The results of surgical treatment of 184 patients for obturation jaundice, caused by choledocholithiasis, were analyzed. Morphological changes of the liver were studied in 20 patients. There were three groups of patients delineated, depending on the obturation jaundice duration: up to 7 days, from 8 to 14 days, more than 15 days, and also a group of patients after the bile outflow restoration. The obturation jaundice occurrence in choledocholithiasis is accompanied by significant morphological changes in the liver, severity of which is enhancing while the obturation jaundice persistence increasing. While persistence of obturation jaundice through 8 days and more the connective tissue volume is enhancing, a relative volume of hepatocytes is reducing and a stromal-parenchymatous index is increasing. The bile outflow restoration secures significant reduction of intensity of alterative and inflammatory changes in hepatic parenchyma, as well as activation of reparative processes in the tissue. In cholangitis, caused by P. aeruginosa and E. coli, according to morphological investigations data, in the liver a diffuse purulent cholangitis on background of chronic changes in accordance to duration of the obturation jaundice persists.

  2. Complex stimulation of peripheral nerve regeneration after deferred neurorrhaphy

    Directory of Open Access Journals (Sweden)

    Ivanov A.N.

    2017-09-01

    Full Text Available The aim is to study the complex stimulation effect including skin autotransplantation and electrical stimulation of the sciatic nerve on microcircular, electrophysiological and morphological changes after deferred neurorrhaphy in rats. Material and methods. The experiment was performed in 50 albino rats divided into control, comparative and experimental groups. In the experimental group, on the background of deferred neurorrhaphy, skin autotransplantation and electrical stimulation of the sciatic nerve had been carried out. In the comparative group only deferred neurorrhaphy was performed. Research methods included laser doppler flowmetry, electroneuromyography and morphological analysis of the operated nerve. Results. Complex stimulation including skin autotransplantation and direct action of electrical pulses on the sciatic nerve after its deferred neurorrhaphy causes restoration of bloodstream in the operated limb, promotes intensification of restoration of nerve fibers. Conclusion. Intensification of sciatic nerve regeneration after deferred neurorrhaphy in rats under the influence of complex stimulation including full-thickness skin graft autotransplantation and direct action of electrical pulses substantiates experimentally appropriateness of clinical testing of the given method for treatment of patients with peripheral nerve injuries.

  3. 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.

  4. 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

  5. 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.

  6. Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

    Directory of Open Access Journals (Sweden)

    Callihan Phillip

    2008-12-01

    Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

  7. Genetic and morphological diversity of Trisetacus species (Eriophyoidea: Phytoptidae) associated with coniferous trees in Poland: phylogeny, barcoding, host and habitat specialization.

    Science.gov (United States)

    Lewandowski, Mariusz; Skoracka, Anna; Szydło, Wiktoria; Kozak, Marcin; Druciarek, Tobiasz; Griffiths, Don A

    2014-08-01

    Eriophyoid species belonging to the genus Trisetacus are economically important as pests of conifers. A narrow host specialization to conifers and some unique morphological characteristics have made these mites interesting subjects for scientific inquiry. In this study, we assessed morphological and genetic variation of seven Trisetacus species originating from six coniferous hosts in Poland by morphometric analysis and molecular sequencing of the mitochondrial cytochrome oxidase subunit I gene and the nuclear D2 region of 28S rDNA. The results confirmed the monophyly of the genus Trisetacus as well as the monophyly of five of the seven species studied. Both DNA sequences were effective in discriminating between six of the seven species tested. Host-dependent genetic and morphological variation in T. silvestris and T. relocatus, and habitat-dependent genetic and morphological variation in T. juniperinus were detected, suggesting the existence of races or even distinct species within these Trisetacus taxa. This is the first molecular phylogenetic analysis of the Trisetacus species. The findings presented here will stimulate further investigations on the evolutionary relationships of Trisetacus as well as the entire Phytoptidae family.

  8. 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).

  9. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  10. 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....

  11. Surface morphology of polyethylene glycol films produced by matrix-assisted pulsed laser evaporation (MAPLE): Dependence on substrate temperature

    DEFF Research Database (Denmark)

    Rodrigo, K.; Czuba, P.; Toftmann, B.

    2006-01-01

    The dependence of the surface morphology on the substrate temperature during film deposition was investigated for polyethylene glycol (PEG) films by matrix-assisted pulsed laser evaporation (MAPLE). The surface structure was studied with a combined technique of optical imaging and AFM measurements...

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  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. 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…

  3. 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.

  4. 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.

  5. MORPHOLOGICAL ADJUSTMENTS OF THE RADIAL NERVE ARE INTENSITY-DEPENDENT

    Directory of Open Access Journals (Sweden)

    Patrícia Oliva Carbone

    Full Text Available ABSTRACT Introduction: Peripheral nerve adaptation is critical for strength gains. However, information about intensity effects on nerve morphology is scarce. Objective: To compare the effects of different intensities of resistance training on radial nerve structures. Methods: Rats were divided into three groups: control (GC, training with 50% (GF1 and training 75% (GF2 of the animal’s body weight. The morphological analysis of the nerve was done by light and transmission electron microscopy. One-way ANOVA and the Tukey’s post hoc test were applied and the significance level was set at p≤0.05. Results: Training groups had an increase of strength compared to GC (p≤0.05. All measured nerve components (mean area and diameter of myelin fibers and axons, mean area and thickness of the myelin sheath, and of neurofilaments and microtubules were higher in GF2 compared to the other (p≤0.05. Conclusion: Results demonstrated greater morphological changes on radial nerve after heavier loads. This can be important for rehabilitation therapies, training, and progression.

  6. Electroconvulsive stimulations prevent stress-induced morphological changes in the hippocampus

    DEFF Research Database (Denmark)

    Hageman, I; Nielsen, M; Wörtwein, Gitta

    2008-01-01

    whether repeated electroconvulsive stimulations (ECSs) could influence such changes in stressed rats. Furthermore, we investigated whether ECSs per se could influence neuronal branching and total length of the CA3 hippocampal neuronal dendritic tree in normal rats. Rats were stressed using the 21-day 6 h...

  7. 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.

  8. Study Of Morphological Changes Of Uterine Horn Of Surri Mouse Depended To Morphine Before Puberty And DuringPuberty

    Directory of Open Access Journals (Sweden)

    Shadkhast M

    2003-11-01

    Full Text Available : Morphine is the most important alkaloid of opium family which is found as much as ten percent in opium, and is in two types the sulfate morphine and the hydrochloride morphine."nMaterials and Methods: In this study morphological changes of uterus of surri mice due to oral consumption of sulfate morphine were studied. It was shown that, female surri mice following gradually increasing of morphine to water (0.1 and 0.01 mg/ml were depended to morphine. Female surri mice were classified in two age groups before puberty and depended to morphine during puberty. Each age group took morphine for 21 days. After finishing the period, the mice anesthetizing were weighted, then were anesthetizing and uterus was studied the length, width and apparent features."nResults&ConcIusion: In this study it was distinguished that length and width of uterine horn, between experimental and control groups, were significant (P< 0.01. Morphological changes such as anemia, the thinness and fragitidily walls of uterus and filiformity of uterine horns were observed."n"n"n"n"n"n 

  9. Light-regulated leaf expansion in two Populus species: dependence on developmentally controlled ion transport.

    Science.gov (United States)

    Stiles, Kari A; Van Volkenburgh, Elizabeth

    2002-07-01

    Leaf growth responses to light have been compared in two species of Populus, P. deltoides and P. trichocarpa. These species differ markedly in morphology, anatomy, and dependence on light during leaf expansion. Light stimulates the growth rate and acidification of cell walls in P. trichocarpa but not in P. deltoides, whereas leaves of P. deltoides maintain growth in the dark. Light-induced growth is promoted in P. deltoides when cells are provided 50-100 mM KCl. In both species, light initially depolarizes, then hyperpolarizes mesophyll plasma membranes. However, in the dark, the resting E(m) of mesophyll cells in P. deltoides, but not in P. trichocarpa, is relatively insensitive to decade changes in external [K+]. Results suggest that light-stimulated leaf growth depends on developmentally regulated cellular mechanisms controlling ion fluxes across the plasma membrane. These developmental differences underlie species-level differences in growth and physiological responses to the photoenvironment.

  10. Dependence of surface morphology on molecular structure and its influence on the properties of OLEDs

    Energy Technology Data Exchange (ETDEWEB)

    Lim, S.H. [Department of Chemical Engineering, Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Ryu, G.Y. [Department of Electric Information and Control Engineering, Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Seo, J.H.; Park, J.H. [Center for Organic Materials and Information Devices (COMID), Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Department of Information Display, Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Youn, S.W. [Department of Chemical Engineering, Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Kim, Y.K. [Center for Organic Materials and Information Devices (COMID), Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Department of Information Display, Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of); Shin, D.M. [Department of Chemical Engineering, Hongik University, 72-1, Sangsu-Dong, Mapo-Gu, Seoul 121-791 (Korea, Republic of)], E-mail: shindm@wow.hongik.ac.kr

    2008-09-15

    Most organic light-emitting diodes (OLEDs) have a multilayer structure composed of organic layers such as a hole injection layer (HIL), a hole transport layer (HTL), an emission layer (EML), an electron transport layer (ETL) and an electron injection layer (EIL) sandwiched between two electrodes. The organic layers are thin solid films with a thickness from a few nano meters to a few tenths nano meter, respectively. Surface morphology of an organic thin solid film in OLEDs depends on the molecular structure of the organic material and has an affect on device performance. To analyze the effect of surface morphology of an organic thin solid film on fluorescence and electroluminescence (EL) properties, thin solid films of 4-(dicyanomethylene)-2-methyl-6-(julolidin-4-yl-vinyl)-4H-pyran (DCM2) and new red fluorophores, (2E,2'E)-3,3'-[4,4''-bis(dimethylamino)-1,1':4',1''-terphenyl-2',5'-diyl] bis[2= -(2-thienyl)acrylonitrile] (ABCV-Th) and (2Z,2'Z)-3,3'-[4,4''-bis(dimethylamino)-1,1':4',1''-terphenyl-2',5'-diyl] bis(2-phenylacrylonitrile) (ABCV-P) were investigated by atomic force microscopy (AFM). The samples for EL and AFM measurement were fabricated by the high-vacuum thermal deposition (8x10{sup -7} Torr) of organic materials onto the surface of indium tin oxide (ITO)-coated glass substrate, in which the layer structures of samples for AFM measurement and those for EL measurement were ITO/NPB (40 nm)/red emitters (80 nm) and ITO/NPB (40 nm)/red emitters (80 nm)/BCP (30 nm)/Liq (2 nm)/Al (100 nm), respectively. The analysis based on AFM measurements well supported that the photoluminescence properties and the device performance were very much dependent upon surface morphology of an organic thin layer.

  11. 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.

  12. 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....

  13. Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth.

    Science.gov (United States)

    Koppes, Abigail N; Nordberg, Andrea L; Paolillo, Gina M; Goodsell, Nicole M; Darwish, Haley A; Zhang, Linxia; Thompson, Deanna M

    2014-02-01

    Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite outgrowth and a more pronounced effect was observed if both peripheral glia (Schwann cells) and neurons were co-stimulated. If electrical stimulation is delivered to an injury site, both the neurons and all resident non-neuronal cells [e.g., Schwann cells, endothelial cells, fibroblasts] will be treated and this biophysical stimuli can influence axonal growth directly or indirectly via changes to the resident, non-neuronal cells. In this work, non-neuronal cells were electrically stimulated, and changes in morphology and neuro-supportive cells were evaluated. Schwann cell response (morphology and orientation) was examined after an 8 h stimulation over a range of DC fields (0-200 mV/mm, DC 1 mA), and changes in orientation were observed. Electrically prestimulating Schwann cells (50 mV/mm) promoted 30% more neurite outgrowth relative to co-stimulating both Schwann cells with neurons, suggesting that electrical stimulation modifies Schwann cell phenotype. Conditioned medium from the electrically prestimulated Schwann cells promoted a 20% increase in total neurite outgrowth and was sustained for 72 h poststimulation. An 11-fold increase in nerve growth factor but not brain-derived neurotrophic factor or glial-derived growth factor was found in the electrically prestimulated Schwann cell-conditioned medium. No significant changes in fibroblast or endothelial morphology and neuro-supportive behavior were observed poststimulation. Electrical stimulation is widely used in

  14. 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

  15. 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)

  16. [DEVELOPMENT OF FUNCTIONAL AND MORPHOLOGICAL CHANGES OF A PANCREAS DEPENDING ON THE DURATION OF OBSTRUCTIVE CHOLESTASIS].

    Science.gov (United States)

    Belyaev, A N; Kostin, S V; Belyaev, S A

    2015-01-01

    To study the severity and timing of the development of functional (reversible) and morphological (irreversible) disturbances in the pancreas, depending on the duration of obstructive cholestasis. Obstructive jaundice in the experiment 18 dogs modeled by applying the loop stranglehold on the common bile duct, followed by observation for 30 days. We measured total bilirubin and fractions aspartate aminotransferase activity (AST) and alanine aminotransferase (ALT), the contents alpha-amylase, pancreatic lipase, glucose, histological examination of the pancreas (magnification of 100 times and 400). On day 3 the common bile duct obstruction bilirubin increased from 7.1 to 286.8 μmol/l, ALT--from 0.17 to 4.18 μmol*h/l, alpha-amylase from 89 to 186 U/L and lipase--to 68 to 179 U/L. Then there was a slight decrease in the parameters studied with repeated their increase to 15 hours. Morphological changes in the first three days were characterized by reversible (swelling), impaired organ that 14-16 days passed in organic (irreversible) changes. Dynamics of fluctuations in the level of liver enzymes in the pancreas and obstructive cholestasis correlates with morphological abnormalities in the pancreas and fit into the concept of general biological organism's reaction to injury.

  17. Text collections for evaluation of Russian morphological taggers

    Directory of Open Access Journals (Sweden)

    Lyashevskaya Olga

    2017-12-01

    Full Text Available The paper describes the preparation and development of the text collections within the framework of MorphoRuEval-2017 shared task, an evaluation campaign designed to stimulate development of the automatic morphological processing technologies for Russian. The main challenge for the organizers was to standardize all available Russian corpora with the manually verified high-quality tagging to a single format (Universal Dependencies CONLL-U. The sources of the data were the disambiguated subcorpus of the Russian National Corpus, SynTagRus, OpenCorpora.org data and GICR corpus with the resolved homonymy, all exhibiting different tagsets, rules for lemmatization, pipeline architecture, technical solutions and error systematicity. The collections includes both normative texts (the news and modern literature and more informal discourse (social media and spoken data, the texts are available under CC BY-NC-SA 3.0 license.

  18. 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

  19. 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

  20. CANDELS OBSERVATIONS OF THE ENVIRONMENTAL DEPENDENCE OF THE COLOR-MASS-MORPHOLOGY RELATION AT z = 1.6

    International Nuclear Information System (INIS)

    Bassett, Robert; Papovich, Casey; Tran, Kim-Vy; Lotz, Jennifer M.; Ferguson, Henry C.; Koekemoer, Anton M.; Bell, Eric F.; Finkelstein, Steven L.; Newman, Jeffrey A.; Almaini, Omar; Lani, Caterina; Cooper, Michael; Croton, Darren; Dekel, Avishai; Kocevski, Dale D.; Koo, David C.; McGrath, Elizabeth J.; McIntosh, Daniel H.; Wechsler, Risa

    2013-01-01

    We study the environmental dependence of color, stellar mass, and morphology by comparing galaxies in a forming cluster to those in the field at z = 1.6 with Hubble Space Telescope near-infrared imaging in the CANDELS/UDS field. We quantify the morphology of the galaxies using the effective radius, r eff , and Sérsic index, n. In both the cluster and field, approximately half of the bulge-dominated galaxies (n > 2) reside on the red sequence of the color-magnitude diagram, and most disk-dominated galaxies (n proj < 1.5 Mpc, which have low Sérsic indices and possibly larger effective radii, more consistent with star-forming galaxies at this epoch and in contrast to other quiescent galaxies. We argue that star-forming galaxies are processed under the influence of the cluster environment at distances greater than the cluster-halo virial radius. Our results are consistent with models where gas accretion onto these galaxies is suppressed from processes associated with the cluster environment.

  1. 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.

  2. 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...

  3. mDia2 and CXCL12/CXCR4 chemokine signaling intersect to drive tumor cell amoeboid morphological transitions.

    Science.gov (United States)

    Wyse, Meghan M; Goicoechea, Silvia; Garcia-Mata, Rafael; Nestor-Kalinoski, Andrea L; Eisenmann, Kathryn M

    2017-03-04

    Morphological plasticity in response to environmental cues in migrating cancer cells requires F-actin cytoskeletal rearrangements. Conserved formin family proteins play critical roles in cell shape, tumor cell motility, invasion and metastasis, in part, through assembly of non-branched actin filaments. Diaphanous-related formin-2 (mDia2/Diaph3/Drf3/Dia) regulates mesenchymal-to-amoeboid morphological conversions and non-apoptotic blebbing in tumor cells by interacting with its inhibitor diaphanous-interacting protein (DIP), and disrupting cortical F-actin assembly and bundling. F-actin disruption is initiated by a CXCL12-dependent mechanism. Downstream CXCL12 signaling partners inducing mDia2-dependent amoeboid conversions remain enigmatic. We found in MDA-MB-231 tumor cells CXCL12 induces DIP and mDia2 interaction in blebs, and engages its receptor CXCR4 to induce RhoA-dependent blebbing. mDia2 and CXCR4 associate in blebs upon CXCL12 stimulation. Both CXCR4 and RhoA are required for CXCL12-induced blebbing. Neither CXCR7 nor other Rho GTPases that activate mDia2 are required for CXCL12-induced blebbing. The Rho Guanine Nucleotide Exchange Factor (GEF) Net1 is required for CXCL12-driven RhoA activation and subsequent blebbing. These results reveal CXCL12 signaling, through CXCR4, directs a Net1/RhoA/mDia-dependent signaling hub to drive cytoskeleton rearrangements to regulate morphological plasticity in tumor cells. These signaling hubs may be conserved during normal and cancer cells responding to chemotactic cues. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle.

    Science.gov (United States)

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; Santos, Thais Caroline Pereira Dos; Dias, Daniel Ventura; Daré, Letícia Rossi; Rosa, Geraldo Marco

    2017-01-01

    To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the animals were euthanized and histological and morphometric analyses were performed. Data were submitted to statistical analysis with a significance level of pprotocolo de corrente russa aplicada três vezes por semanas, durante 45 dias. Ao final, os animais foram eutanasiados e, em seguida, foram realizadas as análises histológica e morfométrica. Os dados foram submetidos à análise estatística, com nível de significância de p<0,05. Os Grupos Experimental Desnervado e o Grupo Experimental Desnervado Tratado apresentaram área de secção transversal da fibra menor quando comparados ao Grupo Controle Final. Entretanto, constatou-se diferença significativa entre o Grupo Experimental Desnervado e o Grupo Experimental Desnervado Tratado, mostrando que a estimulação elétrica minimizou atrofia muscular. Ainda, observou-se que o Grupo Experimental Desnervado Tratado apresentou resultados semelhantes ao Grupo Controle Inicial. A estimulação elétrica por meio da corrente russa foi favorável na manutenção da morfologia do músculo tibial cranial desnervado experimentalmente, minimizando a atrofia muscular.

  5. pH and generation dependent morphologies of PAMAM dendrimers on a graphene substrate.

    Science.gov (United States)

    Gosika, Mounika; Maiti, Prabal K

    2018-03-07

    The adsorption of PAMAM dendrimers at solid/water interfaces has been extensively studied, and is mainly driven by electrostatic and van der Waals interactions between the substrate and the dendrimers. However, the pH dependence of the adsorption driven predominantly by the van der Waals interactions is poorly explored, although it is crucial for investigating the potentiality of these dendrimers in supercapacitors and surface patterning. Motivated by this aspect, we have studied the adsorption behavior of PAMAM dendrimers of generations 2 (G2) to 5 (G5) with pH and salt concentration variation, on a charge neutral graphene substrate, using fully atomistic molecular dynamics simulations. The instantaneous snapshots from our simulations illustrate that the dendrimers deform significantly from their bulk structures. Based on various structural property calculations, we classify the adsorbed dendrimer morphologies into five categories and map them to a phase diagram. Interestingly, the morphologies we report here have striking analogies with those reported in star-polymer adsorption studies. From the fractional contacts and other structural property analyses we find that the deformations are more pronounced at neutral pH as compared to high and low pH. Higher generation dendrimers resist deformation following the deformation trend, G2 > G3 > G4 > G5 at any given pH level. As the adsorption here is mainly driven by van der Waals interactions, we observe no desorption of the dendrimers as the salt molarity is increased, unlike that reported in the electrostatically driven adsorption studies.

  6. 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.

  7. Aging affects morphology but not stimulated secretion of saliva in rats

    African Journals Online (AJOL)

    Body weights, salivary gland weights, salivary flow rates, pH and salivary levels of sodium, potassium, calcium, chloride, bicarbonate, phosphate and total protein were measured and compared. Hematoxylin-eosin stained histological slides of the salivary glands were assessed for morphological changes. Results: Body ...

  8. Morphology of PVD films

    International Nuclear Information System (INIS)

    Carr, M.J.; Grotzky, V.K.; Helms, C.J.; Johns, W.L.; Naimon, E.R.; Rafalski, A.L.; Smith, C.J.

    1982-01-01

    Experimental data show that the morphology of PVD chromium coatings is dependent on substrate temperature, deposition rate, and the oxygen content of the chromium source material. For chromium containing about 700-ppM oxygen, a variety of morphologies can form depending on substrate temperature and deposition rate. For chromium contaning 1000 to 2000 ppM of oxygen, porous coatings of the Type IV variety are produced over essentially the full range of temperatures and rates possible with current coating equipment. For chromium containing less than about 400 ppM of oxygen, dense coatings of the Type I variety are produced over the range of temperatures and rates investigated

  9. The Applications of Morphology Controlled ZnO in Catalysis

    Directory of Open Access Journals (Sweden)

    Yuhai Sun

    2016-11-01

    Full Text Available Zinc oxide (ZnO, with the unique chemical and physical properties of high chemical stability, broad radiation absorption range, high electrochemical coupling coefficient, and high photo-stability, is an attractive multifunctional material which has promoted great interest in many fields. What is more, its properties can be tuned by controllable synthesized morphologies. Therefore, after the success of the abundant morphology controllable synthesis, both the morphology-dependent ZnO properties and their related applications have been extensively investigated. This review concentrates on the properties of morphology-dependent ZnO and their applications in catalysis, mainly involved reactions on green energy and environmental issues, such as CO2 hydrogenation to fuels, methanol steam reforming to generate H2, bio-diesel production, pollutant photo-degradation, etc. The impressive catalytic properties of ZnO are associated with morphology tuned specific microstructures, defects or abilities of electron transportation, etc. The main morphology-dependent promotion mechanisms are discussed and summarized.

  10. 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.

  11. Toward Improved Lifetimes of Organic Solar Cells under Thermal Stress: Substrate-Dependent Morphological Stability of PCDTBT:PCBM Films and Devices.

    Science.gov (United States)

    Li, Zhe; Ho Chiu, Kar; Shahid Ashraf, Raja; Fearn, Sarah; Dattani, Rajeev; Cheng Wong, Him; Tan, Ching-Hong; Wu, Jiaying; Cabral, João T; Durrant, James R

    2015-10-15

    Morphological stability is a key requirement for outdoor operation of organic solar cells. We demonstrate that morphological stability and lifetime of polymer/fullerene based solar cells under thermal stress depend strongly on the substrate interface on which the active layer is deposited. In particular, we find that the stability of benchmark PCDTBT/PCBM solar cells under modest thermal stress is substantially increased in inverted solar cells employing a ZnO substrate compared to conventional devices employing a PSS substrate. This improved stability is observed to correlate with PCBM nucleation at the 50 nm scale, which is shown to be strongly influenced by different substrate interfaces. Employing this approach, we demonstrate remarkable thermal stability for inverted PCDTBT:PC70BM devices on ZnO substrates, with negligible (humidity exposure as widely reported previously, can also demonstrate enhanced morphological stability. As such we show that the choice of suitable substrate interfaces may be a key factor in achieving prolonged lifetimes for organic solar cells under thermal stress conditions.

  12. Chronological changes in astrocytes induced by chronic electrical sensorimotor cortex stimulation in rats.

    Science.gov (United States)

    Morishita, Takashi; Yamashita, Akiko; Katayama, Yoichi; Oshima, Hideki; Nishizaki, Yuji; Shijo, Katsunori; Fukaya, Chikashi; Yamamoto, Takamitsu

    2011-01-01

    Motor cortex stimulation (MCS) is a treatment option for various disorders such as medically refractory pain, poststroke hemiplegia, and movement disorders. However, the exact mechanisms underlying its effects remain unknown. In this study, the effects of long-term chronic MCS were investigated by observing changes in astrocytes. A quadripolar stimulation electrode was implanted on the dura over the sensorimotor cortex of adult rats, and the cortex was continuously stimulated for 3 hours, 1 week, 4 weeks, and 8 weeks. Immunohistochemical staining of microglia (ionized calcium-binding adaptor molecule 1 [Iba1] staining) and astrocytes (glial fibrillary acidic protein [GFAP] staining), and neuronal degeneration histochemistry (Fluoro-Jade B staining) were carried out to investigate the morphological changes following long-term chronic MCS. Iba1 staining and Fluoro-Jade B staining showed no evidence of Iba1-positive microglial changes or neurodegeneration. Following continuous MCS, GFAP-positive astrocytes were enlarged and their number increased in the cortex and the thalamus of the stimulated hemisphere. These findings indicate that chronic electrical stimulation can continuously activate astrocytes and result in morphological and quantitative changes. These changes may be involved in the mechanisms underlying the neuroplasticity effect induced by MCS.

  13. 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.

  14. Graphene oxide reinforced core-shell structured Ag@Cu2O with tunable hierarchical morphologies and their morphology-dependent electrocatalytic properties for bio-sensing applications.

    Science.gov (United States)

    Gan, Tian; Wang, Zhikai; Shi, Zhaoxia; Zheng, Dongyun; Sun, Junyong; Liu, Yanming

    2018-07-30

    In this study, a facile solution approach was developed for the synthesis of a series of core-shell structured Ag@Cu 2 O nanocrystals of various shapes including triangles, spheres, and cubes with well-defined stable heterojunctions. The electrooxidation of dopamine (DA), uric acid (UA), guanine (G), and adenine (A) using these hybrids revealed morphology-dependent sensing properties, with activities and accumulation ability following the order, triangular Ag@Cu 2 O > spherical Ag@Cu 2 O > cubic Ag@Cu 2 O. Further, we constructed a novel graphene oxide (GO) nanosheet-reinforced triangular Ag@Cu 2 O ternary hetero-nanostructure. Such a hybrid with a three-dimensional interconnected hierarchical architecture is suitable for catalysis, since it not only leads to improved interfacial electron transfer, but also readily exposes the highly catalytic Ag@Cu 2 O to the reactants. Therefore, more enhanced electrochemical activities were observed for the oxidation of DA, UA, G, and A. This study provides an efficient way to synthesize morphology-controlled Ag@Cu 2 O heterogeneous catalysts for the fabrication of potential biosensors, and also opens up attractive avenues in the design of multifunctional ternary noble metal-semiconductor-carbon hybrids. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. 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.

  16. Electrical stimulation promotes regeneration of injured oculomotor nerves in dogs

    Directory of Open Access Journals (Sweden)

    Lei Du

    2016-01-01

    Full Text Available Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses (0.7 V, 5 Hz were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oculomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction.

  17. 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

  18. New descriptors of T-wave morphology are independent of heart rate

    DEFF Research Database (Denmark)

    Andersen, Mads Peter; Xue, Joel Q; Graff, Claus

    2008-01-01

    from daytime Holter recordings. Duration parameters (QT, ToTe, TpTe, and others), a number of basic T-wave morphology parameters (amplitude, area, and others) as well as advanced morphology descriptors (asymmetry, flatness, and others) were measured automatically. Heart rate dependence was examined...... by means of analysis of covariance. The results showed clear heart rate dependence for the QT interval (R(2) = 0.53-0.57) and a moderate degree of heart rate dependence for the basic morphology parameters (amplitude, area, and others) (R(2) = 0.17-0.42). Both the advanced T-wave descriptors (asymmetry......T-wave morphology descriptors are sensitive to drug-induced changes and may be a useful addition to the QT interval in cardiac safety trials. Intrasubject heart rate dependence of T-wave morphology was investigated in a sample of 39 healthy individuals. Ten-second electrocardiograms were obtained...

