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Sample records for analysis links glutamatergic

  1. Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression.

    Directory of Open Access Journals (Sweden)

    Adolfo Sequeira

    Full Text Available BACKGROUND: Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations. METHODOLOGY/PRINCIPAL FINDINGS: We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with

  2. Glutamatergic Neurotransmission Links Sensitivity to Volatile Anesthetics with Mitochondrial Function.

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    Zimin, Pavel I; Woods, Christian B; Quintana, Albert; Ramirez, Jan-Marino; Morgan, Philip G; Sedensky, Margaret M

    2016-08-22

    An enigma of modern medicine has persisted for over 150 years. The mechanisms by which volatile anesthetics (VAs) produce their effects (loss of consciousness, analgesia, amnesia, and immobility) remain an unsolved mystery. Many attractive putative molecular targets have failed to produce a significant effect when genetically tested in whole-animal models [1-3]. However, mitochondrial defects increase VA sensitivity in diverse organisms from nematodes to humans [4-6]. Ndufs4 knockout (KO) mice lack a subunit of mitochondrial complex I and are strikingly hypersensitive to VAs yet resistant to the intravenous anesthetic ketamine [7]. The change in VA sensitivity is the largest reported for a mammal. Limiting NDUFS4 loss to a subset of glutamatergic neurons recapitulates the VA hypersensitivity of Ndufs4(KO) mice, while loss in GABAergic or cholinergic neurons does not. Baseline electrophysiologic function of CA1 pyramidal neurons does not differ between Ndufs4(KO) and control mice. Isoflurane concentrations that anesthetize only Ndufs4(KO) mice (0.6%) decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) only in Ndufs4(KO) CA1 neurons, while concentrations effective in control mice (1.2%) decreased sEPSC frequencies in both control and Ndufs4(KO) CA1 pyramidal cells. Spontaneous inhibitory postsynaptic currents (sIPSCs) were not differentially affected between genotypes. The effects of isoflurane were similar on evoked field excitatory postsynaptic potentials (fEPSPs) and paired pulse facilitation (PPF) in KO and control hippocampal slices. We propose that CA1 presynaptic excitatory neurotransmission is hypersensitive to isoflurane in Ndufs4(KO) mice due to the inhibition of pre-existing reduced complex I function, reaching a critical reduction that can no longer meet metabolic demands.

  3. Link Analysis

    Science.gov (United States)

    Donoho, Steve

    Link analysis is a collection of techniques that operate on data that can be represented as nodes and links. This chapter surveys a variety of techniques including subgraph matching, finding cliques and K-plexes, maximizing spread of influence, visualization, finding hubs and authorities, and combining with traditional techniques (classification, clustering, etc). It also surveys applications including social network analysis, viral marketing, Internet search, fraud detection, and crime prevention.

  4. Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression

    OpenAIRE

    Adolfo Sequeira; Firoza Mamdani; Carl Ernst; Vawter, Marquis P.; Bunney, William E.; Veronique Lebel; Sonia Rehal; Tim Klempan; Alain Gratton; Chawki Benkelfat; Rouleau, Guy A.; Naguib Mechawar; Gustavo Turecki

    2009-01-01

    BACKGROUND: Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In t...

  5. Multi-locus genome-wide association analysis supports the role of glutamatergic synaptic transmission in the etiology of major depressive disorder.

    Science.gov (United States)

    Lee, P H; Perlis, R H; Jung, J-Y; Byrne, E M; Rueckert, E; Siburian, R; Haddad, S; Mayerfeld, C E; Heath, A C; Pergadia, M L; Madden, P A F; Boomsma, D I; Penninx, B W; Sklar, P; Martin, N G; Wray, N R; Purcell, S M; Smoller, J W

    2012-11-13

    Major depressive disorder (MDD) is a common psychiatric illness characterized by low mood and loss of interest in pleasurable activities. Despite years of effort, recent genome-wide association studies (GWAS) have identified few susceptibility variants or genes that are robustly associated with MDD. Standard single-SNP (single nucleotide polymorphism)-based GWAS analysis typically has limited power to deal with the extensive heterogeneity and substantial polygenic contribution of individually weak genetic effects underlying the pathogenesis of MDD. Here, we report an alternative, gene-set-based association analysis of MDD in an effort to identify groups of biologically related genetic variants that are involved in the same molecular function or cellular processes and exhibit a significant level of aggregated association with MDD. In particular, we used a text-mining-based data analysis to prioritize candidate gene sets implicated in MDD and conducted a multi-locus association analysis to look for enriched signals of nominally associated MDD susceptibility loci within each of the gene sets. Our primary analysis is based on the meta-analysis of three large MDD GWAS data sets (total N=4346 cases and 4430 controls). After correction for multiple testing, we found that genes involved in glutamatergic synaptic neurotransmission were significantly associated with MDD (set-based association P=6.9 × 10(-4)). This result is consistent with previous studies that support a role of the glutamatergic system in synaptic plasticity and MDD and support the potential utility of targeting glutamatergic neurotransmission in the treatment of MDD.

  6. Central cholinesterase inhibition enhances glutamatergic synaptic transmission.

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    Kozhemyakin, Maxim; Rajasekaran, Karthik; Kapur, Jaideep

    2010-04-01

    Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granule cells synapses by increasing the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in a concentration-dependent fashion. The amplitude of mEPSCs was not increased, which suggested the possibility of enhanced action potential-dependent release. Analysis of EPSCs evoked by minimal stimulation revealed reduced failures and increased amplitude of evoked responses. The ratio of amplitudes of EPSCs evoked by paired stimuli was also altered. The effect of paraoxon on glutamatergic transmission was blocked by the muscarinic antagonist atropine and partially mimicked by carbachol. The nicotinic receptor antagonist α -bungarotoxin did not block the effects of paraoxon; however, nicotine enhanced glutamatergic transmission. These studies suggested that cholinergic overstimulation enhances glutamatergic transmission by enhancing neurotransmitter release from presynaptic terminals.

  7. Glutamatergic Transmission: A Matter of Three.

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    Martínez-Lozada, Zila; Ortega, Arturo

    2015-01-01

    Glutamatergic transmission in the vertebrate brain requires the involvement of glia cells, in a continuous molecular dialogue. Glial glutamate receptors and transporters are key molecules that sense synaptic activity and by these means modify their physiology in the short and long term. Posttranslational modifications that regulate protein-protein interactions and modulate transmitter removal are triggered in glial cells by neuronal released glutamate. Moreover, glutamate signaling cascades in these cells are linked to transcriptional and translational control and are critically involved in the control of the so-called glutamate/glutamine shuttle and by these means in glutamatergic neurotransmission. In this contribution, we summarize our current understanding of the biochemical consequences of glutamate synaptic activity in their surrounding partners and dissect the molecular mechanisms that allow neurons to take control of glia physiology to ensure proper glutamate-mediated neuronal communication.

  8. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy

    Science.gov (United States)

    Caddy, Caroline; Giaroli, Giovanni; White, Thomas P.; Shergill, Sukhwinder S.

    2014-01-01

    The burden of depressive disorders and the frequent inadequacy of their current pharmacological treatments are well established. The anaesthetic and hallucinogenic drug ketamine has provoked much interest over the past decade or so as an extremely rapidly acting antidepressant that does not modify ‘classical’ monoaminergic receptors. Current evidence has shown several ways through which it might exert therapeutic antidepressant actions: blockade of glutamatergic NMDA receptors and relative upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtypes may alter cortical connectivity patterns; through intracellular changes in protein expression, including the proteins mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF); and alteration of intracellular signalling cascades. The clinical evidence demonstrates rapid improvements in mood and suicidal thinking in most participants, although study numbers have generally been small and many trials are unblinded and methodologically weak. There is a small body of work to suggest ketamine might also augment electroconvulsive therapy and potentially have a role as a surgical anaesthetic in depressed patients. A major problem is that the effects of ketamine appear temporary, disappearing after days to weeks (although longer benefits have been sustained in some), and attempts to circumvent this through pharmacological augmentation have been disappointing thus far. These exciting data are providing new insights into neurobiological models of depression, and potentially opening up a new class of antidepressants, but there are significant practical and ethical issues about any future mainstream clinical role it might have. PMID:24688759

  9. [Glutamatergic neurotransmitter system in regulation of the gastrointestinal tract motor activity].

    Science.gov (United States)

    Alekseeva, E V; Popova, T S; Sal'nikov, P S

    2015-01-01

    The review include actual facts, demonstrating high probability of glutamatergic neurotransmitter system role in the regulation of the gastrointestinal tract motor activity. These facts suggest significant role of the glutamatergic neurotransmitter system dysfunction in forming motor activity disorders of the digestive tract, including in patients in critical condition. The analysis is based on results of multiple experimental and clinical researches of glutamic acid and other components of the glutamatergic neurotransmitter system in central nervous system and autonomic nervous system (with the accent on the enteral nervous system) in normal conditions and with functioning changes of the glutamatergic neurotransmitter system in case of inflammation, hupoxia, stress and in critical condition.

