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Sample records for neurochemical systems relevant

  1. Distinct Neurochemical Profiles of Spinocerebellar Ataxias 1, 2, 6, and Cerebellar Multiple System Atrophy

    Science.gov (United States)

    Öz, Gülin; Iltis, Isabelle; Hutter, Diane; Thomas, William; Bushara, Khalaf O.; Gomez, Christopher M.

    2011-01-01

    Hereditary and sporadic neurodegenerative ataxias are movement disorders that affect the cerebellum. Robust and objective biomarkers are critical for treatment trials of ataxias. In addition, such biomarkers may help discriminate between ataxia subtypes because these diseases display substantial overlap in clinical presentation and conventional MRI. Profiles of 10–13 neurochemical concentrations obtained in vivo by high field proton magnetic resonance spectroscopy (1H MRS) can potentially provide ataxia-type specific biomarkers. We compared cerebellar and brainstem neurochemical profiles measured at 4 T from 26 patients with spinocerebellar ataxias (SCA1, N=9; SCA2, N=7; SCA6, N=5) or cerebellar multiple system atrophy (MSA-C, N=5) and 15 age-matched healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA) was used to assess disease severity. The patterns of neurochemical alterations relative to controls differed between ataxia types. Myo-inositol levels in the vermis, myo-inositol, total N-acetylaspartate, total creatine, glutamate, glutamine in the cerebellar hemispheres and myo-inositol, total N-acetylaspartate, glutamate in the pons were significantly different between patient groups (Bonferroni corrected pataxia types. Studies with higher numbers of patients and other ataxias are warranted to further investigate the clinical utility of neurochemical levels as measured by high-field MRS as ataxia biomarkers. PMID:20838948

  2. Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing.

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    Delli Pizzi, Stefano; Chiacchiaretta, Piero; Mantini, Dante; Bubbico, Giovanna; Ferretti, Antonio; Edden, Richard A; Di Giulio, Camillo; Onofrj, Marco; Bonanni, Laura

    2017-04-01

    The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala-mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala-mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1 H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion.

  3. Birdsong "transcriptomics": neurochemical specializations of the oscine song system.

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    Peter V Lovell

    Full Text Available Vocal learning is a rare and complex behavioral trait that serves as a basis for the acquisition of human spoken language. In songbirds, vocal learning and production depend on a set of specialized brain nuclei known as the song system.Using high-throughput functional genomics we have identified approximately 200 novel molecular markers of adult zebra finch HVC, a key node of the song system. These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus. Bioinformatics analysis reveals that several major neuronal cell functions and specific biochemical pathways are the targets of transcriptional regulation in HVC, including: 1 cell-cell and cell-substrate interactions (e.g., cadherin/catenin-mediated adherens junctions, collagen-mediated focal adhesions, and semaphorin-neuropilin/plexin axon guidance pathways; 2 cell excitability (e.g., potassium channel subfamilies, cholinergic and serotonergic receptors, neuropeptides and neuropeptide receptors; 3 signal transduction (e.g., calcium regulatory proteins, regulators of G-protein-related signaling; 4 cell proliferation/death, migration and differentiation (e.g., TGF-beta/BMP and p53 pathways; and 5 regulation of gene expression (candidate retinoid and steroid targets, modulators of chromatin/nucleolar organization. The overall direction of regulation suggest that processes related to cell stability are enhanced, whereas proliferation, growth and plasticity are largely suppressed in adult HVC, consistent with the observation that song in this songbird species is mostly stable in adulthood.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate. The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might

  4. Neurochemical Systems of the Retina Involved in the Control of Movement.

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    Willis, Gregory L; Freelance, Christopher B

    2017-01-01

    Recent studies have revealed that the retina may exert control over deep brain function and may be importantly involved in the etiology, progression, and treatment of disorders such as Parkinson's disease (PD). While such a concept is uncharted territory and even less is known about the mechanism by which this might be achieved, this study was undertaken to determine how retinal dopamine (DA), serotonin (5-HT), and melatonin (MEL) neurotransmitter systems might be involved in the control of movement in their own right. To explore these further, intravitreal (IVIT) injections of DA, 5-HT, and MEL were made 0.5 or 3 h prior to testing horizontal and vertical movement in the open field as well as assessment on three motor tests used routinely to evaluate movement as a preclinical model of PD. The doses of DA (2 µl of 25 and 75 µg/µl), 5-HT (2 µl of 5 and 15 µg/µl), and MEL (2 µl of 5 µg/µl) were chosen because of previous work demonstrating an anatomically precise effect of these transmitters after they were injected directly into the brain. The postinjection times of testing were also chosen on the basis of previous intracerebral and IVIT work intimating the importance of the circadian cycle in determining the efficacy of such effects. 0.5 h after IVIT injection of DA at the 25 and 75 µg/µl doses, significant inhibition of motor function was observed. While IVIT injection of 10 or 30 µg of 5-HT also inhibited motor performance, this was significantly less than that seen with DA. In fact, IVIT injection increases motor performance compared to vehicle injection on some parameters. The IVIT injection of 10 µg of MEL facilitated motor function on many parameters compared to DA, 5-HT, and vehicle injection. When rats were tested 3 h after IVIT injection, the inhibition of vertical movement was also observed compared to controls. The present results illustrate that specific retinal neurotransmitter systems participate in the normal

  5. The endocannabinoid system: A new player in the neurochemical control of vestibular function?

    Science.gov (United States)

    Smith, Paul F; Ashton, John C; Darlington, Cynthia L

    2006-01-01

    The results of recent clinical trials of medicinal cannabinoid drugs show that dizziness and vertigo are commonly reported adverse side-effects. Cannabinoid CB1 receptors were initially thought to be expressed in very low densities in the vestibular nucleus complex (VNC). Recent immunohistochemical studies have challenged this idea and suggested that CB1 receptors may exist in numbers similar to the granule cell layer of the cerebellum. This, together with evidence that brainstem CB1 receptors have a higher efficacy than those in many other parts of the brain and that application of cannabinoids can elicit potent electrophysiological effects in VNC neurons, suggests that CB1 receptors and their endogenous ligands may be important in central vestibular function. In this review, we consider the potential clinical significance of the endocannabinoid system for the development of vestibular disorders, the effects of recreational cannabis use and the therapeutic use of medicinal cannabinoids. Copyright 2006 S. Karger AG, Basel.

  6. Wireless Instantaneous Neurotransmitter Concentration System-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring.

    Science.gov (United States)

    Agnesi, Filippo; Tye, Susannah J; Bledsoe, Jonathan M; Griessenauer, Christoph J; Kimble, Christopher J; Sieck, Gary C; Bennet, Kevin E; Garris, Paul A; Blaha, Charles D; Lee, Kendall H

    2009-10-01

    WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA. By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery.

  7. Simultaneous wireless electrophysiological and neurochemical monitoring

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    Murari, Kartikeya; Mollazadeh, Mohsen; Thakor, Nitish; Cauwenberghs, Gert

    2008-08-01

    Information processing and propagation in the central nervous system is mostly electrical in nature. At synapses, electrical signals cause the release of neurotransmitters like dopamine, glutamate etc., that are sensed by post-synaptic neurons resulting in signal propagation or inhibition. It can be very informative to monitor electrical and neurochemical signals simultaneously to understand the mechanisms underlying normal or abnormal brain function. We present an integrated system for the simultaneous wireless acquisition of neurophysiological and neurochemical activity. Applications of the system to neuroscience include monitoring EEG and glutamate in rat somatosensory cortex following global ischemia.

  8. Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network.

    Science.gov (United States)

    Albers, H Elliott

    2015-01-01

    Arginine-vasotocin (AVT)/arginine vasopressin (AVP) are members of the AVP/oxytocin (OT) superfamily of peptides that are involved in the regulation of social behavior, social cognition and emotion. Comparative studies have revealed that AVT/AVP and their receptors are found throughout the "social behavior neural network (SBNN)" and display the properties expected from a signaling system that controls social behavior (i.e., species, sex and individual differences and modulation by gonadal hormones and social factors). Neurochemical signaling within the SBNN likely involves a complex combination of synaptic mechanisms that co-release multiple chemical signals (e.g., classical neurotransmitters and AVT/AVP as well as other peptides) and non-synaptic mechanisms (i.e., volume transmission). Crosstalk between AVP/OT peptides and receptors within the SBNN is likely. A better understanding of the functional properties of neurochemical signaling in the SBNN will allow for a more refined examination of the relationships between this peptide system and species, sex and individual differences in sociality. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa.

    Science.gov (United States)

    Avena, Nicole M; Bocarsly, Miriam E

    2012-07-01

    Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of restricted eating coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Neurochemical aspects of childhood autism

    NARCIS (Netherlands)

    R.B. Minderaa (Ruud)

    1985-01-01

    textabstractThe topic of this thesis is neurochemical aspects of infantile autism. The experimental work is centered around the most robust and consistant neurochemical finding in child psychiatry, namely that group mean whole blood serotonin (5-Hydroxytryptamine, 5-HT) values are

  11. Integrative pathways linking close family ties to health: A neurochemical perspective.

    Science.gov (United States)

    Uchino, Bert N; Way, Baldwin M

    2017-09-01

    The quality of one's familial life, for better or worse, has been linked to physical health. Such associations are evident across a number of acute and chronic conditions and highlight the widespread impact that close relationships have on physical health. However, the field currently lacks a complete understanding of the integrative biological pathways underlying the association between close relationships and disease risk. This article reviews the main peripheral biological and central nervous system pathways linking positive and negative familial relationship processes to physical health outcomes. It emphasizes the role of neurochemical pathways in mediating the influence of social relationships on health-relevant peripheral physiological systems using the oxytocin system as a model. Such neurochemical approaches are an important step toward a more integrative understanding of complex biological pathways and has novel theoretical and intervention implications. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. SOME NEUROCHEMICAL DISTURBANCES IN MULTIPLE SCLEROSIS

    OpenAIRE

    Vladimir V. Markelov; Maxim V. Trushin

    2006-01-01

    ABSTRACTThe data presented in this manuscript suggest a pivotal role of the central nervous system (CNS) in the regulation of immune status. We describe here that some neurochemical disturbances may provoke development of various diseases including multiple sclerosis. Some theoretic and practical backgrounds, how to improve the multiple sclerosis sufferers and patients with other autoimmune disorders, are also given.RESUMENLos datos que presentamos en este manuscrito, sugieren un papel guia d...

  13. Suicide: Neurochemical Approaches

    Directory of Open Access Journals (Sweden)

    Ritabrata Banerjee

    2013-10-01

    Full Text Available Despite the devastating effect of suicide on numerous lives, there is still a dearthof knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF and Nerve growth factor (NGF are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors trk B and trk A respectively. The present study was performed to examine whether the expression profiles of BDNF and/or trk B as well as NGF and/or trk A were altered in postmortem brain in subjects who commitsuicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed in hippocampus obtained 21 suicide subjects and 19 non-psychiatric control subjects. The protein and mRNA levels of BDNF, trk B and NGF, trk A were determined with Sandwich ELISA, Western Blot and RT PCR respectively. Given the importance of BDNFand NGF along with their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, Trk B and NGF, Trk A in both protein and mRNA levels of postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.

  14. Neurochemical alterations associated with borderline personality disorder.

    Science.gov (United States)

    Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

    2015-01-01

    In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder. © 2015, The Author(s).

  15. Review of relevant studies of isolated systems

    DEFF Research Database (Denmark)

    Hansen, L.H.; Lundsager, P.

    2001-01-01

    The report presents the results of a review of studies relating to integration of wind energy in isolated power supply systems, based on a systematic literature survey. The purpose of the study is to develop a methodology consisting of a set of guidelinesfor wind energy projects in isolated energy......, most notably the IEC/PAS 62111 specification. The amount of wind energy literature related to the subject is excessively large, and a complete review inwhich every relevant abstract is identified and examined is not feasible within the framework of this (or probably any other) study. The review results...... have been organised according to the following keywords: methods & guides, economics, concept ofapplication, system solutions, case studies, financial programmes, dedicated software tools. None of the found references presents methods or tools that contradict the philosophy of Risø's methodology...

  16. Neurochemical and electrophysiological evidence for the existence of a functional gamma-hydroxybutyrate system in NCB-20 neurons.

    Science.gov (United States)

    Kemmel, V; Taleb, O; Perard, A; Andriamampandry, C; Siffert, J C; Mark, J; Maitre, M

    1998-10-01

    Clonal neurohybridoma NCB-20 cells express a valproate-insensitive succinic semialdehyde reductase activity that transforms succinic semialdehyde into gamma-hydroxybutyrate. This activity (1.14+/-0.16 nmol/min/mg protein) was similar to the lowest activity existing in adult rat brain. [3H]gamma-Hydroxybutyrate labels a homogeneous population of sites on NCB-20 cell membranes (Kd=250+/-44.4nM, Bmax=180+/-16.2fmol/mg protein) that apparently represents specific gamma-hydroxybutyrate binding sites characterized previously on brain cell membranes. Finally, an Na+-dependent uptake of [3H]gamma-hydroxybutyrate was expressed in NCB-20 cells with a Km of 35+21.1 microM and a Vmax of 80+/-14.2 pmol/min/mg protein. A three-day treatment with 1 mM dibutyryl-cyclic-AMP induced a three-fold increase in the cellular succinic semialdehyde reductase activity. In parallel, a K+-evoked release of [3H]gamma-hydroxybutyrate occurred. This release was Ca2+ dependent and was not present in undifferentiated cells. Cyclic-AMP treatment induced a decrease of [3H]gamma-hydroxybutyrate binding sites, which could be due to spontaneous gamma-hydroxybutyrate release. Patch-clamp experiments carried out on differentiated NCB-20 cells revealed the presence of Ca2+ conductances which were partially inhibited by 50 microM gamma-hydroxybutyrate. This gamma-hydroxybutyrate-induced effect was blocked by the gamma-hydroxybutyrate receptor antagonist NCS-382, but not by the GABA(B) antagonist CGP-55845. These results demonstrate the presence of an active gamma-hydroxybutyratergic system in NCB-20 cells which possesses the ability to release gamma-hydroxybutyrate. These cells express specific gamma-hydroxybutyrate receptors which modulate Ca2+ currents independently of GABA(B) receptors.

  17. SOME NEUROCHEMICAL DISTURBANCES IN MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Vladimir V. Markelov

    2006-04-01

    Full Text Available ABSTRACTThe data presented in this manuscript suggest a pivotal role of the central nervous system (CNS in the regulation of immune status. We describe here that some neurochemical disturbances may provoke development of various diseases including multiple sclerosis. Some theoretic and practical backgrounds, how to improve the multiple sclerosis sufferers and patients with other autoimmune disorders, are also given.RESUMENLos datos que presentamos en este manuscrito, sugieren un papel guia del sistema nervioso central (SNC en la regulación del estado inmune. Describimos aquí que varias alteraciones neuroquímicas pueden provocar el desarrollo de varias enfermedades, incluyendo esclerosis múltiple. También se comenta acerca del trasfondo teórico y práctico, y cómo mejorar a víctimas y pacientes con esclerosis múltiple y otras alteraciones autoinmunes.

  18. Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance to cannabinoid-induced effects.

    Science.gov (United States)

    Mendiguren, Aitziber; Aostri, Erik; Pineda, Joseba

    2018-01-01

    The cannabinoid system is composed of Gi/o protein-coupled cannabinoid type 1 receptor (CB1) and cannabinoid type 2 (CB2) receptor and endogenous compounds. The CB1 receptor is widely distributed in the central nervous system (CNS) and it is involved in the regulation of common physiological functions. At the neuronal level, the CB1 receptor is mainly placed at GABAergic and glutamatergic axon terminals, where it modulates excitatory and inhibitory synapses. To date, the involvement of CB2 receptor in the regulation of neurotransmission in the CNS has not been clearly shown. The majority of noradrenergic (NA) cells in mammalian tissues are located in the locus coeruleus (LC) while serotonergic (5-HT) cells are mainly distributed in the raphe nuclei including the dorsal raphe nucleus (DRN). In the CNS, NA and 5-HT systems play a crucial role in the control of pain, mood, arousal, sleep-wake cycle, learning/memory, anxiety, and rewarding behaviour. This review summarizes the electrophysiological, neurochemical and behavioural evidences for modulation of the NA/5-HT systems by cannabinoids and the CB1 receptor. Cannabinoids regulate the neuronal activity of NA and 5-HT cells and the release of NA and 5-HT by direct and indirect mechanisms. The interaction between cannabinoid and NA/5-HT systems may underlie several behavioural changes induced by cannabis such as anxiolytic and antidepressant effects or side effects (e.g. disruption of attention). Further research is needed to better understand different aspects of NA and 5-HT systems regulation by cannabinoids, which would be relevant for their use in therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

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    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies.

  20. Carbon Nanofiber Electrode Array for Neurochemical Monitoring

    Science.gov (United States)

    Koehne, Jessica E.

    2017-01-01

    A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report using vertically aligned CNF as neurotransmitter recording electrodes for application in a smart deep brain stimulation (DBS) device. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

  1. Central Neurochemical Ultradian Variability in Depression

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    Ronald M. Salomon

    2006-01-01

    Full Text Available Depression is characterized by blunted behavior and neuroendocrine function that generally improve with antidepressant treatment. This study examined intrinsic variability in brain neurotransmitter function, since it may be a source of blunted behavior and neuroendocrine function in depression and a marker for the illness, and has not previously been analyzed using wavelet decomposition. To measure variability in monoamine metabolites, lumbar cerebrospinal fluid (CSF was collected in serial samples in depressed patients before and after treatment. We hypothesized that changes in variability would be observed after treatment. Mechanisms that control such variability may be critical to the pathophysiology of depression. Method: Time series data was obtained from serial ten-min sampling over a 24-hr period (N = 144 from thirteen depressed patients, with a repeat collection after 5 weeks of antidepressant (sertraline or bupropion treatment. Concentrations of tryptophan (TRP, the monoamine metabolites 5-HIAA (metabolite of serotonin and HVA (metabolite of dopamine, and the HVA:5HIAA ratio were transformed to examine power in slowly (160 min/cycle to rapidly (20 min/cycle occurring events. Power, the sum of the squares of the coefficients in each d (detail wavelet, reflects variability within a limited frequency bandwidth for that wavelet. Pre-treatment to post-treatment comparisons were conducted with repeated measures ANOVA. Results: Antidepressant treatment was associated with increased power in the d2 wavelet from the HVA (p = 0.03 and the HVA:5-HIAA ratio (p = 0.03 series. The d1 and d3 wavelets showed increased power following antidepressant treatment for the ratio series (d1, p = 0.01; d3, p = 0.05. Significant changes in power were not observed for the 5-HIAA data series. Power differences among analytes suggest that the findings are specific to each system. Conclusion: The wavelet transform analysis shows changes in neurochemical signal

  2. Age-Related Neurochemical Changes in the Vestibular Nuclei

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    Paul eSmith

    2016-03-01

    Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  3. Age-Related Neurochemical Changes in the Vestibular Nuclei.

    Science.gov (United States)

    Smith, Paul F

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  4. Neuroanatomical and Neurochemical Basis of Impulsivity

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    Kemal Yazici

    2010-08-01

    tis paradigm, the tendency to prefer small immediate rewards over larger, more delayed reinforcers is measured. İmpulsive choice is defined by a greater tendency to value or choose smaller, more immediate reinforcers. Impulsivity is a multi-faceted behaviour. This behaviour may be studied by subdividing it into different processes neuroanatomically and neurochemically. Neuroanatomical data support the suggestion that behavioral disinhibition (impulsive action / motoric impulsivity and delay-discounting (impulsive choice / decision making differ in the degree to which various components of frontostriatal loops are implicated in their regulation. The dorsal prefrontal cortex does not appear to be involved in mediating impulsive choice, yet does have some role in regulating inhibitory processes. In contrast, there appears to be a pronounced role for the orbitofrontal cortex and basolateral amygdala in controlling impulsive choice. Other structures, however, such as the nucleus accumbens and subthalamic nucleus may be common to both circuits. From the neurochemical perspective, dopamine system and dopamine- 2 (D2 receptors in particular, seems to be closely involved in making impulsive choice. When the noradrenaline system does not function optimally, it might contribute to increased impulsivity. Serotonin might act upon prefrontal cortex to decrease impulsive choices. Interactions between the serotonin and the dopamine systems are important in the regulation of impulsive behaviour. It is possible that various receptor subtypes of the serotonin system may exert differing and even contrasting effects on impulsive behaviour. Although it is very informative to study neurotransmitter systems separately, it should be kept in mind that there are very intimate interactions between the neurotransmitter systems mentioned above. Based on the fact that impulsivity is regulated through multiple neurotransmitters and even more receptors, one may suggest that pharmacotherapy of

  5. WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

    Science.gov (United States)

    Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

    2017-04-01

    There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

  6. Neurochemical measurements in the zebrafish brain

    Directory of Open Access Journals (Sweden)

    Lauren eJones

    2015-09-01

    Full Text Available The zebrafish is an ideal model organism for behavioural genetics and neuroscience. The high conservation of genes and neurotransmitter pathways between zebrafish and other vertebrates permits the translation of research between species. Zebrafish behaviour can be studied at both larval and adult stages and recent research has begun to establish zebrafish models for human disease. Fast scan cyclic voltammetry (FSCV is an electrochemical technique that permits the detection of neurotransmitter release and reuptake. In this study we have used in vitro FSCV to measure the release of analytes in the adult zebrafish telencephalon. We compare different stimulation methods and present a characterisation of neurochemical changes in the wild-type zebrafish brain. This study represents the first FSCV recordings in zebrafish, thus paving the way for neurochemical analysis of the fish brain.

  7. Neurochemical measurements in the zebrafish brain

    Science.gov (United States)

    Jones, Lauren J.; McCutcheon, James E.; Young, Andrew M. J.; Norton, William H. J.

    2015-01-01

    The zebrafish is an ideal model organism for behavioral genetics and neuroscience. The high conservation of genes and neurotransmitter pathways between zebrafish and other vertebrates permits the translation of research between species. Zebrafish behavior can be studied at both larval and adult stages and recent research has begun to establish zebrafish models for human disease. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique that permits the detection of neurotransmitter release and reuptake. In this study we have used in vitro FSCV to measure the release of analytes in the adult zebrafish telencephalon. We compare different stimulation methods and present a characterization of neurochemical changes in the wild-type zebrafish brain. This study represents the first FSCV recordings in zebrafish, thus paving the way for neurochemical analysis of the fish brain. PMID:26441575

  8. Metabolomics reveals distinct neurochemical profiles associated with stress resilience

    Directory of Open Access Journals (Sweden)

    Brooke N. Dulka

    2017-12-01

    Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings

  9. Neural systems supporting and affecting economically relevant behavior

    Directory of Open Access Journals (Sweden)

    Braeutigam S

    2012-05-01

    Full Text Available Sven BraeutigamOxford Centre for Human Brain Activity, University of Oxford, Oxford, United KingdomAbstract: For about a hundred years, theorists and traders alike have tried to unravel and understand the mechanisms and hidden rules underlying and perhaps determining economically relevant behavior. This review focuses on recent developments in neuroeconomics, where the emphasis is placed on two directions of research: first, research exploiting common experiences of urban inhabitants in industrialized societies to provide experimental paradigms with a broader real-life content; second, research based on behavioral genetics, which provides an additional dimension for experimental control and manipulation. In addition, possible limitations of state-of-the-art neuroeconomics research are addressed. It is argued that observations of neuronal systems involved in economic behavior converge to some extent across the technologies and paradigms used. Conceptually, the data available as of today raise the possibility that neuroeconomic research might provide evidence at the neuronal level for the existence of multiple systems of thought and for the importance of conflict. Methodologically, Bayesian approaches in particular may play an important role in identifying mechanisms and establishing causality between patterns of neural activity and economic behavior.Keywords: neuroeconomics, behavioral genetics, decision-making, consumer behavior, neural system

  10. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

    OpenAIRE

    Adkins, Daniel E.; McClay, Joseph L.; VUNCK, SARAH A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; SOUZA,RENAN P. DE; Crowley, James J.; Sullivan, Patrick F; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

    2013-01-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphe...

  11. An adaptable connectionist text-retrieval system with relevance feedback.

    Science.gov (United States)

    Azimi-Sadjadi, M R; Salazar, J; Srinivasan, S; Sheedvash, S

    2007-11-01

    This paper introduces a new connectionist network for certain domain-specific text-retrieval and search applications with expert end users. A new model reference adaptive system is proposed that involves three learning phases. Initial model-reference learning is first performed based upon an ensemble set of input-output of an initial reference model. Model-reference following is needed in dynamic environments where documents are added, deleted, or updated. Relevance feedback learning from multiple expert users then optimally maps the original query using either a score-based or a click-through selection process. The learning can be implemented, in regression or classification modes, using a three-layer network. The first layer is an adaptable layer that performs mapping from query domain to document space. The second and third layers perform document-to-term mapping, search/retrieval, and scoring tasks. The learning algorithms are thoroughly tested on a domain-specific text database that encompasses a wide range of Hewlett Packard (HP) products and for a large number of most commonly used single- and multiterm queries.

  12. Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback.

    Science.gov (United States)

    Van Gompel, Jamie J; Chang, Su-Youne; Goerss, Stephan J; Kim, In Yong; Kimble, Christopher; Bennet, Kevin E; Lee, Kendall H

    2010-08-01

    Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a "smart" DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans.

  13. Autism and Fragile X: Is There a Neurochemical Link?

    Directory of Open Access Journals (Sweden)

    Nagwa A. Meguid

    2014-12-01

    CONCLUSIONS: Autism and Fragile X syndrome share some neurochemical similarities with regards of high Glutamate and GABA levels while Serotonin was significantly different in the 2 disorders and may be used a unique biomarker for autism.

  14. Neurochemical mechanisms underlying responses to psychostimulants

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.S.; Hitzemann, R.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York, Stony Brook, NY (United States)

    1994-11-01

    This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligand that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.

  15. Neurochemical background and approaches in the understanding of motion sickness

    Science.gov (United States)

    Kohl, R. L.

    1982-01-01

    The problems and nature of space motion sickness were defined. The neurochemical and neurophysiological bases of vestibular system function and of the expression of motion sickness wre reviewed. Emphasis was given to the elucidation of the neuropharmacological mechanisms underlying the effects of scopolamine and amphetamine on motion sickness. Characterization of the ascending reticular activating system and the limbic system provided clues to the etiology of the side effects of scopolamine. The interrelationship between central cholinergic pathways and the peripheral (autonomic) expression of motion sickness was described. A correlation between the stress of excessive motion and a variety of hormonal responses to that stress was also detailed. The cholinergic system is involved in the efferent modulation of the vestibular hair cells, as an afferent modulator of the vestibular nuclei, in the activation of cortical and limbic structures, in the expression of motion sickness symptoms and most likely underscores a number of the hormonal changes that occur in stressful motion environments. The role of lecithin in the regulation of the levels of neurotransmitters was characterized as a possible means by which cholinergic neurochemistry can be modulated.

  16. ORIGINAL ARTICLES Canada's health care system: A relevant ...

    African Journals Online (AJOL)

    In the USA, meaningful discussion on the advantages and disadvantages of the Canadian system has been thwarted by ideological mudslinging by defenders of .... based on past budgets, patient load, inflation and salary ... However, South Africa's health care system is more equitable than the USA system in many ways.

  17. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E

    1997-01-01

    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  18. Relevant Costs for Decision in an Effective Controlling System

    Directory of Open Access Journals (Sweden)

    Mihaela TULVINSCHI

    2010-05-01

    Full Text Available Controlling is considered a leading concept in the sense of coordination, planning, control and automation, in order to produce the synthesis necessary in decision making. The purpose of article is to highlight the link between a dynamic accounting system and an effective controlling system. The research method used is based on the idea that the cost analysis in an efficient controlling system involves obtaining accounting information from within the entity which management then uses in decision making. In conclusion, we emphasize that an effective controlling system must provide managers the tools to meet their informational needs.

  19. Canada's health care system: A relevant approach for South Africa ...

    African Journals Online (AJOL)

    Background. While countries such as the USA, South Africa and China debate health reforms to improve access to care while rationalising costs, Canada's health care system has emerged as a notable option. In the USA, meaningful discussion of the advantages and disadvantages of the Canadian system has been ...

  20. Mapping healthcare systems: a policy relevant analytic tool.

    Science.gov (United States)

    Sekhri Feachem, Neelam; Afshar, Ariana; Pruett, Cristina; Avanceña, Anton L V

    2017-07-01

    In the past decade, an international consensus on the value of well-functioning systems has driven considerable health systems research. This research falls into two broad categories. The first provides conceptual frameworks that take complex healthcare systems and create simplified constructs of interactions and functions. The second focuses on granular inputs and outputs. This paper presents a novel translational mapping tool - the University of California, San Francisco mapping tool (the Tool) - which bridges the gap between these two areas of research, creating a platform for multi-country comparative analysis. Using the Murray-Frenk framework, we create a macro-level representation of a country's structure, focusing on how it finances and delivers healthcare. The map visually depicts the fundamental policy questions in healthcare system design: funding sources and amount spent through each source, purchasers, populations covered, provider categories; and the relationship between these entities. We use the Tool to provide a macro-level comparative analysis of the structure of India's and Thailand's healthcare systems. As part of the systems strengthening arsenal, the Tool can stimulate debate about the merits and consequences of different healthcare systems structural designs, using a common framework that fosters multi-country comparative analyses.

  1. The endocannabinoid system and its relevance for nutrition

    DEFF Research Database (Denmark)

    Maccarrone, Mauro; Gasperi, Valeria; Catani, Maria Valeria

    2010-01-01

    Endocannabinoids bind to cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. The biological actions of these polyunsaturated lipids are controlled by key agents responsible for their synthesis, transport and degradation, which together form an endocannabinoid system (ECS...

  2. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-12-01

    Full Text Available Despite accumulating data showing the various neurological actions of vitamin D (VD, its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D administration (50 ng/kg/day or 100 ng/kg/day. Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH and tryptophan hydroxylase 2 (TPH2 expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

  3. Social Stress and Psychosis Risk: Common Neurochemical Substrates?

    Science.gov (United States)

    Mizrahi, Romina

    2016-02-01

    Environmental risk factors have been implicated in the etiology of psychotic disorders, with growing evidence showing the adverse effects of migration, social marginalization, urbanicity, childhood trauma, social defeat, and other adverse experiences on mental health in vulnerable populations. Collectively, social stress may be one mechanism that could link these environmental risk factors. The exact mechanism(s) by which social stress can affect brain function, and in particular the molecular targets involved in psychosis (such as the dopaminergic (DA) system), is (are) not fully understood. In this review, we will discuss the interplay between social environmental risk factors and molecular changes in the human brain; in particular, we will highlight the impact of social stress on three specific neurochemical systems: DA, neuroinflammation/immune, and endocannabinoid (eCB) signaling. We have chosen the latter two molecular pathways based on emerging evidence linking schizophrenia to altered neuroinflammatory processes and cannabis use. We further identify key developmental periods in which social stress interacts with these pathways, suggesting window(s) of opportunities for novel interventions. Taken together, we suggest that they may have a key role in the pathogenesis and disease progression, possibly provide novel treatment options for schizophrenia, and perhaps even prevent it.

  4. Digestive system fistula: a problem still relevant today.

    Science.gov (United States)

    Głuszek, Stanisław; Korczak, Maria; Kot, Marta; Matykiewicz, Jarosław; Kozieł, Dorota

    2011-01-01

    Digestive system fistula originates most frequently as a complication after surgical procedures, less often occurs in the course of inflammatory diseases, but it can also result from neoplasm and injuries. THE AIM OF THE STUDY was to analyze the causes and retrospectively assess the perioperative procedures as well as the results of digestive system fistula treatment. MATERIAL AND METHODS. Own experience in digestive system fistula treatment was presented. The subject group consisted of 32 patients treated at the General Surgery, Oncology and Endocrinology Clinical Department between 01.05.2005 and 30.04.2010 due to different digestive tract diseases. The causes of the occurrence of digestive system fistula, methods and results of treatment were analyzed. RESULTS. The analysis covered 32 patients with digestive system fistula, among them 15 men and 17 women. Average age for men was 57 years (20-78), and for women 61 years (24-88). In 11 patients idiopathic fistula causally connected with primary inflammatory disease (7 cases) and with neoplasm (4 cases) was diagnosed, in 19 patients fistula was the result of complications after surgery, in 2 - after abdominal cavity injury. Recovery from fistula was achieved in 23 patients (72%) with the use of individually planned conservative therapy (TPN, EN, antibiotics, drainage, and others) and surgery, depending on the needs of individual patient. 5 patients (16%) died, whereas in 4 left (12%) recovery wasn't achieved (fistula in palliative patients, with advanced stages of neoplasm - bronchoesophageal fistula, the recurrence of uterine carcinoma). CONCLUSIONS. Recently the results of digestive system fistula treatment showed an improvement which manifests itself in mortality decrease and shortening of fistula healing time. Yet, digestive system fistula as a serious complication still poses a very difficult surgical problem.

  5. Towards a barrier height benchmark set for biologically relevant systems

    Directory of Open Access Journals (Sweden)

    Jimmy C. Kromann

    2016-05-01

    Full Text Available We have collected computed barrier heights and reaction energies (and associated model structures for five enzymes from studies published by Himo and co-workers. Using this data, obtained at the B3LYP/6- 311+G(2d,2p[LANL2DZ]//B3LYP/6-31G(d,p level of theory, we then benchmark PM6, PM7, PM7-TS, and DFTB3 and discuss the influence of system size, bulk solvation, and geometry re-optimization on the error. The mean absolute differences (MADs observed for these five enzyme model systems are similar to those observed for PM6 and PM7 for smaller systems (10–15 kcal/mol, while DFTB results in a MAD that is significantly lower (6 kcal/mol. The MADs for PMx and DFTB3 are each dominated by large errors for a single system and if the system is disregarded the MADs fall to 4–5 kcal/mol. Overall, results for the condensed phase are neither more or less accurate relative to B3LYP than those in the gas phase. With the exception of PM7-TS, the MAD for small and large structural models are very similar, with a maximum deviation of 3 kcal/mol for PM6. Geometry optimization with PM6 shows that for one system this method predicts a different mechanism compared to B3LYP/6-31G(d,p. For the remaining systems, geometry optimization of the large structural model increases the MAD relative to single points, by 2.5 and 1.8 kcal/mol for barriers and reaction energies. For the small structural model, the corresponding MADs decrease by 0.4 and 1.2 kcal/mol, respectively. However, despite these small changes, significant changes in the structures are observed for some systems, such as proton transfer and hydrogen bonding rearrangements. The paper represents the first step in the process of creating a benchmark set of barriers computed for systems that are relatively large and representative of enzymatic reactions, a considerable challenge for any one research group but possible through a concerted effort by the community. We end by outlining steps needed to expand and

  6. Imaging the glutamatergic system in vivo - relevance to schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Bressan, R.A.; Pilowsky, L.S. [Inst. of Psychiatry, London (United Kingdom); Inst. of Nuclear Medicine, University College of London Medical School (United Kingdom)

    2000-11-01

    Schizophrenia is a devastating psychiatric illness. Its pathophysiology is not fully clarified. Animal data, in vitro and indirect in vivo imaging support glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction in the disorder. A lack of suitable ligands has obstructed direct evaluation of the NMDA receptor hypofunction hypothesis of schizophrenia. Many research groups are working towards developing appropriate single-photon emission tomography and positron emission tomography ligands for the NMDA receptor. This paper briefly presents evidence for links between glutamatergic system dysfunction and schizophrenia. It reviews the radioligands to evaluate glutamatergic receptors in vivo and discusses issues in developing novel ligands for the glutamatergic system. (orig.)

  7. Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

    Science.gov (United States)

    Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

    2013-01-01

    During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. PMID:23270605

  8. The endocannabinoid system and appetite: relevance for food reward

    NARCIS (Netherlands)

    Jager, G.; Witkamp, R.F.

    2014-01-01

    Mounting evidence substantiates the central role of the endocannabinoid system (ECS) in the modulation of both homeostatic and hedonic elements of appetite and food intake. Conversely, feeding status and dietary patterns directly influence activity of the ECS. Following a general introduction on the

  9. Anatomy and physiology of respiratory system relevant to anaesthesia

    OpenAIRE

    Apeksh Patwa; Amit Shah

    2015-01-01

    Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation wi...

  10. Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates.

    Science.gov (United States)

    Libero, Lauren E; DeRamus, Thomas P; Lahti, Adrienne C; Deshpande, Gopikrishna; Kana, Rajesh K

    2015-05-01

    Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multimodal imaging to better inform on the neural characteristics most relevant to the disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Dynamic regulation of neurotransmitter specification: relevance to nervous system homeostasis.

    Science.gov (United States)

    Borodinsky, Laura N; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

    2014-03-01

    During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Anatomy and physiology of respiratory system relevant to anaesthesia.

    Science.gov (United States)

    Patwa, Apeksh; Shah, Amit

    2015-09-01

    Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone.

  13. Anatomy and physiology of respiratory system relevant to anaesthesia

    Directory of Open Access Journals (Sweden)

    Apeksh Patwa

    2015-01-01

    Full Text Available Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone.

  14. Relevance of 3d culture systems to study osteosarcoma environment.

    Science.gov (United States)

    De Luca, Angela; Raimondi, Lavinia; Salamanna, Francesca; Carina, Valeria; Costa, Viviana; Bellavia, Daniele; Alessandro, Riccardo; Fini, Milena; Giavaresi, Gianluca

    2018-01-05

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, which preferentially develops lung metastasis. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for patients with metastatic or recurrent OS remains dramatically poor. Novel therapies are therefore required to slow progression and eradicate the disease. Furthermore, to better understand the cellular and molecular mechanisms responsible for OS onset and progression, the development of novel predictive culture systems resembling the native three-dimensional (3D) tumor microenvironment are mandatory. 'Tumor engineering' approaches radically changed the previous scenario, through the development of advanced and alternative 3D cell culture in vitro models able to tightly mimic the in vivo tumor microenvironment.In this review, we will summarize the state of the art in this novel area, illustrating the different methods and techniques employed to realize 3D OS cell culture models and we report the achieved results, which highlight the efficacy of these models in reproducing the tumor milieu. Although data need to be further validated, the scientific studies reviewed here are certainly promising and give new insights into the clinical practice.

  15. Spectroscopic Studies of Molecular Systems relevant in Astrobiology

    Science.gov (United States)

    Fornaro, Teresa

    2016-01-01

    In the Astrobiology context, the study of the physico-chemical interactions involving "building blocks of life" in plausible prebiotic and space-like conditions is fundamental to shed light on the processes that led to emergence of life on Earth as well as to molecular chemical evolution in space. In this PhD Thesis, such issues have been addressed both experimentally and computationally by employing vibrational spectroscopy, which has shown to be an effective tool to investigate the variety of intermolecular interactions that play a key role in self-assembling mechanisms of nucleic acid components and their binding to mineral surfaces. In particular, in order to dissect the contributions of the different interactions to the overall spectroscopic signals and shed light on the intricate experimental data, feasible computational protocols have been developed for the characterization of the spectroscopic properties of such complex systems. This study has been carried out through a multi-step strategy, starting the investigation from the spectroscopic properties of the isolated nucleobases, then studying the perturbation induced by the interaction with another molecule (molecular dimers), towards condensed phases like the molecular solid, up to the case of nucleic acid components adsorbed on minerals. A proper modeling of these weakly bound molecular systems has required, firstly, a validation of dispersion-corrected Density Functional Theory methods for simulating anharmonic vibrational properties. The isolated nucleobases and some of their dimers have been used as benchmark set for identifying a general, reliable and effective computational procedure based on fully anharmonic quantum mechanical computations of the vibrational wavenumbers and infrared intensities within the generalized second order vibrational perturbation theory (GVPT2) approach, combined with the cost-effective dispersion-corrected density functional B3LYP-D3, in conjunction with basis sets of

  16. Myocardial ischaemia in systemic lupus erythematosus: detection and clinical relevance.

    Science.gov (United States)

    Płazak, Wojciech; Gryga, Krzysztof; Sznajd, Jan; Pasowicz, Mieczysław; Musiał, Jacek; Podolec, Piotr

    2011-01-01

    Severe cardiovascular complications are among the most important causes of mortality in systemic lupus erythematosus (SLE) patients. To assess the usefulness of echocardiography, ECG, and coronary artery calcium scoring (CACS) in the detection of myocardial ischaemia in SLE patients compared to single photon emission computerised tomography (SPECT) and to assess their five-year follow-up. In 50 consecutive SLE patients (mean age 39.2 ± 12.9 years, 90% female), clinical assessment, resting and exercise ECG and echocardiography, multidetector computed tomography - based CACS and SPECT studies (Tc-99m sestamibi) were performed. Patients were then followed for five years. SPECT revealed perfusion defects in 25 (50%) patients; persistent defects in 18 (36%) and exercise-induced defects in seven (14%) subjects. No typical ischaemic heart disease clinical symptoms, signs of ischaemia in resting ECG, or left ventricular contractility impairment in echocardiography were observed. Signs of ischaemia in exercise ECG were found in 17 (34%) patients. The CACS ranged from 1 to 843.2 (median 23.15), and coronary calcifications were observed in 12 (24%) patients. Compared to the SPECT study, exercise ECG had 68% sensitivity and 100% specificity in detecting myocardial ischaemia, while CACS had only 28% sensitivity and 58% specificity. During follow-up, one patient who showed myocardial perfusion defects and the highest calcium score (843.2) at baseline, developed CCS II class symptoms of myocardial ischaemia. Coronary angiography was not performed because of severe anaemia; the patient died three months later. In two other patients with perfusion defects and calcium deposits at baseline, CCS I class symptoms were observed; coronary angiography showed only thin calcified coronary plaques that were haemodynamically insignificant. In about half of relatively young, mostly female, SLE patients, SPECT shows myocardial perfusion defects, with coronary calcifications present in one

  17. Ultrafast Structural Dynamics in Combustion Relevant Model Systems

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Peter M. [Brown University

    2014-03-31

    The research project explored the time resolved structural dynamics of important model reaction system using an array of novel methods that were developed specifically for this purpose. They include time resolved electron diffraction, time resolved relativistic electron diffraction, and time resolved Rydberg fingerprint spectroscopy. Toward the end of the funding period, we also developed time-resolved x-ray diffraction, which uses ultrafast x-ray pulses at LCLS. Those experiments are just now blossoming, as the funding period expired. In the following, the time resolved Rydberg Fingerprint Spectroscopy is discussed in some detail, as it has been a very productive method. The binding energy of an electron in a Rydberg state, that is, the energy difference between the Rydberg level and the ground state of the molecular ion, has been found to be a uniquely powerful tool to characterize the molecular structure. To rationalize the structure sensitivity we invoke a picture from electron diffraction: when it passes the molecular ion core, the Rydberg electron experiences a phase shift compared to an electron in a hydrogen atom. This phase shift requires an adjustment of the binding energy of the electron, which is measurable. As in electron diffraction, the phase shift depends on the molecular, geometrical structure, so that a measurement of the electron binding energy can be interpreted as a measurement of the molecule’s structure. Building on this insight, we have developed a structurally sensitive spectroscopy: the molecule is first elevated to the Rydberg state, and the binding energy is then measured using photoelectron spectroscopy. The molecule’s structure is read out as the binding energy spectrum. Since the photoionization can be done with ultrafast laser pulses, the technique is inherently capable of a time resolution in the femtosecond regime. For the purpose of identifying the structures of molecules during chemical reactions, and for the analysis of

  18. Creation of reliable relevance judgments in information retrieval systems evaluation experimentation through crowdsourcing: a review.

    Science.gov (United States)

    Samimi, Parnia; Ravana, Sri Devi

    2014-01-01

    Test collection is used to evaluate the information retrieval systems in laboratory-based evaluation experimentation. In a classic setting, generating relevance judgments involves human assessors and is a costly and time consuming task. Researchers and practitioners are still being challenged in performing reliable and low-cost evaluation of retrieval systems. Crowdsourcing as a novel method of data acquisition is broadly used in many research fields. It has been proven that crowdsourcing is an inexpensive and quick solution as well as a reliable alternative for creating relevance judgments. One of the crowdsourcing applications in IR is to judge relevancy of query document pair. In order to have a successful crowdsourcing experiment, the relevance judgment tasks should be designed precisely to emphasize quality control. This paper is intended to explore different factors that have an influence on the accuracy of relevance judgments accomplished by workers and how to intensify the reliability of judgments in crowdsourcing experiment.

  19. Neurochemical consequence of steroid abuse: stanozolol-induced monoaminergic changes.

    Science.gov (United States)

    Tucci, Paolo; Morgese, Maria Grazia; Colaianna, Marilena; Zotti, Margherita; Schiavone, Stefania; Cuomo, Vincenzo; Trabace, Luigia

    2012-02-01

    An extensive literature has documented adverse effects on mental health in anabolic androgenic steroids (AAS) abusers. Depression seems a common adverse reaction in AAS abusers. Recently it has been reported that in a rat model of AAS abuse stanozolol induces behavioural and biochemical changes related to the pathophysiology of major depressive disorder. In the present study, we used the model of AAS abuse to examine possible changes in the monoaminergic system, a neurobiological substrate of depression, in different brain areas of stanozolol-treated animals. Wistar rats received repeated injections of stanozolol (5mg/kg, s.c.), or vehicle (propylene glycol, 1ml/kg) once daily for 4weeks. Twenty-four hours after last injection, changes of dopamine (DA) and relative metabolite levels, homovanilic acid (HVA) and 3,4-dihydroxy phenylacetic acid (DOPAC), serotonin (5-HT) and its metabolite levels, 5-hydroxy indolacetic acid (5-HIAA), and noradrenaline (NA) amount were investigated in prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (STR) and hippocampus (HIPP). The analysis of data showed that after chronic stanozolol, DA levels were increased in the HIPP and decreased in the PFC. No significant changes were observed in the STR or in the NAC. 5-HT and 5-HIAA levels were decreased in all brain areas investigated after stanozolol exposure; however, the 5-HIAA/5-HT ratio was not altered. Taken together, our data indicate that chronic use of stanozolol significantly affects brain monoamines leading to neurochemical modifications possibly involved in depression and stress-related states. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The Relevancy of Star Classification Systems in the Hotel Industry : Is it still necessary?

    OpenAIRE

    van den Hooff, Rogier

    2015-01-01

    The aim of this thesis is to research the relevancy of star classification systems in the hotel industry. Are the systems still a good representation of classification and are these systems still useful? Currently different opinions regarding the star classification systems are given in the industry. Some doubt it if it is still a good indicator for quality and believe the system is not according to the standards of the modern traveler anymore. Others believe there is a certain need for certi...

  1. Control-relevant modeling and simulation of a SOFC-GT hybrid system

    Directory of Open Access Journals (Sweden)

    Rambabu Kandepu

    2006-07-01

    Full Text Available In this paper, control-relevant models of the most important components in a SOFC-GT hybrid system are described. Dynamic simulations are performed on the overall hybrid system. The model is used to develop a simple control structure, but the simulations show that more elaborate control is needed.

  2. Neurochemical organization of the nucleus paramedianus dorsalis in the human

    OpenAIRE

    Baizer, Joan S.; Baker, James F.; Haas, Kristin; Lima, Raquel

    2007-01-01

    We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla, and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (a...

  3. Perceived Relevance of an Introductory Information Systems Course to Prospective Business Students

    Directory of Open Access Journals (Sweden)

    Irene Govender

    2013-12-01

    Full Text Available The study is designed to examine students’ perceptions of the introductory Information Systems (IS course. It was an exploratory study in which 67 students participated. A quantitative approach was followed making use of questionnaires for the collection of data. Using the theory of reasoned action as a framework, the study explores the factors that influence non-IS major students’ perceived relevance of the IS introductory course. The analysis of collected data included descriptive and inferential statistics. Using multiple regression analysis, the results suggest that overall, the independent variables, relevance of the content, previous IT knowledge, relevance for professional practice, IT preference in courses and peers’ influence may account for 72% of the explanatory power for the dependent variable, perceived relevance of the IS course. In addition, the results have shown some strong predictors (IT preference and peers’ influence that influence students’ perceived relevance of the IS course. Practical work was found to be a strong mediating variable toward positive perceptions of IS. The results of this study suggest that students do indeed perceive the introductory IS course to be relevant and match their professional needs, but more practical work would enhance their learning. Implications for theory and practice are discussed as a result of the behavioural intention to perceive the IS course to be relevant and eventually to recruit more IS students.

  4. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization.

    Science.gov (United States)

    Adkins, D E; McClay, J L; Vunck, S A; Batman, A M; Vann, R E; Clark, S L; Souza, R P; Crowley, J J; Sullivan, P F; van den Oord, E J C G; Beardsley, P M

    2013-11-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In this study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine (MA)-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate, FDR biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. Neurobiology of addiction: insight from neurochemical imaging.

    Science.gov (United States)

    Urban, Nina B L; Martinez, Diana

    2012-06-01

    Neuroimaging studies have been crucial in understanding changes in the various neurotransmitter systems implicated in addiction in the living human brain. Predominantly reduced striatal dopamine transmission appears to play an important role in psychostimulant, alcohol and heroin addiction, while addiction to cannabis may be mediated primarily by the endocannabinoid system. However, the study of other neurotransmitter systems likely involved in addiction, for example glutamate, has been limited by the number and quality of available radiotracers, and data on changes in these systems in the most common addictions are emerging only now. Further studies are needed to understand fully how the interplay of various neurotransmitter systems contributes to addiction and to ultimately help to develop more effective treatment approaches.

  6. Integrative and Goal-Relevant Essay Questions for History and Systems Courses.

    Science.gov (United States)

    Berrenberg, Joy L.

    1990-01-01

    Reports that a goal and item analysis of eight history and systems of psychology textbooks and their accompanying test item files showed that the majority of the essay test items are too narrow in scope to measure the commonly stated course goals. Presents some integrative and goal-relevant essay questions to rectify this shortcoming. Includes a…

  7. Perceived Relevance of Special Education Performance Indicators: Teacher Excellence and Support System

    Science.gov (United States)

    Mrla, Tiffany

    2016-01-01

    A study was conducted to investigate the perceived relevance of using a teacher evaluation rubric with performance indicators specific to special education services in place of the standard rubric for teachers used in the State of Arkansas Teacher Excellence Support System (TESS). Through a multi-method approach, the perceptions of special…

  8. Neuroprotective and neurochemical properties of mint extracts

    DEFF Research Database (Denmark)

    López, Víctor; Martín, Sara; Gómez-Serranillos, Maria Pilar

    2010-01-01

    Mints are aromatic plants with a tradition as medicinal remedies and culinary herbs. With the aim of investigating potential central nervous system (CNS) activities of traditional medicinal plants, four species and one hybrid of the genus Mentha (M. aquatica, M. longifolia, M. pulegium, M......(A) receptor). Mentha x piperita and Mentha aquatica produced significant (p

  9. Integrating unified medical language system and association mining techniques into relevance feedback for biomedical literature search.

    Science.gov (United States)

    Ji, Yanqing; Ying, Hao; Tran, John; Dews, Peter; Massanari, R Michael

    2016-07-19

    Finding highly relevant articles from biomedical databases is challenging not only because it is often difficult to accurately express a user's underlying intention through keywords but also because a keyword-based query normally returns a long list of hits with many citations being unwanted by the user. This paper proposes a novel biomedical literature search system, called BiomedSearch, which supports complex queries and relevance feedback. The system employed association mining techniques to build a k-profile representing a user's relevance feedback. More specifically, we developed a weighted interest measure and an association mining algorithm to find the strength of association between a query and each concept in the article(s) selected by the user as feedback. The top concepts were utilized to form a k-profile used for the next-round search. BiomedSearch relies on Unified Medical Language System (UMLS) knowledge sources to map text files to standard biomedical concepts. It was designed to support queries with any levels of complexity. A prototype of BiomedSearch software was made and it was preliminarily evaluated using the Genomics data from TREC (Text Retrieval Conference) 2006 Genomics Track. Initial experiment results indicated that BiomedSearch increased the mean average precision (MAP) for a set of queries. With UMLS and association mining techniques, BiomedSearch can effectively utilize users' relevance feedback to improve the performance of biomedical literature search.

  10. Benzodiazepine withdrawal: behavioural pharmacology and neurochemical changes.

    Science.gov (United States)

    File, S E; Andrews, N

    1993-01-01

    This paper describes pharmacological treatments that can reverse the anxiogenic response detected in animal tests when rats are withdrawn from chronic treatment with diazepam. Concurrent treatment with the calcium channel antagonist verapamil prevented this withdrawal response and the benzodiazepine-receptor antagonist flumazenil reversed the anxiogenic response and restored the system to a drug-naive state. Other treatments that reversed the anxiogenic response were the GABAB agonist baclofen, the 5-HT1A receptor agonist buspirone, and the 5-HT3 receptor antagonist (R,S)-zacopride (GABA = gamma-aminobutyric acid; 5-HT = 5-hydroxytryptamine). Both the enantiomers of zacopride contributed to this reversal. These behavioural reversals are interpreted in the light of biochemical studies showing increased 45Ca2+ flux and [3H]5-HT release from the hippocampus, during benzodiazepine withdrawal (Fig. 1).

  11. From genes to behavior: investigations of neurochemical signaling come of age for the model crustacean Daphnia pulex.

    Science.gov (United States)

    Christie, Andrew E; McCoole, Matthew D

    2012-08-01

    The cladoceran crustacean Daphnia pulex has served as a standard organism for aquatic toxicity testing for decades. The model organism status of D. pulex rests largely on its remarkable ability to rapidly adapt morphologically, physiologically and behaviorally to a wide range of environmental challenges, as well as on its parthenogenetic reproduction and ease of laboratory culture. As in all multicellular organisms, neurochemical control systems are undoubtedly major contributors to the functional flexibility of Daphnia. Surprisingly, little work has focused on understanding its neurochemistry at any level. Recently, D. pulex has been the subject of extensive genome and transcriptome sequencing, and it is currently the only crustacean with a fully sequenced, publicly accessible genome. Although the molecular work was initiated for gene-based investigations of ecotoxicology and toxicogenomics, the data generated have allowed for investigations into numerous aspects of Daphnia biology, including its neurochemical signaling. This Commentary summarizes our knowledge of D. pulex neurochemistry obtained from recent genomic and transcriptomic studies, and places these data in context with other anatomical, biochemical and physiological experiments using D. pulex and its sister species Daphnia magna. Suggestions as to how the Daphnia molecular data may be useful for future investigations of crustacean neurochemical signaling are also provided.

  12. REM sleep deprivation reverses neurochemical and other depressive-like alterations induced by olfactory bulbectomy.

    Science.gov (United States)

    Maturana, Maira J; Pudell, Cláudia; Targa, Adriano D S; Rodrigues, Laís S; Noseda, Ana Carolina D; Fortes, Mariana H; Dos Santos, Patrícia; Da Cunha, Cláudio; Zanata, Sílvio M; Ferraz, Anete C; Lima, Marcelo M S

    2015-02-01

    There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD.

  13. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value.

    Science.gov (United States)

    Berlth, Felix; Bollschweiler, Elfriede; Drebber, Uta; Hoelscher, Arnulf H; Moenig, Stefan

    2014-05-21

    Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.

  14. THE RELEVANCE OF INTERACTIONS IN INNOVATION SYSTEMS: HOW TO CONSOLIDATE THE FRAMEWORK

    Directory of Open Access Journals (Sweden)

    Jon Mikel ZABALA-ITURRIAGAGOITIA

    2007-12-01

    Full Text Available Innovation Systems constitute an analysis framework which tries to identify the agents, and the interactions produced among them within an innovation system, endowing thus authorities of a tool for the definition of innovation policies. Accordingly, cooperation or interaction related practices become crucial. However, there is a need for the development and implementation of a more sophisticated measures and indicators as regards these interactive patterns, both from a theoretical and a quantitative approach. This papers aims at empirically contributing to highlight the relevance of these interactions. In order to do that, we first start by offering a clear taxonomy of the Spanish regions concerning R&D and innovation activities, to then analyse the extent to which interactions are relevant or not by considering in this case Spain as the unit of analysis between 1995-2002.

  15. Age-related neurochemical changes in the rhesus macaque cochlear nucleus.

    Science.gov (United States)

    Gray, Daniel T; Engle, James R; Recanzone, Gregg H

    2014-05-01

    Neurochemical changes in the expression of various proteins within the central auditory system have been associated with natural aging. These changes may compensate in part for the loss of auditory sensitivity arising from two phenomena of the aging auditory system: cochlear histopathologies and increased excitability of central auditory neurons. Recent studies in the macaque monkey have revealed age-related changes in the density of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPHd) and parvalbumin (PV)-positive cells within the inferior colliculus and superior olivary complex. The cochlear nucleus (CN), which is the first central auditory nucleus, remains unstudied. Since the CN participates in the generation of the auditory brainstem response (ABR) and receives direct innervation from the cochlea, it serves as an ideal nucleus to compare the relationship between these neurochemical changes and the physiological and peripheral changes of the aging auditory system. We used stereological sampling to calculate the densities of NADPHd and PV reactive neurons within the three subdivisions of the CN in middle-aged and aged rhesus macaques. Regression analyses of these values with ABR properties and cochlear histopathologies revealed relationships between these cell types and the changing characteristics of the aging auditory system. Our results indicate that NADPHd expression does change with age in a specific subdivision of the CN, but PV does not. Conversely, PV expression correlated with ABR amplitudes and outer hair cell loss in the cochlea, but NADPHd did not. These results indicate that NADPHd and PV may take part in distinct compensatory efforts of the aging auditory system. Copyright © 2013 Wiley Periodicals, Inc.

  16. Relevant Factors in The Post-Merger Systems Integration and Information Technology in Brazilian Banks

    OpenAIRE

    Marcel Ginotti Pires; Reynaldo Cavalheiro Marcondes

    2017-01-01

    This article discusses the factors present in post-merger integration of Systems and Information Technology (SIT) that lead to positive and negative results in mergers and acquisitions (M & A). The research comprised three of the largest acquiring banks in Brazil. We adopted two methods of research, qualitative, to operationalize the theoretical concepts and quantitative, to test the hypotheses. We interviewed six executives of banks that held relevant experience in M & A pro...

  17. Relevance of Information Systems Strategic Planning Practices in E-Business Contexts

    OpenAIRE

    Ganesan Kannabiran; Srinivasan Sundar

    2011-01-01

    Increasing global competition and advances in Internet technologies have led organizations to consider e-business strategies. However, evolving e-business strategies have been identified as a critical issue faced by corporate planners. The relevance and the use of IS (Information Systems) strategy planning practices in the context of e-business have been argued among researchers. In this paper, the authors investigate whether organizations can successfully improve the IS value in the e-busine...

  18. CESAR cost-efficient methods and processes for safety-relevant embedded systems

    CERN Document Server

    Wahl, Thomas

    2013-01-01

    The book summarizes the findings and contributions of the European ARTEMIS project, CESAR, for improving and enabling interoperability of methods, tools, and processes to meet the demands in embedded systems development across four domains - avionics, automotive, automation, and rail. The contributions give insight to an improved engineering and safety process life-cycle for the development of safety critical systems. They present new concept of engineering tools integration platform to improve the development of safety critical embedded systems and illustrate capacity of this framework for end-user instantiation to specific domain needs and processes. They also advance state-of-the-art in component-based development as well as component and system validation and verification, with tool support. And finally they describe industry relevant evaluated processes and methods especially designed for the embedded systems sector as well as easy adoptable common interoperability principles for software tool integratio...

  19. Knowledge-based driver assistance systems traffic situation description and situation feature relevance

    CERN Document Server

    Huelsen, Michael

    2014-01-01

    The comprehension of a traffic situation plays a major role in driving a vehicle. Interpretable information forms a basis for future projection, decision making and action performing, such as navigating, maneuvering and driving control. Michael Huelsen provides an ontology-based generic traffic situation description capable of supplying various advanced driver assistance systems with relevant information about the current traffic situation of a vehicle and its environment. These systems are enabled to perform reasonable actions and approach visionary goals such as injury and accident free driv

  20. A head and neck lymph node classification using an anatomical grid system while maintaining clinical relevance.

    Science.gov (United States)

    Benninger, Brion; Barrett, Richard

    2011-10-01

    The current classification of head and neck lymph nodes lacks a standardized system that integrates basic anatomy and clinical relevance. Currently, anatomy texts, atlases, and journals used to educate future health care professionals use a classification system that differs from the commonly used clinical nomenclature. As a result, student trainees entering the professional world are confused by lymph node terminology. The purpose of this study was to suggest a lymph node classification system that accurately reflected anatomy and clinical applications. A literature search was conducted on anatomic and clinical texts, atlases, journals, and Web sites. Two recurring classification themes were found from anatomic texts and atlases: superficial and deep chains, and local anatomic structures. Since 1988 the clinical specialties have used a Roman numeral "level" system. The differences between anatomic and clinical classification systems have led to academic frustration. After analysis, a functional classification system was developed that integrated anatomic and clinical terminology from the current classification systems. This suggested system revised the clinically accepted level system approved in 1988 and replaced the terminology with an anatomically derived naming system. This system satisfies the need for a classification that unifies anatomic and clinical applications. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  1. A software system to collect expert relevance ratings of medical record items for specific clinical tasks.