  19. Identification and origin of visible transitions in one dimensional (1D) ZnO nanostructures: Excitation wavelength and morphology dependence study

    Energy Technology Data Exchange (ETDEWEB)

    Baral, Arpit [Centre for Nanoscience and Nanotechnology, Jamia Millia Islamia, New Delhi 110025 (India); Khanuja, Manika, E-mail: manikakhanuja@gmail.com [Centre for Nanoscience and Nanotechnology, Jamia Millia Islamia, New Delhi 110025 (India); Islam, S.S. [Centre for Nanoscience and Nanotechnology, Jamia Millia Islamia, New Delhi 110025 (India); Sharma, Rishabh; Mehta, B.R. [Indian Institute of Technology Delhi, New Delhi 110016 (India)

    2017-03-15

    In this present work, one dimensional (1D) ZnO nanostructures were synthesized by mechanical assisted thermal decomposition process. The samples were characterized by transmission electron microscopy (TEM) for morphology, high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) for structural characterization. Photoluminescence (PL) and Photoluminescence spectra evolution was studied as a function of (i) excitation wavelength (λ{sub Ex:} 310–370 nm) and (ii) morphology (nanoneedles and nanorods). PL spectra were observed to be highly asymmetric with strong dependence on excitation wavelength (λ{sub Ex}). PL spectra categorized into two types as a function of excitation wavelength (λ{sub Ex}): I. λ{sub Ex}≤345 nm and II. λ{sub Ex}≥350 nm. The PL spectra were deconvoluted into multiple Gaussian components for each excitation wavelength. The position of each component is a signature of its origin and corresponds to specific visible transition. The transition involving origin from conduction band (CB) are absent for excitation wavelength λ{sub Ex}≥350 nm. The tunable photoresponse is achieved in 1D ZnO nanostructures by varying (i) excitation wavelength and (ii) morphology: nanoneedles to nanorods. PL intensity increases as aspect ratio decrease from nanoneedles to nanorods morphology. This is attributed to non-radiative quenching by near surface defects.

  20. 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.

  1. 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.

  2. General Mechanism of Morphology Transition and Spreading Area-dependent Phase Diagram of Block Copolymer Self-assembly at the Air/Water Interface

    Science.gov (United States)

    Kim, Dong Hyup; Kim, So Youn

    Block copolymers (BCPs) can be self-assembled forming periodic nanostructures, which have been employed in many applications. While general agreements exist for the phase diagrams of BCP self-assembly in bulk or thin films, a fundamental understanding of BCP structures at the air/water interface still remain elusive. The current study explains morphology transition of BCPs with relative fraction of each block at the air/water interface: block fraction is the only parameter to control the morphology. In this study, we show morphology transitions from spherical to cylindrical and planar structures with neat polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) via reducing the spreading area of BCP solution at the air/water interface. For example, PS-b-P2VP in a fixed block fraction known to form only spheres can experience sphere to cylinder or lamellar transitions depending on the spreading area at the air/water interface. Suggesting a new parameter to control the interfacial assembly of BCPs, a complete phase diagram is drawn with two paramters: relative block fraction and spreading area. We also explain the morphology transition with the combinational description of dewetting mechanism and spring effect of hydrophilic block.

  3. 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.

  4. CANDELS OBSERVATIONS OF THE ENVIRONMENTAL DEPENDENCE OF THE COLOR-MASS-MORPHOLOGY RELATION AT z = 1.6

    Energy Technology Data Exchange (ETDEWEB)

    Bassett, Robert; Papovich, Casey; Tran, Kim-Vy [George P. and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy, College Station, TX 77843-4242 (United States); Lotz, Jennifer M.; Ferguson, Henry C.; Koekemoer, Anton M. [Space Telescope Science Institute, 3700 San Martin Dr., Baltimore, MD 21218 (United States); Bell, Eric F. [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Finkelstein, Steven L. [Department of Astronomy, University of Texas, Austin, TX 78712 (United States); Newman, Jeffrey A. [Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Almaini, Omar; Lani, Caterina [School of Physics and Astronomy, University of Nottingham, Nottingham (United Kingdom); Cooper, Michael [Center for Galaxy Evolution, Department of Physics and Astronomy, University of California, Irvine, 4129 Frederick Reines Hall, Irvine, CA 92697 (United States); Croton, Darren [Centre for Astrophysics and Supercomputing, Swinburne University of Technology, Hawthorn (Australia); Dekel, Avishai [Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel); Kocevski, Dale D.; Koo, David C.; McGrath, Elizabeth J. [UCO/Lick Observatory, Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); McIntosh, Daniel H. [Department of Physics, University of Missouri-Kansas City, 5110 Rockhill Road, Kansas City, MO 64110 (United States); Wechsler, Risa [Kavli Institute for Particle Astrophysics and Cosmology, Physics Department, and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States)

    2013-06-10

    We study the environmental dependence of color, stellar mass, and morphology by comparing galaxies in a forming cluster to those in the field at z = 1.6 with Hubble Space Telescope near-infrared imaging in the CANDELS/UDS field. We quantify the morphology of the galaxies using the effective radius, r{sub eff}, and Sersic index, n. In both the cluster and field, approximately half of the bulge-dominated galaxies (n > 2) reside on the red sequence of the color-magnitude diagram, and most disk-dominated galaxies (n < 2) have colors expected for star-forming galaxies. There is weak evidence that cluster galaxies have redder rest-frame U - B colors and higher stellar masses compared to the field. Star-forming galaxies in both the cluster and field show no significant differences in their morphologies. In contrast, there is evidence that quiescent galaxies in the cluster have larger median effective radii and smaller Sersic indices compared to the field with a significance of 2{sigma}. These differences are most pronounced for galaxies at clustercentric distances 1 Mpc

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Effect of grain morphology on gas bubble swelling in UMo fuels – A 3D microstructure dependent Booth model

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Shenyang, E-mail: shenyang.hu@pnnl.gov; Burkes, Douglas; Lavender, Curt A.; Joshi, Vineet

    2016-11-15

    A three dimensional microstructure dependent swelling model is developed for studying the fission gas swelling kinetics in irradiated nuclear fuels. The model is extended from the Booth model [1] in order to investigate the effect of heterogeneous microstructures on gas bubble swelling kinetics. As an application of the model, the effect of grain morphology, fission gas diffusivity, and spatially dependent fission rate on swelling kinetics are simulated in UMo fuels. It is found that the decrease of grain size, the increase of grain aspect ratio for the grain having the same volume, and the increase of fission gas diffusivity (fission rate) cause the increase of swelling kinetics. Other heterogeneities such as second phases and spatially dependent thermodynamic properties including diffusivity of fission gas, sink and source strength of defects could be naturally integrated into the model to enhance the model capability.

  10. 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

  11. 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

  12. 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

  13. 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...

  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. Cell type dependent morphological adaptation in polyelectrolyte hydrogels governs chondrogenic fate.

    Science.gov (United States)

    Raghothaman, Deepak; Leong, Meng Fatt; Lim, Tze Chiun; Wan, Andrew C A; Ser, Zheng; Lee, Eng Hin; Yang, Zheng

    2016-04-04

    Repair of critical-size articular cartilage defects typically involves delivery of cells in biodegradable, 3D matrices. Differences in the developmental status of mesenchymal stem cells (MSCs) and terminally differentiated mature chondrocytes might be a critical factor in engineering appropriate 3D matrices for articular cartilage tissue engineering. This study examined the relationship between material-driven early cell morphological adaptations and chondrogenic outcomes, by studying the influence of aligned collagen type I (Col I) presentation on chondrocytes and MSC in interfacial polyelectrolyte complexation (IPC)-based hydrogels. In the absence of Col I, both chondrocytes and MSCs adopted rounded cell morphology and formed clusters, with chondrocyte clusters favoring the maintenance of hyaline phenotype, while MSC clusters differentiated to fibro-superficial zone-like chondrocytes. Encapsulated chondrocytes in IPC-Col I hydrogel adopted a fibroblastic morphology forming fibro-superficial zone-like phenotype, which could be reversed by inhibiting actin polymerization using cytochalasin D (CytD). In contrast, adoption of fibroblastic morphology by encapsulated MSCs in IPC-Col I facilitated superior chondrogenesis, generating a mature, hyaline neocartilage tissue. CytD treatment abrogated the elongation of MSCs and brought about a single cell-like state, resulting in insignificant chondrogenic differentiation, underscoring the essential requirement of providing matrix environments that are amenable to cell-cell interactions for robust MSC chondrogenic differentiation. Our study demonstrates that MSCs and culture-expanded chondrocytes favour differential microenvironmental niches and emphasizes the importance of designing biomaterials that meet cell type-specific requirements, in adopting chondrocyte or MSC-based approaches for regenerating hyaline, articular cartilage.

  16. Morphological and physiological features of Arthroderma benhamiae anamorphs isolated in northern Germany.

    Science.gov (United States)

    Brasch, Jochen; Wodarg, Svea

    2015-02-01

    The anamorph of Arthroderma benhamiae is an upcoming zoophilic dermatophyte that only in recent years has gained importance as a cause of tinea in humans. Its identification by conventional methods can cause problems. In this study we have subjected seven genetically confirmed strains of A. benhamiae anamorphs from northern Germany recently identified in our laboratory to a comprehensive assessment. Their macroscopic and microscopic morphology was checked on various agars and enzyme release stimulated by substrates with keratin, hair perforation and other physiological characteristics were tested. All strains were related to the previously described yellow phenotype of the A. benhamiae anamorph and showed a high resemblance among themselves. Coherent features were their uniform thallus morphology on Sabouraud glucose agar with yellow pigmentation, the formation of circuit-like hyphal structures and hyphal connections that had not been described previously, a lack of conidia, thiamine dependence, the spectrum of released enzymes and a good growth on human stratum corneum. With exception of the latter two these criteria are suggested for the identification of this anamorph phenotype that should be evaluated by future observations. Different phenotypes of the A. benhamiae anamorph may prevail in other geographic regions. © 2014 Blackwell Verlag GmbH.

  17. Osteoblast Differentiation Decreases Hypergravity-Stimulated Release of PGE(sub 2)

    Science.gov (United States)

    Searby, Nancy D.; Steele, Charles R.; Globus, Ruth K.

    2002-01-01

    We determined if progressive differentiation of osteoblasts influences their sensitivity to gravitational loading. Osteoblasts were cultured for 4 days (confluent monolayer), 6 days (prenodules), 9 days (nodules) and 19 days (mineralized nodules), then centrifuged at 10 times gravity (g) or 50-g for 3 hours using the NASA Ames 1-ft. Diameter Centrifuge. Stationary controls were placed in an adjacent incubator. Following centrifugation, conditioned media were collected and analyzed for PGE, by ELISA. Microtubules were fluorescently labeled and analyzed by confocal microscopy to determine microtubule network morphology and height. Centrifugation at 10-g reduced microtubule network height by 15% on d4 and 10% on d6, with variable changes in more mature cultures. No major changes in microtubule morphology were observed. PGE(sub 2) release by d4 cultures increased in a dose-dependent fashion (3-fold at 10-g and 6-fold at 50-g relative to controls). D6 cultures produced a 5-fold increase for both 10-g and 50-g. PGE(sub 2) increased only 1.5-fold by d9, and by d19, PGE(sub 2) was not delectable in either the control or hypergravity-stimulated cells. Thus, as osteoblasts differentiate in culture, responsiveness of the microtubule cytoskeleton and the PGE(sub 2) pathway to hypergravity declines.

  18. Meniscus matrix morphological composition: age-dependent evaluation in a swine model

    Directory of Open Access Journals (Sweden)

    Umberto Polito

    2017-06-01

    Full Text Available Menisci are fibro-cartilaginous structures interposed between femoral condyle and tibial plateau, which have multiple functions in the stifle joint: act as shock absorbers, bear loaders and allow joint stability, congruity and lubrication (Sweigart et al., 2004; Proffen et al., 2012. It is well known that meniscal injuries lead to osteoarthritis and for these reasons, menisci are considered important target of investigation. Their important role in the knee wellness is only equalled by their deficiency in proper self-repairing. Nowadays, the gold standard technique is not just to remove the damaged meniscus, but to rebuild it or to replace it. For these reasons, studies are necessary to increase the knowledge about these small but essential structures (Streuli, 1999; Deponti et al., 2013. Composition and morphology are basic fundamental information for the development of engineered meniscal substitutes (Di Giancamillo et al., 2014. The analysis of the morphological, structural and biochemical changes, which occur during growth of the normal menisci, represent the goal of the present study. For this purpose, menisci from adult (7-month old, young (1-month old, and neonates (stillbirths pigs were collected. Cellularity and glycosamiglycans (GAGs deposition were evaluated by ELISA, while Collagen-1 and Collagen-2 were investigated by immunohistochemistry and Western blot analyses. Cellularity (P<0.01, all comparisons and Collagen-1 (P<0.05, neonatal-young vs adult decreased from neonatal to adult stage while GAGs (P<0.01 neonatal vs young-adult and Collagen-2 (P<0.01 neonatal-young vs adult showed the opposite trend. Immunohistochemistry revealed similar changes occurring during animal growth thus revealing that cellular phenotype, cellularity and protein expression, as well as fibers aggregation in the matrix, are dissimilar in the three ages analysed categories. These changes reflect the progressive menisci maturation and hyper-specialisation. We

  19. Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles.

    Science.gov (United States)

    Johnson, Will L; Jindrich, Devin L; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

    2011-12-01

    A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb, which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model, we investigated the suitability of a lumped-parameter model for the prediction of muscle activation during dynamic tasks. Using the validated model, we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury.

  20. 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

  1. 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.

  2. Manganese oxide phases and morphologies: A study on calcination temperature and atmospheric dependence

    Directory of Open Access Journals (Sweden)

    Matthias Augustin

    2015-01-01

    Full Text Available Manganese oxides are one of the most important groups of materials in energy storage science. In order to fully leverage their application potential, precise control of their properties such as particle size, surface area and Mnx+ oxidation state is required. Here, Mn3O4 and Mn5O8 nanoparticles as well as mesoporous α-Mn2O3 particles were synthesized by calcination of Mn(II glycolate nanoparticles obtained through an economical route based on a polyol synthesis. The preparation of the different manganese oxides via one route facilitates assigning actual structure–property relationships. The oxidation process related to the different MnOx species was observed by in situ X-ray diffraction (XRD measurements showing time- and temperature-dependent phase transformations occurring during oxidation of the Mn(II glycolate precursor to α-Mn2O3 via Mn3O4 and Mn5O8 in O2 atmosphere. Detailed structural and morphological investigations using transmission electron microscopy (TEM and powder XRD revealed the dependence of the lattice constants and particle sizes of the MnOx species on the calcination temperature and the presence of an oxidizing or neutral atmosphere. Furthermore, to demonstrate the application potential of the synthesized MnOx species, we studied their catalytic activity for the oxygen reduction reaction in aprotic media. Linear sweep voltammetry revealed the best performance for the mesoporous α-Mn2O3 species.

  3. 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

  4. Morphological alterations in newly born dentate gyrus granule cells that emerge after status epilepticus contribute to make them less excitable.

    Directory of Open Access Journals (Sweden)

    Julián Tejada

    Full Text Available Computer simulations of external current stimulations of dentate gyrus granule cells of rats with Status Epilepticus induced by pilocarpine and control rats were used to evaluate whether morphological differences alone between these cells have an impact on their electrophysiological behavior. The cell models were constructed using morphological information from tridimensional reconstructions with Neurolucida software. To evaluate the effect of morphology differences alone, ion channel conductances, densities and distributions over the dendritic trees of dentate gyrus granule cells were the same for all models. External simulated currents were injected in randomly chosen dendrites belonging to one of three different areas of dentate gyrus granule cell molecular layer: inner molecular layer, medial molecular layer and outer molecular layer. Somatic membrane potentials were recorded to determine firing frequencies and inter-spike intervals. The results show that morphologically altered granule cells from pilocarpine-induced epileptic rats are less excitable than control cells, especially when they are stimulated in the inner molecular layer, which is the target area for mossy fibers that sprout after pilocarpine-induced cell degeneration. This suggests that morphological alterations may act as a protective mechanism to allow dentate gyrus granule cells to cope with the increase of stimulation caused by mossy fiber sprouting.

  5. Salivary gland ultrastructure and cyclic AMP-dependent reactions in Spacelab 3 rats

    International Nuclear Information System (INIS)

    Mednieks, M.I.; Hand, A.R.

    1987-01-01

    Environmental stimuli influencing catecholamine levels induce changes in cyclic AMP-dependent reactions and cell morphology in the rat parotid. Responses of salivary glands to spaceflight were determined by measurement of cyclic AMP-mediated reactions in fresh-frozen salivary glands and by microscopic evaluation of ultrastructure in fixed parotid glands. Decreased cell-free protein phosphorylation, determined by autoradiography, occurred in parotid glands in three of five flight animals. Protein kinase activity ratios were decreased in the soluble and increased in the particulate fractions of Spacelab 3 (SL-3) rat sublingual glands, compared with ground controls. Biochemical analyses show that effects of space flight on salivary glands are similar to those induced experimentally by physiological manipulation or alteration of catecholamine levels. Morphological evaluation of three SL-3 rat parotid glands showed increased numbers of lysosomes, autophagic vacuoles containing degenerating secretory product, and accumulation of lipid droplets. Since these animals lost weight, consistent with disruption of food and water consumption, morphological changes may in part be due to decreased masticatory stimulation, as occurs with reduced food intake or a liquid diet. The observed changes may reflect physiological responses of the gastrointestinal and autonomic systems to effects of spaceflight

  6. 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

  7. From nanodroplets to continuous films: how the morphology of polyelectrolyte multilayers depends on the dielectric permittivity and the surface charge of the supporting substrate

    NARCIS (Netherlands)

    Guillaume-Gentil, Orane; Zahn, Raphael; Lindhoud, Saskia; Graf, Norma; Voros, Janos; Zambelli, Tomaso

    2011-01-01

    Using atomic force microscopy, we investigated how the morphology of layer-by-layer deposited polyelectrolyte multilayers is influenced by the physical properties of the supporting substrate. The surface coverage of the assembly and its topography were found to be dependent on the dielectric

  8. Evaluation of dynamic MRCP after secretin stimulation for biliopancreatic diseases

    International Nuclear Information System (INIS)

    Ohhigashi, Seiji; Nishio, Takeki; Watanabe, Fumihiko; Haradome, Hiroki; Doi, Osamu

    2000-01-01

    Both pancreaticobiliary maljunction and pancreatogastrostomy after pancreatoduodenectomy were analyzed to assess the utility of dynamic MRCP after secretin stimulation. Dynamic MRCP obtained every 60 seconds for 15 minutes after secretin administration revealed the bile and pancreatic fluid kinetics. Calculating the intensity value from the MR images allowed objective estimation of the bile and pancreatic fluid kinetics. Thus, this study demonstrated that dynamic MRCP after secretin stimulation was significantly useful in evaluating not only the morphologic features in pancreaticobiliary maljunction but also pancreatic exocrine function after resection of the pancreas. (author)

  9. Morphology-dependent water budgets and nutrient fluxes in arctic thaw ponds

    Science.gov (United States)

    Koch, Joshua C.; Gurney, Kirsty; Wipfli, Mark S.

    2014-01-01

    Thaw ponds on the Arctic Coastal Plain of Alaska are productive ecosystems, providing habitat and food resources for many fish and bird species. Permafrost in this region creates unique pond morphologies: deep troughs, shallow low-centred polygons (LCPs) and larger coalescent ponds. By monitoring seasonal trends in pond volume and chemistry, we evaluated whether pond morphology and size affect water temperature and desiccation, and nitrogen (N) and phosphorus (P) fluxes. Evaporation was the largest early-summer water flux in all pond types. LCPs dried quickly and displayed high early-summer nutrient concentrations and losses. Troughs consistently received solute-rich subsurface inflows, which accounted for 12 to 42 per cent of their volume and may explain higher P in the troughs. N to P ratios increased and ammonium concentrations decreased with pond volume, suggesting that P and inorganic N availability may limit ecosystem productivity in older, larger ponds. Arctic summer temperatures will likely increase in the future, which may accelerate mid-summer desiccation. Given their morphology, troughs may remain wet, become warmer and derive greater nutrient loads from their thawing banks. Overall, seasonal- to decadal-scale warming may increase ecosystem productivity in troughs relative to other Arctic Coastal Plain ponds. 

  10. UV dosimetry in pollen of Pinus silvestris and stimulation studies of pollen tube growth after irradiation with UV and ionizing radiations

    International Nuclear Information System (INIS)

    Seibold, H.W.

    1976-01-01

    Pollen tube growth after exposure to UV- and ionizing radiation was investigated in Pinus silvestris as a function of different parameters. The preconditions for this are an exact UV dosimetry and the conversion of the UV dose of [erg] into [rad]. In spite of the fact that the calculation methods are theoretically already well known, the experimental determination of the absorbed energy dose, in particular the absorption factors, was complicated by the morphological structure of the pollen. The total-irradiation experiments showed that the stimulation and inhibition of pollen tube growth is highly dependent on the dose/dose rate region chosen. Stimulation is highly dependent on the dose rate after UV irradiation as well as after exposure to ionizing radiation. When the dose rates are very small, the values are practically the same as in non-irradiated controls; with increasing doses rate, stimulation increases, whereas at very high dose rates only growth inhibition is observed. After exposure to ionizing radiation, the quantum energy or wavelength of the radiation has no effect on tube growth; after UV irradiation, on the other hand, there is hardly any stimulation at short wavelengths. As these observations were not sufficient for drawing conclusions on the site of the stimulatory action, partial UV exposure with separate irradiation of the two nuclei and the cytoplasm was also carried out. Stimulation was found in each of the three irradiation sites; although nuclei and cytoplasma react differently and also differ in the initial reaction stages, there is always an anhancement of pollen tube growth. These findings are compared with some of the current hypotheses for an explanation of the stimulatory effect. (orig.) [de

  11. Suitable parameter choice on quantitative morphology of A549 cell in epithelial–mesenchymal transition

    Science.gov (United States)

    Ren, Zhou-Xin; Yu, Hai-Bin; Li, Jian-Sheng; Shen, Jun-Ling; Du, Wen-Sen

    2015-01-01

    Evaluation of morphological changes in cells is an integral part of study on epithelial to mesenchymal transition (EMT), however, only a few papers reported the changes in quantitative parameters and no article compared different parameters for demanding better parameters. In the study, the purpose was to investigate suitable parameters for quantitative evaluation of EMT morphological changes. A549 human lung adenocarcinoma cell line was selected for the study. Some cells were stimulated by transforming growth factor-β1 (TGF-β1) for EMT, and other cells were as control without TGF-β1 stimulation. Subsequently, cells were placed in phase contrast microscope and three arbitrary fields were captured and saved with a personal computer. Using the tools of Photoshop software, some cells in an image were selected, segmented out and exchanged into unique hue, and other part in the image was shifted into another unique hue. The cells were calculated with 29 morphological parameters by Image Pro Plus software. A parameter between cells with or without TGF-β1 stimulation was compared statistically and nine parameters were significantly different between them. Receiver operating characteristic curve (ROC curve) of a parameter was described with SPSS software and F-test was used to compare two areas under the curves (AUCs) in Excel. Among them, roundness and radius ratio were the most AUCs and were significant higher than the other parameters. The results provided a new method with quantitative assessment of cell morphology during EMT, and found out two parameters, roundness and radius ratio, as suitable for quantification. PMID:26182364

  12. 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

  13. ACUTE IRRADIATION EFFECTS ON MORPHOLOGY AND FUNCTION OF RAT SUBMANDIBULAR GLANDS

    NARCIS (Netherlands)

    VISSINK, A; KALICHARAN, D; GRAVENMADE, EJ; JONGEBLOED, WL; LIGEON, EE; NIEUWENHUIS, P; KONINGS, AWT

    1991-01-01

    In this study the morphologic and functional changes were compared after irradiation (single dose, 15 Gy) of rat submandibular salivary glands. Before and 1-10 days after local irradiation of the gland region, samples of submandibular saliva were collected after stimulation by pilocarpine. At the

  14. SU-F-T-661: Dependence of Gold Nano Particles Cluster Morphology On Dose Enhancement of Photon Radiation Therapy Apply for Radiation Biology Effect

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, S [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University (Korea, Republic of); Chung, K; Han, Y; Park, H [Samsung Medical Center, Sungkyunkwan University School of Medicine radiation oncology (Korea, Republic of)

    2016-06-15

    Purpose: Injected gold nano particles (GNPs) to a body for dose enhancement are known to form in the tumorcell cluster morphology. We investigated the dependence of dose enhancement on the morphology characteristic with an approximated morphology model by using Monte Carlo simulations. Methods: For MC simulation, TOPAS version 2.0P-03 was used. GNP cluster morphology was approximated as a body center cubic(BCC) model by placing 8 GNPs at the corner and one at the center of cube with length from 2.59 µm to 0.25 µm located in a 4 µm length water filled cube phantom. 4 µm length square shaped beams of poly-energetic 50, 260 kVp photons were irradiated to the water filled cube phantom with 100 nm diameter GNPs in it. Dose enhancement ratio(DER) was computed as a function of distance from the surface of the GNP at the cube center for 18 cubes geometries. For scoring particles, 10 nm width of concentric shell shaped detector was constructed up to 100 nm from the center. Total dose in a sphere of 100 nm radius of detector were normalized to 2.59 µm length cube morphology. To verified biological effect of BCC model applied to cell survival curve fitting. Results: DER increase as the distance of the GNPs reduces. DER was largest for 0.25 µm length cube. Dependence of GNP distance DER increment was 1.73, 1.60 for 50 kVp, 260 kVp photons, respectively. Also, Using BCC model applied to cell survival curve was well prediction. Conclusion: DER with GNPs was larger when they are closely packed in the phantom. Therefore, better therapeutic effects can be expected with close-packed GNPs. This research was supported by the NRF funded by the Ministry of Science, ICT & Future Planning (2012M3A9B6055201 and 2012R1A1A2042414), Samsung Medical Center grant[GFO1130081].

  15. Biophysical Stimuli: A Review of Electrical and Mechanical Stimulation in Hyaline Cartilage.

    Science.gov (United States)

    Vaca-González, Juan J; Guevara, Johana M; Moncayo, Miguel A; Castro-Abril, Hector; Hata, Yoshie; Garzón-Alvarado, Diego A

    2017-09-01

    Objective Hyaline cartilage degenerative pathologies induce morphologic and biomechanical changes resulting in cartilage tissue damage. In pursuit of therapeutic options, electrical and mechanical stimulation have been proposed for improving tissue engineering approaches for cartilage repair. The purpose of this review was to highlight the effect of electrical stimulation and mechanical stimuli in chondrocyte behavior. Design Different information sources and the MEDLINE database were systematically revised to summarize the different contributions for the past 40 years. Results It has been shown that electric stimulation may increase cell proliferation and stimulate the synthesis of molecules associated with the extracellular matrix of the articular cartilage, such as collagen type II, aggrecan and glycosaminoglycans, while mechanical loads trigger anabolic and catabolic responses in chondrocytes. Conclusion The biophysical stimuli can increase cell proliferation and stimulate molecules associated with hyaline cartilage extracellular matrix maintenance.

  16. 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.

  17. 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.

  18. Morphology dependent field emission characteristics of ZnS/silicon nanoporous pillar array

    Science.gov (United States)

    Wang, Ling Li; Zhao, Cheng Zhou; Kang, Li Ping; Liu, De Wei; Zhao, Hui Chun; Hao, Shan Peng; Zhang, Yuan Kai; Chen, Zhen Ping; Li, Xin Jian

    2016-10-01

    Through depositing zinc sulphide (ZnS) nanoparticals on silicon nanoporous pillar array (Si-NPA) and crater-shaped silicon nanoporous pillar array (c-Si-NPA) by chemical bath deposition (CBD) method, ZnS/Si-NPA and c-ZnS/Si-NPA were prepared and the field emission (FE) properties of them were investigated. The turn-on electric fields of were 3.8 V/mm for ZnS/Si-NPA and 5.0 V/mm for c-ZnS/Si-NPA, respectively. The lower turn-on electric fields of ZnS/Si-NPA than that of c-ZnS/Si-NPA were attributed to the different electric distribution of the field emitters causing by the different surface morphology of the two samples, which was further demonstrated via the simulated results by finite element modeling. The FN curves for the ZnS/Si-NPA showed two-slope behavior. All the results indicate that the morphology play an important role in the FE properties and designing an appropriate top morphology for the emitter is a very efficient way to improve the FE performance.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Temperature dependence of morphology, structural and optical properties of ZnS nanostructures synthesized by wet chemical route

    International Nuclear Information System (INIS)

    Navaneethan, M.; Archana, J.; Nisha, K.D.; Hayakawa, Y.; Ponnusamy, S.; Muthamizhchelvan, C.

    2010-01-01

    Research highlights: → ZnS nanoparticles and nanorods have been synthesized by wet chemical route. → Higher annealing temperature influenced the change in morphology due to aggregation of the nanoparticles. → The temperature dependent optical properties were investigated. → Absorption edge of nanoparticles (295 nm) and nanorods (326 nm) were shifted towards shorter wavelength compared to bulk ZnS (337 nm) due to the quantum confinement effect. → ZnS nanoparticles exhibit high photoluminescence intensity than that of ZnS nanorods annealed at 180 o C. - Abstract: ZnS nanostructures have been synthesized by simple wet chemical route and annealed at two different temperatures of 50 o C and 180 o C. From the measurements of transmission electron microscopy and contact-mode atomic force microscopy, it is found that annealed temperature changes the morphology from nanoparticles to nanorods. The optical properties of the synthesized ZnS nanomaterial have been characterized by UV-visible absorption spectroscopy and photoluminescence spectroscopy. The structural and elemental analyses were carried out by powder X-ray diffraction pattern and energy dispersive X-ray absorption spectroscopy, respectively. Absorption edge of the nanoparticles (295 nm) and nanorods (326 nm) was shifted towards shorter wavelength compared to bulk ZnS (337 nm) due to the quantum confinement effect.