  10. Web Applications of Bibliometrics and Link Analysis

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    Faribourz Droudi

    2010-04-01

    Full Text Available The present study aims to introduce and analyze bibliometric application within Web and also to expounds on the status of link analysis in order to point out its application with respect to the existing web-based information sources. Findings indicate that bibliometrics could have required application in the area of digital resources available through Net. Link analysis is a process by which one could make statistical analysis of correlation between hyperlinks and therefore understand the accuracy, veracity and efficacy of citations within a digital document. Link analysis, in effect, is counted as a part of information ranking algorithm within the web environment. The number, linkage and quality of given links to a website are of utmost importance for ranking/status in the Web. The tools applied in this topic include, page ranking strategy, link analysis algorithm, latent semantic indexing and the classical input-output model. The present study analyzes Big Web and Small Web link analysis and explains the means for utilizing web charts in order to better understand the link analysis process.

  11. Link Analysis in the Mission Planning Lab

    Science.gov (United States)

    McCarthy, Jessica A.; Cervantes, Benjamin W.; Daugherty, Sarah C.; Arroyo, Felipe; Mago, Divyang

    2011-01-01

    The legacy communications link analysis software currently used at Wallops Flight Facility involves processes that are different for command destruct, radar, and telemetry. There is a clear advantage to developing an easy-to-use tool that combines all the processes in one application. Link Analysis in the Mission Planning Lab (MPL) uses custom software and algorithms integrated with Analytical Graphics Inc. Satellite Toolkit (AGI STK). The MPL link analysis tool uses pre/post-mission data to conduct a dynamic link analysis between ground assets and the launch vehicle. Just as the legacy methods do, the MPL link analysis tool calculates signal strength and signal- to-noise according to the accepted processes for command destruct, radar, and telemetry assets. Graphs and other custom data are generated rapidly in formats for reports and presentations. STK is used for analysis as well as to depict plume angles and antenna gain patterns in 3D. The MPL has developed two interfaces with the STK software (see figure). The first interface is an HTML utility, which was developed in Visual Basic to enhance analysis for plume modeling and to offer a more user friendly, flexible tool. A graphical user interface (GUI) written in MATLAB (see figure upper right-hand corner) is also used to quickly depict link budget information for multiple ground assets. This new method yields a dramatic decrease in the time it takes to provide launch managers with the required link budgets to make critical pre-mission decisions. The software code used for these two custom utilities is a product of NASA's MPL.

  12. Link-space formalism for network analysis.

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    Smith, David M D; Lee, Chiu Fan; Onnela, Jukka-Pekka; Johnson, Neil F

    2008-03-01

    We introduce the link-space formalism for analyzing network models with degree-degree correlations. The formalism is based on a statistical description of the fraction of links l(i,j) connecting nodes of degrees i and j. To demonstrate its use, we apply the framework to some pedagogical network models, namely, random attachment, Barabási-Albert preferential attachment, and the classical Erdos and Rényi random graph. For these three models the link-space matrix can be solved analytically. We apply the formalism to a simple one-parameter growing network model whose numerical solution exemplifies the effect of degree-degree correlations for the resulting degree distribution. We also employ the formalism to derive the degree distributions of two very simple network decay models, more specifically, that of random link deletion and random node deletion. The formalism allows detailed analysis of the correlations within networks and we also employ it to derive the form of a perfectly nonassortative network for arbitrary degree distribution.

  13. Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

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    Facciolo Rosa

    2011-01-01

    Full Text Available Abstract Background Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB and hibernating (HIB hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR, 3-(+-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators. Results From the behavioral results it appears that the two glutamatergic compounds exerted distinct effects. In the first case local infusion of basolateral complexes (BLA with NMDAR antagonist caused very great (p Conclusion We conclude that predominant drinking events evoked by glutamatergic mechanisms, in the presence of prevalently down regulated levels of NR1/2A of some telencephalic and hypothalamic areas appear to constitute an important neuronal switch at least during arousal stage of hibernation. The establishment of the type of glutamatergic subtypes that are linked to successful hibernating states, via drinking stimuli, may have useful bearings toward sleeping disorders.

  14. Cannabinoids: Glutamatergic Transmission and Kynurenines.

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    Colín-González, Ana Laura; Aguilera, Gabriela; Santamaría, Abel

    2016-01-01

    The endocannabinoid system (ECS) comprises a complex of receptors, enzymes, and endogenous agonists that are widely distributed in the central nervous system of mammals and participates in a considerable number of neuromodulatory functions, including neurotransmission, immunological control, and cell signaling. In turn, the kynurenine pathway (KP) is the most relevant metabolic route for tryptophan degradation to form the metabolic precursor NAD(+). Recent studies demonstrate that the control exerted by the pharmacological manipulation of the ECS on the glutamatergic system in the brain may offer key information not only on the development of psychiatric disorders like psychosis and schizophrenia-like symptoms, but it also may constitute a solid basis for the development of therapeutic strategies to combat excitotoxic events occurring in neurological disorders like Huntington's disease (HD). Part of the evidence pointing to the last approach is based on experimental protocols demonstrating the efficacy of cannabinoids to prevent the deleterious actions of the endogenous neurotoxin and KP metabolite quinolinic acid (QUIN). These findings intuitively raise the question about what is the precise role of the ECS in tryptophan metabolism through KP and vice versa. In this chapter, we will review basic concepts on the physiology of both the ECS and the KP to finally describe those recent findings combining the components of these two systems and hypothesize the future course that the research in this emerging field will take in the next years.

  15. Linking advanced fracture models to structural analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chiesa, Matteo

    2001-07-01

    Shell structures with defects occur in many situations. The defects are usually introduced during the welding process necessary for joining different parts of the structure. Higher utilization of structural materials leads to a need for accurate numerical tools for reliable prediction of structural response. The direct discretization of the cracked shell structure with solid finite elements in order to perform an integrity assessment of the structure in question leads to large size problems, and makes such analysis infeasible in structural application. In this study a link between local material models and structural analysis is outlined. An ''ad hoc'' element formulation is used in order to connect complex material models to the finite element framework used for structural analysis. An improved elasto-plastic line spring finite element formulation, used in order to take cracks into account, is linked to shell elements which are further linked to beam elements. In this way one obtain a global model of the shell structure that also accounts for local flexibilities and fractures due to defects. An important advantage with such an approach is a direct fracture mechanics assessment e.g. via computed J-integral or CTOD. A recent development in this approach is the notion of two-parameter fracture assessment. This means that the crack tip stress tri-axiality (constraint) is employed in determining the corresponding fracture toughness, giving a much more realistic capacity of cracked structures. The present thesis is organized in six research articles and an introductory chapter that reviews important background literature related to this work. Paper I and II address the performance of shell and line spring finite elements as a cost effective tool for performing the numerical calculation needed to perform a fracture assessment. In Paper II a failure assessment, based on the testing of a constraint-corrected fracture mechanics specimen under tension, is

  16. A Review of Algebraic Link Analysis Algorithms

    Directory of Open Access Journals (Sweden)

    Mini Singh Ahuja

    2012-08-01

    Full Text Available The World Wide Web is a system of interlinked hypertext documents accessed via the Internet. With a web browser, one can view web pages that may contain text, images, videos, and other multimedia and navigate between them by using hyperlinks. Navigation is the process through which the users can achieve their purposes in using Web site, such as to find the information that they need or to complete the transactions that they want to do. Web mining is the application of data mining techniques to extract knowledge from Web data, where at least one of structure (hyperlink or usage (Web log data is used in the mining process (with or without other types of Web data. In this paper we have briefly discussed the web mining technique with major stress to the link analysis algorithms.

  17. Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission.

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    Tassone, Annalisa; Madeo, Graziella; Schirinzi, Tommaso; Vita, Daniela; Puglisi, Francesca; Ponterio, Giulia; Borsini, Franco; Pisani, Antonio; Bonsi, Paola

    2011-09-01

    We investigated the effect of 5-HT6 receptor subtype activation on glutamatergic transmission by means of whole-cell patch-clamp electrophysiological recordings from medium spiny neurons of the striatum and layer V pyramidal neurons of the prefrontal cortex. To this aim, we took advantage of a novel ligand, ST1936, showing nM affinity and agonist activity at the 5-HT6 receptor subtype. Our data show that 5-HT6 receptor activation by ST1936 reduces the frequency of spontaneous excitatory postsynaptic currents, with an IC50 of 1.3 μM. Moreover, 5-HT6 receptor activation also reduced the amplitude of spontaneous excitatory postsynaptic currents recorded from medium spiny neurons, suggesting a mechanism of action involving postsynaptic 5-HT6 receptors, as further confirmed by the paired-pulse analysis on evoked excitatory postsynaptic currents and by recordings of miniature glutamatergic events. The inhibitory effect of ST1936 on glutamatergic transmission was prevented by the selective 5-HT6 receptor antagonist SB258585 and mimicked by a different agonist, WAY-181187. Conversely, in the cortex ST1936 reduced the frequency, but not the amplitude, of spontaneous excitatory postsynaptic currents suggesting a presynaptic or indirect effect of the 5-HT6 receptor.