    Science.gov (United States)

    Harvey, H Benjamin; Krishnaraj, Arun; Alkasab, Tarik K

    2014-02-28

    Development of task-specific electronic medical record (EMR) searches and user interfaces has the potential to improve the efficiency and safety of health care while curbing rising costs. The development of such tools must be data-driven and guided by a strong understanding of practitioner information requirements with respect to specific clinical tasks or scenarios. To acquire this important data, this paper describes a model by which expert practitioners are leveraged to identify which components of the medical record are most relevant to a specific clinical task. We also describe the computer system that was created to efficiently implement this model of data gathering. The system extracts medical record data from the EMR of patients matching a given clinical scenario, de-identifies the data, breaks the data up into separate medical record items (eg, radiology reports, operative notes, laboratory results, etc), presents each individual medical record item to experts under the hypothetical of the given clinical scenario, and records the experts' ratings regarding the relevance of each medical record item to that specific clinical scenario or task. After an iterative process of data collection, these expert relevance ratings can then be pooled and used to design point-of-care EMR searches and user interfaces tailored to the task-specific needs of practitioners.

  2. The gyri of the octopus vertical lobe have distinct neurochemical identities.

    Science.gov (United States)

    Shigeno, Shuichi; Ragsdale, Clifton W

    2015-06-15

    The cephalopod vertical lobe is the largest learning and memory structure known in invertebrate nervous systems. It is part of the visual learning circuit of the central brain, which also includes the superior frontal and subvertical lobes. Despite the well-established functional importance of this system, little is known about neuropil organization of these structures and there is to date no evidence that the five longitudinal gyri of the vertical lobe, perhaps the most distinctive morphological feature of the octopus brain, differ in their connections or molecular identities. We studied the histochemical organization of these structures in hatchling and adult Octopus bimaculoides brains with immunostaining for serotonin, octopus gonadotropin-releasing hormone (oGNRH), and octopressin-neurophysin (OP-NP). Our major finding is that the five lobules forming the vertical lobe gyri have distinct neurochemical signatures. This is most prominent in the hatchling brain, where the median and mediolateral lobules are enriched in OP-NP fibers, the lateral lobule is marked by oGNRH innervation, and serotonin immunostaining heavily labels the median and lateral lobules. A major source of input to the vertical lobe is the superior frontal lobe, which is dominated by a neuropil of interweaving fiber bundles. We have found that this neuropil also has an intrinsic neurochemical organization: it is partitioned into territories alternately enriched or impoverished in oGNRH-containing fascicles. Our findings establish that the constituent lobes of the octopus superior frontal-vertical system have an intricate internal anatomy, one likely to reflect the presence of functional subsystems within cephalopod learning circuitry. © 2015 Wiley Periodicals, Inc.

  3. Previous Ketamine Produces an Enduring Blockade of Neurochemical and Behavioral Effects of Uncontrollable Stress

    Science.gov (United States)

    Dolzani, Samuel D.; Tilden, Scott; Christianson, John P.; Kubala, Kenneth H.; Bartholomay, Kristi; Sperr, Katherine; Ciancio, Nicholas; Watkins, Linda R.; Maier, Steven F.

    2016-01-01

    Recent interest in the antidepressant and anti-stress effects of subanesthetic doses of ketamine, an NMDA receptor antagonist, has identified mechanisms whereby ketamine reverses the effect of stress, but little is known regarding the prophylactic effect ketamine might have on future stressors. Here we investigate the prophylactic effect of ketamine against neurochemical and behavioral changes that follow inescapable, uncontrollable tail shocks (ISs) in Sprague Dawley rats. IS induces increased anxiety, which is dependent on activation of serotonergic (5-HT) dorsal raphe nucleus (DRN) neurons that project to the basolateral amygdala (BLA). Ketamine (10 mg/kg, i.p.) administered 2 h, 1 week, or 2 weeks before IS prevented the increased extracellular levels of 5-HT in the BLA typically produced by IS. In addition, ketamine administered at these time points blocked the decreased juvenile social investigation produced by IS. Microinjection of ketamine into the prelimbic (PL) region of the medial prefrontal cortex duplicated the effects of systemic ketamine, and, conversely, systemic ketamine effects were prevented by pharmacological inhibition of the PL. Although IS does not activate DRN-projecting neurons from the PL, IS did so after ketamine, suggesting that the prophylactic effect of ketamine is a result of altered functioning of this projection. SIGNIFICANCE STATEMENT The reported data show that systemic ketamine, given up to 2 weeks before a stressor, blunts behavioral and neurochemical effects of the stressor. The study also advances understanding of the mechanisms involved and suggests that ketamine acts at the prelimbic cortex to sensitize neurons that project to and inhibit the DRN. PMID:26740657

  4. Relevant Factors in The Post-Merger Systems Integration and Information Technology in Brazilian Banks

    Directory of Open Access Journals (Sweden)

    Marcel Ginotti Pires

    2017-01-01

    Full Text Available This article discusses the factors present in post-merger integration of Systems and Information Technology (SIT that lead to positive and negative results in mergers and acquisitions (M & A. The research comprised three of the largest acquiring banks in Brazil. We adopted two methods of research, qualitative, to operationalize the theoretical concepts and quantitative, to test the hypotheses. We interviewed six executives of banks that held relevant experience in M & A processes. Subsequently, we applied questionnaires to IT professionals who were involved in the SIT integration processes. The results showed that the quality and expertise of the integration teams and managing the integration were the most relevant factors in the processes, with positive results for increased efficiency and the increased capacity of SIT. Negative results were due to failures in exploiting learning opportunities, the loss of employees and the inexpressive record of integration procedures.

  5. Neurochemical and electrical modulation of the Locus coeruleus: contribution to CO2 drive to breathe

    Directory of Open Access Journals (Sweden)

    Debora eDe Carvalho

    2014-08-01

    Full Text Available The Locus coeruleus (LC is a dorsal pontine region, situated bilaterally on the floor of the fourth ventricle. It is considered to be the major source of noradrenergic innervation in the brain. These neurons are highly sensitive to CO2 / pH, and chemical lesions of LC neurons largely attenuate the hypercapnic ventilatory response in unanesthetized adult rats. Developmental dysfunctions in these neurons are linked to pathological conditions such as Rett and sudden infant death syndromes, which can impair the control of the cardio-respiratory system. LC is densely innervated by fibers that contain glutamate, serotonin and ATP, and these neurotransmitters strongly affect LC activity, including central chemoreflexes. Aside from neurochemical modulation, LC neurons are also strongly electrically coupled, specifically through gap junctions, which play a role in the CO2 ventilatory response. This article reviews the available data on the role of chemical and electrical neuromodulation of the LC in the control of ventilation.

  6. System approaches of Weiss and Bertalanffy and their relevance for systems biology today.

    Science.gov (United States)

    Drack, Manfred; Wolkenhauer, Olaf

    2011-06-01

    System approaches in biology have a long history. We focus here on the thinking of Paul A. Weiss and Ludwig von Bertalanffy, who contributed a great deal towards making the system concept operable in biology in the early 20th century. To them, considering whole living systems, which includes their organisation or order, is equally important as the dynamics within systems and the interplay between different levels from molecules over cells to organisms. They also called for taking the intrinsic activity of living systems and the conservation of system states into account. We compare these notions with today's systems biology, which is often a bottom-up approach from molecular dynamics to cellular behaviour. We conclude that bringing together the early heuristics with recent formalisms and novel experimental set-ups can lead to fruitful results and understanding. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Nutrigenomic targeting of carbohydrate craving behavior: can we manage obesity and aberrant craving behaviors with neurochemical pathway manipulation by Immunological Compatible Substances (nutrients) using a Genetic Positioning System (GPS) Map?

    Science.gov (United States)

    Downs, B William; Chen, Amanda L C; Chen, Thomas J H; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Braverman, Dasha; Rhoades, Patrick; Prihoda, Thomas J; Palomo, Tomas; Oscar-Berman, Marlene; Reinking, Jeffrey; Blum, Seth H; DiNubile, Nicholas A; Liu, H H; Blum, Kenneth

    2009-09-01

    Genetic mediated physiological processes that rely on both pharmacological and nutritional principles hold great promise for the successful therapeutic targeting of reduced carbohydrate craving, body-friendly fat loss, healthy body recomposition, and overall wellness. By integrating an assembly of scientific knowledge on inheritable characteristics and environmental mediators of gene expression, we review the relationship of genes, hormones, neurotransmitters, and nutrients as they correct unwanted weight gain coupled with unhappiness. In contrast to a simple one-locus, one-mechanism focus on pharmaceuticals alone, we hypothesize that the use of nutrigenomic treatment targeting multi-physiological neurological, immunological, and metabolic pathways will enable clinicians to intercede in the process of lipogenesis by promoting lipolysis while attenuating aberrant glucose cravings. In turn, this approach will enhance wellness in a safe and predictable manner through the use of a Genetic Positioning System (GPS) Map. The GPS Map, while presently incomplete, ultimately will serve not only as a blueprint for personalized medicine in the treatment of obesity, but also for the development of strategies for reducing many harmful addictive behaviors and promoting optimal health by using substances compatible with the body's immune system.

  8. Nutrigenomic targeting of carbohydrate craving behavior: Can we manage obesity and aberrant craving behaviors with neurochemical pathway manipulation by Immunological Compatible Substances (nutrients) using a Genetic Positioning System (GPS) Map?

    Science.gov (United States)

    Downs, B. William; Chen, Amanda L.C.; Chen, Thomas J.H.; Waite, Roger L.; Braverman, Eric R.; Kerner, Mallory; Braverman, Dasha; Rhoades, Patrick; Prihoda, Thomas J.; Palomo, Tomas; Oscar-Berman, Marlene; Reinking, Jeffrey; Blum, Seth H.; DiNubile, Nicholas A.; Liu, H.H.; Blum, Kenneth

    2013-01-01

    SUMMARY Genetic mediated physiological processes that rely on both pharmacological and nutritional principles hold great promise for the successful therapeutic targeting of reduced carbohydrate craving, body-friendly fat loss, healthy body recomposition, and overall wellness. By integrating an assembly of scientific knowledge on inheritable characteristics and environmental mediators of gene expression, we review the relationship of genes, hormones, neurotransmitters, and nutrients as they correct unwanted weight gain coupled with unhappiness. In contrast to a simple one-locus, one-mechanism focus on pharmaceuticals alone, we hypothesize that the use of nutrigenomic treatment targeting multi-physiological neurological, immunological, and metabolic pathways will enable clinicians to intercede in the process of lipogenesis by promoting lipolysis while attenuating aberrant glucose cravings. In turn, this approach will enhance wellness in a safe and predictable manner through the use of a Genetic Positioning System (GPS) Map. The GPS Map, while presently incomplete, ultimately will serve not only as a blueprint for personalized medicine in the treatment of obesity, but also for the development of strategies for reducing many harmful addictive behaviors and promoting optimal health by using substances compatible with the body’s immune system. PMID:19450935

  9. Unmanned Aircraft Systems for Studying Spatial Abundance of Ungulates: Relevance to Spatial Epidemiology

    Science.gov (United States)

    Barasona, José A.; Mulero-Pázmány, Margarita; Acevedo, Pelayo; Negro, Juan J.; Torres, María J.; Gortázar, Christian; Vicente, Joaquín

    2014-01-01

    Complex ecological and epidemiological systems require multidisciplinary and innovative research. Low cost unmanned aircraft systems (UAS) can provide information on the spatial pattern of hosts’ distribution and abundance, which is crucial as regards modelling the determinants of disease transmission and persistence on a fine spatial scale. In this context we have studied the spatial epidemiology of tuberculosis (TB) in the ungulate community of Doñana National Park (South-western Spain) by modelling species host (red deer, fallow deer and cattle) abundance at fine spatial scale. The use of UAS high-resolution images has allowed us to collect data to model the environmental determinants of host abundance, and in a further step to evaluate their relationships with the spatial risk of TB throughout the ungulate community. We discuss the ecological, epidemiological and logistic conditions under which UAS may contribute to study the wildlife/livestock sanitary interface, where the spatial aggregation of hosts becomes crucial. These findings are relevant for planning and implementing research, fundamentally when managing disease in multi-host systems, and focusing on risky areas. Therefore, managers should prioritize the implementation of control strategies to reduce disease of conservation, economic and social relevance. PMID:25551673

  10. Clozapine protection against gestational cocaine-induced neurochemical abnormalities.

    Science.gov (United States)

    Yablonsky-Alter, Elena; Gashi, Eleonora; Lidsky, Theodore I; Wang, Hoau-Yan; Banerjee, Shailesh P

    2005-01-01

    Clozapine was found to be effective in attenuating cocaine-induced neurochemical effects. We investigate whether clozapine influences in utero cocaine exposure-induced changes in striatal dopamine levels and cortical N-methyl-D-aspartate (NMDA) receptor density in mouse and rat brains. Pregnant mice or rats were injected with cocaine (5 or 10 mg/kg intraperitoneally) or saline every 24 h throughout gestation and continued for 6 weeks following the delivery. Striatal dopamine levels measured by high-pressure liquid chromatography were found to decrease 24 to 33% in gestational cocaine exposed between the ages of 3 to 15 days, but not in 42-day-old pups. The cortical NMDA receptor densities assessed either in the presence of 100 microM glutamate or 30 microM glycine were significantly increased in 15-day-old gestational cocaine-exposed rats. Simultaneous daily administration of 3 mg/kg clozapine with 5 mg/kg cocaine to pregnant mice protected against the decrease in striatal dopamine levels or an increase in the concentration of NMDA receptor measured in the presence of 100 microM glutamate in 15-day-old pups. Clozapine did not affect striatal dopamine levels by itself or when coadministered with cocaine in 42-day-old pups. The results show gestational cocaine may induce neurochemical abnormalities in brain exhibited as an increased glutamate NMDA receptor density together with a decreased striatal dopamine level. These effects of gestational cocaine exposure may be prevented by simultaneous administration of clozapine. Thus clozapine, which is a partial agonist at the NMDA receptor, may be of value in protecting against gestational cocaine-induced adverse effects in the brain.

  11. The Systemic Theory of Living Systems and Relevance to CAM: the Theory (Part III)

    Science.gov (United States)

    2005-01-01

    Western medical science lacks a solid philosophical and theoretical approach to disease cognition and therapeutics. My first two articles provided a framework for a humane medicine based on Modern Biophysics. Its precepts encompass modern therapeutics and CAM. Modern Biophysics and its concepts are presently missing in medicine, whether orthodox or CAM, albeit they probably provide the long sought explanation that bridges the abyss between East and West. Key points that differentiate Systemic from other systems' approaches are ‘Intelligence’, ‘Energy’ and the objective ‘to survive’. The General System Theory (GST) took a forward step by proposing a departure from the mechanistic biological concept—of analyzing parts and processes in isolation—and brought us towards an organismic model. GST examines the system's components and results of their interaction. However, GST still does not go far enough. GST assumes ‘Self-Organization’ as a spontaneous phenomenon, ignoring a causative entity or central controller to all systems: Intelligence. It also neglects ‘Survive’ as the directional motivation common to any living system, and scarcely assigns ‘Energy’ its true inherent value. These three parameters, Intelligence, Energy and Survive, are vital variables to be considered, in our human quest, if we are to achieve a unified theory of life. PMID:16136205

  12. The Systemic Theory of Living Systems and Relevance to CAM: the Theory (Part III

    Directory of Open Access Journals (Sweden)

    José A. Olalde Rangel

    2005-01-01

    Full Text Available Western medical science lacks a solid philosophical and theoretical approach to disease cognition and therapeutics. My first two articles provided a framework for a humane medicine based on Modern Biophysics. Its precepts encompass modern therapeutics and CAM. Modern Biophysics and its concepts are presently missing in medicine, whether orthodox or CAM, albeit they probably provide the long sought explanation that bridges the abyss between East and West. Key points that differentiate Systemic from other systems' approaches are ‘Intelligence’, ‘Energy’ and the objective ‘to survive’. The General System Theory (GST took a forward step by proposing a departure from the mechanistic biological concept—of analyzing parts and processes in isolation—and brought us towards an organismic model. GST examines the system's components and results of their interaction. However, GST still does not go far enough. GST assumes ‘Self-Organization’ as a spontaneous phenomenon, ignoring a causative entity or central controller to all systems: Intelligence. It also neglects ‘Survive’ as the directional motivation common to any living system, and scarcely assigns ‘Energy’ its true inherent value. These three parameters, Intelligence, Energy and Survive, are vital variables to be considered, in our human quest, if we are to achieve a unified theory of life.

  13. The Mechanosensory Lateral Line System Mediates Activation of Socially-Relevant Brain Regions during Territorial Interactions.

    Science.gov (United States)

    Butler, Julie M; Maruska, Karen P

    2016-01-01

    Animals use multiple senses during social interactions and must integrate this information in the brain to make context-dependent behavioral decisions. For fishes, the largest group of vertebrates, the mechanosensory lateral line system provides crucial hydrodynamic information for survival behaviors, but little is known about its function in social communication. Our previous work using the African cichlid fish, Astatotilapia burtoni, provided the first empirical evidence that fish use their lateral line system to detect water movements from conspecifics for mutual assessment and behavioral choices. It is unknown, however, where this socially-relevant mechanosensory information is processed in the brain to elicit adaptive behavioral responses. To examine for the first time in any fish species which brain regions receive contextual mechanosensory information, we quantified expression of the immediate early gene cfos as a proxy for neural activation in sensory and socially-relevant brain nuclei from lateral line-intact and -ablated fish following territorial interactions. Our in situ hybridization results indicate that in addition to known lateral line processing regions, socially-relevant mechanosensory information is processed in the ATn (ventromedial hypothalamus homolog), Dl (putative hippocampus homolog), and Vs (putative medial extended amygdala homolog). In addition, we identified a functional network within the conserved social decision-making network (SDMN) whose co-activity corresponds with mutual assessment and behavioral choice. Lateral line-intact and -ablated fight winners had different patterns of co-activity of these function networks and group identity could be determined solely by activation patterns, indicating the importance of mechanoreception to co-activity of the SDMN. These data show for the first time that the mechanosensory lateral line system provides relevant information to conserved decision-making centers of the brain during territorial

  14. Ideas and perspectives: climate-relevant marine biologically driven mechanisms in Earth system models

    Science.gov (United States)

    Hense, Inga; Stemmler, Irene; Sonntag, Sebastian

    2017-01-01

    The current generation of marine biogeochemical modules in Earth system models (ESMs) considers mainly the effect of marine biota on the carbon cycle. We propose to also implement other biologically driven mechanisms in ESMs so that more climate-relevant feedbacks are captured. We classify these mechanisms in three categories according to their functional role in the Earth system: (1) biogeochemical pumps, which affect the carbon cycling; (2) biological gas and particle shuttles, which affect the atmospheric composition; and (3) biogeophysical mechanisms, which affect the thermal, optical, and mechanical properties of the ocean. To resolve mechanisms from all three classes, we find it sufficient to include five functional groups: bulk phyto- and zooplankton, calcifiers, and coastal gas and surface mat producers. We strongly suggest to account for a larger mechanism diversity in ESMs in the future to improve the quality of climate projections.

  15. Assessing Hospital Physicians' Acceptance of Clinical Information Systems: A Review of the Relevant Literature

    Directory of Open Access Journals (Sweden)

    Bram Pynoo

    2013-06-01

    Full Text Available In view of the tremendous potential benefits of clinical information systems (CIS for the quality of patient care; it is hard to understand why not every CIS is embraced by its targeted users, the physicians. The aim of this study is to propose a framework for assessing hospital physicians' CIS-acceptance that can serve as a guidance for future research into this area. Hereto, a review of the relevant literature was performed in the ISI Web-of-Science database. Eleven studies were withheld from an initial dataset of 797 articles. Results show that just as in business settings, there are four core groups of variables that influence physicians' acceptance of a CIS: its usefulness and ease of use, social norms, and factors in the working environment that facilitate use of the CIS (such as providing computers/workstations, compatibility between the new and existing system.... We also identified some additional variables as predictors of CIS-acceptance.

  16. Neurochemical phenotype of cytoglobin‑expressing neurons in the rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-01-01

    of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic...... of Cygb neurons co-expressing nNOS. Furthermore, it was shown that the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS. Detailed information regarding the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable tool...

  17. Effects of serotonin 2C receptor agonists on the behavioral and neurochemical effects of cocaine in squirrel monkeys.

    Science.gov (United States)

    Manvich, Daniel F; Kimmel, Heather L; Howell, Leonard L

    2012-05-01

    Accumulating evidence indicates that the serotonin system modulates the behavioral and neurochemical effects of cocaine, but the receptor subtypes mediating these effects remain unknown. Recent studies have demonstrated that pharmacological activation of the serotonin 2C receptor (5-HT(2C)R) attenuates the behavioral and neurochemical effects of cocaine in rodents, but such compounds have not been systematically evaluated in nonhuman primates. The present experiments sought to determine the impact of pretreatment with the preferential 5-HT(2C)R agonist m-chlorophenylpiperazine (mCPP) and the selective 5-HT(2C)R agonist Ro 60-0175 [(α-S)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine fumarate] on the behavioral and neurochemical effects of cocaine in squirrel monkeys. In subjects trained to lever-press according to a 300-s fixed-interval schedule of stimulus termination, pretreatment with either 5-HT(2C)R agonist dose-dependently and insurmountably attenuated the behavioral stimulant effects of cocaine. In subjects trained to self-administer cocaine, both compounds dose-dependently and insurmountably attenuated cocaine-induced reinstatement of previously extinguished responding in an antagonist-reversible manner, and the selective agonist Ro 60-0175 also attenuated the reinforcing effects of cocaine during ongoing cocaine self-administration. It is noteworthy that the selective agonist Ro 60-0175 exhibited behavioral specificity because it did not significantly alter nondrug-maintained responding. Finally, in vivo microdialysis studies revealed that pretreatment with Ro 60-0175 caused a reduction of cocaine-induced dopamine increases within the nucleus accumbens, but not the caudate nucleus. These results suggest that 5-HT(2C)R agonists functionally antagonize the behavioral effects of cocaine in nonhuman primates, possibly via a selective modulation of cocaine-induced dopamine increases within the mesolimbic dopamine system and may therefore represent a novel

  18. Degradation of TBC Systems in Environments Relevant to Advanced Gas Turbines for IGCC Systems

    Energy Technology Data Exchange (ETDEWEB)

    Gleeson, Brian [Univ. of Pittsburgh, PA (United States)

    2014-09-30

    Air plasma sprayed (APS) thermal barrier coatings (TBCs) are used to provide thermal insulation for the hottest components in gas turbines. Zirconia stabilized with 7wt% yttria (7YSZ) is the most common ceramic top coat used for turbine blades. The 7YSZ coating can be degraded from the buildup of fly-ash deposits created in the power-generation process. Fly ash from an integrated gasification combined cycle (IGCC) system can result from coal-based syngas. TBCs are also exposed to harsh gas environments containing CO2, SO2, and steam. Degradation from the combined effects of fly ash and harsh gas atmospheres has the potential to severely limit TBC lifetimes. The main objective of this study was to use lab-scale testing to systematically elucidate the interplay between prototypical deposit chemistries (i.e., ash and its constituents, K2SO4, and FeS) and environmental oxidants (i.e., O2, H2O and CO2) on the degradation behavior of advanced TBC systems. Several mechanisms of early TBC failure were identified, as were the specific fly-ash constituents responsible for degradation. The reactivity of MCrAlY bondcoats used in TBC systems was also investigated. The specific roles of oxide and sulfate components were assessed, together with the complex interplay between gas composition, deposit chemistry and alloy reactivity. Bondcoat composition design strategies to mitigate corrosion were established, particularly with regard to controlling phase constitution and the amount of reactive elements the bondcoat contains in order to achieve optimal corrosion resistance.

  19. Integration of Transport-relevant Data within Image Record of the Surveillance System

    Directory of Open Access Journals (Sweden)

    Adam Stančić

    2016-10-01

    Full Text Available Integration of the collected information on the road within the image recorded by the surveillance system forms a unified source of transport-relevant data about the supervised situation. The basic assumption is that the procedure of integration changes the image to the extent that is invisible to the human eye, and the integrated data keep identical content. This assumption has been proven by studying the statistical properties of the image and integrated data using mathematical model modelled in the programming language Python using the combinations of the functions of additional libraries (OpenCV, NumPy, SciPy and Matplotlib. The model has been used to compare the input methods of meta-data and methods of steganographic integration by correcting the coefficients of Discrete Cosine Transform JPEG compressed image. For the procedures of steganographic data processing the steganographic algorithm F5 was used. The review paper analyses the advantages and drawbacks of the integration methods and present the examples of situations in traffic in which the formed unified sources of transport-relevant information could be used.

  20. Methodology for Flight Relevant Arc-Jet Testing of Flexible Thermal Protection Systems

    Science.gov (United States)

    Mazaheri, Alireza; Bruce, Walter E., III; Mesick, Nathaniel J.; Sutton, Kenneth

    2013-01-01

    A methodology to correlate flight aeroheating environments to the arc-jet environment is presented. For a desired hot-wall flight heating rate, the methodology provides the arcjet bulk enthalpy for the corresponding cold-wall heating rate. A series of analyses were conducted to examine the effects of the test sample model holder geometry to the overall performance of the test sample. The analyses were compared with arc-jet test samples and challenges and issues are presented. The transient flight environment was calculated for the Hypersonic Inflatable Aerodynamic Decelerator (HIAD) Earth Atmospheric Reentry Test (HEART) vehicle, which is a planned demonstration vehicle using a large inflatable, flexible thermal protection system to reenter the Earth's atmosphere from the International Space Station. A series of correlations were developed to define the relevant arc-jet test environment to properly approximate the HEART flight environment. The computed arcjet environments were compared with the measured arc-jet values to define the uncertainty of the correlated environment. The results show that for a given flight surface heat flux and a fully-catalytic TPS, the flight relevant arc-jet heat flux increases with the arc-jet bulk enthalpy while for a non-catalytic TPS the arc-jet heat flux decreases with the bulk enthalpy.

  1. Relevance Vector Machines for Enhanced BER Probability in DMT-Based Systems

    Directory of Open Access Journals (Sweden)

    Ashraf A. Tahat

    2010-01-01

    Full Text Available A new channel estimation method for discrete multitone (DMT communication system based on sparse Bayesian learning relevance vector machine (RVM method is presented. The Bayesian frame work is used to obtain sparse solutions for regression tasks with linear models. By exploiting a probabilistic Bayesian learning framework, sparse Bayesian learning provides accurate models for estimation and consequently equalization. We consider frequency domain equalization (FEQ using the proposed channel estimate at both the transmitter (preequalization and receiver (postequalization and compare the resulting bit error rate (BER performance curves for both approaches and various channel estimation techniques. Simulation results show that the proposed RVM-based method is superior to the traditional least squares technique.

  2. Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics

    NARCIS (Netherlands)

    Lelental, N.; Brandner, S.; Kofanova, O.; Blennow, K.; Zetterberg, H.; Andreasson, U.; Engelborghs, S.; Mroczko, B.; Gabryelewicz, T.; Teunissen, C.; Mollenhauer, B.; Parnetti, L.; Chiasserini, D.; Molinuevo, J.L.; Perret-Liaudet, A.; Verbeek, M.M.; Andreasen, N.; Brosseron, F.; Bahl, J.M.; Herukka, S.K.; Hausner, L.; Frolich, L.; Labonte, A.; Poirier, J.; Miller, A.M.; Zilka, N.; Kovacech, B.; Urbani, A.; Suardi, S.; Oliveira, C. de; Baldeiras, I.; Dubois, B.; Rot, U.; Lehmann, S.; Skinningsrud, A.; Betsou, F.; Wiltfang, J.; Gkatzima, O.; Winblad, B.; Buchfelder, M.; Kornhuber, J.; Lewczuk, P.

    2016-01-01

    BACKGROUND: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.

  3. Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics

    NARCIS (Netherlands)

    Lelental, Natalia; Brandner, Sebastian; Kofanova, Olga; Blennow, Kaj; Zetterberg, Henrik; Andreasson, Ulf; Engelborghs, Sebastiaan; Mroczko, Barbara; Gabryelewicz, Tomasz; Teunissen, Charlotte; Mollenhauer, Brit; Parnetti, Lucilla; Chiasserini, Davide; Molinuevo, Jose Luis; Perret-Liaudet, Armand; Verbeek, Marcel M.; Andreasen, Niels; Brosseron, Frederic; Bahl, Justyna M. C.; Herukka, Sanna-Kaisa; Hausner, Lucrezia; Froelich, Lutz; Labonte, Anne; Poirier, Judes; Miller, Anne-Marie; Zilka, Norbert; Kovacech, Branislav; Urbani, Andrea; Suardi, Silvia; Oliveira, Catarina; Baldeiras, Ines; Dubois, Bruno; Rot, Uros; Lehmann, Sylvain; Skinningsrud, Anders; Betsou, Fay; Wiltfang, Jens; Gkatzima, Olymbia; Winblad, Bengt; Buchfelder, Michael; Kornhuber, Johannes; Lewczuk, Piotr

    2016-01-01

    Background: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.

  4. Review of relevant studies of isolated systems[Integration of wind energy

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, L.H.; Lundsager, P.

    2000-12-01

    The report presents the results of a review of studies relating to integration of wind energy in isolated power supply systems, based on a systematic literature survey. The purpose of the study is to develop a methodology consisting of a set of guidelines for wind energy projects in isolated energy systems and a set of tools and models that are operational on an engineering level. The review is based on a literature search in the ETDE Energy Database with a main search covering the period 7/88 to 6/97 and supplemented by partial update periods. A few newer references have been included in the review, most notably the IEC/PAS 62111 specification. The amount of wind energy literature related to the subject is excessively large, and a complete review in which every relevant abstract is identified and examined is not feasible within the framework of this (or probably any other) study. The review results have been organised according to the following keywords: methods & guides, economics, concept of application, system solutions, case studies, financial programmes, dedicated software tools. None of the found references presents methods or tools that contradict the philosophy of Risoe's methodology as it is described in the report. It is therefore concluded that Risoe's methodology makes a good platform for further development. (au)

  5. Degradation of TBC Systems in Environments Relevant to Advanced Gas Turbines for IGCC Systems

    Science.gov (United States)

    Bohna, Nathaniel Allan

    Plasma sprayed (PS) thermal barrier coatings (TBCs) are used to provide thermal insulation for the hottest components in gas turbines. Zirconia stabilized with 7wt% yttria (7YSZ) is the most common ceramic top coat used for turbine blades. The 7YSZ coating can be degraded by the buildup of fly-ash deposits which can arise from the fuel source (coal/biomass) used in the combustion process in gas turbines. Fly-ash from the integrated gasification combined cycle (IGCC) process can result from coal-based syngas and also from ambient air which passes through the system. TBCs are also exposed to harsh gas environments containing CO2, SO2, and steam. As presented in this thesis, degradation from the combined effects of fly-ash and harsh gas atmosphere can severely limit TBC lifetimes. It is well established that degradation at very high temperatures (≥1250°C) from deposits consisting of the oxides CaO-MgO-Al2O3-SiO 2 results from extensive liquid silicate infiltration into the porous top coat of the YSZ. This infiltration causes early failure resulting from chemical and/or mechanical damage to the ceramic layer. Damage resulting from liquid infiltration, however, is not typically considered at relatively lower temperatures around 1100°C because liquid silicates would not be expected to form from the oxides in the deposit. A key focus of this study is to assess the mode and extent of TBC degradation at 1100°C in cases when some amount of liquid forms owing to the presence of K2SO4 as a minor ash constituent. Two types of liquid infiltrations are observed depending on the principal oxide (i.e., CaO or SiO2) in the deposit. The degradation is primarily the result of mechanical damage, which results from infiltration caused by the interaction of liquid K2SO4 with either the CaO or SiO2. The TBCs used in this work are representative of commonly used coatings used in the hottest sections of land-based gas turbines. The specimens consist of 7YSZ top coats deposited on

  6. PME Augmentation to Isotopic Investigations Relevant to Origins of Solar Systems

    Science.gov (United States)

    Yin, Qing-zhu

    We propose to acquire a state-of-the-art, next generation, ultra high precision and high sensitivity thermal ionization mass spectrometer (TIMS) at the University of California, Davis (UC Davis) for isotope cosmochemistry research that is highly relevant to NASA's Origins of Solar Systems program. UC Davis will contribute 10% of the total budget (87,791) from the PI's start-up fund to share the cost of the proposed equipment. We request partial funding (790,118) from the Planetary Major Equipment program to cover the remaining cost of the instrument, as an augmentation to the existing science research award from the Origins of Solar Systems (OSS) program (NNX09AC93G) to the PI (Qing-Zhu Yin). The proposed instrument acquisition is vital to accomplish the research objectives outlined in the original OSS award (NNX09AC93G) and Cosmochemistry award (NNX08AG57G) to the PI. To ensure investigator access to and further development of new techniques that expand our research goals, the PI needs a TIMS as an Investigator Instrument (using NASA terminology). The University of California, Davis is fully committed to supporting isotope geochemistry and cosmochemistry research, as manifested through the promotion of the PI as a tenured faculty member effective July 1, 2008, providing the matching funds for cost sharing of the proposed instrument purchase, and a class-100 clean lab space (640 square feet) for sample handling in the new Earth and Physical Sciences building. The proposed acquisition is highly relevant to the scope of NASA's Origins of Solar Systems program: i.e., to conduct scientific investigations related to understanding the formation and early evolution of planetary systems in the area of analysis of primitive materials, solar nebular processes, star formation and its relationship to planetary system formations. The acquisition will help to generate new data and contribute to the development of new techniques that closely support NASA's activities for future

  7. Phase diagram, thermodynamic investigations, and modelling of systems relevant to lithium-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Fuertauer, Siegfried; Beutl, Alexander; Flanorfer, Hans [Vienna Univ. (Austria). Dept. of Inorganic Chemistry - Functional Materials; Li, Dajian; Cupid, Damian [Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen (Germany). Inst. for Applied Materials - Applied Materials Physics (IAM-AWP); Henriques, David; Giel, Hans; Markus, Thorsten [Mannheim Univ. of Applied Sciences (Germany). Inst. for Thermo- and Fluiddynamics

    2017-11-15

    This article reports on two consecutive joint projects titled ''Experimental Thermodynamics and Phase Relations of New Electrode Materials for Lithium-Ion Batteries'', which were performed in the framework of the WenDeLIB 1473 priority program ''Materials with new Design for Lithium Ion Batteries''. Hundreds of samples were synthesized using experimental techniques specifically developed to deal with highly reactive lithium and lithium-containing compounds to generate electrochemical, phase diagram and crystal structure data in the Cu-Li, Li-Sn, Li-Sb, Cu-Li-Sn, Cu-Li-Sb and selected oxide systems. The thermochemical and phase diagram data were subsequently used to develop self-consistent thermodynamic descriptions of several binary systems. In the present contribution, the experimental techniques, working procedures, results and their relevance to the development of new electrode materials for lithium ion batteries are discussed and summarized. The collaboration between the three groups has resulted in more than fifteen (15) published articles during the six-year funding period.

  8. Formation and Stability of Prebiotically Relevant Vesicular Systems in Terrestrial Geothermal Environments.

    Science.gov (United States)

    Joshi, Manesh Prakash; Samanta, Anupam; Tripathy, Gyana Ranjan; Rajamani, Sudha

    2017-11-30

    Terrestrial geothermal fields and oceanic hydrothermal vents are considered as candidate environments for the emergence of life on Earth. Nevertheless, the ionic strength and salinity of oceans present serious limitations for the self-assembly of amphiphiles, a process that is fundamental for the formation of first protocells. Consequently, we systematically characterized the efficiency of amphiphile assembly, and vesicular stability, in terrestrial geothermal environments, both, under simulated laboratory conditions and in hot spring water samples (collected from Ladakh, India, an Astrobiologically relevant site). Combinations of prebiotically pertinent fatty acids and their derivatives were evaluated for the formation of vesicles in aforesaid scenarios. Additionally, the stability of these vesicles was characterized over multiple dehydration-rehydration cycles, at elevated temperatures. Among the combinations that were tested, mixtures of fatty acid and its glycerol derivatives were found to be the most robust, also resulting in vesicles in all of the hot spring waters that were tested. Importantly, these vesicles were stable at high temperatures, and this fatty acid system retained its vesicle forming propensity, even after multiple cycles of dehydration-rehydration. The remaining systems, however, formed vesicles only in bicine buffer. Our results suggest that certain prebiotic compartments would have had a selective advantage in terrestrial geothermal niches. Significantly, our study highlights the importance of validating results that are obtained under 'buffered' laboratory conditions, by verifying their plausibility in prebiotically analogous environments.

  9. A neurochemical approach to valuation sensitivity over gains and losses.

    Science.gov (United States)

    Zhong, Songfa; Israel, Salomon; Xue, Hong; Sham, Pak C; Ebstein, Richard P; Chew, Soo Hong

    2009-12-07

    Prospect theory proposes the hypothesis that people have diminishing sensitivity in valuing increases in the size of monetary outcomes, for both gains and losses. For decision-making under risk, this implies a tendency to be risk-tolerant over losses while being generally risk averse over gains. We offer a neurochemistry-based model of the diminishing valuation sensitivity hypothesis. Specifically, we propose that dopamine tone modulates the sensitivity towards valuation of gains while serotonin tone modulates the sensitivity towards valuation of losses. Consequently, higher dopamine tone would yield a more concave valuation function over gains while higher serotonin tone would yield a more convex valuation function over losses. Using a neurogenetics strategy to test our neurochemical model, we find that subjects with the 9-repeat allele of DAT1 (lower DA tone) are more risk-tolerant over gains than subjects with the 10-repeat allele, and that subjects with the 10-repeat allele of STin2 (higher 5HT tone) are more risk-tolerant over losses than subjects with the 12-repeat allele. Overall, our results support the implications of our model and provide the first neurogenetics evidence that risk attitudes are partially hard-wired in differentiating between gain- and loss-oriented risks.

  10. Neurochemical Alterations in Sudden Unexplained Perinatal Deaths—A Review

    Directory of Open Access Journals (Sweden)

    Nazeer Muhammad

    2018-01-01

    Full Text Available Sudden unexpected perinatal collapse is a major trauma for the parents of victims. Sudden infant death syndrome (SIDS is unexpected and mysterious death of an apparently healthy neonate from birth till 1 year of age without any known causes, even after thorough postmortem investigations. However, the incidence of sudden intrauterine unexplained death syndrome (SIUDS is seven times higher as compared with SIDS. This observation is approximated 40–80%. Stillbirth is defined as death of a fetus after 20th week of gestation or just before delivery at full term without a known reason. Pakistan has the highest burden of stillbirth in the world. This basis of SIDS, SIUDS, and stillbirths eludes specialists. The purpose of this study is to investigate factors behind failure in control of these unexplained deaths and how research may go ahead with improved prospects. Animal models and physiological data demonstrate that sleep, arousal, and cardiorespiratory malfunctioning are abnormal mechanisms in SIUDS risk factors or in newborn children who subsequently die from SIDS. This review focuses on insights in neuropathology and mechanisms of SIDS and SIUDS in terms of different receptors involved in this major perinatal demise. Several studies conducted in the past decade have confirmed neuropathological and neurochemical anomalies related to serotonin transporter, substance P, acetylcholine α7 nicotine receptors, etc., in sudden unexplained fetal and infant deaths. There is need to focus more on research in this area to unveil the major curtain to neuroprotection by underlying mechanisms leading to such deaths.

  11. Dyslipidemia links obesity to early cerebral neurochemical alterations.

    Science.gov (United States)

    Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Tanaka, Hirofumi

    2013-10-01

    To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy ((1) H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. Copyright © 2013 The Obesity Society.

  12. Proteolytic events are relevant cellular responses during nervous system regeneration of the starfish Marthasterias glacialis.

    Science.gov (United States)

    Ferraz Franco, Catarina; Santos, Romana; Varela Coelho, Ana

    2014-03-17

    The molecular pathways that trigger the amazing intrinsic regenerative ability of echinoderm nervous system are still unknown. In order to approach this subject, a 2D-DIGE proteomic strategy was used, to screen proteome changes during neuronal regeneration in vivo, using starfish (Asteroidea, Echinodermata) as a model. A total of 528 proteins showed significant variations during radial nerve cord regeneration in both soluble and membrane protein-enriched fractions. Several functional classes of proteins known to be involved in axon regeneration events in other model organisms, such as chordates, were identified for the first time in the regenerating echinoderm nervous system. Unexpectedly, most of the identified proteins presented a molecular mass either higher or lower than expected. Such results suggest a functional modulation through protein post-translational modifications, such as proteolysis. Among these are proteins involved in cytoskeleton and microtubule regulators, axon guidance molecules and growth cone modulators, protein de novo synthesis machinery, RNA binding and transport, transcription factors, kinases, lipid signaling effectors and proteins with neuroprotective functions. In summary, the impact of proteolysis during regeneration events is here shown, although requiring further studies to detail on the mechanisms involving this post-transcriptional event on nervous system regeneration. The nervous systems of some organisms present a complete inability of neurons to regrow across a lesion site, which is the case of the adult mammalian central nervous system (CNS). Expanding our knowledge on how other animals regenerate their nervous system offers great potential for groundbreaking biomedical applications towards the enhancement of mammalian CNS regeneration. In order to approach this subject, a 2D-DIGE proteomic strategy was used for the first time, to screen the proteome changes during neuronal regeneration in vivo, using starfish (Asteroidea

  13. Social vs. environmental stress models of depression from a behavioural and neurochemical approach.

    Science.gov (United States)

    Venzala, E; García-García, A L; Elizalde, N; Tordera, R M

    2013-07-01

    Major depression is a mental disorder often preceded by exposure to chronic stress or stressful life events. Recently, animal models based on social conflict such as chronic social defeat stress (CSDS) are proposed to be more relevant to stress-induced human psychopathology compared to environmental models like the chronic mild stress (CMS). However, while CMS reproduces specifically core depressive symptoms such as anhedonia and helplessness, CSDS studies rely on the analysis of stress-induced social avoidance, addressing different neuropsychiatric disorders. Here, we study comparatively the two models from a behavioural and neurochemical approach and their possible relevance to human depression. Mice (C57BL/6) were exposed to CMS or CSDS for six weeks and ten days. Anhedonia was periodically evaluated. A battery of test applied during the fourth week after the stress procedure included motor activity, memory, anxiety, social interaction and helplessness. Subsequently, we examined glutamate, GABA, 5-HT and dopamine levels in the prefrontal cortex, hippocampus and brainstem. CMS induced a clear depressive-like profile including anhedonia, helplessness and memory impairment. CSDS induced anhedonia, hyperactivity, anxiety and social avoidance, signs also common to anxiety and posttraumatic stress disorders. While both models disrupted the excitatory inhibitory balance in the prefrontal cortex, CMS altered importantly this balance in the brainstem. Moreover, CSDS decreased dopamine in the prefrontal cortex and brainstem. We suggests that while depressive-like behaviours might be associated to altered aminoacid neurotransmission in cortical and brain stem areas, CSDS induced anxiety behaviours might be linked to specific alteration of dopaminergic pathways involved in rewarding processes. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  14. Cutoff low systems and their relevance to large-scale extreme precipitation in the European Alps

    Science.gov (United States)

    Awan, N. K.; Formayer, H.

    2017-07-01

    In this paper, we attempt to highlight the relevance of cutoff low systems (CoLs) to large-scale heavy precipitation events within the Alpine region which often lead to catastrophic flooding. The main results of this study are (1) a detailed climatology (1971-1999) of CoLs for the European region, (2) contribution of CoLs to extreme precipitation events in the European Alpine region, (3) identification of regions within the European Alps most affected by extreme precipitation caused by CoLs, and (4) identification of regions where presence of CoLs is related to extreme precipitation in the Alpine region. The findings of this paper suggest that CoLs have a significant correlation with extreme precipitation events and strongly influence the climate of the Alpine region. The total contribution of CoLs to large-scale heavy precipitation events ranges between 20 and 95 % and is most pronounced in the northern and eastern parts of the Alps. More than 80 % of the events occur in the summer season. The area around the Alps and West of Spain (over the Atlantic Ocean) is the most affected region. The location of the center of CoLs that affect the Alpine region most occur on the northern and southern sides of the Alpine ridge.

  15. Perceiving active listening activates the reward system and improves the impression of relevant experiences.

    Science.gov (United States)

    Kawamichi, Hiroaki; Yoshihara, Kazufumi; Sasaki, Akihiro T; Sugawara, Sho K; Tanabe, Hiroki C; Shinohara, Ryoji; Sugisawa, Yuka; Tokutake, Kentaro; Mochizuki, Yukiko; Anme, Tokie; Sadato, Norihiro

    2015-01-01

    Although active listening is an influential behavior, which can affect the social responses of others, the neural correlates underlying its perception have remained unclear. Sensing active listening in social interactions is accompanied by an improvement in the recollected impressions of relevant experiences and is thought to arouse positive feelings. We therefore hypothesized that the recognition of active listening activates the reward system, and that the emotional appraisal of experiences that had been subject to active listening would be improved. To test these hypotheses, we conducted functional magnetic resonance imaging (fMRI) on participants viewing assessments of their own personal experiences made by evaluators with or without active listening attitude. Subjects rated evaluators who showed active listening more positively. Furthermore, they rated episodes more positively when they were evaluated by individuals showing active listening. Neural activation in the ventral striatum was enhanced by perceiving active listening, suggesting that this was processed as rewarding. It also activated the right anterior insula, representing positive emotional reappraisal processes. Furthermore, the mentalizing network was activated when participants were being evaluated, irrespective of active listening behavior. Therefore, perceiving active listening appeared to result in positive emotional appraisal and to invoke mental state attribution to the active listener.

  16. Medically Relevant Assays with a Simple Smartphone and Tablet Based Fluorescence Detection System

    Directory of Open Access Journals (Sweden)

    Piotr Wargocki

    2015-05-01

    Full Text Available Cell phones and smart phones can be reconfigured as biomedical sensor devices but this requires specialized add-ons. In this paper we present a simple cell phone-based portable bioassay platform, which can be used with fluorescent assays in solution. The system consists of a tablet, a polarizer, a smart phone (camera and a box that provides dark readout conditions. The assay in a well plate is placed on the tablet screen acting as an excitation source. A polarizer on top of the well plate separates excitation light from assay fluorescence emission enabling assay readout with a smartphone camera. The assay result is obtained by analysing the intensity of image pixels in an appropriate colour channel. With this device we carried out two assays, for collagenase and trypsin using fluorescein as the detected fluorophore. The results of collagenase assay with the lowest measured concentration of 3.75 µg/mL and 0.938 µg in total in the sample were comparable to those obtained by a microplate reader. The lowest measured amount of trypsin was 930 pg, which is comparable to the low detection limit of 400 pg for this assay obtained in a microplate reader. The device is sensitive enough to be used in point-of-care medical diagnostics of clinically relevant conditions, including arthritis, cystic fibrosis and acute pancreatitis.

  17. The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

    Science.gov (United States)

    Tall, F; Dechomet, M; Riviere, S; Cottin, V; Ballot, E; Tiev, K P; Montin, R; Morin, C; Chantran, Y; Grange, C; Jullien, D; Ninet, J; Chretien, P; Cabane, J; Fabien, N; Johanet, C

    2017-01-01

    Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  18. Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder.

    Science.gov (United States)

    Köhler-Forsberg, Ole; Sylvia, Louisa; Deckersbach, Thilo; Ostacher, Michael Joshua; McInnis, Melvin; Iosifescu, Dan; Bowden, Charles; McElroy, Susan; Calabrese, Joseph; Thase, Michael; Shelton, Richard Charles; Tohen, Mauricio; Kocsis, James; Friedman, Edward; Ketter, Terence; Nierenberg, Andrew Alan

    2017-12-07

    Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19-1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature

  19. Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties

    Directory of Open Access Journals (Sweden)

    Adam J. Schwarz

    2012-01-01

    Full Text Available Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.

  20. Treatment with Trehalose Prevents Behavioral and Neurochemical Deficits Produced in an AAV α-Synuclein Rat Model of Parkinson's Disease.

    Science.gov (United States)

    He, Qing; Koprich, James B; Wang, Ying; Yu, Wen-bo; Xiao, Bao-guo; Brotchie, Jonathan M; Wang, Jian

    2016-05-01

    The accumulation of misfolded α-synuclein in dopamine (DA) neurons is believed to be of major importance in the pathogenesis of Parkinson's disease (PD). Animal models of PD, based on viral-vector-mediated over-expression of α-synuclein, have been developed and show evidence of dopaminergic toxicity, providing us a good tool to investigate potential therapies to interfere with α-synuclein-mediated pathology. An efficient disease-modifying therapeutic molecule should be able to interfere with the neurotoxicity of α-synuclein aggregation. Our study highlighted the ability of an autophagy enhancer, trehalose (at concentrations of 5 and 2% in drinking water), to protect against A53T α-synuclein-mediated DA degeneration in an adeno-associated virus serotype 1/2 (AAV1/2)-based rat model of PD. Behavioral tests and neurochemical analysis demonstrated a significant attenuation in α-synuclein-mediated deficits in motor asymmetry and DA neurodegeneration including impaired DA neuronal survival and DA turnover, as well as α-synuclein accumulation and aggregation in the nigrostriatal system by commencing 5 and 2% trehalose at the same time as delivery of AAV. Trehalose (0.5%) was ineffective on the above behavioral and neurochemical deficits. Further investigation showed that trehalose enhanced autophagy in the striatum by increasing formation of LC3-II. This study supports the concept of using trehalose as a novel therapeutic strategy that might prevent/reverse α-synuclein aggregation for the treatment of PD.

  1. Using position emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression.

    Science.gov (United States)

    Zsido, Rachel G; Villringer, Arno; Sacher, Julia

    2017-12-01

    Ovarian hormones, particularly oestrogen and progesterone, undergo major fluctuations across the female lifespan. These hormone transition periods, such as the transition from pregnancy to postpartum, as well as the transition into menopause (perimenopause), are also known to be times of elevated susceptibility to depression. This study reviews how these transition periods likely influence neurochemical changes in the brain that result in disease vulnerability. While there are known associations between oestrogen/progesterone and different monoaminergic systems, the interactions and their potential implications for mood disorders are relatively unknown. Positron Emission Tomography (PET) allows for the in-vivo quantification of such neurochemical changes, and, thus, can provide valuable insight into how both subtle and dramatic shifts in hormones contribute to the elevated rates of depression during pre-menstrual, post-partum, and perimenopausal periods in a woman's life. As one better understands how to address the challenges of PET studies involving highly vulnerable populations, such as women who have recently given birth, one will gain the insight necessary to design and individualize treatment and therapy. Understanding the precise time-line in younger women when dramatic fluctuations in the hormonal milieu may contribute to brain changes may present a powerful opportunity to intervene before a vulnerable state develops into a diseased state in later life.

  2. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: relevance of animal affective systems to human disorders, with a focus on resilience to adverse events.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Matrov, Denis; Panksepp, Jaak

    2011-10-01

    The search for novel antidepressants may be facilitated by pre-clinical animal models that relay on specific neural circuit and related neurochemical endpoint measures, which are anchored in concrete neuro-anatomical and functional neural-network analyzes. One of the most important initial considerations must be which regions of the brain are candidates for the maladaptive response to depressogenic challenges. Consideration of persistent differences or changes in the activity of cerebral networks can be achieved by mapping oxidative metabolism in ethologically or pathogenetically relevant animal models. Cytochrome oxidase histochemistry is a technique suitable to detect regional long-term brain activity changes relative to control conditions and has been used in a variety of animal models. This work is summarized and indicates that major changes occur mainly in subcortical areas, highlighting specific brain regions where some alterations in regional oxidative metabolism may represent adaptive changes to depressogenic adverse life events, while others may reflect failures of adaptation. Many of these changes in oxidative metabolism may depend upon the integrity of serotonergic neurotransmission, and occur in several brain regions shown by other techniques to be involved in endogenous affective circuits that control emotional behaviors as well as related higher brain regions that integrate learning and cognitive information processing. These brain regions appear as primary targets for further identification of endophenotypes specific to affective disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Neurochemical organization of the nucleus paramedianus dorsalis in the human.

    Science.gov (United States)

    Baizer, Joan S; Baker, James F; Haas, Kristin; Lima, Raquel

    2007-10-24

    We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (antibody SMI-32). In transverse sections, PMD is oval with its long axis aligned with the dorsal border of the brainstem. We identified PMD in eight human brainstems, but found some variability both in its cross-sectional area and in its A-P extent among cases. It includes calretinin immunoreactive large cells with oval or polygonal cell bodies. Cells in PMD are not immunoreactive for either calbindin or parvalbumin, but a few fibers immunoreactive to each protein are found within its central region. Cells in PMD are also immunoreactive to nNOS, and immunoreactivity to a neurofilament protein shows many labeled cells and fibers. No similar region is identified in atlases of the cat, mouse, rat or monkey brain, nor does immunoreactivity to any of the markers that delineate it in the human reveal a comparable region in those species. The territory that PMD occupies is included in PH in other species. Since anatomical and physiological data in animals suggest that PH may have multiple subregions, we suggest that the PMD in human may be a further differentiation of PH and may have functions related to the vestibular control of eye movements.

  4. Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalm, Marie, E-mail: marie.kalm@neuro.gu.se [Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Abel, Edvard [Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Wasling, Pontus [Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Nyman, Jan [Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Hietala, Max Albert [Department of Neurology, Karolinska University Hospital, Stockholm (Sweden); Bremell, Daniel; Hagberg, Lars [Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Elam, Mikael [Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Blennow, Kaj [Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal (Sweden); Björk-Eriksson, Thomas [Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden); Zetterberg, Henrik [Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal (Sweden); UCL Institute of Neurology, London (United Kingdom)

    2014-07-01

    Purpose: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β–related processes could characterize the neurochemical response to cranial radiation. Methods and Materials: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. Results: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. Conclusion: In conclusion, we were able to detect radiation therapy–induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.

  5. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

    Science.gov (United States)

    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Neurochemical factors underlying individual differences in locomotor activity and anxiety-like behavioral responses in zebrafish.

    Science.gov (United States)

    Tran, Steven; Nowicki, Magda; Muraleetharan, Arrujyan; Chatterjee, Diptendu; Gerlai, Robert

    2016-02-04

    Variation among individuals may arise for several reasons, and may have diverse underlying mechanisms. Individual differences have been studied in a variety of species, but recently a new model organism has emerged in this field that offers both sophistication in phenotypical characterization and powerful mechanistic analysis. Recently, zebrafish, one of the favorites of geneticists, have been shown to exhibit consistent individual differences in baseline locomotor activity. In the current study, we further explore this finding and examine whether individual differences in locomotor activity correlate with anxiety-like behavioral measures and with levels of dopamine, serotonin and the metabolites of these neurotransmitters. In addition, we examine whether individual differences in locomotor activity are also associated with reactivity to the locomotor stimulant effects of and neurochemical responses to acute ethanol exposure (30min long, 1% v/v ethanol bath application). Principal component analyses revealed a strong association among anxiety-like responses, locomotor activity, serotonin and dopamine levels. Furthermore, ethanol exposure was found to abolish the locomotion-dependent anxiety-like behavioral and serotonergic responses suggesting that this drug also engages a common underlying pathway. Overall, our results provide support for an important role of the serotonergic system in mediating individual differences in anxiety-like responses and locomotor activity in zebrafish and for a minor modulatory role of the dopaminergic system. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    Science.gov (United States)

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. ETIOLOGY, TRIGGERS AND NEUROCHEMICAL CIRCUITS ASSOCIATED WITH UNEXPECTED, EXPECTED, AND LABORATORY-INDUCED PANIC ATTACKS

    Science.gov (United States)

    Johnson, Philip L.; Federici, Lauren M.; Shekhar, Anantha

    2014-01-01

    Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene x environment and gene x hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states. PMID:25130976

  9. Neurochemical and neuropharmacological aspects of circadian disruptions: an introduction to asynchronization.

    Science.gov (United States)

    Kohyama, Jun

    2011-06-01

    Circadian disruptions are common in modern society, and there is an urgent need for effective treatment strategies. According to standard diagnostic criteria, most adolescents showing both insomnia and daytime sleepiness are diagnosed as having behavioral-induced sleep efficiency syndrome resulting from insomnia due to inadequate sleep hygiene. However, a simple intervention of adequate sleep hygiene often fails to treat them. As a solution to this clinical problem, the present review first overviews the basic neurochemical and neuropharmachological aspects of sleep and circadian rhythm regulation, then explains several circadian disruptions from similar viewpoints, and finally introduces the clinical notion of asynchronization. Asynchronization is designated to explain the pathophysiology/pathogenesis of exhibition of both insomnia and hypersomnia in adolescents, which comprises disturbances in various aspects of biological rhythms. The major triggers for asynchronization are considered to be a combination of light exposure during the night, which disturbs the biological clock and decreases melatonin secretion, as well as a lack of light exposure in the morning, which prohibits normal synchronization of the biological clock to the 24-hour cycle of the earth and decreases the activity of serotonin. In the chronic phase of asynchronization, involvement of both wake- and sleep-promoting systems is suggested. Both conventional and alternative therapeutic approaches for potential treatment of asynchronization are suggested.

  10. Neurochemical dementia diagnostics for Alzheimer's disease and other dementias: an ISO 15189 perspective.

    Science.gov (United States)

    Waedt, Johanna; Kleinow, Martina; Kornhuber, Johannes; Lewczuk, Piotr

    2012-10-01

    Dementia is one of the most common causes of health problems in the elderly populations of Western industrialized countries. A combined analysis of cerebrospinal fluid-based neurochemical dementia diagnostics biomarkers (amyloid-β peptides, total tau and phosphorylated forms of tau) provides sensitivity and specificity in the range of 85% for the diagnosis of Alzheimer's disease, the most common cause of dementia. The alterations occur very early in the course of neurodegeneration, enabling medical follow-up of persons with increased risk of developing dementia. With a growing number of laboratories performing neurochemical dementia diagnostics routinely, it is important to standardize protocols and laboratory performance to enable comparisons of results and their interpretations. Together with the recently published expert guidelines for sample handling and preparation, as well as the interpretation (post-analytical) algorithms developed by experienced centers, ISO 15189 norm provides an extremely useful tool for standardization of neurochemical dementia diagnostics.

  11. A versatile, quantitative analytical method for pharmaceutical relevant lipids in drug delivery systems.

    Science.gov (United States)

    Jeschek, Dominik; Lhota, Gabriele; Wallner, Jakob; Vorauer-Uhl, Karola

    2016-02-05

    Over the past few years, liposomal formulations as drug carrier systems have markedly advanced in pharmaceutical research and development. Therefore, analytical methods to characterize liposome-based formulations are required. One particular issue in liposome analysis is the imbalance of lipid ratios within the vesicle formulations and the detectability of degradation products such as lysophospholipids and fatty acids caused by hydrolysis, especially in low molar ranges. Here, a highly sensitive and selective reversed-phase high-performance liquid chromatography (rp-HPLC) method is described by the combination of an organic solvent/trifluoroacetic acid (TFA) triggered gradient and the application of an evaporative light scattering detector (ELSD). Gain setting adjustments of the ELSD were applied to obtain an optimal detection profile of the analyzed substances. This optimization provides simultaneous separation and quantification of 16 components, including different phosphatidylcholines, phosphatidylglycerols and their degradation products, as well as cholesterol. Parameters such as limit of detection (LOD) and limit of quantification (LOQ) were determined for each of the components and had ranges from 0.25-1.00mg/mL (LOD) and 0.50-2.50μg/mL (LOQ), respectively. The intra-day precision for all analytes is less than 3% (RSD) and inter-day precision is about 8%. The applicability of the method was verified by analyzing two different liposome formulations consisting of DSPC:DPPC:DSPG:Chol (35:35:20:10) and DSPC:DPPC:DSPG (38:38:24). For degradation studies, both formulations were stored at 4°C and at ambient temperature. Additionally, forced degradation experiments were performed to determine hydrolysis mass balances. A total recovery of 96-102% for phospholipid compounds was found. Analytical data revealed that the sensitivity, selectivity, accuracy, and resolution are appropriate for the detection and quantification of phospholipids and their hydrolysis products

  12. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.