  7. 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.

  8. 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.

  9. 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.

  10. Three-dimensional morphological segregation in rich clusters of galaxies

    International Nuclear Information System (INIS)

    Salvador-Sole, E.; Sanroma, M.; Jordana, J.J.R.

    1989-01-01

    The implications of the observed correlation between morphological fractions and projected number density of galaxies in rich clusters are analyzed. It is found that this correlation is the result of a well-defined intrinsic correlation that depends on cluster concentration, whether the observed correlation is strictly universal or not. This dependence is in overall agreement with that expected from the action of mechanisms of environment-induced morphological evolution of galaxies. 30 references

  11. 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

  12. 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

  13. Habitat preference of Zoantharia genera depends on host sponge morphology

    Directory of Open Access Journals (Sweden)

    Alberto Acosta

    2010-08-01

    Full Text Available Studies about sponge-zoanthid symbioses have been focused on understanding the specificity of the association, rather thantesting what are the characteristics that make the host suitable to be colonized. For the first time it is investigated whether the ZoanthariaParazoanthus and Epizoanthus preference is related to the host sponge morphology (shape and mechanical resistance. Materials andmethods. Sponges were categorized according to their shape and mechanical resistance. The presence/absence of zoanthids was recordedin 1,068 sponges at San Andres Island, and their habitat preference was evaluated using indices and confidence intervals. Results. 85Parazoanthus colonies (78% of the total associations and 24 Epizoanthus colonies (22% were associated to sponges (10.2% in total.Parazoanthus uses branched and compressible sponges although prefers encrusting and fragile sponges, while Epizoanthus showes theopposite pattern, it can inhabit encrusting and fragile sponges but prefers branched and compressible sponges. Conclusion. These resultsindicated that sponge morphology is an important trait in zoanthid habitat selection. On the other hand, the similarity in the habitat used byzoanthids suggests the possibility of inter-generic competition if common resources are limited in time and space, while the differentialhabitat preference allows the competitive coexistence of both genera.

  14. Manifold Shape: from Differential Geometry to Mathematical Morphology

    OpenAIRE

    Roerdink, J.B.T.M.

    1994-01-01

    Much progress has been made in extending Euclidean mathematical morphology to more complex structures such as complete lattices or spaces with a non-commutative symmetry group. Such generalizations are important for practical situations such as translation and rotation invariant pattern recognition or shape description of patterns on spherical surfaces. Also in computer vision much use is made of spherical mappings to describe the world as seen by a human or machine observer. Stimulated by th...

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Wetting morphologies on randomly oriented fibers.

    Science.gov (United States)

    Sauret, Alban; Boulogne, François; Soh, Beatrice; Dressaire, Emilie; Stone, Howard A

    2015-06-01

    We characterize the different morphologies adopted by a drop of liquid placed on two randomly oriented fibers, which is a first step toward understanding the wetting of fibrous networks. The present work reviews previous modeling for parallel and touching crossed fibers and extends it to an arbitrary orientation of the fibers characterized by the tilting angle and the minimum spacing distance. Depending on the volume of liquid, the spacing distance between fibers and the angle between the fibers, we highlight that the liquid can adopt three different equilibrium morphologies: 1) a column morphology in which the liquid spreads between the fibers, 2) a mixed morphology where a drop grows at one end of the column or 3) a single drop located at the node. We capture the different morphologies observed using an analytical model that predicts the equilibrium configuration of the liquid based on the geometry of the fibers and the volume of liquid.

  4. Role of codeposited impurities during growth. II. Dependence of morphology on binding and barrier energies

    Science.gov (United States)

    Sathiyanarayanan, Rajesh; Hamouda, Ajmi Bh.; Pimpinelli, A.; Einstein, T. L.

    2011-01-01

    In an accompanying article we showed that surface morphologies obtained through codeposition of a small quantity (2%) of impurities with Cu during growth (step-flow mode, θ = 40 ML) significantly depends on the lateral nearest-neighbor binding energy (ENN) to Cu adatom and the diffusion barrier (Ed) of the impurity atom on Cu(0 0 1). Based on these two energy parameters, ENN and Ed, we classify impurity atoms into four sets. We study island nucleation and growth in the presence of codeposited impurities from different sets in the submonolayer (θ⩽ 0.7 ML) regime. Similar to growth in the step-flow mode, we find different nucleation and growth behavior for impurities from different sets. We characterize these differences through variations of the number of islands (Ni) and the average island size with coverage (θ). Further, we compute the critical nucleus size (i) for all of these cases from the distribution of capture-zone areas using the generalized Wigner distribution.

  5. 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.

  6. 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.

  7. SMU.940 regulates dextran-dependent aggregation and biofilm formation in Streptococcus mutans.

    Science.gov (United States)

    Senpuku, Hidenobu; Yonezawa, Hideo; Yoneda, Saori; Suzuki, Itaru; Nagasawa, Ryo; Narisawa, Naoki

    2018-02-01

    The oral bacterium Streptococcus mutans is the principal agent in the development of dental caries. Biofilm formation by S. mutans requires bacterial attachment, aggregation, and glucan formation on the tooth surface under sucrose supplementation conditions. Our previous microarray analysis of clinical strains identified 74 genes in S. mutans that were related to biofilm morphology; however, the roles of almost all of these genes in biofilm formation are poorly understood. We investigated the effects of 21 genes randomly selected from our previous study regarding S. mutans biofilm formation, regulation by the complement pathway, and responses to competence-stimulating peptide. Eight competence-stimulating peptide-dependent genes were identified, and their roles in biofilm formation and aggregation were examined by mutational analyses of the S. mutansUA159 strain. Of these eight genes, the inactivation of the putative hemolysin III family SMU.940 gene of S. mutansUA159 promoted rapid dextran-dependent aggregation and biofilm formation in tryptic soy broth without dextrose (TSB) with 0.25% glucose and slightly reduced biofilm formation in TSB with 0.25% sucrose. The SMU.940 mutant showed higher expression of GbpC and gbpC gene than wild-type. GbpC is known to be involved in the dextran-dependent aggregation of S. mutans. An SMU.940-gbpC double mutant strain was constructed in the SMU.940 mutant background. The gbpC mutation completely abolished the dextran-dependent aggregation of the SMU.940 mutant. In addition, the aggregation of the mutant was abrogated by dextranase. These findings suggest that SMU.940 controls GbpC expression, and contributes to the regulation of dextran-dependent aggregation and biofilm formation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Observed gas hydrate morphologies in marine sediment

    Energy Technology Data Exchange (ETDEWEB)

    Holland, M.; Schultheiss, P.; Roberts, J.; Druce, M. [Geotek Ltd., Daventry, Northamptonshire (United Kingdom)

    2008-07-01

    The morphology of gas hydrate in marine sediments determines the basic physical properties of the sediment-hydrate matrix and provides information regarding the formation of gas hydrate deposits, and the nature of the disruption that will occur on dissociation. Small-scale morphology is useful in estimating the concentrations of gas hydrate from geophysical data. It is also important for predicting their response to climate change or commercial production. Many remote techniques for gas hydrate detection and quantification depend on hydrate morphology. In this study, morphology of gas hydrate was examined in HYACINTH pressure cores from recent seagoing expeditions. Visual and infrared observations from non-pressurized cores were also used. The expeditions and pressure core analysis were described in detail. This paper described the difference between two types of gas hydrate morphologies, notably pore-filling and grain-displacing. Last, the paper addressed the impact of hydrate morphology. It was concluded that a detailed morphology of gas hydrate is an essential component for a full understanding of the past, present, and future of any gas hydrate environment. 14 refs., 4 figs.

  13. 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...

  14. 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.

  15. 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

  16. Surface Morphology Diagram for Cylinder-Forming Block Copolymer Thin Films

    International Nuclear Information System (INIS)

    Zhang, Xiaohua; Berry, Brian C.; Yager, Kevin G.; Kim, Sangcheol; Jones, Ronald L.; Satija, Sushil; Pickel, Deanna L.; Douglas, Jack F.; Karim, Alamgir

    2008-01-01

    We investigate the effect of annealing temperature (T), film thickness (hf) on the surface morphology of flow coated films of a cylinder forming block copolymer, poly (styrene-block-methyl methacrylate) (PS-b-PMMA). Surface morphology transitions from a perpendicular to a parallel cylinder orientation with respect to the substrate with increasing hf are observed in these model 'frustrated-interaction' films where the substrate interaction is preferential for one of the blocks (PMMA) and nearly neutral for the other interface (polymer-air). In these films a transition occurs from cylinders oriented parallel to the substrate to a mixed or 'hybrid' state where the two orientations coexist followed by a transition to cylinders oriented perpendicularly to the polymer-air interface for larger hf. The characteristic values of hf defining these surface morphological transitions depend on T and we construct a surface morphology diagram as a function of hf and T. The surface morphology diagram is found to depend on the method of film formation (flow coated versus spun cast films) so non-equilibrium effects evidently have a large effect on the surface pattern morphology. In particular, the residual solvent within the film (quantified by neutron reflectivity measurements) in the context of physics of glass-formation can have a large effect on the surface morphology diagram

  17. Time Dependent Assessment of Morphological Changes: Leukodepleted Packed Red Blood Cells Stored in SAGM

    Directory of Open Access Journals (Sweden)

    Ibrahim Mustafa

    2016-01-01

    Full Text Available Usually packed red blood cells (pRBCs require specific conditions in storage procedures to ensure the maximum shelf life of up to 42 days in 2–6°C. However, molecular and biochemical consequences can affect the stored blood cells; these changes are collectively labeled as storage lesions. In this study, the effect of prolonged storage was assessed through investigating morphological changes and evaluating oxidative stress. Samples from leukodepleted pRBC in SAGM stored at 4°C for 42 days were withdrawn aseptically on day 0, day 14, day 28, and day 42. Morphological changes were observed using scanning electron microscopy and correlated with osmotic fragility and hematocrit. Oxidative injury was studied through assessing MDA level as a marker for lipid peroxidation. Osmotic fragility test showed that extended storage time caused increase in the osmotic fragility. The hematocrit increased by 6.6% from day 0 to day 42. The last 2 weeks show alteration in the morphology with the appearance of echinocytes and spherocytes. Storage lesions and morphological alterations appeared to affect RBCs during the storage period. Further studies should be performed to develop strategies that will aid in the improvement of stored pRBC quality and efficacy.

  18. [Physical, chemical and morphological urine examination guidelines for the Analytical Phase from the Intersociety Urinalysis Group].

    Science.gov (United States)

    Manoni, Fabio; Gessoni, Gianluca; Fogazzi, Giovanni Battista; Alessio, Maria Grazia; Caleffi, Alberta; Gambaro, Giovanni; Epifani, Maria Grazia; Pieretti, Barbara; Perego, Angelo; Ottomano, Cosimo; Saccani, Graziella; Valverde, Sara; Secchiero, Sandra

    2016-01-01

    With these guidelines the Intersociety Urinalysis Group (GIAU) aims to stimulate the following aspects: Improvement and standardization of the analytical approach to physical, chemical and morphological urine examination (ECMU). Improvement of the chemical analysis of urine with particular regard to the reconsideration of the diagnostic significance of the parameters that are traditionally evaluated in dipstick analysis together with an increasing awareness of the limits of sensitivity and specificity of this analytical method. Increase the awareness of the importance of professional skills in the field of urinary morphology and the relationship with the clinicians. Implement a policy of evaluation of the analytical quality by using, in addition to traditional internal and external controls, a program for the evaluation of morphological competence. Stimulate the diagnostics industry to focus research efforts and development methodology and instrumental catering on the needs of clinical diagnosis. The hope is to revalue the enormous diagnostic potential of 'ECMU, implementing a urinalysis on personalized diagnostic needs for each patient. Emphasize the value added to ECMU by automated analyzers for the study of the morphology of the corpuscular fraction urine. The hope is to revalue the enormous potential diagnostic of 'ECMU, implementing a urinalysis on personalized diagnostic needs that each patient brings with it.

  19. SDF7, a group of Scoparia dulcis Linn. derived flavonoid compounds, stimulates glucose uptake and regulates adipocytokines in 3T3-F442a adipocytes.

    Science.gov (United States)

    Beh, Joo Ee; Khoo, Li Teng; Latip, Jalifah; Abdullah, Mohd Paud; Alitheen, Noorjahan Baru Mohamed; Adam, Zainah; Ismail, Amin; Hamid, Muhajir

    2013-10-28

    Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes. Morphology and lipid accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated with different concentrations of SDF7 and rosiglitazone were examined followed by the evaluation of glucose uptake activity expressions of insulin signalling downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four cellular fractions (plasma membrane, cytosol, high density microsome and low density microsome). Next, the expression level of adipocytokines (TNF-α, adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of 3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of adiponectin and PPAR-γ of 3T3-F442a adipocytes were induced and compared with basal concentration. It was found that SDF7 was able to induce adipocytes differentiation with great extends of morphological changes, lipid synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport on 3T3-F442a adipocytes are found to be dose independent, time-dependent and plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be able to suppress TNF-α and leptin expressions that were mediated by 3T3-F442a adipocytes, while stimulated adiponectin secretion on the cells. There was a significant expression (p<0.01) of protein kinase C and small G protein TC10 on 3T3-F442a adipocytes

  20. Dose-dependent effects of exogenous gonadotrophins on the ...

    African Journals Online (AJOL)

    We compared the serwn levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and hwnan chorionic gonadotrophin (HCG).

  1. Effect of morphology on the non-ohmic conduction in ZnO nanostructures

    Science.gov (United States)

    Praveen, E.; Jayakumar, K.

    2016-05-01

    Nanostructures of ZnO is synthesized with nanoflower like morphology by simple wet chemical method. The structural, morphological and electrical characterization have been carried out. The temperature dependent electrical characterization of ZnO pellets of thickness 1150 µm is made by the application of 925MPa pressure. The morphological dependence of non-ohmic conduction beyond some arbitrary tunneling potential and grain boundary barrier thickness is compared with the commercially available bulk ZnO. Our results show the suitability of nano-flower like ZnO for the devices like sensors, rectifiers etc.

  2. Morphological changes in human melanoma cells following irradiation with thermal neutrons.

    Science.gov (United States)

    Barkla, D H; Allen, B J; Brown, J K; Mountford, M; Mishima, Y; Ichihashi, M

    1989-01-01

    Morphological changes in two human melanoma cell lines, MM96 and MM418, following irradiation with thermal neutrons, were studied using light and electron microscopy. The results show that the response of human malignant melanoma cells to neutron irradiation is both cell line dependent and dose dependent, and that in any given cell line, some cells are more resistant to irradiation than others, thus demonstrating heterogeneity in respect to radiosensitivity. Cells repopulating MM96 flasks after irradiation were morphologically similar to the cells of origin whereas in MM418 flasks cells differentiated into five morphologically distinct subgroups and showed increased melanization. The results also show that radiation causes distinctive morphological patterns of damage although ultrastructural changes unique to the high LET particles released from boron 10 neutron capture are yet to be identified.

  3. Morphological changes in human melanoma cells following irradiation with thermal neutrons

    International Nuclear Information System (INIS)

    Barkla, D.H.; Allen, B.J.; Brown, J.K.; Mountford, M.; Mishima, Y.; Ichihashi, M.

    1989-01-01

    Morphological changes in two human melanoma cell lines, MM96 and MM418, following irradiation with thermal neutrons, were studied using light and electron microscopy. The results show that the response of human malignant melanoma cells to neutron irradiation is both cell line dependent and dose dependent, and that in any given cell line, some cells are more resistant to irradiation than others, thus demonstrating heterogeneity in respect to radiosensitivity. Cells repopulating MM96 flasks after irradiation were morphologically similar to the cells of origin whereas in MM418 flasks cells differentiated into five morphologically distinct subgroups and showed increased melanization. The results also show that radiation causes distinctive morphological patterns of damage although ultrastructural changes unique to the high LET particles released from boron 10 neutron capture are yet to be identified

  4. The effects of prolonged oral administration of gold nanoparticles on the morphology of hematopoietic and lymphoid organs

    Science.gov (United States)

    Bucharskaya, Alla B.; Pakhomy, Svetlana S.; Zlobina, Olga V.; Maslyakova, Galina N.; Navolokin, Nikita A.; Matveeva, Olga V.; Khlebtsov, Boris N.; Bogatyrev, Vladimir A.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

    2017-02-01

    Currently, the usage of gold nanoparticles as photosensitizers and immunomodulators for plasmonic photothermal therapy has attracted a great attention of researches and end-users. In our work, the influence of prolonged peroral administration of gold nanoparticles (GNPs) with different sizes on the morphological changes of hematopoietic and lymphoid organs was investigated. The 24 white outbred male rats weighing 180-220 g were randomly divided into groups and administered orally for 30 days the suspension of gold nanospheres with diameters of 2, 15 and 50 nm at a dosage of 190 μg/kg of animal body weight. To prevent GNPs aggregation in a tissue and enhance biocompatibility, they were functionalized with thiolated polyethylene glycol. The withdrawal of the animals from the experiment and sampling of spleen, lymph nodes and bone marrow tissues for morphological study were performed a day after the last administration. In the spleen the boundary between the red and white pulp was not clearly differ in all experimental groups, lymphoid follicles were significantly increased in size, containing bright germinative centers represented by large blast cells. The stimulation of lymphocyte and myelocytic series of hematopoiesis was recorded at morphological study of the bone marrow. The number of immunoblasts and large lymphocytes was increased in all structural zones of lymph nodes. The more pronounced changes were found in the group with administration of 15 nm nanoparticles. Thus, the morphological changes of cellular components of hematopoietic organs have size-dependent character and indicate the activation of the migration, proliferation and differentiation of immune cells after prolonged oral administration of GNPs.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Kazuya; Yamamura, Chiaki; Tabata, Ken-ichi [Laboratory of Pharmacoinformatics, Graduate School of Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan); Fujita, Norihisa, E-mail: nori@ph.ritsumei.ac.jp [Laboratory of Pharmacoinformatics, Graduate School of Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan); School of Pharmacy, Ristumeikan University, Kusatsu, Shiga 525-8577 (Japan)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Expression of GPR174 in CHO cells induces morphological changes and proliferation delay. Black-Right-Pointing-Pointer These are due to increase in intracellular cAMP concentration. Black-Right-Pointing-Pointer Lysophosphatidylserine was identified to stimulate GPR174 leading to activate ACase. Black-Right-Pointing-Pointer The potencies of fatty acid moiety on LysoPS were oleoyl Greater-Than-Or-Slanted-Equal-To stearoyl > palmitoyl. Black-Right-Pointing-Pointer We propose that GPR174 is a lysophosphatidylserine receptor. -- Abstract: We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delay of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of G{alpha}{sub s} protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with G{alpha}{sub s}, and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation.

  10. 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.

  11. Alterations of morphology of lymphoid organs and peripheral blood indicators under the influence of gold nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Alla B. Bucharskaya

    2016-01-01

    Full Text Available At present, gold nanoparticles (GNPs are widely used in biomedical applications such as cancer diagnostics and therapy. Accordingly, the potential toxicity hazards of these nanomaterials and human safety concerns are gaining significant attention. Here, we report the effects of prolonged peroral administration of GNPs with different sizes (2, 15 and 50nm on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals. The experiment was conducted on 24 white mongrel male rats weighing 180–220g, gold nanospheres sizes 2, 15 and 50nm were administered orally for 15 days at a dosage of 190μg/kg of animal body weight. The GNPs were conjugated with polyethylene glycol to increase their biocompatibility and bioavailability. The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood, especially pronounced after administration of GNPs with size of 50nm. The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow. The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes, which were showed as the increasing number of immunoblasts and large lymphocytes. The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration, proliferation and differentiation of immune cells indicate the presence of immunostimulation effect of GNPs.

  12. 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...

  13. In situ Raman spectroscopy of LiFePO4: size and morphology dependence during charge and self-discharge.

    Science.gov (United States)

    Wu, Jing; Dathar, Gopi Krishna Phani; Sun, Chunwen; Theivanayagam, Murali G; Applestone, Danielle; Dylla, Anthony G; Manthiram, Arumugam; Henkelman, Graeme; Goodenough, John B; Stevenson, Keith J

    2013-10-25

    Previous studies of the size dependent properties of LiFePO4 have focused on the diffusion rate or phase transformation pathways by bulk analysis techniques such as x-ray diffraction (XRD), neutron diffraction and electrochemistry. In this work, in situ Raman spectroscopy was used to study the surface phase change during charge and self-discharge on a more localized scale for three morphologies of LiFePO4: (1) 25 ± 6 nm width nanorods, (2) 225 ± 6 nm width nanorods and (3) ∼2 μm porous microspheres. Both the large nanorod and microsphere geometries showed incomplete delithiation at the end of charge, which was most likely caused by anti-site defects along the 1D diffusion channels in the bulk of the larger particles. Based on the in situ Raman measurements, all of the morphologies studied exhibited self-discharge with time. Among them, the smallest FePO4 particles self-discharged (lithiated) the fastest. While nanostructuring LiFePO4 can offer advantages in terms of lowering anti-site defects within particles, it also creates new problems due to high surface energies that allow self-discharge. The in situ Raman spectroscopy also showed that carbon coating did not provide significant improvement to the stability of the lithiated particles.

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. Mechanisms of magnetic stimulation of central nervous system neurons.

    Directory of Open Access Journals (Sweden)

    Tamar Pashut

    2011-03-01

    Full Text Available Transcranial magnetic stimulation (TMS is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS.

  19. Mechanisms of magnetic stimulation of central nervous system neurons.

    Science.gov (United States)

    Pashut, Tamar; Wolfus, Shuki; Friedman, Alex; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2011-03-01

    Transcranial magnetic stimulation (TMS) is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS) is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS) with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS.

  20. Size- and morphology-dependent optical properties of ZnS:Al one-dimensional structures

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xianghua, E-mail: xhzeng@yzu.edu.cn; Yan, Shunjun; Cui, Jieya; Liu, Hongfei; Dong, Jing; Xia, Weiwei; Zhou, Min; Chen, Haitao [Yangzhou University, School of Physics Science and Technology & Institute of Optoelectronic Technology (China)

    2015-04-15

    Typical morphology substrates can improve the efficiency of surface-enhanced Raman scattering; the need for SERS substrates of controlled morphology requires an extensive study. In this paper, one-dimensional ZnS:Al nanostructures with the width of approximately 300 nm and the length of tens um, and micro-scale structures with the width of several um and the length of tens um were synthesized via thermal evaporation on Au-coated silicon substrates and were used to study their size effects on Raman scattering and photoluminescent spectra. The photoluminescence spectra reveal the strongest green emission at a 5 at% Al source, which originates from the Al-dopant emission. The Raman spectra reveal that the size and morphology of the ZnS:Al nanowires greatly influences the Raman scattering, whereas the Al-dopant concentration has a lesser effect on the Raman scattering. The observed Raman scattering intensity of the saw-like ZnS:Al nanowires with the width of tens nm was eight times larger than that of the bulk sample. The enhanced Raman scattering can be regarded as multiple scattering and weak exciton—phonon coupling. The branched one-dimensional nanostructure can be used as an ideal substrate to enhance Raman scattering.

  1. Electric field stimulation through a substrate influences Schwann cell and extracellular matrix structure

    Science.gov (United States)

    Nguyen, Hieu T.; Wei, Claudia; Chow, Jacqueline K.; Nguy, Lindsey; Nguyen, Hieu K.; Schmidt, Christine E.

    2013-08-01

    Objective. Electric field (EF) stimulation has been used to cue cell growth for tissue engineering applications. In this study, we explore the electrical parameters and extracellular mechanisms that elicit changes in cell behavior when stimulated through the substrate. Approach. Rat Schwann cell morphology was compared when exposed to EF through the media or a conductive indium tin oxide substrate. Ionic and structural effects were then analyzed on Matrigel and collagen I, respectively. Main results. When stimulating through media, cells had greater alignment perpendicular to the EF with higher current densities (106 mA cm-2 at 245 mV mm-1), and reached maximum alignment within 8 h. Stimulation through the substrate with EF (up to 110 mV mm-1) did not affect Schwann cell orientation, however the EF caused extracellular matrix (ECM) coatings on substrates to peel away, suggesting EF can physically change the ECM. Applying alternating current (ac) 2-1000 Hz signals through the media or substrate both caused cells to flatten and protrude many processes, without preferential alignment. Matrigel exposed to a substrate EF of 10 mV mm-1 for 2 h had a greater calcium concentration near the cathode, but quickly dissipated when the EF was removed. Schwann cells seeded 7 d after gels were exposed to substrate EF still aligned perpendicular to the EF direction. Microscopy of collagen I exposed to substrate EF shows alignment and bundling of fibrils. Significance. These findings demonstrate EF exposure can control Schwann cell alignment and morphology, change ECM bulk/surface architecture, and align ECM structures.

  2. 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

  3. Characteristics of the electrical response of YBCO films with different morphologies to optical irradiation

    International Nuclear Information System (INIS)

    Frack, E.K.; Madhavrao, L.; Patl, R.; Drake, R.E.; Radparvar, M.

    1991-01-01

    The authors have fabricated YBCO films of varying thicknesses (300 Angstrom - 3000 Angstrom) and morphologies, and measured their electrical response to optical radiation. This paper reports on these measurements, emphasizing the dependence on temperature, light chopping frequency, and cryogenic environment. The temperature dependence of the film resistance is determined in part by the film morphology. This morphology may be represented by a simple model consisting of a two-dimensional array of coupled grains. The magnitude of the bolometric response correlates as expected with the sharpness of the superconducting transition. The increased response observed at lower temperatures (non-equilibrium) correlates with the temperature dependence of the resistance above the transition

  4. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

    Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  5. 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.

  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. 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. 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.

  9. 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.

  10. 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

  11. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  12. 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

  13. 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

  14. 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.

  15. Substrate dependent morphologies of self-assembled nanocrystalline manganite films: An atomic force microscopy study

    International Nuclear Information System (INIS)

    Kale, S.N.; Mona, J.; Ganesan, V.; Choudhary, R.J.; Phase, D.M.

    2009-06-01

    Thin films of La 0 .7Sr 0 .3MnO 3 (LSMO) have been deposited on different substrates: Si (001), Al 2 O 3 (AlO) (0001) and LaAlO 3 (LAO) (001), using a pulsed laser deposition system. 100 nm films have been deposited at substrate temperature of 700 deg C and oxygen partial pressure of 400 mTorr. X-Ray diffraction analysis shows a polycrystalline growth of both layers on Si and Al 2 O 3 substrates, while a c-axis oriented growth on LAO substrate. Atomic force microscopy images exhibit interesting island-like morphology of grain size ∼ 250 nm on Si substrate. Similar morphology with much smaller (∼ 150 nm), closely packed islands are seen to grow on AlO substrate. Films on LAO show comparatively a smooth morphology with the grains size less than 100 nm, decorated by characteristic depressions at the grain boundaries. The formation of self-assembled nanostructures can be understood on the basis of film-substrate lattice misfit, strains in the systems and eventual growth of the films to attain energy minimization (author)

  16. Controlling morphology and chain aggregation in semiconducting conjugated polymers: the role of solvent on optical gain in MEH-PPV.

    Science.gov (United States)

    Lampert, Zach E; Reynolds, C Lewis; Papanikolas, John M; Aboelfotoh, M Osama

    2012-10-25

    We report the results of a detailed investigation that addresses the influence of polymer morphology and chain aggregation, as controlled by the chemical nature of the solvent, on the optical gain properties of the conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV). Using the variable stripe length technique in the picosecond regime, we have extensively studied the optical gain performance of asymmetric planar waveguides formed with thin MEH-PPV films spin-cast from concentrated chlorobenzene (CB) and tetrahydrofuran (THF) solutions onto thermally oxidized silicon substrates. CB and THF solvents were chosen based on their known ability to promote and effectively limit aggregate formation, respectively. Very large net gain coefficients are demonstrated, reaching values of 330 and 365 cm(-1), respectively, when optically pumping the waveguides with a maximum energy density of 85 μJ/cm(2). Our results clearly demonstrate that polymer morphology, and hence, the chain conformation dependence of the degree of aggregation in the films as controlled by the solvent, has minimal impact on the net gain. Moreover, the waveguides exhibit low loss coefficients of 10-20 cm(-1) at the ASE wavelength. These results question the importance of polymer morphology and aggregate formation in polymer-based optical devices operating at high excitation densities in the stimulated emission regime as would be characteristic of lasers and optical amplifiers.