  18. Glutamatergic signaling in the brain's white matter.

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    Bakiri, Y; Burzomato, V; Frugier, G; Hamilton, N B; Káradóttir, R; Attwell, D

    2009-01-12

    Glutamatergic signaling has been exceptionally well characterized in the brain's gray matter, where it underlies fast information processing, learning and memory, and also generates the neuronal damage that occurs in pathological conditions such as stroke. The role of glutamatergic signaling in the white matter, an area until recently thought to be devoid of synapses, is less well understood. Here we review what is known, and highlight what is not known, of glutamatergic signaling in the white matter. We focus on how glutamate is released, the location and properties of the receptors it acts on, the interacting molecules that may regulate trafficking or signaling of the receptors, the possible functional roles of glutamate in the white matter, and its pathological effects including the possibility of treating white matter disorders with glutamate receptor blockers.

  19. Astroglia, Glutamatergic Transmission and Psychiatric Diseases.

    Science.gov (United States)

    Verkhratsky, Alexei; Steardo, Luca; Peng, Liang; Parpura, Vladimir

    2016-01-01

    Astrocytes are primary homeostatic cells of the central nervous system. They regulate glutamatergic transmission through the removal of glutamate from the extracellular space and by supplying neurons with glutamine. Glutamatergic transmission is generally believed to be significantly impaired in the contexts of all major neuropsychiatric diseases. In most of these neuropsychiatric diseases, astrocytes show signs of degeneration and atrophy, which is likely to be translated into reduced homeostatic capabilities. Astroglial glutamate uptake/release and glutamate homeostasis are affected in all forms of major psychiatric disorders and represent a common mechanism underlying neurotransmission disbalance, aberrant connectome and overall failure on information processing by neuronal networks, which underlie pathogenesis of neuropsychiatric diseases.

  20. Neuron-glia interactions in glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Schousboe, A; Sickmann, H M; Bak, Lasse Kristoffer;

    2011-01-01

    Glutamatergic neurotransmission accounts for a considerable part of energy consumption related to signaling in the brain. Chemical energy is provided by adenosine triphosphate (ATP) formed in glycolysis and tricarboxylic acid (TCA) cycle combined with oxidative phosphorylation. It is not clear wh...

  1. Analysis Links Zoning Policies and Disparities

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    Shah, Nirvi

    2012-01-01

    Location, location, location. This mantra of real estate agents and their clients alike is now the target of a new report from the Brookings Institution linking housing prices and zoning practices to effectively depriving low-income students of high-quality schools. Using test scores from schools in the 100 largest metropolitan areas in the…

  2. Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells

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    Brill Monika S

    2011-04-01

    Full Text Available Abstract Background While the diversity and spatio-temporal origin of olfactory bulb (OB GABAergic interneurons has been studied in detail, much less is known about the subtypes of glutamatergic OB interneurons. Results We studied the temporal generation and diversity of Neurog2-positive precursor progeny using an inducible genetic fate mapping approach. We show that all subtypes of glutamatergic neurons derive from Neurog2 positive progenitors during development of the OB. Projection neurons, that is, mitral and tufted cells, are produced at early embryonic stages, while a heterogeneous population of glutamatergic juxtaglomerular neurons are generated at later embryonic as well as at perinatal stages. While most juxtaglomerular neurons express the T-Box protein Tbr2, those generated later also express Tbr1. Based on morphological features, these juxtaglomerular cells can be identified as tufted interneurons and short axon cells, respectively. Finally, targeted electroporation experiments provide evidence that while the majority of OB glutamatergic neurons are generated from intrabulbar progenitors, a small portion of them originate from extrabulbar regions at perinatal ages. Conclusions We provide the first comprehensive analysis of the temporal and spatial generation of OB glutamatergic neurons and identify distinct populations of juxtaglomerular interneurons that differ in their antigenic properties and time of origin.

  3. Link Graph Analysis for Adult Images Classification

    CERN Document Server

    Kharitonov, Evgeny; Muchnik, Ilya; Romanenko, Fedor; Belyaev, Dmitry; Kotlyarov, Dmitry

    2010-01-01

    In order to protect an image search engine's users from undesirable results adult images' classifier should be built. The information about links from websites to images is employed to create such a classifier. These links are represented as a bipartite website-image graph. Each vertex is equipped with scores of adultness and decentness. The scores for image vertexes are initialized with zero, those for website vertexes are initialized according to a text-based website classifier. An iterative algorithm that propagates scores within a website-image graph is described. The scores obtained are used to classify images by choosing an appropriate threshold. The experiments on Internet-scale data have shown that the algorithm under consideration increases classification recall by 17% in comparison with a simple algorithm which classifies an image as adult if it is connected with at least one adult site (at the same precision level).

  4. Dispersion penalty analysis for VSR-1 optical links

    Institute of Scientific and Technical Information of China (English)

    JIA Jiu-chun; CHEN Hong-da; CHEN Xiong-bin; ZHOU Yi

    2006-01-01

    This paper presents an approach to calculate dispersion penalty for VSR-1 optical links.Based on parameters of a specific VSR-1 link,dispersion penalties are computed for various modal dispersion bandwidths respectively.The worst-case eye closure is expressed numerically by using the signal waveform at time 0,and the signal waveform is obtained in frequency domain through FFT algorithm.By this approach,the dispersion penalty is determined by the shape of transfer functions of the various components in the links.To simplify the derivation of multimode fiber link transfer function,a Gaussian form of normalized impulse response is used.This calculation approach can be used to estimate the worst-case dispersion penalty of VSR-1 links in the link budget analysis.

  5. Linking Safety Analysis to Safety Requirements

    DEFF Research Database (Denmark)

    Hansen, Kirsten Mark

    the same system model and that this model is formalized in a real-time, interval logic, based on a conventional dynamic systems model with a state over time. The three safety analysis techniques are interpreted in this model and it is shown how to derive safety requirements for components of a system.......Software for safety critical systems must deal with the hazards identified by safety analysistechniques: Fault trees, event trees,and cause consequence diagrams can be interpreted as safety requirements and used in the design activity. We propose that the safety analysis and the system design use...

  6. VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

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    Benagiano Vincenzo

    2011-11-01

    Full Text Available Abstract Background The aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1. Results The examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2 and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively. The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons. Conclusion The present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

  7. Disrupted-in-schizophrenia (DISC1 functions presynaptically at glutamatergic synapses.

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    Brady J Maher

    Full Text Available The pathophysiology of schizophrenia is believed to involve defects in synaptic transmission, and the function of many schizophrenia-associated genes, including DISC1, have been linked to synaptic function at glutamatergic synapses. Here we develop a rodent model via in utero electroporation to assay the presynaptic function of DISC1 at glutamatergic synapses. We used a combination of mosaic transgene expression, RNAi knockdown and optogenetics to restrict both genetic manipulation and synaptic stimulation of glutamatergic neurons presynaptic to other layer 2/3 neocortical pyramidal neurons that were then targeted for whole-cell patch-clamp recording. We show that expression of the DISC1 c-terminal truncation variant that is associated with Schizophrenia alters the frequency of mEPSCs and the kinetics of evoked glutamate release. In addition, we show that expression level of DISC1 is correlated with the probability of glutamate release such that increased DISC1 expression results in paired-pulse depression and RNAi knockdown of DISC1 produces paired-pulse facilitation. Overall, our results support a direct presynaptic function for the schizophrenia-associated gene, DISC1.

  8. Network worlds : from link analysis to virtual places.

    Energy Technology Data Exchange (ETDEWEB)

    Joslyn, C. (Cliff)

    2002-01-01

    Significant progress is being made in knowledge systems through recent advances in the science of very large networks. Attention is now turning in many quarters to the potential impact on counter-terrorism methods. After reviewing some of these advances, we will discuss the difference between such 'network analytic' approaches, which focus on large, homogeneous graph strucures, and what we are calling 'link analytic' approaches, which focus on somewhat smaller graphs with heterogeneous link types. We use this venue to begin the process of rigorously defining link analysis methods, especially the concept of chaining of views of multidimensional databases. We conclude with some speculation on potential connections to virtual world architectures.

  9. Glutamatergic and HPA-axis pathway genes in bipolar disorder comorbid with alcohol- and substance use disorders.

    Science.gov (United States)

    Dalvie, Shareefa; Fabbri, Chiara; Ramesar, Raj; Serretti, Alessandro; Stein, Dan J

    2016-02-01

    Glutamatergic neurotransmission has been shown to be dysregulated in bipolar disorder (BD), alcohol use disorder (AUD) and substance use disorder (SUD). Similarly, disruption in the hypothalamic-pituitary-adrenal (HPA)-axis has also been observed in these conditions. BD is often comorbid with AUD and SUD. The effects of the glutamatergic and HPA systems have not been extensively examined in individuals with BD-AUD and BD-SUD comorbidity. The aim of this investigation was to determine whether variants in the glutamatergic pathway and HPA-axis are associated with BD-AUD and BD-SUD comorbidity. The research cohort consisted of 498 individuals with BD type I from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A subset of the cohort had comorbid current AUD and current SUD. A total of 1935 SNPs from both the glutamatergic and HPA pathways were selected from the STEP-BD genome-wide dataset. To identify population stratification, IBS clustering was performed using the program Plink 1.07. Single SNP association and gene-based association testing were conducted using logistic regression. A pathway analysis of glutamatergic and HPA genes was performed, after imputation using IMPUTE2. No single SNP was associated with BD-AUD or BD-SUD comorbidity after correction for multiple testing. However, from the gene-based analysis, the gene PRKCI was significantly associated with BD-AUD. The pathway analysis provided overall negative findings, although several genes including GRIN2B showed high percentage of associated SNPs for BD-AUD. Even though the glutamatergic and HPA pathways may not be involved in BD-AUD and BD-SUD comorbidity, PRKCI deserves further investigation in BD-AUD.