    2005-01-01

    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and

  13. A Formal Characterization of Relevant Information in Multi-Agent Systems

    Science.gov (United States)

    2009-10-01

    reduce all the Grice’s maxims to one and define a cognitive psychological theory, the Relevance Theory, based on the following informal definition: An...Conference iTrust. (2004) [17] Sadek, D.: Le dialogue homme-machine : de l’ ergonomie des interfaces à l’ agent intelligent dia- loguant. In: Nouvelles interfaces hommemachine, Lavoisier Editeur, Arago 18 (1996) 277–321

  14. Clinical decision support systems differ in their ability to identify clinically relevant drug interactions of immunosuppressants in kidney transplant patients.

    Science.gov (United States)

    Amkreutz, J; Koch, A; Buendgens, L; Trautwein, C; Eisert, A

    2017-06-01

    In kidney transplant patients, clinically relevant drug-drug interactions (DDIs) with immunosuppressants potentially lead to serious adverse drug events (ADEs). The aim of this study was (i) to show that five clinical decision support systems (CDSSs) differ in their ability to identify clinically relevant potential DDIs (pDDIs) of immunosuppressants in kidney transplant patients and (ii) to compare CDSSs in terms of their ability to identify clinically relevant pDDIs in this context. All pDDIs being possible between nine immunosuppressants and 234 comedication drugs were identified for 264 intensive care unit (ICU) kidney transplant patients from 1999 to 2010. For pDDI identification, five CDSSs were used: DRUG-REAX® , ID PHARMA CHECK® , Lexi-Interact, mediQ and Meona. PDDIs from high severity categories were defined as clinically relevant. Classification of pDDIs as clinically relevant/non-clinically relevant by a clinical pharmacist using Stockley's Drug Interactions was employed as benchmark. We analysed inter-rater agreement, sensitivity, specificity, positive predictive value and negative predictive value. Clinical decision support systems generated a total of 759 pDDI alerts. A total of 240 pDDI alerts were in high severity categories. A total of 391 different pDDIs were identified. Only 5% (n = 35) of different pDDIs were identified by all CDSSs. A total of 49 pDDIs were classified as clinically relevant by clinical pharmacists' rating using Stockley's Drug Interactions. Meona (0·72) has the highest inter-rater agreement with the benchmark for clinically relevant pDDIs. ID PHARMA CHECK® and mediQ show highest sensitivities (0·74, respectively). Meona has the highest specificity (0·99) and positive predictive value (0·89). Five CDSSs differ in their ability to identify clinically relevant pDDIs of immunosuppressants in kidney transplant patients. Data may assist in selecting CDSSs for kidney transplant patients in the ICU. Using CDSSs to identify

  15. Why relevance theory is relevant for lexicography

    DEFF Research Database (Denmark)

    Bothma, Theo; Tarp, Sven

    2014-01-01

    This article starts by providing a brief summary of relevance theory in information science in relation to the function theory of lexicography, explaining the different types of relevance, viz. objective system relevance and the subjective types of relevance, i.e. topical, cognitive, situational...... that is very important for lexicography as well as for information science, viz. functional relevance. Since all lexicographic work is ultimately aimed at satisfying users’ information needs, the article then discusses why the lexicographer should take note of all these types of relevance when planning a new...... dictionary project, identifying new tasks and responsibilities of the modern lexicographer. The article furthermore discusses how relevance theory impacts on teaching dictionary culture and reference skills. By integrating insights from lexicography and information science, the article contributes to new...

  16. Radio-controlled automatic gas meter-reading system; Releve automatique de compteur par radio

    Energy Technology Data Exchange (ETDEWEB)

    Yasui, M. [Osaka Gas Co., Ltd (Japan); Ishikawa, K.; Fujiwara, J. [Tokyo Gas Co., Ltd. (Japan); Ichihashi, T. [Toho Gas Co., Ltd. (Japan)

    2000-07-01

    In Japan, an automatic gas meter-reading system is in operation, also incorporating the functions of monitoring for abnormalities in gas use and remote-controlled emergency gas supply shutoff. This system has been realized by linking microcomputer-controlled gas meters(It's called 'Intelligent gas mater') equipped with automatic shutoff mechanism to the gas utility company operation center via communication lines. While the present system uses cable communication lines, we of Tokyo Gas Co., Ltd., Osaka Gas Co., Ltd. and Toho Gas Co., Ltd., have jointly developed a new system based on radio communication. This paper introduces this new system. While radio-controlled meter-reading systems are used in many countries around the world solely for automatic meter reading, our recently developed system is also capable of monitoring for abnormalities in gas use and remote-controlled emergency gas supply shutoff, thanks to its almost real-time two-way communication function. The new system can serve for a period of ten years without recharging. It is also characterized by its applicability as different systems according to purposes: 1) conventional automatic meter-reading system (terminal network control unit or T-NCU), 2) large-scale radio-controlled meter-reading system, and 3) portable terminal-type radio-controlled meter-reading system. (authors)

  17. Costs Systems: Relevance, Feasibility And Usefulness According To Public Officials In The State Of Paraná (Brazil

    Directory of Open Access Journals (Sweden)

    Luciane Maria Gonçalves Franco

    2013-06-01

    Full Text Available The aim in this study is to get to know the level of understanding and adoption of cost systems in cities in the State of Paraná. A descriptive study with a qualitative approach was undertaken. Data were collected through the application of a questionnaire in 67 cities in the State of Paraná. Descriptive analysis was used and Spearman’s correlation coefficient was applied to achieve the research objective. Among the study results, the following stand out: the incipient nature of knowledge about the relevance, feasibility and usefulness of a cost system; resulting from public officials’ limited knowledge, mainly about topics related to the budgetary and financial feasibility of adopting cost systems; an environment for the cost system, implemented costs systems and operating systems; although the answers obtained to proposals about cost information and control were significantly coherent.

  18. Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat.

    Science.gov (United States)

    Serra, Veronica; Fattore, Liana; Scherma, Maria; Collu, Roberto; Spano, Maria Sabrina; Fratta, Walter; Fadda, Paola

    2015-01-01

    Salvinorin A is a recreational drug derived from Salvia divinorum, a sage species long used as an entheogen. While salvinorin A has potent hallucinogenic properties, its abuse potential has not been assessed consistently in controlled behavioural and neurochemical studies in rodents. This study aimed to assess salvinorin A abuse potential by measuring its capacity to establish and maintain self-administration behaviour and to modify dopamine (DA) levels in the nucleus accumbens (NAcc) of rats. Male Lister Hooded (LH) and Sprague-Dawley (SD) rats were allowed to self-administer salvinorin A (0.5 or 1.0 μg/kg/infusion) intravenously 2 h/day for 20 days under a continuous schedule of reinforcement and lever pressing as operandum. LH rats discriminated between the active and inactive levers but did not reach the acquisition criterion for stable self-administration (≥12 active responses vs ≤5 inactive responses for at least 5 consecutive days). SD rats discriminated between the two levers at the lower dose only but, like LH rats, never acquired stable self-administration behaviour. Systemic salvinorin A increased extracellular DA in the NAcc shell of both LH (at ≥40 μg/kg) and SD rats (at ≥5 μg/kg), but injection into the ventral tegmental area (VTA) induced no significant change in NAcc DA concentration in LH rats and only brief elevations in SD rats. Salvinorin A differs from other commonly abused compounds since although it affects accumbal dopamine transmission, yet it is unable, at least at the tested doses, to sustain stable intravenous self-administration behaviour.

  19. Neurochemical characterization of neurons expressing melanin-concentrating hormone receptor 1 in the mouse hypothalamus1

    Science.gov (United States)

    Chee, Melissa J. S.; Pissios, Pavlos; Maratos-Flier, Eleftheria

    2013-01-01

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts via MCH receptor 1 (MCHR1) in the mouse. It promotes positive energy balance thus mice lacking MCH or MCHR1 are lean, hyperactive, and resistant to diet-induced obesity. Identifying the cellular targets of MCH is an important step to understanding the mechanisms underlying MCH actions. We generated the Mchr1-cre mouse that expressed cre recombinase driven by the MCHR1 promoter and crossed it with a tdTomato reporter mouse. The resulting Mchr1-cre/tdTomato progeny expressed easily detectable tdTomato fluorescence in MCHR1 neurons, which were found throughout the olfactory system, striatum, and hypothalamus. To chemically identify MCH-targeted cell populations that play a role in energy balance, MCHR1 hypothalamic neurons were characterized by colabeling select hypothalamic neuropeptides with tdTomato fluorescence. TdTomato fluorescence colocalized with dynorphin, oxytocin, vasopressin, enkephalin, thyrothropin-releasing hormone, and corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus. In the lateral hypothalamus, neurotensin but neither orexin nor MCH neurons expressed tdTomato. In the arcuate nucleus, both Neuropeptide Y and proopiomelanocortin cells expressed tdTomato. We further demonstrated that some of these arcuate neurons were also targets of leptin action. Interestingly, MCHR1 was expressed in the vast majority of leptin-sensitive proopiomelanocortin neurons, highlighting their importance for the orexigenic actions of MCH. Taken together, this study supports the use of the Mchr1-cre mouse for outlining the neuroanatomical distribution and neurochemical phenotype of MCHR1 neurons. PMID:23605441

  20. Neurochemical characterization of neurons expressing melanin-concentrating hormone receptor 1 in the mouse hypothalamus.

    Science.gov (United States)

    Chee, Melissa J S; Pissios, Pavlos; Maratos-Flier, Eleftheria

    2013-07-01

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts via MCH receptor 1 (MCHR1) in the mouse. It promotes positive energy balance; thus, mice lacking MCH or MCHR1 are lean, hyperactive, and resistant to diet-induced obesity. Identifying the cellular targets of MCH is an important step to understanding the mechanisms underlying MCH actions. We generated the Mchr1-cre mouse that expresses cre recombinase driven by the MCHR1 promoter and crossed it with a tdTomato reporter mouse. The resulting Mchr1-cre/tdTomato progeny expressed easily detectable tdTomato fluorescence in MCHR1 neurons, which were found throughout the olfactory system, striatum, and hypothalamus. To chemically identify MCH-targeted cell populations that play a role in energy balance, MCHR1 hypothalamic neurons were characterized by colabeling select hypothalamic neuropeptides with tdTomato fluorescence. TdTomato fluorescence colocalized with dynorphin, oxytocin, vasopressin, enkephalin, thyrothropin-releasing hormone, and corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus. In the lateral hypothalamus, neurotensin, but neither orexin nor MCH neurons, expressed tdTomato. In the arcuate nucleus, both Neuropeptide Y and proopiomelanocortin cells expressed tdTomato. We further demonstrated that some of these arcuate neurons were also targets of leptin action. Interestingly, MCHR1 was expressed in the vast majority of leptin-sensitive proopiomelanocortin neurons, highlighting their importance for the orexigenic actions of MCH. Taken together, this study supports the use of the Mchr1-cre mouse for outlining the neuroanatomical distribution and neurochemical phenotype of MCHR1 neurons. Copyright © 2012 Wiley Periodicals, Inc.

  1. Petrinet-based specification of safety relevant train control systems; Petrinetz-basierte Spezifikation sicherheitsrelevanter Eisenbahnleitsysteme

    Energy Technology Data Exchange (ETDEWEB)

    Einer, S.; Schnieder, E. [Technische Univ. Braunschweig (Germany). Inst. fuer Regelungs- und Automatisierungstechnik; Slovak, R. [Zilina Univ. (Czechoslovakia). Lehrstuhl fuer Informations- und Sicherungssysteme

    2000-07-01

    Higher Standards in performance and safety of future train control systems profit from the use of formal methods for the efficient system development in this domain. This paper considers the use of formal methods in the system requirements specification as the early phase in the system development process. The goal is proving the correctness of the specified requirements and to apply the global safety requirements to the system components. Aspects to be contained within the requirements specification are explained and an approach for modelling the train control system formally using timed petrinets is introduced. (orig.) [German] Erhoehte Anforderungen an Leistungsfaehigkeit und Sicherheit zukuenftiger Eisenbahnsicherungssysteme profitieren vom Einsatz formaler Techniken zur effizienten Systementwicklung in diesem Bereich. Dieser Beitrag betrachtet die Aufgabe, formale Techniken bereits in der Entwicklungsphase der Anforderungsspezifikation anzuwenden, mit dem Ziel, fruehzeitig die Korrektheit der Anforderungen ueberpruefen zu koennen und die Sicherheitsforderungen des Systems auf Anforderungen an einzelne Komponenten zu uebertragen. Es wird erlaeutert, welche Aspekte des Eisenbahnsicherungssystems dazu bereits in der Anforderungsspezifikation betrachtet werden muessen und wie diese unter Verwendung von zeitbewerteten Petrinetzen in einem formalen Modell des Systems abgebildet werden koennen. (orig.)

  2. The History of Education and its Social Relevance: Approaches and Systemic Perspectives

    Directory of Open Access Journals (Sweden)

    Serge Tomamichel

    2015-12-01

    Full Text Available The history of education, together with related historiographical output, reveals an ambiguous picture, especially in France. Although the infatuation for commemorations and other memorial duties cannot be denied, doubt is cast upon its very presence and identity in scientific research and university education in the face of a new, growing demand for social relevance. The issue raised here is not so much an argument against its evolution within a group social movement that the historian has but little grasp upon, but rather the search for new forms of «making the history of education» in the face of these new demands. Viewed under the lens of a «model of analysis of historiographical activity», the issue posed on the plane of History in general will be to find historiographical configurations able to integrate a certain type of social relevance without, however, betraying the roots of historical research. Such so-called «translatable», historiographical output, are interlinked with and dependent upon the existence of a «historiographical habitus» that must be contributed to and reinforced by education practitioners, as well as a kind of «decisional memory-making» function. However this dual role is subordinate to certain philosophical and epistemological conditions, namely: to accept the existence of anthropological invariables; to conceive the history of society as a complex web woven from the various interdependent strands of societal features; to define the history of education as a historical anthropology of education; and to favour modelling (an example is provided as a means of restoring the historical reality. How to reference this article Tomamichel, S. (2016. L’histoire de l’éducation confrontée à son utilité sociale: approches et perspectives systémiques. Espacio, Tiempo y Educación, 3(1, 149-176. doi: http://dx.doi.org/10.14516/ete.2016.003.001.9

  3. Genetic traits of relevance to sustainability of smallholder sheep farming systems in South Africa

    NARCIS (Netherlands)

    Molotsi, Annelin; Dube, Bekezela; Oosting, Simon; Marandure, Tawanda; Mapiye, Cletos; Cloete, Schalk; Dzama, Kennedy

    2017-01-01

    Sustainable livestock production is important to ensure continuous availability of resources for future generations. Most smallholder livestock farming systems in developing countries have been perceived to be environmentally, socially and economically unsustainable. Farming with livestock that is

  4. Cutting the gordian knot-development and biological relevance of hepatitis C virus cell culture systems.

    Science.gov (United States)

    Gottwein, Judith M; Bukh, Jens

    2008-01-01

    Worldwide approximately 180 million people are chronically infected with hepatitis C virus (HCV). HCV isolates exhibit extensive genetic heterogeneity and have been grouped in six genotypes and various subtypes. Additionally, several naturally occurring intergenotypic recombinants have been described. Research on the viral life cycle, efficient therapeutics, and a vaccine has been hampered by the absence of suitable cell culture systems. The first system permitting studies of the full viral life cycle was intrahepatic transfection of RNA transcripts of HCV consensus complementary DNA (cDNA) clones into chimpanzees. However, such full-length clones were not infectious in vitro. The development of the replicon system and HCV pseudo-particles allowed in vitro studies of certain aspects of the viral life cycle, RNA replication, and viral entry, respectively. Identification of the genotype 2 isolate JFH1, which for unknown reasons showed an exceptional replication capability and resulted in formation of infectious viral particles in the human hepatoma cell line Huh7, led in 2005 to the development of the first full viral life cycle in vitro systems. JFH1-based systems now enable in vitro studies of the function of viral proteins, their interaction with each other and host proteins, new antivirals, and neutralizing antibodies in the context of the full viral life cycle. However, several challenges remain, including development of cell culture systems for all major HCV genotypes and identification of other susceptible cell lines.

  5. Infectious Disease Surveillance in the Big Data Era: Towards Faster and Locally Relevant Systems.

    Science.gov (United States)

    Simonsen, Lone; Gog, Julia R; Olson, Don; Viboud, Cécile

    2016-12-01

    While big data have proven immensely useful in fields such as marketing and earth sciences, public health is still relying on more traditional surveillance systems and awaiting the fruits of a big data revolution. A new generation of big data surveillance systems is needed to achieve rapid, flexible, and local tracking of infectious diseases, especially for emerging pathogens. In this opinion piece, we reflect on the long and distinguished history of disease surveillance and discuss recent developments related to use of big data. We start with a brief review of traditional systems relying on clinical and laboratory reports. We then examine how large-volume medical claims data can, with great spatiotemporal resolution, help elucidate local disease patterns. Finally, we review efforts to develop surveillance systems based on digital and social data streams, including the recent rise and fall of Google Flu Trends. We conclude by advocating for increased use of hybrid systems combining information from traditional surveillance and big data sources, which seems the most promising option moving forward. Throughout the article, we use influenza as an exemplar of an emerging and reemerging infection which has traditionally been considered a model system for surveillance and modeling. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Gómez-Canela, Cristian; Tornero-Cañadas, Daniel; Prats, Eva; Piña, Benjamí; Tauler, Romà; Raldúa, Demetrio

    2018-02-01

    There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model.

  7. Materials degradation in fission reactors: Lessons learned of relevance to fusion reactor systems

    Science.gov (United States)

    Was, Gary S.

    2007-08-01

    The management of materials in power reactor systems has become a critically important activity in assuring the safe, reliable and economical operation of these facilities. Over the years, the commercial nuclear power reactor industry has faced numerous 'surprises' and unexpected occurrences in materials. Mitigation strategies have sometimes solved one problem at the expense of creating another. Other problems have been solved successfully and have motivated the development of techniques to foresee problems before they occur. This paper focuses on three aspects of fission reactor experience that may benefit future fusion systems. The first is identification of parameters and processes that have had a large impact on the behavior of materials in fission systems such as temperature, dose rate, surface condition, gradients, metallurgical variability and effects of the environment. The second is the development of materials performance and failure models to provide a basis for assuring component integrity. Last is the development of proactive materials management programs that identify and pre-empt degradation processes before they can become problems. These aspects of LWR experience along with the growing experience with materials in the more demanding advanced fission reactor systems form the basis for a set of 'lessons learned' to aid in the successful management of materials in fusion reactor systems.

  8. Neural representation of calling songs and their behavioral relevance in the grasshopper auditory system

    Directory of Open Access Journals (Sweden)

    Gundula eMeckenhäuser

    2014-12-01

    Full Text Available Acoustic communication plays a key role for mate attraction in grasshoppers. Males use songs to advertise themselves to females. Females evaluate the song pattern, a repetitive structure of sound syllables separated by short pauses, to recognize a conspecific male and as proxy to its fitness. In their natural habitat females often receive songs with degraded temporal structure. Perturbations may, for example, result from the overlap with other songs. We studied the response behavior of females to songs that show different signal degradations. A perturbation of an otherwise attractive song at later positions in the syllable diminished the behavioral response, whereas the same perturbation at the onset of a syllable did not affect song attractiveness. We applied naïve Bayes classifiers to the spike trains of identified neurons in the auditory pathway to explore how sensory evidence about the acoustic stimulus and its attractiveness is represented in the neuronal responses. We find that populations of three or more neurons were sufficient to reliably decode the acoustic stimulus and to predict its behavioral relevance from the single-trial integrated firing rate. A simple model of decision making simulates the female response behavior. It computes for each syllable the likelihood for the presence of an attractive song pattern as evidenced by the population firing rate. Integration across syllables allows the likelihood to reach a decision threshold and to elicit the behavioral response. The close match between model performance and animal behavior shows that a spike rate code is sufficient to enable song pattern recognition.

  9. Modeling systems relevant to the biodiesel production using the CPA equation of state

    DEFF Research Database (Denmark)

    Tsivintzelis, Ioannis; Ali, Shahid; Kontogeorgis, Georgios

    2016-01-01

    show smooth trends with carbon chain length, permitting extrapolation for systems for which data are not available. Finally, the estimated parameters and correlations were used for the prediction of liquid-liquid equilibrium of one ternary and one multicomponent mixture. The results showed...... estimated by adjusting model predictions to recent DIPPR correlations and carefully selected literature data. Then, the performance of CPA was evaluated in correlating the vapor – liquid and liquid – liquid equilibrium of binary systems containing fatty acids and their esters, glycerides, water, alcohols...... and/or glycerol. Satisfactory correlation results were obtained using one (water-acids, alcohols/water - glycerol) or two (systems containing fatty acid esters with water, alcohols or glycerol and mixtures containing glycerides and alcohols) interaction parameters. Moreover, the interaction parameters...

  10. The innate immune system and diabetes mellitus: the relevance of periodontitis? A hypothesis.

    Science.gov (United States)

    Lazenby, Martin G; Crook, Martin A

    2010-08-05

    About a decade ago, a hypothesis was proposed suggesting that the innate immune system, including acute-phase reactants, contribute to the development of T2DM [Type 2 DM (diabetes mellitus)] and the metabolic syndrome. In this model, it was hypothesized that the innate immune system modulates the effects of many factors, including genes, fetal programming, nutrition and aging, upon the later development of metabolic problems associated with insulin resistance. In this present article, we expand this hypothesis by looking at the involvement of periodontitis in DM and its complications. Periodontitis is a common inflammatory process involving the innate immune system and is associated with DM. We will also illustrate how dental disease is important in patients with DM and could be implicated in various diabetic complications.

  11. Hominid evolution of the arteriovenous system through the cranial base and its relevance for craniosynostosis.

    Science.gov (United States)

    Kunz, Alexandra R; Iliadis, Charalampos

    2007-12-01

    This paper discusses how the evolving hominid architecture of the arteriovenous system through the cranial base diverted foreseeable pathology in the human brain. Bipedal upright posture was an early adaptation in mosaic morphological pattern changes in hominid evolution; a key feature, the ability of blood to flow either to vertebral or internal jugular venous systems. Encephalization punctuated hominid evolution, its vulnerable feature, a lower threshold for thermal damage. Comparative analysis of ape and human skulls show "fingerprint" structures, revealing big changes in pattern complexity of the cranial vascular tree. Clues to structural/functional changes span data for apes, humans, and hominid fossils. Here, the increasing vascular network, Australopithecus to Homo sapiens, necessitated changes in the blood flow patterns. The transverse-sigmoid (T/S) and occipital-marginal (O/M) venous networks accommodated hydrostatic changes of blood flow, regulating temperature uniquely: the O/M system enlarged, allowing blood to flow straight down into the vertebral plexus without cooling, and added a vast network of emissary/diploic veins, acting as a brain cooling "radiator." This O/M system was fixed in the Australopithecus robustus lineage, p = 0.000001; high frequencies of emissary foramen were selected for over time. Ontologically, the human neonatal O/M system is fully developed; emissary/diploic veins are established by age 5, setting conditions for selective brain cooling. The Radiator Theory is the evolution of the functionally efficient brain cooling system, fixed in the A. robustus lineage, tying hydrostatic consequences of bipedalism with release of a "thermal constraint" on the encephalizing brain, and reflected in our own ontogeny.

  12. Socio-technical systems and interaction design - 21st century relevance.

    Science.gov (United States)

    Maguire, Martin

    2014-03-01

    This paper focuses on the relationship between the socio-technical system and the user-technology interface. It looks at specific aspects of the organisational context such as multiple user roles, job change, work processes and workflows, technical infrastructure, and the challenges they present for the interaction designer. The implications of trends such as more mobile and flexible working, the use of social media, and the growth of the virtual organisation, are also considered. The paper also reviews rapidly evolving technologies such as pervasive systems and artificial intelligence, and the skills that workers will need to engage with them. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  13. Identification of relevant indicators to use in a management system of turistic information for the department of Casanare

    Directory of Open Access Journals (Sweden)

    Otty Sarmiento Barrios

    2017-07-01

    Full Text Available In the Department of Casanare, Colombia (Casanare State, tourism has not been seen as an influential and important activity for its Regional Economic Development, therefore, there are no strategic guidelines to allow planning a competitive tourist system in the region. In this sense, this paper intends to present a diagnosis and analysis of the information found within the different participants of the tourism sector. The main objective is to determine the relevant indicators for the evaluation and monitoring of tourism tendencies in this Department, taking as reference the indicator systems presented in most representative information systems at a national and international level. As a conclusion, these results will be used as the basis needed to build a tourist information system for the Department of Casanare.

  14. Pilot Study: Polygraph Decision Support System Using Event Resolution Imaging for the Relevant/Irrelevant Format

    Science.gov (United States)

    2003-02-19

    several potential computer applications were considered ( Kubis , 1962; Yankee, 1968; Burch, 1969). In the second phase, researchers used various...1992). Neural Networks and Fuzzy Systems, New Jersey: Prentice-Hall. Kubis , J. F. (1962). Studies in Lie Detection, Fordham University, New York, NY

  15. Policy-Relevant Systematic Reviews to Strengthen Health Systems: Models and Mechanisms to Support Their Production

    Science.gov (United States)

    Oliver, Sandra; Dickson, Kelly

    2016-01-01

    Support for producing systematic reviews about health systems is less well developed than for those about clinical practice. From interviewing policy makers and systematic reviewers we identified institutional mechanisms which bring systematic reviews and policy priorities closer by harnessing organisational and individual motivations, emphasising…

  16. Membrane transporters and drug development: relevance to pharmacogenomics, nutrigenomics, epigenetics, and systems biology.

    Science.gov (United States)

    Yan, Qing

    2010-01-01

    The study of membrane transporters may result in breakthroughs in the discovery of new drugs and the development of safer drugs. Membrane transporters are essential for fundamental cellular functions and normal physiological processes. These molecules influence drug absorption and distribution and play key roles in drug therapeutic effects. A primary goal of current research in drug discovery and development is to fully understand the interactions between transporters and drugs at both the system levels in the human body and the individual level for personalized therapy. Systematic studies of membrane transporters will help in not only better understanding of diseases from the systems biology point of view but also better drug design and development. The exploration of both pharmacogenomics and systems biology in transporters is necessary to connect individuals' genetic profiles with systematic drug responses in the human body. Understanding of gene-diet interactions and the effects of epigenetic changes on transporter gene expression may help improve clinical drug efficacy. The integration of pharmacogenomics, nutrigenomics, epigenetics, and systems biology may enable us to move from disease treatment to disease prevention and optimal health. The key issues in such integrative understanding include the correlations between structure and function, genotype and phenotype, and systematic interactions among transporters, other proteins, nutrients, drugs, and the environment. The exploration in these key issues may ultimately contribute to personalized medicine with high efficacy but less toxicity.

  17. Nature and hydrological relevance of the Shalbatana complex underground cavernous system

    Science.gov (United States)

    Rodriguez, Jose Alexis Palmero; Sasaki, Sho; Miyamoto, Hideaki

    2003-03-01

    The geomorphology of the North East trending long fractured depression between the Ganges Chasma and the Shalbatana Vallis headwater source region is examined and interpreted to be the result of collapse of part of an extensive underground cavernous system. We propose that this cavernous system undermines at least a valley, which extends from the vicinities of the Ganges Chasma and terminates in the Shalbatana Vallis headwater source region and the Aromatum Chaos. We believe that the origin of this cavernous system was related to the formation and interconnection of discrete cavernous bodies and propose a hypothesis, which involves the interaction of permafrost and intrusive magmatism to explain their formation. The Shalbatana Vallis headwater source is interpreted as produced by a Noachian impact crater and surface collapse over part of the underground cavernous system. Finally, we propose that the water sources, which were involved in the excavation of the Shalbatana and Ravis outflow channels might have included water segregated from the permafrost through interaction of intrusive magmatism and permafrost, water drained from a paleolake in the Ganges Chasma and water released from the catastrophic evacuation of confined aquifers.

  18. INDUSTRIAL CONTROL SYSTEM CYBER SECURITY: QUESTIONS AND ANSWERS RELEVANT TO NUCLEAR FACILITIES, SAFEGUARDS AND SECURITY

    Energy Technology Data Exchange (ETDEWEB)

    Robert S. Anderson; Mark Schanfein; Trond Bjornard; Paul Moskowitz

    2011-07-01

    Typical questions surrounding industrial control system (ICS) cyber security always lead back to: What could a cyber attack do to my system(s) and; how much should I worry about it? These two leading questions represent only a fraction of questions asked when discussing cyber security as it applies to any program, company, business, or organization. The intent of this paper is to open a dialog of important pertinent questions and answers that managers of nuclear facilities engaged in nuclear facility security and safeguards should examine, i.e., what questions should be asked; and how do the answers affect an organization's ability to effectively safeguard and secure nuclear material. When a cyber intrusion is reported, what does that mean? Can an intrusion be detected or go un-noticed? Are nuclear security or safeguards systems potentially vulnerable? What about the digital systems employed in process monitoring, and international safeguards? Organizations expend considerable efforts to ensure that their facilities can maintain continuity of operations against physical threats. However, cyber threats particularly on ICSs may not be well known or understood, and often do not receive adequate attention. With the disclosure of the Stuxnet virus that has recently attacked nuclear infrastructure, many organizations have recognized the need for an urgent interest in cyber attacks and defenses against them. Several questions arise including discussions about the insider threat, adequate cyber protections, program readiness, encryption, and many more. These questions, among others, are discussed so as to raise the awareness and shed light on ways to protect nuclear facilities and materials against such attacks.

  19. The global stock of research evidence relevant to health systems policymaking.

    Science.gov (United States)

    Wilson, Michael G; Moat, Kaelan A; Lavis, John N

    2013-09-04

    Policymakers and stakeholders need immediate access to many types of research evidence to make informed decisions about the full range of questions that may arise regarding health systems. We examined all types of research evidence about governance, financial and delivery arrangements, and implementation strategies within health systems contained in Health Systems Evidence (HSE) (http://www.healthsystemsevidence.org). The research evidence types include evidence briefs for policy, overviews of systematic reviews, systematic reviews of effects, systematic reviews addressing other questions, systematic reviews in progress, systematic reviews being planned, economic evaluations, and health reform and health system descriptions. Specifically, we describe their distribution across health system topics and domains, trends in their production over time, availability of supplemental content in various languages, and the extent to which they focus on low- and middle-income countries (LMICs), as well as (for systematic reviews) their methodological quality and the availability of user-friendly summaries. As of July 2013, HSE contained 2,629 systematic reviews of effects (of which 501 are Cochrane reviews), 614 systematic reviews addressing other questions, 283 systematic reviews in progress, 186 systematic reviews being planned, 140 review-derived products (evidence briefs and overviews of systematic reviews), 1,669 economic evaluations, 1,092 health reform descriptions, and 209 health system descriptions. Most systematic reviews address topics related to delivery arrangements (n = 2,663) or implementation strategies (n = 1,653) with far fewer addressing financial (n = 241) or governance arrangements (n = 231). In addition, 2,928 systematic reviews have been quality appraised with moderate AMSTAR ratings found for reviews addressing governance (5.6/11), financial (5.9/11), and delivery (6.3/11) arrangements and implementation strategies (6.5/11); 1,075 systematic reviews

  20. Creating European guidelines for Chiropractic Incident Reporting and Learning Systems (CIRLS: relevance and structure

    Directory of Open Access Journals (Sweden)

    Wangler Martin

    2011-04-01

    Full Text Available Abstract Background In 2009, the heads of the Executive Council of the European Chiropractors' Union (ECU and the European Academy of Chiropractic (EAC involved in the European Committee for Standardization (CEN process for the chiropractic profession, set out to establish European guidelines for the reporting of adverse reactions to chiropractic treatment. There were a number of reasons for this: first, to improve the overall quality of patient care by aiming to reduce the application of potentially harmful interventions and to facilitate the treatment of patients within the context of achieving maximum benefit with a minimum risk of harm; second, to inform the training objectives for the Graduate Education and Continuing Professional Development programmes of all 19 ECU member nations, regarding knowledge and skills to be acquired for maximising patient safety; and third, to develop a guideline on patient safety incident reporting as it is likely to be part of future CEN standards for ECU member nations. Objective To introduce patient safety incident reporting within the context of chiropractic practice in Europe and to help individual countries and their national professional associations to develop or improve reporting and learning systems. Discussion Providing health care of any kind, including the provision of chiropractic treatment, can be a complex and, at times, a risky activity. Safety in healthcare cannot be guaranteed, it can only be improved. One of the most important aspects of any learning and reporting system lies in the appropriate use of the data and information it gathers. Reporting should not just be seen as a vehicle for obtaining information on patient safety issues, but also be utilised as a tool to facilitate learning, advance quality improvement and to ultimately minimise the rate of the occurrence of errors linked to patient care. Conclusions Before a reporting and learning system can be established it has to be clear

  1. Cost-Efficient Methods and Processes for Safety Relevant Embedded Systems (CESAR) - An Objective Overview

    Science.gov (United States)

    Jolliffe, Graham

    For developing embedded safety critical systems, industrial companies have to face increasing complexity and variety coupled with increasing regulatory constraints, while costs, performances and time to market are constantly challenged. This has led to a profusion of enablers (new processes, methods and tools), which are neither integrated nor interoperable because they have been developed more or less independently (addressing only a part of the complexity: e.g. Safety) in the absence of internationally recognized open standards. CESAR has been established under ARTEMIS, the European Union's Joint Technology Initiative for research in embedded systems, with the aim to improve this situation and this pa-per will explain what CESAR's objectives are, how they are expected to be achieved and, in particular, how current best practice can ensure that safety engineering requirements can be met.

  2. RELEVANT FACTORS TO INCREASE THE ACCURACY, FEASIBILITY AND SUCCESS OF JOB PERFORMANCE EVALUATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    Dolores Díaz Cabrera

    2014-05-01

    Full Text Available The situation of economic crisis in Spain has motivated an increasing interest in employee performance evaluation in organizations. On the other hand, it is also producing greater resistance to this evaluation on the part of appraisees, who regard these processes with suspicion and concern in these times of economic difficulties. Therefore, in economic situations like the current one, it is very important to develop assessment scales that facilitate the effectiveness, credibility and success of these systems. The general goal of this work is to provide results that can help evaluation systems to be viewed positively by organizations as well as by their members. For this it is necessary that: (a the response scales used offer precise and reliable data; and (b the procedures applied to assess performance are perceived as fair and reliable by the participants.

  3. The relevance of cartographic scale in interactive and multimedia cartographic information systems

    Directory of Open Access Journals (Sweden)

    Mirjanka Lechthaler

    2004-09-01

    Full Text Available The application of new technologies in the processes of gathering, analysing, transforming, visualizing and communicating of space data and geoinformation offers a great challenge for cartography. Cartographic information provision as described in several cartographic models, which is included in cartographic information systems depend on the graphical presentation/visualization at certain scales. That necessitates a need to define the capacity or content borders (geometry and semantic for cognition and communication. However, currently we need and use maps as a vehicle for transportation of spatial and temporal information. Graphic constructions of geoanalogies, linked with interaction, multimedia sequences and animations, support effective geocommunication, bridging the gaps imposed by having to work at pre-defined scales. This paper illustrates two interactive information systems, which were conceptualised and prototyped at the Institute of Cartography and Geomedia Technique, Vienna University of Technology.

  4. Relevance of ferromagnetic correlations for the electron spin resonance in Kondo lattice systems.

    Science.gov (United States)

    Krellner, C; Förster, T; Jeevan, H; Geibel, C; Sichelschmidt, J

    2008-02-15

    Electron spin resonance (ESR) measurements of the ferromagnetic (FM) Kondo lattice system CeRuPO show a well defined ESR signal which is related to the Ce3+ magnetism. In contrast, no ESR could be observed in the antiferromagnetic (AFM) homologue CeOsPO. Additionally, we detect an ESR signal in ferromagnetic YbRh while it was absent in a number of Ce or Yb intermetallic compounds with dominant AFM exchange. Thus, the observation of an ESR signal in a Kondo lattice is neither specific to Yb nor to the proximity to a quantum critical point, but seems to be connected to the presence of FM fluctuations. These conclusions not only provide a basic concept to understand the ESR in Kondo lattice systems even well below the Kondo temperature (as observed in YbRh2Si2) but point out ESR as a prime method to investigate directly the spin dynamics of the Kondo ion.

  5. Dentists' knowledge and opinions of oral-systemic disease relationships: relevance to patient care and education.

    Science.gov (United States)

    Paquette, David W; Bell, Kathryn P; Phillips, Ceib; Offenbacher, Steven; Wilder, Rebecca S

    2015-06-01

    Population studies consistently support associations between poor oral (periodontal) health and systemic diseases such as cardiovascular disease (CVD) and diabetes. The aim of this study was to assess the knowledge of dentists and document their opinions regarding the evidence on oral-systemic disease relationships. A survey consisting of 39 items was developed and mailed to 1,350 licensed dentists in North Carolina. After three mailings, 667 dentists (49%) meeting inclusion criteria responded. The respondents were predominantly male (76.3%), in solo practice (59.5%), and in non-rural settings (74%). More than 75% of these dentists correctly identified risk factors like diet, genetics, smoking, obesity, and physical inactivity for CVD and diabetes. The majority rated the evidence linking periodontal disease with CVD and diabetes as strong (71% and 67%, respectively). These dentists were most comfortable inquiring about patients' tobacco habits (93%), treating patients with diabetes (89%) or CVD (84%) and concurrent periodontal disease, and discussing diabetes-periodontal disease risks with patients (88%). Fewer respondents were comfortable asking patients about alcohol consumption (54%) or providing alcohol counseling (49%). Most agreed that dentists should be trained to identify risk factors (96%) or actively manage systemically diseased patients (74%). Over 90% agreed that medical and dental professionals should be taught to practice more collaboratively. These data indicate that these dentists were knowledgeable about oral-systemic health associations, had mixed comfort levels translating the evidence into clinical practice, but expressed support for interprofessional education to improve their readiness to actively participate in their patients' overall health management.

  6. Assessment of a combined gas chromatography mass spectrometer sensor system for detecting biologically relevant volatile compounds.

    Science.gov (United States)

    Gould, Oliver; Wieczorek, Tom; de Lacy Costello, Ben; Persad, Raj; Ratcliffe, Norman

    2017-12-06

    There have been a number of studies in which metal oxide sensors (MOS) have replaced conventional analytical detectors in gas chromatography systems. However, despite the use of these instruments in a range of applications including breath research the sensor responses (i.e. resistance changes w.r.t. concentration of VCs) remain largely unreported. This paper addresses that issue by comparing the response of a metal oxide sensor directly with a mass spectrometer (MS), whereby both detectors are interfaced to the same GC column using an s-swafer. It was demonstrated that the sensitivity of an in-house fabricated ZnO/SnO 2 thick film MOS was superior to a modern MS for the detection of a wide range of volatile compounds (VCs) of different functionalities and masses. Better techniques for detection and quantification of these VCs is valuable, as many of these compounds are commonly reported throughout the scientific literature. This is also the first published report of a combined GC-MS sensor system. These two different detector technologies when combined, should enhance discriminatory abilities to aid disease diagnoses using volatiles from e.g. breath, and bodily fluids. Twenty-nine chemical standards have been tested using solid phase micro-extraction; 25 of these compounds are found on human breath. In all but two instances the sensor exhibited the same or superior limit of detection compared to the MS. Twelve stool samples from healthy participants were analysed; the sensor detected, on average 1.6 peaks more per sample than the MS. Similarly, analysing the headspace of E. coli broth cultures the sensor detected 6.9 more peaks per sample versus the MS. This greater sensitivity is primarily a function of the superior limits of detection of the metal oxide sensor. This shows that systems based on the combination of chromatography systems with solid state sensors shows promise for a range of applications.

  7. The human sympathetic nervous system: its relevance in hypertension and heart failure.

    Science.gov (United States)

    Parati, Gianfranco; Esler, Murray

    2012-05-01

    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  8. Is progression of periodontitis relevantly influenced by systemic antibiotics? A clinical randomized trial.

    Science.gov (United States)

    Harks, Inga; Koch, Raphael; Eickholz, Peter; Hoffmann, Thomas; Kim, Ti-Sun; Kocher, Thomas; Meyle, Joerg; Kaner, Doğan; Schlagenhauf, Ulrich; Doering, Stephan; Holtfreter, Birte; Gravemeier, Martina; Harmsen, Dag; Ehmke, Benjamin

    2015-09-01

    We investigated the long-term impact of adjunctive systemic antibiotics on periodontal disease progression. Periodontal therapy is frequently supplemented by systemic antibiotics, although its impact on the course of disease is still unclear. This prospective, randomized, double-blind, placebo-controlled multi-centre trial comprising patients suffering from moderate to severe periodontitis evaluated the impact of rational adjunctive use of systemic amoxicillin 500 mg plus metronidazole 400 mg (3x/day, 7 days) on attachment loss. The primary outcome was the percentage of sites showing further attachment loss (PSAL) ≥1.3 mm after the 27.5 months observation period. Standardized therapy comprised mechanical debridement in conjunction with antibiotics or placebo administration, and maintenance therapy at 3 months intervals. From 506 participating patients, 406 were included in the intention to treat analysis. Median PSAL observed in placebo group was 7.8% compared to 5.3% in antibiotics group (Q25 4.7%/Q75 14.1%; Q25 3.1%/Q75 9.9%; p antibiotics showed a small absolute, although statistically significant, additional reduction in further attachment loss. Therapists should consider the patient's overall risk for periodontal disease when deciding for or against adjunctive antibiotics prescription. © 2015 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

  9. Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy.

    Science.gov (United States)

    Duarte, João M N; Do, Kim Q; Gruetter, Rolf

    2014-07-01

    Alterations to brain homeostasis during development are reflected in the neurochemical profile determined noninvasively by (1)H magnetic resonance spectroscopy. We determined longitudinal biochemical modifications in the cortex, hippocampus, and striatum of C57BL/6 mice aged between 3 and 24 months . The regional neurochemical profile evolution indicated that aging induces general modifications of neurotransmission processes (reduced GABA and glutamate), primary energy metabolism (altered glucose, alanine, and lactate) and turnover of lipid membranes (modification of choline-containing compounds and phosphorylethanolamine), which are all probably involved in the frequently observed age-related cognitive decline. Interestingly, the neurochemical profile was different in male and female mice, particularly in the levels of taurine that may be under the control of estrogen receptors. These neurochemical profiles constitute the basal concentrations in cortex, hippocampus, and striatum of healthy aging male and female mice. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The Carnitine Palmitoyl Transferase (CPT) System and Possible Relevance for Neuropsychiatric and Neurological Conditions.

    Science.gov (United States)

    Virmani, Ashraf; Pinto, Luigi; Bauermann, Otto; Zerelli, Saf; Diedenhofen, Andreas; Binienda, Zbigniew K; Ali, Syed F; van der Leij, Feike R

    2015-10-01

    The carnitine palmitoyl transferase (CPT) system is a multiprotein complex with catalytic activity localized within a core represented by CPT1 and CPT2 in the outer and inner membrane of the mitochondria, respectively. Two proteins, the acyl-CoA synthase and a translocase also form part of this system. This system is crucial for the mitochondrial beta-oxidation of long-chain fatty acids. CPT1 has two well-known isoforms, CPT1a and CPT1b. CPT1a is the hepatic isoform and CPT1b is typically muscular; both are normally utilized by the organism for metabolic processes throughout the body. There is a strong evidence for their involvement in various disease states, e.g., metabolic syndrome, cardiovascular diseases, and in diabetes mellitus type 2. Recently, a new, third isoform of CPT was described, CPT1c. This is a neuronal isoform and is prevalently localized in brain regions such as hypothalamus, amygdala, and hippocampus. These brain regions play an important role in control of food intake and neuropsychiatric and neurological diseases. CPT activity has been implicated in several neurological and social diseases mainly related to the alteration of insulin equilibrium in the brain. These pathologies include Parkinson's disease, Alzheimer's disease, and schizophrenia. Evolution of both Parkinson's disease and Alzheimer's disease is in some way linked to brain insulin and related metabolic dysfunctions with putative links also with the diabetes type 2. Studies show that in the CNS, CPT1c affects ceramide levels, endocannabionoids, and oxidative processes and may play an important role in various brain functions such as learning.

  11. Topological phase transition of a fractal spin system: The relevance of the network complexity

    Directory of Open Access Journals (Sweden)

    Felipe Torres

    2016-05-01

    Full Text Available A new type of collective excitations, due to the topology of a complex random network that can be characterized by a fractal dimension DF, is investigated. We show analytically that these excitations generate phase transitions due to the non-periodic topology of the DF > 1 complex network. An Ising system, with long range interactions, is studied in detail to support the claim. The analytic treatment is possible because the evaluation of the partition function can be decomposed into closed factor loops, in spite of the architectural complexity. The removal of the infrared divergences leads to an unconventional phase transition, with spin correlations that are robust against thermal fluctuations.

  12. Anti-Ballistic Missile Treaty: Is it Still Relevant? A Primer on the Systems and Issues

    Science.gov (United States)

    1999-04-01

    online: http://www.armscontrol.org/ACT/sep97/focsept.htm]. Lewis, George N. and Postol , Theodore A., �Future challenges to Ballistic Missile Defense...systems ( THAAD and Navy Theater-Wide) are capable of defending large areas from missiles with ranges up to 3,500 km. Lewis and Yingbo note that the...6. 13 The Army�s Patriot Advanced Capability-3 (PAC-3); the Theater High-Altitude Area Defense ( THAAD ); the Navy Area Defense; and the Navy Theater

  13. A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept

    NARCIS (Netherlands)

    Janssen, F.W.; Oostra, Jaap; van Oorschot, Arie; van Blitterswijk, Clemens

    2006-01-01

    In an effort to produce clinically relevant volumes of tissue-engineered bone products, we report a direct perfusion bioreactor system. Goat bone marrow stromal cells (GBMSCs) were dynamically seeded and proliferated in this system in relevant volumes (10 cc) of small sized macroporous biphasic

  14. Interactive content-based image retrieval (CBIR) computer-aided diagnosis (CADx) system for ultrasound breast masses using relevance feedback

    Science.gov (United States)

    Cho, Hyun-chong; Hadjiiski, Lubomir; Sahiner, Berkman; Chan, Heang-Ping; Paramagul, Chintana; Helvie, Mark; Nees, Alexis V.

    2012-03-01

    We designed a Content-Based Image Retrieval (CBIR) Computer-Aided Diagnosis (CADx) system to assist radiologists in characterizing masses on ultrasound images. The CADx system retrieves masses that are similar to a query mass from a reference library based on computer-extracted features that describe texture, width-to-height ratio, and posterior shadowing of a mass. Retrieval is performed with k nearest neighbor (k-NN) method using Euclidean distance similarity measure and Rocchio relevance feedback algorithm (RRF). In this study, we evaluated the similarity between the query and the retrieved masses with relevance feedback using our interactive CBIR CADx system. The similarity assessment and feedback were provided by experienced radiologists' visual judgment. For training the RRF parameters, similarities of 1891 image pairs obtained from 62 masses were rated by 3 MQSA radiologists using a 9-point scale (9=most similar). A leave-one-out method was used in training. For each query mass, 5 most similar masses were retrieved from the reference library using radiologists' similarity ratings, which were then used by RRF to retrieve another 5 masses for the same query. The best RRF parameters were chosen based on three simulated observer experiments, each of which used one of the radiologists' ratings for retrieval and relevance feedback. For testing, 100 independent query masses on 100 images and 121 reference masses on 230 images were collected. Three radiologists rated the similarity between the query and the computer-retrieved masses. Average similarity ratings without and with RRF were 5.39 and 5.64 on the training set and 5.78 and 6.02 on the test set, respectively. The average Az values without and with RRF were 0.86+/-0.03 and 0.87+/-0.03 on the training set and 0.91+/-0.03 and 0.90+/-0.03 on the test set, respectively. This study demonstrated that RRF improved the similarity of the retrieved masses.

  15. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia A. Thorp

    2015-01-01

    Full Text Available Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS. Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.

  16. Individual differences in the locus coeruleus-norepinephrine system: Relevance to stress-induced cardiovascular vulnerability.

    Science.gov (United States)

    Wood, Christopher S; Valentino, Rita J; Wood, Susan K

    2017-04-01

    Repeated exposure to psychosocial stress is a robust sympathomimetic stressor and as such has adverse effects on cardiovascular health. While the neurocircuitry involved remains unclear, the physiological and anatomical characteristics of the locus coeruleus (LC)-norepinephrine (NE) system suggest that it is poised to contribute to stress-induced cardiovascular vulnerability. A major theme throughout is to review studies that shed light on the role that the LC may play in individual differences in vulnerability to social stress-induced cardiovascular dysfunction. Recent findings are discussed that support a unique plasticity in afferent regulation of the LC, resulting in either excitatory or inhibitory input to the LC during establishment of different stress coping strategies. This contrasting regulation of the LC by either afferent regulation, or distinct differences in stress-induced neuroinflammation would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The goal of this review is to highlight recent developments in the interplay between the LC-NE and cardiovascular systems during repeated stress in an effort to advance therapeutic treatments for the development of stress-induced cardiovascular vulnerability. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A dispersed alarm system for the elderly and its relevance to local general practitioners

    Science.gov (United States)

    McWhirter, Malcolm

    1987-01-01

    This paper describes the use of a dispersed alarm system for the elderly in the Central region of Scotland. Information from referral forms, questionnaires completed by wardens after a call and client registers were used to investigate the population served, sources of referral and the way the service was used. All the general practitioners working in the area covered by the service were sent a questionnaire asking for their views of the service. In May 1984 the alarm system covered 861 clients in private housing and 1259 in sheltered housing. Over 50% of referrals were from the health services and the most common reasons for referral were poor mobility and falls. False alarms accounted for 40% of calls and they were more likely to be from clients in sheltered housing than in private housing. Of genuine calls 71% were due to illness or disability with 25% due to falls. All of the general practitioners responding to the questionnaire were aware of a patient in their practice covered by the service and considered that the service provided useful 24-hour support for the elderly at risk because of frailty and disability PMID:3448211

  18. Immune surveillance of the central nervous system in multiple sclerosis– Relevance for therapy and experimental models

    Science.gov (United States)

    Hussain, Rehana Z.; Hayardeny, Liat; Cravens, Petra C.; Yarovinsky, Felix; Eagar, Todd N.; Arellano, Benjamine; Deason, Krystin; Castro-Rojas, Cyd; Stüve, Olaf

    2015-01-01

    Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS. However, many of the agents that are currently approved or in clinical development also have severe potential adverse effects that stem from the very mechanisms that mediate their beneficial effects by interfering with CNS immune surveillance. This review will outline the main cellular components of the innate and adaptive immune system that participate in host defense and maintain immune surveillance of the CNS. Their pathogenic role in MS and its animal model experimental autoimmune encephalomyelitis (EAE) is also discussed. Furthermore, an experimental model is introduced that may assist in evaluating the effect of therapeutic interventions on leukocyte homeostasis and function within the CNS. This model or similar models may become a useful tool in the repertoire of pre-clinical tests of pharmacological agents to better explore their potential for adverse events. PMID:25282087

  19. Enhanced chlorine dioxide decay in the presence of metal oxides: Relevance to drinking water distribution systems

    KAUST Repository

    Liu, Chao

    2013-07-19

    Chlorine dioxide (ClO2) decay in the presence of typical metal oxides occurring in distribution systems was investigated. Metal oxides generally enhanced ClO2 decay in a second-order process via three pathways: (1) catalytic disproportionation with equimolar formation of chlorite and chlorate, (2) reaction to chlorite and oxygen, and (3) oxidation of a metal in a reduced form (e.g., cuprous oxide) to a higher oxidation state. Cupric oxide (CuO) and nickel oxide (NiO) showed significantly stronger abilities than goethite (α-FeOOH) to catalyze the ClO2 disproportionation (pathway 1), which predominated at higher initial ClO2 concentrations (56-81 μM). At lower initial ClO2 concentrations (13-31 μM), pathway 2 also contributed. The CuO-enhanced ClO2 decay is a base-assisted reaction with a third-order rate constant of 1.5 × 10 6 M-2 s-1 in the presence of 0.1 g L -1 CuO at 21 ± 1 C, which is 4-5 orders of magnitude higher than in the absence of CuO. The presence of natural organic matter (NOM) significantly enhanced the formation of chlorite and decreased the ClO 2 disproportionation in the CuO-ClO2 system, probably because of a higher reactivity of CuO-activated ClO2 with NOM. Furthermore, a kinetic model was developed to simulate CuO-enhanced ClO 2 decay at various pH values. Model simulations that agree well with the experimental data include a pre-equilibrium step with the rapid formation of a complex, namely, CuO-activated Cl2O4. The reaction of this complex with OH- is the rate-limiting and pH-dependent step for the overall reaction, producing chlorite and an intermediate that further forms chlorate and oxygen in parallel. These novel findings suggest that the possible ClO2 loss and the formation of chlorite/chlorate should be carefully considered in drinking water distribution systems containing copper pipes. © 2013 American Chemical Society.

  20. Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

    Science.gov (United States)

    Revett, Timothy J.; Baker, Glen B.; Jhamandas, Jack; Kar, Satyabrata

    2013-01-01

    Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness. PMID:22894822

  1. Glutamate system, amyloid ß peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology.

    Science.gov (United States)

    Revett, Timothy J; Baker, Glen B; Jhamandas, Jack; Kar, Satyabrata

    2013-01-01

    Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid ß peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid ß and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid ß production, but also amyloid ß can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness.

  2. In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

    OpenAIRE

    Raman, Lakshmi; Tkac, Ivan; Ennis, Kathleen; Georgieff, Michael K.; Gruetter, Rolf; Rao, Raghavendra

    2005-01-01

    The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using i...

  3. Immunostaining of Biocytin-filled and Processed Sections for Neurochemical Markers.

    Science.gov (United States)

    Swietek, Bogumila; Gupta, Akshay; Proddutur, Archana; Santhakumar, Vijayalakshmi

    2016-12-31

    Electrophysiological recordings of cells using the patch clamp technique have allowed for the identification of different neuronal types based on firing patterns. The inclusion of biocytin/neurobiotin in the recording electrode permits post-hoc recovery of morphological details, which are necessary to determine the dendritic arborization and the regions targeted by the axons of the recorded neurons. However, given the presence of morphologically similar neurons with distinct neurochemical identities and functions, immunohistochemical staining for cell-type-specific proteins is essential to definitively identify neurons. To maintain network connectivity, brain sections for physiological recordings are prepared at a thickness of 300 µm or greater. However, this thickness often hinders immunohistological postprocessing due to issues with antibody penetration, necessitating the resectioning of the tissue. Resectioning of slices is a challenging art, often resulting in the loss of tissue and morphology of the cells from which electrophysiological data was obtained, rendering the data unusable. Since recovery of morphology would limit data loss and guide in the selection of neuronal markers, we have adopted a strategy of recovering cell morphology first, followed by secondary immunostaining. We introduce a practical approach to biocytin filling during physiological recordings and subsequent serial immunostaining for the recovery of morphology, followed by the restaining of sections to determine the neurochemical identity. We report that sections that were filled with biocytin, fixed with paraformaldehyde (PFA), stained, and coverslipped can be removed and restained with a second primary antibody days later. This restaining involves the removal of the coverslip, the washing of sections in a buffer solution, and the incubation of primary and secondary antibodies to reveal the neurochemical identity. The method is advantageous for eliminating data loss due to an inability

  4. Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

    Science.gov (United States)

    de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

    2017-09-04

    The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of (1)H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The SADI Personal Health Lens: A Web Browser-Based System for Identifying Personally Relevant Drug Interactions.

    Science.gov (United States)

    Vandervalk, Ben; McCarthy, E Luke; Cruz-Toledo, José; Klein, Artjom; Baker, Christopher J O; Dumontier, Michel; Wilkinson, Mark D

    2013-04-05

    The Web provides widespread access to vast quantities of health-related information that can improve quality-of-life through better understanding of personal symptoms, medical conditions, and available treatments. Unfortunately, identifying a credible and personally relevant subset of information can be a time-consuming and challenging task for users without a medical background. The objective of the Personal Health Lens system is to aid users when reading health-related webpages by providing warnings about personally relevant drug interactions. More broadly, we wish to present a prototype for a novel, generalizable approach to facilitating interactions between a patient, their practitioner(s), and the Web. We utilized a distributed, Semantic Web-based architecture for recognizing personally dangerous drugs consisting of: (1) a private, local triple store of personal health information, (2) Semantic Web services, following the Semantic Automated Discovery and Integration (SADI) design pattern, for text mining and identifying substance interactions, (3) a bookmarklet to trigger analysis of a webpage and annotate it with personalized warnings, and (4) a semantic query that acts as an abstract template of the analytical workflow to be enacted by the system. A prototype implementation of the system is provided in the form of a Java standalone executable JAR file. The JAR file bundles all components of the system: the personal health database, locally-running versions of the SADI services, and a javascript bookmarklet that triggers analysis of a webpage. In addition, the demonstration includes a hypothetical personal health profile, allowing the system to be used immediately without configuration. Usage instructions are provided. The main strength of the Personal Health Lens system is its ability to organize medical information and to present it to the user in a personalized and contextually relevant manner. While this prototype was limited to a single knowledge domain

  6. Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?

    Science.gov (United States)

    Paquet, Joseph; Goebel, Jean-Christophe; Delaunay, Camille; Pinzano, Astrid; Grossin, Laurent; Cournil-Henrionnet, Christel; Gillet, Pierre; Netter, Patrick; Jouzeau, Jean-Yves; Moulin, David

    2012-03-13

    We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis. We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease. The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed. Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies.

  7. Feeding Systems and the Gut Microbiome: Gut-Brain Interactions With Relevance to Psychiatric Conditions.

    Science.gov (United States)

    Mason, Brittany L

    2017-06-08

    Physical and mental health is dependent on the environment, and feeding is a prime example of this environmental exchange. While the hypothalamus controls both feeding behavior and the stress response, the integration of the neural control centers and the peripheral gut allows for disruption in the gastrointestinal systems and dysfunctional communication to the brain. The purpose of this review is to familiarize clinicians with the physiology controlling feeding behavior and its implications for psychiatric conditions, such as anorexia nervosa and depression. Growing understanding of how integrated bacterial life is in the body has shown that gut bacteria regulate basic physiologic processes and are implicated in various disease states and contribute to regulation of mood. Responses to stress have effects on feeding behavior and mood and the regulation of the stress response by the gut microbiota could contribute to the dysfunction seen in patients with psychiatric illnesses. Gut microbiota may contribute to dysfunction in psychiatric illnesses. New opportunities to modulate existing gut microbiota using probiotics could be novel targets for clinical interventions. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  8. Induction of gram-negative bacterial growth by neurochemical containing banana (Musa x paradisiaca) extracts.

    Science.gov (United States)

    Lyte, M

    1997-09-15

    Bananas contain large quantities of neurochemicals. Extracts from the peel and pulp of bananas in increasing stages of ripening were prepared and evaluated for their ability to modulate the growth of non-pathogenic and pathogenic bacteria. Extracts from the peel, and to a much lesser degree the pulp, increased the growth of Gram-negative bacterial strains Escherichia coli O157:H7, Shigella flexneri, Enterobacter cloacae and Salmonella typhimurium, as well as two non-pathogenic E. coli strains, in direct relation to the content of norepinephrine and dopamine, but not serotonin. The growth of Gram-positive bacteria was not altered by any of the extracts. Supplementation of vehicle and pulp cultures with norepinephrine or dopamine yielded growth equivalent to peel cultures. Total organic analysis of extracts further demonstrated that the differential effects of peel and pulp on bacterial growth was not nutritionally based, but due to norepinephrine and dopamine. These results suggest that neurochemicals contained within foodstuffs may influence the growth of pathogenic and indigenous bacteria through direct neurochemical-bacterial interactions.