  17. Dose- and time-dependent radiation inhibition of RNA and glycosaminoglycan synthesis in embryonic cartilage: an in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, M.; Thierens, H.; De Ridder, L. (Ghent Rijksuniversiteit (Belgium))

    1990-05-01

    Radiation effects on the RNA and glycosaminoglycan (GAG) synthesis of embryonic cartilaginous tibiae were studied in vitro during a 4- or 7-day culture period. Before culture, tibiae received single radiation doses of 20, 50 or 100 Gy. A limited, dose-dependent immediate effect on RNA and GAG synthesis was found. This effect was unchanged for 2 days. After this period a time-dependent delayed effect was observed. For each radiation dose, and for each precursor, the same time-related pattern was found. At the end of the culture period acid phosphatase activity, an early indicator of apoptosis, was higher in irradiated tibiae than in controls. No other morphological ultrastructural differences were observed at this time. The authors conclude that metabolic alterations are probably due to stimulation of initial stages of the apoptotic process in the irradiated cartilage cells. (author).

  18. Functional and morphological alterations of the stomach in case of irradiation of the para-aortic area

    Energy Technology Data Exchange (ETDEWEB)

    Beyer-Enke, S.A.; Gladisch, R.; Heine, M.; Georgi, M.

    1987-12-01

    Six assays were conducted in order to determine some functional and morphological parameters of the gastric mucosa in patients who underwent Co/sup 60/ irradiations of the para-aortic area. Slight as well as marked morphological alterations were observed whereas the functional alterations were found to be marked in all cases. Basal gastric secretion and serum gastrin level showed a continous reduction, however, in case of severe gastritis the stimulated secretion was increased. A possible correlation with increased tissue histamine levels is discussed.

  19. 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

  20. [Vestibular compensation studies]. [Vestibular Compensation and Morphological Studies

    Science.gov (United States)

    Perachio, Adrian A. (Principal Investigator)

    1996-01-01

    The following topics are reported: neurophysiological studies on MVN neurons during vestibular compensation; effects of spinal cord lesions on VNC neurons during compensation; a closed-loop vestibular compensation model for horizontally canal-related MVN neurons; spatiotemporal convergence in VNC neurons; contributions of irregularly firing vestibular afferents to linear and angular VOR's; application to flight studies; metabolic measures in vestibular neurons; immediate early gene expression following vestibular stimulation; morphological studies on primary afferents, central vestibular pathways, vestibular efferent projection to the vestibular end organs, and three-dimensional morphometry and imaging.

  1. Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses.

    Science.gov (United States)

    Zeituni, Erin M; Wilson, Meredith H; Zheng, Xiaobin; Iglesias, Pablo A; Sepanski, Michael A; Siddiqi, Mahmud A; Anderson, Jennifer L; Zheng, Yixian; Farber, Steven A

    2016-11-04

    Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery. Dietary and pharmacological manipulation of zebrafish larvae demonstrated that these subcellular changes are specific to triglyceride absorption. The transcriptional changes that occur simultaneously with these morphological changes were determined using RNA sequencing, revealing a cohort of up-regulated genes associated with lipid droplet formation and lipid transport via lipoprotein particles. Using a microsomal triglyceride transfer protein (MTP) inhibitor to block β-lipoprotein particle formation, we demonstrate that the transcriptional response to a high-fat meal is associated with the transfer of ER triglyceride to nascent β-lipoproteins, possibly through the activation of Creb3l3/cyclic AMP-responsive element-binding protein. These data suggest that a transient increase in ER lipids is the likely mediator of the initial physiological response of intestinal enterocytes to dietary lipid. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses*

    Science.gov (United States)

    Zeituni, Erin M.; Wilson, Meredith H.; Zheng, Xiaobin; Iglesias, Pablo A.; Sepanski, Michael A.; Siddiqi, Mahmud A.; Anderson, Jennifer L.; Zheng, Yixian; Farber, Steven A.

    2016-01-01

    Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery. Dietary and pharmacological manipulation of zebrafish larvae demonstrated that these subcellular changes are specific to triglyceride absorption. The transcriptional changes that occur simultaneously with these morphological changes were determined using RNA sequencing, revealing a cohort of up-regulated genes associated with lipid droplet formation and lipid transport via lipoprotein particles. Using a microsomal triglyceride transfer protein (MTP) inhibitor to block β-lipoprotein particle formation, we demonstrate that the transcriptional response to a high-fat meal is associated with the transfer of ER triglyceride to nascent β-lipoproteins, possibly through the activation of Creb3l3/cyclic AMP-responsive element-binding protein. These data suggest that a transient increase in ER lipids is the likely mediator of the initial physiological response of intestinal enterocytes to dietary lipid. PMID:27655916

  3. Fast algorithm for Morphological Filters

    International Nuclear Information System (INIS)

    Lou Shan; Jiang Xiangqian; Scott, Paul J

    2011-01-01

    In surface metrology, morphological filters, which evolved from the envelope filtering system (E-system) work well for functional prediction of surface finish in the analysis of surfaces in contact. The naive algorithms are time consuming, especially for areal data, and not generally adopted in real practice. A fast algorithm is proposed based on the alpha shape. The hull obtained by rolling the alpha ball is equivalent to the morphological opening/closing in theory. The algorithm depends on Delaunay triangulation with time complexity O(nlogn). In comparison to the naive algorithms it generates the opening and closing envelope without combining dilation and erosion. Edge distortion is corrected by reflective padding for open profiles/surfaces. Spikes in the sample data are detected and points interpolated to prevent singularities. The proposed algorithm works well both for morphological profile and area filters. Examples are presented to demonstrate the validity and superiority on efficiency of this algorithm over the naive algorithm.

  4. [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.

  5. 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 ...

  6. 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

  7. Nuclear stimulated desorption as a potential tool for surface study

    International Nuclear Information System (INIS)

    Nir, Dror.

    1993-03-01

    The described research work constitutes a base for an experimental method to be implemented in the study of solid surfaces. Nuclear Stimulated Desorption (NSD) is a new mode of experimentation in thin film and surface physics. It Is based on the interplay between nuclear phenomena (reactions and spontaneous decays), and atomic - scale induced effects on surfaces and very thin films. One may distinguish between two generically different relationships between the two. First, the dynamics of the nuclear reaction -primarily the recoil of the nucleus - may effect the position of the atom or molecule containing it. Second, the nuclear reaction (or decay) may serve as an analytical indicator of the whereabouts of the atom, or molecule, in question. In nuclear stimulated desorption, both thee aspects combine in an essential way. Namely, one employs a series of two consecutive decays (normally weak decays or isomeric transition) . The first of these decays causes the nucleus to desorb from a surface onto which it had been placed; the second serves to determine the position of the daughter and thereby the characteristics of the primary desorption . The essential feature in NSD is that it occurs almost exclusively from the outermost surface layer. This is because we choose to work with nuclei whose recoil energy Is of the same order of magnitude of the binding energy of the atom to the surface . Furthermore, the desorption probability and its angular (and temporal) characteristics, depend on the features (topology, morphology) of its immediate neighborhood. This work describes experiments which were designed to give relevant, phenomenological information about the outgoing flux of the radioactive daughters (for specifically chosen nuclear species) , and in particular the magnitude of the flux, its time dependence and its charged state. In addition. the basic phenomena itself is being distinguished from competing processes (thermal desorption, in particular). We will now

  8. Formation of broccoli-like morphology of tantalum powder

    International Nuclear Information System (INIS)

    Suzuki, Ryosuke O.; Baba, Masahiko; Ono, Youhei; Yamamoto, Kosuke

    2005-01-01

    'Broccoli'-like morphology of Ta powder was found when Ca reduces Ta 2 O 5 in the molten CaCl 2 . It consisted of fine particles and branches, and it was different from the conventional spherical particles. The formation of this morphology depended on the stacking methods of the starting materials. Eight types of filling methods proved that the branch was formed when the CaO-enriched region was locally produced near the oxide

  9. Release of superoxide and change in morphology by neutrophils in response to phorbol esters: antagonism by inhibitors of calcium-binding proteins

    Science.gov (United States)

    1985-01-01

    The ability of phorbol derivatives to function as stimulating agents for superoxide (O2-) release by guinea pig neutrophils has been evaluated and compared to the known ability of each compound to activate protein kinase C. Those that activate the kinase also stimulate O2- release, while those that are inactive with respect to the kinase have no effect on O2- release. The same correlation was observed with respect to the ability of phorbol esters to induce morphological changes in neutrophils, i.e., vesiculation and reduction in granule content. Certain phenothiazines and naphthalene sulfonamides that are known antagonists of calcium-binding proteins blocked both phorbol ester-induced O2- release and morphological changes in these cells. PMID:2993312

  10. Modulation of the expression of chondroitin sulfate proteoglycan in stimulated human monocytes

    International Nuclear Information System (INIS)

    Uhlin-Hansen, L.; Eskeland, T.; Kolset, S.O.

    1989-01-01

    Proteoglycan biosynthesis was studied in human monocytes and monocyte-derived macrophages (MDM) after exposure to typical activators of the monocyte/macrophage system: interferon-gamma (IFN-gamma), lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). By morphological examination, both monocytes and MDM were stimulated by these activators. Treatment with IFN-gamma resulted in a slight decrease in the expression of [35S]chondroitin sulfate proteoglycan (CSPG) in both monocytes and MDM, whereas LPS treatment increased the [35S]CSPG expression 1.8 and 2.2 times, respectively. PMA, in contrast, decreased the CSPG expression 0.4 times in monocytes, whereas MDM were stimulated to increase the biosynthesis 1.9 times. An increase in the sulfate density of the chondroitin sulfate chains was evident following differentiation of monocytes into MDM due to the expression of disulfated disaccharide units of the chondroitin sulfate E type (CS-E). However, monocytes exposed to PMA did also express disaccharides of the chondroitin sulfate E type. Furthermore, the expression of CS-E in MDM was increased 2 times following PMA treatment. An inactive phorbol ester, phorbol 12,13-diacetate, did not affect the expression of CS-E in either monocytes or MDM when compared with control cultures, suggesting that protein kinase C-dependent signal pathways may be involved in the regulation of sulfation of CSPG. Exposure to LPS or IFN-gamma did not lead to any changes in the sulfation of the chondroitin sulfate chains

  11. 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...

  12. 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.

  13. [Comparative studies on the toxicity of various dielectrics--petroleum derivatives used in the electroerosion technic. V. Functional, morphological and cytoenzymatic changes in the kidneys of rats chronically exposed to petroleum hydrocarbons].

    Science.gov (United States)

    Starek, A; Kamiński, M

    1982-01-01

    The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.

  14. Comparative studies on the toxicity of various dielectrics--petroleum derivatives used in the electroerosion technic. V. Functional, morphological and cytoenzymatic changes in the kidneys of rats chronically exposed to petroleum hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Starek, A.; Kaminski, M.

    1982-01-01

    The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.

  15. Morphological dependency of cutaneous blood flow and sweating during compensable heat stress when heat-loss requirements are matched across participants.

    Science.gov (United States)

    Notley, Sean R; Park, Joonhee; Tagami, Kyoko; Ohnishi, Norikazu; Taylor, Nigel A S

    2016-07-01

    Human heat loss is thought, in part, to be morphologically related. It was therefore hypothesized that when heat-loss requirements and body temperatures were matched, that the mass-specific surface area alone could significantly explain both cutaneous vascular and sudomotor responses during compensable exercise. These thermoeffector responses were examined in 36 men with widely varying mass-specific surface areas (range, 232.3-292.7 cm(2)/kg), but of similar age, aerobic fitness, and adiposity. Subjects completed two trials under compensable conditions (28.1°C, 36.8% relative humidity), each involving rest (20 min) and steady-state cycling (45 min) at two matched metabolic heat-production rates (light, ∼135 W/m(2); moderate, ∼200 W/m(2)). Following equivalent mean body temperature changes, forearm blood flow and vascular conductance (r = 0.63 and r = 0.65) shared significant, positive associations with the mass-specific surface area during light work (P < 0.05), explaining ∼45% of the vasomotor variation. Conversely, during light and moderate work, whole body sweat rate, as well as local sweat rate and sudomotor sensitivity at three of four measured sites, revealed moderate, negative relationships with the mass-specific surface area (correlation coefficient range -0.37 to -0.73, P < 0.05). Moreover, those relationships could uniquely account for between 10 and 53% of those sweating responses (P < 0.05). Therefore, both thermoeffector responses displayed a significant morphological dependency in the presence of equivalent thermoafferent drive. Indeed, up to half of the interindividual variation in these effector responses could now be explained through morphological differences and the first principles governing heat transfer. Copyright © 2016 the American Physiological Society.

  16. Does the hearing sensitivity in thorny catfishes depend on swim bladder morphology?

    Directory of Open Access Journals (Sweden)

    Angelika Zebedin

    Full Text Available BACKGROUND: Thorny catfishes exhibit large variations in swim bladder morphology. These organs are of different sizes, forms and may have simple or branched diverticula. The swim bladder plays an important role in otophysans because it enhances their hearing sensitivity by transmitting sound pressure fluctuations via ossicles to the inner ear. METHODOLOGY/PRINCIPAL FINDINGS: To investigate if a form-function relationship exists, the swim bladder morphology and hearing ability were analyzed in six species. The morphology was quantified by measuring the length, width and height and calculating a standardized swim bladder length (sSBL, which was then used to calculate the relative swim bladder length (rSBL. Hearing was measured using the auditory evoked potential (AEP recording technique. Two species had simple apple-shaped and four species heart-shaped (cordiform bladders. One of the latter species had short unbranched diverticula on the terminal margin, two had a secondary bladder and two had many long, branched diverticula. The rSBL differed significantly between most of the species. All species were able to detect frequencies between 70 Hz and 6 kHz, with lowest thresholds found between 0.5 and 1 kHz (60 dB re 1 µPa. Hearing curves were U-shaped except in Hemidoras morrisi in which it was ramp-like. Mean hearing thresholds of species possessing smaller rSBLs were slightly lower (maximum 8.5 dB than those of species having larger rSBLs. CONCLUSIONS/SIGNIFICANCE: The current findings reveal a relationship between swim bladder form and its function among thorny catfishes. Relatively smaller swim bladders resulted in relatively better hearing. This is in contrast to a prior inter-familial study on catfishes in which species with large unpaired bladders possessed higher sensitivity at higher frequencies than species having tiny paired and encapsulated bladders.

  17. Reasons for betel quid chewing amongst dependent and non-dependent betel quid chewing adolescents: a school-based cross-sectional survey.

    Science.gov (United States)

    Hussain, Azmina; Zaheer, Sidra; Shafique, Kashif

    2018-05-09

    Betel quid (BQ) chewing in children is initiated in their adolescence. It is pivotal to understand adolescents' reasons behind chewing BQ. In this study, we aimed to evaluate the reasons for BQ chewing amongst adolescents using reasons for betel quid chewing scale (RBCS) and their associated dependency on it. This is a cross-sectional school based survey. Out of 2200 adolescents from 26 schools of Karachi, 874 BQ chewers were assessed for their reasons of BQ chewing and dependency on it. Regression analyses were employed to report crude and adjusted (after adjusting for all reasons of BQ chewing) effect sizes with 95% confidence interval and P-value was set significant at < 0.05. Students who believed that BQ chewing relaxes them (stimulation construct) were twice as likely to be dependent on BQ (OR = 2.36, 95% CI (1.20-4.65) as compared with others. Participants who thought it eases their decision making (stimulation construct), were sizably more likely to be dependent on BQ (OR = 9.65, 95% CI (4.15-22.43) than those who did not consider ease in decision making important. Adolescents who considered not chewing as rude (social/cultural construct), were thrice more likely to be dependent on BQ (OR = 2.50, 95% CI (1.11-5.63) than others. Stimulation remained fundamental chewing reason followed by social/cultural trigger amongst adolescents. Any future intervention may get favorable results if it addresses ways to overcome stimulation and social/cultural barriers that are strongly associated with BQ chewing and dependency.

  18. Decision-making style, nicotine and caffeine use and dependence.

    Science.gov (United States)

    Phillips, James G; Ogeil, Rowan P

    2015-11-01

    As therapeutic interventions are being developed utilising telehealth and mobile phones, it is important to understand how substance-dependent individuals will respond to offers of online assistance. The present paper considered the following: (1) how decision-making style is associated with use and dependence upon commonly used stimulants and (2) how it influences behavioural responses to electronic offers of further information about these drugs. An online survey examined patterns of nicotine and caffeine use, administered Severity of Dependence Scales for caffeine and nicotine and assessed decision-making style using the Melbourne Decision Making Questionnaire and mood using the Kessler Distress Scale. Upon completing these scales, the 181 participants with a mean age of 28.14 years were offered further information online. Stimulant dependence was associated with psychological distress. Caffeine dependence was linked to hypervigilance (panic). Decisional self-esteem varied with stimulant dependence and Kessler Distress Scale score. Participants with high decisional self-esteem declined electronic offers of further information. Confidence rather than defensive avoidance was a factor in reducing information-seeking behaviours on the Internet. Copyright © 2015 John Wiley & Sons, Ltd.

  19. 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.

  20. 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

  1. 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...

  2. 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

  3. Formation of broccoli-like morphology of tantalum powder

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Ryosuke O [Department of Energy Science and Technology, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan); Baba, Masahiko [Department of Energy Science and Technology, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan); Ono, Youhei [Department of Energy Science and Technology, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan); Yamamoto, Kosuke [Department of Energy Science and Technology, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan)

    2005-03-08

    'Broccoli'-like morphology of Ta powder was found when Ca reduces Ta{sub 2}O{sub 5} in the molten CaCl{sub 2}. It consisted of fine particles and branches, and it was different from the conventional spherical particles. The formation of this morphology depended on the stacking methods of the starting materials. Eight types of filling methods proved that the branch was formed when the CaO-enriched region was locally produced near the oxide.

  4. Effects of luminal nutrient absorption, intraluminal physical stimulation, and intravenous parenteral alimentation on the recovery responses of duodenal villus morphology following feed withdrawal in chickens.

    Science.gov (United States)

    Tarachai, P; Yamauchi, K

    2000-11-01

    The aim of this study was to clarify which of the following three factors induces villus morphological recovery best: enteral nutrient absorption, intraluminal physical stimulation, or intravenous parenteral alimentation. At 142 d, male White Leghorn chickens (Gallus gallus domesticus) were divided into eight groups of five birds each as follows: 1) access given ad libitum to a commercial layer mash diet (CP, 17.5%; ME, 2,830 kcal/kg) (control), 2) 5-d feed withdrawal (feed withdrawal), 3) 3-d feed withdrawal (3-FW), followed by refeeding the same diet as the control for 2 d (refeeding), 4) 3-FW followed by force-feeding enteral hyperalimentation (enteral), 5) 3-FW followed by force-feeding an indigestible (nonabsorbable) substance (kaolin), 6) 3-FW followed by force-feeding water for 2 d (force-fed control), 7) 3-FW followed by parenteral hyperalimentation (parenteral), and 8) 3-FW followed by no alimentation (sham control) for 2 d. In the refeeding and enteral groups, BW significantly recovered (P alimentation, but by enteral nutrient absorption.

  5. Effect of the microstructural morphology on UO{sub 2} powders

    Energy Technology Data Exchange (ETDEWEB)

    Ziouane, Y.; Lalleman, S.; Leturcq, G. [CEA, Centre de Marcoule, Nuclear Energy Division, RadioChemistry and Processes Department, SERA, LED, F-30207 Bagnols sur Ceze (France); Arab-Chapelet, B. [CEA, Centre de Marcoule, Nuclear Energy Division, RadioChemistry and Processes Department, SERA, LCAR, F-30207 Bagnols sur Ceze (France)

    2016-07-01

    Several UO{sub 2} powders with different morphologies were synthesized and characterized. Three different morphologies were synthesized thanks to sol-gel process (big heap of about 200 μm wide consisting of sintered crystallites) on the one hand, and to oxalic precipitations (one square platelet morphology and one hexagonal stick morphology) on the other hand. Significant differences in dissolution kinetics were observed. Therefore, the morphology of the powders was found to be a key parameter that has to be considered in the studies of UO{sub 2} dissolution kinetics. The second part of the study consists in dissolving in nitric acid in in the same operating conditions three UO{sub 2} powders having different crystallites sizes. It was shown that dissolution kinetics is dependent on the morphology at the micrometer scale but also on the powder oxygen stoichiometry. (authors)

  6. Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzumiya Junji

    2011-07-01

    Full Text Available Abstract Background Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP production by adjacent stromal cells. Its first Ig domain (ECI contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active. Methods The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production. Results ECI carrying a chitobiose unit, ECI-(GlcNAc 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man3(GlcNAc2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc2. Conclusions Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.

  7. Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers.

    Science.gov (United States)

    Lanjakornsiripan, Darin; Pior, Baek-Jun; Kawaguchi, Daichi; Furutachi, Shohei; Tahara, Tomoaki; Katsuyama, Yu; Suzuki, Yutaka; Fukazawa, Yugo; Gotoh, Yukiko

    2018-04-24

    Non-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorial volume, and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated in reeler and Dab1 conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite for the observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.

  8. Morphological type correlation between nearest neighbor pairs of galaxies

    Science.gov (United States)

    Yamagata, Tomohiko

    1990-01-01

    Although the morphological type of galaxies is one of the most fundamental properties of galaxies, its origin and evolutionary processes, if any, are not yet fully understood. It has been established that the galaxy morphology strongly depends on the environment in which the galaxy resides (e.g., Dressler 1980). Galaxy pairs correspond to the smallest scales of galaxy clustering and may provide important clues to how the environment influences the formation and evolution of galaxies. Several investigators pointed out that there is a tendency for pair galaxies to have similar morphological types (Karachentsev and Karachentseva 1974, Page 1975, Noerdlinger 1979). Here, researchers analyze morphological type correlation for 18,364 nearest neighbor pairs of galaxies identified in the magnetic tape version of the Center for Astrophysics Redshift Catalogue.

  9. Effects of in vitro hypoxia on depolarization-stimulated accumulation of inositol phosphates in synaptosomes

    International Nuclear Information System (INIS)

    Huang, H.M.; Gibson, G.E.

    1989-01-01

    The effects of potassium and in vitro histotoxic hypoxia on phosphatidylinositol turnover in rat cortical synaptosomes were determined. [2- 3 H] Inositol prelabelled rat synaptosomes were prepared from cerebral cortex slices that had been incubated with [2- 3 H] inositol. Depolarization with 60 mM KCl increased [2- 3 H] inositol phosphates in a time dependent manner. Depolarization with 60 mM KCl increased [2- 3 H]inositol trisphosphate transiently at 5 s. K + induced rapid formation of [2- 3 H] inositol monophosphate with time. One minute of hypoxia enhance sium-stimulate [2 3 H]inositol bisphosphate and maintained an elevated level for at least 5 min. K + stimulated gradual formation of [2- 3 H] inositol monophosphate with time. One minute of hypoxia enhanced potassium-stimulated [2- 3 H] inositol bisphosphate formation. However, 30 min of hypoxia impaired potassium-stimulated accumulation of [2- 3 H]inositol phosphates. The effects of histotoxic hypoxia were all dependent upon calcium in the medium and on K + -depolarization. Thus, hypoxia altered the K + induced accumulation of inositol phosphates in prelabelled synaptosomes in a time dependent, biphasic manner that was calcium dependent

  10. 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

  11. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat

    OpenAIRE

    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P. Andy; Sun, Tao

    2013-01-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral sei...

  12. 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

  13. T-wave morphology analysis of competitive athletes

    DEFF Research Database (Denmark)

    Hong, L; Andersen, Lars Juel; Graff, Claus

    2015-01-01

    BACKGROUND: T-wave morphology has been shown to be more sensitive than QT and QTc interval to describe repolarization abnormalities. The electrocardiogram (ECG) performed in athletes may manifest abnormalities, including repolarization alterations. The aim of this study was to investigate...... the characteristics of T-wave morphology features in athletes. METHODS: Eighty male elite athletes, consisting of 40 Tour de France cyclists (age 27±5years), 40 soccer players (age 26±6years) and 40 healthy men (age 27±5years) were included. RESULTS: Sinus bradycardia, left ventricular (LV) hypertrophy, incomplete...... interval, and repolarization features than the control group. CONCLUSIONS: T-wave morphology of athletes is different from non-athletes, depending of the sport. Decreased potassium current in cardiomyocytes associated with LVH may contribute to these changes....

  14. 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.

  15. Characterization of E-cadherin-dependent and -independent events in a new model of c-Fos-mediated epithelial-mesenchymal transition

    International Nuclear Information System (INIS)

    Mejlvang, Jakob; Kriajevska, Marina; Berditchevski, Fedor; Bronstein, Igor; Lukanidin, Eugene M.; Pringle, J. Howard; Mellon, J. Kilian; Tulchinsky, Eugene M.

    2007-01-01

    Fos proteins have been implicated in control of tumorigenesis-related genetic programs including invasion, angiogenesis, cell proliferation and apoptosis. In this study, we demonstrate that c-Fos is able to induce mesenchymal transition in murine tumorigenic epithelial cell lines. Expression of c-Fos in MT1TC1 cells led to prominent alterations in cell morphology, increased expression of mesenchymal markers, vimentin and S100A4, DNA methylation-dependent down-regulation of E-cadherin and abrogation of cell-cell adhesion. In addition, c-Fos induced a strong β-catenin-independent proliferative response in MT1TC1 cells and stimulated cell motility, invasion and adhesion to different extracellular matrix proteins. To explore whether loss of E-cadherin plays a role in c-Fos-mediated mesenchymal transition, we expressed wild-type E-cadherin and two different E-cadherin mutants in MT1TC1/c-fos cells. Expression of wild-type E-cadherin restored epithelioid morphology and enhanced cellular levels of catenins. However, exogenous E-cadherin did not influence expression of c-Fos-dependent genes, only partly suppressed growth of MT1TC1/c-fos cells and produced no effect on c-Fos-stimulated cell motility and invasion in matrigel. On the other hand, re-expression of E-cadherin specifically negated c-Fos-induced adhesion to collagen type I, but not to laminin or fibronectin. Of interest, mutant E-cadherin which lacks the ability to form functional adhesive complexes had an opposite, potentiating effect on cell adhesion to collagen I. These data suggest that cell adhesion to collagen I is regulated by the functional state of E-cadherin. Overall, our data demonstrate that, with the exception of adhesion to collagen I, c-Fos is dominant over E-cadherin in relation to the aspects of mesenchymal transition assayed in this study

  16. Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

    Science.gov (United States)

    Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

    2005-04-01

    Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

  17. 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.

  18. Magnetic anisotropy induced by crystallographic orientation and morphological alignment in directionally-solidified eutectic Mn-Sb alloy

    Energy Technology Data Exchange (ETDEWEB)

    Lou, Chang-Sheng [School of Materials Science and Engineering, Shenyang Ligong University, Shenyang 110159 (China); Key Laboratory of Electromagnetic Processing of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Liu, Tie, E-mail: liutie@epm.neu.edu.cn [Key Laboratory of Electromagnetic Processing of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Dong, Meng; Wu, Chun; Shao, Jian-Guo; Wang, Qiang [Key Laboratory of Electromagnetic Processing of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China)

    2017-02-15

    The influences of the crystallographic orientation and morphological alignment upon the magnetic anisotropic behavior of polycrystalline materials were investigated. Microstructures obtained in eutectic Mn-Sb alloys via directional solidification simultaneously displayed crystallographic orientation and morphological alignment. Both the crystallographic orientation and the morphological alignment were able to induce magnetic anisotropy in the alloys, wherein the influence of the crystallographic orientation and the morphological alignment upon the magnetic anisotropic behavior of the alloys strongly depended upon their directions and exhibited either mutual promotion or competition. These findings may provide useful guidance for the fabrication design of functional magnetic materials. - Highlights: • We study effects of orientation in crystal and morphology on magnetic anisotropy. • Both orientation in crystal and morphology can induce magnetic anisotropy. • Their effects depend on direction and exhibit either mutual promotion or competition.

  19. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Science.gov (United States)

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  20. 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.

  1. Reconstructing the Morphology of an Evolving Coronal Mass Ejection

    Science.gov (United States)

    2009-01-01

    694, 707 Wood, B. E., Howard, R. A ., Thernisien, A ., Plunkett, S. P., & Socker, D. G. 2009b, Sol. Phys., 259, 163 Wood, B. E., Karovska , M., Chen, J...Reconstructing the Morphology of an Evolving Coronal Mass Ejection B. E. Wood, R. A . Howard, D. G. Socker Naval Research Laboratory, Space Science...mission, we empirically reconstruct the time-dependent three-dimensional morphology of a coronal mass ejection (CME) from 2008 June 1, which exhibits

  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. 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.

  4. 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 ...

  5. 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

  6. Morphology control of brushite prepared by aqueous solution synthesis

    Directory of Open Access Journals (Sweden)

    T. Toshima

    2014-03-01

    Full Text Available Dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O, also known as brushite, is one of the important bioceramics due to not only diseases factors such as kidney stone and plaque formation but also purpose as fluoride insolubilization material. It is used medicinally to supply calcium, and is of interest for its unique properties in biological and pathological mineralization. It is important to control the crystal morphology of brushite since its chemical reactivity depends strongly on its surface properties; thus, its morphology is a key issue for its applications as a functional material or precursor for other bioceramics. Here, we report the effects of the initial pH and the Ca and phosphate ion concentrations on the morphology of DCPD particles during aqueous solution synthesis. Crystal morphologies were analyzed by scanning electron microscopy and X-ray diffraction. The morphology phase diagram of DCPD crystallization revealed that increasing the initial pH and/or ion concentration transformed DCPD morphology from petal-like into plate-like structures.