  10. Metabotropic glutamatergic receptors and their ligands in drug addiction.

    Science.gov (United States)

    Pomierny-Chamioło, Lucyna; Rup, Kinga; Pomierny, Bartosz; Niedzielska, Ewa; Kalivas, Peter W; Filip, Małgorzata

    2014-06-01

    Glutamatergic excitatory transmission is implicated in physiological and pathological conditions like learning, memory, neuronal plasticity and emotions, while glutamatergic abnormalities are reported in numerous neurological and psychiatric disorders, including neurodegenerative diseases, epilepsy, stroke, traumatic brain injury, depression, anxiety, schizophrenia and pain. Also, several lines of evidence have accumulated indicating a pivotal role for glutamatergic neurotransmission in mediating addictive behaviors. Among the proteins regulating glutamatergic transmission, the metabotropic glutamate receptors (mGluR) are being developed as pharmacological targets for treating many neuropsychiatric disorders, including drug addiction. In this review we describe the molecular structure of mGluRs and their distribution, physiology and pharmacology in the central nervous system, as well as their use as targets in preclinical studies of drug addiction.

  11. The effects of stress on glutamatergic transmission in the brain.

    Science.gov (United States)

    Yuan, Ti-Fei; Hou, Gonglin

    2015-01-01

    Stress leads to detrimental effects on brain functions and results in various diseases. Recent studies highlight the involvement of glutamatergic transmission in pathogenesis of depressive behaviors and fears. Acute stress generates different impacts on the excitatory transmission compared to chronic stress. Different neuromodulators and epigenetic factors also participate in the alteration of synaptic transmission and the regulation of synaptic plasticity. Restoration of the glutamatergic transmission in stress-affected brain areas therefore provides novel directions of therapeutic interventions against stress.

  12. Unsupervised action classification using space-time link analysis

    DEFF Research Database (Denmark)

    Liu, Haowei; Feris, Rogerio; Krüger, Volker

    2010-01-01

    In this paper we address the problem of unsupervised discovery of action classes in video data. Different from all existing methods thus far proposed for this task, we present a space-time link analysis approach which matches the performance of traditional unsupervised action categorization metho...... matching for action classification. We present an experiment to demonstrate that our approach is capable of handling cluttered backgrounds, activities with subtle movements, and video data from moving cameras....

  13. Role of nucleus accumbens glutamatergic plasticity in drug addiction.

    Science.gov (United States)

    Quintero, Gabriel C

    2013-01-01

    . Antagonism of the CP-AMPARs reduces cravings. It is necessary to pursue further exploration of the AMPA receptor subunit composition and variations at the level of the NAc for a better understanding of glutamatergic plastic changes. It is known that cocaine and morphine are able to induce changes in dendritic spine morphology by modifying actin cycling. These changes include an initial increase in spine head diameter and increases in AMPA receptor expression, followed by a second stage of spine head diameter retraction and reduction of the AMPA receptors' expression in spines. Besides glutamate and dopamine, other factors, like brain-derived neurotrophic factor (BDNF), can influence NAc activity and induce changes in dendritic spine density. BDNF also induces drug-related behaviors like self-administration and relapse. Neither apoptosis nor neurogenesis plays a relevant role in the neurobiological processes subjacent to cocaine addiction in adults (rodent or human). Different therapeutic drugs like N-acetylcysteine (NAC), modafinil, acamprosate, and topiramate have been tested in preclinical and/or clinical models for alleviating drug relapse. Moreover, these therapeutic drugs target the glutamatergic circuitry between the PFC and the NAc. NAC and acamprosate have shown inconsistent results in clinical trials. Modafinil and topiramate have shown some success, but more clinical trials are necessary. Based on the current review findings, it could be recommendable to explore therapeutic approaches that include synergism between different drugs and neurotransmitter systems. The discrepancy in the results of some therapeutic drugs between preclinical versus clinical trials for alleviating relapse or drug dependence could be linked to the scarce exploration of preclinical models that mimic polydrug abuse patterns, for example, cocaine plus alcohol. At the clinical level, the pattern of polydrug consumption is a phenomenon of considerable frequency. Finally, as a complement at the

  14. Bibliometric analysis of scientific production about Linked Data

    Directory of Open Access Journals (Sweden)

    Leandro Dal Pizzol

    2015-09-01

    Full Text Available Introduction: Since Tim Berners-Lee coined the term Linked Data in 2006, many studies have emerged based on this initiative. Whether in the form of information access initiatives, whether in applications based on this data type, the interest in this new way to publish and consume information on the Web is increasingly in focus. Objective: In this paper, we present a bibliometric review with the aim of contributing to a better understanding and clarification of concepts and terms associated with the area of Linked Data. Methodology: We have used the Web of Science (WoS, Scopus, EBSCO and IEEE scientific databases, in order to find the existing studies about Linked Data until October 2012. Results: We have mapped 148 scientific papers that address the above issue, written by 409 authors from 160 institutions from 30 different countries. Through the analysis of the articles, it was found that researches about Linked Data are concentrated in a small authors group, suggesting future research opportunities. Conclusions: Synthesizing the information related to the scientific publications in a given area allows building a theoretical background that supports the development of future researches.

  15. Lrp4 in astrocytes modulates glutamatergic transmission.

    Science.gov (United States)

    Sun, Xiang-Dong; Li, Lei; Liu, Fang; Huang, Zhi-Hui; Bean, Jonathan C; Jiao, Hui-Feng; Barik, Arnab; Kim, Seon-Myung; Wu, Haitao; Shen, Chengyong; Tian, Yun; Lin, Thiri W; Bates, Ryan; Sathyamurthy, Anupama; Chen, Yong-Jun; Yin, Dong-Min; Xiong, Lei; Lin, Hui-Ping; Hu, Jin-Xia; Li, Bao-Ming; Gao, Tian-Ming; Xiong, Wen-Cheng; Mei, Lin

    2016-08-01

    Neurotransmission requires precise control of neurotransmitter release from axon terminals. This process is regulated by glial cells; however, the underlying mechanisms are not fully understood. We found that glutamate release in the brain was impaired in mice lacking low-density lipoprotein receptor-related protein 4 (Lrp4), a protein that is critical for neuromuscular junction formation. Electrophysiological studies revealed compromised release probability in astrocyte-specific Lrp4 knockout mice. Lrp4 mutant astrocytes suppressed glutamatergic transmission by enhancing the release of ATP, whose level was elevated in the hippocampus of Lrp4 mutant mice. Consequently, the mutant mice were impaired in locomotor activity and spatial memory and were resistant to seizure induction. These impairments could be ameliorated by blocking the adenosine A1 receptor. The results reveal a critical role for Lrp4, in response to agrin, in modulating astrocytic ATP release and synaptic transmission. Our findings provide insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.

  16. Linking Design to Business Strategy Through Functional Analysis

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    1997-01-01

    The paper discusses how designers, conducting design projects in specific organization's, can assure that the design of IT is appropriately linked to the organizations overall business strategy. A case study is presented in the form of a design project in a small public organization. Functional...... analysis was used as a means to clarify how a specific needed information system could support the organization's new business strategy. Using functional analysis in the design project had a powerful effect: it seriously challenged the organization's business strategy and revealed that the system...... to the relation between an organization's IT-projects and its business strategy and by suggesting that it is the responsibility of the designers, conducting design projects, to assure that this task is taken proper care of. Practical guidelines for this purpose are given....

  17. Semantic analysis of links in the musical Wikipedia

    DEFF Research Database (Denmark)

    Mølgaard, Lasse Lohilahti; Hansen, Lars Kai; Larsen, Jan

    2008-01-01

    Wikipedia has significant potential in music information retrieval research. In this work we analyze the of the link structure in the musical Wikipedia. Wikipedia links differ in certain ways from links on the Web at large. There are an over-abundance of internal links in Wikipedia, links...... are generated automatically, and they may even maliciously be used to promote certain topics. Wikipedia has been analyzed recently using methods fromWeb and text mining, however, the fact the link structure is different from the Web’s makes this approach questionable. To better understand the link structure...