  9. Neudesin is involved in anxiety behavior: structural and neurochemical correlates

    Directory of Open Access Journals (Sweden)

    Ashley eNovais

    2013-09-01

    Full Text Available Neudesin (also known as neuron derived neurotrophic factor, Nenf is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional and cognitive dimensions of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze, light/dark box and novelty suppressed feeding tests, but not in the acoustic startle test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

  10. A Patchwork of Marriages: The Legal Relevance of Marriage in a Plural Legal System

    Directory of Open Access Journals (Sweden)

    Elsje Bonthuys

    2016-12-01

    Full Text Available Like many former colonies, South Africa has a plural system of family law which has historically recognized the polygynous marriages practiced by the indigenous African inhabitants of the country. However, recognition of these marriages by way of legal pluralism does not afford them equal status with the monogamous Judaeo-Christian marriage imported by European colonisers, nor does it ensure gender equality within families. Instead, the interaction between the colonial and apartheid socio-economic oppression of black people on the one hand, and legal pluralism on the other hand, produces a highly complex family law system, accurately described as ‘a patchwork of patriarchies.’ This paper argues that a far more radical transformation of family law, and one which is more likely to enhance gender equality, would be to move away from conjugality, or a sexual bond, as the basis of marriage and family law. The aim of this shift would be legal rules which recognize those relationships of kinship which have been central to African family practices and which have assisted many families to weather the multiple forms of colonial and white domination. A move away from conjugality as the primary basis of family law would also acknowledge the ever decreasing incidence of marriage and nuclear families, which characterizes contemporary South African society and would place the focus of legal regulation on the protection of socially valuable relationships, rather than the protection of marriage as an institution. Al igual que otras antiguas colonias, Sudáfrica tiene un sistema de derecho de familia plural, que ha reconocido históricamente los matrimonios en poliginia practicados por personas indígenas africanas. Sin embargo, el reconocimiento de estos matrimonios mediante pluralismo jurídico no les garantiza el mismo estatus que el matrimonio monogámico judeocristiano, ni garantiza la igualdad de género dentro de las familias. Al contrario, la

  11. Nanopore Confinement of C-O-H Fluids Relevant to Subsurface Energy Systems

    Science.gov (United States)

    Cole, D. R.

    2016-12-01

    narrow pores can produce a shift in the equilibrium distribution of mixed volatiles present in adjoining fractures (aka the bulk portion of the system).

  12. Bacterial-based systems for expression and purification of recombinant Lassa virus proteins of immunological relevance

    Directory of Open Access Journals (Sweden)

    Cashman Kathleen A

    2008-06-01

    Full Text Available Abstract Background There is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of Lassa fever. In this regard, recombinant Lassa virus (LASV proteins may serve as valuable tools in diverse antiviral applications. Bacterial-based systems were engineered for expression and purification of recombinant LASV nucleoprotein (NP, glycoprotein 1 (GP1, and glycoprotein 2 (GP2. Results Full-length NP and the ectodomains of GP1 and GP2 were generated as maltose-binding protein (MBP fusions in the Rosetta strains of Escherichia coli (E. coli using pMAL-c2x vectors. Average fusion protein yields per liter of culture for MBP-NP, MBP-GP1, and MBP-GP2 were 10 mg, 9 mg, and 9 mg, respectively. Each protein was captured from cell lysates using amylose resin, cleaved with Factor Xa, and purified using size-exclusion chromatography (SEC. Fermentation cultures resulted in average yields per liter of 1.6 mg, 1.5 mg, and 0.7 mg of purified NP, GP1 and GP2, respectively. LASV-specific antibodies in human convalescent sera specifically detected each of the purified recombinant LASV proteins, highlighting their utility in diagnostic applications. In addition, mouse hyperimmune ascitic fluids (MHAF against a panel of Old and New World arenaviruses demonstrated selective cross reactivity with LASV proteins in Western blot and enzyme-linked immunosorbent assay (ELISA. Conclusion These results demonstrate the potential for developing broadly reactive immunological assays that employ all three arenaviral proteins individually and in combination.

  13. Organic compounds in hydrothermal systems on the Russian Far East: relevance to the origin of life

    Science.gov (United States)

    Kompanichenko, Vladimir

    instance, Simoneit et al. (2) established that the light oil associated with the Uzon caldera in Kamchatka was formed by pyrolysis of buried algal mats. More interesting would be to determine that the aromatics and alkanes are products of a Fischer-Tropsch type synthesis. Intermediately the possible in-put of the abiotic organics is confirmed with the availability of Cl-alkanes in the hot solution because these compounds cannot be produced in a living organism. Besides, concentrations of even and uneven carbon atoms are similar in the juvenile hot water from the central zone of Kuldur field (the intracontinental part) that indicates their probable abiotic origination, while the uneven carbon atoms much prevail over the even ones (in 5 times) in the lower-temperature meteoric water on the flank. The detected organic compounds could enter into the composi-tion of various prebiotic microsystems or aggregates existed in the changeable hydrothermal media suitable for the origin of life. It follows of the inversion approach to the origin of life (Kompanichenko, 2008) that synthesis of other biologically important molecules (sugars, ATP, nucleotides), which are not typical for hydrothermal medium, started at the moment of the in-version the ratio "free energy contribution to entropy contribution" in the network of chemical reactions. The re-organized and turned into negentropy way network might promote the syn-thesis of these molecules under higher temperature conditions than revealed for the laboratory experiments in Vitro (50-60C). References. 1. Mukhin L.M., Bondarev V.B., Vakin E.A., Iljukhina I.I., Kalinichenko V.I., Milekhina E.I., Safonova E.N., 1979. Amino acids in hydrothermal systems in Southern Kam-chatka. Doklady AN USSR 244 (4), 974-977, (In Russian). 2. Simoneit, B., Deamer, D.W. and Kompanichenko, V. 2009. Characterization of hydrothermally generated oil from the Uzon Caldera, Kamchatka. Applied Geochemistry 24: 303-309. 3. Kompanichenko V.N. 2008. Three stages of

  14. Identification of relevant concepts of functioning in daily life in people with systemic lupus erythematosus: A patient Delphi exercise.

    Science.gov (United States)

    Bauernfeind, Bettina; Aringer, Martin; Prodinger, Birgit; Kirchberger, Inge; Machold, Klaus; Smolen, Josef; Stamm, Tanja

    2009-01-15

    To identify the most important and relevant concepts of daily functioning from the perspective of patients with systemic lupus erythematosus (SLE). We conducted a consensus-building, 3-round, electronic mail survey with SLE patients using the Delphi technique. The Delphi technique is a structured communication process with 4 key characteristics: anonymity, iteration with controlled feedback, statistical group response, and informed input. The concepts contained in the answers of the patients were extracted and linked to the International Classification of Functioning, Disability and Health (ICF). Of the total 225 participants, 194 (86.2%) completed the questionnaires from all 3 Delphi rounds. In total, after the third Delphi round, 307 concepts were identified. Ninety concepts (55 in the domain body functions and structures, 16 in activities and participation, and 19 in environmental factors) were considered relevant by at least 50% of the participants in the third round and linked to the ICF. Twelve concepts were considered important by at least 75% of the participants. The high number of concepts resulting from this large-scale patient Delphi approach underlines the great variety of SLE patients' problems in daily functioning. The results of this patient Delphi project supplement the findings of our focus-group study in establishing a comprehensive overview of the patient perspective in SLE.

  15. The Complexity of Food Systems: Defining Relevant Attributes and Indicators for the Evaluation of Food Supply Chains in Spain

    Directory of Open Access Journals (Sweden)

    Gonzalo Gamboa

    2016-05-01

    Full Text Available The wide-ranging literature on food systems provides multiple perspectives and world views. Various stakeholders define food and food systems in non-equivalent ways. The perception of the performance of food systems is determined by these specific perspectives, and a wide variety of policies responding to different aims are proposed and implemented accordingly. This paper sets out to demonstrate that the pre-analytical adoption of different narratives about the food system leads to non-equivalent assessments of the performance of food supply chains. In order to do so, we (i identify a set of relevant narratives on food supply chains in Spanish and Catalan contexts; (ii identify the pertinent attributes needed to describe and represent food supply chains within the different perspectives or narratives; and (iii carry out an integrated assessment of three organic tomato supply chains from the different perspectives. In doing so, the paper proposes an analysis of narratives to enable the analyst to characterize the performance of food supply chains from different perspectives and to identify the expected trade-offs of integrated assessment, associating them with the legitimate-but-contrasting views found among the social actors involved.

  16. Mercury associated neurochemical response in Arctic barnacle goslings (Branta leucopsis)

    NARCIS (Netherlands)

    Brink, van den Nico W.; Scheiber, Isabella B.R.; Jong, de Margje E.; Braun, Anna; Arini, Adeline; Basu, Niladri; Berg, van den Hans; Komdeur, Jan; Loonen, Maarten J.J.E.

    2018-01-01

    There remains great concern over mercury pollution in the Arctic, though relatively little is known about impacts on biota that inhabit Arctic terrestrial systems. To help address this, the current study was performed with barnacle goslings (Branta leucopsis) from a coal mine-impacted site and a

  17. Spatial resolution measurements of the advanced radiographic capability x-ray imaging system at energies relevant to Compton radiography

    Science.gov (United States)

    Hall, G. N.; Izumi, N.; Landen, O. L.; Tommasini, R.; Holder, J. P.; Hargrove, D.; Bradley, D. K.; Lumbard, A.; Cruz, J. G.; Piston, K.; Lee, J. J.; Romano, E.; Bell, P. M.; Carpenter, A. C.; Palmer, N. E.; Felker, B.; Rekow, V.; Allen, F. V.

    2016-11-01

    Compton radiography provides a means to measure the integrity, ρR and symmetry of the DT fuel in an inertial confinement fusion implosion near peak compression. Upcoming experiments at the National Ignition Facility will use the ARC (Advanced Radiography Capability) laser to drive backlighter sources for Compton radiography experiments and will use the newly commissioned AXIS (ARC X-ray Imaging System) instrument as the detector. AXIS uses a dual-MCP (micro-channel plate) to provide gating and high DQE at the 40-200 keV x-ray range required for Compton radiography, but introduces many effects that contribute to the spatial resolution. Experiments were performed at energies relevant to Compton radiography to begin characterization of the spatial resolution of the AXIS diagnostic.

  18. Spatial resolution measurements of the advanced radiographic capability x-ray imaging system at energies relevant to Compton radiography

    Energy Technology Data Exchange (ETDEWEB)

    Hall, G. N., E-mail: hall98@llnl.gov; Izumi, N.; Landen, O. L.; Tommasini, R.; Holder, J. P.; Hargrove, D.; Bradley, D. K.; Lumbard, A.; Cruz, J. G.; Piston, K.; Bell, P. M.; Carpenter, A. C.; Palmer, N. E.; Felker, B.; Rekow, V.; Allen, F. V. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States); Lee, J. J.; Romano, E. [National Security Technologies LLC, 161 S Vasco Rd., Livermore, California 94551 (United States)

    2016-11-15

    Compton radiography provides a means to measure the integrity, ρR and symmetry of the DT fuel in an inertial confinement fusion implosion near peak compression. Upcoming experiments at the National Ignition Facility will use the ARC (Advanced Radiography Capability) laser to drive backlighter sources for Compton radiography experiments and will use the newly commissioned AXIS (ARC X-ray Imaging System) instrument as the detector. AXIS uses a dual-MCP (micro-channel plate) to provide gating and high DQE at the 40–200 keV x-ray range required for Compton radiography, but introduces many effects that contribute to the spatial resolution. Experiments were performed at energies relevant to Compton radiography to begin characterization of the spatial resolution of the AXIS diagnostic.

  19. Neural and neurochemical basis of reinforcement-guided decision making.

    Science.gov (United States)

    Khani, Abbas; Rainer, Gregor

    2016-08-01

    Decision making is an adaptive behavior that takes into account several internal and external input variables and leads to the choice of a course of action over other available and often competing alternatives. While it has been studied in diverse fields ranging from mathematics, economics, ecology, and ethology to psychology and neuroscience, recent cross talk among perspectives from different fields has yielded novel descriptions of decision processes. Reinforcement-guided decision making models are based on economic and reinforcement learning theories, and their focus is on the maximization of acquired benefit over a defined period of time. Studies based on reinforcement-guided decision making have implicated a large network of neural circuits across the brain. This network includes a wide range of cortical (e.g., orbitofrontal cortex and anterior cingulate cortex) and subcortical (e.g., nucleus accumbens and subthalamic nucleus) brain areas and uses several neurotransmitter systems (e.g., dopaminergic and serotonergic systems) to communicate and process decision-related information. This review discusses distinct as well as overlapping contributions of these networks and neurotransmitter systems to the processing of decision making. We end the review by touching on neural circuitry and neuromodulatory regulation of exploratory decision making. Copyright © 2016 the American Physiological Society.

  20. Theophylline, adenosine receptor antagonist prevents behavioral, biochemical and neurochemical changes associated with an animal model of tardive dyskinesia.

    Science.gov (United States)

    Bishnoi, Mahendra; Chopra, Kanwaljit; Kulkarni, Shrinivas K

    2007-01-01

    Tardive dyskinesia is considered to be the late onset adverse effect of prolonged administration of typical neuroleptic drugs. Adenosine is now widely accepted as the major inhibitory neuromodulators in the central nervous system besides GABA. Antagonists of A2A receptors are known to confer protection against neuronal damage caused by toxins and reactive oxygen species. The present study investigated the effect of adenosine receptor antagonist, theophylline (25 and 50 mg/kg, ip) in an animal model of tardive dyskinesia by using different behavioral (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase)) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg ip for 21 days) significantly increased vacuous chewing movements (VCMs), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by theophylline. Chronic administration of haloperidol also resulted in the increased dopamine receptor sensitivity as evidenced by increased locomotor activity and stereotypic rearing. Further, it also decreased % retention time in elevated plus maze paradigm. Pretreatment with theophylline reversed these behavioral changes. Chronic administration of haloperidol also induced oxidative damage in all the brain regions which was prevented by theophylline, especially in the striatum. Chronic administration of haloperidol resulted in a decrease in dopamine levels which was reversed by treatment with theophylline (at higher doses). The findings of the present study suggested the involvement of adenosinergic receptor system in the development of tardive dyskinesia and possible therapeutic potential of theophylline in this disorder.

  1. Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation.

    Science.gov (United States)

    Settell, Megan L; Testini, Paola; Cho, Shinho; Lee, Jannifer H; Blaha, Charles D; Jo, Hang J; Lee, Kendall H; Min, Hoon-Ki

    2017-01-01

    Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI). Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V). Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected modulation of the neural circuitry associated with VTA-DBS was characterized in a large animal. Our findings suggest that VTA-DBS could affect the activity of neural systems and brain regions implicated in

  2. Relevant Concepts of Functioning for Patients With Systemic Lupus Erythematosus Identified in a Delphi Exercise of Experts and a Literature Review

    National Research Council Canada - National Science Library

    Leuchten, Nicolai; Bauernfeind, Bettina; Kuttner, Johannes; Stamm, Tanja; Smolen, Josef S; Pisetsky, David S; Aringer, Martin

    2014-01-01

    To identify in a Delphi exercise of international systemic lupus erythematosus (SLE) experts and a systematic literature review the most relevant concepts that impact on the functioning of SLE patients...

  3. Skill acquisition while operating in-vehicle information systems: interface design determines the level of safety-relevant distractions.

    Science.gov (United States)

    Jahn, Georg; Krems, Josef F; Gelau, Christhard

    2009-04-01

    This study tested whether the ease of learning to use human-machine interfaces of in-vehicle information systems (IVIS) can be assessed at standstill. Assessing the attentional demand of IVIS should include an evaluation of ease of learning, because the use of IVIS at low skill levels may create safety-relevant distractions. Skill acquisition in operating IVIS was quantified by fitting the power law of practice to training data sets collected in a driving study and at standstill. Participants practiced manual destination entry with two route guidance systems differing in cognitive demand. In Experiment 1, a sample of middle-aged participants was trained while steering routes of varying driving demands. In Experiment 2, another sample of middle-aged participants was trained at standstill. In Experiment 1, display glance times were less affected by driving demands than by total task times and decreased at slightly higher speed-up rates (0.02 higher on average) than task times collected at standstill in Experiment 2. The system interface that minimized cognitive demand was operated more quickly and was easier to learn. Its system delays increased static task times, which still predicted 58% of variance in display glance times compared with even 76% for the second system. The ease of learning to use an IVIS interface and the decrease in attentional demand with training can be assessed at standstill. Fitting the power law of practice to static task times yields parameters that predict display glance times while driving, which makes it possible to compare interfaces with regard to ease of learning.

  4. Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication

    Directory of Open Access Journals (Sweden)

    E. Roda

    2016-01-01

    Full Text Available Introduction. Chronic poisoning may result in home setting after mercury (Hg vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg monitoring were performed from admission (t0, until 1 year later (t2, paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs. At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1–4.5; UHg 0.1–4.5, associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0–16.0. At t1 (two days after DMSA-mobilization test, BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes. At t2 (eight months after two cycles of DMSA chelating therapy ending, gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp. and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes. Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

  5. Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication.

    Science.gov (United States)

    Roda, E; Giampreti, A; Vecchio, S; Apostoli, P; Coccini, T

    2016-01-01

    Introduction. Chronic poisoning may result in home setting after mercury (Hg) vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg) monitoring were performed from admission (t0), until 1 year later (t2), paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs). At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1-4.5; UHg 0.1-4.5), associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0-16.0). At t1 (two days after DMSA-mobilization test), BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes). At t2 (eight months after two cycles of DMSA chelating therapy ending), gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp.) and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes). Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

  6. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features.

    Science.gov (United States)

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer's disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be

  7. Creation of the relevant next: How living systems capture the power of the adjacent possible through sign use.

    Science.gov (United States)

    Favareau, Donald F

    2015-12-01

    Stuart Kauffman's revolutionary notion of the Adjacent Possible as an organizing principle in nature shares much in common with logician Charles S. Peirce's understanding of the universe as an ever-unfolding 'process ontology' of possibility space that is brought about through the recursive interaction of genuine possibility, transiently actualized order, and emergent (but never fully deterministic) lawfulness. Proceeding from these three fundamental categories of becoming-as-being, Peirce developed a complimentary logic of sign relations that, along with Estonian biologist Jakob von Uexküll's action-as-meaning-imprinting Umwelt theory, informs the work that is currently being undertaken under the aegis of Biosemiotics. In this paper, I will highlight the deep affinities between Kauffman's notion of the Adjacent Possible and Biosemiotics' hybrid Peircean/Uexküllian "sign" concept, by which living systems - both as individuals and in the aggregate (i.e., as co-actors, communities and lineages) - "capture" relevant aspects of their relations with the immediately given Adjacent Possible and preserve those recipes for future interaction possibilities as biologically instantiated signs. By so doing, living systems move into the Adjacent Possible by "collapsing the wave function" of possibility not just probabilistically, but guided by system-internal values arising from previously captured sign relations that are biologically instantiated as replicable system biases and generative constraints. The influence of such valenced and end-directed action in the world introduces into the universe the phenomenon of the Relevant (and not just deterministic, or even stochastic) Next. My argument in this paper is that organisms live out their lives perpetually confronted with negotiating the omnipresent Relevant Next, and are informed by the biological capture of their (and their lineage's) previous engagements in doing so. And because that "capture" of previous agent

  8. Simultaneous-Fault Diagnosis of Automotive Engine Ignition Systems Using Prior Domain Knowledge and Relevance Vector Machine

    Directory of Open Access Journals (Sweden)

    Chi-Man Vong

    2013-01-01

    Full Text Available Engine ignition patterns can be analyzed to identify the engine fault according to both the specific prior domain knowledge and the shape features of the patterns. One of the challenges in ignition system diagnosis is that more than one fault may appear at a time. This kind of problem refers to simultaneous-fault diagnosis. Another challenge is the acquisition of a large amount of costly simultaneous-fault ignition patterns for constructing the diagnostic system because the number of the training patterns depends on the combination of different single faults. The above problems could be resolved by the proposed framework combining feature extraction, probabilistic classification, and decision threshold optimization. With the proposed framework, the features of the single faults in a simultaneous-fault pattern are extracted and then detected using a new probabilistic classifier, namely, pairwise coupling relevance vector machine, which is trained with single-fault patterns only. Therefore, the training dataset of simultaneous-fault patterns is not necessary. Experimental results show that the proposed framework performs well for both single-fault and simultaneous-fault diagnoses and is superior to the existing approach.

  9. Review of Relevant System Development Life Cycles (SDLCs in Service-Oriented Software Engineering (SoSE

    Directory of Open Access Journals (Sweden)

    L. Rodríguez-Martínez

    2012-04-01

    Full Text Available Service-oriented software engineering (SoSE is a new paradigm for building software systems, fostered by the availability of a new -but already mature- computing technology based on services. SoSE advances the current object-oriented and the component-based software engineering paradigms. Under that new paradigm, multiple software-system development life cycle (SDLC methodologies have been proposed; however, none of them have gained a total acceptance as the dominant SDLC in SoSE. On this theoretical and practical situation, we believe that a research is required to reach more standardized and stabilized knowledge about SDLCs in SoSE. Thus, this article reviews nine recent SDLCs proposed for SoSE with the aim to present a descriptive-comparative landscape of a relevant range of SDLCs for SoSE. Such description-comparison is guided by two criteria: (i the extent of completeness of each SDLC, with respect to the proposed phases, activities and delivered artifacts, and (ii the extent of the Boehm-Turner’s Rigor-Agility balance. Our results suggest that only three of the nine SDLCs studied already provide the best level of completeness and Rigor-Agility. Finally, we consider that the reported descriptivecomparative framework and their findings from each SDLC can be useful also for comparing and elaborating future SDLCs in SoSE.

  10. Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: a model for Parkinson's disease.

    Science.gov (United States)

    Sundström, E; Fredriksson, A; Archer, T

    1990-10-01

    The long-term effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on pre- and postsynaptic structures of the nigrostriatal and mesolimbic dopamine (DA) system in adult C57BL/6 mice (2 x 40 mg/kg s.c.) was investigated using neurochemical and behavioral methods. It was found that MPTP induced a severe depletion of striatal DA levels (-80%) that persists for 4 weeks after treatment, with less severe effects in nucleus accumbens (-36%) and the olfactory tubercle (-52%). These depletions are associated with decreased tyrosine hydroxylase (TH) activity as determined in vivo and increased turnover of DA. MPTP treatment did not induce any change in the DA2-receptor as determined by [3H]spiperone binding or by two different behavioral tests, i.e. apomorphine-induced climbing and apomorphine-induced stereotypies. No significant weight loss during 4 weeks after MPTP was found. The spontaneous motor activity in these mice was profoundly and persistently depressed (-66%) as a result of the MPTP-induced DA denervation and the motor deficit was completely reversed by L-DOPA treatment. We suggest that MPTP-treated C57BL/6 mice may serve as a suitable model for Parkinson's disease.

  11. Cannabinoids for the Treatment of Schizophrenia? A Balanced Neurochemical Framework for Both Adverse and Therapeutic Effects of Cannabis Use

    Directory of Open Access Journals (Sweden)

    Carissa M. Coulston

    2011-01-01

    Full Text Available Recent studies have found that cannabinoids may improve neuropsychological performance, ameliorate negative symptoms, and have antipsychotic properties for a subgroup of the schizophrenia population. These findings are in contrast to the longstanding history of adverse consequences of cannabis use, predominantly on the positive symptoms, and a balanced neurochemical basis for these opposing views is lacking. This paper details a review of the neurobiological substrates of schizophrenia and the neurochemical effects of cannabis use in the normal population, in both cortical (in particular prefrontal and subcortical brain regions. The aim of this paper is to provide a holistic neurochemical framework in which to understand how cannabinoids may impair, or indeed, serve to ameliorate the positive and negative symptoms as well as cognitive impairment. Directions in which future research can proceed to resolve the discrepancies are briefly discussed.

  12. Neural network modelling and dynamical system theory: are they relevant to study the governing dynamics of association football players?

    Science.gov (United States)

    Dutt-Mazumder, Aviroop; Button, Chris; Robins, Anthony; Bartlett, Roger

    2011-12-01

    Recent studies have explored the organization of player movements in team sports using a range of statistical tools. However, the factors that best explain the performance of association football teams remain elusive. Arguably, this is due to the high-dimensional behavioural outputs that illustrate the complex, evolving configurations typical of team games. According to dynamical system analysts, movement patterns in team sports exhibit nonlinear self-organizing features. Nonlinear processing tools (i.e. Artificial Neural Networks; ANNs) are becoming increasingly popular to investigate the coordination of participants in sports competitions. ANNs are well suited to describing high-dimensional data sets with nonlinear attributes, however, limited information concerning the processes required to apply ANNs exists. This review investigates the relative value of various ANN learning approaches used in sports performance analysis of team sports focusing on potential applications for association football. Sixty-two research sources were summarized and reviewed from electronic literature search engines such as SPORTDiscus, Google Scholar, IEEE Xplore, Scirus, ScienceDirect and Elsevier. Typical ANN learning algorithms can be adapted to perform pattern recognition and pattern classification. Particularly, dimensionality reduction by a Kohonen feature map (KFM) can compress chaotic high-dimensional datasets into low-dimensional relevant information. Such information would be useful for developing effective training drills that should enhance self-organizing coordination among players. We conclude that ANN-based qualitative analysis is a promising approach to understand the dynamical attributes of association football players.

  13. Microdialysis Coupled with LC-MS/MS for In Vivo Neurochemical Monitoring.

    Science.gov (United States)

    Zestos, Alexander G; Kennedy, Robert T

    2017-09-01

    Microdialysis is a powerful sampling technique used to monitor small molecules in vivo. Despite the many applications of microdialysis sampling, it is limited by the method of analyzing the resulting samples. An emerging technique for analysis of microdialysis samples is liquid chromatography-tandem mass spectrometry (LC-MS/MS). This technique is highly versatile, allowing multiplexed analysis of neurotransmitters, metabolites, and neuropeptides. Using LC-MS/MS for polar neurotransmitters is hampered by weak retention reverse phase LC columns. Several derivatization reagents have been utilized to enhance separation and resolution of neurochemicals in dialysate samples including benzoyl chloride (BzCl), dansyl chloride, formaldehyde, ethylchloroformate, and propionic anhydride. BzCl reacts with amine and phenol groups so that many neurotransmitters can be labeled. Besides improving separation on reverse phase columns, this reagent also increases sensitivity. It is available in a heavy form so that it can be used to make stable-isotope labeled internal standard for improved quantification. Using BzCl with LC-MS/MS has allowed for measuring as many as 70 neurochemicals in a single assay. With slightly different conditions, LC-MS/MS has also been used for monitoring endocannabinoids. LC-MS/MS is also useful for neuropeptide assay because it allows for highly sensitive, sequence specific measurement of most peptides. These advances have allowed for multiplexed neurotransmitter measurements in behavioral, circuit analysis, and drug effect studies.

  14. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.

    Science.gov (United States)

    Blennow, K; Jonsson, M; Andreasen, N; Rosengren, L; Wallin, A; Hellström, P A; Zetterberg, H

    2011-04-01

    Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons. © 2010 John Wiley & Sons A/S.

  15. Neurochemical effects of extended exposure to white spirit vapour at three concentration levels.

    Science.gov (United States)

    Savolainen, H; Pfäffli, P

    1982-03-01

    Male Wistar rats were exposed to 575 (100 ppm), 2875 (500 ppm) or 5750 mg/m3 (1000 ppm) white spirit vapour for 4-17 weeks 5 days a week, 6 h daily. Perirenal fat solvent concentration corresponded in composition and concentration to those of the vapour at all times. The neurochemical effects included a dose-dependent decrease in the cerebellar succinate dehydrogenase activity for 8 weeks while creatine kinase activity increased after 12 weeks. The specific creatine kinase activity in the glial cell fraction, a marker for astroglia, did not increase suggesting proliferation of astroglial cells in the homogenate. The serum creatine kinase activity originating mainly from striated muscle was below the control range at the two higher concentrations after 12 weeks. Simultaneous analyses for isolated muscle membrane sialic acid and uronic acid residues showed decreased concentrations in proportion to lipid phosphorus or total membrane protein. Thus, the white spirit mixture has neurochemical effects possibly caused by paraffins and the same components may have caused the muscle cell membrane effects. The lowest exposure concentration represents a virtual 'no effect' level for rats in the 17-week exposure.

  16. The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects.

    Science.gov (United States)

    Cotter, Rachel; Pei, Yue; Mus, Liudmila; Harmeier, Anja; Gainetdinov, Raul R; Hoener, Marius C; Canales, Juan J

    2015-01-01

    The newly discovered trace amine-associated receptor 1 (TAAR1) has the ability to regulate both dopamine function and psychostimulant action. Here, we tested in rats the ability of RO5203648, a selective TAAR1 partial agonist, to modulate the physiological and behavioral effects of methamphetamine (METH). In experiment 1, RO5203468 dose- and time-dependently altered METH-induced locomotor activity, manifested as an early attenuation followed by a late potentiation of METH's stimulating effects. In experiment 2, rats received a 14-day treatment regimen during which RO5203648 was co-administered with METH. RO5203648 dose-dependently attenuated METH-stimulated hyperactivity, with the effects becoming more apparent as the treatments progressed. After chronic exposure and 3-day withdrawal, rats were tested for locomotor sensitization. RO5203648 administration during the sensitizing phase prevented the development of METH sensitization. However, RO5203648, at the high dose, cross-sensitized with METH. In experiment 3, RO5203648 dose-dependently blocked METH self-administration without affecting operant responding maintained by sucrose, and exhibited lack of reinforcing efficacy when tested as a METH's substitute. Neurochemical data showed that RO5203648 did not affect METH-mediated DA efflux and uptake inhibition in striatal synaptosomes. In vivo, however, RO5203648 was able to transiently inhibit METH-induced accumulation of extracellular DA levels in the nucleus accumbens. Taken together, these data highlight the significant potential of TAAR1 to modulate METH's neurochemical and behavioral effects.

  17. The relevance of WHO injury surveillance guidelines for evaluation: learning from the aboriginal community-centered injury surveillance system (ACCISS) and two institution-based systems.

    Science.gov (United States)

    Auer, Anna M; Dobmeier, Teresa M; Haglund, Bo Ja; Tillgren, Per

    2011-09-29

    Over the past three decades, the capacity to develop and implement injury surveillance systems (ISS) has grown worldwide and is reflected by the diversity of data gathering environments in which ISS operate. The capacity to evaluate ISS, however, is less advanced and existing evaluation guidelines are ambiguous. Furthermore, the applied relevance of these guidelines to evaluate ISS operating in various settings is unclear. The aim of this paper was to examine how the World Health Organization (WHO) injury surveillance guidelines have been applied to evaluate systems operating in three different contexts. The attributes of a good surveillance system as well as instructions for conducting evaluations, outlined in the WHO injury surveillance guidelines, were used to develop an analytical framework. Using this framework, a comparative analysis of the application of the guidelines was conducted using; the Aboriginal Community-Centered Injury Surveillance System (ACCISS) from Canada, the Shantou-Emergency Department Injury Surveillance Project (S-EDISP) from China, and the Yorkhill-Canadian Hospitals Injury Reporting and Prevention Program (Y-CHIRPP) imported from Canada and implemented in Scotland. The WHO guidelines provide only a basic platform for evaluation. The guidelines over emphasize epidemiologic attributes and methods and under emphasize public health and injury prevention perspectives requiring adaptation for context-based relevance. Evaluation elements related to the dissemination and use of knowledge, acceptability, and the sustainability of ISS are notably inadequate. From a public health perspective, alternative reference points are required for re-conceptualizing evaluation paradigms. This paper offers an ISS evaluation template that considers how the WHO guidelines could be adapted and applied. Findings suggest that attributes of a good surveillance system, when used as evaluation metrics, cannot be weighted equally across ISS. In addition, the

  18. The relevance of WHO injury surveillance guidelines for evaluation: learning from the aboriginal community-centered injury surveillance system (ACCISS and two institution-based systems

    Directory of Open Access Journals (Sweden)

    Auer Anna M

    2011-09-01

    Full Text Available Abstract Background Over the past three decades, the capacity to develop and implement injury surveillance systems (ISS has grown worldwide and is reflected by the diversity of data gathering environments in which ISS operate. The capacity to evaluate ISS, however, is less advanced and existing evaluation guidelines are ambiguous. Furthermore, the applied relevance of these guidelines to evaluate ISS operating in various settings is unclear. The aim of this paper was to examine how the World Health Organization (WHO injury surveillance guidelines have been applied to evaluate systems operating in three different contexts. Methods The attributes of a good surveillance system as well as instructions for conducting evaluations, outlined in the WHO injury surveillance guidelines, were used to develop an analytical framework. Using this framework, a comparative analysis of the application of the guidelines was conducted using; the Aboriginal Community-Centered Injury Surveillance System (ACCISS from Canada, the Shantou-Emergency Department Injury Surveillance Project (S-EDISP from China, and the Yorkhill-Canadian Hospitals Injury Reporting and Prevention Program (Y-CHIRPP imported from Canada and implemented in Scotland. Results The WHO guidelines provide only a basic platform for evaluation. The guidelines over emphasize epidemiologic attributes and methods and under emphasize public health and injury prevention perspectives requiring adaptation for context-based relevance. Evaluation elements related to the dissemination and use of knowledge, acceptability, and the sustainability of ISS are notably inadequate. From a public health perspective, alternative reference points are required for re-conceptualizing evaluation paradigms. This paper offers an ISS evaluation template that considers how the WHO guidelines could be adapted and applied. Conclusions Findings suggest that attributes of a good surveillance system, when used as evaluation metrics

  19. Our Solar System 2050: Advancing the Science, Technology, and Societal Relevance of Planetary Exploration Through Public Participation

    Science.gov (United States)

    Kaminski, A. P.; Bowman, C. D.; Buquo, L. E.; Conrad, P. G.; Davis, R. M.; Domagal-Goldman, S.; Pirtle, Z. T.; Skytland, N. G.; Tahu, G. J.; Thaller, M. L.; Viotti, M. A.

    2017-02-01

    We show how citizen science, crowdsourcing, prize competitions, and other modalities can expand public participation and prove valuable for enhancing the science, technology, and societal relevance of planetary exploration over the next few decades.

  20. Time-resolved and steady-state studies of biologically and chemically relevant systems using laser, absorption, and fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, Charles Ashley [Iowa State Univ., Ames, IA (United States)

    2014-12-20

    In Chapter 2 several experimental and data analysis methods used in this thesis are described. In Chapter 3 steady-state fluorescence spectroscopy was used to determine the concentration of the efflux pump inhibitors (EPIs), pheophorbide a and pyropheophorbide a, in the feces of animals and it was found that their levels far exceed those reported to be inhibitory to efflux pumps. In Chapter 4 the solvation dynamics of 6-Propionyl-2-(N,Ndimethyl) aminonaphthalene (PRODAN) was studied in reverse micelles. The two fluorescent states of PRODAN solvate on different time scales and as such care must be exercised in solvation dynamic studies involving it and its analogs. In Chapter 5 we studied the experimental and theoretical solvation dynamics of coumarin 153 (C153) in wild-type (WT) and modified myoglobins. Based on the nuclear magnetic resonance (NMR) spectroscopy and time-resolved fluorescence studies, we have concluded that it is important to thoroughly characterize the structure of a protein and probe system before comparing the theoretical and experimental results. In Chapter 6 the photophysical and spectral properties of a derivative of the medically relevant compound curcumin called cyclocurcumin was studied. Based on NMR, fluorescence, and absorption studies, the ground- and excited-states of cyclocurcumin are complicated by the existence of multiple structural isomers. In Chapter 7 the hydrolysis of cellulose by a pure form of cellulase in an ionic liquid, HEMA, and its aqueous mixtures at various temperatures were studied with the goal of increasing the cellulose to glucose conversion for biofuel production. It was found that HEMA imparts an additional stability to cellulase and can allow for faster conversion of cellulose to glucose using a pre-treatment step in comparison to only buffer.

  1. Applying Time-sharing technique in a multimodal compact low-power CMOS neurochip for simultaneous neurochemical and action potential recording.

    Science.gov (United States)

    Poustinchi, Mohammad; Stacey, R Greg; Musallam, Sam

    2014-01-01

    Brain is an electrochemical system and recent studies suggest simultaneous measurement of interrelated brain's electrical and neurochemical activity may lead to better understanding of brain function in addition to developing optimal neural prosthetics. By exploiting opamp Time-sharing technique to minimized power dissipation and silicon area, we have fabricated a power efficient implantable CMOS microsystem for simultaneous measurement of Action Potential (AP) and neurotransmitter concentration. Both AP-recording and neurotransmitter sensing subsystems share a single 653 nW amplifier which senses picoscale to microscale current that corresponds to micromolar neurotransmitter concentration and microscale AP voltage. This microsystem is fabricated in CMOS 0.18 μm technology and tested using recorded signals from dorsal premotor cortex (PMd) area of a macaque monkey in our lab.

  2. Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and Reproductive Changes in Rats

    Directory of Open Access Journals (Sweden)

    David Fotsing

    2017-09-01

    Full Text Available Gladiolus dalenii is a plant commonly used in many regions of Cameroon as a cure for various diseases like headaches, epilepsy, schizophrenia, and mood disorders. Recent studies have revealed that the aqueous extract of G. dalenii (AEGD exhibited antidepressant-like properties in rats. Therefore, we hypothesized that the AEGD could protect from the stress-induced behavioral, neurochemical, and reproductive changes in rats. The objective of the present study was to elucidate the effect of the AEGD on behavioral, neurochemical, and reproductive characteristics, using female rats subjected to chronic immobilization stress. The chronic immobilization stress (3 h per day for 28 days was applied to induce female reproductive and behavioral impairments in rats. The immobilization stress was provoked in rats by putting them separately inside cylindrical restrainers with ventilated doors at ambient temperature. The plant extract was given to rats orally everyday during 28 days, 5 min before induction of stress. On a daily basis, a vaginal smear was made to assess the duration of the different phases of the estrous cycle and at the end of the 28 days of chronic immobilization stress, the rat’s behavior was assessed in the elevated plus maze. They were sacrificed by cervical disruption. The organs were weighed, the ovary histology done, and the biochemical parameters assessed. The findings of this research revealed that G. dalenii increased the entries and the time of open arm exploration in the elevated plus maze. Evaluation of the biochemical parameters levels indicated that there was a significant reduction in the corticosterone, progesterone, and prolactin levels in the G. dalenii aqueous extract treated rats compared to stressed rats whereas the levels of serotonin, triglycerides, adrenaline, cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing hormone were significantly increased in the stressed rats treated with, G. dalenii

  3. Cerebellar neurochemical alterations in spinocerebellar ataxia type 14 appear to include glutathione deficiency.

    Science.gov (United States)

    Doss, Sarah; Rinnenthal, Jan Leo; Schmitz-Hübsch, Tanja; Brandt, Alexander U; Papazoglou, Sebastian; Lux, Silke; Maul, Stephan; Würfel, Jens; Endres, Matthias; Klockgether, Thomas; Minnerop, Martina; Paul, Friedemann

    2015-08-01

    Autosomal dominant ataxia type 14 (SCA14) is a rare usually adult-onset progressive disorder with cerebellar neurodegeneration caused by mutations in protein kinase C gamma. We set out to examine cerebellar and extracerebellar neurochemical changes in SCA14 by MR spectroscopy. In 13 SCA14 patients and 13 healthy sex- and age-matched controls, 3-T single-voxel brain proton MR spectroscopy was performed in a cerebellar voxel of interest (VOI) at TE = 30 ms to obtain a neurochemical profile of metabolites with short relaxation times. In the cerebellum and in additional VOIs in the prefrontal cortex, motor cortex, and somatosensory cortex, a second measurement was performed at TE = 144 ms to mainly extract the total N-acetyl-aspartate (tNAA) signal besides the signals for total creatine (tCr) and total choline (tCho). The cerebellar neurochemical profile revealed a decrease in glutathione (6.12E-06 ± 2.50E-06 versus 8.91E-06 ± 3.03E-06; p = 0028) and tNAA (3.78E-05 ± 5.67E-06 versus 4.25E-05 ± 5.15E-06; p = 0023) and a trend for reduced glutamate (2.63E-05 ± 6.48E-06 versus 3.15E-05 ± 7.61E-06; p = 0062) in SCA14 compared to controls. In the tNAA-focused measurement, cerebellar tNAA (296.6 ± 42.6 versus 351.7 ± 16.5; p = 0004) and tCr (272.1 ± 25.2 versus 303.2 ± 31.4; p = 0004) were reduced, while the prefrontal, somatosensory and motor cortex remained unaffected compared to controls. Neuronal pathology in SCA14 detected by MR spectroscopy was restricted to the cerebellum and did not comprise cortical regions. In the cerebellum, we found in addition to signs of neurodegeneration a glutathione reduction, which has been associated with cellular damage by oxidative stress in other neurodegenerative diseases such as Parkinson's disease and Friedreich's ataxia.

  4. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Eggers Pedersen, Kathrine; Basu, Niladri; Letcher, Robert; Greaves, Alana K; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

    2015-04-01

    Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; rp=0.83, p=0.041, n=6) and across brain regions (e.g. ∑PFCA; rp=0.47, p=0.001, ∑PFSA; rp=0.44, p>0.001; n=50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp=0.33, p=0.02 and PFDoDA; rp=0.34, p=0.014; n=52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp=-0.95, p=0.013, n=5) and across brain regions (e.g.

  5. A Novel Relevance Feedback Approach Based on Similarity Measure Modification in an X-Ray Image Retrieval System Based on Fuzzy Representation Using Fuzzy Attributed Relational Graph

    Directory of Open Access Journals (Sweden)

    Hossien Pourghassem

    2011-04-01

    Full Text Available Relevance feedback approaches is used to improve the performance of content-based image retrieval systems. In this paper, a novel relevance feedback approach based on similarity measure modification in an X-ray image retrieval system based on fuzzy representation using fuzzy attributed relational graph (FARG is presented. In this approach, optimum weight of each feature in feature vector is calculated using similarity rate between query image and relevant and irrelevant images in user feedback. The calculated weight is used to tune fuzzy graph matching algorithm as a modifier parameter in similarity measure. The standard deviation of the retrieved image features is applied to calculate the optimum weight. The proposed image retrieval system uses a FARG for representation of images, a fuzzy matching graph algorithm as similarity measure and a semantic classifier based on merging scheme for determination of the search space in image database. To evaluate relevance feedback approach in the proposed system, a standard X-ray image database consisting of 10000 images in 57 classes is used. The improvement of the evaluation parameters shows proficiency and efficiency of the proposed system.

  6. Perioperative Temperature Measurement Considerations Relevant to Reporting Requirements for National Quality Programs Using Data From Anesthesia Information Management Systems.

    Science.gov (United States)

    Epstein, Richard H; Dexter, Franklin; Hofer, Ira S; Rodriguez, Luis I; Schwenk, Eric S; Maga, Joni M; Hindman, Bradley J

    2017-06-08

    Perioperative hypothermia may increase the incidences of wound infection, blood loss, transfusion, and cardiac morbidity. U.S. national quality programs for perioperative normothermia specify the presence of at least 1 "body temperature" ≥35.5°C during the interval from 30 minutes before to 15 minutes after the anesthesia end time. Using data from 4 academic hospitals, we evaluated timing and measurement considerations relevant to the current requirements to guide hospitals wishing to report perioperative temperature measures using electronic data sources. Anesthesia information management system databases from 4 hospitals were queried to obtain intraoperative temperatures and intervals to the anesthesia end time from discontinuation of temperature monitoring, end of surgery, and extubation. Inclusion criteria included age >16 years, use of a tracheal tube or supraglottic airway, and case duration ≥60 minutes. The end-of-case temperature was determined as the maximum intraoperative temperature recorded within 30 minutes before the anesthesia end time (ie, the temperature that would be used for reporting purposes). The fractions of cases with intervals >30 minutes between the last intraoperative temperature and the anesthesia end time were determined. Among the hospitals, averages (binned by quarters) of 34.5% to 59.5% of cases had intraoperative temperature monitoring discontinued >30 minutes before the anesthesia end time. Even if temperature measurement had been continued until extubation, averages of 5.9% to 20.8% of cases would have exceeded the allowed 30-minute window. Averages of 8.9% to 21.3% of cases had end-of-case intraoperative temperatures <35.5°C (ie, a quality measure failure). Because of timing considerations, a substantial fraction of cases would have been ineligible to use the end-of-case intraoperative temperature for national quality program reporting. Thus, retrieval of postanesthesia care unit temperatures would have been necessary. A

  7. Neurochemical changes in the hippocampus and prefrontal cortex associated with electroacupuncture for learning and memory impairment.

    Science.gov (United States)

    He, Jian; Zhao, Congkuai; Liu, Weilin; Huang, Jia; Liang, Shengxiang; Chen, Lidian; Tao, Jing

    2018-02-01

    Electroacupuncture (EA) has been widely used to treat cognitive impairment following cerebral ischemia. However, the functional mechanisms of EA have not been fully elucidated. The aim of the present study was to investigate whether EA at the GV 20 and DU 24 acupoints can improve the learning and memory ability via alteration of the neurochemical metabolism in the hippocampus (HPC) and prefrontal cortex (PFC) of rats with ischemia and reperfusion (I/R) injury. Sprague‑Dawley male rats were randomly divided into three groups, namely the sham group (n=12), the middle cerebral artery occlusion (MCAO) group (n=12) and the EA treatment (MCAO + EA) group (n=12). MCAO was performed to establish the left focal cerebral I/R injury model, and the GV 20 and DU 24 acupoints were then stimulated with EA for 30 min per time, once daily, for 7 consecutive days. The Morris water maze (MWM) test was used to assess learning and memory ability. T2‑weighted imaging was used to assess the cerebral infarct volume. Magnetic resonance spectroscopy was used to assess neurochemical metabolism of HPC and PFC. The neurological scores of the MCAO + EA group were significantly reduced compared with those of the MCAO group 7 days after EA treatment (Pplatform area was significantly higher in the MCAO + EA group compared with that in the MCAO group (P0.05). The ratios of NAA/Cr, Cho/Cr and Glu/Cr of left‑to‑right PFC were elevated (Plearning and memory ability, possibly through increasing the levels of NAA and Cho in the HPC and PFC of rats with I/R injury.

  8. Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

    Science.gov (United States)

    Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.

    2013-01-01

    A current and major unanswered question is why the highly sensitive central CO2/H+ chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇E/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase–expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex. PMID:23869058

  9. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-02-07

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  10. Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts.

    Science.gov (United States)

    Pintelon, Isabel; Brouns, Inge; De Proost, Ian; Van Meir, Frans; Timmermans, Jean-Pierre; Adriaensen, Dirk

    2007-05-01

    Today, diagnosis and treatment of chest pain related to pathologic changes in the visceral pleura are often difficult. Data in the literature on the sensory innervation of the visceral pleura are sparse. The present study aimed at identifying sensory end-organs in the visceral pleura, and at obtaining more information about neurochemical coding. The immunocytochemcial data are mainly based on whole mounts of the visceral pleura of control and vagally denervated rats. It was shown that innervation of the rat visceral pleura is characterized by nerve bundles that enter in the hilus region and gradually split into slender bundles with a few nerve fibers. Separate nerve fibers regularly give rise to characteristic laminar terminals. Because of their unique association with the elastic fibers of the visceral pleura, we decided to refer to them as "visceral pleura receptors" (VPRs). Cryostat sections of rat lungs confirmed a predominant location on mediastinal and interlobar lung surfaces. VPRs can specifically be visualized by protein gene product 9.5 immunostaining, and were shown to express vesicular glutamate transporters, calbindin D28K, Na+/K+-ATPase, and P2X3 ATP-receptors. The sensory nerve fibers giving rise to VPRs appeared to be myelinated and to have a spinal origin. Because several of the investigated proteins have been reported as markers for sensory terminals in other organs, the present study revealed that VPRs display the neurochemical characteristics of mechanosensory and/or nociceptive terminals. The development of a live staining method, using AM1-43, showed that VPRs can be visualized in living tissue, offering an interesting model for future physiologic studies.

  11. Mercury exposure and neurochemical biomarkers in multiple brain regions of Wisconsin river otters (Lontra canadensis).

    Science.gov (United States)

    Dornbos, Peter; Strom, Sean; Basu, Niladri

    2013-04-01

    River otters are fish-eating wildlife that bioaccumulate high levels of mercury (Hg). Mercury is a proven neurotoxicant to mammalian wildlife, but little is known about the underlying, sub-clinical effects. Here, the overall goal was to increase understanding of Hg's neurological risk to otters. First, Hg values across several brain regions and tissues were characterized. Second, in three brain regions with known sensitivity to Hg (brainstem, cerebellum, and occipital cortex), potential associations among Hg levels and neurochemical biomarkers [N-methyl-D-aspartic acid (NMDA) and gamma-aminobutyric acid (GABAA) receptor] were explored. There were no significant differences in Hg levels across eight brain regions (rank order, highest to lowest: frontal cortex, cerebellum, temporal cortex, occipital cortex, parietal cortex, basal ganglia, brainstem, and thalamus), with mean values ranging from 0.7 to 1.3 ug/g dry weight. These brain levels were significantly lower than mean values in the muscle (2.1 ± 1.4 ug/g), liver (4.7 ± 4.3 ug/g), and fur (8.8 ± 4.8 ug/g). While a significant association was found between Hg and NMDA receptor levels in the brain stem (P = 0.028, rp = -0.293), no relationships were found in the cerebellum and occipital cortex. For the GABA receptor, no relationships were found. The lack of consistent Hg-associated neurochemical changes is likely due to low brain Hg levels in these river otters, which are amongst the lowest reported.

  12. The trace amine-associated receptor 1 modulates methamphetamine’s neurochemical and behavioural effects

    Directory of Open Access Journals (Sweden)

    Rachel eCotter

    2015-02-01

    Full Text Available The newly discovered trace amine-associated receptor 1 (TAAR1 has the ability to regulate both dopamine function and psychostimulant action. Here, we tested in rats the ability of RO5203648, a selective TAAR1 partial agonist, to modulate the physiological and behavioural effects of methamphetamine (METH. In experiment 1, RO5203468 dose- and time-dependently altered METH-induced locomotor activity, manifested as an early attenuation followed by a late potentiation of METH’s stimulating effects. In experiment 2, rats received a 14-day treatment regimen during which RO5203648 was co-administered with METH. RO5203648 dose-dependently attenuated METH-stimulated hyperactivity, with the effects becoming more apparent as the treatments progressed. After chronic exposure and 3-day withdrawal, rats were tested for locomotor sensitization. RO5203648 administration during the sensitizing phase prevented the development of METH sensitization. However, RO5203648, at the high dose, cross-sensitized with METH. In experiment 3, RO5203648 dose-dependently blocked METH self-administration without affecting operant responding maintained by sucrose, and exhibited lack of reinforcing efficacy when tested as a METH’s substitute. Neurochemical data showed that RO5203648 did not affect METH-mediated DA efflux and uptake inhibition in striatal synaptosomes. In vivo, however, RO5203648 was able to transiently inhibit METH-induced accumulation of extracellular DA levels in the nucleus accumbens. Taken together, these data highlight the significant potential of TAAR1 to modulate METH’s neurochemical and behavioural effects.

  13. An allosteric enhancer of M4 muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine

    Science.gov (United States)

    Dencker, Ditte; Weikop, Pia; Sørensen, Gunnar; Woldbye, David P. D.; Wörtwein, Gitta; Wess, Jürgen; Fink-Jensen, Anders

    2014-01-01

    Rationale The mesostriatal dopamine system plays a key role in mediating the reinforcing effects of psychostimulant drugs like cocaine. The muscarinic M4 acetylcholine receptor subtype is centrally involved in regulation of dopamine release in striatal areas. Consequently, striatal M4 receptors could be a novel target for modulating psychostimulant effects of cocaine. Objectives For the first time, we here addressed this issue by investigating the effects of a novel selective positive allosteric modulator of M4 receptors, VU0152100, on cocaine-induced behavioral and neurochemical effects in mice. Methods To investigate the effect of VU0152100 on the acute reinforcing effects of cocaine, we use an acute-cocaine self-administration model. We used in vivo microdialysis to investigate whether the effects of VU0152100 in the behavioral studies were mediated via effects on dopaminergic neurotransmission. In addition the effect of VU0152100 on cocaine-induced hyperactivity and rotarod performance was evaluated. Results We found that VU0152100 caused a prominent reduction in cocaine self-administration, cocaine-induced hyperlocomotion, and cocaine-induced striatal dopamine increase, without affecting motor performance. Consistent with these effects of VU0152100 being mediated via M4 receptors, its inhibitory effects on cocaine-induced increases in striatal dopamine were abolished in M4 receptor knockout mice. Furthermore, selective deletion of the M4 receptor gene in dopamine D1 receptor-expressing neurons resulted in a partial reduction of the VU0152100 effect, indicating that VU0152100 partly regulates dopaminergic neurotransmission via M4 receptors co-localized with D1 receptors. Conclusions These results show that positive allosteric modulators of the M4 receptor deserve attention as agents in the future treatment of cocaine abuse. PMID:22648127

  14. User perspectives on relevance criteria

    DEFF Research Database (Denmark)

    Maglaughlin, Kelly L.; Sonnenwald, Diane H.

    2002-01-01

    implications for relevance feedback in information retrieval systems, suggesting that systems accept and utilize multiple positive and negative relevance criteria from users. Systems designers may want to focus on supporting content criteria followed by full text criteria as these may provide the greatest cost...

  15. Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: a prospective cohort study.

    Science.gov (United States)

    Muhič, Neža; Mrhar, Ales; Brvar, Miran

    2017-07-01

    Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated. Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems. DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.

  16. Modelling Spatio-Temporal Relevancy in Urban Context-Aware Pervasive Systems Using Voronoi Continuous Range Query and Multi-Interval Algebra

    Directory of Open Access Journals (Sweden)

    Najmeh Neysani Samany

    2013-01-01

    Full Text Available Space and time are two dominant factors in context-aware pervasive systems which determine whether an entity is related to the moving user or not. This paper specifically addresses the use of spatio-temporal relations for detecting spatio-temporally relevant contexts to the user. The main contribution of this work is that the proposed model is sensitive to the velocity and direction of the user and applies customized Multi Interval Algebra (MIA with Voronoi Continuous Range Query (VCRQ to introduce spatio-temporally relevant contexts according to their arrangement in space. In this implementation the Spatio-Temporal Relevancy Model for Context-Aware Systems (STRMCAS helps the tourist to find his/her preferred areas that are spatio-temporally relevant. The experimental results in a scenario of tourist navigation are evaluated with respect to the accuracy of the model, performance time and satisfaction of users in 30 iterations of the algorithm. The evaluation process demonstrated the efficiency of the model in real-world applications.

  17. Antidepressant-like activity of the endogenous amine, 1-methyl-1,2,3,4-tetrahydroisoquinoline in the behavioral despair test in the rat, and its neurochemical correlates: a comparison with the classical antidepressant, imipramine.

    Science.gov (United States)

    Wąsik, Agnieszka; Możdżeń, Edyta; Romańska, Irena; Michaluk, Jerzy; Antkiewicz-Michaluk, Lucyna

    2013-01-30

    Disturbances in noradrenergic and serotonergic transmissions have been postulated to form neurochemical background of depression. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous substance which exhibits neuroprotective, antiaddictive and monoamine oxidase (MAO)-inhibiting properties. In the present study, we tested antidepressant-like effects of 1MeTIQ in comparison with the tricyclic antidepressant, imipramine in the forced swimming test in the rat. Additionally, in neurochemical studies, we estimated the rate of monoamine (dopamine, noradrenaline and serotonin) metabolism in the rat brain structures. The findings have shown that 1MeTIQ similarly to imipramine produced a dose-dependent antidepressant-like effect in the forced swimming test. The neurochemical data showed that 1MeTIQ produced a significant elevation of serotonin concentration in the brain structures with simultaneous reduction of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Moreover, 1MeTIQ slightly increased noradrenaline level but induced a significant elevation of its metabolite, 3-metoxy-4-hydroxyphenylglycol (MHPG). Furthermore, 1MeTIQ affected also dopamine metabolism, and decreased the level of 3,4-dihydroxyphenylacetic acid (DOPAC) with a simultaneous significant increase in the concentration of 3-methoxytyramine (3-MT) in all investigated structures. Such mechanism of action leads to a decrease in the production of free radicals during MAO-dependent dopamine oxidation in the brain. In conclusion, we suggest that antidepressant-like activity of 1MeTIQ is based on the unique and complex mechanism of action in which the activation of monoaminergic systems and scavenging of free radicals plays a crucial role. 1MeTIQ as an endogenous compound may be beneficial from the clinical point of view as a new safer and more efficient antidepressant. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Neurochemical features of endomorphin-2-containing neurons in the submucosal plexus of the rat colon.

    Science.gov (United States)

    Li, Jun-Ping; Zhang, Ting; Gao, Chang-Jun; Kou, Zhen-Zhen; Jiao, Xu-Wen; Zhang, Lian-Xiang; Wu, Zhen-Yu; He, Zhong-Yi; Li, Yun-Qing

    2015-09-14

    To investigate the distribution and neurochemical phenotype of endomorphin-2 (EM-2)-containing neurons in the submucosal plexus of the rat colon. The mid-colons between the right and left flexures were removed from rats, and transferred into Kreb's solution. For whole-mount preparations, the mucosal, outer longitudinal muscle and inner circular muscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole-mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides, and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT), nitric oxide synthetase (NOS), neuron-specific enolase (NSE), substance P (SP) and vasoactive intestinal peptide (VIP). After staining, all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP, ChAT, NOS, NSE, SP and VIP, ganglia, which have a clear boundary and neuronal cell outline, were randomly selected from each specimen for this analysis. In the submucosal plexus of the mid-colon, many EM-2-immunoreactive (IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 ± 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2-IR neurons were also immunopositive for ChAT, SP, VIP or NOS. EM-2-IR nerve fibers coursed near ChAT-IR neurons, and some of these fibers were even distributed around ChAT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers, but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons that were also positive for

  19. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD.

  20. Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

    Science.gov (United States)

    Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

    2016-06-01

    The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

  1. Current systematic carbon-cycle observations and the need for implementing a policy-relevant carbon observing system

    Science.gov (United States)

    P. Ciais; A. J. Dolman; A. Bombelli; R. Duren; A. Peregon; P. J. Rayner; C. Miller; N. Gobron; G. Kinderman; G. Marland; N. Gruber; F. Chevallier; R. J. Andres; G. Balsamo; L. Bopp; F.-M. Bréon; G. Broquet; R. Dargaville; T. J. Battin; A. Borges; H. Bovensmann; M. Buchwitz; J. Butler; J. G. Canadell; R. B. Cook; R. DeFries; R. Engelen; K. R. Gurney; C. Heinze; M. Heimann; A. Held; M. Henry; B. Law; S. Luyssaert; J. Miller; T. Moriyama; C. Moulin; R. B. Myneni; C. Nussli; M. Obersteiner; D. Ojima; Y. Pan; J.-D. Paris; S. L. Piao; B. Poulter; S. Plummer; S. Quegan; P. Raymond; M. Reichstein; L. Rivier; C. Sabine; D. Schimel; O. Tarasova; R. Valentini; R. Wang; G. van der Werf; D. Wickland; M. Williams; C. Zehner

    2014-01-01

    A globally integrated carbon observation and analysis system is needed to improve the fundamental understanding of the global carbon cycle, to improve our ability to project future changes, and to verify the effectiveness of policies aiming to reduce greenhouse gas emissions and increase carbon sequestration. Building an integrated carbon observation system requires...