  7. 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

  8. Radiation dosimetry by optically stimulated phosphorescence of CaF2:Mn

    International Nuclear Information System (INIS)

    Bernhardt, R.

    1974-01-01

    In addition to the light emission which occurs in TL, trapped electrons in CaF 2 :Mn can also be released by stimulation with visible and UV light. The measurement of stimulated light emission is disturbed by illumination. But there is an optically-stimulated phosphorescence, which permits to separate measurement of stimulated light emission and illumination. A theory is given. During illumination a part of the released electrons are captured by flat traps, which are emptied at room temperature. A dose dependent signal can be measured at a defined time after the stimulating pulse of visible light. Dosimeters (CaF 2 :Mn teflon disks) were illuminated by the light of a tungsten lamp. The dose response curve was found to be linear from 1 to 10 5 rads. The response curve obtained for optical stimulation was similar to the TL-response curve. Fading of the optically-stimulated signal was higher than TL-fading. Repeated readings of a single sample are possible. The number of readings is dependent on illumination conditions. Accuracy of sample to sample was about 3.5% (standard deviation). There are two background signals. (1) Post-irradiation phosphorescence occurs. Flat traps are also filled after 60 Co gamma excitation. The measurement of the signal is possible after decay of post-irradiation phosphorescence. (2) There is an optically-excited phosphorescence, which also occurs if all trapped electrons are released. The lower limit of dose measurements is given by deviations of optically-excited emission and the dark-current of the photomultiplier tube. (author)

  9. 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.

  10. PSYCHOMETRIC EVALUATION OF SYMPTOMS AND CLINICAL DYNAMICS OF SCHIZOPHRENIA IN DEPENDING ON CONSTITUTIONALLY-MORPHOLOGICAL TYPE OF THE PATIENTS

    Directory of Open Access Journals (Sweden)

    F. F. Mikilev

    2016-01-01

    Full Text Available The purpose of this study was to research the psychometrical parameters and the clinical-dynamic features of patients with schizophrenia in depending on their constitutionally-morphological type.Material and methods. The examination of 86 patients with schizophrenia who are hospitalized at Department of endogenous mental disorders of Mental Health Research Institute was conducted. The study included patients of age from 18 to 65 years old with prescription of catamnesis at least 1 year and whose state at the time of examination corresponded to the diagnostic criteria for schizophrenia from the ICD-10 (International Classification of Diseases 10th Revision. The examination included filling in a modified version of Basic Card of Standardized Description of the Patient with Schizophrenia and his Relative, Positive and Negative Syndrome Scale (PANSS, Clinical Global Impression Scale (CGI. In addition to that patients were examined using anthropometrical method by V.V. Bunak. Statistical significance of differences in the data was evaluated using the Kruskal – Wallis test by ranks, the Mann – Whitney U-test, and Pearson’s chi-squared test. The correlation analysis was performed by the Spearman’s rank correlation test. The K-Means Cluster Analysis was used to determine of the qualitative interrelation and conjugation between the clinical characteristics of the examined.The results of the study revealed that many parameters of the functioning in these patient groups have statistically significant differences. Use of the K-Means Cluster Analysis was allowed to reveal the internal structure of the data, to group the individual observations according to their degree of similarity.Conclusions. The obtained data leads to the assumption that the constitutionally-morphological type of patients has an impact on the clinical course of schizophrenia, as well as their adaptation abilities. Asthenic constitutionally-morphological type is a factor of

  11. MORPHOLOGICAL AND BIOREFLECTING CHARACTERISTICS OF TAPETUM LUCIDUM IN DOGS AND COWS

    Directory of Open Access Journals (Sweden)

    Pamela Bejdić

    2013-09-01

    Full Text Available Tapetum lucidum is the specially modifided, bio-reflecting tissue layer, which at most vertebrates covers the biggest part of the middle eye tunic, the chorioidea. Physiologically, the most important role of this layer is to reflect light which passes through the retina back to it, causing the secondary stimulation of the photoreceptors. In the dim light ambient conditions when the pupil is dilated, reflected beams of the light create the visual effect of the “animals' eyes shining in the dark“, while exiting the eyes. The aims of this study are to define bio-reflecting and morphological charachteristics of the tapetum lucidum in the dog and cow eyes. Because the tapetum lucidum is an adaptive structure of the eye on poorly illuminated environment, the results of our research indicate that the anatomy of the eye, particulary shape of the pupil, placement of the eyes on the animals' head, and diet, all affect the morphology and bio-reflecting characteristics of this structure.Key words: tapetum lucidum, eyeshine, morphology

  12. Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

    Science.gov (United States)

    Jezernik, Saso; Sinkjaer, Thomas; Morari, Manfred

    2010-08-01

    In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

  13. Morphological Processing during Visual Word Recognition in Hebrew as a First and a Second Language

    Science.gov (United States)

    Norman, Tal; Degani, Tamar; Peleg, Orna

    2017-01-01

    The present study examined whether sublexical morphological processing takes place during visual word-recognition in Hebrew, and whether morphological decomposition of written words depends on lexical activation of the complete word. Furthermore, it examined whether morphological processing is similar when reading Hebrew as a first language (L1)…

  14. 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)

  15. Effect of Ag doping on the properties of ZnO thin films for UV stimulated emission

    Science.gov (United States)

    Razeen, Ahmed S.; Gadallah, A.-S.; El-Nahass, M. M.

    2018-06-01

    Ag doped ZnO thin films have been prepared using sol-gel spin coating method, with different doping concentrations. Structural and morphological properties of the films have been investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Thin films have been optically pumped and stimulated emission has been observed with strong peaks in the UV region. The UV stimulated emission is found to be due to exciton-exciton scattering, and Ag doping promoted this process by increasing the excitons concentrations in the ZnO lattice. Output-input intensity relation and peak emission, FWHM, and quantum efficiency relations with pump intensity have been reported. The threshold for which stimulated emission started has been evaluated to be about 18 MW/cm2 with quantum efficiency of about 58.7%. Mechanisms explaining the role of Ag in enhancement of stimulated emission from ZnO thin films have been proposed.

  16. 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.

  17. Morphology Is a Link to the Past: Examining Formative and Secular Galactic Evolution through Morphology

    Science.gov (United States)

    Galloway, Melanie A.

    Galaxy morphology is one of the primary keys to understanding a galaxy's evolutionary history. External mechanisms (environment/clustering, mergers) have a strong impact on the formative evolution of the major galactic components (disk, bulge, Hubble type), while internal instabilities created by bars, spiral arms, or other substructures drive secular evolution via the rearrangement of material within the disk. This thesis will explore several ways in which morphology impacts the dynamics and evolution of a galaxy using visual classifications from several Galaxy Zoo projects. The first half of this work will detail the motivations of using morphology to study galaxy evolution, and describe how morphology is measured, debiased, and interpreted using crowdsourced classification data via Galaxy Zoo. The second half will present scientific studies which make use of these classifications; first by focusing on the morphology of galaxies in the local Universe (z color. These results are consistent with a cosmological model in which bar-driven fueling contributes to the growth of black holes, but other dynamical mechanisms must also play a significant role. Next, the morphological dependence on wavelength is studied in Chapter 5 by comparing the optical morphological classifications from GZ2 to classifications done on infrared images in GZ:UKIDSS. Consistent morphologies were found in both sets and similar bar fractions, which confirms that for most galaxies, both old and young stellar populations follow similar spatial distributions. Last, the morphological changes in galaxy populations are computed as a function of their age using classifications from Galaxy Zoo: Hubble (Chapter 6). The evolution of the passive disc population from z = 1 to z = 0.3 was studied in a sample of 20,000 galaxies from the COSMOS field and morphologically classified by the Galaxy Zoo: Hubble project. It was found that the fraction of disc galaxies that are red, as well as the fraction of red

  18. Genetic Determinism vs. Phenotypic Plasticity in Protist Morphology.

    Science.gov (United States)

    Mulot, Matthieu; Marcisz, Katarzyna; Grandgirard, Lara; Lara, Enrique; Kosakyan, Anush; Robroek, Bjorn J M; Lamentowicz, Mariusz; Payne, Richard J; Mitchell, Edward A D

    2017-11-01

    Untangling the relationships between morphology and phylogeny is key to building a reliable taxonomy, but is especially challenging for protists, where the existence of cryptic or pseudocryptic species makes finding relevant discriminant traits difficult. Here we use Hyalosphenia papilio (a testate amoeba) as a model species to investigate the contribution of phylogeny and phenotypic plasticity in its morphology. We study the response of H. papilio morphology (shape and pores number) to environmental variables in (i) a manipulative experiment with controlled conditions (water level), (ii) an observational study of a within-site natural ecological gradient (water level), and (iii) an observational study across 37 European peatlands (climate). We showed that H. papilio morphology is correlated to environmental conditions (climate and water depth) as well as geography, while no relationship between morphology and phylogeny was brought to light. The relative contribution of genetic inheritance and phenotypic plasticity in shaping morphology varies depending on the taxonomic group and the trait under consideration. Thus, our data call for a reassessment of taxonomy based on morphology alone. This clearly calls for a substantial increase in taxonomic research on these globally still under-studied organisms leading to a reassessment of estimates of global microbial eukaryotic diversity. © 2017 The Author(s) Journal of Eukaryotic Microbiology © 2017 International Society of Protistologists.

  19. 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. 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.

  20. Generic model of morphological changes in growing colonies of fungi

    Science.gov (United States)

    López, Juan M.; Jensen, Henrik J.

    2002-02-01

    Fungal colonies are able to exhibit different morphologies depending on the environmental conditions. This allows them to cope with and adapt to external changes. When grown in solid or semisolid media the bulk of the colony is compact and several morphological transitions have been reported to occur as the external conditions are varied. Here we show how a unified simple mathematical model, which includes the effect of the accumulation of toxic metabolites, can account for the morphological changes observed. Our numerical results are in excellent agreement with experiments carried out with the fungus Aspergillus oryzae on solid agar.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. [Stimulation of proliferation by carnosine: cellular and transcriptome approaches].

    Science.gov (United States)

    Vishniakova, Kh S; Babizhaev, M A; Aliper, A M; Buzdin, A A; Kudriavtseva, A V; Egorov, E E

    2014-01-01

    Concentration of endogenous dipeptide carnosine in human muscle tissue reaches tens of millimoles. For more than 100 years of research, a lot of data concerning carnosine functions were accumulated, among which anti-aging effects are regarded most important. Heire, effect of carnosine in cell cultures was studied. It has been found that apart from the known action--an increase of the Hayflick limit and morphological rejuvenation--carnosine stimulates cell division in colony-forming assays and in the course of transition of cells to the quiescent state. The analysis of the transcriptome showed that carnosine-induced changes are mainly related to positive regulation of the cell cycle at all levels, from the onset of the DNA synthesis to chromosome condensation. One can suppose that the revealed stimulation of the cell cycle account for the carnosine-induced rejuvenation processes and a high concentration ofcarnosine in muscle tissue is required for the muscle recovery (regeneration) after excess loads.

  6. Spatial and temporal changes in the morphology of preosteoblastic cells seeded on microstructured tantalum surfaces

    DEFF Research Database (Denmark)

    Justesen, Jørn; Lorentzen, M.; Andersen, L. K.

    2009-01-01

    It has been widely reported that surface morphology on the micrometer scale affects cell function as well as cell shape. In this study, we have systematically compared the influence of 13 topographically micropatterned tantalum surfaces on the temporal development of morphology, including spreading......, and length of preosteoblastic cells (MC3T3-E1). Cells were examined after 0.5, 1, 4, and 24 h on different Ta microstructures with vertical dimensions (heights) of 0.25 and 1.6 mu m. Cell morphologies depended upon the underlying Surface topography, and the length and spreading of cells varied as a function...... to depend on the distance between the pillars with one specific pillar Structure exhibiting a decreased spreading combined with a radical change in morphology of the cells. Interestingly, this morphology on the particular pillar structure was associated with a markedly different distribution of the actio...

  7. Separation of integrin-dependent adhesion from morphological changes based on differential PLC specificities.

    Science.gov (United States)

    Wooten, D K; Teague, T K; McIntyre, B W

    1999-01-01

    In normal lymphocytes an inside-out signal up-regulating integrin adhesion is followed by a ligand-mediated outside-in cell spreading signal. Protein kinase C (PKC) inhibition blocks lymphocyte adherence to and spreading on fibronectin. In contrast, putative PLC inhibitors yield distinct differences with respect to adhesion and morphology. The phosphatidylinositol-specific phospholipase C (PLC) inhibitor neomycin blocked spreading of CD3/CD28-activated T cells on fibronectin by disrupting adhesion. Furthermore, when an additional inside-out signal for fibronectin adhesion is unnecessary such as with HPB-ALL T leukemic or phorbol-myristate-acetate-treated normal T cells, neomycin treatment does not alter adhesion or morphology. However, the phosphatidylcholine-specific PLC inhibitor D609 abrogates cell spreading without affecting adhesion to fibronectin in these cells as well as the CD3/CD28-activated T cells. These results strongly suggest that inside-out signaling for the integrin alpha4beta1 in lymphocytes proceeds through phosphatidylinositol-specific PLC and PKC, whereas the outside-in signal utilizes phosphatidylcholine-specific PLC and PKC.

  8. 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...

  9. A PRIMER ON UNIFYING DEBRIS DISK MORPHOLOGIES

    International Nuclear Information System (INIS)

    Lee, Eve J.; Chiang, Eugene

    2016-01-01

    A “minimum model” for debris disks consists of a narrow ring of parent bodies, secularly forced by a single planet on a possibly eccentric orbit, colliding to produce dust grains that are perturbed by stellar radiation pressure. We demonstrate how this minimum model can reproduce a wide variety of disk morphologies imaged in scattered starlight. Five broad categories of disk shape can be captured: “rings,” “needles,” “ships-and-wakes,” “bars,” and “moths (a.k.a. fans),” depending on the viewing geometry. Moths can also sport “double wings.” We explain the origin of morphological features from first principles, exploring the dependence on planet eccentricity, disk inclination dispersion, and the parent body orbital phases at which dust grains are born. A key determinant in disk appearance is the degree to which dust grain orbits are apsidally aligned. Our study of a simple steady-state (secularly relaxed) disk should serve as a reference for more detailed models tailored to individual systems. We use the intuition gained from our guidebook of disk morphologies to interpret, informally, the images of a number of real-world debris disks. These interpretations suggest that the farthest reaches of planetary systems are perturbed by eccentric planets, possibly just a few Earth masses each.

  10. A Primer on Unifying Debris Disk Morphologies

    Science.gov (United States)

    Lee, Eve J.; Chiang, Eugene

    2016-08-01

    A “minimum model” for debris disks consists of a narrow ring of parent bodies, secularly forced by a single planet on a possibly eccentric orbit, colliding to produce dust grains that are perturbed by stellar radiation pressure. We demonstrate how this minimum model can reproduce a wide variety of disk morphologies imaged in scattered starlight. Five broad categories of disk shape can be captured: “rings,” “needles,” “ships-and-wakes,” “bars,” and “moths (a.k.a. fans),” depending on the viewing geometry. Moths can also sport “double wings.” We explain the origin of morphological features from first principles, exploring the dependence on planet eccentricity, disk inclination dispersion, and the parent body orbital phases at which dust grains are born. A key determinant in disk appearance is the degree to which dust grain orbits are apsidally aligned. Our study of a simple steady-state (secularly relaxed) disk should serve as a reference for more detailed models tailored to individual systems. We use the intuition gained from our guidebook of disk morphologies to interpret, informally, the images of a number of real-world debris disks. These interpretations suggest that the farthest reaches of planetary systems are perturbed by eccentric planets, possibly just a few Earth masses each.

  11. A PRIMER ON UNIFYING DEBRIS DISK MORPHOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eve J.; Chiang, Eugene, E-mail: evelee@berkeley.edu, E-mail: echiang@astro.berkeley.edu [Department of Astronomy, University of California Berkeley, Berkeley, CA 94720-3411 (United States)

    2016-08-20

    A “minimum model” for debris disks consists of a narrow ring of parent bodies, secularly forced by a single planet on a possibly eccentric orbit, colliding to produce dust grains that are perturbed by stellar radiation pressure. We demonstrate how this minimum model can reproduce a wide variety of disk morphologies imaged in scattered starlight. Five broad categories of disk shape can be captured: “rings,” “needles,” “ships-and-wakes,” “bars,” and “moths (a.k.a. fans),” depending on the viewing geometry. Moths can also sport “double wings.” We explain the origin of morphological features from first principles, exploring the dependence on planet eccentricity, disk inclination dispersion, and the parent body orbital phases at which dust grains are born. A key determinant in disk appearance is the degree to which dust grain orbits are apsidally aligned. Our study of a simple steady-state (secularly relaxed) disk should serve as a reference for more detailed models tailored to individual systems. We use the intuition gained from our guidebook of disk morphologies to interpret, informally, the images of a number of real-world debris disks. These interpretations suggest that the farthest reaches of planetary systems are perturbed by eccentric planets, possibly just a few Earth masses each.

  12. 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

  13. Morphological correlates of hearing loss after cochlear implantation and electro-acoustic stimulation in a hearing-impaired Guinea pig model.

    Science.gov (United States)

    Reiss, Lina A J; Stark, Gemaine; Nguyen-Huynh, Anh T; Spear, Kayce A; Zhang, Hongzheng; Tanaka, Chiemi; Li, Hongzhe

    2015-09-01

    Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 h of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and

  14. Nanoscale Morphology Evolution Under Ion Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Aziz, Michael J. [President & Fellows of Harvard College, Cambridge, MA (United States)

    2014-11-10

    We showed that the half-century-old paradigm of morphological instability under irradiation due to the curvature-dependence of the sputter yield, can account neither for the phase diagram nor the amplification or decay rates that we measure in the simplest possible experimental system -- an elemental semiconductor with an amorphous surface under noble-gas ion irradiation; We showed that a model of pattern formation based on the impact-induced redistribution of atoms that do not get sputtered away explains our experimental observations; We developed a first-principles, parameter-free approach for predicting morphology evolution, starting with molecular dynamics simulations of single ion impacts, lasting picoseconds, and upscaling through a rigorous crater-function formalism to develop a partial differential equation that predicts morphology evolution on time scales more than twelve orders of magnitude longer than can be covered by the molecular dynamics; We performed the first quantitative comparison of the contributions to morphological instability from sputter removal and from impact-induced redistribution of atoms that are removed, and showed that the former is negligible compared to the latter; We established a new paradigm for impact-induced morphology evolution based on crater functions that incorporate both redistribution and sputter effects; and We developed a model of nanopore closure by irradiation-induced stress and irradiationenhanced fluidity, for the near-surface irradiation regime in which nuclear stopping predominates, and showed that it explains many aspects of pore closure kinetics that we measure experimentally.

  15. Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

    Science.gov (United States)

    Grisendi, Valentina; La Marca, Antonio

    2017-06-01

    In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

  16. 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

  17. Immunohistochemical and Morphofunctional Studies of Skeletal Muscle Tissues with Electric Nerve Stimulation by In Vivo Cryotechnique

    International Nuclear Information System (INIS)

    Fukasawa, Yuki; Ohno, Nobuhiko; Saitoh, Yurika; Saigusa, Takeshi; Arita, Jun; Ohno, Shinichi

    2015-01-01

    In this study, morphological and immunohistochemical alterations of skeletal muscle tissues during persistent contraction were examined by in vivo cryotechnique (IVCT). Contraction of gastrocnemius muscles was induced by sciatic nerve stimulation. The IVCT was performed immediately, 3 min or 10 min after the stimulation start. Prominent ripples of muscle fibers or wavy deformation of sarcolemma were detected immediately after the stimulation, but they gradually diminished to normal levels during the stimulation. The relative ratio of sarcomere and A band lengths was the highest in the control group, but it immediately decreased to the lowest level and then gradually recovered at 3 min or 10 min. Although histochemical intensity of PAS reaction was almost homogeneous in muscle tissues of the control group or immediately after the stimulation, it decreased at 3 min or 10 min. Serum albumin was immunolocalized as dot-like patterns within some muscle fibers at 3 min stimulation. These patterns became more prominent at 10 min, and the dots got larger and saccular in some sarcoplasmic regions. However, IgG1 and IgM were immunolocalized in blood vessels under nerve stimulation conditions. Therefore, IVCT was useful to capture the morphofunctional and metabolic changes of heterogeneous muscle fibers during the persistent contraction

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  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. Indirect Low-Intensity Ultrasonic Stimulation for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hyoungshin Park

    2010-01-01

    Full Text Available Low-intensity ultrasound (LIUS treatment has been shown to increase mass transport, which could benefit tissue grafts during the immediate postimplant period, when blood supply to the implanted tissue is suboptimal. In this in vitro study, we investigated effects of LIUS stimulation on dye diffusion, proliferation, metabolism, and tropomyosin expression of muscle cells (C2C12 and on tissue viability and gene expression of human adipose tissue organoids. We found that LIUS increased dye diffusion within adjacent tissue culture wells and caused anisotropic diffusion patterns. This effect was confirmed by a hydrophone measurement resulting in acoustic pressure 150–341 Pa in wells. Cellular studies showed that LIUS significantly increased proliferation, metabolic activity, and expression of tropomyosin. Adipose tissue treated with LIUS showed significantly increased metabolic activity and the cells had similar morphology to normal unilocular adipocytes. Gene analysis showed that tumor necrosis factor-alpha expression (a marker for tissue damage was significantly lower for stimulated organoids than for control groups. Our data suggests that LIUS could be a useful modality for improving graft survival in vivo.

  5. Semantic growth of morphological families in English

    Directory of Open Access Journals (Sweden)

    Henry Regina

    2013-01-01

    Full Text Available This paper explores the question of when and how morphological families are formed in one’s mental lexicon, by analyzing age-of-acquisition norms to morphological families (e.g., booking, bookshelf, check book and their shared morphemes (book. We demonstrate that the speed of growth and the size of the family depend on how early the shared morpheme is acquired and how many connections the family has at the time a new concept is incorporated in the family. These findings dovetail perfectly with the Semantic Growth model of connectivity in semantic networks by Steyvers and Tenenbaum (2005. We discuss implications of our findings for theories of vocabulary acquisition.

  6. Morphology Evolution of Polycarbonate-Polystyrene Blends During Compounding

    DEFF Research Database (Denmark)

    Chuai, Chengzhi; Almdal, Kristoffer; Johannsen, Ib

    2001-01-01

    The morphology evolution of polycarbonate-polystyrene (PC/PS) blends during the compounding process in three blending methods of industrial relevance, namely melt blending, re-melt blending in a twin-screw extruder and tri-melt blending in an injection-moulding machine, was investigated using......-empirical model. The results show that the formation of co-continuous morphology strongly depends on blend composition and melt blending method, whereas the model prediction for phase inversion deviates from the experimental values. Further, we found that the initial mechanism of morphology evolution involves...... scanning electron microscopy (SEM) Co examine nine blend compositions. Blends were prepared at compositions where phase inversion was expected to occur according to model predictions. The experimental results were compared to the values of the point of phase inversion calculated with the semi...

  7. 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.

  8. 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

  9. Different methods to alter surface morphology of high aspect ratio structures

    Energy Technology Data Exchange (ETDEWEB)

    Leber, M., E-mail: moritz.leber@utah.edu [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Shandhi, M.M.H. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Hogan, A. [Blackrock Microsystems, Salt Lake City, UT (United States); Solzbacher, F. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Bhandari, R.; Negi, S. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Blackrock Microsystems, Salt Lake City, UT (United States)

    2016-03-01

    Graphical abstract: Surface engineering of high aspect ratio silicon structures. - Highlights: • Multiple roughening techniques for high aspect ratio devices were investigated. • Modification of surface morphology of high aspect ratio silicon devices (1:15). • Decrease of 76% in impedance proves significant increase in surface area. - Abstract: In various applications such as neural prostheses or solar cells, there is a need to alter the surface morphology of high aspect ratio structures so that the real surface area is greater than geometrical area. The change in surface morphology enhances the devices functionality. One of the applications of altering the surface morphology is of neural implants such as the Utah electrode array (UEA) that communicate with single neurons by charge injection induced stimulation or by recording electrical neural signals. For high selectivity between single cells of the nervous system, the electrode surface area is required to be as small as possible, while the impedance is required to be as low as possible for good signal to noise ratios (SNR) during neural recording. For stimulation, high charge injection and charge transfer capacities of the electrodes are required, which increase with the electrode surface. Traditionally, researchers have worked with either increasing the roughness of the existing metallization (platinum grey, black) or other materials such as Iridium Oxide and PEDOT. All of these previously investigated methods lead to more complicated metal deposition processes that are difficult to control and often have a critical impact on the mechanical properties of the metal films. Therefore, a modification of the surface underneath the electrode's coating will increase its surface area while maintaining the standard and well controlled metal deposition process. In this work, the surfaces of the silicon micro-needles were engineered by creating a defined microstructure on the electrodes surface using several

  10. Membrane-associated proteolytic activity in Escherichia coli that is stimulated by ATP

    International Nuclear Information System (INIS)

    Klemes, Y.; Voellmy, R.W.; Goldberg, A.L.

    1986-01-01

    The degradation of proteins in bacteria requires metabolism energy. One important enzyme in this process is protease La, a soluble ATP-dependent protease encoded by the lon gene. However, lon mutants that lack a functional protease La still show some ATP-dependent protein breakdown. The authors have reported an ATP-stimulated endoproteolytic activity associated with the inner membrane of E. coli. This ATP-stimulated activity is found in normal levels in membranes derived from lon mutants, including strains carrying insertions in the lon gene. The membrane-bound activity hydrolyzes 14 C-methylglobin at a linear rate for up to 3 hours. These fractions also contain appreciable proteolytic activity that is not affected by ATP. The stimulation by ATP requires the presence of Mg 2+ . Nonhydrolyzable ATP analogs (e.g. AMPPNP or ATP-γ-S) and ADP do not enhance proteolysis. Unlike protease La, the membrane-associated enzyme does not degrade the fluorometric substrate, Glt-Ala-Ala-Phe-MNA, in an ATP-stimulated fashion, and its level is not influenced by high temperature of by the gene which regulates the heat-shock response. The enzyme is inhibited by dichloroisocoumarin and certain peptide chloromethyl ketones. They conclude that E. coli contain at least two ATP-dependent proteases with distinct specificities: one is soluble and the other is membrane-associated

  11. 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

  12. 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...

  13. 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...

  14. 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.

  15. Early Maladaptive Schemas in Opiate and Stimulant Users

    Directory of Open Access Journals (Sweden)

    Zahra Karami

    2015-06-01

    Full Text Available Objectives: Early maladaptive schemas are valid representations of unpleasant childhood experiences that shape a person’s viewpoints of the world, and lead to clinical symptoms such as depression, personality disorders, and substance abuse. Given the importance of this matter, we conducted a research on early maladaptive schemas in substance-abusers, to allow more appropriate preventive measures to be taken with a better understanding of the issue. Methods: For this descriptive-comparative study, 115 patients (91 opiate users and 24 stimulant users visiting drug addiction treatment centers were selected through convenience sampling from persons who were admitted to substance abuse treatment centers (Methadone Maintenance therapy centers, addiction treatment camps and self-help groups and Narcotics Anonymous (NA of Yasuj. Data were collected using a Demographic Information Questionnaire and Young’s Schema Questionnaire-Short Form (SQ-SF. Data analysis was done with ANOVA and t-tests. Results: The results showed a significant difference (P<0.05 between users of opiates and stimulants in terms of vulnerability to harm or illness, enmeshment, subjugation, emotional inhibition, entitlement, insufficient self-control/self-discipline, emotional  deprivation, social isolation, defectiveness, failure/shame, and dependence. The average score of the stimulant-users was higher than that of opiate-users in all the schemas except for the dimensions of abandonment, mistrust, and unrelenting standards. Discussion: Stimulant users have more early maladaptive schemas and are at a greater risk of psychological vulnerability. Early maladaptive schemas can be used by clinicians and researchers as a psychopathology and treatment method for substance dependence disorder.

  16. Dosimetry based on thermally and optically stimulated luminescence

    Energy Technology Data Exchange (ETDEWEB)

    Agersnap Larsen, Niels

    1999-01-01

    Thermally Stimulated Luminescence (TL) and Optically Stimulated Luminescence (OSL) properties of quartz and {alpha}-Al{sub 2}O{sub 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 {alpha}-Al{sub 2}O{sub 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 {alpha}Al{sub 2}O{sub 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 {gamma}-irradiated {alpha}Al{sub 2}O{sub 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) 8 tabs., 59 ills., 90 refs.

  17. A model for the generation and interconversion of ER morphologies

    OpenAIRE

    Shemesh, Tom; Klemm, Robin W.; Romano, Fabian B.; Wang, Songyu; Vaughan, Joshua; Zhuang, Xiaowei; Tukachinsky, Hanna; Kozlov, Michael M.; Rapoport, Tom A.