  18. Blind links, a big challenge in the linked data idea: Analysis of Persian Subject Headings

    Directory of Open Access Journals (Sweden)

    Atefeh Sharif

    2014-12-01

    Full Text Available In this survey, Linked data concept as exposing, sharing, and connecting pieces of data, information, and knowledge on the Semantic Web and some potential problems in converting Persian subject headings (PSHs Records into linked data were discussed. A data set (11233 records of PSHs was searched in three information retrieval systems including National Library of Iran (NLI online catalog, Library of Congress (LC online catalog and NOSA books. Correct links between Persian and English subject headings in the 9519 common records of two catalogs were recorded. The results indicate that the links between Persian and English subjects in 20% of records were failed. The maximum error was associated with the anonymous databases (6/7 % in NLI online catalog. It is recommended to preprocess the PSHs records before any conversion projects. It seems that, during the preprocessing, the potential errors could be identified and corrected.

  19. Design and Analysis of Underwater Acoustic Networks with Reflected Links

    Science.gov (United States)

    Emokpae, Lloyd

    -of-sight (LOS) and NLOS links by utilizing directional antennas, which will boost the signal-to-noise ratio (SNR) at the receiver while promoting NLOS usage. In our model, we employ a directional underwater acoustic antenna composed of an array of hydrophones that can be summed up at various phases and amplitudes resulting in a beam-former. We have also adopted a practical multimodal directional transducer concept which generates both directional and omni-directional beam patterns by combining the fundamental vibration modes of a cylindrical acoustic radiator. This allows the transducer to be electrically controlled and steered by simply adjusting the electrical voltage weights. A prototype acoustic modem is then developed to utilize the multimodal directional transducer for both LOS and NLOS communication. The acoustic modem has also been used as a platform for empirically validating our SBR communication model in a tank and with empirical data. Networking protocols have been developed to exploit the SBR communication model. These protocols include node discovery and localization, directional medium access control (D-MAC) and geographical routing. In node discovery and localization, each node will utilize SBR-based range measurements to its neighbors to determine their relative position. The D-MAC protocol utilizes directional antennas to increase the network throughput due to the spatial efficiency of the antenna model. In the proposed reflection-enabled directional MAC protocol (RED-MAC), each source node will be able to determine if an obstacle is blocking the LOS link to the destination and switch to the best NLOS link by utilizing surface/bottom reflections. Finally, we have developed a geographical routing algorithm which aims to establish the best stable route from a source node to a destination node. The optimized route is selected to achieve maximum network throughput. Extensive analysis of the network throughput when utilizing directional antennas is also presented

  20. PRELIMINARY PHYTOCHEMICAL ANALYSIS OF ACTINIOPTERIS RADIATA (SWARTZ LINK.

    Directory of Open Access Journals (Sweden)

    R. Manonmani

    2013-06-01

    Full Text Available The objective of the present study was to find out the presence of preliminary phytochemicals in six different solvent extracts of Actiniopteris radiata (Swartz link. by qualitative screening methods. The solvent used for the extraction of leaf and rhizome powder were ethanol, petroleum ether, chloroform, acetone, DMSO and aqueous. The secondary metabolites such as steroids, triterpenoids, reducing sugars, sugars, alkaloids, phenolic compounds, catechins, flavonoids, saponins, tannins, anthroquinones and amino acids were screened by using standard methods. The phytochemical analysis of the ethanolic extract of both (leaf & rhizome revealed the presence of most active constituents than the other solvents. The ethanolic rhizome extracts of Actiniopteris radiata showed higher amount of phytochemicals when compared with the ethanolic leaf extracts.

  1. The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain.

    Science.gov (United States)

    Okerlund, Nathan D; Stanley, Robert E; Cheyette, Benjamin N R

    2016-07-01

    The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment.

  2. Developmental patterning of glutamatergic synapses onto retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    Schubert Timm

    2008-03-01

    Full Text Available Abstract Background Neurons receive excitatory synaptic inputs that are distributed across their dendritic arbors at densities and with spatial patterns that influence their output. How specific synaptic distributions are attained during development is not well understood. The distribution of glutamatergic inputs across the dendritic arbors of mammalian retinal ganglion cells (RGCs has long been correlated to the spatial receptive field profiles of these neurons. Thus, determining how glutamatergic inputs are patterned onto RGC dendritic arbors during development could provide insight into the cellular mechanisms that shape their functional receptive fields. Results We transfected developing and mature mouse RGCs with plasmids encoding fluorescent proteins that label their dendrites and glutamatergic postsynaptic sites. We found that as dendritic density (dendritic length per unit area of dendritic field decreases with maturation, the density of synapses along the dendrites increases. These changes appear coordinated such that RGCs attain the mature average density of postsynaptic sites per unit area (areal density by the time synaptic function emerges. Furthermore, stereotypic centro-peripheral gradients in the areal density of synapses across the arbor of RGCs are established at an early developmental stage. Conclusion The spatial pattern of glutamatergic inputs onto RGCs arises early in synaptogenesis despite ensuing reorganization of dendritic structure. We raise the possibility that these early patterns of synaptic distributions may arise from constraints placed on the number of contacts presynaptic neurons are able to make with the RGCs.

  3. Energy substrates to support glutamatergic and GABAergic synaptic function

    DEFF Research Database (Denmark)

    Schousboe, Arne; Bak, Lasse K; Sickmann, Helle M;

    2007-01-01

    Maintenance of glutamatergic and GABAergic activity requires a continuous supply of energy since the exocytotic processes as well as high affinity glutamate and GABA uptake and subsequent metabolism of glutamate to glutamine are energy demanding processes. The main energy substrate for the brain ...

  4. Glutamatergic Signaling at the Vestibular Hair Cell Calyx Synapse

    NARCIS (Netherlands)

    Sadeghi, Soroush G.; Pyott, Sonja J.; Yu, Zhou; Glowatzki, Elisabeth

    2014-01-01

    In the vestibular periphery a unique postsynaptic terminal, the calyx, completely covers the basolateral walls of type I hair cells and receives input from multiple ribbon synapses. To date, the functional role of this specialized synapse remains elusive. There is limited data supporting glutamaterg

  5. Serotonin modulates glutamatergic transmission to neurons in the lateral habenula.

    Science.gov (United States)

    Xie, Guiqin; Zuo, Wanhong; Wu, Liangzhi; Li, Wenting; Wu, Wei; Bekker, Alex; Ye, Jiang-Hong

    2016-04-01

    The lateral habenula (LHb) is bilaterally connected with serotoninergic raphe nuclei, and expresses high density of serotonin receptors. However, actions of serotonin on the excitatory synaptic transmission to LHb neurons have not been thoroughly investigated. The LHb contains two anatomically and functionally distinct regions: lateral (LHbl) and medial (LHbm) divisions. We compared serotonin's effects on glutamatergic transmission across the LHb in rat brains. Serotonin bi-directionally and differentially modulated glutamatergic transmission. Serotonin inhibited glutamatergic transmission in higher percentage of LHbl neurons but potentiated in higher percentage of LHbm neurons. Magnitude of potentiation was greater in LHbm than in LHbl. Type 2 and 3 serotonin receptor antagonists attenuated serotonin's potentiation. The serotonin reuptake blocker, and the type 2 and 3 receptor agonists facilitated glutamatergic transmission in both LHbl and LHbm neurons. Thus, serotonin via activating its type 2, 3 receptors, increased glutamate release at nerve terminals in some LHb neurons. Our data demonstrated that serotonin affects both LHbm and LHbl. Serotonin might play an important role in processing information between the LHb and its downstream-targeted structures during decision-making. It may also contribute to a homeostatic balance underlying the neural circuitry between the LHb and raphe nuclei.

  6. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.

    Science.gov (United States)

    Menniti, Frank S; Lindsley, Craig W; Conn, P Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A

    2013-01-01

    Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved.

  7. The Communication Link and Error ANalysis (CLEAN) simulator

    Science.gov (United States)

    Ebel, William J.; Ingels, Frank M.; Crowe, Shane

    1993-01-01

    During the period July 1, 1993 through December 30, 1993, significant developments to the Communication Link and Error ANalysis (CLEAN) simulator were completed and include: (1) Soft decision Viterbi decoding; (2) node synchronization for the Soft decision Viterbi decoder; (3) insertion/deletion error programs; (4) convolutional encoder; (5) programs to investigate new convolutional codes; (6) pseudo-noise sequence generator; (7) soft decision data generator; (8) RICE compression/decompression (integration of RICE code generated by Pen-Shu Yeh at Goddard Space Flight Center); (9) Markov Chain channel modeling; (10) percent complete indicator when a program is executed; (11) header documentation; and (12) help utility. The CLEAN simulation tool is now capable of simulating a very wide variety of satellite communication links including the TDRSS downlink with RFI. The RICE compression/decompression schemes allow studies to be performed on error effects on RICE decompressed data. The Markov Chain modeling programs allow channels with memory to be simulated. Memory results from filtering, forward error correction encoding/decoding, differential encoding/decoding, channel RFI, nonlinear transponders and from many other satellite system processes. Besides the development of the simulation, a study was performed to determine whether the PCI provides a performance improvement for the TDRSS downlink. There exist RFI with several duty cycles for the TDRSS downlink. We conclude that the PCI does not improve performance for any of these interferers except possibly one which occurs for the TDRS East. Therefore, the usefulness of the PCI is a function of the time spent transmitting data to the WSGT through the TDRS East transponder.