  2. Genetic or pharmacological blockade of noradrenaline synthesis enhances the neurochemical, behavioural, and neurotoxic effects of methamphetamine

    Science.gov (United States)

    Weinshenker, David; Ferrucci, Michela; Busceti, Carla L.; Biagioni, Francesca; Lazzeri, Gloria; Liles, L. Cameron; Lenzi, Paola; Murri, Luigi; Paparelli, Antonio; Fornai, Francesco

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the locus coeruleus (LC), the major brain noradrenergic nucleus, exacerbate the damage to nigrostriatal dopamine (DA) terminals caused by the psychostimulant methamphetamine (METH). However, because noradrenergic terminals contain other neuromodulators and the noradrenaline (NA) transporter, which may act as a neuroprotective buffer, it was unclear whether this enhancement of METH neurotoxicity was caused by the loss of noradrenergic innervation or the loss of NA itself. We addressed the specific role of NA by comparing the effects of METH in mice with noradrenergic lesions (DSP-4) and those with intact noradrenergic terminals but specifically lacking NA (genetic or acute pharmacological blockade of the NA biosynthetic enzyme dopamine β-hydroxylase; DBH). We found that genetic deletion of DBH (DBH −/− mice) and acute treatment of wild-type mice with a DBH inhibitor (fusaric acid) recapitulated the effects of DSP-4 lesions on METH responses. All three methods of NA depletion enhanced striatal DA release, extracellular oxidative stress (as measured by in vivo microdialysis of DA and 2,3-dihydroxybenzoic acid), and behavioural stereotypies following repeated METH administration. These effects accompanied a worsening of the striatal DA neuron terminal damage and ultrastructural changes to medium spiny neurons. We conclude that NA itself is neuroprotective and plays a fundamental role in the sensitivity of striatal DA terminals to the neurochemical, behavioural, and neurotoxic effects of METH. PMID:18042179

  3. Genetic or pharmacological blockade of noradrenaline synthesis enhances the neurochemical, behavioral, and neurotoxic effects of methamphetamine.

    Science.gov (United States)

    Weinshenker, David; Ferrucci, Michela; Busceti, Carla L; Biagioni, Francesca; Lazzeri, Gloria; Liles, L Cameron; Lenzi, Paola; Pasquali, Livia; Murri, Luigi; Paparelli, Antonio; Fornai, Francesco

    2008-04-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the locus coeruleus, the major brain noradrenergic nucleus, exacerbate the damage to nigrostriatal dopamine (DA) terminals caused by the psychostimulant methamphetamine (METH). However, because noradrenergic terminals contain other neuromodulators and the noradrenaline (NA) transporter, which may act as a neuroprotective buffer, it was unclear whether this enhancement of METH neurotoxicity was caused by the loss of noradrenergic innervation or the loss of NA itself. We addressed the specific role of NA by comparing the effects of METH in mice with noradrenergic lesions (DSP-4) and those with intact noradrenergic terminals but specifically lacking NA (genetic or acute pharmacological blockade of the NA biosynthetic enzyme dopamine beta-hydroxylase; DBH). We found that genetic deletion of DBH (DBH-/- mice) and acute treatment of wild-type mice with a DBH inhibitor (fusaric acid) recapitulated the effects of DSP-4 lesions on METH responses. All three methods of NA depletion enhanced striatal DA release, extracellular oxidative stress (as measured by in vivo microdialysis of DA and 2,3-dihydroxybenzoic acid), and behavioral stereotypies following repeated METH administration. These effects accompanied a worsening of the striatal DA neuron terminal damage and ultrastructural changes to medium spiny neurons. We conclude that NA itself is neuroprotective and plays a fundamental role in the sensitivity of striatal DA terminals to the neurochemical, behavioral, and neurotoxic effects of METH.

  4. Tris(2-chloroethyl)phosphate increases ambulatory activity in mice: pharmacological analyses of its neurochemical mechanism.

    Science.gov (United States)

    Umezu, T; Yonemoto, J; Soma, Y; Suzuki, T

    1998-01-01

    The present study was conducted to clarify the acute effect of tris(2-chloroethyl)phosphate (TRCP), an organophosphate flame-retardant, on spontaneous ambulatory activity (AA) in male ICR mice and to examine the neurochemical mechanism of this effect. Single dose administration of 200 mg/kg i.p. of TRCP increased AA in ICR mice. Neither the nicotinic cholinergic antagonist mecamylamine (MA) nor the muscarinic cholinergic antagonist scopolamine (SCP) affected the AA response to TRCP. On the other hand, the benzodiazepine agonist diazepam (DZ), the GABAA agonist muscimol (MUS) and the GABAB agonist baclofen (BAC) all attenuated the effect of TRCP. DZ and MUS blocked the increase of AA within the first 10 min after administration of TRCP. These drugs did not attenuate the AA-increasing effect of SCP, suggesting that the mechanism of TRCP action is distinct from that of SCP. MUS and BAC did, but DZ did not, inhibit the AA increasing effect of the dopaminergic agonist apomorphine (APO), suggesting that dopamine is involved in the control of AA, and that GABA can affect AA through interaction with dopaminergic neurons. These results suggest that TRCP acts as a GABA antagonist and not as a cholinergic agonist, and that TRCP increases AA in ICR mice through a GABAergic mechanism.

  5. Mercury exposure and neurochemical impacts in bald eagles across several Great Lakes states.

    Science.gov (United States)

    Rutkiewicz, Jennifer; Nam, Dong-Ha; Cooley, Thomas; Neumann, Kay; Padilla, Irene Bueno; Route, William; Strom, Sean; Basu, Niladri

    2011-10-01

    In this study, we assessed mercury (Hg) exposure in several tissues (brain, liver, and breast and primary feathers) in bald eagles (Haliaeetus leucocephalus) collected from across five Great Lakes states (Iowa, Michigan, Minnesota, Ohio, and Wisconsin) between 2002-2010, and assessed relationships between brain Hg and neurochemical receptors (NMDA and GABA(A)) and enzymes (glutamine synthetase (GS) and glutamic acid decarboxylase (GAD)). Brain total Hg (THg) levels (dry weight basis) averaged 2.80 μg/g (range: 0.2-34.01), and levels were highest in Michigan birds. THg levels in liver (r(p) = 0.805) and breast feathers (r(p) = 0.611) significantly correlated with those in brain. Brain Hg was not associated with binding to the GABA(A) receptor. Brain THg and inorganic Hg (IHg) were significantly positively correlated with GS activity (THg r(p) = 0.190; IHg r(p) = 0.188) and negatively correlated with NMDA receptor levels (THg r(p) = -0245; IHg r(p) = -0.282), and IHg was negatively correlated with GAD activity (r(s) = -0.196). We also report upon Hg demethylation and relationships between Hg and Se in brain and liver. These results suggest that bald eagles in the Great Lakes region are exposed to Hg at levels capable of causing subclinical neurological damage, and that when tissue burdens are related to proposed avian thresholds approximately 14-27% of eagles studied here may be at risk.

  6. Neurochemical imaging of Alzheimer`s disease and other degenerative dementias

    Energy Technology Data Exchange (ETDEWEB)

    Frey, K.A.; Minoshima, S.; Kuhl, D.E. [Ann Arbor, Univ. of Michigan, MI (United States). Dept. of Internal Medicine. Division of Nuclear Medicine

    1998-09-01

    A wide variety of neurochemical and functional imaging approaches have been applied to the study of progressive dementias, particularly Alzheimer`s disease (Ad) and related disorders. Despite considerable progress in the past decade, the cause(s) of most cases of Ad remain undetermined and preventive or protective therapies are lacking. Specifically-designed imaging procedures have permitted the testing of pathophysiological hypotheses of the etiology and progression of Ad, and have yielded important insights in several areas including the potential roles of cerebral cortical cholinergic lesions, cellular inflammation, and losses of cortical synapses. From the perspective of clinical diagnosis, PET glucose metabolism imaging with use of ({sup 18}F)2-fluorodeoxyglucose (FDG) is the most sensitive and specific imaging modality yet identified. The overall performance of PET FDG is favorable for routine clinical evaluation of suspected Ad, and will likely gain increasing utilization in the near future. Assessments of glucose metabolism and other, specific aspects of neurochemistry in Ad will provide direct measures of therapeutic drug actions and may permit distinction of symptomatic versus disease-modifying therapies as they are developed and introduced in clinical trials.

  7. Curcumin ameliorates reserpine-induced pain-depression dyad: behavioural, biochemical, neurochemical and molecular evidences.

    Science.gov (United States)

    Arora, V; Kuhad, A; Tiwari, V; Chopra, K

    2011-11-01

    An apparent clinical relationship between pain and depression has long been recognized. Depression and pain are often diagnosed in the same patients. The emerging concept for pain-depression pathogenesis is the dysfunction of biogenic amine-mediated pain-depression control and the possible involvement of nitrodative stress-induced neurogenic inflammation. The present study was designed to investigate the effect of curcumin on reserpine-induced pain-depression dyad in rats. Administration of reserpine (1mg/kg subcutaneous daily for three consecutive days) led to a significant decrease in nociceptive threshold as evident from reduced paw withdrawal threshold in Randall Sellitto and von-Frey hair test as well as significant increase in immobility time in forced swim test. This behavioural deficit was integrated with decrease in the biogenic amine (dopamine, norepinephrine and serotonin) levels along with increased substance P concentration, nitrodative stress, inflammatory cytokines, NF-κβ and caspase-3 levels in different brain regions (cortex and hippocampus) of the reserpinised rats. Curcumin (100, 200, 300mg/kg; ip) dose dependently ameliorated the behavioural deficits associated with pain and depression by restoring behavioural, biochemical, neurochemical and molecular alterations against reserpine-induced pain-depression dyad in rats. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral anophthalmia.

    Science.gov (United States)

    Coullon, Gaelle S L; Emir, Uzay E; Fine, Ione; Watkins, Kate E; Bridge, Holly

    2015-09-01

    Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, (1)H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests that the lack of visual input from the eyes might have delayed or arrested the maturation of this cortical region. High levels of choline and glutamate/glutamine are consistent with enhanced excitatory circuits in the anophthalmic occipital cortex, which could reflect a shift toward enhanced plasticity or sensitivity that could in turn mediate or unmask cross-modal responses. Finally, it is possible that the change in function of the occipital cortex results in biochemical profiles that resemble those of auditory, language, or somatosensory cortex. Copyright © 2015 the American Physiological Society.

  9. Matching Office Information Systems (OIS Curriculum To Relevant Standards: Students, School Mission, Regional Business Needs, and National Curriculum

    Directory of Open Access Journals (Sweden)

    Arlene August

    1998-01-01

    Full Text Available This paper examines the process and outcome of a major curriculum update for the Office Information Systems (OIS major in the Office Information Systems Department in the School of Computer Science and Information Systems (CSIS at Pace University. The curriculum was updated to better prepare our students for success as end-user specialists in today’s flattened organizations. The changes made were based on modules recommended from the Office Systems Research Association (OSRA--recommendations that were both reliable and valid. OSRA’s national curriculum was flexible enough to allow us to incorporate regional business demands as well as adhere to CSIS’s mission statement. The success of this curriculum, now two years old, is measured by the success of our graduates (B.Sc. degree in obtaining meaningful employment.

  10. A systematic review of the role of the nociceptin receptor system in stress, cognition, and reward: relevance to schizophrenia.

    Science.gov (United States)

    Khan, Muhammad Saad; Boileau, Isabelle; Kolla, Nathan; Mizrahi, Romina

    2018-02-02

    Schizophrenia is a debilitating neuropsychiatric illness that is characterized by positive, negative, and cognitive symptoms. Research over the past two decades suggests that the nociceptin receptor system may be involved in domains affected in schizophrenia, based on evidence aligning it with hallmark features of the disorder. First, aberrant glutamatergic and striatal dopaminergic function are associated with psychotic symptoms, and the nociceptin receptor system has been shown to regulate dopamine and glutamate transmission. Second, stress is a critical risk factor for first break and relapse in schizophrenia, and evidence suggests that the nociceptin receptor system is also directly involved in stress modulation. Third, cognitive deficits are prevalent in schizophrenia, and the nociceptin receptor system has significant impact on learning and working memory. Last, reward processing is disrupted in schizophrenia, and nociceptin signaling has been shown to regulate reward cue salience. These findings provide the foundation for the involvement of the nociceptin receptor system in the pathophysiology of schizophrenia and outline the need for future research into this system.

  11. The main but not the accessory olfactory system is involved in the processing of socially relevant chemosignals in ungulates.

    Directory of Open Access Journals (Sweden)

    Matthieu eKELLER

    2012-09-01

    Full Text Available Ungulates like sheep and goats have, like many other mammalian species, two complementary olfactory systems. The relative role played by these two systems has long been of interest regarding the sensory control of social behavior. The study of ungulate social behavior could represent a complimentary alternative to rodent studies because they live in a more natural environment and their social behaviors depend heavily on olfaction. In addition, the relative size of the main olfactory bulb (in comparison to the accessory olfactory bulb is more developped than in many other lissencephalic species like rodents. In this review, we present data showing a clear involvement of the main olfactory system in two well-characterized social situations under olfactory control in ungulates, namely maternal behavior and offspring recognition at birth and the reactivation of the gonadotropic axis of females exposed to males during the anestrous season. In conclusion, we discuss the apparent discrepancy between the absence of evidence for a role of the vomeronasal system in ungulate social behavior and the existence of a developed accessory olfactory system in these species.

  12. Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

    Directory of Open Access Journals (Sweden)

    Cecilia Csölle

    Full Text Available Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7 results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/- displayed decreased immobility in the tail suspension test (TST and an attenuated anhedonia response in the sucrose preference test (SPT following bacterial endotoxin (LPS challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [(3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5. An increased 5-bromo-2-deoxyuridine (BrdU incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [(3H]5-HT and an elevated number of [(3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus.

  13. Jugular venous overflow of noradrenaline from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans

    Science.gov (United States)

    Mitchell, David A; Lambert, Gavin; Secher, Niels H; Raven, Peter B; van Lieshout, Johannes; Esler, Murray D

    2009-01-01

    A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A database was assembled of fifty-six healthy subjects in whom total body noradrenaline spillover (indicative of whole body sympathetic nervous activity), brain noradrenaline spillover and brain lipophlic noradrenaline metabolite (3,4-dihydroxyphenolglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG)) overflow rates were measured. These measurements were also made following ganglion blockade (trimethaphan, n= 6), central sympathetic inhibition (clonidine, n= 4) and neuronal noradrenaline uptake blockade (desipramine, n= 13) and in a group of patients (n= 9) with pure autonomic failure (PAF). The mean brain noradrenline spillover and brain noradrenaline metabolite overflow in healthy subjects were 12.5 ± 1.8, and 186.4 ± 25 ng min−1, respectively, with unilateral jugular venous sampling for both. Total body noradrenaline spillover was 605.8 ng min−1± 34.4 ng min−1. As expected, trimethaphan infusion lowered brain noradrenaline spillover (P= 0.03), but perhaps surprisingly increased jugular overflow of brain metabolites (P= 0.01). Suppression of sympathetic nervous outflow with clonidine lowered brain noradrenaline spillover (P= 0.004), without changing brain metabolite overflow (P= 0.3). Neuronal noradrenaline uptake block with desipramine lowered the transcranial plasma extraction of tritiated noradrenaline (P= 0.001). The PAF patients had 77% lower brain noradrenaline spillover than healthy recruits (P= 0.06), indicating that in them sympathetic nerve degeneration extended to the cerebral circulation, but metabolites overflow was similar to healthy subjects (P= 0.3). The invariable discordance between noradrenline spillover and noradrenaline metabolite overflow

  14. Policy Analysis: The Effect of the New Scheduling System on Student Trips to Campus and Other Relevant Variables.

    Science.gov (United States)

    Murphy, Michael T.; And Others

    A study was conducted to assess the effects of a new class scheduling system at Harford Community College (HCC), which substituted 75-minute classes twice a week and 150-minute classes once a week for regular three 50-minute classes in order to save energy by reducing student travel to college. The study sought to determine the effects of these…

  15. Doctor-patient communication in different European health care systems: relevance and performance from the patients' perspective.

    NARCIS (Netherlands)

    Brink-Muinen, A. van den; Verhaak, P.F.M.; Bensing, J.M.; Bahrs, O.; Deveugele, M.; Gask, L.; Leiva, F.; Mead, N.; Messerli, V.; Oppizzi, L.; Peltenburg, M.; Perez, A.

    2000-01-01

    Our aim is to investigate differences between European health care systems in the importance attached by patients to different aspects of doctor-patient communication and the GPs' performance of these aspects, both being from the patients' perspective. 3658 patients of 190 GPs in six European

  16. Relevance of warm conveyor belts for the dynamics of weather systems and the radiation budget in the extra-tropics

    Science.gov (United States)

    Joos, Hanna

    2014-05-01

    PV. In the second part, the relevance of WCBs for the liquid and ice water path as well as the cloud radiative forcing is presented. An existing WCB climatology which is based on the ERA-Interim dataset is used in order to calculate the liquid and ice water path as well as the short and longwave cloud forcing which are associated with WCBs. The results show that in the storm track regions a considerable amount of the condensate and cloud forcing is related to WCBs.

  17. Identifying and characterising health policy and system-relevant documents in Uganda: a scoping review to develop a framework for the development of a one-stop shop.

    Science.gov (United States)

    Mutatina, Boniface; Basaza, Robert; Obuku, Ekwaro; Lavis, John N; Sewankambo, Nelson

    2017-02-06

    Health policymakers in low- and middle-income countries continue to face difficulties in accessing and using research evidence for decision-making. This study aimed to identify and provide a refined categorisation of the policy documents necessary for building the content of a one-stop shop for documents relevant to health policy and systems in Uganda. The on-line resource is to facilitate timely access to well-packaged evidence for decision-making. We conducted a scoping review of Uganda-specific, health policy, and systems-relevant documents produced between 2000 and 2014. Our methods borrowed heavily from the 2005 Arksey and O'Malley approach for scoping reviews and involved five steps, which that include identification of the research question; identification of relevant documents; screening and selection of the documents; charting of the data; and collating, summarising and reporting results. We searched for the documents from websites of relevant government institutions, non-governmental organisations, health professional councils and associations, religious medical bureaus and research networks. We presented the review findings as numerical analyses of the volume and nature of documents and trends over time in the form of tables and charts. We identified a total of 265 documents including policies, strategies, plans, guidelines, rapid response summaries, evidence briefs for policy, and dialogue reports. The top three clusters of national priority areas addressed in the documents were governance, coordination, monitoring and evaluation (28%); disease prevention, mitigation, and control (23%); and health education, promotion, environmental health and nutrition (15%). The least addressed were curative, palliative care, rehabilitative services and health infrastructure, each addressed in three documents (1%), and early childhood development in one document. The volume of documents increased over the past 15 years; however, the distribution of the different

  18. Rapid assessment of infrastructure of primary health care facilities - a relevant instrument for health care systems management.

    Science.gov (United States)

    Scholz, Stefan; Ngoli, Baltazar; Flessa, Steffen

    2015-05-01

    Health care infrastructure constitutes a major component of the structural quality of a health system. Infrastructural deficiencies of health services are reported in literature and research. A number of instruments exist for the assessment of infrastructure. However, no easy-to-use instruments to assess health facility infrastructure in developing countries are available. Present tools are not applicable for a rapid assessment by health facility staff. Therefore, health information systems lack data on facility infrastructure. A rapid assessment tool for the infrastructure of primary health care facilities was developed by the authors and pilot-tested in Tanzania. The tool measures the quality of all infrastructural components comprehensively and with high standardization. Ratings use a 2-1-0 scheme which is frequently used in Tanzanian health care services. Infrastructural indicators and indices are obtained from the assessment and serve for reporting and tracing of interventions. The tool was pilot-tested in Tanga Region (Tanzania). The pilot test covered seven primary care facilities in the range between dispensary and district hospital. The assessment encompassed the facilities as entities as well as 42 facility buildings and 80 pieces of technical medical equipment. A full assessment of facility infrastructure was undertaken by health care professionals while the rapid assessment was performed by facility staff. Serious infrastructural deficiencies were revealed. The rapid assessment tool proved a reliable instrument of routine data collection by health facility staff. The authors recommend integrating the rapid assessment tool in the health information systems of developing countries. Health authorities in a decentralized health system are thus enabled to detect infrastructural deficiencies and trace the effects of interventions. The tool can lay the data foundation for district facility infrastructure management.

  19. Assessment of a combined gas chromatography mass spectrometer sensor (GC-MSS) system for detecting biologically relevant volatile compounds (VCs).

    Science.gov (United States)

    Gould, Oliver; Wieczorek, Tomas; de Lacy Costello, Ben P J; Persad, Raj; Ratcliffe, Norman

    2017-09-26

    There have been a number of studies in which metal oxide sensors (MOS) have replaced conventional analytical detectors in gas chromatography systems. However, despite the use of these instruments in a range of applications including breath research the sensor responses (i.e. resistance changes w.r.t. concentration of VCs) remain largely unreported. This paper addresses that issue by comparing the response of a metal oxide sensor directly with a mass spectrometer (MS), whereby both detectors are interfaced to the same GC column using an s-swafer. It was demonstrated that the sensitivity of an in-house fabricated ZnO/ SnO2 thick film MOS was superior to a modern MS for the detection of a wide range of volatile compounds (VCs) of different functionalities and masses. Better techniques for detection and quantification of these VCs is valuable, as many of these compounds are commonly reported throughout the scientific literature. This is also the first published report of a combined GC-MS sensor system. These 2 different detector technologies when combined, should enhance discriminatory abilities to aid disease diagnoses using volatiles from e.g. breath, and bodily fluids. 29 chemical standards have been tested using solid phase micro-extraction; 25 of these compounds are found on human breath. In all but 2 instances the sensor exhibited the same or superior limit of detection compared to the MS. 12 stool samples from healthy participants were analysed, the sensor detected, on average 1.6 peaks more per sample than the MS. Similarly analysing the headspace of E. coli broth cultures the sensor detected 6.9 more peaks per sample versus the MS. This greater sensitivity is primarily a function of the superior limits of detection of the metal oxide sensor. This shows that systems based on the combination of chromatography systems with solid state sensors shows promise for a range of applications. © 2017 IOP Publishing Ltd.

  20. New insights into atmospherically relevant reaction systems using direct analysis in real-time mass spectrometry (DART-MS)

    Science.gov (United States)

    Zhao, Yue; Fairhurst, Michelle C.; Wingen, Lisa M.; Perraud, Véronique; Ezell, Michael J.; Finlayson-Pitts, Barbara J.

    2017-04-01

    The application of direct analysis in real-time mass spectrometry (DART-MS), which is finding increasing use in atmospheric chemistry, to two different laboratory model systems for airborne particles is investigated: (1) submicron C3-C7 dicarboxylic acid (diacid) particles reacted with gas-phase trimethylamine (TMA) or butylamine (BA) and (2) secondary organic aerosol (SOA) particles from the ozonolysis of α-cedrene. The diacid particles exhibit a clear odd-even pattern in their chemical reactivity toward TMA and BA, with the odd-carbon diacid particles being substantially more reactive than even ones. The ratio of base to diacid in reacted particles, determined using known diacid-base mixtures, was compared to that measured by high-resolution time-of-flight aerosol mass spectrometry (HR-ToF-AMS), which vaporizes the whole particle. Results show that DART-MS probes ˜ 30 nm of the surface layer, consistent with other studies on different systems. For α-cedrene SOA particles, it is shown that varying the temperature of the particle stream as it enters the DART-MS ionization region can distinguish between specific components with the same molecular mass but different vapor pressures. These results demonstrate the utility of DART-MS for (1) examining reactivity of heterogeneous model systems for atmospheric particles and (2) probing components of SOA particles based on volatility.

  1. A Clinical Decision Support System for Chronic Pain Management in Primary Care: Usability testing and its relevance

    Directory of Open Access Journals (Sweden)

    Kalpana Maria Nair

    2015-08-01

    Full Text Available Background Clinical decision support systems (CDSSs that are integrated into electronic medical records may be useful for encouraging practice change compliant with clinical practice guidelines.Objective To engage end users to inform early phase CDSS development through a process of usability testing.Method A sequential exploratory mixed method approach was used. Interprofessional clinician participants (seven in iteration 1 and six in iteration 2 were asked to ‘think aloud’ while performing various tasks on the CDSS and then complete the System Usability Scale (SUS. Changes were made to the CDSS after each iteration.Results Barriers and facilitators were identified: systemic; user interface (most numerous barriers; content (most numerous facilitators and technical. The mean SUS score was 81.1 (SD = 12.02 in iteration 1 and 70.40 (SD = 6.78 in iteration 2 (p > 0.05.Conclusions Qualitative data from usability testing were valuable in the CDSS development process. SUS scores were of limited value at this development stage. 

  2. Photonic Integrated Circuit (PIC) Device Structures: Background, Fabrication Ecosystem, Relevance to Space Systems Applications, and Discussion of Related Radiation Effects

    Science.gov (United States)

    Alt, Shannon

    2016-01-01

    Electronic integrated circuits are considered one of the most significant technological advances of the 20th century, with demonstrated impact in their ability to incorporate successively higher numbers transistors and construct electronic devices onto a single CMOS chip. Photonic integrated circuits (PICs) exist as the optical analog to integrated circuits; however, in place of transistors, PICs consist of numerous scaled optical components, including such "building-block" structures as waveguides, MMIs, lasers, and optical ring resonators. The ability to construct electronic and photonic components on a single microsystems platform offers transformative potential for the development of technologies in fields including communications, biomedical device development, autonomous navigation, and chemical and atmospheric sensing. Developing on-chip systems that provide new avenues for integration and replacement of bulk optical and electro-optic components also reduces size, weight, power and cost (SWaP-C) limitations, which are important in the selection of instrumentation for specific flight projects. The number of applications currently emerging for complex photonics systems-particularly in data communications-warrants additional investigations when considering reliability for space systems development. This Body of Knowledge document seeks to provide an overview of existing integrated photonics architectures; the current state of design, development, and fabrication ecosystems in the United States and Europe; and potential space applications, with emphasis given to associated radiation effects and reliability.

  3. Joint project. Retention of radionuclides relevant for final disposal in natural clay rock and saline systems. Subproject 2. Geochemical behavior and transport of radionuclides in saline systems in the presence of repository-relevant organics. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Schmeide, Katja; Fritsch, Katharina; Lippold, Holger [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Inst. of Ressource Ecology; and others

    2016-08-01

    The objective of this project was to study the influence of increased salinities on interaction processes in the system radionuclide - organics - clay - aquifer. For this purpose, complexation, redox, sorption, and diffusion studies were performed under variation of the ionic strength (up to 4 mol kg{sup -1}) and the background electrolyte. The U(VI) complexation by propionate was studied in dependence on ionic strength (up to 4 mol kg{sup -1} NaClO{sub 4}) by TRLFS, ATR FT-IR spectroscopy, and DFT calculations. An influence of ionic strength on stability constants was detected, depending on the charge of the respective complexes. The conditional stability constants, determined for 1:1, 1:2, and 1:3 complexes at specific ionic strengths, were extrapolated to zero ionic strength. The interaction of the bacteria Sporomusa sp. MT-2.99 and Paenibacillus sp. MT-2.2 cells, isolated from Opalinus Clay, with Pu was studied. The experiments can be divided into such without an electron donor where biosorption is favored and such with addition of Na-pyruvate as an electron donor stimulating also bioreduction processes. Moreover, experiments were performed to study the interactions of the halophilic archaeon Halobacterium noricense DSM-15987 with U(VI), Eu(III), and Cm(III) in 3 M NaCl solutions. Research for improving process understanding with respect to the mobility of multivalent metals in systems containing humic matter was focused on the reversibility of elementary processes and on their interaction. Kinetic stabilization processes in the dynamics of humate complexation equilibria were quantified in isotope exchange studies. The influence of high salinity on the mobilizing potential of humic-like clay organics was systematically investigated and was described by modeling. The sorption of Tc(VII)/Tc(IV) onto the iron(II)-containing minerals magnetite and siderite was studied by means of batch sorption experiments, ATR FT-IR and X-ray absorption spectroscopy. The strong Tc

  4. Peptidergic nerve fibers in the urethra: Morphological and neurochemical characteristics in female mice of reproductive age.

    Science.gov (United States)

    Barry, Christine M; Ji, Esther; Sharma, Harman; Yap, Pauline; Spencer, Nicholas J; Matusica, Dusan; Haberberger, Rainer V

    2017-10-20

    Peptidergic nerve fibers provide important contributions to urethral function. Urethral innervation of female mice is not well documented. To determine the distribution and projection sites of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the urethra of wild-type control mice and compare innervation characteristics between the proximal and distal urethra of young nullipara and older multipara mice. Furthermore, to identify the location and neurochemical coding of the spinal afferent nerve endings in the urethra, whose sensory neurons reside in lumbosacral dorsal root ganglia (DRG). Multiple labeling immunohistochemistry of urethral sections of nulliparous (6-8 weeks old), and multiparous (9-12 months old) mice, and anterograde axonal tracing from L5-S2 (DRG) in vivo. Abundant VIP-, CGRP-, SP-, and NPY-immunoreactive nerve fibers were identified in the adventitia, muscularis, and lamina propria of proximal and distal segments of the urethra. A proportion of fibers were closely associated with blood vessels, glands, and cells immunoreactive for PGP9.5. The epithelium contained abundant nerve fibers immunoreactive for CGRP and/or SP. Epithelial innervation was increased in the distal urethra of multipara mice. Abundant fibers were traced from L5-S2 DRG to all urethral regions. We present the first identification of spinal afferent endings in the urethra. Peptidergic nerve fibers, including multiple populations of spinal afferents, provide rich innervation of the female mouse urethra. The morphology of fibers in the epithelium and other regions suggests multiple nerve-cell interactions impacting on urethral function. © 2017 Wiley Periodicals, Inc.

  5. Morphological and neurochemical differences in peptidergic nerve fibers of the mouse vagina.

    Science.gov (United States)

    Barry, Christine M; Ji, Esther; Sharma, Harman; Beukes, Lara; Vilimas, Patricia I; DeGraaf, Yvette C; Matusica, Dusan; Haberberger, Rainer V

    2017-07-01

    The vagina is innervated by a complex arrangement of sensory, sympathetic, and parasympathetic nerve fibers that contain classical transmitters plus an array of neuropeptides and enzymes known to regulate diverse processes including blood flow and nociception. The neurochemical characteristics and distributions of peptide-containing nerves in the mouse vagina are unknown. This study used multiple labeling immunohistochemistry, confocal maging and analysis to investigate the presence and colocalization of the peptides vasoactive intestinal polypeptide (VIP), calcitonin-gene related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and the nitric oxide synthesizing enzyme neuronal nitric oxide synthase (nNOS) in nerve fibers of the murine vaginal wall. We compared cervical and vulvar areas of the vagina in young nullipara and older multipara C57Bl/6 mice, and identified differences including that small ganglia were restricted to cervical segments, epithelial fibers were mainly present in vulvar segments and most nerve fibers were found in the lamina propria of the cervical region of the vagina, where a higher number of fibers containing immunoreactivity for VIP, CGRP, SP, or nNOS were found. Two populations of VIP-containing fibers were identified: fibers containing CGRP and fibers containing VIP but not CGRP. Differences between young and older mice were present in multiple layers of the vaginal wall, with older mice showing overall loss of innervation of epithelium of the proximal vagina and reduced proportions of VIP, CGRP, and SP containing nerve fibers in the distal epithelium. The distal vagina also showed increased vascularization and perivascular fibers containing NPY. Immunolabeling of ganglia associated with the vagina indicated the likely origin of some peptidergic fibers. Our results reveal regional differences and age- or parity-related changes in innervation of the mouse vagina, effecting the distribution of neuropeptides with diverse roles

  6. Neurochemically defined cell columns in the nucleus prepositus hypoglossi of the cat and monkey.

    Science.gov (United States)

    Baizer, Joan S; Baker, James F

    2006-06-13

    Many studies have shown that the nucleus prepositus hypoglossi (PH) participates with the vestibular nuclear complex, the cerebellum and the oculomotor nuclei in the control of eye movements. We have looked at the neurochemical organization of PH in the cat and monkey using a recently developed antibody, 8B3, that recognizes a chondroitin sulfate proteoglycan. In the cat, immunoreactivity to 8B3 labels a set of cells in PH. On frontal sections, these cells form a cluster that is seen over the entire anterior-posterior (A-P) extent of PH, but the number of cells in the cluster changes with A-P level. Earlier studies have identified an A-P cell column in PH of the cat whose neurons synthesize nitric oxide. We have used both single- and double-label protocols to investigate the relation between the two cell groups. Single-label studies show spatial overlap but that the cells immunoreactive to nitric oxide synthase (nNOS) are more numerous than cells immunoreactive to 8B3. Double-label studies show that all cells immunoreactive to 8B3 were also immunoreactive to nNOS, but, as suggested by the single-label data, there are many nNOS-immunoreactive cells not immunoreactive to 8B3. Populations of 8B3 and nNOS-immunoreactive cells are also found in PH of squirrel and macaque monkeys. The results suggest that nNOS-immunoreactive cells in PH may consist of two functionally different populations.

  7. Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.

    LENUS (Irish Health Repository)

    Hampel, H

    2012-02-01

    In the earliest clinical stages of Alzheimer\\'s Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.

  8. NMR-Based Metabolic Profiling Reveals Neurochemical Alterations in the Brain of Rats Treated with Sorafenib.

    Science.gov (United States)

    Du, Changman; Shao, Xue; Zhu, Ruiming; Li, Yan; Zhao, Qian; Fu, Dengqi; Gu, Hui; Kong, Jueying; Luo, Li; Long, Hailei; Deng, Pengchi; Wang, Huijuan; Hu, Chunyan; Zhao, Yinglan; Cen, Xiaobo

    2015-11-01

    Sorafenib, an active multi-kinase inhibitor, has been widely used as a chemotherapy drug to treat advanced clear-cell renal cell carcinoma patients. In spite of the relative safety, sorafenib has been shown to exert a negative impact on cognitive functioning in cancer patients, specifically on learning and memory; however, the underlying mechanism remains unclear. In this study, an NMR-based metabolomics approach was applied to investigate the neurochemical effects of sorafenib in rats. Male rats were once daily administrated with 120 mg/kg sorafenib by gavage for 3, 7, and 28 days, respectively. NMR-based metabolomics coupled with histopathology examinations for hippocampus, prefrontal cortex (PFC), and striatum were performed. The (1)H NMR spectra data were analyzed by using multivariate pattern recognition techniques to show the time-dependent biochemical variations induced by sorafenib. Excellent separation was obtained and distinguishing metabolites were observed between sorafenib-treated and control rats. A total of 36 differential metabolites in hippocampus of rats treated with sorafenib were identified, some of which were significantly changed. Furthermore, these modified metabolites mainly reflected the disturbances in neurotransmitters, energy metabolism, membrane, and amino acids. However, only a few metabolites in PFC and striatum were altered by sorafenib. Additionally, no apparent histological changes in these three brain regions were observed in sorafenib-treated rats. Together, our findings demonstrate the disturbed metabonomics pathways, especially, in hippocampus, which may underlie the sorafenib-induced cognitive deficits in patients. This work also shows the advantage of NMR-based metabolomics over traditional approach on the study of biochemical effects of drugs.

  9. A clash of values: Fear-relevant stimuli can enhance or corrupt adaptive behavior through competition between Pavlovian and instrumental valuation systems.

    Science.gov (United States)

    Lindström, Björn; Golkar, Armita; Olsson, Andreas

    2015-10-01

    Humans and nonhuman primates preferentially learn to fear and avoid archetypical fear-relevant stimuli. Yet how these learning biases influence adaptive behavior, the basic mechanistic underpinnings of these biases, and how they interact with learning experiences during the life span of an individual remain unknown. To study this, we investigated how 4 classes of fear-relevant stimuli (snakes, threatening in-group faces, racial out-group faces, and guns) influenced adaptive behavior. We showed that stimulus-driven biases have a dramatic influence that can either promote or corrupt adaptive behavior depending on how a bias relates to the environment. We quantified and compared the effects of different fear-relevant stimuli on instrumental behavior using a computational reinforcement learning model that formalized the idea that the bias reflects competition between an instrumental and a Pavlovian valuation system. These results were further clarified by 2 independent rating studies showing that perceived danger of the stimuli corresponded well with their influence on adaptive behavior. (c) 2015 APA, all rights reserved).

  10. Immune surveillance of the central nervous system in multiple sclerosis--relevance for therapy and experimental models.

    Science.gov (United States)

    Hussain, Rehana Z; Hayardeny, Liat; Cravens, Petra C; Yarovinsky, Felix; Eagar, Todd N; Arellano, Benjamine; Deason, Krystin; Castro-Rojas, Cyd; Stüve, Olaf

    2014-11-15

    Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS. However, many of the agents that are currently approved or in clinical development also have severe potential adverse effects that stem from the very mechanisms that mediate their beneficial effects by interfering with CNS immune surveillance. This review will outline the main cellular components of the innate and adaptive immune system that participate in host defense and maintain immune surveillance of the CNS. Their pathogenic role in MS and its animal model experimental autoimmune encephalomyelitis (EAE) is also discussed. Furthermore, an experimental model is introduced that may assist in evaluating the effect of therapeutic interventions on leukocyte homeostasis and function within the CNS. This model or similar models may become a useful tool in the repertoire of pre-clinical tests of pharmacological agents to better explore their potential for adverse events. Published by Elsevier B.V.

  11. Local High-Dose Radiotherapy Induces Systemic Immunomodulating Effects of Potential Therapeutic Relevance in Oligometastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Elena Muraro

    2017-11-01

    Full Text Available Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC patients, the use of stereotactic body radiotherapy (SBRT favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs, improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to “switch on” the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models. Twenty-one BC patients with ≤6 metastases were treated with 3 daily doses of 10 Gy with SBRT. Blood samples for immune profiling were collected before and after treatment. One month after treatment a third of patients displayed the boosting or even the de novo appearance of polyfunctional CD4+ and CD8+ T cell responses against known BC TAAs (survivin, mammaglobin-A, HER2, through intracellular staining in flow cytometry. Half of patients showed increased numbers of activated natural killer (NK cells, measured with multispectral flow cytometry, immediately after the first dose of SBRT. Interestingly, high levels of activated NK cells at diagnosis correlated with a longer progression-free survival. BC in vitro models, treated with the same SBRT modality, showed enhanced expression of MHC class-I and class-II, major histocompatibility complex class I-related chain A/B, and Fas molecules, and increased release of pro-inflammatory cytokines, such as IL-1β and TNF-α. Consistently, we noticed enhanced production of perforin by CD4+ T cells when patients’ lymphocytes were cultured in the presence of irradiated BC cell line, compared to untreated targets. Besides immunogenic effects, SBRT also enhanced the percentages of circulating regulatory T cells, and increased indoleamine 2

  12. Insight into the Local Solvent Environment of Biologically Relevant Iron-nitroysl Systems through Two-Dimensional Infrared Spectroscopy

    Science.gov (United States)

    Brookes, Jennifer Faith

    Iron-nitrosyl systems, particularly in the form of heme proteins, with their iron metal active sites play an important role in biological systems. Heme proteins act as storage, transporters, and receptors for nitric oxide (NO), a signaling molecule that is important in immune, nervous, and cardiovascular systems of mammals. By better understanding the local environment of the active site of NO binding heme proteins we can gain insight into disease in which the NO pathways have been implicated. This is an important step to being able to develop pharmaceuticals targeting NO pathways in humans. Sodium nitroprusside ((SNP, Na2[Fe(CN)5is NO]·2H 2O) investigated as a model system for the active site of nitric oxide binding heme proteins. Using two-dimensional infrared spectroscopy (2D IR) to obtain dephasing dynamics of the nitrosyl stretch (nuNO) in a series of solvents we are able to better understand the local environment of the more complicated metalloproteins. Rigorous line shape analysis is performed by using nonlinear response theory to simulate 2D IR spectra which are then fit to experimental data in an iterative process to extract frequency-frequency correlation functions (FFCFs). The time scales obtained are then correlated to empirical solvent polarity parameters. The analysis of the 2D IR lineshapes reveal that the spectral diffusion timescale of the nuNO in SNP varies from 0.8 -- 4 ps and is negatively correlated with the empirical solvent polarity scales. We continue to investigate NO binding of metalloproteins through 2D IR experiments on nitrophorin 4 (NP4). NP4 is a pH-sensitive NO transporter protein present in the salivary gland of the blood sucking insect Rhodius prolixus which undergoes a pH sensitive structural change between a closed and open conformation allowing for the storage and delivery of NO. The two structures are observed spectroscopically as two distinct pH-dependent nu NO frequencies at ~1904 and ~1917 cm-1. We obtain FFCFs by globally

  13. Role of Transporters in Central Nervous System Drug Delivery and Blood-Brain Barrier Protection: Relevance to Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Hrvoje Brzica

    2017-03-01

    Full Text Available Ischemic stroke is a leading cause of morbidity and mortality in the United States. The only approved pharmacologic treatment for ischemic stroke is thrombolysis via recombinant tissue plasminogen activator (r-tPA. A short therapeutic window and serious adverse events (ie, hemorrhage, excitotoxicity greatly limit r-tPA therapy, which indicates an essential need to develop novel stroke treatment paradigms. Transporters expressed at the blood-brain barrier (BBB provide a significant opportunity to advance stroke therapy via central nervous system delivery of drugs that have neuroprotective properties. Examples of such transporters include organic anion–transporting polypeptides (Oatps and organic cation transporters (Octs. In addition, multidrug resistance proteins (Mrps are transporter targets in brain microvascular endothelial cells that can be exploited to preserve BBB integrity in the setting of stroke. Here, we review current knowledge on stroke pharmacotherapy and demonstrate how endogenous BBB transporters can be targeted for improvement of ischemic stroke treatment.

  14. A Synthesis of Relevant Literature on the Development of Emotional Competence: Implications for Design of Augmentative and Alternative Communication Systems.

    Science.gov (United States)

    Na, Ji Young; Wilkinson, Krista; Karny, Meredith; Blackstone, Sarah; Stifter, Cynthia

    2016-08-01

    Emotional competence refers to the ability to identify, respond to, and manage one's own and others' emotions. Emotional competence is critical to many functional outcomes, including making and maintaining friends, academic success, and community integration. There appears to be a link between the development of language and the development of emotional competence in children who use speech. Little information is available about these issues in children who rely on augmentative and alternative communication (AAC). In this article, we consider how AAC systems can be designed to support communication about emotions and the development of emotional competence. Because limited research exists on communication about emotions in a context of aided AAC, theory and research from other fields (e.g., psychology, linguistics, child development) is reviewed to identify key features of emotional competence and their possible implications for AAC design and intervention. The reviewed literature indicated that the research and clinical attention to emotional competence in children with disabilities is encouraging. However, the ideas have not been considered specifically in the context of aided AAC. On the basis of the reviewed literature, we offer practical suggestions for system design and AAC use for communication about emotions with children who have significant disabilities. Three key elements of discussing emotions (i.e., emotion name, reason, and solution) are suggested for inclusion in order to provide these children with opportunities for a full range of discussion about emotions. We argue that supporting communication about emotions is as important for children who use AAC as it is for children who are learning speech. This article offers a means to integrate information from other fields for the purpose of enriching AAC supports.

  15. Deep learning relevance

    DEFF Research Database (Denmark)

    Lioma, Christina; Larsen, Birger; Petersen, Casper

    2016-01-01

    train a Recurrent Neural Network (RNN) on existing relevant information to that query. We then use the RNN to "deep learn" a single, synthetic, and we assume, relevant document for that query. We design a crowdsourcing experiment to assess how relevant the "deep learned" document is, compared...... to existing relevant documents. Users are shown a query and four wordclouds (of three existing relevant documents and our deep learned synthetic document). The synthetic document is ranked on average most relevant of all....

  16. Extended Paper: Reconceptualising Foundational Assumptions of Resilience: A Cross-Cultural, Spatial Systems Domain of Relevance for Agency and Phenomenology in Resilience

    Directory of Open Access Journals (Sweden)

    Paul Downes

    2017-04-01

    Full Text Available This article seeks to amplify Bronfenbrenner‘s (1979 concerns with concentric structured, nested systems and phenomenology, for Ungar‘s (2012 extension of resilience to systems based on Bronfenbrenner‘s (1979, 1995 socio-ecological paradigm. Resilience rests on interconnected assumptions regarding space, agency and system blockage, as well as the role of individual phenomenological dimensions. This article proposes a specific model of dynamic spatial systems of relation to underpin agency and phenomenology in resilience, building on a reinterpretation of Lévi-Strauss‘ (1962, 1963, 1973 cross-cultural observations of contrasts between concentric and diametric spatial systems; space is a key bridge between material, symbolic and interpersonal domains of relevance for resilience. Agency in resilience is interpreted in terms of movement between concentric and diametric spatial systems at social and school microsystem levels, as well as for individual phenomenology. Space is not just an object of analysis but an active constituent part of educational and developmental processes pertaining to resilience, as a malleable background contingent condition for causal trajectories. This framework of spatial-relational agency shifts focus for resilience from bouncing back into shape, towards transition points in space, moving from diametric spaces of splitting to concentric spatial relations of assumed connection across different system levels.

  17. Predicting crash-relevant violations at stop sign-controlled intersections for the development of an intersection driver assistance system.

    Science.gov (United States)

    Scanlon, John M; Sherony, Rini; Gabler, Hampton C

    2016-09-01

    Intersection crashes resulted in over 5,000 fatalities in the United States in 2014. Intersection Advanced Driver Assistance Systems (I-ADAS) are active safety systems that seek to help drivers safely traverse intersections. I-ADAS uses onboard sensors to detect oncoming vehicles and, in the event of an imminent crash, can either alert the driver or take autonomous evasive action. The objective of this study was to develop and evaluate a predictive model for detecting whether a stop sign violation was imminent. Passenger vehicle intersection approaches were extracted from a data set of typical driver behavior (100-Car Naturalistic Driving Study) and violations (event data recorders downloaded from real-world crashes) and were assigned weighting factors based on real-world frequency. A k-fold cross-validation procedure was then used to develop and evaluate 3 hypothetical stop sign warning algorithms (i.e., early, intermediate, and delayed) for detecting an impending violation during the intersection approach. Violation detection models were developed using logistic regression models that evaluate likelihood of a violation at various locations along the intersection approach. Two potential indicators of driver intent to stop-that is, required deceleration parameter (RDP) and brake application-were used to develop the predictive models. The earliest violation detection opportunity was then evaluated for each detection algorithm in order to (1) evaluate the violation detection accuracy and (2) compare braking demand versus maximum braking capabilities. A total of 38 violating and 658 nonviolating approaches were used in the analysis. All 3 algorithms were able to detect a violation at some point during the intersection approach. The early detection algorithm, as designed, was able to detect violations earlier than all other algorithms during the intersection approach but gave false alarms for 22.3% of approaches. In contrast, the delayed detection algorithm sacrificed

  18. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments

    Science.gov (United States)

    Zhao, Min; Kong, Lei; Qu, Hong

    2014-01-01

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X chromosome. In addition, these genes were enriched in target lists of seven transcription factors and sixteen microRNAs. Using a network-based approach, we further reconstructed an IQ-related pathway from known human pathway interaction data. Based on this reconstructed pathway, we incorporated enriched drugs and described the importance of dopamine and norepinephrine systems in IQ-related biological process. These findings not only reveal several testable genes and processes related to IQ scores, but also have potential therapeutic implications for IQ-related mental disorders. PMID:24566931

  19. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments.

    Science.gov (United States)

    Zhao, Min; Kong, Lei; Qu, Hong

    2014-02-25

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X chromosome. In addition, these genes were enriched in target lists of seven transcription factors and sixteen microRNAs. Using a network-based approach, we further reconstructed an IQ-related pathway from known human pathway interaction data. Based on this reconstructed pathway, we incorporated enriched drugs and described the importance of dopamine and norepinephrine systems in IQ-related biological process. These findings not only reveal several testable genes and processes related to IQ scores, but also have potential therapeutic implications for IQ-related mental disorders.

  20. Chemical reactions in the nitrogen-acetone ice induced by cosmic ray analogues: relevance for the Solar system

    Science.gov (United States)

    de Barros, A. L. F.; Andrade, D. P. P.; da Silveira, E. F.; Alcantara, K. F.; Boduch, P.; Rothard, H.

    2018-02-01

    The radiolysis of 10:1 nitrogen:acetone mixture, condensed at 11 K, by 40 MeV 58Ni11 + ions is studied. These results are representative of studies concerning Solar system objects, such as transneptunian objects, exposed to cosmic rays. Bombardment by cosmic rays triggers chemical reactions leading to synthesis of larger molecules. In this work, destruction cross-sections of acetone and nitrogen molecules in solid phase are determined and compared with those for pure acetone. The N2 column density decreases very fast indicating that, under irradiation, nitrogen leaves quickly a porous sample. The most abundant molecular species formed in the radiolysis are C3H6, C2H6, N3, CO, CH4 and CO2. Some N-bearing species are also formed, but with low production yield. Dissolving acetone in nitrogen decreases the formation cross-sections of CH4, CO2 and H2CO, while increases those for CO and C2H6 species. This fact may explain the presence of C2H6 in Pluto's surface where CH4 is not pure, but diluted in an N2 matrix. The formation of more complex molecules, such as HNCO and, possibly, glycine is observed, suggesting the formation of small prebiotic species in objects beyond Neptune from acetone diluted in a N2 matrix irradiated by cosmic rays.

  1. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  2. Regulatory functions and pathological relevance of the MECP2 3′UTR in the central nervous system

    Directory of Open Access Journals (Sweden)

    Heather McGowan

    2015-01-01

    Full Text Available Methyl-CpG-binding protein 2 (MeCP2, encoded by the gene MECP2, is a transcriptional regulator and chromatin-remodeling protein, which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system (CNS. Highly enriched in post-migratory neurons, MeCP2 is needed for neuronal maturation, including dendritic arborization and the development of synapses. Loss-of-function mutations in MECP2 cause Rett syndrome (RTT, a debilitating neurodevelopmental disorder characterized by a phase of normal development, followed by the progressive loss of milestones and cognitive disability. While a great deal has been discovered about the structure, function, and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT, including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders, much about this multifunctional protein remains enigmatic. One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range, the limits of which may depend upon the cell type and developmental time point. As such, MeCP2 is amenable to complex, multifactorial regulation. Here, we summarize the role of the MECP2 3' untranslated region (UTR in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.

  3. Multidimensional scaling of diffuse gliomas: application to the 2016 World Health Organization classification system with prognostically relevant molecular subtype discovery.

    Science.gov (United States)

    Cimino, Patrick J; Zager, Michael; McFerrin, Lisa; Wirsching, Hans-Georg; Bolouri, Hamid; Hentschel, Bettina; von Deimling, Andreas; Jones, David; Reifenberger, Guido; Weller, Michael; Holland, Eric C

    2017-05-22

    Recent updating of the World Health Organization (WHO) classification of central nervous system (CNS) tumors in 2016 demonstrates the first organized effort to restructure brain tumor classification by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS tumor diagnostic criteria also attempt to reduce interobserver variability of histological interpretation and provide more accurate stratification related to clinical outcome. As an example, diffuse gliomas (WHO grades II-IV) are now molecularly stratified based upon isocitrate dehydrogenase 1 or 2 (IDH) mutational status, with gliomas of WHO grades II and III being substratified according to 1p/19q codeletion status. For now, grading of diffuse gliomas is still dependent upon histological parameters. Independent of WHO classification criteria, multidimensional scaling analysis of molecular signatures for diffuse gliomas from The Cancer Genome Atlas (TCGA) has identified distinct molecular subgroups, and allows for their visualization in 2-dimensional (2D) space. Using the web-based platform Oncoscape as a tool, we applied multidimensional scaling-derived molecular groups to the 2D visualization of the 2016 WHO classification of diffuse gliomas. Here we show that molecular multidimensional scaling of TCGA data provides 2D clustering that represents the 2016 WHO classification of diffuse gliomas. Additionally, we used this platform to successfully identify and define novel copy-number alteration-based molecular subtypes, which are independent of WHO grading, as well as predictive of clinical outcome. The prognostic utility of these molecular subtypes was further validated using an independent data set of the German Glioma Network prospective glioblastoma patient cohort.

  4. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    Science.gov (United States)

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. Application range affected by software failures in safety relevant instrumentation and control systems of nuclear power plants; Auswirkungsbereiche von Softwarefehlern in sicherheitstechnisch wichtigen Einrichtungen von Kernkraftwerken

    Energy Technology Data Exchange (ETDEWEB)

    Jopen, Manuela; Mbonjo, Herve; Sommer, Dagmar; Ulrich, Birte

    2017-03-15

    This report presents results that have been developed within a BMUB-funded research project (Promotion Code 3614R01304). The overall objective of this project was to broaden the knowledge base of GRS regarding software failures and their impact in software-based instrumentation and control (I and C) systems. To this end, relevant definitions and terms in standards and publications (DIN, IEEE standards, IAEA standards, NUREG publications) as well as in the German safety requirements for nuclear power plants were analyzed first. In particular, it was found that the term ''software fault'' is defined differently and partly contradictory in the considered literature sources. For this reason, a definition of software fault was developed on the basis of the software life cycle of software-based I and C systems within the framework of this project, which takes into account the various aspects relevant to software faults and their related effects. It turns out that software failures result from latent faults in a software-based control system, which can lead to a non-compliant behavior of a software-based I and C system. Hereby a distinction should be made between programming faults and specification faults. In a further step, operational experience with software failures in software-based I and C systems in nuclear facilities and in nonnuclear sector was investigated. The identified events were analyzed with regard to their cause and impacts and the analysis results were summarized. Based on the developed definition of software failure and on the COMPSIS-classification scheme for events related to software based I and C systems, the COCS-classification scheme was developed to classify events from operating experience with software failures, in which the events are classified according to the criteria ''cause'', ''affected system'', ''impact'' and ''CCF potential''. This

  6. Expanding neurochemical investigations with multi-modal recording: simultaneous fast-scan cyclic voltammetry, iontophoresis, and patch clamp measurements

    Science.gov (United States)

    Kirkpatrick, D. C.; McKinney, C. J.; Manis, P. B.

    2016-01-01

    Multi-modal recording describes the simultaneous collection of information across distinct domains. Compared to isolated measurements, such studies can more easily determine relationships between varieties of phenomena. This is useful for neurochemical investigations which examine cellular activity in response to changes in the local chemical environment. In this study, we demonstrate a method to perform simultaneous patch clamp measurements with fast-scan cyclic voltammetry (FSCV) using optically isolated instrumentation. A model circuit simulating concurrent measurements was used to predict the electrical interference between instruments. No significant impact was anticipated between methods, and predictions were largely confirmed experimentally. One exception was due to capacitive coupling of the FSCV potential waveform into the patch clamp amplifier. However, capacitive transients measured in whole-cell current clamp recordings were well below the level of biological signals, which allowed the activity of cells to be easily determined. Next, the activity of medium spiny neurons (MSNs) was examined in the presence of an FSCV electrode to determine how the exogenous potential impacted nearby cells. The activities of both resting and active MSNs were unaffected by the FSCV waveform. Additionally, application of an iontophoretic current, used to locally deliver drugs and other neurochemicals, did not affect neighboring cells. Finally, MSN activity was monitored during iontophoretic delivery of glutamate, an excitatory neurotransmitter. Membrane depolarization and cell firing were observed concurrently with chemical changes around the cell resulting from delivery. In all, we show how combined electrophysiological and electrochemical measurements can relate information between domains and increase the power of neurochemical investigations. PMID:27314130

  7. System characterization of neuronal excitability in the hippocampus and its relevance to observed dynamics of spontaneous seizure-like transitions

    Science.gov (United States)

    Zalay, Osbert C.; Serletis, Demitre; Carlen, Peter L.; Bardakjian, Berj L.

    2010-06-01

    Most forms of epilepsy are marked by seizure episodes that arise spontaneously. The low-magnesium/high-potassium (low-Mg2+/high-K+) experimental model of epilepsy is an acute model that produces spontaneous, recurring seizure-like events (SLEs). To elucidate the nature of spontaneous seizure transitions and their relationship to neuronal excitability, whole-cell recordings from the intact hippocampus were undertaken in vitro, and the response of hippocampal CA3 neurons to Gaussian white noise injection was obtained before and after treatment with various concentrations of low-Mg2+/high-K+ solution. A second-order Volterra kernel model was estimated for each of the input-output response pairs. The spectral energy of the responses was also computed, providing a quantitative measure of neuronal excitability. Changes in duration and amplitude of the first-order kernel correlated positively with the spectral energy increase following treatment with low-Mg2+/high-K+ solution, suggesting that variations in neuronal excitability are coded by the system kernels, in part by differences to the profile of the first-order kernel. In particular, kernel duration was more sensitive than amplitude to changes in spectral energy, and correlated more strongly with kernel area. An oscillator network model of the hippocampal CA3 was constructed to investigate the relationship of kernel duration to network excitability, and the model was able to generate spontaneous, recurrent SLEs by increasing the duration of a mode function analogous to the first-order kernel. Results from the model indicated that disruption to the dynamic balance of feedback was responsible for seizure-like transitions and the observed intermittency of SLEs. A physiological candidate for feedback imbalance consistent with the network model is the destabilizing interaction of extracellular potassium and paroxysmal neuronal activation. Altogether, these results (1) validate a mathematical model for epileptiform

  8. Relevant concepts of functioning for patients with systemic lupus erythematosus identified in a Delphi exercise of experts and a literature review.

    Science.gov (United States)

    Leuchten, Nicolai; Bauernfeind, Bettina; Kuttner, Johannes; Stamm, Tanja; Smolen, Josef S; Pisetsky, David S; Aringer, Martin

    2014-12-01

    To identify in a Delphi exercise of international systemic lupus erythematosus (SLE) experts and a systematic literature review the most relevant concepts that impact on the functioning of SLE patients. Sixty SLE experts participated in all rounds of a 3-round e-mail-based Delphi exercise; for the literature review, 573 manuscripts out of 4 decades were analyzed. Concepts in the first Delphi round and from the literature were linked to categories of the International Classification of Functioning, Disability and Health (ICF). Categories were voted on individually in a feedback-driven Delphi process, and ranked by frequency in the literature, respectively. In the Delphi exercise, at least 80% of the participants found 30 categories of the domain body functions and structures, and 3 categories in the domain activities and participation and environmental factors important. In general, the categories identified in the literature review overlapped with those in the Delphi exercise with regard to body functions and structures, while showing some differences in other domains. The highest agreement concerned the ICF categories "joints," "skin and related structures," "fatiguability," "immunological system functions," and "handling stress and other psychological demands." Agreement with an earlier patient Delphi exercise was considerable. A 3-step Delphi exercise of 60 SLE experts and a literature review identified a wide spectrum of relevant ICF categories with impact on functioning of SLE patients. The categories derived from these approaches overlap with each other and with those of a patient Delphi exercise. Copyright © 2014 by the American College of Rheumatology.

  9. Elevated mercury exposure and neurochemical alterations in little brown bats (Myotis lucifugus) from a site with historical mercury contamination.

    Science.gov (United States)

    Nam, Dong-Ha; Yates, David; Ardapple, Pedro; Evers, David C; Schmerfeld, John; Basu, Niladri

    2012-05-01

    Despite evidence of persistent methylmercury (MeHg) contamination in the South River (Virginia, USA) ecosystem, there is little information concerning MeHg-associated neurological impacts in resident wildlife. Here we determined mercury (Hg) concentrations in tissues of insectivorous little brown bats (Myotis lucifugus) collected from a reference site and a MeHg-contaminated site in the South River ecosystem. We also explored whether neurochemical biomarkers (monoamine oxidase, MAO; acetylcholinesterase, ChE; muscarinic acetylcholine receptor, mAChR; N-methyl-D-aspartate receptor, NMDAR) previously shown to be altered by MeHg in other wildlife were associated with brain Hg levels in these bats. Concentrations of Hg (total and MeHg) in tissues were significantly higher (10-40 fold difference) in South River bats when compared to reference sites. Mean tissue mercury levels (71.9 ppm dw in liver, 7.14 ppm dw in brain, 132 ppm fw in fur) in the South River bats exceed (sub)-clinical thresholds in mammals. When compared to the South River bats, animals from the reference site showed a greater ability to demethylate MeHg in brain (33.1% of total Hg was MeHg vs. 65.5%) and liver (8.9% of total Hg was MeHg vs. 50.8%) thus suggesting differences in their ability to detoxify and eliminate Hg. In terms of Hg-associated neurochemical biomarker responses, interesting biphasic responses were observed with an inflection point between 1 and 5 ppm dw in the brain. In the reference bats Hg-associated decreases in MAO (r = -0.61; p exposures, differences in Hg metabolism, and the importance of the aforementioned neurochemicals in multiple facets of animal health, altered or perhaps even a lack of expected neurochemical responses in Hg-contaminated bats raise questions about the ecological and physiological impacts of Hg on the bat population as well as the broader ecosystem in the South River.

  10. Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury.