    2014-01-01

    The endoplasmic reticulum (ER) is an important membrane-bound organelle in all eukaryotic cells. Depending on cell type and functional state, the ER membrane can adopt different morphologies, including a network of interconnected tubules, and sheets that can contain fenestrations or be stacked on top of each other. How these different morphologies are generated is unclear. Here, we present a comprehensive theoretical model that explains the formation and interconversion of virtually all known...

  18. Morphology-dependent crossover effects in heterogeneous nucleation of peritectic materials studied via the phase-field method for Al-Ni

    International Nuclear Information System (INIS)

    Siquieri, R; Emmerich, H

    2009-01-01

    The application of phase-field modeling to nucleation as a phenomenon at the nanoscale is justified, if one takes into account the great success of continuum approaches in nanofluidics as proven by the many comparisons to experiments. Employed in this manner it provides an approach allowing us to account for effects of the physical diffuseness of a nucleus' interface and thereby go beyond classical nucleation theory (Granasy and James 2000 J. Chem. Phys. 113 9810; Emmerich and Siquieri 2006 J. Phys.: Condens. Matter 18 11121). Here we extend the focus of previous work in this field and address the question of how far the phase-field method can also be applied to gain further insight into nucleation statistics, in particular the nucleation prefactor appearing in the nucleation rate. In this context we describe in detail a morphology-dependent crossover effect noticeable for the nucleation rate at small driving forces.

  19. Ribosomal Protein S6 Kinase (RSK-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein

    Directory of Open Access Journals (Sweden)

    Zhang Rui-Wen

    2011-05-01

    Full Text Available Abstract Background Epithelial to mesenchymal transition (EMT occurs during cancer cell invasion and malignant metastasis. Features of EMT include spindle-like cell morphology, loss of epithelial cellular markers and gain of mesenchymal phenotype. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein (MSP has been implicated in cellular EMT program; however, the major signaling determinant(s responsible for MSP-induced EMT is unknown. Results The study presented here demonstrates that RSK2, a downstream signaling protein of the Ras-Erk1/2 pathway, is the principal molecule that links MSP-activated RON signaling to complete EMT. Using MDCK cells expressing RON as a model, a spindle-shape based screen was conducted, which identifies RSK2 among various intracellular proteins as a potential signaling molecule responsible for MSP-induced EMT. MSP stimulation dissociated RSK2 with Erk1/2 and promoted RSK2 nuclear translocation. MSP strongly induced RSK2 phosphorylation in a dose-dependent manner. These effects relied on RON and Erk1/2 phosphorylation, which is significantly potentiated by transforming growth factor (TGF-β1, an EMT-inducing cytokine. Specific RSK inhibitor SL0101 completely prevented MSP-induced RSK phosphorylation, which results in inhibition of MSP-induced spindle-like morphology and suppression of cell migration associated with EMT. In HT-29 cancer cells that barely express RSK2, forced RSK2 expression results in EMT-like phenotype upon MSP stimulation. Moreover, specific siRNA-mediated silencing of RSK2 but not RSK1 in L3.6pl pancreatic cancer cells significantly inhibited MSP-induced EMT-like phenotype and cell migration. Conclusions MSP-induced RSK2 activation is a critical determinant linking RON signaling to cellular EMT program. Inhibition of RSK2 activity may provide a therapeutic opportunity for blocking RON-mediated cancer cell migration and subsequent invasion.

  20. 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

  1. Hole-Transfer Dependence on Blend Morphology and Energy Level Alignment in Polymer: ITIC Photovoltaic Materials.

    Science.gov (United States)

    Eastham, Nicholas D; Logsdon, Jenna L; Manley, Eric F; Aldrich, Thomas J; Leonardi, Matthew J; Wang, Gang; Powers-Riggs, Natalia E; Young, Ryan M; Chen, Lin X; Wasielewski, Michael R; Melkonyan, Ferdinand S; Chang, Robert P H; Marks, Tobin J

    2018-01-01

    Bulk-heterojunction organic photovoltaic materials containing nonfullerene acceptors (NFAs) have seen remarkable advances in the past year, finally surpassing fullerenes in performance. Indeed, acceptors based on indacenodithiophene (IDT) have become synonymous with high power conversion efficiencies (PCEs). Nevertheless, NFAs have yet to achieve fill factors (FFs) comparable to those of the highest-performing fullerene-based materials. To address this seeming anomaly, this study examines a high efficiency IDT-based acceptor, ITIC, paired with three donor polymers known to achieve high FFs with fullerenes, PTPD3T, PBTI3T, and PBTSA3T. Excellent PCEs up to 8.43% are achieved from PTPD3T:ITIC blends, reflecting good charge transport, optimal morphology, and efficient ITIC to PTPD3T hole-transfer, as observed by femtosecond transient absorption spectroscopy. Hole-transfer is observed from ITIC to PBTI3T and PBTSA3T, but less efficiently, reflecting measurably inferior morphology and nonoptimal energy level alignment, resulting in PCEs of 5.34% and 4.65%, respectively. This work demonstrates the importance of proper morphology and kinetics of ITIC → donor polymer hole-transfer in boosting the performance of polymer:ITIC photovoltaic bulk heterojunction blends. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. 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.

  3. 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.

  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. Neuron Morphology Influences Axon Initial Segment Plasticity123

    Science.gov (United States)

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  6. MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis.

    Science.gov (United States)

    Madzak, Adnan; Olesen, Søren Schou; Lykke Poulsen, Jakob; Bolvig Mark, Esben; Mohr Drewes, Asbjørn; Frøkjær, Jens Brøndum

    2017-11-01

    The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02-4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=-0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

  7. Environmental impact on morphological and anatomical structure of ...

    African Journals Online (AJOL)

    Morphological and anatomical structure of Tansy (Tanacetum vulgare L.) from two specific locations in one town, depending on environmental conditions, were carried out: anthropogenic Ada Huja (polluted zone) and non anthropogenic Topcider park (unpolluted). Study included the diferences in the structure of leaves, ...

  8. 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...

  9. 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 ...

  10. Atrial granular cells of the snail Achatina fulica release proteins into hemolymph after stimulation of the heart nerve.

    Science.gov (United States)

    Shabelnikov, Sergej V; Bystrova, Olga A; Ivanov, Vadim A; Margulis, Boris A; Martynova, Marina

    2009-10-01

    The atrium of the gastropod mollusc Achatina fulica receives rich innervation and contains numerous granular cells (GCs). We studied the atrial innervation and discovered that axon profiles typical in appearance of peptidergic neurons form close unspecialized membrane contacts with GCs. Then, we investigated, at both morphological and biochemical levels, the effect of electrical stimulation of the heart nerve on GCs of Achatina heart perfused in situ. The ultrastructural study demonstrated changes in granule morphology consistent with secretion. These events included alteration of granule content, intracellular granule fusion and formation of complex degranulation channels, within which the granule matrix solubilized. It was shown that electrical stimulation resulted in a significant increase of the total protein concentration in the perfusate. Furthermore, SDS-PAGE analysis of the perfusate revealed three new proteins with molecular masses of 16, 22, and 57 kDa. Affinity-purified polyclonal antibodies against the 16 kDa protein were obtained; the whole-mount immunofluorescence technique revealed the presence of this protein in the granules of atrial GCs. In GCs of the stimulated atrium, a progressive loss of their granular content was observed. The results suggest that the central nervous system can modulate the secretory activity of the atrial GCs through non-synaptic pathways.

  11. Exploring the morphological and electronic properties of silicene superstructures

    International Nuclear Information System (INIS)

    Grazianetti, Carlo; Chiappe, Daniele; Cinquanta, Eugenio; Tallarida, Grazia; Fanciulli, Marco; Molle, Alessandro

    2014-01-01

    Silicene, the Si counterpart of graphene, grows on Ag(111) forming domains. Investigation, by means of scanning tunneling microscopy, of morphological properties is carried out by considering post-deposition process. Particular attention is here addressed to the post-deposition annealing temperature, which plays an important role in determining the resulting morphology. On the other hand, electronic properties are probed by scanning tunneling spectroscopy and a position-dependent local density of states results, which can be understood in terms of symmetry breaking in the honeycomb lattice.

  12. Exploring the morphological and electronic properties of silicene superstructures

    Energy Technology Data Exchange (ETDEWEB)

    Grazianetti, Carlo, E-mail: carlo.grazianetti@mdm.imm.cnr.it [Laboratorio MDM, IMM-CNR, via C. Olivetti 2, I-20864 Agrate Brianza, MB (Italy); Dipartimento di Scienza dei Materiali, Università degli Studi di Milano Bicocca, via R. Cozzi 53, I-20126 Milano, MI (Italy); Chiappe, Daniele; Cinquanta, Eugenio; Tallarida, Grazia [Laboratorio MDM, IMM-CNR, via C. Olivetti 2, I-20864 Agrate Brianza, MB (Italy); Fanciulli, Marco [Laboratorio MDM, IMM-CNR, via C. Olivetti 2, I-20864 Agrate Brianza, MB (Italy); Dipartimento di Scienza dei Materiali, Università degli Studi di Milano Bicocca, via R. Cozzi 53, I-20126 Milano, MI (Italy); Molle, Alessandro, E-mail: alessandro.molle@mdm.imm.cnr.it [Laboratorio MDM, IMM-CNR, via C. Olivetti 2, I-20864 Agrate Brianza, MB (Italy)

    2014-02-01

    Silicene, the Si counterpart of graphene, grows on Ag(111) forming domains. Investigation, by means of scanning tunneling microscopy, of morphological properties is carried out by considering post-deposition process. Particular attention is here addressed to the post-deposition annealing temperature, which plays an important role in determining the resulting morphology. On the other hand, electronic properties are probed by scanning tunneling spectroscopy and a position-dependent local density of states results, which can be understood in terms of symmetry breaking in the honeycomb lattice.

  13. Platelet-rich plasma stimulates osteoblastic differentiation in the presence of BMPs

    International Nuclear Information System (INIS)

    Tomoyasu, Akihiro; Higashio, Kanji; Kanomata, Kazuhiro; Goto, Masaaki; Kodaira, Kunihiko; Serizawa, Hiroko; Suda, Tatsuo; Nakamura, Atsushi; Nojima, Junya; Fukuda, Toru; Katagiri, Takenobu

    2007-01-01

    Platelet-rich plasma (PRP) is clinically used as an autologous blood product to stimulate bone formation in vivo. In the present study, we examined the effects of PRP on proliferation and osteoblast differentiation in vitro in the presence of bone morphogenetic proteins (BMPs). PRP and its soluble fraction stimulated osteoblastic differentiation of myoblasts and osteoblastic cells in the presence of BMP-2, BMP-4, BMP-6 or BMP-7. The soluble PRP fraction stimulated osteoblastic differentiation in 3D cultures using scaffolds made of collagen or hydroxyapatite. Moreover, heparin-binding fractions obtained from serum also stimulated osteoblastic differentiation in the presence of BMP-4. These results suggested that platelets contain not only growth factors for proliferation but also novel potentiator(s) for BMP-dependent osteoblastic differentiation

  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. 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

  16. 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.

  17. Comparison of temperament and character personality traits in opiate and stimulant addicts

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadeghi Pouya

    2016-11-01

    Full Text Available Background: Phenomenon of addiction as one of the social problems has a high prevalence, especially among youth. The aim of the present study was to compare personality traits based on the temperament and character inventory in opiate and stimulant addicts in Tehran.  Methods: In the present quasi-experimental study, 60 male addicts (30 opiate and 30 stimulant addicts who referred to addiction treatment centers in the suburbs of Tehran were selected through convenience sampling method and were studied using Temperament and Character Inventory (TCI. The participants were sorted according to their age and education.    Results: There was a significant difference between the two groups with regard to harm avoidance, reward dependence, cooperativeness, and self-transcendence traits. Thus, opiate addicts had higher levels of harm avoidance, reward dependence, and cooperativeness, and stimulant addicts had higher levels of self-transcendence. The significance level was set at P<0.01.  Conclusion: The obtained results showed that there was a significant difference between opiate and stimulant addicts. Opiate addicts gained higher scores, compared with stimulant addicts, in Temperament and Character Inventory variables. The obtained results also showed that stimulant addicts were suffering from more severe disorders than opiate addicts. Based on the means of the values of the TCI, personality traits reflecting personality disorders are detectable and predictable in substance abusers. This new understanding is important in the prevention and treatment of addiction.

  18. Excitatory amino acid-stimulated uptake of 22Na+ in primary astrocyte cultures

    International Nuclear Information System (INIS)

    Kimelberg, H.K.; Pang, S.; Treble, D.H.

    1989-01-01

    In this study we have found that L-glutamic acid, as well as being taken up by a Na+-dependent mechanism, will stimulate the uptake of 22Na+ by primary astrocyte cultures from rat brain in the presence of ouabain. By simultaneously measuring the uptake of 22Na+ and L-3H-glutamate a stoichiometry of 2-3 Na+ per glutamate was measured, implying electrogenic uptake. Increasing the medium K+ concentration to depolarize the cells inhibited L-3H-glutamate uptake, while calculations of the energetics of the observed L-3H-glutamate accumulation also supported an electrogenic mechanism of at least 2 Na+:1 glutamate. In contrast, kinetic analysis of the Na+ dependence of L-3H-glutamate uptake indicated a stoichiometry of Na+ to glutamate of 1:1, but further analysis showed that the stoichiometry cannot be resolved by purely kinetic studies. Studies with glutamate analogs, however, showed that kainic acid was a very effective stimulant of 22Na+ uptake, but 3H-kainic acid showed no Na+ -dependent uptake. Furthermore, while L-3H-glutamate uptake was very sensitive to lowered temperatures, glutamate-stimulated 22Na+ uptake was relatively insensitive. These results indicate that glutamate-stimulated uptake of 22Na+ in primary astrocytes cultures cannot be explained solely by cotransport of Na+ with glutamate, and they suggest that direct kainic acid-type receptor induced stimulation of Na+ uptake also occurs. Since both receptor and uptake effects involve transport of Na+, accurate measurements of the Na+ :glutamate stoichiometry for uptake can only be done using completely specific inhibitors of these 2 systems

  19. Preliminary observations of the effect of solutal convection on crystal morphology

    Science.gov (United States)

    Broom, M. Beth H.; Witherow, William K.; Snyder, Robert S.; Carter, Daniel C.

    1988-01-01

    Studies to examine the effect of solutal convection on crystal morphology using sucrose as a model system were initiated. Aspect ratios, defined as the width of the 100-plane-oriented face over the width of the 001-plane-oriented face, were determined for oriented crystals which were grown with either the 001-oriented or the 100-oriented face perpendicular to the convective flow. The dependence of the crystal morphology on orientation is much greater for crystals grown with one face occluded than for crystals grown suspended in solution. Many factors appear to interact in a complex fashion to influence crystal morphology.

  20. 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.

  1. Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1β-stimulated SK-N-SH cells.

    Science.gov (United States)

    Velagapudi, Ravikanth; Baco, Gina; Khela, Sunjeet; Okorji, Uchechukwu; Olajide, Olumayokun

    2016-06-01

    Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1β-stimulated SK-N-SH cells. An enzyme immunoassay (EIA) was used to measure prostaglandin E2 (PGE2) production from supernatants of IL-1β-stimulated SK-N-SH cells. Expression of COX-2, phospho-IκB, and phospho-IKK proteins was evaluated, while NF-κB reporter gene assay was carried out in TNFα-stimulated HEK293 cells to determine the effect of PWE on NF-κB transactivation. Levels of BACE-1 and Aβ in SK-N-SH cells stimulated with IL-1β were measured with an in cell ELISA. PWE (25-200 μg/ml) dose dependently reduced COX-2-dependent PGE2 production in SK-N-SH cells stimulated with IL-1β. Phosphorylation of IκB and IKK was significantly (p pomegranate inhibits inflammation, as well as amyloidogenesis in IL-1β-stimulated SK-N-SH cells. We propose that pomegranate is a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer's disease.

  2. Mechanical properties and morphology of poly(etheretherKetone)

    Science.gov (United States)

    Cebe, Peggy; Chung, Shirley; Gupta, Amitava; Hong, Su-Don

    1987-01-01

    Mechanical properties and morphology of poly(etheretherketone) (PEEK) were studied for samples having different thermal histories. Isothermal and rate-dependent crystallization were studied to ascertain the relationship between crystallinity/morphology and processing condition. Degree of crystallinity and microstructure were controlled by cooling the melt at different rates, ranging from quenching to slowly cooling, and by annealing amorphous material above the glass transition temperature Tg. It is found that degree of crystallinity was not as important as processing history in determining the room temperature mechanical properties. Samples with the same degree of crystallinity had very different tensile properties, depending on rate of cooling from the melt. All samples yielded by shear band formation and necked down. Quenched films had the largest breaking strains, drawing to 270 percent. Slowly cooled films exhibited ductile failure at relatively low strains. Best combined mechanical properties were obtained from semicrystalline films cooled at intermediate rates from the melt.

  3. 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

  4. 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

  5. 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

  6. Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence.

    Science.gov (United States)

    Ersche, Karen D; Turton, Abigail J; Chamberlain, Samuel R; Müller, Ulrich; Bullmore, Edward T; Robbins, Trevor W

    2012-09-01

    Not everyone who takes drugs becomes addicted, but the likelihood of developing drug addiction is greater in people with a family history of drug or alcohol dependence. Relatively little is known about how genetic risk mediates the development of drug dependence. By comparing the phenotypic profile of individuals with and without a family history of addiction, the authors sought to clarify the extent to which cognitive dysfunction and personality traits are shared by family members--and therefore likely to have predated drug dependence--and which aspects are specific to drug-dependent individuals. The authors assessed cognitive function and personality traits associated with drug dependence in stimulant-dependent individuals (N=50), their biological siblings without a history of drug dependence (N=50), and unrelated healthy volunteers (N=50). Cognitive function was significantly impaired in the stimulant-dependent individuals across a range of domains. Deficits in executive function and response control were identified in both the stimulant-dependent individuals and in their non-drug-dependent siblings. Drug-dependent individuals and their siblings also exhibited elevated anxious-impulsive personality traits relative to healthy comparison volunteers. Deficits in executive function and response regulation as well as anxious-impulsive personality traits may represent endophenotypes associated with the risk of developing cocaine or amphetamine dependence. The identification of addiction endophenotypes may be useful in facilitating the rational development of therapeutic and preventive strategies.

  7. 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

  8. The parachute morphology as equilibrium morphology of vesicle-polymer hybrids?

    NARCIS (Netherlands)

    Jung, M.; Hubert, D.H.W.; Herk, van A.M.; German, A.L.

    2000-01-01

    Polymerisation in vesicles leads to novel polymer colloid morphologies. Two morphologies are currently reported: the triple-shell and the parachute morphology. The termodynamic analysis of these two morphologies, presented here, stresses the importance of considering interfacial energies between

  9. Local mechanical stimulation induces components of the pathogen defense response in parsley

    Science.gov (United States)

    Gus-Mayer, Sabine; Naton, Beatrix; Hahlbrock, Klaus; Schmelzer, Elmon

    1998-01-01

    Cell suspension cultures of parsley (Petroselinum crispum) have previously been used as a suitable system for studies of the nonhost resistance response to Phytophthora sojae. In this study, we replaced the penetrating fungus by local mechanical stimulation by using a needle of the same diameter as a fungal hypha, by local application of a structurally defined fungus-derived elicitor, or by a combination of the two stimuli. Similar to the fungal infection hypha, the local mechanical stimulus alone induced the translocation of cytoplasm and nucleus to the site of stimulation, the generation of intracellular reactive oxygen intermediates (ROI), and the expression of some, but not all, elicitor-responsive genes. When the elicitor was applied locally to the cell surface without mechanical stimulation, intracellular ROI also accumulated rapidly, but morphological changes were not detected. A combination of the mechanical stimulus with simultaneous application of low doses of elicitor closely simulated early reactions to fungal infection, including cytoplasmic aggregation, nuclear migration, and ROI accumulation. By contrast, cytoplasmic rearrangements were impaired at high elicitor concentrations. Neither papilla formation nor hypersensitive cell death occurred under the conditions tested. These results suggest that mechanical stimulation by the invading fungus is responsible for the observed intracellular rearrangements and may trigger some of the previously demonstrated changes in the activity of elicitor-responsive genes, whereas chemical stimulation is required for additional biochemical processes. As yet unidentified signals may be involved in papilla formation and hypersensitive cell death. PMID:9653198

  10. 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.

  11. 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.

  12. Task-dependent vestibular feedback responses in reaching.

    Science.gov (United States)

    Keyser, Johannes; Medendorp, W Pieter; Selen, Luc P J

    2017-07-01

    When reaching for an earth-fixed object during self-rotation, the motor system should appropriately integrate vestibular signals and sensory predictions to compensate for the intervening motion and its induced inertial forces. While it is well established that this integration occurs rapidly, it is unknown whether vestibular feedback is specifically processed dependent on the behavioral goal. Here, we studied whether vestibular signals evoke fixed responses with the aim to preserve the hand trajectory in space or are processed more flexibly, correcting trajectories only in task-relevant spatial dimensions. We used galvanic vestibular stimulation to perturb reaching movements toward a narrow or a wide target. Results show that the same vestibular stimulation led to smaller trajectory corrections to the wide than the narrow target. We interpret this reduced compensation as a task-dependent modulation of vestibular feedback responses, tuned to minimally intervene with the task-irrelevant dimension of the reach. These task-dependent vestibular feedback corrections are in accordance with a central prediction of optimal feedback control theory and mirror the sophistication seen in feedback responses to mechanical and visual perturbations of the upper limb. NEW & NOTEWORTHY Correcting limb movements for external perturbations is a hallmark of flexible sensorimotor behavior. While visual and mechanical perturbations are corrected in a task-dependent manner, it is unclear whether a vestibular perturbation, naturally arising when the body moves, is selectively processed in reach control. We show, using galvanic vestibular stimulation, that reach corrections to vestibular perturbations are task dependent, consistent with a prediction of optimal feedback control theory. Copyright © 2017 the American Physiological Society.

  13. Effects of Electrical Stimulation in Sympathetic Neuron-Cardiomyocyte Co-cultures

    Science.gov (United States)

    Takeuchi, Akimasa; Tani, Hiromasa; Mori, Masahide; Moriguchi, Hiroyuki; Kotani, Kiyoshi; Lee, Jong-Kook; Noshiro, Makoto; Jimbo, Yasuhiko

    The sympathetic nervous system is one of the principal sources for regulating cardiovascular functions. Little is known, however, about the network-level interactions between sympathetic neurons and cardiomyocytes. In this study, a semi-separated co-culture system of superior cervical ganglion (SCG) neurons and ventricular myocytes (VMs) was developed by using a polydimethylsyloxane (PDMS) chamber placed on a microelectrode-array (MEA) substrate. Neurites of SCG neurons passed through a conduit of the chamber and reached VMs. Evoked activities of SCG neurons were observed from several electrodes immediately after applying constant-voltage stimulation (1 V, 1 ms, biphasic square pulses) to SCG neurons by using 32 electrodes. Furthermore, this stimulation was applied to SCG neurons at the frequency of 1, 5 and 10 Hz. After applying these three kinds of stimulations, mean minute contraction rate of VMs increased with an increase in the frequency of stimulation. These results suggest that changes in contraction rate of VMs after applying electrical stimulations to SCG neurons depend on frequencies of these stimulations and that the heart-regulating mechanisms as well as that in the body were formed in this co-culture system.

  14. Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability.

    Directory of Open Access Journals (Sweden)

    Cibele V Falkenberg

    2017-03-01

    Full Text Available Kidney podocytes' function depends on fingerlike projections (foot processes that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology.

  15. 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.

  16. Cortical deactivation induced by visual stimulation in human slow-wave sleep

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Law, Ian; Lund, Torben E

    2002-01-01

    . It is unresolved whether this negative BOLD response pattern is of developmental neurobiological origin particular to a given age or to a general effect of sleep or sedative drugs. To further elucidate this issue, we used fMRI and positron emission tomography (PET) to study the brain activation pattern during......It has previously been demonstrated that sleeping and sedated young children respond with a paradoxical decrease in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the rostro-medial occipital visual cortex during visual stimulation...... visual stimulation in spontaneously sleeping adult volunteers. In five sleeping volunteers fMRI studies confirmed a robust signal decrease during stimulation in the rostro-medial occipital cortex. A similar relative decrease at the same location was found during visual stimulation...

  17. Morphological changes in the neurons of hypothalamus and ependyma of the third cerebral ventricle of sheep after irradiation

    International Nuclear Information System (INIS)

    Stanikova, A.; Pastorova, B.; Maracek, I.; Sopkova, D.; Halagan, J.

    2004-01-01

    We focused on changes in the hypothalamic neuro-secretion, morphology of brain ventricle ependyma of sheep after irradiation and hormonal stimulation. We observed sheep in anoestrus. Synchronization was ensured with Agelin for 10 days. On day 5 after the instillation of sponges, we started with irradiation lasting for 5 days (2.5 Gy) and on day 10 we stimulated the sheep with SG and FSH. The samples from hypothalamus intended for REM, were processed according to Murakami et al. (1977). Hormonal treatment in combination with irradiation produced qualitative changes, more marked in the ependyma than in the hypothalamus. (authors)

  18. Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

    Science.gov (United States)

    Vidal, Jose; Ghovanloo, Maysam

    2013-01-01

    We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

  19. 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)

  20. 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.

  1. 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.

  2. Transcranial direct current stimulation in patients with Alzheimer’s disease: Challenges and responses

    Directory of Open Access Journals (Sweden)

    Hong Yuan

    2015-09-01

    Full Text Available The use of transcranial direct current stimulation (tDCS as a noninvasive therapeutic approach for Alzheimer’s disease (AD has gained increasing attention. Research regarding the utility of tDCS in AD is inconsistent. In this study, we reviewed the importance of individual diversity among AD patients, starting from the uninformative mean results. We also demonstrated variation among AD patients. Highly educated patients seem to benefit more; education also seems to modulate baseline measurements and the results. Individual cortical morphology also affects the current distribution, which influences the effectiveness of stimulation. We suggest the use of structural MRI to distinguish inter-individual variability; high-resolution modeling can also be used to predict current distributions and should be combined with cognitive training (CT along with tDCS.

  3. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  4. Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice.

    Science.gov (United States)

    Park, Sunmee; Bandi, Akhil; Lee, Christian R; Margolis, David J

    2016-06-08

    We discovered that optical stimulation of the mystacial pad in Emx1-Cre;Ai27D transgenic mice induces whisker movements due to activation of ChR2 expressed in muscles controlling retraction and protraction. Using high-speed videography in anesthetized mice, we characterize the amplitude of whisker protractions evoked by varying the intensity, duration, and frequency of optogenetic stimulation. Recordings from primary somatosensory cortex (S1) in anesthetized mice indicated that optogenetic whisker pad stimulation evokes robust yet longer latency responses than mechanical whisker stimulation. In head-fixed mice trained to report optogenetic whisker pad stimulation, psychometric curves showed similar dependence on stimulus duration as evoked whisker movements and S1 activity. Furthermore, optogenetic stimulation of S1 in expert mice was sufficient to substitute for peripheral stimulation. We conclude that whisker protractions evoked by optogenetic activation of whisker pad muscles results in cortical activity and sensory perception, consistent with the coding of evoked whisker movements by reafferent sensory input.

  5. 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.

  6. Repeated stimulation by LPS promotes the senescence of DPSCs via TLR4/MyD88-NF-κB-p53/p21 signaling.

    Science.gov (United States)

    Feng, Guijuan; Zheng, Ke; Cao, Tong; Zhang, Jinlong; Lian, Min; Huang, Dan; Wei, Changbo; Gu, Zhifeng; Feng, Xingmei

    2018-02-26

    Dental pulp stem cells (DPSCs), one type of mesenchymal stem cells, are considered to be a type of tool cells for regenerative medicine and tissue engineering. Our previous studies found that the stimulation with lipopolysaccharide (LPS) might introduce senescence of DPSCs, and this senescence would have a positive correlation with the concentration of LPS. The β-galactosidase (SA-β-gal) staining was used to evaluate the senescence of DPSCs and immunofluorescence to show the morphology of DPSCs. Our findings suggested that the activity of SA-β-gal has increased after repeated stimulation with LPS and the morphology of DPSCs has changed with the stimulation with LPS. We also found that LPS bound to the Toll-like receptor 4 (TLR4)/myeloid differentiation factor (MyD) 88 signaling pathway. Protein and mRNA expression of TLR4, MyD88 were enhanced in DPSCs with LPS stimulation, resulting in the activation of nuclear factor-κB (NF-κB) signaling, which exhibited the expression of p65 improved in the nucleus while the decreasing of IκB-α. Simultaneously, the expression of p53 and p21, the downstream proteins of the NF-κB signaling, has increased. In summary, DPSCs tend to undergo senescence after repeated stimulation in an inflammatory microenvironment. Ultimately, these findings may lead to a new direction for cell-based therapy in oral diseases and other regenerative medicines.