  8. Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Han Seol-Heui

    2010-11-01

    Full Text Available Abstract Background Prenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD. The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC and in vivo FASD models. Methods Neural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4 g/kg/day diluted with normal saline from E7 to E16 for in vivo FASD animal models. Expression level of proteins was investigated by western blot analysis and immunocytochemical assays. MTT was used for cell viability. Proliferative activity of NPCs was identified by BrdU incorporation, immunocytochemistry and FACS analysis. Results Reduced proliferation of NPCs by ethanol was demonstrated using BrdU incorporation, immunocytochemistry and FACS analysis. In addition, ethanol induced the imbalance between glutamatergic and GABAergic neuronal differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD with concomitant decrease in the expression of Mash1. Similar pattern of expression of those transcription factors was observed using an in vivo model of FASD as well as the increased expression of PSD-95 and decreased expression of GAD67. Conclusions These results suggest that ethanol induces hyper-differentiation of glutamatergic neuron through Pax6 pathway, which may underlie the hyper-excitability phenotype such as hyperactivity or seizure susceptibility in FASD patients.

  9. Role of nucleus accumbens glutamatergic plasticity in drug addiction

    Directory of Open Access Journals (Sweden)

    Quintero GC

    2013-09-01

    -isoxazolepropionic acid (AMPA receptors at the level of the NAc. Also, cocaine self-administration and withdrawal induce the formation of subunit glutamate receptor 2 (GluA2, lacking the Ca2+-permeable AMPA receptors (CP-AMPARs at the level of the NAc. Antagonism of the CP-AMPARs reduces cravings. It is necessary to pursue further exploration of the AMPA receptor subunit composition and variations at the level of the NAc for a better understanding of glutamatergic plastic changes. It is known that cocaine and morphine are able to induce changes in dendritic spine morphology by modifying actin cycling. These changes include an initial increase in spine head diameter and increases in AMPA receptor expression, followed by a second stage of spine head diameter retraction and reduction of the AMPA receptors’ expression in spines. Besides glutamate and dopamine, other factors, like brain-derived neurotrophic factor (BDNF, can influence NAc activity and induce changes in dendritic spine density. BDNF also induces drug-related behaviors like self-administration and relapse. Neither apoptosis nor neurogenesis plays a relevant role in the neurobiological processes subjacent to cocaine addiction in adults (rodent or human. Different therapeutic drugs like N-acetylcysteine (NAC, modafinil, acamprosate, and topiramate have been tested in preclinical and/or clinical models for alleviating drug relapse. Moreover, these therapeutic drugs target the glutamatergic circuitry between the PFC and the NAc. NAC and acamprosate have shown inconsistent results in clinical trials. Modafinil and topiramate have shown some success, but more clinical trials are necessary. Based on the current review findings, it could be recommendable to explore therapeutic approaches that include synergism between different drugs and neurotransmitter systems. The discrepancy in the results of some therapeutic drugs between preclinical versus clinical trials for alleviating relapse or drug dependence could be linked to the

  10. Scalable Text and Link Analysis with Mixed-Topic Link Models

    CERN Document Server

    Zhu, Yaojia; Getoor, Lise; Moore, Cristopher

    2013-01-01

    Many data sets contain rich information about objects, as well as pairwise relations between them. For instance, in networks of websites, scientific papers, and other documents, each node has content consisting of a collection of words, as well as hyperlinks or citations to other nodes. In order to perform inference on such data sets, and make predictions and recommendations, it is useful to have models that are able to capture the processes which generate the text at each node and the links between them. In this paper, we combine classic ideas in topic modeling with a variant of the mixed-membership block model recently developed in the statistical physics community. The resulting model has the advantage that its parameters, including the mixture of topics of each document and the resulting overlapping communities, can be inferred with a simple and scalable expectation-maximization algorithm. We test our model on three data sets, performing unsupervised topic classification and link prediction. For both task...

  11. FEA Based Analysis of Composite Torque Link for a Passenger Aircraft Landing Gear

    Directory of Open Access Journals (Sweden)

    R. Arravind

    2013-08-01

    Full Text Available In the implementation of a composite landing gear technology program was started, a composite torque link for transport airplane landing gear applications was developed. The torque link was designed by finite element analysis and analysis for maximum stress condition. The torque link was fabricated by Resin Transfer Moulding (RTM for which a tooling concept was developed. Static tests demonstrated the load carrying capabilities in undamaged and damaged condition of the torque link since all specimens failed beyond their Design Ultimate Load level for that case we are hereby carryout the analysis process in order to find the ultimate load and yield stress for the torque link.

  12. Significance-linked connected component analysis for wavelet image coding.

    Science.gov (United States)

    Chai, B B; Vass, J; Zhuang, X

    1999-01-01

    Recent success in wavelet image coding is mainly attributed to a recognition of the importance of data organization and representation. There have been several very competitive wavelet coders developed, namely, Shapiro's (1993) embedded zerotree wavelets (EZW), Servetto et al.'s (1995) morphological representation of wavelet data (MRWD), and Said and Pearlman's (see IEEE Trans. Circuits Syst. Video Technol., vol.6, p.245-50, 1996) set partitioning in hierarchical trees (SPIHT). We develop a novel wavelet image coder called significance-linked connected component analysis (SLCCA) of wavelet coefficients that extends MRWD by exploiting both within-subband clustering of significant coefficients and cross-subband dependency in significant fields. Extensive computer experiments on both natural and texture images show convincingly that the proposed SLCCA outperforms EZW, MRWD, and SPIHT. For example, for the Barbara image, at 0.25 b/pixel, SLCCA outperforms EZW, MRWD, and SPIHT by 1.41 dB, 0.32 dB, and 0.60 dB in PSNR, respectively. It is also observed that SLCCA works extremely well for images with a large portion of texture. For eight typical 256x256 grayscale texture images compressed at 0.40 b/pixel, SLCCA outperforms SPIHT by 0.16 dB-0.63 dB in PSNR. This performance is achieved without using any optimal bit allocation procedure. Thus both the encoding and decoding procedures are fast.

  13. Linking Ayurveda and Western medicine by integrative analysis.

    Science.gov (United States)

    Fauzi, Fazlin Mohd; Koutsoukas, Alexios; Lowe, Robert; Joshi, Kalpana; Fan, Tai-Ping; Glen, Robert C; Bender, Andreas

    2013-04-01

    In this article, we discuss our recent work in elucidating the mode-of-action of compounds used in traditional medicine including Ayurvedic medicine. Using computational ('in silico') approach, we predict potential targets for Ayurvedic anti-cancer compounds, obtained from the Indian Plant Anticancer Database given its chemical structure. In our analysis, we observed that: (i) the targets predicted can be connected to cancer pathogenesis i.e. steroid-5-alpha reductase 1 and 2 and estrogen receptor-β, and (ii) predominantly hormone-dependent cancer targets were predicted for the anti-cancer compounds. Through the use of our in silico target prediction, we conclude that understanding how traditional medicine such as Ayurveda work through linking with the 'western' understanding of chemistry and protein targets can be a fruitful avenue in addition to bridging the gap between the two different schools of thinking. Given that compounds used in Ayurveda have been tested and used for thousands of years (although not in the same approach as Western medicine), they can potentially be developed into potential new drugs. Hence, to further advance the case of Ayurvedic medicine, we put forward some suggestions namely: (a) employing and integrating novel analytical methods given the advancements of 'omics' and (b) sharing experimental data and clinical results on studies done on Ayurvedic compounds in an easy and accessible way.

  14. Linking of total elbow prosthesis during surgery; a biomechanical analysis

    NARCIS (Netherlands)

    Vos, M.J. de; Wagener, M.L.; Hendriks, J.C.M.; Eygendaal, D.; Verdonschot, N.J.J.

    2013-01-01

    BACKGROUND: Presently, 2 types of elbow prostheses are used: unlinked and linked. The Latitude total elbow prosthesis allows the surgeon to decide during the implantation whether the prosthesis is placed unlinked or linked, and whether the native radial head is retained, resected, or replaced. The p

  15. Signaling by postsynaptic AMPA receptors in glutamatergic synapse maturation

    OpenAIRE

    2010-01-01

    Excitatory transmission in the brain is largely mediated by synapses containing the neurotransmitter glutamate. Neuronal circuitry is first established early in brain development requiring the formation of vast numbers of glutamatergic synapses at individual sites of contact made between presynaptic axons and postsynaptic dendrites. Despite mounting efforts in the last decade to identify the complex molecular mechanisms underlying initial synaptogenesis and the subsequent steps of synapse m...