    Science.gov (United States)

    Züchner, Mark; Kondratskaya, Elena; Sylte, Camilla B; Glover, Joel C; Boulland, Jean-Luc

    2018-01-15

    Spinal compression injury targeted to the neonatal upper lumbar spinal cord, the region of highest hindlimb locomotor rhythmogenicity, leads to an initial paralysis of the hindlimbs. Behavioural recovery is evident within a few days and approaches normal function within about 3 weeks. Fictive locomotion in the isolated injured spinal cord cannot be elicited by a neurochemical cocktail containing NMDA, dopamine and serotonin 1 day post-injury, but can 3 days post-injury as readily as in the uninjured spinal cord. Low frequency coordinated rhythmic activity can be elicited in the isolated uninjured spinal cord by NMDA + dopamine (without serotonin), but not in the isolated injured spinal cord. In both the injured and uninjured spinal cord, eliciting bona fide fictive locomotion requires the additional presence of serotonin. Following incomplete compression injury in the thoracic spinal cord of neonatal mice 1 day after birth (P1), we previously reported that virtually normal hindlimb locomotor function is recovered within about 3 weeks despite substantial permanent thoracic tissue loss. Here, we asked whether similar recovery occurs following lumbar injury that impacts more directly on the locomotor central pattern generator (CPG). As in thoracic injuries, lumbar injuries caused about 90% neuronal loss at the injury site and increased serotonergic innervation below the injury. Motor recovery was slower after lumbar than thoracic injury, but virtually normal function was attained by P25 in both cases. Locomotor CPG status was tested by eliciting fictive locomotion in isolated spinal cords using a widely used neurochemical cocktail (NMDA, dopamine, serotonin). No fictive locomotion could be elicited 1 day post-injury, but could within 3 days post-injury as readily as in age-matched uninjured control spinal cords. Burst patterning and coordination were largely similar in injured and control spinal cords but there were differences. Notably, in both groups there

  11. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance.

    Science.gov (United States)

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates.

  12. Re: making health and care systems fit for and ageing population. Why we wrote it, who we wrote it for, and how relevant it might be to Canada.

    Science.gov (United States)

    Oliver, David

    2014-12-01

    In response to the commentary((1)) in this month's Canadian Geriatrics Journal by Andrew and Rockwood on the recent paper I co-wrote with King's Fund colleagues-"Making Health and Care Systems Fit for an Ageing Population"((2))-I wanted to pen a very personal response, not least because of my visits to health systems in Ontario and Alberta and conversations with many Canadian colleagues that are fresh in my mind. The paper was certainly the most important and influential thing I have written, and was an attempt to weave all the elements of good practice in health care for older people into one overarching narrative. Whilst its biggest target audience is UK health services, I hope it has some relevance to Canada and might stimulate some constructive conversations.

  13. A state-of-the-art review of transportation systems evaluation techniques relevant to air transportation, volume 1. [urban planning and urban transportation using decision theory

    Science.gov (United States)

    Haefner, L. E.

    1975-01-01

    Mathematical and philosophical approaches are presented for evaluation and implementation of ground and air transportation systems. Basic decision processes are examined that are used for cost analyses and planning (i.e, statistical decision theory, linear and dynamic programming, optimization, game theory). The effects on the environment and the community that a transportation system may have are discussed and modelled. Algorithmic structures are examined and selected bibliographic annotations are included. Transportation dynamic models were developed. Citizen participation in transportation projects (i.e, in Maryland and Massachusetts) is discussed. The relevance of the modelling and evaluation approaches to air transportation (i.e, airport planning) is examined in a case study in St. Louis, Missouri.

  14. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson’s Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

    Directory of Open Access Journals (Sweden)

    Dayane Pessoa de Araújo

    2013-01-01

    Full Text Available This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg alone or associated with L-DOPA using an animal model of Parkinson’s disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment.

  15. Interferon-gamma deficiency modifies the motor and co-morbid behavioral pathology and neurochemical changes provoked by the pesticide paraquat.

    Science.gov (United States)

    Litteljohn, D; Mangano, E; Shukla, N; Hayley, S

    2009-12-29

    In addition to nigrostriatal pathology and corresponding motor disturbances, Parkinson's disease (PD) is often characterized by co-morbid neuropsychiatric symptoms, most notably anxiety and depression. Separate lines of evidence indicate that inflammatory processes associated with microglial activation and cytokine release may be fundamental to the progression of both PD and its co-morbid psychiatric pathology. Accordingly, we assessed the contribution of the pro-inflammatory cytokine, interferon-gamma (IFN-gamma), to a range of PD-like pathology provoked by the ecologically relevant herbicide and dopamine (DA) toxin, paraquat. To this end, paraquat provoked overt motor impairment (reduced home-cage activity and impaired vertical climbing) and signs of anxiety-like behavior (reduced open field exploration) in wild-type but not IFN-gamma-deficient mice. Correspondingly, paraquat promoted somewhat divergent variations in neurochemical activity among wild-type and IFN-gamma null mice at brain sites important for both motor (striatum) and co-morbid affective pathologies (dorsal hippocampus, medial prefrontal cortex, and locus coeruleus). Specifically, the herbicide provoked a dosing regimen-dependent reduction in striatal DA levels that was prevented by IFN-gamma deficiency. In addition, the herbicide influenced serotonergic and noradrenergic activity within the dorsal hippocampus and medial prefrontal cortex; and elevated noradrenergic activity within the locus coeruleus. Although genetic ablation of IFN-gamma had relatively few effects on monoamine variations within the locus coeruleus and prefrontal cortex, loss of the pro-inflammatory cytokine did normalize the paraquat-induced noradrenergic alterations within the hippocampus. These findings further elucidate the functional implications of paraquat intoxication and suggest an important role for IFN-gamma in the striatal and motor pathology, as well as the co-morbid behavioral and hippocampal changes induced by

  16. Cerebellar neurochemical and histopathological changes in rat model of Parkinson's disease induced by intrastriatal injection of rotenone.

    Science.gov (United States)

    Khadrawy, Yasser A; Mourad, Iman M; Mohammed, Haitham S; Noor, Neveen A; Aboul Ezz, Heba S

    2017-01-01

    The aim of the present work was to investigate the neurochemical changes induced in the cerebellum of rat model of Parkinson's disease (PD). Rats were divided into two groups; control and rat model of PD induced by the intrastriatal injection of rotenone. As compared to control, a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine were observed in the cerebellum of rat model of PD. This was associated with a significant increase in lipid peroxidation, nitric oxide and tumor necrosis factor-α and a significant decrease in reduced glutathione. A significant decrease in acetylcholinesterase and a significant increase in Na+,K+-ATPase were recorded in the cerebellum of rat model of PD. In addition the cerebellar sections from rat model of PD showed marked necrosis of Purkinje cells, irregular damaged cells, cytoplasmic shrinkage, necrosis and perineuronal vacuolation. The present results indicate that the disturbance in the balance between the excitatory and inhibitory amino acids may have a role in the pathogenesis of PD. According to the present neurochemical and histopathological changes, the cerebellum should be taken into consideration during the treatment of PD.

  17. Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical.

    Science.gov (United States)

    Bhatt, Prakash Chandra; Pathak, Shruti; Kumar, Vikas; Panda, Bibhu Prasad

    2018-02-01

    The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE). NN treatment led to a significant increase in TLT in the retention trials as compared to acquisition trial TLT suggesting an improved learning and memory in rats. Further, treatment of NN caused an increase in the activity of AChE (42%), accompanied with a reduced activity of glutathione (42%), superoxide dismutase (43%) and catalase (41%). It also decreased the level of lipid peroxidation (28%) and protein carbonyl contents (30%) in hippocampus as compared to those treated with colchicine alone, suggesting a possible neuroprotective efficacy of NN. Interestingly, in silico studies also demonstrated an effective amyloid-β and BACE-1 inhibition activity. These findings clearly indicated that NN reversed colchicine-induced behavioral and neurochemical alterations through potent antioxidant activity and could possibly impart beneficial effects in cognitive defects associated with Alzheimer's disease.

  18. Neuroendocrine and neurochemical impact of aggressive social interactions in submissive and dominant mice: implications for stress-related disorders.

    Science.gov (United States)

    Audet, Marie-Claude; Anisman, Hymie

    2010-04-01

    Social conflicts may engender stress-related behavioural and physiological disturbances in the victims of aggression. In addition, stress-like neurochemical changes and ensuing depressive and anxiety symptoms might also be evident in the perpetrators of aggressive acts. The present investigation assessed basal levels of circulating corticosterone and of brain serotonin (5-HT) and norepinephrine (NE) in pre-identified submissive and dominant mice. In addition, brain neurochemical changes were determined following a single or three 15-min aggressive episodes both in submissive mice and in those that dominated the aggressive interplay. Three minutes after single and repeated confrontations, plasma corticosterone levels and 5-HT utilization within the prefrontal cortex (PFC) and hippocampus were increased to a comparable extent in submissive and dominant animals. Interestingly, however, NE utilization within the PFC and hippocampus was augmented to a greater level in submissive mice. These results suggest that 5-HT neuronal functioning was generally responsive to aggressive events, irrespective of social rank, whereas NE neuronal activity within the PFC and hippocampus was more sensitive to the submissive/dominance attributes of the social situation. It is possible that NE and 5-HT variations associated with an aggressive experience contribute to depressive- and anxiety-like manifestations typically observed after such psychosocial stressors, particularly in submissive mice. However, given that 5-HT changes occur irrespective of social rank, these data suggest that a toll is taken on both submissive and dominant mice, leaving them vulnerable to stress-related pathology.

  19. Similarities and differences of emotions in human-machine and human-human interactions: what kind of emotions are relevant for future companion systems?

    Science.gov (United States)

    Walter, Steffen; Wendt, Cornelia; Böhnke, Jan; Crawcour, Stephen; Tan, Jun-Wen; Chan, Andre; Limbrecht, Kerstin; Gruss, Sascha; Traue, Harald C

    2014-01-01

    Cognitive-technical intelligence is envisioned to be constantly available and capable of adapting to the user's emotions. However, the question is: what specific emotions should be reliably recognised by intelligent systems? Hence, in this study, we have attempted to identify similarities and differences of emotions between human-human (HHI) and human-machine interactions (HMI). We focused on what emotions in the experienced scenarios of HMI are retroactively reflected as compared with HHI. The sample consisted of N = 145 participants, who were divided into two groups. Positive and negative scenario descriptions of HMI and HHI were given by the first and second groups, respectively. Subsequently, the participants evaluated their respective scenarios with the help of 94 adjectives relating to emotions. The correlations between the occurrences of emotions in the HMI versus HHI were very high. The results do not support the statement that only a few emotions in HMI are relevant.

  20. Choice reaching with a LEGO arm robot (CoRLEGO): The motor system guides visual attention to movement-relevant information.

    Science.gov (United States)

    Strauss, Soeren; Woodgate, Philip J W; Sami, Saber A; Heinke, Dietmar

    2015-12-01

    We present an extension of a neurobiologically inspired robotics model, termed CoRLEGO (Choice reaching with a LEGO arm robot). CoRLEGO models experimental evidence from choice reaching tasks (CRT). In a CRT participants are asked to rapidly reach and touch an item presented on the screen. These experiments show that non-target items can divert the reaching movement away from the ideal trajectory to the target item. This is seen as evidence attentional selection of reaching targets can leak into the motor system. Using competitive target selection and topological representations of motor parameters (dynamic neural fields) CoRLEGO is able to mimic this leakage effect. Furthermore if the reaching target is determined by its colour oddity (i.e. a green square among red squares or vice versa), the reaching trajectories become straighter with repetitions of the target colour (colour streaks). This colour priming effect can also be modelled with CoRLEGO. The paper also presents an extension of CoRLEGO. This extension mimics findings that transcranial direct current stimulation (tDCS) over the motor cortex modulates the colour priming effect (Woodgate et al., 2015). The results with the new CoRLEGO suggest that feedback connections from the motor system to the brain's attentional system (parietal cortex) guide visual attention to extract movement-relevant information (i.e. colour) from visual stimuli. This paper adds to growing evidence that there is a close interaction between the motor system and the attention system. This evidence contradicts the traditional conceptualization of the motor system as the endpoint of a serial chain of processing stages. At the end of the paper we discuss CoRLEGO's predictions and also lessons for neurobiologically inspired robotics emerging from this work. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  1. Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

    Science.gov (United States)

    Gordon, Tessa; Gordon, Karen

    2010-01-01

    Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

  2. Building integrated health systems in central and eastern Europe: an analysis of WHO and World Bank views and their relevance to health systems in transition.

    Science.gov (United States)

    Delnoij, Diana M J; Klazinga, Niek S; van der Velden, Koos

    2003-09-01

    Two questions are addressed. i) What are the views on health and health systems as expressed in the World Development Report 2000/2001 of the WB and the World Health Report 2000 and Health 21 of the World Health Organization, and how compatible are those views? ii) To what extent will compliance of CEEC and NIS with the WHO and WB recommendations result in health systems that produce maximum health for all by adequately addressing the needs of their populations? The reports prepared by the World Bank and the World Health Organization were assessed against the theoretical framework of a needs-based public health approach. It is observed that the WHO and WB approaches are currently converging, although there remain differences in their respective focuses. The main merit of the WHO approach is its focus on performance and the systems approach towards health (care). The merit of the WB view is the integrated approach to health, education and poverty. It is argued that CEEC and NIS need to anticipate an ageing population and growing numbers of chronically ill. This calls for integrated health care systems and more integrated funding and payment systems. The recommendations provided in the WHR and the WDR with regard to integrated care and integrated financing remain rather abstract. Advisors of CEEC and NIS on health care reform and Western assistance projects should focus more on future needs, in order to avoid building health systems that consistently lag behind the needs of their populations.

  3. Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

    Science.gov (United States)

    Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

    2017-10-01

    Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T3) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

  4. Measuring clinically relevant endpoints in a serum-free, three-dimensional, primary cell culture system of human osteoarthritic articular chondrocytes.

    Science.gov (United States)

    Bundens, Grace; Buckley, Andrea; Milton, LaBraya; Behling, Kathryn; Chmielewski, Sarah; Cho, Ellen; Lozano-Torres, Xiomara; Selim, Abdulhafez; Lackman, Richard; George-Weinstein, Mindy; Miller, Lawrence; D'Angelo, Marina

    2017-08-15

    Osteoarthritis (OA) is characterized by degeneration of articular cartilage within the joint, inflammation and pain. The purpose of this study was to develop a primary, serum free cell culture system of human osteoarthritic articular chondrocytes (HOACs) with which to study manifestations of the disease process. Joint tissues were obtained from OA patients undergoing total knee arthroplasty (TKA). HOACs isolated from the femoral condyles and tibial plateau of the same side were combined, plated in three-dimensional, alginate beads and cultured for five days in serum, hormone and protein free medium. More living cells were obtained from the femoral condyles than the tibial plateau. The optimal plating density was 2.5 × 106 cells/ml of alginate. The amounts of DNA, RNA, proteoglycans and total collagen were similar in cultures prepared from the sides of least and greatest pathology. More type 1 than type 2 collagen was detected in the medium on days 2 and 5. A greater percentage of type 1 than type 2 collagen was degraded. The inflammatory cytokine interleukin-1 beta was present in the medium and alginate associated matrix. Although variation in the metabolic profiles between subjects was observed, HOACs from all patients continued to reflect the OA phenotype for five days in culture. This serum free, three-dimensional primary culture system of HOACs provides a platform with which to measure clinically relevant endpoints of OA and screen potential disease modifying OA therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Reagent-free monitoring of multiple clinically relevant parameters in human blood plasma using a mid-infrared quantum cascade laser based sensor system.

    Science.gov (United States)

    Brandstetter, Markus; Sumalowitsch, Tamara; Genner, Andreas; Posch, Andreas E; Herwig, Christoph; Drolz, Andreas; Fuhrmann, Valentin; Perkmann, Thomas; Lendl, Bernhard

    2013-07-21

    We present a semi-automated point-of-care (POC) sensor approach for the simultaneous and reagent-free determination of clinically relevant parameters in blood plasma. The portable sensor system performed direct mid-infrared (MIR) transmission measurements of blood plasma samples using a broadly tunable external-cavity quantum cascade laser source with high spectral power density. This enabled the use of a flow cell with a long path length (165 μm) which resulted in high signal-to-noise ratios and a rugged system, insensitive to clogging. Multivariate calibration models were built using well established Partial-Least-Squares (PLS) regression analysis. Selection of spectral pre-processing procedures was optimized by an automated evaluation algorithm. Several analytes, including glucose, lactate, triglycerides, cholesterol, total protein as well as albumin, were successfully quantified in routinely taken blood plasma samples from 67 critically ill patients. Although relying on a spectral range from 1030 cm(-1) to 1230 cm(-1), which is optimal for glucose and lactate but rather unusual for protein analysis, it was possible to selectively determine the albumin and total protein concentrations with sufficient accuracy for POC application.

  6. Exploring the limitations of the Hantzsch method used for quantification of hydroxyl radicals in systems of relevance for interfacial radiation chemistry

    Science.gov (United States)

    Yang, Miao; Soroka, Inna; Jonsson, Mats

    2017-01-01

    In the presence of Tris or methanol, hydroxyl radicals in systems of relevance for interfacial radiation chemistry can be quantified indirectly via the Hantzsch method by determining the amount of the scavenging product formaldehyde formed. In this work, the influence of the presence of H2O2 on the Hantzsch method using acetoacetanilide (AAA) as derivatization reagent is studied. The experiments show that the measured CH2O concentration deviates from the actual concentration in the presence of H2O2 and the deviation increases with increasing [H2O2]0/[CH2O]0. The deviation is negative, i.e., the measured formaldehyde concentration is lower than the actual concentration. This leads to an underestimation of the hydroxyl radical production in systems containing significant amount of H2O2. The main reason for the deviation is found to be three coupled equilibria involving H2O2, CH2O and the derivative produced in the Hantzsch method.

  7. Safety of High Speed Guided Ground Transportation Systems - An Overview of Biological Effects and Mechanisms Relevant to EMF Exposures from Mass Transit and Electric Rail Systems

    Science.gov (United States)

    1993-08-01

    The U.S. has implemented a national initiative to develop maglev (magnetic levitation) and other high-speed rail (HSR) : systems. There are concerns for potential adverse health effects of the Extremely Lou Frequency (3-3,000 Hz) electric : and magne...

  8. Effect of Feeding Intensity and Milking System on Nutritionally Relevant Milk Components in Dairy Farming Systems in the North East of England

    DEFF Research Database (Denmark)

    Stergiadis, Sokratis; Leifert, Carlo; Seal, Chris J.

    2012-01-01

    with increasing feeding intensity (organic outdoor ≥ conventional outdoor ≥ conventional indoors). Milking system intensification (use of robotic milking parlors) had a more limited effect on milk composition, but increased mastitis incidence. Multivariate analyses indicated that differences in milk quality were...

  9. Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences-Comorbidities Network Study.

    Science.gov (United States)

    Houben-Wilke, Sarah; Jörres, Rudolf A; Bals, Robert; Franssen, Frits M E; Gläser, Sven; Holle, Rolf; Karch, Annika; Koch, Armin; Magnussen, Helgo; Obst, Anne; Schulz, Holger; Spruit, Martijn A; Wacker, Margarethe E; Welte, Tobias; Wouters, Emiel F M; Vogelmeier, Claus; Watz, Henrik

    2017-01-15

    Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. The ankle-brachial index was used to diagnose PAD (ankle-brachial index ≤ 0.9). The 6-minute-walk distance, health status (St. George's Respiratory Questionnaire), COPD Assessment Test, and EuroQol-5-Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences-Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I-IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences-Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6-minute-walk distance (356 [108] vs. 422 [103] m, P COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol-5-Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

  10. Grading apical vertebral rotation without a computed tomography scan: a clinically relevant system based on the radiographic appearance of bilateral pedicle screws.

    Science.gov (United States)

    Upasani, Vidyadhar V; Chambers, Reid C; Dalal, Ali H; Shah, Suken A; Lehman, Ronald A; Newton, Peter O

    2009-08-01

    Bench-top and retrospective analysis to assess vertebral rotation based on the appearance of bilateral pedicle screws in patients with adolescent idiopathic scoliosis (AIS). To develop a clinically relevant radiographic grading system for evaluating postoperative thoracic apical vertebral rotation that would correlate with computed tomography (CT) measures of rotation. The 3-column vertebral body control provided by bilateral pedicle screws has enabled scoliosis surgeons to develop advanced techniques of direct vertebral derotation. Our ability to accurately quantify spinal deformity in the axial plane, however, continues to be limited. Trigonometry was used to define the relationship between the position of bilateral pedicle screws and vertebral rotation. This relationship was validated using digital photographs of a bench-top model. The mathematical relationships were then used to calculate vertebral rotation from standing postoperative, posteroanterior radiographs in AIS patients and correlated with postoperative CT measures of rotation. Fourteen digital photographs of the bench-top model were independently analyzed twice by 3 coauthors. The mathematically calculated degree of rotation was found to correlate significantly with the actual degree of rotation (r = 0.99; P < 0.001) and the intra- and interobserver reliability for these measurements were both excellent (kappa = 0.98 and kappa = 0.97, respectively). In the retrospective analysis of 17 AIS patients, the average absolute difference between the radiographic measurement of rotation and the CT measure was only 1.9 degrees +/- 2.0 degrees (r = 0.92; P < 0.001). Based on these correlations a simple radiographic grading system for postoperative apical vertebral rotation was developed. An accurate assessment of vertebral rotation can be performed radiographically, using screw lengths and screw tip-to-rod distances of bilateral segmental pedicle screws and a trigonometric calculation. These data support the use

  11. Is hospital information system relevant to detect surgical site infection? Findings from a prospective surveillance study in posterior instrumented spinal surgery.

    Science.gov (United States)

    Boetto, J; Chan-Seng, E; Lonjon, G; Pech, J; Lotthé, A; Lonjon, N

    2015-11-01

    Spinal instrumentation has a high rate of surgical site infection (SSI), but results greatly vary depending on surveillance methodology, surgical procedures, or quality of follow-up. Our aim was to study true incidence of SSI in spinal surgery by significant data collection, and to compare it with the results obtained through the hospital information system. This work is a single center prospective cohort study that included all patients consecutively operated on for spinal instrumentation by posterior approach over a six-month period regardless the etiology. For all patients, a "high definition" prospective method of surveillance was performed by the infection control (IC) department during at least 12 months after surgery. Results were then compared with findings from automatic surveillance though the hospital information system (HIS). One hundred and fifty-four patients were included. We found no hardly difference between "high definition" and automatic surveillance through the HIS, even if HIS tended to under-estimate the infection rate: rate of surgical site infection was 2.60% and gross SSI incidence rate via the hospital information system was 1.95%. Smoking and alcohol consumption were significantly related to a SSI. Our SSI rates to reflect the true incidence of infectious complications in posterior instrumented adult spinal surgery in our hospital and these results were consistent with the lower levels of published infection rate. In-house surveillance by surgeons only is insufficiently sensitive. Further studies with more patients and a longer inclusion time are needed to conclude if SSI case detection through the HIS could be a relevant and effective alternative method. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. A remote reading system for gas and water meters; Systeme de releve a distance des compteurs de gaz et d'eau

    Energy Technology Data Exchange (ETDEWEB)

    Fasoli, L. [Societa Italiana per il Gas (Italy)

    2000-07-01

    As early as ten years ago Italgas did recognize the importance of applying remote meter reading not only for large-volume gas consumers, but also for household gas users. Consequently, since the late 80's Italgas has been spending a great deal of effort into a research program aimed at finding the most efficient solution for remote meter reading. The solution advocated by Italgas was obtained under the assumption that the equipment to be installed should offer not only provisions for meter reading, but also for a number of additional value added services that the user may be interested to acquire and that can increase the returns from the investment. As a consequence of this choice, meter reading should not be done by a portable equipment, but rather by using a fixed communication network. Therefore, the remote reading system concerned comprises equipment for automatic transfer of meter data to the billing center: via radio from the meter to a concentrator and via telephone from the concentrator to the billing center. This report is divided into 3 sections, covering system architecture, electrical characteristics and description of a practical field test. (authors)

  13. Behavioral and Neurochemical Studies in Stressed and Unstressed Rats Fed on Protein, Carbohydrate and Fat Rich Diet

    Directory of Open Access Journals (Sweden)

    Samia Moin§, Saida Haider*, Saima Khaliq1, Saiqa Tabassum and Darakhshan J. Haleem

    2012-05-01

    Full Text Available Stress produces behavioral and neurochemical deficits. To study the relationship between adaptation to stress and macronutrient intake, the present study was designed to monitor the effects of different diets on feed intake, growth rate and serotonin (5-Hydroxytryptamine, 5-HT metabolism following exposure to restraint stress in rats. Rats were divided into four groups (n=12 as control, sugar, protein and fat rich diet fed rats. After 5 weeks of treatment animals of each group were divided into unrestrained and restrained animals (n=6. Rats of restrained group were given immobilization stress for 2 hours/day for 5 days. Food intake and growth rates of unrestrained and restrained rats were monitored daily. Rats were decapitated on 6th day to collect brain samples for neurochemical estimation. Results show that sugar diet fed rats produced adaptation to stress early as compared to normal diet fed rats. Food intake and growth rates of unrestrained and restrained rats were comparable on 3rd day in sugar diet fed rats and on 4th day in normal diet fed rats. Stress decreased food intake and growth rates of protein and fat treated rats. Repeated stress did not alter brain 5-HT and 5-HIAA levels of normal diet fed rats and sugar diet fed rats. Protein diet fed restrained rats showed elevated brain 5-HT levels. Fat diet fed restrained rats significantly decreased brain TRP and 5-HIAA levels. Finding suggested that carbohydrate diet might protect against stressful conditions. Study also showed that nutritional status could alter different behaviors in response to a stressful environment.

  14. Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence.

    Science.gov (United States)

    Bishnoi, Mahendra; Chopra, Kanwaljit; Rongzhu, Lu; Kulkarni, Shrinivas K

    2011-10-01

    Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects, particularly the irregular movements of chorionic type. This limitation presents a marked therapeutic challenge. The present study investigates the molecular etiology of haloperidol neurotoxicity and the role of curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The redox status of haloperidol-treated brains along with NO, TNF-α, NF-kappaB p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21 days) produced orofacial dyskinetic movements which were coupled with marked increase in oxidative stress parameters, TNF-α, caspase-3 activity in cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the striatum. Neurochemically, chronic administration of haloperidol resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin. The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days) produced mild oxidative stress but did not alter any other parameters. Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days) dose-dependently prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol. Curcumin per se (50 mg/kg) did not show any side effects. Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct to haloperidol treatment and provided initial clues to the underlying molecular mechanisms in haloperidol neurotoxicity. This study also provides a rationale for the combination of piperine and curcumin.

  15. Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

    Science.gov (United States)

    Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

    2014-10-03

    Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The Suprachiasmatic Nucleus of the Dromedary Camel (Camelus dromedarius: Cytoarchitecture and Neurochemical Anatomy

    Directory of Open Access Journals (Sweden)

    Khalid El Allali

    2017-11-01

    Full Text Available In mammals, biological rhythms are driven by a master circadian clock located in the suprachiasmatic nucleus (SCN of the hypothalamus. Recently, we have demonstrated that in the camel, the daily cycle of environmental temperature is able to entrain the master clock. This raises several questions about the structure and function of the SCN in this species. The current work is the first neuroanatomical investigation of the camel SCN. We carried out a cartography and cytoarchitectural study of the nucleus and then studied its cell types and chemical neuroanatomy. Relevant neuropeptides involved in the circadian system were investigated, including arginine-vasopressin (AVP, vasoactive intestinal polypeptide (VIP, met-enkephalin (Met-Enk, neuropeptide Y (NPY, as well as oxytocin (OT. The neurotransmitter serotonin (5-HT and the enzymes tyrosine hydroxylase (TH and aromatic L-amino acid decarboxylase (AADC were also studied. The camel SCN is a large and elongated nucleus, extending rostrocaudally for 9.55 ± 0.10 mm. Based on histological and immunofluorescence findings, we subdivided the camel SCN into rostral/preoptic (rSCN, middle/main body (mSCN and caudal/retrochiasmatic (cSCN divisions. Among mammals, the rSCN is unusual and appears as an assembly of neurons that protrudes from the main mass of the hypothalamus. The mSCN exhibits the triangular shape described in rodents, while the cSCN is located in the retrochiasmatic area. As expected, VIP-immunoreactive (ir neurons were observed in the ventral part of mSCN. AVP-ir neurons were located in the rSCN and mSCN. Results also showed the presence of OT-ir and TH-ir neurons which seem to be a peculiarity of the camel SCN. OT-ir neurons were either scattered or gathered in one isolated cluster, while TH-ir neurons constituted two defined populations, dorsal parvicellular and ventral magnocellular neurons, respectively. TH colocalized with VIP in some rSCN neurons. Moreover, a high density of Met

  17. Investigation of droplet nucleation in CCS relevant systems – Design and testing of a CO2 branch of the mixture preparation device

    Directory of Open Access Journals (Sweden)

    Vinš Václav

    2017-01-01

    Full Text Available A unique in-house designed experimental apparatus for investigation of nucleation of droplets in CCS relevant systems is being developed by our team. The nucleation is measured with the help of a rapid pressure drop within an expansion chamber. In this study, a CO2 branch representing an important part of the mixture preparation device (MPD was designed, assembled and tested. MPD is intended for preparation of CO2-rich mixtures in a sense of accurate setting of flow rates of individual gaseous components through the experimental section with the expansion chamber. In the CO2 branch, the saturated liquid CO2 coming from a cylinder with a dip tube is pressurized by a supercritical pump with a constant flow rate to the pressures of up to 340 bar. The required mass flow of the supercritical CO2 of up to 180 g/h at pressures between 74 bar and 150 bar is accurately tuned with a help of a set of stainless steel capillary tubes with inner diameter of 0.1 mm. Some of the tubes are submerged in a thermostatic bath set to a constant temperature of 70 °C in order to assure the supercritical flow conditions of CO2. Needed lengths of the capillary tubes were determined with a help of a one-dimensional numerical model allowing prediction of both isothermal and adiabatic flow conditions.

  18. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, C.O.; Fronek, Z.; Koo, M.; McDevitt, H.O. (Stanford Univ. School of Medicine, CA (USA)); Lewis, G.C. (Genentech Inc., San Francisco, CA (USA)); Hansen, J.A. (Fred Hutchinson Cancer Research Center, Seattle, WA (USA))

    1990-02-01

    The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotype is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.

  19. Field-relevant doses of the systemic insecticide fipronil and fungicide pyraclostrobin impair mandibular and hypopharyngeal glands in nurse honeybees (Apis mellifera).

    Science.gov (United States)

    Zaluski, Rodrigo; Justulin, Luis Antonio; Orsi, Ricardo de Oliveira

    2017-11-09

    Global decreases in bee populations emphasize the importance of assessing how environmental stressors affect colony maintenance, especially considering the extreme task specialization observed in honeybee societies. Royal jelly, a protein secretion essential to colony nutrition, is produced by nurse honeybees, and development of bee mandibular glands, which comprise a reservoir surrounded by secretory cells and hypopharyngeal glands that are shaped by acini, is directly associated with production of this secretion. Here, we examined individual and combined effects of the systemic fungicide pyraclostrobin and insecticide fipronil in field-relevant doses (850 and 2.5 ppb, respectively) on mandibular and hypopharyngeal glands in nurse honeybees. Six days of pesticide treatment decreased secretory cell height in mandibular glands. When pyraclostrobin and fipronil were combined, the reservoir volume in mandibular glands also decreased. The total number of acini in hypopharyngeal glands was not affected, but pesticide treatment reduced the number of larger acini while increasing smaller acini. These morphological impairments appeared to reduce royal jelly secretion by nurse honeybees and consequently hampered colony maintenance. Overall, pesticide exposure in doses close to those experienced by bees in the field impaired brood-food glands in nurse honeybees, a change that could negatively influence development, survival, and colony maintenance.

  20. The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

    Science.gov (United States)

    Helley, M P; Abate, W; Jackson, S K; Bennett, J H; Thompson, S W N

    2015-12-03

    The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

    Science.gov (United States)

    Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohamed; Barathidasan, Rajamani; SaravanaBabu, Chidambaram; Guillemin, Gilles J; Khan, Mohammed A S

    2016-01-01

    Parkinson's disease (PD) is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic) neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS) such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS), a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks) of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor) impairments, levels and expressions of dopamine (DA), serotonin (5-HT), DAergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporters-2 (VMAT 2) and α-synuclein in nigrostriatal (striatum (ST) and substantia nigra (SN)) and extra-nigrostriatal (hippocampus, cortex and cerebellum) tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  2. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Udaiyappan Janakiraman

    Full Text Available Parkinson's disease (PD is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS, a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt. with probenecid (250 mg/kg, s.c. (MPTP/p induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor impairments, levels and expressions of dopamine (DA, serotonin (5-HT, DAergic markers such as tyrosine hydroxylase (TH, dopamine transporter (DAT, vesicular monoamine transporters-2 (VMAT 2 and α-synuclein in nigrostriatal (striatum (ST and substantia nigra (SN and extra-nigrostriatal (hippocampus, cortex and cerebellum tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  3. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kostadinova, Radina; Boess, Franziska [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Applegate, Dawn [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Suter, Laura; Weiser, Thomas; Singer, Thomas [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Naughton, Brian [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Roth, Adrian, E-mail: adrian_b.roth@roche.com [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland)

    2013-04-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  4. Relevance Matrices in LVQ

    NARCIS (Netherlands)

    Schneider, Petra; Biehl, Michael; Hammer, Barbara; Verleysen, Michel

    2007-01-01

    We propose a new matrix learning scheme to extend Generalized Relevance Learning Vector Quantization (GRLVQ). By introducing a full matrix of relevance factors in the distance measure, correlations between different features and their importance for the classification scheme can be taken into

  5. Relevance and Effectiveness of the WHO Global Code Practice on the International Recruitment of Health Personnel – Ethical and Systems Perspectives

    Directory of Open Access Journals (Sweden)

    Ruairi Brugha

    2015-06-01

    Full Text Available The relevance and effectiveness of the World Health Organization’s (WHO’s Global Code of Practice on the International Recruitment of Health Personnel is being reviewed in 2015. The Code, which is a set of ethical norms and principles adopted by the World Health Assembly (WHA in 2010, urges members states to train and retain the health personnel they need, thereby limiting demand for international migration, especially from the under-staffed health systems in low- and middle-income countries. Most countries failed to submit a first report in 2012 on implementation of the Code, including those source countries whose health systems are most under threat from the recruitment of their doctors and nurses, often to work in 4 major destination countries: the United States, United Kingdom, Canada and Australia. Political commitment by source country Ministers of Health needs to have been achieved at the May 2015 WHA to ensure better reporting by these countries on Code implementation for it to be effective. This paper uses ethics and health systems perspectives to analyse some of the drivers of international recruitment. The balance of competing ethics principles, which are contained in the Code’s articles, reflects a tension that was evident during the drafting of the Code between 2007 and 2010. In 2007-2008, the right of health personnel to migrate was seen as a preeminent principle by US representatives on the Global Council which co-drafted the Code. Consensus on how to balance competing ethical principles – giving due recognition on the one hand to the obligations of health workers to the countries that trained them and the need for distributive justice given the global inequities of health workforce distribution in relation to need, and the right to migrate on the other hand – was only possible after President Obama took office in January 2009. It is in the interests of all countries to implement the Global Code and not just those that

  6. The relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of non-melanoma skin cancer (NMSC)

    Science.gov (United States)

    Reichrath, Jörg; Reichrath, Sandra

    2013-01-01

    Solar UV (UV)-B-radiation exerts both beneficial and adverse effects on human health. On the one hand, it is the most important environmental risk factor for the development of non-melanoma skin cancer [NMSC; most importantly basal (BCC) and squamous (SCC) cell carcinomas], that represent the most common malignancies in Caucasian populations. On the other hand, the human body’s requirements of vitamin D are mainly achieved by UV-B-induced cutaneous photosynthesis. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer has been convincingly demonstrated. In line with these findings, epidemiologic and laboratory investigations now indicate that vitamin D and its metabolites have a risk reducing effect for NMSC. Potential mechanisms of action include inhibition of the hedgehog signaling pathway (BCC) and modulation of p53-mediated DNA damage response (SCC). As a consequence of these new findings it can be concluded that UV-B-radiation exerts both beneficial and adverse effects on risk and prognosis of NMSC. It can be assumed that many independent factors, including frequency and dose of UV-B exposure, skin area exposed, and individual factors (such as skin type and genetic determinants of the skin`s vitamin D status and of signaling pathways that are involved in the tumorigenesis of NMSC) determine whether UV-B exposure promotes or inhibits tumorigenesis of NMSC. Moreover, these findings may help to explain many of the differential effects of UV-B radiation on risk of NMSC, including variation in the dose-dependent risk for development of SCC in situ (actinic keratosis, AK), invasive SCC, and BCC. In this review, we analyze the relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of NMSC and give an overview of present concepts and future perspectives. PMID:24494041

  7. The relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of non-melanoma skin cancer (NMSC): Present concepts and future perspectives.

    Science.gov (United States)

    Reichrath, Jörg; Reichrath, Sandra

    2013-01-01

    Solar UV (UV)-B-radiation exerts both beneficial and adverse effects on human health. On the one hand, it is the most important environmental risk factor for the development of non-melanoma skin cancer [NMSC; most importantly basal (BCC) and squamous (SCC) cell carcinomas], that represent the most common malignancies in Caucasian populations. On the other hand, the human body's requirements of vitamin D are mainly achieved by UV-B-induced cutaneous photosynthesis. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer has been convincingly demonstrated. In line with these findings, epidemiologic and laboratory investigations now indicate that vitamin D and its metabolites have a risk reducing effect for NMSC. Potential mechanisms of action include inhibition of the hedgehog signaling pathway (BCC) and modulation of p53-mediated DNA damage response (SCC). As a consequence of these new findings it can be concluded that UV-B-radiation exerts both beneficial and adverse effects on risk and prognosis of NMSC. It can be assumed that many independent factors, including frequency and dose of UV-B exposure, skin area exposed, and individual factors (such as skin type and genetic determinants of the skin`s vitamin D status and of signaling pathways that are involved in the tumorigenesis of NMSC) determine whether UV-B exposure promotes or inhibits tumorigenesis of NMSC. Moreover, these findings may help to explain many of the differential effects of UV-B radiation on risk of NMSC, including variation in the dose-dependent risk for development of SCC in situ (actinic keratosis, AK), invasive SCC, and BCC. In this review, we analyze the relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of NMSC and give an overview of present concepts and future perspectives.

  8. In vivo relevance of polymorphic Interleukin 8 promoter haplotype for the systemic immune response to LPS in Holstein-Friesian calves.

    Science.gov (United States)

    Stojkovic, Bojan; McLoughlin, Rachel M; Meade, Kieran G

    2016-12-01

    Interleukin 8, also known as CXC chemokine ligand 8 (CXCL8), is a critical chemokine in the recruitment of leukocytes to sites of infection and is a potent mediator of inflammation. We previously discovered 29 polymorphic sites in the promoter region of the bovine Interleukin 8 gene, which segregate into two distinct haplotypes, denoted IL8-h1 and IL8-h2. Population genetic analysis of these two haplotypes showed significant inter-breed differences in haplotype frequency, which is suggestive of selection acting at this locus. Furthermore functional characterisation identified that IL8-h2 was more active in mammary epithelial cells stimulated with the bacterial endotoxin, LPS. However, the in vivo relevance of these functional differences in the IL8 gene has not been ascertained. Therefore, in the current study, we tested the hypothesis that IL8 haplotype would result in variation in the systemic immune response to LPS challenge in Holstein-Friesian (HF) calves. A Taqman assay was designed to genotype both Jersey and HF calves, from which 20 healthy HF calves (representing IL8-h1 and IL8-h2) from the same farm were subjected to LPS stimulation via jugular venepuncture (100ng/kg). Systemic immune profiling was subsequently performed up to 216h post-challenge. Haematological analysis showed perturbations in leukocyte populations of cells but only the lymphocyte response was significantly different between IL8-h1 and IL8-h2. IL8 expression levels were significantly different between haplogroups, at both the gene expression and protein levels (P<0.05). Circulating neutrophils were subsequently purified from each haplogroup to measure potential haplotype specific effects on neutrophil migration and bacterial killing but no significant differences were detected, which is likely due to the low circulating levels of IL8. We conclude that IL8 haplotype significantly affects IL8 expression profile in response to bacterial endotoxin in vivo, and the significant increase in IL8

  9. Culturally Relevant Cyberbullying Prevention

    OpenAIRE

    Phillips, Gregory John

    2017-01-01

    In this action research study, I, along with a student intervention committee of 14 members, developed a cyberbullying intervention for a large urban high school on the west coast. This high school contained a predominantly African American student population. I aimed to discover culturally relevant cyberbullying prevention strategies for African American students. The intervention committee selected video safety messages featuring African American actors as the most culturally relevant cyber...

  10. Experimental Studies of Selected Aqueous Electrochemical Systems Relevant for Materials Processing in the Fabrications of Microelectronic Components and Direct Alcohol Fuel Cells

    Science.gov (United States)

    Shi, Xingzhao

    A broad range of electrochemical techniques are employed in this dissertation to investigate a selected set of aqueous electrochemical systems that are relevant for materials processing in the fabrication of microelectronic devices and direct alcohol fuel cells. In terms of technical applications, this work covers three main experimental systems: (i) chemical mechanical planarization (CMP), (ii) electro-less nickel deposition, and (iii) direct alkaline glycerol fuel cells. The first two areas are related to electronic device fabrications and the third topic is related to cost-effective energy conversion. The common electrochemical aspect of these different systems is that, in all these cases the active material characteristics are governed by complex (often multi-step) reactions occurring at metal-liquid (aqueous) interfaces. Electro-analytical techniques are ideally suited for studying the detailed mechanisms of such reactions, and the present investigation is largely focused on developing adequate analytical strategies for probing these reaction mechanisms. In the fabrication of integrated circuits, certain steps of materials processing involve CMP of Al deposited on thin layers of diffusion barrier materials like Ta/TaN, Co, or Ti/TiN. A specific example of this situation is found in the processing of replacement metal gates used for high-k/metal-gate transistors. Since the commonly used barrier materials are nobler than Al, the Al interface in contact with the barrier can become prone to galvanic corrosion in the wet CMP environment. Using model systems of coupon electrodes and two specific barrier metals, Ta and Co, the electrochemical factors responsible for these corrosion effects are investigated here in a moderately acidic (pH = 4.0) abrasive-free solution. The techniques of cyclic voltammetry and impedance spectroscopy are combined with strategic measurements of galvanic currents and open circuit potentials (OCPs). L-ascorbic acid (AA) is employed as a

  11. Transplacental exposure to AZT induces adverse neurochemical and behavioral effects in a mouse model: protection by L-acetylcarnitine.

    Directory of Open Access Journals (Sweden)

    Anna Rita Zuena

    Full Text Available Maternal-fetal HIV-1 transmission can be prevented by administration of AZT, alone or in combination with other antiretroviral drugs to pregnant HIV-1-infected women and their newborns. In spite of the benefits deriving from this life-saving prophylactic therapy, there is still considerable uncertainty on the potential long-term adverse effects of antiretroviral drugs on exposed children. Clinical and experimental studies have consistently shown the occurrence of mitochondrial dysfunction and increased oxidative stress following prenatal treatment with antiretroviral drugs, and clinical evidence suggests that the developing brain is one of the targets of the toxic action of these compounds possibly resulting in behavioral problems. We intended to verify the effects on brain and behavior of mice exposed during gestation to AZT, the backbone of antiretroviral therapy during human pregnancy. We hypothesized that glutamate, a neurotransmitter involved in excitotoxicity and behavioral plasticity, could be one of the major actors in AZT-induced neurochemical and behavioral alterations. We also assessed the antioxidant and neuroprotective effect of L-acetylcarnitine, a compound that improves mitochondrial function and is successfully used to treat antiretroviral-induced polyneuropathy in HIV-1 patients. We found that transplacental exposure to AZT given per os to pregnant mice from day 10 of pregnancy to delivery impaired in the adult offspring spatial learning and memory, enhanced corticosterone release in response to acute stress, increased brain oxidative stress also at birth and markedly reduced expression of mGluR1 and mGluR5 subtypes and GluR1 subunit of AMPA receptors in the hippocampus. Notably, administration during the entire pregnancy of L-acetylcarnitine was effective in preventing/ameliorating the neurochemical, neuroendocrine and behavioral adverse effects induced by AZT in the offspring. The present preclinical findings provide a

  12. Paradoxical sleep deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research

    Directory of Open Access Journals (Sweden)

    Sergio Tufik

    2009-09-01

    Full Text Available Sleep comprises approximately one-third of a person's lifetime, but its impact on health and medical conditions remains partially unrecognized. The prevalence of sleep disorders is increasing in modern societies, with significant repercussions on people's well-being. This article reviews past and current literature on the paradoxical sleep deprivation method as well as data on its consequences to animals, ranging from behavioral changes to alterations in the gene expression. More specifically, we highlight relevant experimental studies and our group's contribution over the last three decades.O sono ocupa cerca de um terço de nossas vidas, entretanto seu impacto na saúde e sua influência nas condições patológicas ainda não foi completamente elucidado. A prevalência dos distúrbios de sono é cada vez maior, sobretudo nas regiões mais industrializadas, repercutindo diretamente no bem-estar da população. Este artigo tem como objetivo sintetizar e atualizar a literatura a respeito do método de privação de sono paradoxal e seu panorama de conseqüências desde comportamentais até genéticas em animais. Ainda, destacamos a contribuição e relevância dos estudos experimentais realizados por nosso grupo nas ultimas três décadas.

  13. OVERVIEW OF THE RELEVANT INDICATORS OF DEFAULTED AND NON-DEFAULTED COMPANIES AND POSSIBILITIES OF IMPROVEMENT FOR THE RATING SYSTEMS USED BY THE ROMANIAN COMMERCIAL BANKS

    Directory of Open Access Journals (Sweden)

    Kovacs Ildiko

    2011-12-01

    Full Text Available Since the beginning of the financial and economic crises many news came to light which discussed the increasing number of non-performing loans, and the fact that as a result of the company break-downs, the bank portfolios have also gone worse and worse. In this paper our goal is to find out which internal factors influence the solvency of a company, therefore, to point out the weaknesses of the current Romanian rating systems, which as we will see, do not take into only relevant criteria when according a loan to a company. In order to conduct this study, we choose 18 indicators from several categories to predict bankruptcy. Some of the indicators mentioned above are really common in the international and the Romanian literature (e.g. ROA, ROE, ROS, assets turnover ratio, some of them are less. On a sample of 3000 Romanian companies we use the T-test statistical method to find out if an indicator is significant or not. The sample consists of companies (defaulted and non-defaulted as well which have presented their financial statements (balance, profit and loss account between 1999 and 2008. For each company a set of 18 financial indicators was calculated, but the results obtained show that only 8 of them is significant in predicting bankruptcy: ROA, assets turnover ratio, equity/total assets, general leverage, current assets to total assets, cash to total assets, total assets and sales. In the next step, by analyzing the obligatory forms used in credit lending, we conclude which indicators are used by different Romanian commercial banks. We found that only four out of seven banks calculate all of the significant indicators identified in the first part of the paper. Finally, we made a proposal about which quantitative indicators should the banks use to minimize the credit losses and to avoid the overdue payments. In addition, we consider that the banks should pay attention to the qualitative factors as well to effectively filter out non

  14. Challenge and perspective: the relevance of ultraviolet (UV) radiation and the vitamin D endocrine system (VDES) for psoriasis and other inflammatory skin diseases.

    Science.gov (United States)

    Reichrath, Jörg; Saternus, Roman; Vogt, Thomas

    2017-03-16

    During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites. Human keratinocytes contain the enzymatic machinery (CYP27B1) for the synthesis of the biologically most active natural vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), representing an autonomous vitamin D3 pathway. Cutaneous production of 1,25(OH)2D3 may mediate intracrine, autocrine and paracrine effects on keratinocytes and on neighboring cells. Many skin cells (including keratinocytes, sebocytes, fibroblasts, melanocytes, macrophages and other skin immune cells) express the vitamin D receptor (VDR), an absolute pre-requisite for exerting genomic effects of 1,25(OH)2D3 and analogs. The VDR is a member of the superfamily of trans-acting transcriptional regulatory factors, which also contains the steroid and thyroid hormone receptors as well as the retinoid-X receptors (RXR) and retinoic acid receptors (RAR). A large body of evidence, including cDNA microarray analyses of mRNAs, indicates that as many as 500-1000 genes may be controlled by VDR ligands that regulate a broad variety of cellular functions including growth, differentiation, and apoptosis. Clinical and laboratory investigations, including the observation that 1,25(OH)2D3 is very effective in inducing the terminal differentiation and in inhibiting the proliferation of cultured human keratinocytes have resulted in the use of 1

  15. Korrek, volledig, relevant

    DEFF Research Database (Denmark)

    Bergenholtz, Henning; Gouws, Rufus

    2007-01-01

    as detrimental to the status of a dictionary as a container of linguistic knowledge. This paper shows that, from a lexicographic perspective, such a distinction is not relevant. What is important is that definitions should contain information that is relevant to and needed by the target users of that specific......In explanatory dictionaries, both general language dictionaries and dictionaries dealing with languages for special purposes, the lexicographic definition is an important item to present the meaning of a given lemma. Due to a strong linguistic bias, resulting from an approach prevalent in the early...

  16. In vivo magnetic resonance studies reveal neuroanatomical and neurochemical abnormalities in the serine racemase knockout mouse model of schizophrenia.

    Science.gov (United States)

    Puhl, Matthew D; Mintzopoulos, Dionyssios; Jensen, J Eric; Gillis, Timothy E; Konopaske, Glenn T; Kaufman, Marc J; Coyle, Joseph T

    2015-01-01

    Decreased availability of the N-methyl-D-aspartate receptor (NMDAR) co-agonist D-serine is thought to promote NMDAR hypofunction and contribute to the pathophysiology of schizophrenia, including neuroanatomical abnormalities, such as cortical atrophy and ventricular enlargement, and neurochemical abnormalities, such as aberrant glutamate and γ-aminobutyric acid (GABA) signaling. It is thought that these abnormalities directly relate to the negative symptoms and cognitive impairments that are hallmarks of the disorder. Because of the genetic complexity of schizophrenia, animal models of the disorder are extremely valuable for the study of genetically predisposing factors. Our laboratory developed a transgenic mouse model lacking serine racemase (SR), the synthetic enzyme of d-serine, polymorphisms of which are associated with schizophrenia. Null mutants (SR-/-) exhibit NMDAR hypofunction and cognitive impairments. We used 9.4 T magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to compare in vivo brain structure and neurochemistry in wildtype (WT) and SR-/- mice. Mice were anesthetized with isoflurane for MRI and MRS scans. Compared to WT controls, SR-/- mice exhibited 23% larger ventricular volumes (pcomparable to those previously reported in humans with schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Magnesium Sulfate Prevents Neurochemical and Long-Term Behavioral Consequences of Neonatal Excitotoxic Lesions: Comparison Between Male and Female Mice.

    Science.gov (United States)

    Daher, Ismaël; Le Dieu-Lugon, Bérénice; Dourmap, Nathalie; Lecuyer, Matthieu; Ramet, Lauriane; Gomila, Cathy; Ausseil, Jérôme; Marret, Stéphane; Leroux, Philippe; Roy, Vincent; El Mestikawy, Salah; Daumas, Stéphanie; Gonzalez, Bruno; Leroux-Nicollet, Isabelle; Cleren, Carine

    2017-10-01

    Magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery is proposed as a neuroprotective strategy against neurological alterations such as cerebral palsy in newborns. However, long-term beneficial or adverse effects of MgSO4 and sex-specific sensitivity remain to be investigated. We conducted behavioral and neurochemical studies of MgSO4 effects in males and females, from the perinatal period to adolescence in a mouse model of cerebral neonatal lesion. The lesion was produced in 5-day-old (P5) pups by ibotenate intracortical injection. MgSO4 (600 mg/kg, i.p.) prior to ibotenate prevented lesion-induced sensorimotor alterations in both sexes at P6 and P7. The lesion increased glutamate level at P10 in the prefrontal cortex, which was prevented by MgSO4 in males. In neonatally lesioned adolescent mice, males exhibited more sequelae than females in motor and cognitive functions. In the perirhinal cortex of adolescent mice, the neonatal lesion induced an increase in vesicular glutamate transporter 1 density in males only, which was negatively correlated with cognitive scores. Long-term sequelae were prevented by neonatal MgSO4 administration. MgSO4 never induced short- or long-term deleterious effect on its own. These results also strongly suggest that sex-specific neuroprotection should be foreseen in preterm infants. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  18. The Relevance of Literature.

    Science.gov (United States)

    Dunham, L. L.

    1971-01-01

    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  19. Is Information Still Relevant?

    Science.gov (United States)

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  20. A synthetic five amino acid propeptide increases dopamine neuron differentiation and neurochemical function

    Science.gov (United States)

    Littrell, OM; Fuqua, JL; Richardson, AD; Turchan-Cholewo, J.; Hascup, ER; Huettl, P; Pomerleau, F; Bradley, LH; Gash, DM; Gerhardt, GA

    2012-01-01

    A major consequence of Parkinson’s disease (PD) involves the loss of dopaminergic neurons in the substantia nigra (SN) and a subsequent loss of dopamine (DA) in the striatum. We have shown that glial cell line-derived neurotrophic factor (GDNF) shows robust restorative and protective effects for DA neurons in rats, non-human primates and possibly in humans. Despite GDNF’s therapeutic potential, its clinical value has been questioned due to its limited diffusion to target areas from its large size and chemical structure. Several comparatively smaller peptides are thought to be generated from the prosequence. A five amino-acid peptide, dopamine neuron stimulating peptide-5 (DNSP-5), has been proposed to demonstrate biological activity relevant to neurodegenerative disease. We tested the in vitro effects of DNSP-5 in primary dopaminergic neurons dissected from the ventral mesencephalon of E14 Sprague Dawley rat fetuses. Cells were treated with several doses (0.03, 0.1, 1.0, 10.0 ng/mL) of GDNF, DNSP-5, or an equivalent volume of citrate buffer (vehicle). Morphological features of tyrosine hydroxylase positive neurons were quantified for each dose. DNSP-5 significantly increased (p<0.001) all differentiation parameters compared to citrate vehicle (at one or more dose). For in vivo studies, a unilateral DNSP-5 treatment (30 µg) was administered directly to the SN. Microdialysis in the ipsilateral striatum was performed 28 days after treatment to determine extracellular levels of DA and its primary metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). A single treatment significantly increased (~66%) extracellular DA levels compared to vehicle, while DA metabolites were unchanged. Finally, the protective effects of DNSP-5 against staurosporine-induced cytotoxicity were investigated in a neuronal cell line showing substantial protection by DNSP-5. Altogether, these studies strongly indicate biological activity of DNSP-5 and suggest that DNSP-5 has

  1. Identifying relevant areas of functioning in children and youth with Cerebral Palsy using the ICF-CY coding system: from whose perspective?

    Science.gov (United States)

    Schiariti, Veronica; Mâsse, Louise C

    2014-09-01

    A standardized methodology endorsed by the World Health Organization was used to select the most relevant International Classification of Functioning, Disability and Health for children and youth (ICF-CY) categories to inform the development of the ICF Core Sets for CY with Cerebral Palsy (CP). The aim of this study was to appraise comparatively the results of the four studies included in the preparatory phase of the project exploring relevant areas of functioning in CY with CP. ICF-CY categories identified in the preparatory studies - systematic review, global expert survey, qualitative study, and clinical study - were ranked. We compared the ranking percentile scores of the categories across studies. Each study emphasized different ICF-CY components and provided unique categories. Professionals from the health, education and social sectors described areas of functioning that were well distributed across the ICF-CY components (global expert survey), CY with CP and caregivers highlighted areas within the components activity and participation (a & p) and environmental factors (qualitative study), while the research community and clinical encounters mainly focused on body functions and a & p (systematic review and clinical study). This study highlights the need to consider all relevant perspectives when describing the functional profile of CY with CP. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. Identification and distribution of neuronal nitric oxide synthase and neurochemical markers in the neuroepithelial cells of the gill and the skin in the giant mudskipper, Periophthalmodon schlosseri.

    Science.gov (United States)

    Zaccone, Giacomo; Lauriano, Eugenia Rita; Kuciel, Michał; Capillo, Gioele; Pergolizzi, Simona; Alesci, Alessio; Ishimatsu, Atsushi; Ip, Yuen Kwong; Icardo, Jose M

    2017-08-05

    Mudskippers are amphibious fishes living in mudflats and mangroves. These fishes hold air in their large buccopharyngeal-opercular cavities where respiratory gas exchange takes place via the gills and higher vascularized epithelium lining the cavities and also the skin epidermis. Although aerial ventilation response to changes in ambient gas concentration has been studied in mudskippers, the localization and distribution of respiratory chemoreceptors, their neurochemical coding and function as well as physiological evidence for the gill or skin as site for O2 and CO2 sensing are currently not known. In the present study we assessed the distribution of serotonin, acetylcholine, catecholamines and nitric oxide in the neuroepithelial cells (NECs) of the mudskipper gill and skin epithelium using immunohistochemistry and confocal microscopy. Colocalization studies showed that 5-HT is coexpressed with nNOS, Na+/K+-ATPase, TH and VAChT; nNOS is coexpressed with Na+/K+-ATPase and TH in the skin. In the gill 5-HT is coexpressed with nNOS and VAhHT and nNOS is coexpressed with Na+/K+-ATPase and TH. Acetylcholine is also expressed in chain and proximal neurons projecting to the efferent filament artery and branchial smooth muscle. The serotonergic cells c labeled with VAChT, nNOS and TH, thus indicating the presence of NEC populations and the possibility that these neurotransmitters (other than serotonin) may act as primary transmitters in the hypoxic reflex in fish gills. Immunolabeling with TH antibodies revealed that NECs in the gill and the skin are innervated by catecholaminergic nerves, thus suggesting that these cells are involved in a central control of branchial functions through their relationships with the sympathetic branchial nervous system. The Na+/K+-ATPase in mitochondria-rich cells (MRCs), which are most concentrated in the gill lamellar epithelium, is colabeled with nNOS and associated with TH nerve terminals. TH-immunopositive fine varicosities were also

  3. Behavioral and neurochemical analysis of ongoing bone cancer pain in rats.

    Science.gov (United States)

    Remeniuk, Bethany; Sukhtankar, Devki; Okun, Alec; Navratilova, Edita; Xie, Jennifer Y; King, Tamara; Porreca, Frank

    2015-10-01

    Cancer-induced bone pain is described as dull, aching ongoing pain. Ongoing bone cancer pain was characterized after intratibial injection of breast cancer cells in rats. Cancer produced time-dependent bone remodeling and tactile hypersensitivity but no spontaneous flinching. Conditioned place preference (CPP) and enhanced dopamine (DA) release in the nucleus accumbens (NAc) shell was observed after peripheral nerve block (PNB) selectively in tumor-bearing rats revealing nociceptive-driven ongoing pain. Oral diclofenac reversed tumor-induced tactile hypersensitivity but did not block PNB-induced CPP or NAc DA release. Tumor-induced tactile hypersensitivity, and PNB-induced CPP and NAc DA release, was blocked by prior subcutaneous implantation of a morphine pellet. In sham rats, morphine produced a modest but sustained increase in NAc DA release. In contrast, morphine produced a transient 5-fold higher NAc DA release in tumor bearing rats compared with sham morphine rats. The possibility that this increased NAc DA release reflected the reward of pain relief was tested by irreversible blockade of rostral anterior cingulate cortex (rACC) μ-opioid receptors (MORs). The rACC MOR blockade prevented the morphine-induced transient increased NAc DA release in tumor bearing rats but did not affect morphine-induced effects in sham-operated animals. Consistent with clinical experience, ongoing cancer pain was controlled by morphine but not by a dose of diclofenac that reversed evoked hypersensitivity. Additionally, the intrinsic reward of morphine can be dissociated from the reward of relief of cancer pain by blockade of rACC MOR. This approach allows mechanistic and therapeutic assessment of ongoing cancer pain with likely translation relevance.

  4. Clinical Relevance of Adipokines

    Directory of Open Access Journals (Sweden)

    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  5. Oxytocin release in magnocellular nuclei: neurochemical mediators and functional significance during gestation

    Science.gov (United States)

    Armstrong, William E.; Crowley, William R.