  7. 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

  8. Early Arabidopsis root hair growth stimulation by pathogenic strains of Pseudomonas syringae.

    Science.gov (United States)

    Pecenková, Tamara; Janda, Martin; Ortmannová, Jitka; Hajná, Vladimíra; Stehlíková, Zuzana; Žárský, Viktor

    2017-09-01

    Selected beneficial Pseudomonas spp. strains have the ability to influence root architecture in Arabidopsis thaliana by inhibiting primary root elongation and promoting lateral root and root hair formation. A crucial role for auxin in this long-term (1week), long-distance plant-microbe interaction has been demonstrated. Arabidopsis seedlings were cultivated in vitro on vertical plates and inoculated with pathogenic strains Pseudomonas syringae pv. maculicola (Psm) and P. syringae pv. tomato DC3000 (Pst), as well as Agrobacterium tumefaciens (Atu) and Escherichia coli (Eco). Root hair lengths were measured after 24 and 48h of direct exposure to each bacterial strain. Several Arabidopsis mutants with impaired responses to pathogens, impaired ethylene perception and defects in the exocyst vesicle tethering complex that is involved in secretion were also analysed. Arabidopsis seedling roots infected with Psm or Pst responded similarly to when infected with plant growth-promoting rhizobacteria; root hair growth was stimulated and primary root growth was inhibited. Other plant- and soil-adapted bacteria induced similar root hair responses. The most compromised root hair growth stimulation response was found for the knockout mutants exo70A1 and ein2. The single immune pathways dependent on salicylic acid, jasmonic acid and PAD4 are not directly involved in root hair growth stimulation; however, in the mutual cross-talk with ethylene, they indirectly modify the extent of the stimulation of root hair growth. The Flg22 peptide does not initiate root hair stimulation as intact bacteria do, but pretreatment with Flg22 prior to Psm inoculation abolished root hair growth stimulation in an FLS2 receptor kinase-dependent manner. These early response phenomena are not associated with changes in auxin levels, as monitored with the pDR5::GUS auxin reporter. Early stimulation of root hair growth is an effect of an unidentified component of living plant pathogenic bacteria. The root

  9. 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.

  10. Morphology dependent electrical transport behavior in gold nanostructures

    International Nuclear Information System (INIS)

    Alkhatib, A.; Souier, T.; Chiesa, M.

    2011-01-01

    The mechanism of electron transport in ultra-thin gold films is investigated and its dependence on the gold islands size is reported. For gold films of thickness below 38 nm, the electrical transport occurs by tunneling within electrically discontinuous islands of gold. Simmons model for metal-insulator-metal junction describes the non-ohmic experimental current-voltage curves obtained by means of conductive atomic force microscopy. Field emission is the predominant transport for thicknesses below 23 nm while direct tunneling occurs in thicker films. The transition between the two regimes is controlled by the gold islands size and their inter-distance.

  11. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  13. 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

  14. 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...

  15. Optogenetic stimulation in a computational model of the basal ganglia biases action selection and reward prediction error.

    Science.gov (United States)

    Berthet, Pierre; Lansner, Anders

    2014-01-01

    Optogenetic stimulation of specific types of medium spiny neurons (MSNs) in the striatum has been shown to bias the selection of mice in a two choices task. This shift is dependent on the localisation and on the intensity of the stimulation but also on the recent reward history. We have implemented a way to simulate this increased activity produced by the optical flash in our computational model of the basal ganglia (BG). This abstract model features the direct and indirect pathways commonly described in biology, and a reward prediction pathway (RP). The framework is similar to Actor-Critic methods and to the ventral/dorsal distinction in the striatum. We thus investigated the impact on the selection caused by an added stimulation in each of the three pathways. We were able to reproduce in our model the bias in action selection observed in mice. Our results also showed that biasing the reward prediction is sufficient to create a modification in the action selection. However, we had to increase the percentage of trials with stimulation relative to that in experiments in order to impact the selection. We found that increasing only the reward prediction had a different effect if the stimulation in RP was action dependent (only for a specific action) or not. We further looked at the evolution of the change in the weights depending on the stage of learning within a block. A bias in RP impacts the plasticity differently depending on that stage but also on the outcome. It remains to experimentally test how the dopaminergic neurons are affected by specific stimulations of neurons in the striatum and to relate data to predictions of our model.

  16. Frequency-dependence of the slow force response.

    Science.gov (United States)

    von Lewinski, Dirk; Zhu, Danan; Khafaga, Mounir; Kockskamper, Jens; Maier, Lars S; Hasenfuss, Gerd; Pieske, Burkert

    2008-05-01

    Stretch induces biphasic inotropic effects in mammalian myocardium. A delayed component (slow force response, SFR) has been demonstrated in various species, however, experimental conditions varied and the underlying mechanisms are controversial. The physiological relevance of the SFR is poorly understood. Experiments were performed in ventricular muscle strips from failing human hearts and non-failing rabbit hearts. Upon stretch, twitch force was assessed at basal conditions (1 Hz, 37 degrees C) and after changing stimulation frequency with and without blockade of the Na+/H+-exchanger-1 (NHE1) or reverse-mode Na+/Ca2+-exchange (NCX). Action potential duration (APD) was assessed using floating electrodes. Low stimulation rates (0.2 Hz) potentiated and higher stimulation rates (2 and 3 Hz) reduced the SFR. The extent of SFR inhibition by NHE1 or NCX inhibition was not affected by stimulation rate. APD decreased at 0.2 Hz but was not altered at higher stimulation rates. The data demonstrate frequency-dependence of the SFR with greater positive inotropic effects at lower stimulation rates. Subcellular mechanisms underlying the SFR are not fundamentally affected by stimulation rate. The SFR may have more pronounced physiological effects at lower heart rates.

  17. 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)

  18. 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.

  19. Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

    Science.gov (United States)

    Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767

  20. Modulation of human time processing by subthalamic deep brain stimulation.

    Science.gov (United States)

    Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.

  1. 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.

  2. Morphological evolution of dissolving feldspar particles with anisotropic surface kinetics and implications for dissolution rate normalization and grain size dependence: A kinetic modeling study

    Science.gov (United States)

    Zhang, Li; Lüttge, Andreas

    2009-11-01

    With previous two-dimensional (2D) simulations based on surface-specific feldspar dissolution succeeding in relating the macroscopic feldspar kinetics to the molecular-scale surface reactions of Si and Al atoms ( Zhang and Lüttge, 2008, 2009), we extended our modeling effort to three-dimensional (3D) feldspar particle dissolution simulations. Bearing on the same theoretical basis, the 3D feldspar particle dissolution simulations have verified the anisotropic surface kinetics observed in the 2D surface-specific simulations. The combined effect of saturation state, pH, and temperature on the surface kinetics anisotropy has been subsequently evaluated, found offering diverse options for morphological evolution of dissolving feldspar nanoparticles with varying grain sizes and starting shapes. Among the three primary faces on the simulated feldspar surface, the (1 0 0) face has the biggest dissolution rate across an extensively wide saturation state range and thus acquires a higher percentage of the surface area upon dissolution. The slowest dissolution occurs to either (0 0 1) or (0 1 0) faces depending on the bond energies of Si-(O)-Si ( ΦSi-O-Si/ kT) and Al-(O)-Si ( ΦAl-O-Si/ kT). When the ratio of ΦSi-O-Si/ kT to ΦAl-O-Si/ kT changes from 6:3 to 7:5, the dissolution rates of three primary faces change from the trend of (1 0 0) > (0 1 0) > (0 0 1) to the trend of (1 0 0) > (0 0 1) > (0 1 0). The rate difference between faces becomes more distinct and accordingly edge rounding becomes more significant. Feldspar nanoparticles also experience an increasing degree of edge rounding from far-from-equilibrium to close-to-equilibrium. Furthermore, we assessed the connection between the continuous morphological modification and the variation in the bulk dissolution rate during the dissolution of a single feldspar particle. Different normalization treatments equivalent to the commonly used mass, cube assumption, sphere assumption, geometric surface area, and reactive

  3. [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.

  4. 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.

  5. EUV stimulated emission from MgO pumped by FEL pulses

    Directory of Open Access Journals (Sweden)

    Philippe Jonnard

    2017-09-01

    Full Text Available Stimulated emission is a fundamental process in nature that deserves to be investigated and understood in the extreme ultra-violet (EUV and x-ray regimes. Today, this is definitely possible through high energy density free electron laser (FEL beams. In this context, we give evidence for soft-x-ray stimulated emission from a magnesium oxide solid target pumped by EUV FEL pulses formed in the regime of travelling-wave amplified spontaneous emission in backward geometry. Our results combine two effects separately reported in previous works: emission in a privileged direction and existence of a material-dependent threshold for the stimulated emission. We develop a novel theoretical framework, based on coupled rate and transport equations taking into account the solid-density plasma state of the target. Our model accounts for both observed mechanisms that are the privileged direction for the stimulated emission of the Mg L2,3 characteristic emission and the pumping threshold.

  6. 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.

  7. Do caffeine-containing analgesics promote dependence? A review and evaluation.

    Science.gov (United States)

    Feinstein, A R; Heinemann, L A; Dalessio, D; Fox, J M; Goldstein, J; Haag, G; Ladewig, D; O'Brien, C P

    2000-11-01

    Debates about the suspected association between kidney disease and use of analgesics have led to concern about whether caffeine could stimulate an undesirable overuse of phenacetin-free combined analgesics. A committee was asked to critically review the pertinent literature and to suggest guides for clinical practice and for consideration of international regulatory authorities. A group of international scientists, jointly selected by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry. All invited experts evaluated relevant literature and reports and added further information and comments. Caffeine has a synergistic effectiveness with analgesics. Although caffeine has a dependence potential, the potential is low. Experimental data regarding dependence potential for caffeine alone may not correspond to the conditions in patients with pain. Withdrawal is not likely to cause stimulation or sustainment of analgesic intake. For drug-induced headache, no single or combined analgesic was consistently identified as causative, and no evidence exists for a special role of caffeine. Strong dependence behavior was observed only in patients using phenacetin-containing preparations, coformulated with antipyretics/analgesics and caffeine. This finding may have led to the impression that caffeine stimulates overuse of analgesics. Although more experimental and long-term data would be desirable to show possible mechanisms of dependence and to offer unequivocal proof of safety, the committee concluded that the available evidence does not support the claim that analgesics coformulated with caffeine, in the absence of phenacetin, stimulate or sustain overuse.

  8. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    Science.gov (United States)

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-01-01

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

  9. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    2015-07-01

    Full Text Available Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  10. Wetting morphologies and their transitions in grooved substrates

    Energy Technology Data Exchange (ETDEWEB)

    Seemann, Ralf; Bommer, Stefan; Herrmann, Carsten; Michler, Dominik [Experimental Physics, Saarland University, D-66123 Saarbruecken (Germany); Brinkmann, Martin; Herminghaus, Stephan; Khare, Krishnacharya; Kostourou, Konstantina; Gurevich, Evgeny [Max Planck Institute for Dynamics and Self-Organization, D-37073 Goettingen (Germany); Law, Bruce M; McBride, Sean, E-mail: r.seemann@physik.uni-saarland.de [Department of Physics, Kansas State University, Manhattan, KS 66506 (United States)

    2011-05-11

    When exposed to a partially wetting liquid, many natural and artificial surfaces equipped with complex topographies display a rich variety of liquid interfacial morphologies. In the present article, we focus on a few simple paradigmatic surface topographies and elaborate on the statics and dynamics of the resulting wetting morphologies. It is demonstrated that the spectrum of wetting morphologies increases with increasing complexity of the groove structure. On elastically deformable substrates, additional structures in the liquid morphologies can be observed, which are caused by deformations of the groove geometry in the presence of capillary forces. The emergence of certain liquid morphologies in grooves can be actively controlled by changes in wettability and geometry. For electrically conducting solid substrates, the apparent contact angle can be varied by electrowetting. This allows, depending on groove geometry, a reversible or irreversible transport of liquid along surface grooves. In the case of irreversible liquid transport in triangular grooves, the dynamics of the emerging instability is sensitive to the apparent hydrodynamic slip at the substrate. On elastic substrates, the geometry can be varied in a straightforward manner by stretching or relaxing the sample. The imbibition velocity in deformable grooves is significantly reduced compared to solid grooves, which is a result of the microscopic deformation of the elastic groove material close to the three phase contact line.

  11. Mental health disorders among homeless, substance-dependent men who have sex with men.

    Science.gov (United States)

    Fletcher, Jesse B; Reback, Cathy J

    2017-07-01

    Homelessness is associated with increased prevalence of mental health disorders, substance use disorders and mental health/substance use disorder comorbidity in the United States of America. Gay, bisexual and other men who have sex with men (MSM) living in the United States are at increased risk for homelessness, and have also evidenced elevated mental health and substance use disorder prevalence relative to their non-MSM male counterparts. Secondary analysis of data from a randomised controlled trial estimating the diagnostic prevalence of substance use/mental health disorder comorbidity among a sample of homeless, substance-dependent MSM (DSM-IV verified; n = 131). The most prevalent substance use/mental health disorder comorbidities were stimulant dependence comorbid with at least one depressive disorder (28%), alcohol dependence comorbid with at least one depressive disorder (26%) and stimulant dependence comorbid with antisocial personality disorder (25%). Diagnostic depression and antisocial personality disorder both demonstrated high rates of prevalence among homeless, substance-dependent (particularly stimulant and alcohol dependent) MSM. [Fletcher JB, Reback CJ. Mental health disorders among homeless, substance-dependent men who have sex with men. Drug Alcohol Rev 2016;36:555-559]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

  12. Ultraviolet radiation stimulates the release of arachidonic acid from mammalian cells in culture

    International Nuclear Information System (INIS)

    De Leo, V.A.; Hanson, D.; Weinstein, I.B.; Harber, L.C.

    1985-01-01

    C3H 10T1/2 cells in culture were prelabelled with [ 3 H]arachidonic acid and exposed to UVB radiation. Almost immediately after irradiation cells released labelled arachidonate metabolites into media in a dose dependent manner. This release was inhibited by removing calcium ions from the system and by the addition of dexamethasone and parabromophenacyl bromide to the system. This suggests that the UVB stimulated release of arachidonic acid from membrane phospholipids is, in part, mediated by a phospholipase A 2 enzyme system. Thin layer chromatographic examination of media extracts revealed a dose dependent UVB stimulation of prostaglandin production by cultured cells. (author)

  13. 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.

  14. Effectiveness of diaphragmatic stimulation with single-channel electrodes in rabbits

    Directory of Open Access Journals (Sweden)

    Rodrigo Guellner Ghedini

    2013-06-01

    Full Text Available Every year, a large number of individuals become dependent on mechanical ventilation because of a loss of diaphragm function. The most common causes are cervical spinal trauma and neuromuscular diseases. We have developed an experimental model to evaluate the performance of electrical stimulation of the diaphragm in rabbits using single-channel electrodes implanted directly into the muscle. Various current intensities (10, 16, 20, and 26 mA produced tidal volumes above the baseline value, showing that this model is effective for the study of diaphragm performance at different levels of electrical stimulation

  15. Morphological and Photometric Properties of Active and Non-Active ...

    African Journals Online (AJOL)

    kagoyire

    2Mbarara University of Science and Technology, Fac. of Science, Physics Department, P.O.. Box 1410 ... evolutionary transition from the blue cloud to the red sequence galaxies. ... galaxies, we studied their properties in the green valley, and established the ..... The Morphological Content and Environmental Dependence of.

  16. New trends in the study of podoplanin as a cell morphological regulator

    Directory of Open Access Journals (Sweden)

    Yoshihiko Sawa

    2010-08-01

    Full Text Available Podoplanin is a mucin-type glycoprotein firstly identified in podocytes, which is homologous to the type I alveolar cell specific T1α-2 antigen and to the oncofetal antigen M2A recognized by the D2-40 antibody. Podoplanin possesses a platelet aggregation-stimulating domain causes the platelet aggregation on cancer cells by the binding activity to CLEC-2. Podoplanin also contributes to the formation of membrane-actin structures. The increased podoplanin expression is found in squamous cell carcinomas at the invasive edge. It has been reported that the podoplanin induces an actin cytoskeleton rearrangement dependent on the RhoA GTPase activation to phosphorylate ezrin and facilitates an epithelial-mesenchymal transition (EMT which induces the single cell migration of cancer cells. However, the podoplanin-expressing cancer cells often express E-cadherin and migrate in a collective manner, suggesting that there are podoplanin-induced alternative pathways for the actin cytoskeleton rearrangement independent of the RhoA activation and EMT. The strong expression of podoplanin is present in salivary gland myoepithelial cells, and in enamel epithelia and odontoblasts of the tooth germ for a bell stage. Podoplanin may act as a cell morphological regulator in normal and cancer cells.

  17. 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

  18. 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

  19. 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

  20. The Angiotensin II Type 1 Receptor Antagonist Losartan Affects NHE1-Dependent Melanoma Cell Behavior

    Directory of Open Access Journals (Sweden)

    Daniel Navin Olschewski

    2018-03-01

    Full Text Available Background/Aims: The peptide hormone angiotensin II (ATII plays a prominent role in regulating vasoconstriction and blood pressure. Its primary target is the angiotensin II receptor type 1 (AT1, the stimulation of which induces an increase in cytosolic [Ca2+] and calmodulin activation. Ca2+-bound (activated calmodulin stimulates the activity of the Na+/ H+ exchanger isoform 1 (NHE1; and increased NHE1 activity is known to promote melanoma cell motility. The competitive AT1 receptor inhibitor losartan is often used to lower blood pressure in hypertensive patients. Since AT1 mediates ATII-stimulated NHE1 activity, we set out to investigate whether ATII and losartan have an impact on NHE1-dependent behavior of human melanoma (MV3 cells. Methods: ATII receptor expression was verified by PCR, F-actin was visualized using fluorescently labeled phalloidin, and cytosolic [Ca2+] and pH were determined ratiometrically using Fura-2 and BCECF, respectively. MV3 cell behavior was analyzed using migration, adhesion, invasion and proliferation assays. Results: MV3 cells express both AT1 and the angiotensin II receptor type 2 (AT2. Stimulation of MV3 cells with ATII increased NHE1 activity which could be counteracted by both losartan and the Ca2+/ calmodulin inhibitor ophiobolin-A. ATII stimulation induced a decrease in MV3 cell migration and a more spherical cell morphology accompanied by an increase in the density of F-actin. Independently of the presence of ATII, both NHE1 and migratory activity were reduced when AT1 was blocked by losartan. On the other hand, losartan clearly increased cell adhesion to, and the invasion of, a collagen type I substrate. The AT2 inhibitor PD123319 did not affect NHE1 activity, proliferation and migration, but increased adhesion and invasion. Conclusion: Losartan inhibits NHE1 activity and the migration of human melanoma cells. At the same time, losartan promotes MV3 cell adhesion and invasion. The therapeutic use of AT1

  1. CORRELATIONS OF QUASAR OPTICAL SPECTRA WITH RADIO MORPHOLOGY

    International Nuclear Information System (INIS)

    Kimball, Amy E.; Ivezic, Zeljko; Wiita, Paul J.; Schneider, Donald P.

    2011-01-01

    Using the largest homogeneous quasar sample with high-quality optical spectra and robust radio morphology classifications assembled to date, we investigate relationships between radio and optical properties with unprecedented statistical power. The sample consists of 4714 radio quasars from FIRST with S 20 ≥ 2 mJy and with spectra from the Sloan Digital Sky Survey (SDSS). Radio morphology classes include core-only (core), core-lobe (lobe), core-jet (jet), lobe-core-lobe (triple), and double-lobe. Electronic tables of the quasar samples, along with spectral composites for individual morphology classes, are made available. We examine the optical colors of these subsamples and find that radio quasars with core emission unresolved by FIRST (on ∼5'' scale) have a redder color distribution than radio-quiet quasars (S 20 ∼ I ) are correlated, which supports the hypothesis that both parameters are indicative of line-of-sight orientation. We investigate spectral line equivalent widths (EWs) as a function of R and R I , including the O [III] narrow line doublet and the C IV λ1549 and Mg II λ2799 broad lines. We find that the rest EWs of the broad lines correlate positively with R I at the 4σ-8σ level. However, we find no strong dependence of EW on R, in contrast to previously published results. A possible interpretation of these results is that EWs of quasar emission lines increase as the line-of-sight angle to the radio-jet axis decreases. These results are in stark contrast to commonly accepted orientation-based theories, which suggest that continuum emission should increase as the angle to the radio-jet axis decreases, resulting in smaller EWs of emission lines (assumed isotropic). Finally, we observe the Baldwin effect in our sample and find that it does not depend strongly on quasar radio morphology.

  2. High frequency repetitive sensory stimulation improves temporal discrimination in healthy subjects.

    Science.gov (United States)

    Erro, Roberto; Rocchi, Lorenzo; Antelmi, Elena; Palladino, Raffaele; Tinazzi, Michele; Rothwell, John; Bhatia, Kailash P

    2016-01-01

    High frequency electrical stimulation of an area of skin on a finger improves two-point spatial discrimination in the stimulated area, likely depending on plastic changes in the somatosensory cortex. However, it is unknown whether improvement also applies to temporal discrimination. Twelve young and ten elderly volunteers underwent the stimulation protocol onto the palmar skin of the right index finger. Somatosensory temporal discrimination threshold (STDT) was evaluated before and immediately after stimulation as well as 2.5h and 24h later. There was a significant reduction in somatosensory temporal threshold only on the stimulated finger. The effect was reversible, with STDT returning to the baseline values within 24h, and was smaller in the elderly than in the young participants. High frequency stimulation of the skin focally improves temporal discrimination in the area of stimulation. Given previous suggestions that the perceptual effects rely on plastic changes in the somatosensory cortex, our results are consistent with the idea that the timing of sensory stimuli is, at least partially, encoded in the primary somatosensory cortex. Such a protocol could potentially be used as a therapeutic intervention to ameliorate physiological decline in the elderly or in other disorders of sensorimotor integration. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. 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...

  4. 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.

  5. Maternal tissue is involved in stimulant reception by seeds of the parasitic plant Orobanche.

    Science.gov (United States)

    Plakhine, Dina; Tadmor, Yaakov; Ziadne, Hammam; Joel, Daniel M

    2012-04-01

    A fundamental element in the evolution of obligate root-parasitic angiosperms is their ability to germinate only in response to chemical stimulation by roots, to ensure contact with a nearby nourishing host. The aim of this study was to explore inheritance of the unique germination control in this group of plants. Analysis was made of the segregation of spontaneous (non-induced) germination that appeared in hybrid progenies derived from crosses between Orobanche cernua and O. cumana, which, like all other Orobanche species, are totally dependent on chemical stimulation for the onset of germination, and show negligible spontaneous germination in their natural seed populations. F(1) and F(2) seeds did not germinate in the absence of chemical stimulation, but significant spontaneous germination was found in some F(3) seed families. This indicates that the prevention of non-induced germination in Orobanche seeds, i.e. dependence on an external chemical stimulation for seed germination, is genetically controlled, that this genetic control is expressed in a seed tissue with maternal origin (presumably the perisperm that originates from the nucellus) and that genetic variation for this trait exists in Orobanche species. Similar segregation results were obtained in reciprocal crosses, suggesting that stimulated germination is controlled by nuclear genes.

  6. Morphology of the porous silicon obtained by electrochemical anodization method

    Science.gov (United States)

    Bertel H, S. D.; Dussán C, A.; Diaz P, J. M.

    2018-04-01

    In this report, the dependence of porous silicon with the synthesis parameters and their correlation with the optical and morphological properties is studied. The P-type silicon-crystalline samples and orientation were prepared by electrochemical anodization and were characterized using SEM in order to know the evolution of the pore morphology. It was observed that the porosity and thickness of the samples increased with the increase of the concentration in the solution and a high pore density (70%) with a pore size between 40nm and 1.5μm.

  7. Cosmic web and environmental dependence of screening: Vainshtein vs. chameleon

    Energy Technology Data Exchange (ETDEWEB)

    Falck, Bridget; Koyama, Kazuya; Zhao, Gong-Bo, E-mail: bridget.falck@port.ac.uk, E-mail: kazuya.koyama@port.ac.uk, E-mail: gong-bo.zhao@port.ac.uk [Institute of Cosmology and Gravitation, University of Portsmouth, Burnaby Road, Portsmouth (United Kingdom)

    2015-07-01

    Theories which modify general relativity to explain the accelerated expansion of the Universe often use screening mechanisms to satisfy constraints on Solar System scales. We investigate the effects of the cosmic web and the local environmental density of dark matter halos on the screening properties of the Vainshtein and chameleon screening mechanisms. We compare the cosmic web morphology of dark matter particles, mass functions of dark matter halos, mass and radial dependence of screening, velocity dispersions and peculiar velocities, and environmental dependence of screening mechanisms in f(R) and nDGP models. Using the ORIGAMI cosmic web identification routine we find that the Vainshtein mechanism depends on the cosmic web morphology of dark matter particles, since these are defined according to the dimensionality of their collapse, while the chameleon mechanism shows no morphology dependence. The chameleon screening of halos and their velocity dispersions depend on halo mass, and small halos and subhalos can be environmentally screened in the chameleon mechanism. On the other hand, the screening of halos in the Vainshtein mechanism does not depend on mass nor environment, and their velocity dispersions are suppressed. The peculiar velocities of halos in the Vainshtein mechanism are enhanced because screened objects can still feel the fifth force generated by external fields, while peculiar velocities of chameleon halos are suppressed when the halo centers are screened.

  8. Cosmic web and environmental dependence of screening: Vainshtein vs. chameleon

    International Nuclear Information System (INIS)

    Falck, Bridget; Koyama, Kazuya; Zhao, Gong-Bo

    2015-01-01

    Theories which modify general relativity to explain the accelerated expansion of the Universe often use screening mechanisms to satisfy constraints on Solar System scales. We investigate the effects of the cosmic web and the local environmental density of dark matter halos on the screening properties of the Vainshtein and chameleon screening mechanisms. We compare the cosmic web morphology of dark matter particles, mass functions of dark matter halos, mass and radial dependence of screening, velocity dispersions and peculiar velocities, and environmental dependence of screening mechanisms in f(R) and nDGP models. Using the ORIGAMI cosmic web identification routine we find that the Vainshtein mechanism depends on the cosmic web morphology of dark matter particles, since these are defined according to the dimensionality of their collapse, while the chameleon mechanism shows no morphology dependence. The chameleon screening of halos and their velocity dispersions depend on halo mass, and small halos and subhalos can be environmentally screened in the chameleon mechanism. On the other hand, the screening of halos in the Vainshtein mechanism does not depend on mass nor environment, and their velocity dispersions are suppressed. The peculiar velocities of halos in the Vainshtein mechanism are enhanced because screened objects can still feel the fifth force generated by external fields, while peculiar velocities of chameleon halos are suppressed when the halo centers are screened

  9. 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.

  10. 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

  11. 5-YEAR SURVIVAL OF PATIENTS WITH STAGE II UTERINE CANCER DEPENDING ON MORPHOLOGIC FEATURES OF TUMOR

    Directory of Open Access Journals (Sweden)

    Ye. A. Mustafina

    2008-01-01

    Full Text Available Retrospective data of treatment results of 109 patients with rarely observed stage II uterine cancer, admitted to N.N. Blokhin Russian Cancer Research Center from 1980 to 2000 is analyzed. Correlation of overall 5-year survival rates of stage IIA and IIB uterine can- cer patients with a number of tumor morphologic features is studied. The influence of some non-elucidated morphologic features of stage IIA and IIB uterine cancer such as the degree of cellular anaplasia, the depth of tumor invasion into the uterine neck, lymho- vascular invasion into the myometrium and uterine neck, microscopic vessels density in the area of the most extensive invasion, the presence of necrotic areas in the tumor tissue on long-term treatment results are analyzed.

  12. Xenopus laevis Retinal Ganglion Cell Dendritic Arbors Develop Independently of Visual Stimulation

    Directory of Open Access Journals (Sweden)

    Barbara Lom

    2004-01-01

    Full Text Available Newly formed neurons must locate their appropriate target cells and then form synaptic connections with these targets in order to establish a functional nervous system. In the vertebrate retina, retinal ganglion cell (RGC dendrites extend from the cell body and form synapses with nearby amacrine and bipolar cells. RGC axons, however, exit the retina and synapse with the dendrites of midbrain neurons in the optic tectum. We examined how visual stimulation influenced Xenopus RGC dendritic arborization. Neuronal activity is known to be an important factor in shaping dendritic and axonal arborization. Thus, we reared tadpoles in dark and light environments then used rhodamine dextran retrograde labeling to identify RGCs in the retina. When we compared RGC dendritic arbors from tadpoles reared in dark and light environments, we found no morphological differences, suggesting that physiological visual activity did not contribute to the morphological development of Xenopus RGC dendritic arbors.

  13. 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.

  14. Morphology of the human atrioventricular node is age dependent: a feature of potential clinical significance

    NARCIS (Netherlands)

    Waki, K.; Kim, J. S.; Becker, A. E.