  16. Ultradian corticosterone pulses balance glutamatergic transmission and synaptic plasticity.

    Science.gov (United States)

    Sarabdjitsingh, Ratna Angela; Jezequel, Julie; Pasricha, Natasha; Mikasova, Lenka; Kerkhofs, Amber; Karst, Henk; Groc, Laurent; Joëls, Marian

    2014-09-30

    The rodent adrenal hormone corticosterone (CORT) reaches the brain in hourly ultradian pulses, with a steep rise in amplitude before awakening. The impact of a single CORT pulse on glutamatergic transmission is well documented, but it remains poorly understood how consecutive pulses impact on glutamate receptor trafficking and synaptic plasticity. By using high-resolution imaging and electrophysiological approaches, we report that a single pulse of CORT to hippocampal networks causes synaptic enrichment of glutamate receptors and increased responses to spontaneously released glutamatergic vesicles, collectively abrogating the ability to subsequently induce synaptic long-term potentiation. Strikingly, a second pulse of CORT one hour after the first--mimicking ultradian pulses--completely normalizes all aspects of glutamate transmission investigated, restoring the plastic range of the synapse. The effect of the second pulse is precisely timed and depends on a nongenomic glucocorticoid receptor-dependent pathway. This normalizing effect through a sequence of CORT pulses--as seen around awakening--may ensure that hippocampal glutamatergic synapses remain fully responsive and able to encode new stress-related information when daily activities start.

  17. Analysis of sensory ratings data with cumulative link models

    DEFF Research Database (Denmark)

    Christensen, Rune Haubo Bojesen; Brockhoff, Per B.

    2013-01-01

    Examples of categorical rating scales include discrete preference, liking and hedonic rating scales. Data obtained on these scales are often analyzed with normal linear regression methods or with omnibus Pearson chi2 tests. In this paper we propose to use cumulative link models that allow...... for regression methods similar to linear models while respecting the categorical nature of the observations. We describe how cumulative link models are related to the omnibus chi2 tests and how they can lead to more powerful tests in the non-replicated setting. For replicated categorical ratings data we present...... a quasi-likelihood approach and a mixed effects approach both being extensions of cumulative link models. We contrast population-average and subject-specific interpretations based on these models and discuss how different approaches lead to different tests. In replicated settings, naive tests that ignore...

  18. Feasibility analysis of WDM links for radar applications

    Directory of Open Access Journals (Sweden)

    D. Meena

    2015-03-01

    Full Text Available Active phased array antennas enhances the performance of modern radars by using multiple low power transmit/receive modules in place of a high power transmitter in conventional radars. Fully distributed phased array radars demand the distribution of various signals in radio frequency (RF and digital domain for real time operation. This is normally achieved through complex and bulky coaxial distribution networks. In this work, we intend to tap the inherent advantages of fiber links with wavelength division multiplexed (WDM technology and a feasibility study to adapt these links for radar applications is carried out. This is done by analysing various parameters like amplitude, delay, frequency and phase variation response of various radar waveforms over WDM links. This also includes performance evaluation of non-linear frequency modulation (NLFM signals, known for better signal to noise ratio (SNR to specific side lobe levels. NLFM waveforms are further analysed using pulse compression (PC technique. Link evaluation is also carried out using a standard simulation environment and is then experimentally verified with other waveforms like RF continuous wave (CW, pulsed RF and digital signals. Synchronization signals are generated from this variable duty cycle digital signals during real time radar operation. During evaluation of digital signals, variable transient effects for different duty cycles are observed from an amplifier configuration. A suppression method is proposed to eliminate this transient effects. Further, the link delay response is investigated using different lengths of fiber spools. It can be inferred from the experimental results that WDM links are capable of handling various signals significant to radar applications.

  19. Effective Focused Crawling Based on Content and Link Structure Analysis

    OpenAIRE

    Pal, Anshika; Tomar, Deepak Singh; S. C. Shrivastava

    2009-01-01

    A focused crawler traverses the web selecting out relevant pages to a predefined topic and neglecting those out of concern. While surfing the internet it is difficult to deal with irrelevant pages and to predict which links lead to quality pages. In this paper a technique of effective focused crawling is implemented to improve the quality of web navigation. To check the similarity of web pages w.r.t. topic keywords a similarity function is used and the priorities of extracted out links are al...

  20. Queueing analysis of a shared voice-data link

    Science.gov (United States)

    Friedman, D. U.

    1981-11-01

    We consider a link shared by some number of off-hook phone callers and a data queue. The allocation of capacity to voice and data depends on the level of speaker activity (number of talkspurt). A Markov chain model is adopted for this activity, and the resulting data queue performance is analyzed.

  1. Early sequential formation of functional GABA(A) and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus.

    Science.gov (United States)

    Hennou, Sonia; Khalilov, Ilgam; Diabira, Diabé; Ben-Ari, Yehezkel; Gozlan, Henri

    2002-07-01

    During postnatal development of CA1 pyramidal neurons, GABAergic synapses are excitatory and established prior to glutamatergic synapses. As interneurons are generated before pyramidal cells, we have tested the hypothesis that the GABAergic interneuronal network is operative before glutamate pyramidal neurons and provides the initial patterns of activity. We patch-clamp recorded interneurons in foetal (69 neurons) and neonatal P0 (162 neurons) hippocampal slices and performed a morphofunctional analysis of biocytin-filled neurons. At P0, three types of interneurons were found: (i) non-innervated "silent" interneurons (5%) with no spontaneous or evoked synaptic currents; (ii) G interneurons (17%) with GABA(A) synapses only; and (iii) GG interneurons with GABA and glutamatergic synapses (78%). Relying on the neuronal capacitance, cell body size and arborization of dendrites and axons, the three types of interneurons correspond to three stages of development with non-innervated neurons and interneurons with GABA(A) and glutamatergic synapses being, respectively, the least and the most developed. Recordings from both pyramidal neurons and interneurons in foetuses (E18-20) revealed that the majority of interneurons (65%) had functional synapses whereas nearly 90% of pyramidal neurons were quiescent. Therefore, interneurons follow the same GABA-glutamate sequence of synapse formation but earlier than the principal cells. Interneurons are the source and the target of the first synapses formed in the hippocampus and are thus in a position to modulate the development of the hippocampus in the foetal stage.

  2. Path Analysis: A Link between Family Theory and Reseach.

    Science.gov (United States)

    Rank, Mark R.; Sabatelli, Ronald M.

    This paper discusses path analysis and the applicability of this methodology to the field of family studies. The statistical assumptions made in path analysis are presented along with a description of the two types of models within path analysis, i.e., recursive and non-recursive. Methods of calculating in the path model and the advantages of…

  3. A Link Network Analysis of Iranian Research Institute Websites: Overt and Covert Relationships

    OpenAIRE

    Zahra Noroozi; Mohammad Javad Hashemzadeh

    2014-01-01

    The research investigates the link and networks of Iranian research institute websites using webometrics and the link analysis method. The population includes the websites of 23 research institutes and centers in Iran. The data were collected using the Webometric Analyst software. The network diagram shows the mutual link strength among the set of research institute websites in Iran, and depicts the pattern of internal relationships among these websites. Iranian research institute websites ...

  4. Performance Analysis of "WBC over DVB-H" Link Layer

    Directory of Open Access Journals (Sweden)

    Ji Zhanlin

    2010-01-01

    Full Text Available This paper presents two novel smart cross-layer error-control coding schemes for improving the error protection of service advertisements that are broadcast to mobile terminals on wireless billboard channels (WBCs established over a digital video broadcast-handheld (DVB-H infrastructure. These are the smart section erasure (SSE and smart transport stream erasure (STSE schemes, which are jointly executed by the link layer and service layer cross-layer algorithms. The new schemes are analysed and compared to existing schemes. The solution enables the "WBC over DVB-H" system to operate with good flexibility, and in a more reliable way and with greater throughput efficiency than the standard IP datacasting supported in DVB-H.

  5. Boundaries, links and clusters: a new paradigm in spatial analysis?

    Science.gov (United States)

    Jacquez, Geoff M; Kaufmann, Andy; Goovaerts, Pierre

    2008-12-01

    This paper develops and applies new techniques for the simultaneous detection of boundaries and clusters within a probabilistic framework. The new statistic "little b" (written b(ij)) evaluates boundaries between adjacent areas with different values, as well as links between adjacent areas with similar values. Clusters of high values (hotspots) and low values (coldspots) are then constructed by joining areas abutting locations that are significantly high (e.g., an unusually high disease rate) and that are connected through a "link" such that the values in the adjoining areas are not significantly different. Two techniques are proposed and evaluated for accomplishing cluster construction: "big B" and the "ladder" approach. We compare the statistical power and empirical Type I and Type II error of these approaches to those of wombling and the local Moran test. Significance may be evaluated using distribution theory based on the product of two continuous (e.g., non-discrete) variables. We also provide a "distribution free" algorithm based on resampling of the observed values. The methods are applied to simulated data for which the locations of boundaries and clusters is known, and compared and contrasted with clusters found using the local Moran statistic and with polygon Womble boundaries. The little b approach to boundary detection is comparable to polygon wombling in terms of Type I error, Type II error and empirical statistical power. For cluster detection, both the big B and ladder approaches have lower Type I and Type II error and are more powerful than the local Moran statistic. The new methods are not constrained to find clusters of a pre-specified shape, such as circles, ellipses and donuts, and yield a more accurate description of geographic variation than alternative cluster tests that presuppose a specific cluster shape. We recommend these techniques over existing cluster and boundary detection methods that do not provide such a comprehensive description