    2010-01-01

    When released from dendrites within the supraoptic (SON) and paraventricular (PVN) nuclei (intranuclear release) during suckling, oxytocin exerts autocrine and paracrine effects on oxytocin neurons that are necessary for the unique timing and episodic pattern of oxytocin release into the systemic circulation that is characteristic of lactation. Recent reports have shown that stimulation of central noradrenergic and histaminergic receptors are both necessary for intranuclear release of oxytocin in response to suckling. In addition, in vitro studies indicate that excitatory amino acids may also be critical for central oxytocin secretion, although in vivo experiments have not provided direct support for this hypothesis. In addition to a critical role in intranuclear oxytocin release during lactation, norepinephrine has also been shown to stimulate central oxytocin during gestation. Stimulation of central oxytocin receptors during gestation appears critical for normal systemic oxytocin secretion in responses to suckling during the subsequent period of lactation. Oxytocin receptor blockade during pregnancy alters normal timing of systemic oxytocin release during suckling and reduces milk delivery. Several adaptations occur in the central oxytocin system that are necessary for determining the unique response characteristic observed during parturition and gestation. Central oxytocin receptor stimulation during gestation has been implicated in pregnancy-related morphological changes in magnocellular oxytocin neurons, disinhibition of oxytocin neurons to GABA, and adaptations in membrane response characteristics of oxytocin neurons. In conclusion, intranuclear oxytocin release during gestation and lactation are critical for establishing, and then evoking the unique pattern of systemic oxytocin secretion in response to the suckling offspring necessary for adequate milk delivery. Furthermore, activation of central noradrenergic receptors appears to be critical for release of

  6. Linking task analysis to information relevance.

    Science.gov (United States)

    Durso, Francis T; Sethumadhavan, Arathi; Crutchfield, Jerry

    2008-10-01

    The main objective of this study is to present a methodology for computing information relevance. Relevance is a pervasive term used in several domains, such as pragmatics, information science, and psychology. Quantifying the relevance of information can be helpful in effective display design. Displays should be designed so that the more relevant information is more easily accessed. This procedure focuses on computing the relevance of a piece of information by taking into account three aspects of tasks that use the information: the number of different tasks that make use of the information, the frequency of occurrence of those tasks, and the criticality of those tasks. The methodology can be used to compute the aggregate relevance of a piece of information for a particular component of a system or for the entire system. This methodology was illustrated using the domain of air traffic control (ATC). In support of the validity of the methodology, we were able to confirm the value of weather information and traffic information in ATC towers. The method can be used to derive information relevance, a characteristic of information that has implications for display design for any domain. Designers can use information about aggregate relevance to design information displays that feature the most relevant information.

  7. Oxytocin release in magnocellular nuclei: neurochemical mediators and functional significance during gestation

    OpenAIRE

    Bealer, Steven L.; Armstrong, William E.; Crowley, William R

    2010-01-01

    When released from dendrites within the supraoptic (SON) and paraventricular (PVN) nuclei (intranuclear release) during suckling, oxytocin exerts autocrine and paracrine effects on oxytocin neurons that are necessary for the unique timing and episodic pattern of oxytocin release into the systemic circulation that is characteristic of lactation. Recent reports have shown that stimulation of central noradrenergic and histaminergic receptors are both necessary for intranuclear release of oxytoci...

  8. Behavioral and neurochemical effects of chronic L-DOPA treatment on nonmotor sequelae in the hemiparkinsonian rat.

    Science.gov (United States)

    Eskow Jaunarajs, Karen L; Dupre, Kristin B; Ostock, Corinne Y; Button, Thomas; Deak, Terrence; Bishop, Christopher

    2010-10-01

    Depression and anxiety are the prevalent nonmotor symptoms that worsen quality of life for Parkinson's disease (PD) patients. Although dopamine (DA) cell loss is a commonly proposed mechanism, the reported efficacy of DA replacement therapy with L-DOPA on affective symptoms is inconsistent. To delineate the effects of DA denervation and chronic L-DOPA treatment on affective behaviors, male Sprague-Dawley rats received unilateral 6-hydroxydopamine or sham lesions and were treated daily with L-DOPA (12 mg/kg+benserazide, 15 mg/kg, subcutaneously) or vehicle (0.9% NaCl, 0.1% ascorbic acid) for 28 days before commencing investigations into anxiety (locomotor chambers, social interaction) and depression-like behaviors (forced swim test) during the OFF phase of L-DOPA. One hour after the final treatments, rats were killed and striatum, prefrontal cortex, hippocampus, and amygdala were analyzed through high-performance liquid chromatography for monoamine levels. In locomotor chambers and social interaction, DA lesions exerted mild anxiogenic effects. Surprisingly, chronic L-DOPA treatment did not improve these effects. Although DA lesion reduced climbing behaviors on day 2 of exposure to the forced swim test, chronic L-DOPA treatment did not reverse these effects. Neurochemically, L-DOPA treatment in hemiparkinsonian rats reduced norepinephrine levels in the prefrontal cortex, striatum, and hippocampus. Collectively, these data suggest that chronic L-DOPA therapy in severely DA-lesioned rats does not improve nonmotor symptoms and may impair nondopaminergic processes, indicating that long-term L-DOPA therapy does not exert necessary neuroplastic changes for improving affect.

  9. Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells.

    Science.gov (United States)

    Li, Xiangtang; Hu, Hankun; Zhao, Shulin; Liu, Yi-Ming

    2016-05-17

    Chemical stimulus-induced neurotransmitter release from neuronal cells is well-documented. However, the dynamic changes in neurochemical release remain to be fully explored. In this work, a three-layered microfluidic chip was fabricated and evaluated for studying the dynamics of neurotransmitter release from PC-12 cells. The chip features integration of a nanoliter sized chamber for cell perfusion, pneumatic pressure valves for fluidic control, a microfluidic channel for electrophoretic separation, and a nanoelectrospray emitter for ionization in MS detection. Deploying this platform, a microchip electrophoresis-mass spectrometric method (MCE-MS) was developed to simultaneously quantify important neurotransmitters, including dopamine (DA), serotonin (5-HT), aspartic acid (Asp), and glutamic acid (Glu) without need for labeling or enrichment. Monitoring neurotransmitter release from PC-12 cells exposed to KCl (or alcohol) revealed that all four neurotransmitters investigated were released. Two release patterns were observed, one for the two monoamine neurotransmitters (i.e., DA and 5-HT) and another for the two amino acid neurotransmitters. Release dynamics for the two monoamine neurotransmitters was significantly different. The cells released DA most quickly and heavily in response to the stimulation. After exposure to the chemical stimulus for 4 min, the DA level in the perfusate from the cells was 86% lower than that at the beginning. Very interestingly, the cells started to release 5-HT in large quantities when they stopped releasing DA. These results suggest that DA and 5-HT are packaged into different vesicle pools and they are mobilized differently in response to chemical stimuli. The microfluidic platform proposed is proven useful for monitoring cellular release in biological studies.

  10. Effects of polychlorinated biphenyl (PCB) on regulation of thyroid-, growth-, and neurochemically related developmental processes in young rats

    Energy Technology Data Exchange (ETDEWEB)

    Juarez de Ku, L.M.

    1992-01-01

    Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than or in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.

  11. The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains.

    Science.gov (United States)

    Eicher, J D; Stein, C M; Deng, F; Ciesla, A A; Powers, N R; Boada, R; Smith, S D; Pennington, B F; Iyengar, S K; Lewis, B A; Gruen, J R

    2015-04-01

    A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples - Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) - and then combined results by meta-analysis. DYX2 markers, specifically those in the 3' untranslated region of DCDC2 (P = 1.43 × 10(-4) ), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10(-2) ) and DRD2 (P = 9.22 × 10(-3) ) and nicotinic-related genes CHRNA3 (P = 2.51 × 10(-3) ) and BDNF (P = 8.14 × 10(-3) ) with case-control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated. © 2015 The Authors. Genes, Brain and Behavior published by

  12. Neurochemical and Neuroanatomical Plasticity Following Memory Training and Yoga Interventions in Older Adults with Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Hongyu Yang

    2016-11-01

    Full Text Available Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET and a mind-body practice (yogic meditation, in healthy seniors with mild cognitive impairment (MCI using structural magnetic resonance imaging (MRI and proton magnetic resonance spectroscopy (1H-MRS. Senior participants (age ≥ 55 years with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini yoga for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC and bilateral hippocampus were measured by structural MRI and 1H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamate-glutamine (Glx, choline-containing compounds (Cho, including glycerophosphocholine and phosphocholine, gamma-aminobutyric acid (GABA, and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG. In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. 1H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with mild cognitive impairment. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes.

  13. HISTAMINE H3 RECEPTOR INVERSE AGONISTS ON COGNITIVE AND MOTOR PROCESSES: RELEVANCE TO ALZHEIMER’S DISEASE, ADHD, SCHIZOPHRENIA AND DRUG ABUSE

    Directory of Open Access Journals (Sweden)

    Divya eVohora

    2012-10-01

    Full Text Available Histamine H3 receptor antagonists/ inverse agonists possess potential to treat diverse disease states of the central nervous system (CNS. Cognitive dysfunction and motor impairments are the hallmark of multifarious neurodegenerative and/or psychiatric disorders. This review presents the various neurobiological/ neurochemical evidences available so far following H3 receptor inverse agonists/ antagonists in the pathophysiology of Alzheimer’s disease (AD, attention-deficit hyperactivity disorder (ADHD, schizophrenia and drug abuse each of which is accompanied by deficits of some aspects of cognitive and/or motor functions. Whether the H3 receptor inverse agonism modulates the neurochemical basis underlying the disease condition or affects only the cognitive/motor component of the disease process is discussed with the aim to provide a rationale for their use in diverse disease states that are interlinked and are accompanied by some common motor, cognitive and attentional deficits.

  14. Extended Paper: Reconceptualising Foundational Assumptions of Resilience: A Cross-Cultural, Spatial Systems Domain of Relevance for Agency and Phenomenology in Resilience

    Science.gov (United States)

    Downes, Paul

    2017-01-01

    This article seeks to amplify Bronfenbrenner's (1979) concerns with concentric structured, nested systems and phenomenology, for Ungar's (2012) extension of resilience to systems based on Bronfenbrenner's (1979, 1995) socio-ecological paradigm. Resilience rests on interconnected assumptions regarding space, agency and system blockage, as well as…

  15. System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability

    DEFF Research Database (Denmark)

    Xiao, Zhenyu; Chang, Jer-Gung; Hendriks, Ivo A

    2015-01-01

    Genotoxic agents can cause replication fork stalling in dividing cells due to DNA lesions, eventually leading to replication fork collapse when the damage is not repaired. Small Ubiquitin-like Modifiers (SUMOs) are known to counteract replication stress, nevertheless, only a small number...... of relevant SUMO target proteins are known. To address this, we have purified and identified SUMO-2 target proteins regulated by replication stress in human cells. The developed methodology enabled single step purification of His10-SUMO-2 conjugates under denaturing conditions with high yield and high purity....... Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 hours of Hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and 2 proteins were down-regulated for SUMOylation, whereas after 24 hours, 35 proteins were up...

  16. Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice

    Science.gov (United States)

    Xue, Xue; Yang, Jing-Yu; He, Yi; Wang, Li-Rong; Liu, Ping; Yu, Li-Sha; Bi, Guo-Hua; Zhu, Ming-Ming; Liu, Yue-Yang; Xiang, Rong-Wu; Yang, Xiao-Ting; Fan, Xin-Yu; Wang, Xiao-Min; Qi, Jia; Zhang, Hong-Jie; Wei, Tuo; Cui, Wei; Ge, Guang-Lu; Xi, Zheng-Xiong; Wu, Chun-Fu; Liang, Xing-Jie

    2016-07-01

    Methamphetamine (METH) abuse is a serious social and health problem worldwide. At present, there are no effective medications to treat METH addiction. Here, we report that aggregated single-walled carbon nanotubes (aSWNTs) significantly inhibited METH self-administration, METH-induced conditioned place preference and METH- or cue-induced relapse to drug-seeking behaviour in mice. The use of aSWNTs alone did not significantly alter the mesolimbic dopamine system, whereas pretreatment with aSWNTs attenuated METH-induced increases in extracellular dopamine in the ventral striatum. Electrochemical assays suggest that aSWNTs facilitated dopamine oxidation. In addition, aSWNTs attenuated METH-induced increases in tyrosine hydroxylase or synaptic protein expression. These findings suggest that aSWNTs may have therapeutic effects for treatment of METH addiction by oxidation of METH-enhanced extracellular dopamine in the striatum.

  17. Effects of microcystin-LR and cylindrospermopsin on plant-soil systems: A review of their relevance for agricultural plant quality and public health.

    Science.gov (United States)

    Machado, J; Campos, A; Vasconcelos, V; Freitas, M

    2017-02-01

    Toxic cyanobacterial blooms are recognized as an emerging environmental threat worldwide. Although microcystin-LR is the most frequently documented cyanotoxin, studies on cylindrospermopsin have been increasing due to the invasive nature of cylindrospermopsin-producing cyanobacteria. The number of studies regarding the effects of cyanotoxins on agricultural plants has increased in recent years, and it has been suggested that the presence of microcystin-LR and cylindrospermopsin in irrigation water may cause toxic effects in edible plants. The uptake of these cyanotoxins by agricultural plants has been shown to induce morphological and physiological changes that lead to a potential loss of productivity. There is also evidence that edible terrestrial plants can bioaccumulate cyanotoxins in their tissues in a concentration dependent-manner. Moreover, the number of consecutive cycles of watering and planting in addition to the potential persistence of microcystin-LR and cylindrospermopsin in the environment are likely to result in groundwater contamination. The use of cyanotoxin-contaminated water for agricultural purposes may therefore represent a threat to both food security and food safety. However, the deleterious effects of cyanotoxins on agricultural plants and public health seem to be dependent on the concentrations studied, which in most cases are non-environmentally relevant. Interestingly, at ecologically relevant concentrations, the productivity and nutritional quality of some agricultural plants seem not to be impaired and may even be enhanced. However, studies assessing if the potential tolerance of agricultural plants to these concentrations can result in cyanotoxin and allergen accumulation in the edible tissues are lacking. This review combines the most current information available regarding this topic with a realistic assessment of the impact of cyanobacterial toxins on agricultural plants, groundwater quality and public health. Copyright © 2016

  18. Neurochemical differences in learning and memory paradigms among rats supplemented with anthocyanin-rich blueberry diets and exposed to acute doses of 56Fe particles

    Science.gov (United States)

    Poulose, Shibu M.; Rabin, Bernard M.; Bielinski, Donna F.; Kelly, Megan E.; Miller, Marshall G.; Thanthaeng, Nopporn; Shukitt-Hale, Barbara

    2017-02-01

    The protective effects of anthocyanin-rich blueberries (BB) on brain health are well documented and are particularly important under conditions of high oxidative stress, which can lead to "accelerated aging." One such scenario is exposure to space radiation, consisting of high-energy and -charge particles (HZE), which are known to cause cognitive dysfunction and deleterious neurochemical alterations. We recently tested the behavioral and neurochemical effects of acute exposure to HZE particles such as 56Fe, within 24-48 h after exposure, and found that radiation primarily affects memory and not learning. Importantly, we observed that specific brain regions failed to upregulate antioxidant and anti-inflammatory mechanisms in response to this insult. To further examine these endogenous response mechanisms, we have supplemented young rats with diets rich in BB, which are known to contain high amounts of antioxidant-phytochemicals, prior to irradiation. Exposure to 56Fe caused significant neurochemical changes in hippocampus and frontal cortex, the two critical regions of the brain involved in cognitive function. BB supplementation significantly attenuated protein carbonylation, which was significantly increased by exposure to 56Fe in the hippocampus and frontal cortex. Moreover, BB supplementation significantly reduced radiation-induced elevations in NADPH-oxidoreductase-2 (NOX2) and cyclooxygenase-2 (COX-2), and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and frontal cortex. Overall results indicate that 56Fe particles may induce their toxic effects on hippocampus and frontal cortex by reactive oxygen species (ROS) overload, which can cause alterations in the neuronal environment, eventually leading to hippocampal neuronal death and subsequent impairment of cognitive function. Blueberry supplementation provides an effective preventative measure to reduce the ROS load on the CNS in an event of acute HZE exposure.

  19. Neurochemical abnormalities in the brainstem of the Sudden Infant Death Syndrome (SIDS).

    Science.gov (United States)

    Machaalani, Rita; Waters, Karen A

    2014-12-01

    The brainstem has been a focus in Sudden Infant Death Syndrome (SIDS) research for 30 years. Physiological and animal model data show that cardiorespiratory, sleep, and arousal mechanisms are abnormal after exposure to SIDS risk factors or in infants who subsequently die from SIDS. As the brainstem houses the regulatory centres for these functions, it is the most likely site to find abnormalities. True to this hypothesis, data derived over the last 30 years shows that the brainstem of infants who died from SIDS exhibits abnormalities in a number of major neurotransmitter and receptor systems including: catecholamines, neuropeptides, acetylcholinergic, indole amines (predominantly serotonin and its receptors), amino acids (predominantly glutamate), brain derived neurotrophic growth factor (BDNF), and some cytokines. A pattern is emerging of particular brainstem nuclei being consistently affected including the dorsal motor nucleus of the vagus (DMNV), nucleus of the solitary tract (NTS), arcuate nucleus (AN) and raphe. We discuss the implications of these findings and directions that this may lead in future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. [Comparative neurochemical and physiological characteristics of catalepsy-like rest and sleep].

    Science.gov (United States)

    Demin, N N; Karmanova, I G; Rubinskaia, N L; Khomutetskaia, O E

    1977-01-01

    In vertebrates (excluding mammals), the rest is presented also by a special functional condition of the catalepsy type. In hens, its total duration is higher in the day-time, than in the twilight; it is completely absent at night. This natural condition in hens may be imitated by photogenic catalepsy which is developed in response to rhythmic illumination of animals. Cytospectrophotometric investigation of single cells of the supraoptic nucleus indicates that with respect to absence of changes in absolute content (per 1 cell) of protein in the neurons cataleptiform rest in hens does not differ from the sleep in rats. However, in contrast to sleep this immobilization is associated with the decrease of RNA content of the neurons, as well as with the absence of accumulation of proteins and RNA in gliocytes. During cataleptiform rest, insiginficant changes were found in the content of proteins and RNA in cells of ectomammilar nucleus of the additional optic system and thalamic round nucleus. Cataleptiform (photogenic) immobilization in hens is presumably a metabolically passive form of rest as compared to the sleep in rats, which is characterized by anabolic processes in the brain.

  1. 3,5,6,7,8,3′,4′-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation

    Science.gov (United States)

    Sawamoto, Atsushi; Okuyama, Satoshi; Amakura, Yoshiaki; Yoshimura, Morio; Yamada, Takashi; Yokogoshi, Hidehiko; Nakajima, Mitsunari

    2017-01-01

    We previously reported that the subcutaneous administration of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), a citrus polymethoxyflavone, attenuated depressive-like behavior and increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of a corticosterone-induced depression-like mouse model. We herein demonstrated that (1) HMF was detectable in the brain 10 and 30 min after its oral administration, (2) orally administered HMF improved chronic unpredictable mild stress (CUMS)-induced pathological conditions, including body weight loss and depressive-like behavior, and CUMS-induced neurochemical changes, such as reduction in BDNF expression, decrease in neurogenesis, and decreased level of phosphorylated calcium-calmodulin-dependent protein kinase II in the hippocampus, and (3) these effects of HMF were inhibited by the pre-administration of U0126, a mitogen-activated protein (MAP) kinase inhibitor. These results suggest that orally administered HMF is beneficial for the upregulation of BDNF in the hippocampus via the extracellular signal-regulated kinase1/2 (ERK1/2)/MAP system, which may account for its antidepression effects. PMID:29023414

  2. 3,5,6,7,8,3′,4′-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation

    Directory of Open Access Journals (Sweden)

    Atsushi Sawamoto

    2017-10-01

    Full Text Available We previously reported that the subcutaneous administration of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF, a citrus polymethoxyflavone, attenuated depressive-like behavior and increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus of a corticosterone-induced depression-like mouse model. We herein demonstrated that (1 HMF was detectable in the brain 10 and 30 min after its oral administration, (2 orally administered HMF improved chronic unpredictable mild stress (CUMS-induced pathological conditions, including body weight loss and depressive-like behavior, and CUMS-induced neurochemical changes, such as reduction in BDNF expression, decrease in neurogenesis, and decreased level of phosphorylated calcium-calmodulin-dependent protein kinase II in the hippocampus, and (3 these effects of HMF were inhibited by the pre-administration of U0126, a mitogen-activated protein (MAP kinase inhibitor. These results suggest that orally administered HMF is beneficial for the upregulation of BDNF in the hippocampus via the extracellular signal-regulated kinase1/2 (ERK1/2/MAP system, which may account for its antidepression effects.

  3. Differences in neurochemical profiles of two gadid species under ocean warming and acidification.

    Science.gov (United States)

    Schmidt, Matthias; Windisch, Heidrun Sigrid; Ludwichowski, Kai-Uwe; Seegert, Sean Lando Levin; Pörtner, Hans-Otto; Storch, Daniela; Bock, Christian

    2017-01-01

    system of Gadus morhua close to the optimum of the temperature range. Since a former study showed that juvenile G. morhua might be slightly more behaviourally resilient to CO2 at this respective temperature, we conclude that the observed change of GABAergic metabolism could be involved in counteracting OA induced behavioural changes. This may serve as a fitness advantage of this respective species compared to B. saida in a future warmer, more acidified polar ocean.

  4. Relevant areas of functioning in children with cerebral palsy based on the international classification of functioning, disability and health coding system: a clinical perspective.

    Science.gov (United States)

    Schiariti, Veronica; Mâsse, Louise C

    2015-02-01

    In the context of the development of the International Classification of Functioning, Disability and Health Core Sets for children and youth with cerebral palsy, an evidence-based methodology was implemented to select the most relevant categories out of the entire classification. The aim of this study was to describe the contribution of the clinical perspective to select categories of functioning in children and youth with cerebral palsy. We conducted a chart review of clinical assessments of children and youth with cerebral palsy aged 0 to 18 years in a tertiary level center. In total, 129 International Classification of Functioning categories were covered in clinical encounters: representing 19% body structures, 33% body functions, 37% activity and participation, and 11% environmental factors. Our findings can guide clinical assessments and goal-setting of this population. This important perspective will inform the development of the International Classification of Functioning, Disability and Health Core Sets for children and youth with cerebral palsy. © The Author(s) 2014.

  5. Avicequinone C Isolated from Avicennia marina Exhibits 5α-Reductase-Type 1 Inhibitory Activity Using an Androgenic Alopecia Relevant Cell-Based Assay System

    Directory of Open Access Journals (Sweden)

    Ruchy Jain

    2014-05-01

    Full Text Available Avicennia marina (AM exhibits various biological activities and has been traditionally used in Egypt to cure skin diseases. In this study, the methanolic heartwood extract of AM was evaluated for inhibitory activity against 5α-reductase (5α-R [E.C.1.3.99.5], the enzyme responsible for the over-production of 5α-dihydrotestosterone (5α-DHT causing androgenic alopecia (AGA. An AGA-relevant cell-based assay was developed using human hair dermal papilla cells (HHDPCs, the main regulator of hair growth and the only cells within the hair follicle that are the direct site of 5α-DHT action, combined with a non-radioactive thin layer chromatography (TLC detection technique. The results revealed that AM is a potent 5α-R type 1 (5α-R1 inhibitor, reducing the 5α-DHT production by 52% at the final concentration of 10 µg/mL. Activity-guided fractionation has led to the identification of avicequinone C, a furanonaphthaquinone, as a 5α-R1 inhibitor with an IC50 of 9.94 ± 0.33 µg/mL or 38.8 ± 1.29 µM. This paper is the first to report anti-androgenic activity through 5α-R1 inhibition of AM and avicequinone C.

  6. Identifying Critical States through the Relevance Index

    Directory of Open Access Journals (Sweden)

    Andrea Roli

    2017-02-01

    Full Text Available The identification of critical states is a major task in complex systems, and the availability of measures to detect such conditions is of utmost importance. In general, criticality refers to the existence of two qualitatively different behaviors that the same system can exhibit, depending on the values of some parameters. In this paper, we show that the relevance index may be effectively used to identify critical states in complex systems. The relevance index was originally developed to identify relevant sets of variables in dynamical systems, but in this paper, we show that it is also able to capture features of criticality. The index is applied to two prominent examples showing slightly different meanings of criticality, namely the Ising model and random Boolean networks. Results show that this index is maximized at critical states and is robust with respect to system size and sampling effort. It can therefore be used to detect criticality.

  7. Role of the endocannabinoid system in brain functions relevant for schizophrenia: an overview of human challenge studies with cannabis or ∆9-tetrahydrocannabinol (THC).

    Science.gov (United States)

    Bossong, Matthijs G; Jansma, J Martijn; Bhattacharyya, Sagnik; Ramsey, Nick F

    2014-07-03

    Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology of schizophrenia, which signifies a potential application for this system in the treatment of this disorder. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of schizophrenia. Here we review human studies that investigated acute effects of cannabis or ∆9-tetrahydrocannabinol (THC) on brain functions that are implicated in schizophrenia. Results suggest that the impact of THC administration depends on the difficulty of the task performed. Impaired performance of cognitive paradigms is reported on more challenging tasks, which is associated with both activity deficits in temporal and prefrontal areas and a failure to deactivate regions of the default mode network. Comparable reductions in prefrontal activity and impairments in deactivation of the default mode network are seen in patients during performance of cognitive paradigms. Normal performance levels after THC administration demonstrated for less demanding tasks are shown to be related to either increased neural effort in task-specific regions ('neurophysiological inefficiency'), or recruitment of alternative brain areas, which suggests a change in strategy to meet cognitive demands. Particularly a pattern of performance and brain activity corresponding with an inefficient working memory system is consistently demonstrated in patients. These similarities in brain function between intoxicated healthy volunteers and schizophrenia patients provide an argument for a role of the endocannabinoid system in symptoms of schizophrenia, and further emphasize this system as a potential novel target for treatment of these symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Brain hemispheric differences in the neurochemical effects of lead, prenatal stress, and the combination and their amelioration by behavioral experience.

    Science.gov (United States)

    Cory-Slechta, Deborah A; Weston, Douglas; Liu, Sue; Allen, Joshua L

    2013-04-01

    Brain lateralization, critical to mediation of cognitive functions and to "multitasking," is disrupted in conditions such as attention deficit disorder and schizophrenia. Both low-level lead (Pb) exposure and prenatal stress (PS) have been associated with mesocorticolimbic system-mediated executive-function cognitive and attention deficits. Mesocorticolimbic systems demonstrate significant laterality. Thus, altered brain lateralization could play a role in this behavioral toxicity. This study examined laterality of mesocorticolimbic monoamines (frontal cortex, nucleus accumbens, striatum, midbrain) and amino acids (frontal cortex) in male and female rats subjected to lifetime Pb exposure (0 or 50 ppm in drinking water), PS (restraint stress on gestational days 16-17), or the combination with and without repeated learning behavioral experience. Control males exhibited prominent laterality, particularly in midbrain and also in frontal cortex and striatum; females exhibited less laterality, and this was primarily striatal. Lateralized Pb ± PS induced neurotransmitter changes were assessed only in males because of limited sample sizes of Pb + PS females. In males, Pb ± PS changes occurred in left hemisphere of frontal cortex and right hemisphere of midbrain. Behavioral experience modified the laterality of Pb ± PS-induced neurotransmitter changes in a region-dependent manner. Notably, behavioral experience eliminated Pb ± PS neurotransmitter changes in males. These findings underscore the critical need to evaluate both sexes and brain hemispheres for the mechanistic understanding of sex-dependent differences in neuro- and behavioral toxicity. Furthermore, assessment of central nervous system mechanisms in the absence of behavioral experience, shown here for males, may constitute less relevant models of human health effects.

  9. An introduction to the life cycle assessment (LCA) of bioelectrochemical systems (BES) for sustainable energy and product generation: Relevance and key aspects

    DEFF Research Database (Denmark)

    Pant, Deepak; Singh, Anoop; Bogaert, Gilbert Van

    2011-01-01

    Bioelectrochemical systems (BESs) are devices capable of converting organic waste fraction present in wastewaters into useful energy vectors such as electricity or hydrogen. In recent years a large amount of research has been done on these unique systems in order to improve their performance both...... in terms of waste treatment as well as electric current production. Already there are plans to upscale this technology to convince the end-users of its potential. However, there are not many studies available on the life cycle of these systems with the current state of the art. In this article...... saving in cost and electric power produced should be factored as well. The results of LCA should show that with current knowledge and existing materials, how well the MFCs compares with the existing treatment methods such as anaerobic digestion. Further, given the amount of research going...

  10. Role of quantity of additional food to predators as a control in predator-prey systems with relevance to pest management and biological conservation.

    Science.gov (United States)

    Srinivasu, P D N; Prasad, B S R V

    2011-10-01

    Necessity to understand the role of additional food as a tool in biological control programs is being increasingly felt, particularly due to its eco-friendly nature. A thorough mathematical analysis in this direction revealed the vital role of quality and quantity of the additional food in the controllability of the predator-prey systems. In this article controllability of the additional food--provided predator-prey system is studied from perspectives of pest eradication and biological conservation. Time optimal paths have been constructed to drive the state of the system to a desired terminal state by choosing quantity of the additional food as control variable. The theory developed in this article has been illustrated by solving problems related to pest eradication and biological conservation.

  11. Using an integrated information system to reduce interruptions and the number of non-relevant contacts in the inpatient pharmacy at tertiary hospital

    Directory of Open Access Journals (Sweden)

    Saleh Binobaid

    2017-07-01

    The research design is based on a quasi-experiment using pre-post testing using the continuous improvement approach. The improvement project is performed using a six-step method. A survey was conducted in Prince Sultan Military Medical City (PSMMC to measure the volume and types of telephone calls before and after implementation to evaluate the impact of the new system. Beforehand of the system implementation, during the two-week measurement period, all pharmacies received 4466 calls and the majority were follow-up calls. Subsequently of the integrated system rollout, there was a significant reduction (p > 0.001 in the volume of telephone calls to 2630 calls; besides, the calls nature turned out to be more professional inquiries (p > 0.001. As a result, avoidable interruptions and workload were decreased.

  12. Investigations on the magnetic field coupling of automotive high voltage systems to determine relevant parameters for an EMR-optimized designing

    Science.gov (United States)

    Krause, David; John, Werner; Weigel, Robert

    2016-03-01

    The implementation of electrical drive trains in modern vehicles is a new challenge for EMC development. This contribution depicts a variety of investigations on magnetic field coupling of automotive high-voltage (HV) systems in order to fulfil the requirements of an EMR-optimized designing. The theoretical background is discussed within the scope of current analysis, including the determination of current paths and spectral behaviour. It furthermore presents models of shielded HV cables with particular focus on the magnetic shielding efficiency. Derived findings are validated by experimental measurements of a state-of-the-art demonstrator on system level. Finally EMC design rules are discussed in the context of minimized magnetic fields.

  13. L-Edge X-ray Absorption Spectroscopy of Dilute Systems Relevant to Metalloproteins Using an X-ray Free-Electron Laser

    NARCIS (Netherlands)

    Mitzner, Rolf; Rehanek, Jens; Kern, Jan; Gul, Sheraz; Hattne, Johan; Taguchi, Taketo; Alonso-Mori, Roberto; Tran, Rosalie; Weniger, Christian; Schroeder, Henning; Quevedo, Wilson; Laksmono, Hartawan; Sierra, Raymond G.; Han, Guangye; Lassalle-Kaiser, Benedikt; Koroidov, Sergey; Kubicek, Katharina; Schreck, Simon; Kunnus, Kristjan; Brzhezinskaya, Maria; Firsov, Alexander; Minitti, Michael P.; Turner, Joshua J.; Moeller, Stefan; Sauter, Nicholas K.; Bogan, Michael J.; Nordlund, Dennis; Schlotter, William F.; Messinger, Johannes; Borovik, Andrew; Techert, Simone; de Groot, Frank M. F.|info:eu-repo/dai/nl/08747610X; Foehlisch, Alexander; Erko, Alexei; Bergmann, Uwe; Yachandra, Vittal K.; Wernet, Philippe; Yano, Junko

    2013-01-01

    L-edge spectroscopy of 3d transition metals provides important electronic structure information and has been used in many fields. However, the use of this method for studying dilute aqueous systems, such as metalloenzymes, has not been prevalent because of severe radiation damage and the lack of

  14. Relevance of in vitro tests of adhesive and composite dental materials. A review in 3 parts. Part 3: in vitro tests of adhesive systems.

    Science.gov (United States)

    Heintze, Siegward D; Zimmerli, Brigitte

    2011-01-01

    In the third part of this review of laboratory testing, methods of testing adhesive systems are evaluated. Test set-ups that are used to analyze the restorative material in combination with the adhesive system are presented. Currently, there is no standardized protocol available for the evaluation of adhesives. This complicates any direct comparisons of values between different testing institutes. Therefore, the statistically evaluated ranking of the different adhesives is more important than mean values. Depending on the testing institute, a correlation between bond strength measurements and clinical outcomes may exist. Qualitative analysis of adhesive/tooth interaction can help explain the functioning of a system, but the depth of penetration of the adhesive cannot predict bond strength. Indirect bond measurements or analyses of the interactions of adhesive and composite materials, such as dye penetration or marginal analysis, do not correlate or correlate only partially with clinical findings. Adhesive systems should be tested in vitro and compared to a well-known standard adhesive before they are used in the clinic. Water storage of specimens for several months before testing increases the predictability of the bonding performance of the tested adhesive.

  15. Multi-agent System for Obtaining Relevant Genes in Expression Analysis between Young and Older Women with Triple Negative Breast Cancer.

    Science.gov (United States)

    González-Briones, Alfonso; Ramos, Juan; De Paz, Juan Francisco; Corchado, Juan Manuel

    2015-10-21

    Triple negative breast cancer is an aggressive form of breast cancer. Despite treatment with chemotherapy, relapses are frequent and response to these treatments is not the same in younger women as in older women. Therefore, the identification of genes that cause this difference is required. The identification of therapeutic targets is one of the sought after goals to develop new drugs. Within the range of different hybridization techniques, the developed system uses expression array analysis to measure the expression of the signal levels of thousands of genes in a given sample. Probesets of Gene 1.0 ST GeneChip arrays provide categorical genome transcript coverage, providing a measurement of the expression level of the sample. This paper proposes a multi-agent system to manage information of expression arrays, with the goal of providing an intuitive system that is also extensible to analyze and interpret the results. The roles of agent integrate different types of techniques, statistical and data mining methods that select a set of genes, searching techniques that find pathways in which such genes participate, and an information extraction procedure that applies a CBR system to check if these genes are involved in the disease.

  16. Injection chamber test stands for optical testing of GDI injection systems in practically relevant engine conditions; Einspritzkammerpruefstaende fuer die optische Untersuchung von BDE-Einspritzduesen unter motorisch relevanten Bedingungen

    Energy Technology Data Exchange (ETDEWEB)

    Ipp, W.; Lindner, R.; Goldluecke, J.; Schmitz, I.; Leipertz, A. [Erlangen Univ. (Germany). Lehrstuhl fuer Technische Thermodynamik; Lutz, M. [Energie und Systemtechnik, ESYTEC GmbH, Erlangen (Germany)

    2005-07-01

    In GDI engines, the injection system has a significant effect on mixture formation, combustion and pollutant emissions. Therefore it is of basic interest to analyze the injection process at engine relevant conditions, for which contactless optical measurement techniques are particularly suitable. To investigate the specific behavior of the injection system it is required to separate the fuel propagation and evaporation processes from the influence of air motion and wall-interaction as it occurs inside the engine. For this purpose pressure vessels with optical accesses are used which are able to work at engine relevant conditions, regarding pressure as well as temperature. Beside this, for planning of an optical injection test bench, special demands have to be considered like the optimal and multifunctional use of optical measurement techniques, size, handling and safety, the utilization of existing resources as well as internal company regulations of the customer and last but not least, the costs. Considering these aspects the Department for Engineering Thermodynamics (LTT) of the University of Erlangen and the company ESYTEC Energie- und Systemtechnik GmbH have designed and constructed several optical test benches, some of them also for GDI systems. In this contribution the requirements for the optical investigation of GDI injection systems are discussed and an example of an already working test rig is shown. (orig.)

  17. [Correlation of neurochemical metabolism with memory function in young adult patients with first-episode depression studied with proton magnetic resonance spectroscopy].

    Science.gov (United States)

    Liu, Weibo; Yu, Hualiang; Jiang, Biao; Zheng, Leilei; Yu, Shaohua; Pan, Bing; Yu, Risheng

    2013-07-01

    To investigate the correlation of neurochemical metabolism in hippocampus with memory function in young adult patients with first-episode depression. Twenty patients with first-episode depression (patient group) and fifteen health subjects (control group) were enrolled in the study. The neurochemical metabolism, including the levels of N-acetylaspartate (NAA), Choline (Cho), Creatine (Cr), Myoinositol (mI) were measured by proton magnetic resonance spectroscope (1H-MRS) in bilateral hippocampus. Wechsler Memory Scale (WMS) were used to examine the memory function in both groups. The memory quotient (89.15 ±6.62) of patient group was significantly lower than that of controls (P memory,short-term memory and immediate memory in patients were also lower than those of controls (Pmemory deficit and abnormal metabolism function of neuron cell in hippocampus coexist in young adult patients with first-episode depression, and the lower NAA/Cr and higher mI/Cr ratio in the left hippocampus may result in the memory deficit.

  18. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes.

    Science.gov (United States)

    Bhutani, Mohit Kumar; Bishnoi, Mahendra; Kulkarni, Shrinivas K

    2009-03-01

    Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

  19. Technical complications during veno-venous extracorporeal membrane oxygenation and their relevance predicting a system-exchange--retrospective analysis of 265 cases.

    Directory of Open Access Journals (Sweden)

    Matthias Lubnow

    Full Text Available OBJECTIVES: Technical complications are a known hazard in veno-venous extracorporeal membrane oxygenation (vvECMO. Identifying these complications and predictive factors indicating a developing system-exchange was the goal of the study. METHODS: Retrospective study on prospectively collected data of technical complications including 265 adult patients (Regensburg ECMO Registry, 2009-2013 with acute respiratory failure treated with vvECMO. Alterations in blood flow resistance, gas transfer capability, hemolysis, coagulation and hemostasis parameters were evaluated in conjunction with a system-exchange in all patients with at least one exchange (n = 83. RESULTS: Values presented as median (interquartile range. Patient age was 50(36-60 years, the SOFA score 11(8-14.3 and the Murray lung injury Score 3.33(3.3-3.7. Cumulative ECMO support time 3411 days, 9(6-15 days per patient. Mechanical failure of the blood pump (n = 5, MO (n = 2 or cannula (n = 1 accounted for 10% of the exchanges. Acute clot formation within the pump head (visible clots, increase in plasma free hemoglobin (frHb, serum lactate dehydrogenase (LDH, n = 13 and MO (increase in pressure drop across the MO, n = 16 required an urgent system-exchange, of which nearly 50% could be foreseen by measuring the parameters mentioned below. Reasons for an elective system-exchange were worsening of gas transfer capability (n = 10 and device-related coagulation disorders (n = 32, either local fibrinolysis in the MO due to clot formation (increased D-dimers [DD], decreased platelet count; n = 24, or device-induced hyperfibrinolysis (increased DD, decreased fibrinogen [FG], decreased platelet count, diffuse bleeding tendency; n = 8, which could be reversed after system-exchange. Four MOs were exchanged due to suspicion of infection. CONCLUSIONS: The majority of ECMO system-exchanges could be predicted by regular inspection of the complete ECMO circuit, evaluation of gas exchange, pressure drop

  20. Medically Relevant Acinetobacter Species Require a Type II Secretion System and Specific Membrane-Associated Chaperones for the Export of Multiple Substrates and Full Virulence.

    Science.gov (United States)

    Harding, Christian M; Kinsella, Rachel L; Palmer, Lauren D; Skaar, Eric P; Feldman, Mario F

    2016-01-01

    Acinetobacter baumannii, A. nosocomialis, and A. pittii have recently emerged as opportunistic human pathogens capable of causing severe human disease; however, the molecular mechanisms employed by Acinetobacter to cause disease remain poorly understood. Many pathogenic members of the genus Acinetobacter contain genes predicted to encode proteins required for the biogenesis of a type II secretion system (T2SS), which have been shown to mediate virulence in many Gram-negative organisms. Here we demonstrate that Acinetobacter nosocomialis strain M2 produces a functional T2SS, which is required for full virulence in both the Galleria mellonella and murine pulmonary infection models. Importantly, this is the first bona fide secretion system shown to be required for virulence in Acinetobacter. Using bioinformatics, proteomics, and mutational analyses, we show that Acinetobacter employs its T2SS to export multiple substrates, including the lipases LipA and LipH as well as the protease CpaA. Furthermore, the Acinetobacter T2SS, which is found scattered amongst five distinct loci, does not contain a dedicated pseudopilin peptidase, but instead relies on the type IV prepilin peptidase, reinforcing the common ancestry of these two systems. Lastly, two of the three secreted proteins characterized in this study require specific chaperones for secretion. These chaperones contain an N-terminal transmembrane domain, are encoded adjacently to their cognate effector, and their disruption abolishes type II secretion of their cognate effector. Bioinformatic analysis identified putative chaperones located adjacent to multiple previously known type II effectors from several Gram-negative bacteria, which suggests that T2SS chaperones constitute a separate class of membrane-associated chaperones mediating type II secretion.

  1. Quantum mechanical calculations of conformationally relevant 1H and 13C NMR chemical shifts of N-, O-, and S-substituted calixarene systems.

    Science.gov (United States)

    Bifulco, Giuseppe; Riccio, Raffaele; Gaeta, Carmine; Neri, Placido

    2007-01-01

    QM GIAO calculations of (13)C and (1)H chemical shift values of the ArCH(2)Ar group in N-, O-, and S-substituted calixarene systems were performed with a hybrid DFT functional MPW1PW91 and 6-31G(d,p) basis set. A good reproduction of experimental data was obtained for some representative calixarenes and for a series of simplified calixarene models. This allowed the derivation of chemical shift surfaces versus phi and chi dihedral angles. The applicability of chemical shift surfaces in the study of calixarene conformational features is illustrated.

  2. [A new stage of development of gerontology and geriatrics in Russia: problems of creation of a geriatric care system. Part 1. Relevance, regulatory infrastructure].

    Science.gov (United States)

    Anisimov, V N; Serpov, V Yu; Finagentov, A V; Khavinson, V Kh

    2017-01-01

    This article is a 1st part of the analytical review, focused on a new step in development of geriatrics in Russia. Creation of state system geriatric care as important part of state politics in the area of enhancement of quality of life was proved. General aspects of improvement of social support of disable elderly persons in condition of restricted budget and interagency separation was presented. Establishment of unified system of medical social support and gerotechnologies for the elderly was substantiated, as a mechanism facilitated life activity and decreasing of demographic loading on economic status of regions of Russian Federation. Legislative and normative regulations of gerontology and geriatric development were observed as well. Accepted legislative and normative acts were analyzed for period since 1977 to 2014. The necessity of approaches to regulation modernization for elderly was demonstrated. Analytical review on number of legislative state documents issued after meeting of Presidium of State Council of the Russian Federation being in August 2014 was also presented. Applicability of these documents for realization new strategy of gerontology and geriatrics development in Russia was proved.

  3. Resetting the neurohormonal balance in heart failure (HF): the relevance of the natriuretic peptide (NP) system to the clinical management of patients with HF.

    Science.gov (United States)

    Rubattu, Speranza; Triposkiadis, Filippos

    2017-05-01

    The natriuretic peptide (NP) system, which includes atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide, has an important role in cardiovascular homeostasis, promoting a number of physiological effects including diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system. Heart failure (HF) is associated with defects in NP processing and synthesis, and there is a strong relationship between NP levels and disease state. NPs are useful biomarkers in HF, and their use in diagnosis and evaluation of prognosis is well established, particularly in patients with HF with reduced ejection fraction (HFrEF). There has also been interest in their use to guide disease management and therapeutic decision making. An understanding of NPs in HF has also resulted in interest in synthetic NPs for the treatment of HF and in treatments that target neprilysin, a protease that degrades NPs. A novel drug, the angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696), which simultaneously inhibits neprilysin and blocks the angiotensin II type I receptor, was shown to have a favorable efficacy and safety profile in patients with HFrEF and has been approved for use in such patients in Europe and the USA. In light of the development of treatments that target neprilysin and of recent data in relation to synthetic NPs, it is timely to review the current understanding of the role of NPs in HF and their use in diagnosis, evaluating prognosis and guiding treatment, as well as their place in HF therapy.

  4. Telecommunication Support System Using Keywords and Their Relevant Information in Videoconferencing — Presentation Method for Keeping Audience's Concentration at Distance Lectures

    Science.gov (United States)

    Asai, Kikuo; Kondo, Kimio; Kobayashi, Hideaki; Saito, Fumihiko

    We developed a prototype system to support telecommunication by using keywords selected by the speaker in a videoconference. In the traditional presentation style, a speaker talks and uses audiovisual materials, and the audience at remote sites looks at these materials. Unfortunately, the audience often loses concentration and attention during the talk. To overcome this problem, we investigate a keyword presentation style, in which the speaker holds keyword cards that enable the audience to see additional information. Although keyword captions were originally intended for use in video materials for learning foreign languages, they can also be used to improve the quality of distance lectures in videoconferences. Our prototype system recognizes printed keywords in a video image at a server, and transfers the data to clients as multimedia functions such as language translation, three-dimensional (3D) model visualization, and audio reproduction. The additional information is collocated to the keyword cards in the display window, thus forming a spatial relationship between them. We conducted an experiment to investigate the properties of the keyword presentation style for an audience. The results suggest the potential of the keyword presentation style for improving the audience's concentration and attention in distance lectures by providing an environment that facilitates eye contact during videoconferencing.

  5. Size-dependent distribution of radiocesium in riverbed sediments and its relevance to the migration of radiocesium in river systems after the Fukushima Daiichi Nuclear Power Plant accident.

    Science.gov (United States)

    Tanaka, Kazuya; Iwatani, Hokuto; Sakaguchi, Aya; Fan, Qiaohui; Takahashi, Yoshio

    2015-01-01

    We investigated the particle size distribution of radiocesium in riverbed sediments after the Fukushima Daiichi Nuclear Power Plant accident. Riverbed sediments were collected in the Abukuma River system in Fukushima and Miyagi Prefectures. The collected sediments were separated into 11 fractions, ranging from granular size (>2000 μm) to clay size (<2 μm) fractions. Cesium-137 concentrations were higher in the smaller particle size fractions, possibly reflecting specific surface areas and the mineralogy, in particular the clay mineral content. A gap in (137)Cs concentration was observed between the silt size and sand size fractions of riverbed sediments at downstream sites, whereas riverbed sediments at an upstream site did not show such a concentration gap. It is likely that selective transport of small particles in suspended state from upstream areas resulted in an accumulation of radiocesium in downstream areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Comparison of the physiological relevance of systemic vs. portal insulin delivery to evaluate whole body glucose flux during an insulin clamp.

    Science.gov (United States)

    Farmer, Tiffany D; Jenkins, Erin C; O'Brien, Tracy P; McCoy, Gregory A; Havlik, Allison E; Nass, Erik R; Nicholson, Wendell E; Printz, Richard L; Shiota, Masakazu

    2015-02-01

    To understand the underlying pathology of metabolic diseases, such as diabetes, an accurate determination of whole body glucose flux needs to be made by a method that maintains key physiological features. One such feature is a positive differential in insulin concentration between the portal venous and systemic arterial circulation (P/S-IG). P/S-IG during the determination of the relative contribution of liver and extra-liver tissues/organs to whole body glucose flux during an insulin clamp with either systemic (SID) or portal (PID) insulin delivery was examined with insulin infusion rates of 1, 2, and 5 mU·kg(-1)·min(-1) under either euglycemic or hyperglycemic conditions in 6-h-fasted conscious normal rats. A P/S-IG was initially determined with endogenous insulin secretion to exist with a value of 2.07. During an insulin clamp, while inhibiting endogenous insulin secretion by somatostatin, P/S-IG remained at 2.2 with PID, whereas, P/S-IG disappeared completely with SID, which exhibited higher arterial and lower portal insulin levels compared with PID. Consequently, glucose disappearance rates and muscle glycogen synthetic rates were higher, but suppression of endogenous glucose production and liver glycogen synthetic rates were lower with SID compared with PID. When the insulin clamp was performed with SID at 2 and 5 mU·kg(-1)·min(-1) without managing endogenous insulin secretion under euglycemic but not hyperglycemic conditions, endogenous insulin secretion was completely suppressed with SID, and the P/S-IG disappeared. Thus, compared with PID, an insulin clamp with SID underestimates the contribution of liver in response to insulin to whole body glucose flux. Copyright © 2015 the American Physiological Society.

  7. PERMCAT experiments with tritium at high helium flow rates relevant for the tritium extraction systems using the CAPER facility at TLK

    Energy Technology Data Exchange (ETDEWEB)

    Bükki-Deme, András, E-mail: andras.buekki-deme@kit.edu; Demange, David; Le, Thanh-Long; Fanghänel, Eleonore; Simon, Karl-Heinz

    2016-11-01

    Highlights: • We examined PERMCAT reactor efficiency processing tritiated water at high Helium carrier flow rates. • We have found that – as expected from previous studies – that the swamping ratio (ratio between the impurity and purge side flow rates) has a key effect on the decontamination factors. • On the other hand, some rather unexpected effects tend to show that the limiting phenomena of such specific operation of PERMCAT reactors (at high impurity flow rates, thus short residence time) lies on the kinetics of the isotope exchange reactions. - Abstract: Experiments are still necessary to consolidate the processes retained for the Tritium Extraction Systems of the European ITER Test Blanket Modules (TBM). A PERMCAT reactor combines a catalyst promoting isotope exchange reactions and a Pd/Ag membrane allowing tritium recovery from complex gaseous mixtures containing tritium in different chemical forms. Originally developed for the Tokamak Exhaust Processing, the PERMCAT process is also candidate to detritiate the water arising from an adsorption column installed in the TBM ancillary systems. We discuss the results of an extensive experimental campaign using a PERMCAT reactor to process Q{sub 2}O containing impurity gas mixtures at high flow rates. Two different experimental configurations were studied, namely PERMCAT stand-alone, and PERMCAT in combination with a zeolite molecular sieve bed (MSB, previously loaded with Q{sub 2}O) under regeneration. On the one hand, many expected behaviors were observed, such as the key influence of the swamping ratio (ratio between the impurity and purge side flow rates) on the decontamination factors. On the other hand, some rather unexpected effects tend to show that the limiting phenomena of such specific operation of PERMCAT reactors (at high flow rates, thus short residence time) lies on the kinetics of the isotope exchange reactions.

  8. Domains of health-related quality of life important and relevant to multiethnic English-speaking Asian systemic lupus erythematosus patients: a focus group study.

    Science.gov (United States)

    Ow, Yen Ling Mandy; Thumboo, Julian; Cella, David; Cheung, Yin Bun; Yong Fong, Kok; Wee, Hwee Lin

    2011-06-01

    To identify health-related quality of life (HRQOL) domains of importance to multiethnic Asian systemic lupus erythematosus (SLE) patients, to identify content gaps in existing SLE-specific HRQOL measures, and to determine whether the Patient-Reported Outcomes Measurement Information System (PROMIS) item banks could serve as a core set of questions for HRQOL assessment among SLE patients. English-speaking patients with physician-diagnosed SLE from a specialist clinic in a tertiary care hospital in Singapore and a patient support group were recruited. Thematic analysis was performed to distill themes from transcripts through open coding by 2 independent coders and axial coding for refinement of categories. Items from 3 existing SLE-specific measures and PROMIS Version 1.0 Item Banks were compared with identified subthemes. Twenty-seven female and 2 male participants (21 Chinese, 4 Malay, 3 Indian, 1 other) ages 23-62 years participated in 6 focus groups and 2 individual interviews, respectively. Twenty-one domains and 92 subthemes were identified. Domains of family, relationships, stigma and discrimination, and freedom were unaddressed by existing SLE-specific measures. Forty subthemes from 14 domains were addressed by the PROMIS Version 1.0 Item Banks (Physical Function, Pain, Fatigue, Sleep Disturbance, Sleep-Related Impairment, Anger, Anxiety, and Depression banks). Family and stigma and discrimination (identified as content gaps) may be accentuated in the Asian sociocultural context. PROMIS item banks have tremendous potential to serve as a core set of items for HRQOL assessment in SLE patients. Additional items may be written to fill the gaps in existing PROMIS item banks. Copyright © 2011 by the American College of Rheumatology.

  9. The placebo response: neurobiological and clinical issues of neurological relevance.

    Science.gov (United States)

    Pollo, Antonella; Benedetti, Fabrizio

    2009-01-01

    The recent upsurge in placebo research has demonstrated the sound neurobiological substrate of a phenomenon once believed to be only patient mystification, or at best a variable to control in clinical trials, bringing about a new awareness of its potential exploitation to the patient's benefit and framing it as a positive context effect, with the power to influence the therapy outcome. Placebo effects have been described both in the experimental setting and in different clinical conditions, many of which are of neurological interest. Multiple mechanisms have been described, namely conditioning and cognitive factors like expectation, desire, and reward. A body of evidence from neurochemical, pharmacological, and neuroimaging studies points to the involvement of neural pathways specific to single conditions, such as the activation of the endogenous antinociceptive system during placebo analgesia or the release of dopamine in the striatum of parkinsonian patients experiencing placebo reduction of motor impairment. The possible clinical applications of placebo studies range from the design of clinical trials incorporating specific recommendations and minimizing the use of placebo arms to the optimization of the context surrounding the patient, in order to maximize the placebo component present in any treatment.

  10. Evaluation of the Vitek MS Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry System for Identification of Clinically Relevant Filamentous Fungi

    Science.gov (United States)

    McMullen, Allison R.; Wallace, Meghan A.; Pincus, David H.; Wilkey, Kathy

    2016-01-01

    Invasive fungal infections have a high rate of morbidity and mortality, and accurate identification is necessary to guide appropriate antifungal therapy. With the increasing incidence of invasive disease attributed to filamentous fungi, rapid and accurate species-level identification of these pathogens is necessary. Traditional methods for identification of filamentous fungi can be slow and may lack resolution. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has emerged as a rapid and accurate method for identification of bacteria and yeasts, but a paucity of data exists on the performance characteristics of this method for identification of filamentous fungi. The objective of our study was to evaluate the accuracy of the Vitek MS for mold identification. A total of 319 mold isolates representing 43 genera recovered from clinical specimens were evaluated. Of these isolates, 213 (66.8%) were correctly identified using the Vitek MS Knowledge Base, version 3.0 database. When a modified SARAMIS (Spectral Archive and Microbial Identification System) database was used to augment the version 3.0 Knowledge Base, 245 (76.8%) isolates were correctly identified. Unidentified isolates were subcultured for repeat testing; 71/319 (22.3%) remained unidentified. Of the unidentified isolates, 69 were not in the database. Only 3 (0.9%) isolates were misidentified by MALDI-TOF MS (including Aspergillus amoenus [n = 2] and Aspergillus calidoustus [n = 1]) although 10 (3.1%) of the original phenotypic identifications were not correct. In addition, this methodology was able to accurately identify 133/144 (93.6%) Aspergillus sp. isolates to the species level. MALDI-TOF MS has the potential to expedite mold identification, and misidentifications are rare. PMID:27225405

  11. Evaluation of the Vitek MS Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry System for Identification of Clinically Relevant Filamentous Fungi.

    Science.gov (United States)

    McMullen, Allison R; Wallace, Meghan A; Pincus, David H; Wilkey, Kathy; Burnham, C A

    2016-08-01

    Invasive fungal infections have a high rate of morbidity and mortality, and accurate identification is necessary to guide appropriate antifungal therapy. With the increasing incidence of invasive disease attributed to filamentous fungi, rapid and accurate species-level identification of these pathogens is necessary. Traditional methods for identification of filamentous fungi can be slow and may lack resolution. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a rapid and accurate method for identification of bacteria and yeasts, but a paucity of data exists on the performance characteristics of this method for identification of filamentous fungi. The objective of our study was to evaluate the accuracy of the Vitek MS for mold identification. A total of 319 mold isolates representing 43 genera recovered from clinical specimens were evaluated. Of these isolates, 213 (66.8%) were correctly identified using the Vitek MS Knowledge Base, version 3.0 database. When a modified SARAMIS (Spectral Archive and Microbial Identification System) database was used to augment the version 3.0 Knowledge Base, 245 (76.8%) isolates were correctly identified. Unidentified isolates were subcultured for repeat testing; 71/319 (22.3%) remained unidentified. Of the unidentified isolates, 69 were not in the database. Only 3 (0.9%) isolates were misidentified by MALDI-TOF MS (including Aspergillus amoenus [n = 2] and Aspergillus calidoustus [n = 1]) although 10 (3.1%) of the original phenotypic identifications were not correct. In addition, this methodology was able to accurately identify 133/144 (93.6%) Aspergillus sp. isolates to the species level. MALDI-TOF MS has the potential to expedite mold identification, and misidentifications are rare. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Multimedia search engine with relevance feedback

    Science.gov (United States)

    Ciocca, Gianluigi; Schettini, Raimondo

    2001-12-01

    We present here a web-based protytpe for the interactive search of items in quality electronic catalogues. The system based on a multimedia information retrieval architecture, allows the user to query a multimedia database according to several retrieval strategies, and progressively refine the system's response by indicating the relevance, or non-relevance of the items retrieved. Once a subset of images meeting the user's information needs have been identified, these images can be displayed in a virtual exhibition that can be visited interactively by the user exploiting VRML technology.

  13. Submerged Medium Voltage Cable Systems at Nuclear Power Plants. A Review of Research Efforts Relevant to Aging Mechanisms and Condition Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Jason [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bernstein, Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); White, II, Gregory Von [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Glover, Steven F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Neely, Jason C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pena, Gary [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Williamson, Kenneth Martin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Zutavern, Fred J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gelbard, Fred [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    and industrial literature was performed to identify : 1) findings regarding the degradation mechanisms of submerged cabling and 2) condition monitoring methods that may prove useful in predict ing the remaining lifetime of submerged medium voltage p ower cables . The re search was conducted by a multi - disciplinary team , and s ources includ ed official NRC reports, n ational l aboratory reports , IEEE standards, conference and journal proceedings , magazine articles , PhD dissertations , and discussions with experts . The purpose of this work was to establish the current state - of - the - art in material degradation modeling and cable condition monitoring techniques and to identify research gaps . Subsequently, future areas of focus are recommended to address these research gaps and thus strengthen the efficacy of the NRC's developing cable condition monitoring program . Results of this literature review and details of the test ing recommendations are presented in this report . FOREWORD To ensure the safe, re liable, and cost - effective long - term operation of nuclear power plants, many systems, structures, and components must be continuously evaluated. The Nuclear Regulatory Commission (NRC) has identified that cables in submerged environments are of concern, particularly as plants are seeking license renewal. To date, there is a lack of consensus on aging and degradation mechanisms even though the area of submerged cables has been extensively studied. Consequently, the ability to make lifetime predictions for submerged cable does not yet exist. The NRC has engaged Sandia National Laboratories (SNL) to lead a coordinated effort to help elucidate the aging and degradation of cables in submerged environments by collaborating with cable manufacturers, utilities, universities, and other government agencies. A team of SNL experts was assembled from the laboratories including electrical condition monitoring, mat erial science, polymer degradation, plasma physics

  14. Hydrotectonics; principles and relevance

    Science.gov (United States)

    Kopf, R.W.