    2000-01-01

    Advances in catheter ablation procedures have created the need to understand better the morphology of the AV node (AVN), particularly as it relates to age. This study was based on 40 normally structured hearts obtained at autopsy from patients without a history of tachyarrhythmia in the following

  15. Peroxiredoxin II is an antioxidant enzyme that negatively regulates collagen-stimulated platelet function.

    Science.gov (United States)

    Jang, Ji Yong; Wang, Su Bin; Min, Ji Hyun; Chae, Yun Hee; Baek, Jin Young; Yu, Dae-Yeul; Chang, Tong-Shin

    2015-05-01

    Collagen-induced platelet signaling is mediated by binding to the primary receptor glycoprotein VI (GPVI). Reactive oxygen species produced in response to collagen have been found to be responsible for the propagation of GPVI signaling pathways in platelets. Therefore, it has been suggested that antioxidant enzymes could down-regulate GPVI-stimulated platelet activation. Although the antioxidant enzyme peroxiredoxin II (PrxII) has emerged as having a role in negatively regulating signaling through various receptors by eliminating H2O2 generated upon receptor stimulation, the function of PrxII in collagen-stimulated platelets is not known. We tested the hypothesis that PrxII negatively regulates collagen-stimulated platelet activation. We analyzed PrxII-deficient murine platelets. PrxII deficiency enhanced GPVI-mediated platelet activation through the defective elimination of H2O2 and the impaired protection of SH2 domain-containing tyrosine phosphatase 2 (SHP-2) against oxidative inactivation, which resulted in increased tyrosine phosphorylation of key components for the GPVI signaling cascade, including Syk, Btk, and phospholipase Cγ2. Interestingly, PrxII-mediated antioxidative protection of SHP-2 appeared to occur in the lipid rafts. PrxII-deficient platelets exhibited increased adhesion and aggregation upon collagen stimulation. Furthermore, in vivo experiments demonstrated that PrxII deficiency facilitated platelet-dependent thrombus formation in injured carotid arteries. This study reveals that PrxII functions as a protective antioxidant enzyme against collagen-stimulated platelet activation and platelet-dependent thrombosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Morphology targets: What do seedling morphological attributes tell us?

    Science.gov (United States)

    Jeremiah R. Pinto

    2011-01-01

    Morphology is classically defined as the form and structure of individual organisms, as distinct from their anatomy or physiology. We use morphological targets in the nursery because they are easy to measure, and because we can often quantitatively link seedling morphological traits with survival and growth performance in the field. In the 20 years since the Target...

  17. Model-based Vestibular Afferent Stimulation: Modular Workflow for Analyzing Stimulation Scenarios in Patient Specific and Statistical Vestibular Anatomy

    Directory of Open Access Journals (Sweden)

    Michael Handler

    2017-12-01

    Full Text Available Our sense of balance and spatial orientation strongly depends on the correct functionality of our vestibular system. Vestibular dysfunction can lead to blurred vision and impaired balance and spatial orientation, causing a significant decrease in quality of life. Recent studies have shown that vestibular implants offer a possible treatment for patients with vestibular dysfunction. The close proximity of the vestibular nerve bundles, the facial nerve and the cochlear nerve poses a major challenge to targeted stimulation of the vestibular system. Modeling the electrical stimulation of the vestibular system allows for an efficient analysis of stimulation scenarios previous to time and cost intensive in vivo experiments. Current models are based on animal data or CAD models of human anatomy. In this work, a (semi-automatic modular workflow is presented for the stepwise transformation of segmented vestibular anatomy data of human vestibular specimens to an electrical model and subsequently analyzed. The steps of this workflow include (i the transformation of labeled datasets to a tetrahedra mesh, (ii nerve fiber anisotropy and fiber computation as a basis for neuron models, (iii inclusion of arbitrary electrode designs, (iv simulation of quasistationary potential distributions, and (v analysis of stimulus waveforms on the stimulation outcome. Results obtained by the workflow based on human datasets and the average shape of a statistical model revealed a high qualitative agreement and a quantitatively comparable range compared to data from literature, respectively. Based on our workflow, a detailed analysis of intra- and extra-labyrinthine electrode configurations with various stimulation waveforms and electrode designs can be performed on patient specific anatomy, making this framework a valuable tool for current optimization questions concerning vestibular implants in humans.

  18. Seed selection by earthworms : chemical seed properties matter more than morphological traits

    OpenAIRE

    Clause, J.; Forey, E.; Eisenhauer, N.; Seal, C.E.; Soudey, A.; Colville, L.; Barot, Sébastien

    2017-01-01

    Aims : The passage of seeds through the earthworm gut potentially damages seeds, altering seed and seedling performances depending on seed traits. This work was conducted to study to what extent chemical and morphological seed traits determine the seed attractiveness for earthworms. Methods : We tested seed selection via the ingestion and digestion of 23 grassland plant species spanning a range of 14 morphological and chemical traits by two common earthworm species: the anecic Lumbricus te...

  19. 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.

  20. Temporal code-driven stimulation: definition and application to electric fish signaling

    Directory of Open Access Journals (Sweden)

    Angel Lareo

    2016-10-01

    Full Text Available Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox.

  1. Localized Induced Current Stimulation to Neuronal Culture Using Soft Magnetic Material

    Science.gov (United States)

    Saito, Atsushi; Saito, Aki; Moriguchi, Hiroyuki; Kotani, Kiyoshi; Jimbo, Yasuhiko

    To establish precisely focused magnetic stimulation, we developed a Mu-meal based low-frequency localized induced current (LIC) stimulation system with micro-fabricated dual cell-culture chamber. The dual cell-culture chamber was arranged in a concentric circle manner. Between the inner and outer chambers, 4 or 8 connecting micro-channels were fabricated using polydimethylsiloxane (PDMS). Rat cortical neurons were separately cultured in outer and inner chambers. Through the micro-channels, functional synaptic connections were formed. Mu-metal that has very high magnetic permeability was aligned along the outer circle, which allowed us of LIC stimulation to the cells in the outer chamber. Applying low-frequency magnetic fields to the Mu-metal, induced currents were generated and the electrical activity of the cells in the outer chamber was modified depending on the stimulation intensity. Following the modified activity in the outer circles, the cells in the inner chamber also showed slightly depressed activity patterns. These results suggested that our system would be promising for localized stimulation of neuronal networks and highly regulation of network activities.

  2. 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.

  3. NaGd(MoO4)2 nanocrystals with diverse morphologies: controlled synthesis, growth mechanism, photoluminescence and thermometric properties.

    Science.gov (United States)

    Li, Anming; Xu, Dekang; Lin, Hao; Yang, Shenghong; Shao, Yuanzhi; Zhang, Yueli

    2016-08-10

    Pure tetragonal phase, uniform and well-crystallized sodium gadolinium molybdate (NaGd(MoO4)2) nanocrystals with diverse morphologies, e.g. nanocylinders, nanocubes and square nanoplates have been selectively synthesized via oleic acid-mediated hydrothermal method. The phase, structure, morphology and composition of the as-synthesized products are studied. Contents of both sodium molybdate and oleic acid of the precursor solutions are found to affect the morphologies of the products significantly, and oleic acid plays a key role in the morphology-controlled synthesis of NaGd(MoO4)2 nanocrystals with diverse morphologies. Growth mechanism of NaGd(MoO4)2 nanocrystals is proposed based on time-dependent morphology evolution and X-ray diffraction analysis. Morphology-dependent down-shifting photoluminescence properties of NaGd(MoO4)2: Eu(3+) nanocrystals, and upconversion photoluminescence properties of NaGd(MoO4)2: Yb(3+)/Er(3+) and Yb(3+)/Tm(3+) nanoplates are investigated in detail. Charge transfer band in the down-shifting excitation spectra shows a slight blue-shift, and the luminescence intensities and lifetimes of Eu(3+) are decreased gradually with the morphology of the nanocrystals varying from nanocubes to thin square nanoplates. Upconversion energy transfer mechanisms of NaGd(MoO4)2: Yb(3+)/Er(3+), Yb(3+)/Tm(3+) nanoplates are proposed based on the energy level scheme and power dependence of upconversion emissions. Thermometric properties of NaGd(MoO4)2: Yb(3+)/Er(3+) nanoplates are investigated, and the maximum sensitivity is determined to be 0.01333 K(-1) at 285 K.

  4. 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

  5. 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.

  6. Electrical stimulation of dog pudendal nerve regulates the excitatory pudendal-to-bladder reflex

    Directory of Open Access Journals (Sweden)

    Yan-he Ju

    2016-01-01

    Full Text Available Pudendal nerve plays an important role in urine storage and voiding. Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury. We had confirmed the inhibitory pudendal-to-bladder reflex by stimulating either the branch or the trunk of the pudendal nerve. This study explored the excitatory pudendal-to-bladder reflex in beagle dogs, with intact or injured spinal cord, by electrical stimulation of the pudendal nerve trunk. The optimal stimulation frequency was approximately 15-25 Hz. This excitatory effect was dependent to some extent on the bladder volume. We conclude that stimulation of the pudendal nerve trunk is a promising method to modulate bladder function.

  7. 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.

  8. Evaluation of high-perimeter electrode designs for deep brain stimulation

    Science.gov (United States)

    Howell, Bryan; Grill, Warren M.

    2014-08-01

    Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, complications including infections and mis-programing following surgical replacement of the battery-powered implantable pulse generator adversely impact the safety profile of this therapy. We sought to decrease power consumption and extend battery life by modifying the electrode geometry to increase stimulation efficiency. The specific goal of this study was to determine whether electrode contact perimeter or area had a greater effect on increasing stimulation efficiency. Approach. Finite-element method (FEM) models of eight prototype electrode designs were used to calculate the electrode access resistance, and the FEM models were coupled with cable models of passing axons to quantify stimulation efficiency. We also measured in vitro the electrical properties of the prototype electrode designs and measured in vivo the stimulation efficiency following acute implantation in anesthetized cats. Main results. Area had a greater effect than perimeter on altering the electrode access resistance; electrode (access or dynamic) resistance alone did not predict stimulation efficiency because efficiency was dependent on the shape of the potential distribution in the tissue; and, quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. Significance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

    Science.gov (United States)

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

    2015-04-01

    Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. 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

  15. The Immunoexpression of FSH-R in the Ductuli Efferentes and the Epididymis of Men and Rat: Effect of FSH on the Morphology and Steroidogenic Activity of Rat Epididymal Epithelial Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Małgorzata Świder-Al-Amawi

    2010-01-01

    Full Text Available The Sertoli cells were regarded as the only target for FSH in male reproductive system. The expression of FSH receptor (FSH-R was detected also in epithelial cells of the caput epididymis of rat and monkey. We showed in the immunohistochemistry study the expression of FSH-R in rat and human ductuli efferentes and the caput, corpus, and cauda epididymis, moreover, by Western blot analysis in the caput and cauda epididymis of rat. Additionally, we presented that the morphology of rat epididymal epithelial cells in vitro was affected by FSH, and FSH stimulation resulted in the increase of 17β-estradiol synthesis by rat caput epididymal cells in dose-depended manner. In conclusion, the identification of FSH receptors in human and rat epididymides supports our results that the epididymis is a target organ not only for LH but additionally for FSH. On the basis of the results we showed for the first time that morphology of epididymal epithelial cells and epididymal steroidogenesis can be regulated by FSH.

  16. 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.

  17. 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...

  18. Morphological changes in ultrafast laser ablation plumes with varying spot size.

    Science.gov (United States)

    Harilal, S S; Diwakar, P K; Polek, M P; Phillips, M C

    2015-06-15

    We investigated the role of spot size on plume morphology during ultrafast laser ablation of metal targets. Our results show that the spatial features of fs LA plumes are strongly dependent on the focal spot size. Two-dimensional self-emission images showed that the shape of the ultrafast laser ablation plumes changes from spherical to cylindrical with an increasing spot size from 100 to 600 μm. The changes in plume morphology and internal structures are related to ion emission dynamics from the plasma, where broader angular ion distribution and faster ions are noticed for the smallest spot size used. The present results clearly show that the morphological changes in the plume with spot size are independent of laser pulse width.

  19. 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.

  20. Morphology and function of the forelimb in arboreal frogs: specializations for grasping ability?

    Science.gov (United States)

    Manzano, Adriana S; Abdala, Virginia; Herrel, Anthony

    2008-09-01

    Frogs are characterized by a unique morphology associated with their saltatory lifestyle. Although variation in the form and function of the pelvic girdle and associated appendicular system related to specialized locomotor modes such as swimming or burrowing has been documented, the forelimbs have typically been viewed as relatively unspecialized. Yet, previous authors have noted versatility in forelimb function among arboreal frogs associated with feeding. Here we study the morphology and function of the forelimb and hand during locomotion in two species of arboreal frogs (Litoria caerulea and Phyllomedusa bicolor). Our data show a complex arrangement of the distal forelimb and hand musculature with some notable differences between species. Analyses of high-speed video and video fluoroscopy recordings show that forelimbs are used in alternating fashion in a diagonal sequence footfall pattern and that the position of the hand is adjusted when walking on substrates of different diameters. Electromyographic recordings show that the flexors of the hand are active during substrate contact, suggesting the use of gripping to generate a stabilizing torque. Measurements of grasping forces in vivo and during stimulation experiments show that both species, are capable of executing a so-called power grip but also indicates marked differences between species, in the magnitude of forces generated. Stimulation experiments showed an increased control of digit flexion in the more specialized of the two species, allowing it to execute a precision grip paralleled only by that seen in primates.

  1. Network connectivity and individual responses to brain stimulation in the human motor system.

    Science.gov (United States)

    Cárdenas-Morales, Lizbeth; Volz, Lukas J; Michely, Jochen; Rehme, Anne K; Pool, Eva-Maria; Nettekoven, Charlotte; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2014-07-01

    The mechanisms driving cortical plasticity in response to brain stimulation are still incompletely understood. We here explored whether neural activity and connectivity in the motor system relate to the magnitude of cortical plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Twelve right-handed volunteers underwent functional magnetic resonance imaging during rest and while performing a simple hand motor task. Resting-state functional connectivity, task-induced activation, and task-related effective connectivity were assessed for a network of key motor areas. We then investigated the effects of intermittent theta-burst stimulation (iTBS) on motor-evoked potentials (MEP) for up to 25 min after stimulation over left primary motor cortex (M1) or parieto-occipital vertex (for control). ITBS-induced increases in MEP amplitudes correlated negatively with movement-related fMRI activity in left M1. Control iTBS had no effect on M1 excitability. Subjects with better response to M1-iTBS featured stronger preinterventional effective connectivity between left premotor areas and left M1. In contrast, resting-state connectivity did not predict iTBS aftereffects. Plasticity-related changes in M1 following brain stimulation seem to depend not only on local factors but also on interconnected brain regions. Predominantly activity-dependent properties of the cortical motor system are indicative of excitability changes following induction of cortical plasticity with rTMS. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Crack layer morphology and toughness characterization in steels

    Science.gov (United States)

    Chudnovsky, A.; Bessendorf, M.

    1983-01-01

    Both the macro studies of crack layer propagation are presented. The crack extension resistance parameter R sub 1 based on the morphological study of microdefects is introduced. Experimental study of the history dependent nature of G sub c supports the representation of G sub c as a product of specific enthalpy of damage (material constant) and R sub 1. The latter accounts for the history dependence. The observation of nonmonotonic crack growth under monotonic changes of J as well as statistical features of the critical energy release rate (variance of G sub c) indicate the validity of the proposed damage characterization.

  3. Calcium and osmotic stimulation in renin release from isolated rat glomeruli

    DEFF Research Database (Denmark)

    Skøtt, O

    1986-01-01

    of the RR rate preceding the stimulus. Removal of calcium stimulated the RR by 10 times (n = 5, p less than 0.001) and a subsequent decrease in osmolality of 20 mOsm/kg stimulated the RR proportionally to that observed in the series containing 2 mM calcium. A decrease in osmolality was able to stimulate RR......The effects of changes in osmolality and calcium concentration on renin release (RR) from isolated superfused rat glomeruli were studied. The undisturbed RR followed a first order fall with a half-time of about 100 min (n = 45). Changes in the osmolality between 270 and 350 mOsm/kg resulted in dose......-dependent changes in the RR rates. Hypoosmotic treatment stimulated the RR transiently, whereas hyperosmotic treatment produced a sustained inhibition. The dose-response relationship was log-linear between 270 and 320 mOsm/kg. A decrease in osmolality of 20 mOsm/kg gave proportional increases in RR irrespectively...

  4. Adrenaline potentiates PI 3-kinase in platelets stimulated with thrombin and SFRLLN: role of secreted ADP.

    Science.gov (United States)

    Selheim, F; Frøyset, A K; Strand, I; Vassbotn, F S; Holmsen, H

    2000-11-17

    Adrenaline significantly potentiated late thrombin- and SFRLLN-induced PtdIns(3,4)P(2) production. Furthermore, the potentiating effect of adrenaline on thrombin-induced PtdIns(3, 4)P(2) production was independent on secreted ADP, whereas, the effect of adrenaline on SFRLLN-induced PtdIns(3,4)P(2) production was completely dependent of secreted ADP. However, the ADP-dependent accumulation of PtdIns(3,4)P(2) was not required for irreversible platelet aggregation induced by SFRLLN in the presence of adrenaline. It is concluded that adrenaline can replace secreted ADP to potentiate PtdIns(3,4)P(2) production in thrombin-stimulated but not in SFRLLN-stimulated platelets, thus demonstrating a qualitative difference between platelet stimulation by thrombin and the thrombin receptor activating peptide SFRLLN.

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

    Science.gov (United States)

    Ponnath, Abhilash; Farris, Hamilton E

    2014-01-01

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

  6. Angiotensin II stimulates superoxide production by nitric oxide synthase in thick ascending limbs.

    Science.gov (United States)

    Gonzalez-Vicente, Agustin; Saikumar, Jagannath H; Massey, Katherine J; Hong, Nancy J; Dominici, Fernando P; Carretero, Oscar A; Garvin, Jeffrey L

    2016-02-01

    Angiotensin II (Ang II) causes nitric oxide synthase (NOS) to become a source of superoxide (O2 (-)) via a protein kinase C (PKC)-dependent process in endothelial cells. Ang II stimulates both NO and O2 (-) production in thick ascending limbs. We hypothesized that Ang II causes O2 (-) production by NOS in thick ascending limbs via a PKC-dependent mechanism. NO production was measured in isolated rat thick ascending limbs using DAF-FM, whereas O2 (-) was measured in thick ascending limb suspensions using the lucigenin assay. Consistent stimulation of NO was observed with 1 nmol/L Ang II (P thick ascending limbs via a PKC- and NADPH oxidase-dependent process; and (2) the effect of Ang II is not due to limited substrate. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. Morphological response to competition for light in the clonal Trifolium repens (Fabaceae).

    Science.gov (United States)

    Bittebiere, Anne-Kristel; Renaud, Nolwenn; Clément, Bernard; Mony, Cendrine

    2012-04-01

    Plant communities in temperate zones are dominated by clonal plants that can plastically modify their growth characteristics in response to competition. Given that plants compete with one another, and the implications this has for species coexistence, we conducted a study to assess how clonal species morphologically respond to competition for light depending on its intensity and heterogeneity, which are determined by the competitor species. We assessed the morphological response to competition for light of the clonal species Trifolium repens L. by measuring its growth performance, and vertical and horizontal growth traits. We used five competitive environments, i.e., one without competitor and four differing by their competitor species creating different conditions of competition intensity and heterogeneity. The morphological response of Trifolium repens to competition for light depended on the competitor identity. Competition intensity and heterogeneity, determined by competitor identity, had an interactive effect on most traits. The increase in petiole elongation and specific leaf area due to increased competition intensity was observed only at low to intermediate competition heterogeneity. Competition heterogeneity promoted the elongation of clone connections allowing space exploration. Our results demonstrated that the intensity and heterogeneity of competition, which depended on competitor identity, are of primary importance in determining the plastic response of Trifolium repens. This emphasizes that it is important to consider the fine-scale spatial distribution of individuals when studying their interactions within plant communities.

  8. 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

  9. Morphology control in polymer blend fibers—a high throughput computing approach

    Science.gov (United States)

    Sesha Sarath Pokuri, Balaji; Ganapathysubramanian, Baskar

    2016-08-01

    Fibers made from polymer blends have conventionally enjoyed wide use, particularly in textiles. This wide applicability is primarily aided by the ease of manufacturing such fibers. More recently, the ability to tailor the internal morphology of polymer blend fibers by carefully designing processing conditions has enabled such fibers to be used in technologically relevant applications. Some examples include anisotropic insulating properties for heat and anisotropic wicking of moisture, coaxial morphologies for optical applications as well as fibers with high internal surface area for filtration and catalysis applications. However, identifying the appropriate processing conditions from the large space of possibilities using conventional trial-and-error approaches is a tedious and resource-intensive process. Here, we illustrate a high throughput computational approach to rapidly explore and characterize how processing conditions (specifically blend ratio and evaporation rates) affect the internal morphology of polymer blends during solvent based fabrication. We focus on a PS: PMMA system and identify two distinct classes of morphologies formed due to variations in the processing conditions. We subsequently map the processing conditions to the morphology class, thus constructing a ‘phase diagram’ that enables rapid identification of processing parameters for specific morphology class. We finally demonstrate the potential for time dependent processing conditions to get desired features of the morphology. This opens up the possibility of rational stage-wise design of processing pathways for tailored fiber morphology using high throughput computing.

  10. Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MED-EL standard electrode array

    Directory of Open Access Journals (Sweden)

    Helbig Silke

    2009-12-01

    Full Text Available Abstract Background The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea. Methods Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™ feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Results Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusions Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue

  11. 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...

  12. Multiscale Morphology of Nanoporous Copper Made from Intermetallic Phases

    International Nuclear Information System (INIS)

    Egle, Tobias; Harvard University, Cambridge, MA; Barroo, Cédric; Janvelyan, Nare; Baumgaertel, Andreas C.

    2017-01-01

    Many application-relevant properties of nanoporous metals critically depend on their multiscale architecture. For example, the intrinsically high step-edge density of curved surfaces at the nanoscale provides highly reactive sites for catalysis, whereas the macroscale pore and grain morphology determines the macroscopic properties, such as mass transport, electrical conductivity, or mechanical properties. Here, in this work, we systematically study the effects of alloy composition and dealloying conditions on the multiscale morphology of nanoporous copper (np-Cu) made from various commercial Zn–Cu precursor alloys. Using a combination of X-ray diffraction, electron backscatter diffraction, and focused ion beam cross-sectional analysis, our results reveal that the macroscopic grain structure of the starting alloy surprisingly survives the dealloying process, despite a change in crystal structure from body-centered cubic (Zn–Cu starting alloy) to face-centered cubic (Cu). The nanoscale structure can be controlled by the acid used for dealloying with HCl leading to a larger and more faceted ligament morphology compared to that of H_3PO_4. Finally, anhydrous ethanol dehydrogenation was used as a probe reaction to test the effect of the nanoscale ligament morphology on the apparent activation energy of the reaction.

  13. Structure and Morphology Effects on the Optical Properties of Bimetallic Nanoparticle Films Laser Deposited on a Glass Substrate

    Directory of Open Access Journals (Sweden)

    A. O. Kucherik

    2017-01-01

    Full Text Available Moving nanosecond laser system is used for laser-assisted thermodiffusion deposition of metallic nanoparticles from water-based colloidal solutions. The results obtained for both gold and silver nanoparticles show that film morphology strongly depends on laser scanning speed and the number of passages. We show, furthermore, the possibility of producing bimetallic Au:Ag thin films by laser irradiation of the mixed solutions. As a result of several laser scans, granular nanometric films are found to grow with a well-controlled composition, thickness, and morphology. By changing laser scanning parameters, film morphology can be varied from island structures to quasi-periodic arrays. The optical properties of the deposited structures are found to depend on the film composition, thickness, and mean separation between the particles. The transparency spectra of the deposited films are shown to be defined by their morphology.

  14. Seeding of Polariton Stimulation in a Homogeneously Broadened Microcavity

    DEFF Research Database (Denmark)

    Østergaard, John Erland; Langbein, Wolfgang Werner; Jensen, Jacob Riis

    2000-01-01

    In time-resolved light emission from a high-quality semiconductor microcavity after pulsed excitation suitable for angle-resonant polariton-polariton scattering on the lower-polariton branch, we find strong evidence for final-state stimulation of this process. The self-stimulated emission...... and the intensity of this emission can be controlled. The time-resolved data and the density dependences are in agreement with a rate equation model neglecting polarization mixing effects. This model gives a coupling coefficient of b(LP,k)=0 = 2.4 x 10(-9) cm(4) s(-1) for the stimulated angle-resonant polariton......, following single-pulse excitation, appears on a fast time scale of only a few lens of ps with a maximum at 15 ps. This is in striking contrast to the photoluminescence decay time of 110 ps observed in the low-density limit. By injection of polaritons into the final state by a seeding pulse, the dynamics...

  15. Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

    Science.gov (United States)

    Nettekoven, Charlotte; Volz, Lukas J; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2014-05-14

    Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. Copyright © 2014 the authors 0270-6474/14/346849-11$15.00/0.

  16. 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

  17. Pharmacokinetic variability of long-acting stimulants in the treatment of children and adults with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Ermer, James C; Adeyi, Ben A; Pucci, Michael L

    2010-12-01

    Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies for attention-deficit hyperactivity disorder, a common neurobehavioural disorder in children and adults. A number of long-acting stimulant formulations have been developed with the aim of providing once-daily dosing, employing various means to extend duration of action, including a transdermal delivery system, an osmotic-release oral system, capsules with a mixture of immediate- and delayed-release beads, and prodrug technology. Coefficients of variance of pharmacokinetic measures can estimate the levels of pharmacokinetic variability based on the measurable variance between different individuals receiving the same dose of stimulant (interindividual variability) and within the same individual over multiple administrations (intraindividual variability). Differences in formulation clearly impact pharmacokinetic profiles. Many medications exhibit wide interindividual variability in clinical response. Stimulants with low levels of inter- and intraindividual variability may be better suited to provide consistent levels of medication to patients. The pharmacokinetic profile of stimulants using pH-dependent bead technology can vary depending on food consumption or concomitant administration of medications that alter gastric pH. While delivery of methylphenidate with the transdermal delivery system would be unaffected by gastrointestinal factors, intersubject variability is nonetheless substantial. Unlike the beaded formulations and, to some extent (when considering total exposure) the osmotic-release formulation, systemic exposure to amfetamine with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected by such factors, likely owing to its dependence on systemic enzymatic cleavage of the precursor molecule, which occurs primarily in the blood involving red blood cells. The high capacity but as yet unidentified enzymatic system for conversion of lisdexamfetamine

  18. Flow and fouling in membrane filters: Effects of membrane morphology

    Science.gov (United States)

    Sanaei, Pejman; Cummings, Linda J.

    2015-11-01

    Membrane filters are widely-used in microfiltration applications. Many types of filter membranes are produced commercially, for different filtration applications, but broadly speaking the requirements are to achieve fine control of separation, with low power consumption. The answer to this problem might seem obvious: select the membrane with the largest pore size and void fraction consistent with the separation requirements. However, membrane fouling (an inevitable consequence of successful filtration) is a complicated process, which depends on many parameters other than membrane pore size and void fraction; and which itself greatly affects the filtration process and membrane functionality. In this work we formulate mathematical models that can (i) account for the membrane internal morphology (internal structure, pore size & shape, etc.); (ii) fouling of membranes with specific morphology; and (iii) make some predictions as to what type of membrane morphology might offer optimum filtration performance.

  19. A Mobile Early Stimulation Program to Support Children with Developmental Delays in Brazil.

    Science.gov (United States)

    Dias, Raquel da Luz; Silva, Kátia Cristina Correa Guimarães; Lima, Marcela Raquel de Oliveira; Alves, João Guilherme Bezerra; Abidi, Syed Sibte Raza

    2018-01-01

    Developmental delay is a deviation development from the normative milestones during the childhood and it may be caused by neurological disorders. Early stimulation is a standardized and simple technique to treat developmental delays in children (aged 0-3 years), allowing them to reach the best development possible and to mitigate neuropsychomotor sequelae. However, the outcomes of the treatment depending on the involvement of the family, to continue the activities at home on a daily basis. To empower and educate parents of children with neurodevelopmental delays to administer standardized early stimulation programs at home, we developed a mobile early stimulation program that provides timely and evidence-based clinical decision support to health professionals and a personalized guidance to parents about how to administer early stimulation to their child at home.

  20. fMRI activation during spike and wave discharges evoked by photic stimulation

    DEFF Research Database (Denmark)

    Moeller, Friederike; Siebner, Hartwig R; Ahlgrimm, Nils

    2009-01-01

    Photoparoxysmal response (PPR) is an electroencephalographic (EEG) trait characterized by the occurrence of epileptiform discharges in response to visual stimulation. Studying this trait helps to learn about mechanisms of epileptogenicity. While simultaneous recordings of EEG and functional MRI...... intermittent photic stimulation (IPS) in a 3 T MR scanner. PPR was elicited in 6 subjects, four diagnosed with idiopathic generalised epilepsy and two with tension-type headache. Because PPR is preceded by synchronization of cortical gamma oscillations, blood oxygenation level-dependent (BOLD) signal changes...