    1982-01-01

    Hydrotectonics combines the principles of hydraulics and rock mechanics. The hypothesis assumes that: (1) no faults are truly planar, (2) opposing noncongruent wavy wallrock surfaces form chambers and bottlenecks along the fault, and (3) most thrusting occurs beneath the water table. These physical constraints permit the following dynamics. Shear displacement accompanying faulting must constantly change the volume of each chamber. Addition of ground water liquefies dry fault breccia to a heavy incompressible viscous muddy breccia I call fault slurry. When the volume of a chamber along a thrust fault decreases faster than its fault slurry can escape laterally, overpressurized slurry is hydraulically injected into the base of near-vertical fractures in the otherwise impervious overriding plate. Breccia pipes commonly form where such fissures intersect. Alternating decrease and increase in volume of the chamber subjects this injection slurry to reversible surges that not only raft and abrade huge clasts sporadically spalled from the walls of the conduit but also act as a forceful hydraulic ram which periodically widens the conduit and extends its top. If the pipe perforates a petroleum reservoir, leaking hydrocarbons float to its top. Sudden faulting may generate a powerful water hammer that can be amplified at some distal narrow ends of the anastomosing plumbing system, where the shock may produce shatter cones. If vented on the Earth's surface, the muddy breccia, now called extrusion slurry, forms a mud volcano. This hypothesis suggests that many highly disturbed features presently attributed to such catastrophic processes as subsurface explosions or meteorite impacts are due to the rheology of tectonic slurry in an intermittently reactivated pressure-relief tube rooted in a powerful reciprocating hydrotectonic pump activated by a long-lived deep-seated thrust fault.

  15. Specific features of learning with nociceptive electrical reinforcement in rats of different genetic strains: role of brain neurotransmitter systems.

    Science.gov (United States)

    Kalyuzhnyi, A L; Litvinova, S V; Shulgovskii, V V; Panchenko, L F

    2005-01-01

    The interaction between neurotransmitter systems and opioid system in rats of different strains was studied during learning and emotional stress. The interaction between noradrenergic, serotoninergic, and opioid systems in the brain is the main neurochemical mechanism underlying learning reinforced by nociceptive electrical stimulation, which determine individual differences in the rate and type of learning.

  16. Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats.

    Science.gov (United States)

    Páleníček, Tomáš; Fujáková, Michaela; Brunovský, Martin; Horáček, Jiří; Gorman, Ingmar; Balíková, Marie; Rambousek, Lukáš; Syslová, Kamila; Kačer, Petr; Zach, Petr; Bubeníková-Valešová, Věra; Tylš, Filip; Kubešová, Anna; Puskarčíková, Jana; Höschl, Cyril

    2013-01-01

    Behavioral, neurochemical and pharmaco-EEG profiles of a new synthetic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats were examined. Locomotor effects, prepulse inhibition (PPI) of acoustic startle reaction (ASR), dopamine and its metabolite levels in nucleus accumbens (NAc), EEG power spectra and coherence in freely moving rats were analysed. Amphetamine was used as a reference compound. 2C-B had a biphasic effect on locomotion with initial inhibitory followed by excitatory effect; amphetamine induced only hyperlocomotion. Both drugs induced deficits in the PPI; however they had opposite effects on ASR. 2C-B increased dopamine but decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the NAc. Low doses of 2C-B induced a decrease in EEG power spectra and coherence. On the contrary, high dose of 2C-B 50 mg/kg had a temporally biphasic effect with an initial decrease followed by an increase in EEG power; decrease as well as increase in EEG coherence was observed. Amphetamine mainly induced an increase in EEG power and coherence in theta and alpha bands. Increases in the theta and alpha power and coherence in 2C-B and amphetamine were temporally linked to an increase in locomotor activity and DA levels in NAc. 2C-B is a centrally active compound similar to other hallucinogens, entactogens and stimulants. Increased dopamine and decreased DOPAC in the NAc may reflect its psychotomimetic and addictive potential and monoaminoxidase inhibition. Alterations in brain functional connectivity reflected the behavioral and neurochemical changes produced by the drug; a correlation between EEG changes and locomotor behavior was observed.

  17. Modulatory effect of cilostazol on tramadol-induced behavioral and neurochemical alterations in rats challenged across the forced swim despair test

    Directory of Open Access Journals (Sweden)

    Noha M. Gamil

    2016-06-01

    Full Text Available Pain-associated depression is encountered clinically in some cases such as cancer, chronic neuropathy, and after operations. Tramadol is an opioid analgesic drug that may modulate monoaminergic neurotransmission by inhibition of noradrenaline and serotonin reuptake that may contribute to its antidepressant-like effects. Clinically, tramadol is used either alone or in combination with other NSAIDs in the treatment of cases associated with pain and depression, e.g. low back pain, spinal cord injury, and post-operative pain management. However, tramadol monotherapy as an antidepressant is impeded by severe adverse effects including seizures and serotonin syndrome. Interestingly, phosphodiesterase-III inhibitors demonstrated novel promising antidepressant effects. Among which, cilostazol was reported to attenuate depression in post-stroke cases, geriatrics and patients undergoing carotid artery stenting. Therefore, this study was carried out to investigate the possible antidepressant-like effects of tramadol and/or cilostazol on the behavioral level in experimental animals, and to examine the neurochemical and biochemical effects of tramadol, cilostazol and their combination in rats, in order to explore the probable mechanisms of action underlying their effects. To achieve our target, male albino mice and rats were randomly allocated into five groups and administered either vehicle for control, fluoxetine (20 mg/kg, p.o., tramadol HCl (20 mg/kg, p.o., cilostazol (100 mg/kg, p.o., or combination of both tramadol and cilostazol. At day 14, mice and rats were challenged in the tail suspension test and forced swim test, respectively. Rats were sacrificed and brains were isolated for determination of brain monoamines, MDA, NO, SOD, and TNF-α. The current results showed that concurrent administration of cilostazol to tramadol-treated animals modulated depression on the behavioral level, and showed ameliorative neurochemical and biochemical effects

  18. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Science.gov (United States)

    Robins, Meridith T; Lu, Julie; van Rijn, Richard M

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  19. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Meridith T Robins

    Full Text Available The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61 exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  20. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  1. Relevance theory: pragmatics and cognition.

    Science.gov (United States)

    Wearing, Catherine J

    2015-01-01

    Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication. © 2014 John Wiley & Sons, Ltd.

  2. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  3. Relevance Feedback in Content Based Image Retrieval: A Review

    Directory of Open Access Journals (Sweden)

    Manesh B. Kokare

    2011-01-01

    Full Text Available This paper provides an overview of the technical achievements in the research area of relevance feedback (RF in content-based image retrieval (CBIR. Relevance feedback is a powerful technique in CBIR systems, in order to improve the performance of CBIR effectively. It is an open research area to the researcher to reduce the semantic gap between low-level features and high level concepts. The paper covers the current state of art of the research in relevance feedback in CBIR, various relevance feedback techniques and issues in relevance feedback are discussed in detail.

  4. The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene- and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana Digestive Tract Infection on Gene Expression

    Science.gov (United States)

    Baldascino, Elena; Di Cristina, Giulia; Tedesco, Perla; Hobbs, Carl; Shaw, Tanya J.; Ponte, Giovanna; Andrews, Paul L. R.

    2017-01-01

    The gastric ganglion is the largest visceral ganglion in cephalopods. It is connected to the brain and is implicated in regulation of digestive tract functions. Here we have investigated the neurochemical complexity (through in silico gene expression analysis and immunohistochemistry) of the gastric ganglion in Octopus vulgaris and tested whether the expression of a selected number of genes was influenced by the magnitude of digestive tract parasitic infection by Aggregata octopiana. Novel evidence was obtained for putative peptide and non-peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine, molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin–related peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were also identified in this context for the first time. We report evidence for acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide related peptide, and receptors for cephalotocin and octopressin, confirming previous publications. The effects of Aggregata observed here extend those previously described by showing effects on the gastric ganglion; in animals with a higher level of infection, genes implicated in inflammation (NFκB, fascin, serpinB10 and the toll-like 3 receptor) increased their relative expression, but TNF-α gene expression was lower as was expression of other genes implicated in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione peroxidase). Elevated Aggregata levels in the octopuses corresponded to an increase in the expression of the cholecystokininA receptor and the small cardioactive peptide-related peptide. In contrast, we observed decreased relative expression of cephalotocin, dopamine β-hydroxylase, peptide PRQFV-amide, and tachykinin-related peptide genes. A discussion is provided on (i) potential roles of the various molecules in food intake

  5. The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene- and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana Digestive Tract Infection on Gene Expression

    Directory of Open Access Journals (Sweden)

    Elena Baldascino

    2017-12-01

    Full Text Available The gastric ganglion is the largest visceral ganglion in cephalopods. It is connected to the brain and is implicated in regulation of digestive tract functions. Here we have investigated the neurochemical complexity (through in silico gene expression analysis and immunohistochemistry of the gastric ganglion in Octopus vulgaris and tested whether the expression of a selected number of genes was influenced by the magnitude of digestive tract parasitic infection by Aggregata octopiana. Novel evidence was obtained for putative peptide and non-peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine, molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin–related peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were also identified in this context for the first time. We report evidence for acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide related peptide, and receptors for cephalotocin and octopressin, confirming previous publications. The effects of Aggregata observed here extend those previously described by showing effects on the gastric ganglion; in animals with a higher level of infection, genes implicated in inflammation (NFκB, fascin, serpinB10 and the toll-like 3 receptor increased their relative expression, but TNF-α gene expression was lower as was expression of other genes implicated in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione peroxidase. Elevated Aggregata levels in the octopuses corresponded to an increase in the expression of the cholecystokininA receptor and the small cardioactive peptide-related peptide. In contrast, we observed decreased relative expression of cephalotocin, dopamine β-hydroxylase, peptide PRQFV-amide, and tachykinin-related peptide genes. A discussion is provided on (i potential roles of the various molecules

  6. SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

    Energy Technology Data Exchange (ETDEWEB)

    Lim, S-I; Yoo, C-H [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

  7. Anormalidades neuropatológicas e neuroquímicas no transtorno afetivo bipolar Neuropathological and neurochemical abnormalities in bipolar disorder

    Directory of Open Access Journals (Sweden)

    Benício Noronha Frey

    2004-09-01

    Full Text Available OBJETIVOS: Estudos pós-mortem, farmacológicos, de neuroimagem e em modelos animais têm demonstrado uma possível associação de mecanismos de sinalização intracelular na fisiopatologia do transtorno afetivo bipolar (TAB. Esse trabalho tem como objetivo revisar os achados em neuropatologia e bioquímica celular. MÉTODOS: Foi realizada uma pesquisa ao MEDLINE, entre 1980 e 2003, tendo sido utilizados os unitermos: bipolar disorder, signaling, second messengers e postmortem, além de referências cruzadas dos artigos selecionados. RESULTADOS: uropatológicos demonstraram uma diminuição do número de células neuronais e gliais, principalmente no córtex pré-frontal de pacientes bipolares. Estudos neuroquímicos demonstraram alterações nas vias do AMPc, fosfatidilinositol, Wnt/GSK-3beta e Ca++ intracelular nesses pacientes. CONCLUSÃO: Os achados de alterações neuropatológicas e neuroquímicas no TAB podem estar relacionados com a fisiopatologia deste transtorno e com os efeitos dos estabilizadores de humor. No entanto, mais estudos são necessários para esclarecer o papel das cascatas de sinalização intracelular na patogênese deste transtorno.OBJECTIVES: Postmortem, pharmacological, neuroimaging, and animal model studies have demonstrated a possible association of intracellular signaling mechanisms in the pathophysiology of bipolar disorder. The objective of this paper is to review the findings in neuropathology and cellular biochemistry. METHODS: We performed a MEDLINE research, between 1980-2003, using bipolar disorder, signaling, second messengers, and postmortem as keywords, and cross-references. RESULTS: Neuropathological studies reported a decrease in neuronal and glial cells, mainly in the prefrontal cortex of bipolar patients. Neurochemical studies reported dysfunction in cAMP, phosphoinositide, Wnt/GSK-3b, and intracellular Ca++ pathways in these patients. CONCLUSION: The neuropathological and neurochemical abnormalities

  8. Arctic Climate Forcing Observations to Improve Earth System Models: Measurements at High Frequency, Fine Spatial Resolution, and Climatically Relevant Spatial Scales with the use of the Recently Deployed NGEE-Arctic Tram

    Science.gov (United States)

    Curtis, J. B.; Serbin, S.; Dafflon, B.; Raz Yaseef, N.; Torn, M. S.; Cook, P. J.; Lewin, K. F.; Wullschleger, S. D.

    2014-12-01

    In order to improve the representation of the land surface and subsurface properties and their associated feedbacks with climate forcings, climate change, and drivers in Earth System Models (ESMs), detailed observations need to be made at climatically relevant spatial and temporal scales. Pan-Arctic spatial heterogeneity and temporal variation present major challenges to the current generation of ESMs. To enable highly spatially resolved and high temporal frequency measurements for the independent validation of modeled energy and greenhouse gas surface fluxes at core to intermediate scales, we have developed, tested, and deployed an automated observational platform, the Next Generation Ecosystem Experiment (NGEE)-Arctic Tram. The NGEE-Arctic Tram, installed on the Barrow Environmental Observatory (BEO) near Barrow, AK in mid May 2014, consists of 65 meters of elevated track and a fully automated cart carrying a suite of radiation and remote sensing instrumentation. The tram transect is located within the NGEE eddy covariance tower footprint to help better understand the relative contribution of different landforms (e.g. low center vs high center polygonal tundra and associated vegetation) to the overall energy budget of the footprint. Electrical resistivity tomography (ERT), soil moisture, and soil temperature sensors are acquired autonomously and co-located with the tram to link subsurface properties with surface observations. To complement the high frequency and fine spatial resolution of the tram, during the summer field seasons of 2013 and 2014 a portable version of the NGEE-Arctic Tram (also know as the portable energy pole or PEP); was used to characterize surface albedo, NDVI, surface temperature, and photosynthetically active radiation (PAR) across two ~500 m BEO transects co-located with subsurface ERT and ground penetrating radar (GPR) measurements. In addition, a ~ 3 Km transect across three drained thaw-lake basins (DTLB) of different climate

  9. The Relevant Physical Trace in Criminal Investigation

    Directory of Open Access Journals (Sweden)

    Durdica Hazard

    2016-01-01

    Full Text Available A criminal investigation requires the forensic scientist to search and to interpret vestiges of a criminal act that happened in the past. The forensic scientist is one of the many stakeholders who take part in the information quest within the criminal justice system. She reads the investigation scene in search of physical traces that should enable her to tell the story of the offense/crime that allegedly occurred. The challenge for any investigator is to detect and recognize relevant physical traces in order to provide clues for investigation and intelligence purposes, and that will constitute sound and relevant evidence for the court. This article shows how important it is to consider the relevancy of physical traces from the beginning of the investigation and what might influence the evaluation process. The exchange and management of information between the investigation stakeholders are important. Relevancy is a dimension that needs to be understood from the standpoints of law enforcement personnel and forensic scientists with the aim of strengthening investigation and ultimately the overall judicial process.

  10. The importance of being relevant

    Directory of Open Access Journals (Sweden)

    Snehlata eJaswal

    2012-08-01

    Full Text Available This review aims at an understanding of the binding process by synthesizing the extant perspectives regarding binding. It begins with a consideration of the biological explanations of binding, viz., conjunctive coding, synchrony, and reentrant mechanisms. Thereafter binding is reviewed as a psychological process guided by top down signals. The stages and types of binding proposed by various researchers are discussed in this section. The next section introduces Working Memory as the executive directing the top-down signals. After that it is described how Working Memory works by selecting relevant sensory input, followed by a detailed consideration of the debate regarding objects vs. features with the conclusion that relevance is the key factor determining what is processed. The next section considers other factors affecting the selection of relevant input. Then, we shift focus to describe what happens to irrelevant input – whether it is discarded at the outset or is gradually inhibited, and whether inhibition is a perceptual or post-perceptual process. The concluding section describes the process of binding as currently understood on the basis of the literature included in the review. To summarize, it appears that initially the ‘object’ is conceptualized as an instantaneous bundle of all features. However, only relevant features of stimuli are gradually integrated to form a stable representation of the object. Concomitantly, irrelevant features are removed from the object representations. Empirical evidence suggests that the inhibition of irrelevant features occurs over time and is thus presumably a process within Working Memory.

  11. Regularization in Matrix Relevance Learning

    NARCIS (Netherlands)

    Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael

    A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can

  12. Making Plant Biology Curricula Relevant.

    Science.gov (United States)

    Hershey, David R.

    1992-01-01

    Reviews rationale, purposes, challenges, and relevance of hands-on, plant biology curricula that have been developed in response to the limited use of plants in biology education. Discusses methods to maintain both instructional rigor and student interest in the following topics: cut flowers, container-growing media, fertilizers, hydroponics,…

  13. BIBLE TRANSLATION AND RELEVANCE THEORY

    African Journals Online (AJOL)

    Wilss's text book (Wilss 1982) suggests that the situation in general translation theory is not very different. It was precisely this model of communication theory that was challenged by Sperber and Wilson's relevance theory (Sperber & Wilson 1986; see also Wilson & Sperber 1987). Set within this context this paper seeks to ...

  14. Lexicography and the Relevance Criterion

    African Journals Online (AJOL)

    This will be done within the framework of the function theory .... Gouws (2011) supports this vision and stresses that learning from each other .... specific type of need, e.g. to solve a communicative or cognitive problem, ..... According to Borlund (2000) "the judgement of situational relevance ..... Management 36(4): 533-550.

  15. Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats.

    Science.gov (United States)

    de Araújo, Dayane Pessoa; Camboim, Thaisa Gracielle Martins; Silva, Ana Patrícia Magalhães; Silva, Caio da Fonseca; de Sousa, Rebeca Canuto; Barbosa, Mabson Delâno Alves; Oliveira, Lucidio Clebeson; Cavalcanti, José Rodolfo Lopes de Paiva; Lucena, Eudes Euler de Souza; Guzen, Fausto Pierdoná

    2017-07-01

    Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (ω-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and ω-3 (1 g/kg) in the treatment of TD induced by chronic use of haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or ω-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and ω-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and ω-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with ω-3 reduced the extrapyramidal effects produced by chronic use of HAL.

  16. Towards a neurochemical profile of the amygdala using short-TE1H magnetic resonance spectroscopy at 3 T.

    Science.gov (United States)

    Schubert, Florian; Kühn, Simone; Gallinat, Jürgen; Mekle, Ralf; Ittermann, Bernd

    2017-05-01

    The amygdala plays a key role in emotional learning and in the processing of emotions. As disturbed amygdala function has been linked to several psychiatric conditions, a knowledge of its biochemistry, especially neurotransmitter levels, is highly desirable. The spin echo full intensity acquired localized (SPECIAL) sequence, together with a transmit/receive coil, was used to perform very short-TE magnetic resonance spectroscopy at 3 T to determine the neurochemical profile in a spectroscopic voxel containing the amygdala in 21 healthy adult subjects. For spectral analysis, advanced data processing was applied in combination with a macromolecule baseline measured in the anterior cingulate for spectral fitting. The concentrations of total N-acetylaspartate, total creatine, total choline, myo-inositol and, for the first time, glutamate were quantified with high reliability (uncertainties far below 10%). For these metabolites, the inter-individual variability, reflected by the relative standard deviations for the cohort studied, varied between 12% (glutamate) and 22% (myo-inositol). Glutamine and glutathione could also be determined, albeit with lower precision. Retest on four subjects showed good reproducibility. The devised method allows the determination of metabolite concentrations in the amygdala voxel, including glutamate, provides an estimation of glutamine and glutathione, and may help in the study of disturbed amygdala metabolism in pathologies such as anxiety disorder, autism and major depression. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Toward an in Vivo Neurochemical Profile: Quantification of 18 Metabolites in Short-Echo-Time 1H NMR Spectra of the Rat Brain

    Science.gov (United States)

    Pfeuffer, Josef; Tkáč , Ivan; Provencher, Stephen W.; Gruetter, Rolf

    1999-11-01

    Localized in vivo1H NMR spectroscopy was performed with 2-ms echo time in the rat brain at 9.4 T. Frequency domain analysis with LCModel showed that the in vivo spectra can be explained by 18 metabolite model solution spectra and a highly structured background, which was attributed to resonances with fivefold shorter in vivo T1 than metabolites. The high spectral resolution (full width at half maximum approximately 0.025 ppm) and sensitivity (signal-to-noise ratio approximately 45 from a 63-μL volume, 512 scans) was used for the simultaneous measurement of the concentrations of metabolites previously difficult to quantify in 1H spectra. The strongly represented signals of N-acetylaspartate, glutamate, taurine, myo-inositol, creatine, phosphocreatine, glutamine, and lactate were quantified with Cramér-Rao lower bounds below 4%. Choline groups, phosphorylethanolamine, glucose, glutathione, γ-aminobutyric acid, N-acetylaspartylglutamate, and alanine were below 13%, whereas aspartate and scyllo-inositol were below 22%. Intra-assay variation was assessed from a time series of 3-min spectra, and the coefficient of variation was similar to the calculated Cramér-Rao lower bounds. Interassay variation was determined from 31 pooled spectra, and the coefficient of variation for total creatine was 7%. Tissue concentrations were found to be in very good agreement with neurochemical data from the literature.

  18. The Relevance of Aggression and the Aggression of Relevance: The Rise of the Accreditation Marketing Machine

    Science.gov (United States)

    Lowrie, Anthony

    2008-01-01

    Purpose: The purpose of this paper is to illustrate how language functions to construct relevance at moments of articulation and how language functions as an aggressive marketing practice to promote a self-regulated (production-oriented) system of accreditation. Design/methodology/approach: Drawing on the political theory of Laclau and Lacanian…

  19. Monochloramine Cometabolism by Nitrifying Biofilm Relevant ...

    Science.gov (United States)

    Recently, biological monochloramine removal (i.e., cometabolism) by a pure culture ammonia–oxidizing bacteria, Nitrosomonas europaea, and a nitrifying mixed–culture have been shown to increase monochloramine demand. Although important, these previous suspended culture batch kinetic experiments were not representative of drinking water distribution systems where bacteria grow predominantly as biofilm attached to pipe walls or sediments and physiological differences may exist between suspension and biofilm growth. Therefore, the current research was an important next step in extending the previous results to investigate monochloramine cometabolism by biofilm grown in annular reactors under drinking water relevant conditions. Estimated monochloramine cometabolism kinetics were similar to those of ammonia metabolism, and monochloramine cometabolism was a significant loss mechanism (25–40% of the observed monochloramine loss). These results demonstrated that monochloramine cometabolism occurred in drinking water relevant nitrifying biofilm; thus, cometabolism may be a significant contribution to monochloramine loss during nitrification episodes in distribution systems. Investigate whether or not nitrifying biofilm can biologically transform monochloramine under drinking water relevant conditions.

  20. Final Report (BMWi Project No.: 02 E 10971): Joint project: Retention of radionuclides relevant for final disposal in natural clay rock and saline systems - Subproject 2: Geochemical behavior and transport of radionuclides in saline systems in the prese

    Energy Technology Data Exchange (ETDEWEB)

    Schmeide, Katja [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Fritsch, Katharina [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Lippold, Holger [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Poetsch, Maria [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Kulenkampff, Johannes [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Lippmann-Pipke, Johanna [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Jordan, Norbert [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Joseph, Claudia [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Moll, Henry [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Cherkouk, Andrea [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology; Bader, Miriam [Helmholtz-Zentrum Dresden, (Germany). Inst. of Resource Ecology

    2016-02-29

    The objective of this project was to study the influence of increased salinities on interaction processes in the system radionuclide – organics – clay – aquifer. For this, complexation, redox, sorption, and diffusion studies were performed under variation of the ionic strength (up to 4 mol kg-1) and the background electrolyte (NaCl, CaCl2, MgCl2).

  1. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice

    National Research Council Canada - National Science Library

    Wu, Huali; Feng, Junyi; Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang; Shang, Jing

    2016-01-01

    ... and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems...

  2. A Generative Theory of Relevance

    Science.gov (United States)

    2004-09-01

    latent representation space . 2We need the Fubini -Tonelli theorem because the parameter space h is uncountable and the information representation space i...models can be expressed in a simple common form that is a direct consequence of De-Finetti’s representation theorem . We draw several unexpected...who defines relevance in terms of entailment (as in theorem -proving). Suppose G represents a logical proposition corresponding to a user’s request

  3. Association of Surgical Treatment, Systemic Therapy, and Survival in Patients With Abdominal Visceral Melanoma Metastases, 1965-2014: Relevance of Surgical Cure in the Era of Modern Systemic Therapy.

    Science.gov (United States)

    Deutsch, Gary B; Flaherty, Devin C; Kirchoff, Daniel D; Bailey, Mariel; Vitug, Sarah; Foshag, Leland J; Faries, Mark B; Bilchik, Anton J

    2017-07-01

    Systemic therapy for metastatic melanoma has evolved rapidly during the last decade, and patient treatment has become more complex. To evaluate the survival benefit achieved through surgical resection of melanoma metastatic to the abdominal viscera in patients treated in the modern treatment environment. This retrospective review of the institutional melanoma database from the John Wayne Cancer Institute at Providence St Johns Health Center, a tertiary-level melanoma referral center, included 1623 patients with melanoma diagnosed as having potentially resectable abdominal metastases before (1969-2003) and after (2004-2014) advances in systemic therapy. Overall survival (OS). Of the 1623 patients identified in the database with abdominal melanoma metastases, 1097 were men (67.6%), and the mean (SD) age was 54.6 (14.6) years. Of the patients with metastatic melanoma, 1623 (320 [19.7%] in the 2004-2014 period) had abdominal metastases, including 336 (20.7%) with metastases in the gastrointestinal tract, 697 (42.9%) in the liver, 138 (8.5%) in the adrenal glands, 38 (2.3%) in the pancreas, 109 (6.7%) in the spleen, and 305 (18.8%) with multiple sites. Median OS was superior in surgical (n = 392; 18.0 months) vs nonsurgical (n = 1231; 7.0 months) patients (P < .001). The most favorable 1-year and 2-year OS was seen after surgery for gastrointestinal tract (52% and 41%) and liver (51% and 38%) metastases, respectively. Multivariable analysis found increasing age (hazard ratio [HR], 1.01; 95% CI, 1.00-1.01; P = .02) and the presence of ulceration (HR, 1.21; 95% CI, 1.01-1.45; P = .04) were associated with a worse OS. Alternatively, treatment with metastasectomy (HR, 0.59; 95% CI, 0.46-0.74; P < .001) and metastases involving the gastrointestinal tract (HR, 0.65; 95% CI, 0.48-0.87; P = .004) were associated with a better OS. The systemic treatment era did not significantly affect outcomes (HR, 0.82; 95% CI, 0.67-1.02; P = .15). Overall

  4. An allosteric enhancer of M(4) muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine

    DEFF Research Database (Denmark)

    Nielsen, Ditte Dencker; Weikop, Pia; Sørensen, Gunnar

    2012-01-01

    The mesostriatal dopamine system plays a key role in mediating the reinforcing effects of psychostimulant drugs like cocaine. The muscarinic M(4) acetylcholine receptor subtype is centrally involved in the regulation of dopamine release in striatal areas. Consequently, striatal M(4) receptors could...... be a novel target for modulating psychostimulant effects of cocaine....

  5. Expression of mature micro-RNA involved in the functioning of p53-dependent system of maintaining the genome stability of the individuals exposed to radiation at clinically relevant doses

    Directory of Open Access Journals (Sweden)

    Shulenina L.V.

    2014-12-01

    Full Text Available Purpose: to explore the content of mature micro-RNA involved in the functioning of p53-dependent system of maintaining the genome stability in the blood of patients in distant time after irradiation at clinically relevant doses and to compare these micro-RNA with the development of malignant tumors in the period of late consequences of radiation injury. Materials and methods. We used the blood samples of patients with acute radiation syndrome (ARS, acute radiation syndrome with the development of local radiation injury (ARS+LRI and local radiation injury (LRI obtained through 1-51 year after radiation injury. The mature mir34a, mir21, mir145, mir16, mir125b, Iet7a which contained in the common fractions of RNA were reverse transcribed by using specific "stem-loop" — primers. The relative amount of micro-RNA in blood of patients by real-time PCR. Statistical analysis of the results was carried out using the non-parametric Mann —Whitney test. Data are presented as median and quartiles, normalized to median of control group accepted for 1. Results. We found a significant reduction of content of mir34a, mir21 in the blood of patients with a diagnosis ARS and the increase of content of mir145 in patients with LRI. Analysis of the individual values of micro-RNA expression in the blood of patients whose cancer was detected, except for patients with a bazalioma, showed consistency of changes with risk of carcinogenesis. Conclusion. For the first time was investigated the functional activity of p53-dependent system of maintaining the genome stability by measuring of micro-RNA in the blood of patients after many years post radiation injury. We found a significant reduction of content of mir34a, mir21 in blood of patients with ARS, and increased mir145 in patients with LRI. Our results suggest that further research with groups of patients, and analysis the dynamics of micro-RNA content would allow for use the micro-RNA as indicators of risk of late

  6. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice

    OpenAIRE

    Huali Wu; Junyi Feng; Wenting Lv; Qiaoling Huang; Mengsi Fu; Minxuan Cai; Qiangqiang He; Jing Shang

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or...

  7. Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

    Science.gov (United States)

    Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

    2012-01-01

    Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

  8. Reinforcing and neurochemical effects of the “bath salts” constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats

    Science.gov (United States)

    Schindler, Charles W.; Thorndike, Eric B.; Goldberg, Steven R.; Lehner, Kurt R.; Cozzi, Nicholas V.; Brandt, Simon D.; Baumann, Michael H.

    2015-01-01

    Rationale 3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called “bath salts” products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine and serotonin (5-HT). Objectives We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV. Methods To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats. Results MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly, and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. By contrast, methylone self-administration (0.3 & 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT. Conclusions Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats suggesting these drugs possess significant abuse liability in humans. PMID:26319160

  9. Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats.

    Science.gov (United States)

    Schindler, Charles W; Thorndike, Eric B; Goldberg, Steven R; Lehner, Kurt R; Cozzi, Nicholas V; Brandt, Simon D; Baumann, Michael H

    2016-05-01

    3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called "bath salts" products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT). We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV. To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats. MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT. Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans.

  10. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Huali Wu

    Full Text Available Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose. Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%. Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly

  11. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

    Science.gov (United States)

    Wu, Huali; Feng, Junyi; Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang; Shang, Jing

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  12. Situating relevance: exploring individual relevance assessments in context

    Directory of Open Access Journals (Sweden)

    Theresa Dirndorfer Anderson

    2001-01-01

    Full Text Available This paper discusses some of the challenges encountered whilst researching and writing a thesis that explores individual understandings of relevance and topic. It is based upon a discussion paper and presentation prepared as part of the Doctoral Workshop held during the ISIC 2000 Conference in Borås, Sweden. The focus of this paper is the doing of qualitative research. To provide a framework for this discussion, the key assumptions that have shaped the author's thesis are presented in the first section of this paper. The paper then focuses on some of the dilemmas of qualitative research encountered during the research and writing of this thesis, giving particular attention to the notion of context and the writing of qualitative research. Forthcoming results from the thesis are mentioned in the closing section. A Thesis Summary is also provided at the end of this paper.

  13. Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy123

    Science.gov (United States)

    Reyes, Beverly A. S.; Zitnik, Gerard; Foster, Celia; Van Bockstaele, Elisabeth J.

    2015-01-01

    Abstract Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident–intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies. PMID:26634226

  14. The role of the endocannabinoid system in Alzheimer's disease: facts and hypotheses.

    Science.gov (United States)

    Bisogno, Tiziana; Di Marzo, Vincenzo

    2008-01-01

    Unlike other neuroinflammatory disorders, like Parkinson's disease, Huntington's disease and multiple sclerosis, little is still known of the role of the endocannabinoid system in Alzheimer's disease (AD). This is partly due to the poor availability of animal models that are really relevant to the human disease, and to the complexity of AD as compared to other neurological states. Nevertheless, the available data indicate that endocannabinoids are likely to play in this disorder a role similar to that suggested in other neurodegenerative diseases, that is, to represent an endogenous adaptive response aimed at counteracting both the neurochemical and inflammatory consequences of beta-amyloid-induced tau protein hyperactivity, possibly the most important underlying cause of AD. Furthermore, plant and synthetic cannabinoids, and particularly the non-psychotropic cannabidiol, might also exert other, non-cannabinoid receptor-mediated protective effects, including, but not limited to, anti-oxidant actions. There is evidence, from in vivo studies on beta-amyloid-induced neurotoxicity, also for a possible causative role of endocannabinoids in the impairment in memory retention, which is typical of AD. This might open the way to the use of cannabinoid receptor antagonists as therapeutic drugs for the treatment of cognitive deficits in the more advanced phases of this disorder. The scant, but nevertheless important literature on the regulation and role of the endocannabinoid system in AD, and on the potential treatment of this disorder with cannabinoids and endocannabinoid-based drugs, are discussed in this mini-review.

  15. Simultaneous fMRI-PET of the opioidergic pain system in human brain

    DEFF Research Database (Denmark)

    Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M

    2014-01-01

    MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically...... and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting that pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change...... in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo....

  16. The LAILAPS search engine: relevance ranking in life science databases.

    Science.gov (United States)

    Lange, Matthias; Spies, Karl; Bargsten, Joachim; Haberhauer, Gregor; Klapperstück, Matthias; Leps, Michael; Weinel, Christian; Wünschiers, Röbbe; Weissbach, Mandy; Stein, Jens; Scholz, Uwe

    2010-01-15

    Search engines and retrieval systems are popular tools at a life science desktop. The manual inspection of hundreds of database entries, that reflect a life science concept or fact, is a time intensive daily work. Hereby, not the number of query results matters, but the relevance does. In this paper, we present the LAILAPS search engine for life science databases. The concept is to combine a novel feature model for relevance ranking, a machine learning approach to model user relevance profiles, ranking improvement by user feedback tracking and an intuitive and slim web user interface, that estimates relevance rank by tracking user interactions. Queries are formulated as simple keyword lists and will be expanded by synonyms. Supporting a flexible text index and a simple data import format, LAILAPS can easily be used both as search engine for comprehensive integrated life science databases and for small in-house project databases. With a set of features, extracted from each database hit in combination with user relevance preferences, a neural network predicts user specific relevance scores. Using expert knowledge as training data for a predefined neural network or using users own relevance training sets, a reliable relevance ranking of database hits has been implemented. In this paper, we present the LAILAPS system, the concepts, benchmarks and use cases. LAILAPS is public available for SWISSPROT data at http://lailaps.ipk-gatersleben.de.

  17. Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE)

    DEFF Research Database (Denmark)

    Li, Yan; Eskelund, Amanda; Zhou, H

    2015-01-01

    Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential...... pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction...... is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent...

  18. Early Paradoxical Increase of Dopamine: A Neurochemical Study of Olfactory Bulb in Asymptomatic and Symptomatic MPTP Treated Monkeys

    Science.gov (United States)

    Pifl, Christian; Reither, Harald; del Rey, Natalia Lopez-Gonzalez; Cavada, Carmen; Obeso, Jose A.; Blesa, Javier

    2017-01-01

    Parkinson’s disease (PD) is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB) pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and their metabolites, of noradrenaline (NA) and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated Macaca fascicularis in different stages, including monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism. DA was increased compared to controls, while neither NA and 5-HT nor the amino acid neurotransmitters were significantly changed. Furthermore, DA increased before stable motor deficits appear with +51% in asymptomatic and +96% in recovered monkeys. Unchanged DA metabolites suggest a special metabolic profile of the newly formed DA neurons. Significant correlation of homovanillic acid (HVA) with taurine single values within the four MPTP groups and of aspartate with taurine within the asymptomatic and recovered MPTP groups, but not within the controls suggest interactions in the OB between taurine and the DA system and taurine and the excitatory neurotransmitter triggered by MPTP. This first investigation of OB in various stages after MPTP administration suggests that the DA increase seems to be an early phenomenon, not requiring profound nigrostriatal neurodegeneration or PD symptoms. PMID:28611598

  19. Early Paradoxical Increase of Dopamine: A Neurochemical Study of Olfactory Bulb in Asymptomatic and Symptomatic MPTP Treated Monkeys

    Directory of Open Access Journals (Sweden)

    Christian Pifl

    2017-05-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA and serotonin (5-hydroxytryptamine, 5-HT and their metabolites, of noradrenaline (NA and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP treated Macaca fascicularis in different stages, including monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism. DA was increased compared to controls, while neither NA and 5-HT nor the amino acid neurotransmitters were significantly changed. Furthermore, DA increased before stable motor deficits appear with +51% in asymptomatic and +96% in recovered monkeys. Unchanged DA metabolites suggest a special metabolic profile of the newly formed DA neurons. Significant correlation of homovanillic acid (HVA with taurine single values within the four MPTP groups and of aspartate with taurine within the asymptomatic and recovered MPTP groups, but not within the controls suggest interactions in the OB between taurine and the DA system and taurine and the excitatory neurotransmitter triggered by MPTP. This first investigation of OB in various stages after MPTP administration suggests that the DA increase seems to be an early phenomenon, not requiring profound nigrostriatal neurodegeneration or PD symptoms.

  20. The Relevance of Hegel's Logic

    Directory of Open Access Journals (Sweden)

    John W Burbidge

    2007-12-01

    Full Text Available Hegel defines his Logic as the science that thinks about thinking.nbsp; But when we interpret that work as outlining what happens when we reason we are vulnerable to Fregersquo;s charge of psychologism.nbsp; I use Hegelrsquo;s tripartite distinction among understanding, dialectical and speculative reason as operations of pure thought to suggest how thinking can work with objective concepts.nbsp; In the last analysis, however, our ability to move from the subjective contingency of representations and ideas to the pure concepts we think develops from mechanical memory, which separates sign from sense so hat we can focus simply on the latter.nbsp; By becoming aware of the connections that underlie our thinking processes we may be able to both move beyond the abstractions of symbolic logic and clarify what informal logicians call relevance.

  1. The Improved Relevance Voxel Machine

    DEFF Research Database (Denmark)

    Ganz, Melanie; Sabuncu, Mert; Van Leemput, Koen

    Machine (RVM) [4] in 2001. While the concept of RVM was intriguing, problems with the approach were the run time which is approximately cubic in the number of basis functions as well as the greedy optimization. Hence, different approaches to overcome these shortcomings were developed, e.g. [5] or [6......The concept of sparse Bayesian learning has received much attention in the machine learning literature as a means of achieving parsimonious representations of features used in regression and classification. It is an important family of algorithms for sparse signal recovery and compressed sensing......] as well as Tipping himself in [7] (FastRVM). Recently, Sabuncu and Van Leemput [8, 9] extended the relevance vector machine by incorporating an additional spatial regularization term in the Gaussian prior on the regression weights or classification features (RVoxM). RVoxM encourages spatial clustering...

  2. Relevancy Ranking of Satellite Dataset Search Results

    Science.gov (United States)

    Lynnes, Christopher; Quinn, Patrick; Norton, James

    2017-01-01

    As the Variety of Earth science datasets increases, science researchers find it more challenging to discover and select the datasets that best fit their needs. The most common way of search providers to address this problem is to rank the datasets returned for a query by their likely relevance to the user. Large web page search engines typically use text matching supplemented with reverse link counts, semantic annotations and user intent modeling. However, this produces uneven results when applied to dataset metadata records simply externalized as a web page. Fortunately, data and search provides have decades of experience in serving data user communities, allowing them to form heuristics that leverage the structure in the metadata together with knowledge about the user community. Some of these heuristics include specific ways of matching the user input to the essential measurements in the dataset and determining overlaps of time range and spatial areas. Heuristics based on the novelty of the datasets can prioritize later, better versions of data over similar predecessors. And knowledge of how different user types and communities use data can be brought to bear in cases where characteristics of the user (discipline, expertise) or their intent (applications, research) can be divined. The Earth Observing System Data and Information System has begun implementing some of these heuristics in the relevancy algorithm of its Common Metadata Repository search engine.

  3. Equilibration Time Scales of Physically Relevant Observables

    Directory of Open Access Journals (Sweden)

    Luis Pedro García-Pintos

    2017-08-01

    Full Text Available We address the problem of understanding, from first principles, the conditions under which a quantum system equilibrates rapidly with respect to a concrete observable. On the one hand, previously known general upper bounds on the time scales of equilibration were unrealistically long, with times scaling linearly with the dimension of the Hilbert space. These bounds proved to be tight since particular constructions of observables scaling in this way were found. On the other hand, the computed equilibration time scales for certain classes of typical measurements, or under the evolution of typical Hamiltonians, are unrealistically short. However, most physically relevant situations fall outside these two classes. In this paper, we provide a new upper bound on the equilibration time scales which, under some physically reasonable conditions, give much more realistic results than previously known. In particular, we apply this result to the paradigmatic case of a system interacting with a thermal bath, where we obtain an upper bound for the equilibration time scale independent of the size of the bath. In this way, we find general conditions that single out observables with realistic equilibration times within a physically relevant setup.

  4. Health Systems Research With Relevance To district Health Management System

    Directory of Open Access Journals (Sweden)

    Deodhar N.S

    1993-01-01

    Full Text Available Three hundred women coming for early termination of pregnancy were studied to highlight their socio-demographic profiles. MTP was most common in the age group 21-30 years and 75% of them had parity of 3 or less. No method of contraception or a method with a high failure rate was used by 85.3% women. In 28.7% a previous medical termination and a history of Up to 5 abortions were obtained. The emphasis to these patients must be on education about contraception, unwanted pregnancies should be avoided but abortion should not be used as a form of planning their families.

  5. Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.

    Science.gov (United States)

    Pereira, Pedro A; Neves, João; Vilela, Manuel; Sousa, Sérgio; Cruz, Catarina; Madeira, M Dulce

    2014-01-01

    Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE

    Directory of Open Access Journals (Sweden)

    Yan Li

    2015-07-01

    Full Text Available Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr murine model of lupus, depression-like behavior and cognitive dysfunction is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent with previous studies, MRL/lpr mice had increased depression-like behavior and visuospatial memory impairment. Plasma levels of different inflammatory molecules (Haptoglobin, interleukin 10 (IL-10, interferon γ-inducible protein 10 (IP-10/CXCL10, lymphotactin, macrophage inhibitory protein 3β (MIP-3β/CCL19, monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12, vascular cell adhesion molecule 1 (VCAM-1, lymphotactin and interferon γ (IFN-γ were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3-hydroxykynurenine, 3-hydroxynthranilic acid and quinolinic acid. Therefore, our study suggests that increased cytokine expression may be critical in the regulation subtle aspects of brain function in NP-SLE via induction of IDO and tryptophan/kynurenine metabolism.

  7. Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

    Science.gov (United States)

    Ullah, Ihsan; Subhan, Fazal; Ayaz, Muhammad; Shah, Rehmat; Ali, Gowhar; Haq, Ikram Ul; Ullah, Sami

    2015-02-26

    Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.

  8. Vygotsky's Crisis: Argument, context, relevance.

    Science.gov (United States)

    Hyman, Ludmila

    2012-06-01

    Vygotsky's The Historical Significance of the Crisis in Psychology (1926-1927) is an important text in the history and philosophy of psychology that has only become available to scholars in 1982 in Russian, and in 1997 in English. The goal of this paper is to introduce Vygotsky's conception of psychology to a wider audience. I argue that Vygotsky's argument about the "crisis" in psychology and its resolution can be fully understood only in the context of his social and political thinking. Vygotsky shared the enthusiasm, widespread among Russian leftist intelligentsia in the 1920s, that Soviet society had launched an unprecedented social experiment: The socialist revolution opened the way for establishing social conditions that would let the individual flourish. For Vygotsky, this meant that "a new man" of the future would become "the first and only species in biology that would create itself." He envisioned psychology as a science that would serve this humanist teleology. I propose that The Crisis is relevant today insofar as it helps us define a fundamental problem: How can we systematically account for the development of knowledge in psychology? I evaluate how Vygotsky addresses this problem as a historian of the crisis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Repeated, Intermittent Social Defeat across the Entire Juvenile Period Resulted in Behavioral, Physiological, Hormonal, Immunological, and Neurochemical Alterations in Young Adult Male Golden Hamsters

    Science.gov (United States)

    Yu, Wei-Chun; Liu, Ching-Yi; Lai, Wen-Sung

    2016-01-01

    The developing brain is vulnerable to social defeat during the juvenile period. As complements of human studies, animal models of social defeat provide a straightforward approach to investigating the functional and neurobiological consequences of social defeats. Taking advantage of agonist behavior and social defeat in male golden hamster, a set of 6 experiments was conducted to investigate the consequences at multiple levels in young adulthood resulting from repeated, intermittent social defeats or “social threats” across the entire juvenile period. Male hamsters at postnatal day 28 (P28) were randomly assigned to either the social defeat, “social threat”, or arena control group, and they correspondingly received a series of nine social interaction trials (i.e., either social defeat, “social threat”, or arena control conditions) from P33 to P66. At the behavioral level (Experiment 1), we found that repeated social defeats (but not “social threats”) significantly impacted locomotor activity in the familiar context and social interaction in the familiar/unfamiliar social contexts. At the physiological and hormonal levels (Experiments 2 and 3), repeated social defeat significantly enhanced the cortisol and norepinephrine concentrations in blood. Enlargement of the spleen was also found in the social defeat and “social threat” groups. At the immunological level (Experiment 4), the social defeat group showed lower levels of pro-inflammatory cytokines in the hypothalamus and hippocampus but higher concentration of IL-6 in the striatum compared to the other two groups. At the neurochemical level (Experiment 5), the socially defeated hamsters mainly displayed reductions of dopamine, dopamine metabolites, and 5-HT levels in the striatum and decreased level of 5-HT in the hippocampus. In Experiment 6, an increase in the spine density of hippocampal CA1 pyramidal neurons was specifically observed in the “social threat” group. Collectively, our

  10. Disabled People as Culturally Relevant Teachers

    Directory of Open Access Journals (Sweden)

    Gail Pritchard

    2010-04-01

    Full Text Available This paper contends that disabled teachers are in such short supply as to be invisible even amongst minority teachers from already vastly marginalised populations. This is not simply because discriminatory practices are embedded within employment policies of educational systems, but deeply held socio-cultural attitudes also prevent disabled people accessing and attaining basic and later, higher levels of academic achievement. The central argument here is a simple one; disabled people as teachers offer a unique knowledge standpoint, challenge the animosity of dominant cultural beliefs around disability as analogous with passivity or non-achieving, and provide a source of resistance, solace and resolution for students they teach. Disabled people as educators enact exemplary pedagogic justice and socially inclusive practice. The aim of this paper is to explore the benefits to students and places of higher education alike of embracing both the person and the role of the teacher with disability as culturally relevant educators. Keywords: minority teachers, marginality, disability, cultural relevance, higher education

  11. Insight4News: Connecting News to Relevant Social Conversations

    OpenAIRE

    Shi, Bichen; Ifrim, Georgiana; Hurley, Neil J.

    2014-01-01

    We present the Insight4News system that connects news articles to social conversations, as echoed in microblogs such as Twitter. Insight4News tracks feeds from mainstream media, e.g., BBC, Irish Times, and extracts relevant topics that summarize the tweet activity around each article, recommends relevant hashtags, and presents complementary views and statistics on the tweet activity, related news articles, and timeline of the story with regard to Twitter reaction. The user can track their own...

  12. Laboratory Animal Medicine: Teaching for Relevance

    Science.gov (United States)

    Harkness, J. E.

    1977-01-01

    A mechanism for augmenting the relevance of instruction in laboratory animal medicine is suggested: the identification of practice-relevant content. This identification helps foster a positive attitude toward the subject and facilitates the retention of information. (LBH)

  13. Does relevance matter in academic policy research?

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars.......A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars....

  14. Evaluating societal relevance of research

    NARCIS (Netherlands)

    Wilbertz, Johannes

    2013-01-01

    Scientific research is performed to elucidate how the world around us is functioning. One dimension of the acquired knowledge is that it can be used to develop various sectors of society such as industry, education, governmental practices, the health system or social cohesion. A main characteristic

  15. Neurochemical Profile of Dementia Pugilistica

    OpenAIRE

    Kokjohn, Tyler A.; Maarouf, Chera L.; Daugs, Ian D.; Hunter, Jesse M.; Charisse M Whiteside; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A.; Sabbagh, Marwan N; Beach, Thomas G; Roher, Alex E.

    2013-01-01

    Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in th...

  16. The Need for Culturally Relevant Dance Education

    Science.gov (United States)

    McCarthy-Brown, Nyama

    2009-01-01

    There is a need for culturally relevant teaching in dance education. Many dance teachers have heard the buzz words "culturally relevant teaching methods." Yet these dance educators acknowledge that the "dance culture" is not always synonymous with "culturally relevant." This paper examines the issue of culturally…

  17. The Personal Relevance of the Social Studies.

    Science.gov (United States)

    VanSickle, Ronald L.

    1990-01-01

    Conceptualizes a personal-relevance framework derived from Ronald L. VanSickle's five areas of life integrated with four general motivating goals from Abraham Maslow's hierarchy of needs and Richard and Patricia Schmuck's social motivation theory. Illustrates ways to apply the personal relevance framework to make social studies more relevant to…

  18. Socially Relevant Knowledge Based Telemedicine

    Science.gov (United States)

    2010-10-01

    can make voi ce calls to each other using Skype (free computer-to-computer calling). The integration of Skype with the system has two major benefits ...Shirmohammadi, S. (2007). Accessibility and scalability in collaborative eCommerce environments. Digital Information Management, 2007. ICDIM 󈧋. 2nd...further. Visualization of workflow is another benefit of using this tool. In ad- dition to enhancing our understanding of clinical workflow, such

  19. Climate Relevant Processes On The Barents Shelf

    Science.gov (United States)

    Hatten, K.; Schrum, C.; Harms, I.

    The Artic Shelf, and especially the Barents Shelf , are key regions in the North At- lantic climate system. Climatic relevant processes on the shelf are on the one hand the water mass transformation and on the other hand the strong air/sea exchange. Air/sea interaction and resulting sea ice development cause water mass transformation and de- velopment of cold and salty deep water on the shelf region. The outflow of this dense water mass into the Arctic Ocean is responsible for the stabilization of the permanent halocline in the Arctic Ocean and therefore for the isolation of the cold and fresh arctic surface water from the saltier and warmer Atlantic deep water in the Arctic Ocean, and thus for preservation of the Arctic Ocean sea ice. The second climatic relevant process, the direct air/sea exchange, i.e. the annual mean heat release to the atmosphere, plays a key role as energy source for the atmosphere. Both processes are subject to strong inter-annual variability and influenced by mesoscale structures in the ice field, and thus can be assumed to be less good described by the large scale atmospheric and oceanic models. This was the background of the development of a regional eddy resolving model of the Barents Sea. Results of a multi-year model simulation will be presented and related to flux estimates from global atmospheric re-analysis, to highlight the in- fluence of mesoscale variability in the sea ice coverage on the air sea exchange and on the water mass transformation.

  20. Biology relevant to space radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M. [Oak Ridge National Lab., TN (United States)

    1997-04-30

    There are only very limited data on the health effects to humans from the two major components of the radiations in space, namely protons and heavy ions. As a result, predictions of the accompanying effects must be based either on (1) data generated through studies of experimental systems exposed on earth at rates and fluences higher than those in space, or (2) extrapolations from studies of gamma and x rays. Better information is needed about the doses, dose rates, and the energy and LET spectra of the radiations at the organ level that are anticipated to be encountered during extended space missions. In particular, there is a need for better estimates of the relationship between radiation quality and biological effects. In the case of deterministic effects, it is the threshold that is important. The possibility of the occurrence of a large solar particle event (SPE) requires that such effects be considered during extended space missions. Analyses suggest, however, that it is feasible to provide sufficient shielding so as to reduce such effects to acceptable levels, particularly if the dose rates can be limited. If these analyses prove correct, the primary biological risks will be the stochastic effects (latent cancer induction). The contribution of one large SPE to the risk of stochastic effects while undesirable will not be large in comparison to the potential total dose on a mission of long duration.

  1. Antioxidant relevance to human health.

    Science.gov (United States)

    Wahlqvist, Mark L

    2013-01-01

    Human ecology requires both oxygen and water with the generation from food of an immediate energy source, ATP, by oxidative phosphorylation. A continuing balance between oxidation and antioxidation is necessary for longer less-disabled lives, taking account of oxidative stresses and the critical roles of oxidants in defence against infection, tissue repair and signalling. Antioxidant capacity is derived both exogenously (from food, beverage and sunlight) and endogenously (from enzymatic and non-enzymatic pathways). A number of oxidant food factors service antioxidant metallo-enzymes. The capacity operates extra- or intracellularly. Uric acid is the major antioxidant in primate blood. Uric acid synthesis is increased by dietary fructose from fruit, sugary foods and drinks. This indirect antioxidant effect of fruit is separate from that attributable to its flavonoids. Alcohol also increases serum uric acid. Urate excess and retention is associated with disease. The high prevalence of hyperuricaemia in NE Asia presents a major public health dilemma in regard to putative benefits and risks. Foods with high antioxidant activity include berries, nuts and legumes, tomatoes and sweet potato leaves. Each of the antioxidants in these foods is pleiotropic being inter-alia anti-inflammatory, anti-angiogenic or anti-neoplastic. Moreover, food matrices and patterns contribute to the safety of antioxidant consumption. There is no evidence to date that isolated antioxidants as food supplements improve health outcomes or survival; and some that indicate unacceptable risk. Their use as biomarkers of food cannot justify their isolated use. Nevertheless, a spectrum of dietary pluripotential antioxidants for tissues, metabolic and immune systems is advantageous.

  2. Investigación neuroquímica cerebral y aplicación preventiva para la reducción de los índices de criminalidad/Neurochemical brain research and it’s preventive application to reduce the crime statistics

    Directory of Open Access Journals (Sweden)

    Osvaldo Tieghi (Argentina

    2014-01-01

    Full Text Available Investigación neuroquímica cerebral y aplicación preventiva para la reducción de los índices de criminalidad Neurochemical brain research and it’s preventive application to reduce the crime statistics

  3. Toxcast and the Use of Human Relevant In Vitro Exposures ...

    Science.gov (United States)

    The path for incorporating new approach methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. These challenges include sufficient coverage of toxicological mechanisms to meaningfully interpret negative test results, development of increasingly relevant test systems, computational modeling to integrate experimental data, putting results in a dose and exposure context, characterizing uncertainty, and efficient validation of the test systems and computational models. The presentation will cover progress at the U.S. EPA in systematically addressing each of these challenges and delivering more human-relevant risk-based assessments. This abstract does not necessarily reflect U.S. EPA policy. Presentation at the British Toxicological Society Annual Congress on ToxCast and the Use of Human Relevant In Vitro Exposures: Incorporating high-throughput exposure and toxicity testing data for 21st century risk assessments .

  4. Relevance: An Interdisciplinary and Information Science Perspective

    Directory of Open Access Journals (Sweden)

    Howard Greisdorf

    2000-01-01

    Full Text Available Although relevance has represented a key concept in the field of information science for evaluating information retrieval effectiveness, the broader context established by interdisciplinary frameworks could provide greater depth and breadth to on-going research in the field. This work provides an overview of the nature of relevance in the field of information science with a cursory view of how cross-disciplinary approaches to relevance could represent avenues for further investigation into the evaluative characteristics of relevance as a means for enhanced understanding of human information behavior.

  5. The relevance of developmental-psychobiological metatheory to developmental neuropsychology.

    Science.gov (United States)

    Gottlieb, G

    2001-01-01

    This article reviews 4 aspects of developmental-psychobiological metatheory that are of particular relevance to developmental conceptions of neuropsychology: probabilistic epigenesis, the various roles of experience in affecting the development of the nervous system, and the developmental principles of equifinality and equipotentiality, the latter being especially pertinent to the understanding of compensatory phenomena observed in studies of early brain damage.

  6. Relevance of information warfare models to critical infrastructure ...

    African Journals Online (AJOL)

    This article illustrates the relevance of information warfare models to critical infrastructure protection. Analogies of information warfare models to those of information security and information systems were used to deconstruct the models into their fundamental components and this will be discussed. The models were applied ...

  7. Neurochemical and structural markers in the brain predicting best choice-of-treatment in patients with schizophrenia - The Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II) study

    DEFF Research Database (Denmark)

    Jessen, Kasper; Bojesen, Kirsten Borup; Sigvard, Anne Mette

    the progressive loss of brain tissue and social functions seen in many patients. Aim of PECANS II: To test if persistently high levels of glutamate and loss of brain tissue and social functions characterize a subgroup of patients with poor treatment response, while dopaminergic disturbances characterize another...... as markers for best-choice-of-treatment. Further, the results can pave the way for the development of new antipsychotic medication modulating glutamatergic disturbances and lead to better prevention strategies for the progressive loss of brain tissue and social functions in a treatment resistant subgroup...... disturbances with positron emission tomography (PET) scanning, and loss of brain tissue with analysis of a structural MR-scanning revealing loss of cortical thickness and surface area. Neurochemical and structural disturbances are compared with treatment response and level of function as measured by various...

  8. Relevance and problem choice in design science

    NARCIS (Netherlands)

    Wieringa, Roelf J.

    2010-01-01

    The supposed opposition of rigor versus relevance is based on the mistaken idea that rigor consists of linear technology transfer combined with positivistic science, and ignores the context-dependence of relevance as well as the incorporation of conditions of practice necessary for applicability of

  9. Does relevance matter in academic policy research

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research, and if so, to whom/what should it matter......A reflection on whether relevance matters in tourism policy research, and if so, to whom/what should it matter...

  10. Translation as secondary communication. The relevance theory ...

    African Journals Online (AJOL)

    Ernst-August Gutt started one of the greatest translation debates of the past ten years when he suggested that relevance theory holds the key to providing a unified account of translation. The bulk of the debate has been between practitioners of functional equivalence and advocates of a relevance theoretic approach to ...

  11. A cognitive approach to relevance of science

    NARCIS (Netherlands)

    Rip, Arie

    1997-01-01

    The Starnberg finalization thesis offered a cognitive diagnosis of the relevance of science. With the present changes in science and its links with society, this remains important, but needs to be broadened. Relevance occurred and continues to occur locally, and can be taken up in local¿cosmopolitan

  12. Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick.

    Science.gov (United States)

    Gruss, M; Bock, J; Braun, K

    2003-11-01

    In vivo microdialysis and behavioural studies in the domestic chick have shown that glutamatergic as well as monoaminergic neurotransmission in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) is altered after auditory filial imprinting. In the present study, using pharmaco-behavioural and in vivo microdialysis approaches, the role of dopaminergic neurotransmission in this juvenile learning event was further evaluated. The results revealed that: (i) the systemic application of the potent dopamine receptor antagonist haloperidol (7.5 mg/kg) strongly impairs auditory filial imprinting; (ii) systemic haloperidol induces a tetrodotoxin-sensitive increase of extracellular levels of the dopamine metabolite, homovanillic acid, in the MNH, whereas the levels of glutamate, taurine and the serotonin metabolite, 5-hydroxyindole-3-acetic acid, remain unchanged; (iii) haloperidol (0.01, 0.1, 1 mm) infused locally into the MNH increases glutamate, taurine and 5- hydroxyindole-3-acetic acid levels in a dose-dependent manner, whereas homovanillic acid levels remain unchanged; (iv) systemic haloperidol infusion reinforces the N-methyl-d-aspartate receptor-mediated inhibitory modulation of the dopaminergic neurotransmission within the MNH. These results indicate that the modulation of dopaminergic function and its interaction with other neurotransmitter systems in a higher associative forebrain region of the juvenile avian brain displays similar neurochemical characteristics as the adult mammalian prefrontal cortex. Furthermore, we were able to show that the pharmacological manipulation of monoaminergic regulatory mechanisms interferes with learning and memory formation, events which in a similar fashion might occur in young or adult mammals.

  13. Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity.

    Science.gov (United States)

    Autrup, H; Warwick, G P

    1975-11-01

    The system involved in the reduction of 2-[4'-di(2''-bromopropyl) aminophenylazolbenzoic acid (CB10-252), an agent designed for treating primary liver cell cancer, has been demonstrated to be localised mainly in the 108 000 X g supernatant fraction of rat liver homogenate. It is also present in other organs particularly in the spleen. DAB-azoreductase as shown previously is present almost entirely in the microsomal fraction and is found in high concentration only in liver. The pH maximum for CB10-252-azoreductase implying the importance of the 2'-carboxyl group in determining substrate specificity. The use of enzyme inhibitors and other additives showed that CB10-252 WAS NOT AXANTHINE OXIDASE OR DIHYDROFOLATE REDUCTASE. Its activity was not affected by carbon monoxide, phenobarbitone (PB), or 3-methylcholanthrene (MC) pretreatment. Enhancement of the activity by ferrous ions and FAD indicated that at least part of the reduction system could involve a flavoprotein with FAD as the prosthetic group. The activity of CB10-252-azoreductase and methylred-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems.

  14. The foundation of the concept of relevance