  6. Interrelation among several important links in seismic risk analysis

    Institute of Scientific and Technical Information of China (English)

    HUANG Wei-qiong; WU Xuan

    2006-01-01

    In order to further reveal the interrelation among division of seismic statistical regions, delimitation of potential seismic sources and estimation of seismicity parameters, we select 21 representative sites located in different places within the range of 100°~120°E, 29°~42°N to study the influences of seismicity parameter uncertainties of statistical regions on seismic risk estimations of these sites in the inhomogeneous and homogeneous distribution models. Combining the results from this study and previous ones, we can see that different schemes for dividing seismic statistical regions can change the seismic data in a statistical region. The uncertain data and additional uncertainty in selecting time intervals for seismic statistics will result in uncertainty of seismicity parameters estimation in a statistical region. For the homogeneous model, the larger the variation of this uncertainty is, the greater the uncertain influence on the seismic risk estimation of a site will be, which means that the division of seismic statistical regions makes a major contribution. In a seismic statistical region, the delimitation of potential sources and variant weight assignment of spatial distribution functions can raise the estimated values of ground motion parameters in the place where great earthquake might occur and its vicinity. In these places, the influence of uncertainty in potential source delimitation is very obvious, especially on the absolute magnitude of ground motion parameters (e.g., intensity), which means that the link of potential source delimitation makes a major effect. Generally speaking, the link of potential source delimitation affects mainly the sites located in the potential sources with the highest and second-high upper-limit earthquake magnitudes or in the vicinity of those with the highest upper-limit magnitude. While for the sites located in the potential sources with low upper-limit magnitudes, the uncertainty influence of statistical

  7. An Open Data Format for Visualization and Analysis of Cross-Linked Mass Spectrometry Results.

    Science.gov (United States)

    Hoopmann, Michael R; Mendoza, Luis; Deutsch, Eric W; Shteynberg, David; Moritz, Robert L

    2016-11-01

    Protein-protein interactions are an important element in the understanding of protein function, and chemical cross-linking shotgun mass spectrometry is rapidly becoming a routine approach to identify these specific interfaces and topographical interactions. Protein cross-link data analysis is aided by dozens of algorithm choices, but hindered by a lack of a common format for representing results. Consequently, interoperability between algorithms and pipelines utilizing chemical cross-linking remains a challenge. pepXML is an open, widely-used format for representing spectral search algorithm results that has facilitated information exchange and pipeline development for typical shotgun mass spectrometry analyses. We describe an extension of this format to incorporate cross-linking spectral search results. We demonstrate application of the extension by representing results of multiple cross-linking search algorithms. In addition, we demonstrate adapting existing pepXML-supporting software pipelines to analyze protein cross-linking results formatted in pepXML. Graphical Abstract ᅟ.

  8. A pressurized nitrogen counterbalance to cortical glutamatergic pathway stimulation.

    Science.gov (United States)

    Vallee, Nicolas; Rostain, Jean-Claude; Risso, Jean-Jacques

    2010-05-01

    Previous microdialysis studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by nitrogen narcosis. We sought to establish the hypothetical role of the glutamatergic corticostriatal pathway because of the glutamate deficiency which occurs in the basal ganglia in this hyperbaric syndrome. Retrodialysis with 1 mM of Saclofen and 100 mM of KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of glutamate by 95.2% and no changes in dopamine levels. Under 3 MPa of nitrogen and with the infusion, the rate of striatal glutamate decreased by 51.3%, to a greater extent than under pressurised nitrogen alone (-23.8%). The rate of dopamine decreased, which also occurred under pressurised nitrogen (-36.9 and -31.4%, respectively). In conclusion, the function of the corticostriatal pathway is affected by nitrogen under pressure. This suggests that the nitrogen-induced break point seems to be located at the glutamatergic striatopetal neurons.

  9. Using Link Analysis Technique with a Modified Shortest-Path Algorithm to Fight Money Laundering

    Institute of Scientific and Technical Information of China (English)

    CHEN Yunkai; MAI Quanwen; LU Zhengding

    2006-01-01

    Effective link analysis techniques are needed to help law enforcement and intelligence agencies fight money laundering.This paper presents a link analysis technique that uses a modified shortest-path algorithms to identify the strongest association paths between entities in a money laundering network.Based on two-tree Dijkstra and Priority-First-Search (PFS) algorithm, a modified algorithm is presented.To apply the algorithm, a network representation transformation is made first.

  10. Outage Probability Analysis of FSO Links over Foggy Channel

    KAUST Repository

    Esmail, Maged Abdullah

    2017-02-22

    Outdoor Free space optic (FSO) communication systems are sensitive to atmospheric impairments such as turbulence and fog, in addition to being subject to pointing errors. Fog is particularly severe because it induces an attenuation that may vary from few dBs up to few hundreds of dBs per kilometer. Pointing errors also distort the link alignment and cause signal fading. In this paper, we investigate and analyze the FSO systems performance under fog conditions and pointing errors in terms of outage probability. We then study the impact of several effective communication mitigation techniques that can improve the system performance including multi-hop, transmit laser selection (TLS) and hybrid RF/FSO transmission. Closed-form expressions for the outage probability are derived and practical and comprehensive numerical examples are suggested to assess the obtained results. We found that the FSO system has limited performance that prevents applying FSO in wireless microcells that have a 500 m minimum cell radius. The performance degrades more when pointing errors appear. Increasing the transmitted power can improve the performance under light to moderate fog. However, under thick and dense fog the improvement is negligible. Using mitigation techniques can play a major role in improving the range and outage probability.

  11. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    Science.gov (United States)

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment.

  12. Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Naaijen, J; Bralten, J; Poelmans, G

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance...... within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms......, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome...

  13. Managing coopetition through horizontal supply chain relations : Linking dyadic and network levels of analysis

    NARCIS (Netherlands)

    Wilhelm, Miriam M.

    2011-01-01

    A growing research stream has expanded the level of analysis beyond single buyer-supplier relations to the network, including supplier-supplier relations. These supplier-supplier relations may constitute a missing link between the traditional analysis of the dyadic and the network level of analysis

  14. A Link Network Analysis of Iranian Research Institute Websites: Overt and Covert Relationships

    Directory of Open Access Journals (Sweden)

    Zahra Noroozi

    2014-03-01

    Full Text Available The research investigates the link and networks of Iranian research institute websites using webometrics and the link analysis method. The population includes the websites of 23 research institutes and centers in Iran. The data were collected using the Webometric Analyst software. The network diagram shows the mutual link strength among the set of research institute websites in Iran, and depicts the pattern of internal relationships among these websites. Iranian research institute websites are not in good conditions in link exchange and the cooperation with each other. In addition, the colink diagrams illustrated the covert relationships among Iranian research institutes suggesting that the common topics and contents have been the most important elements of colink creation among Iranian research institute websites. It was found that the websites of Scientific Information Database (SID, Iranian Research Institute for Information Science and Technology (IRANDOC, and National Library and Archives of I.R of Iran (NLAI were in a better condition than those of other websites as regards the total in-links and out-links. Also, the first to the third ranks were dedicated to IRANDOC, SID, and NLAI websites respectively in in-link numbers and visibility. The analysis of Uniform Resource Locators (URLs of in-links and out-links of Iranian research institute websites showed that the maximum number of in-link to these websites was reserved for the domains .ir and .com. The websites of Iranian research institutes and centers dedicated most of their out-links to scientific, religious, and fun websites, followed by the ones for universities and the institutes of higher education.

  15. Strengthening the weak link: Built Environment modelling for loss analysis

    Science.gov (United States)

    Millinship, I.

    2012-04-01

    Methods to analyse insured losses from a range of natural perils, including pricing by primary insurers and catastrophe modelling by reinsurers, typically lack sufficient exposure information. Understanding the hazard intensity in terms of spatial severity and frequency is only the first step towards quantifying the risk of a catastrophic event. For any given event we need to know: Are any structures affected? What type of buildings are they? How much damaged occurred? How much will the repairs cost? To achieve this, detailed exposure information is required to assess the likely damage and to effectively calculate the resultant loss. Modelling exposures in the Built Environment therefore plays as important a role in understanding re/insurance risk as characterising the physical hazard. Across both primary insurance books and aggregated reinsurance portfolios, the location of a property (a risk) and its monetary value is typically known. Exactly what that risk is in terms of detailed property descriptors including structure type and rebuild cost - and therefore its vulnerability to loss - is often omitted. This data deficiency is a primary source of variations between modelled losses and the actual claims value. Built Environment models are therefore required at a high resolution to describe building attributes that relate vulnerability to property damage. However, national-scale household-level datasets are often not computationally practical in catastrophe models and data must be aggregated. In order to provide more accurate risk analysis, we have developed and applied a methodology for Built Environment modelling for incorporation into a range of re/insurance applications, including operational models for different international regions and different perils and covering residential, commercial and industry exposures. Illustrated examples are presented, including exposure modelling suitable for aggregated reinsurance analysis for the UK and bespoke high resolution

  16. Making the link between critical appraisal, thinking and analysis.

    Science.gov (United States)

    Whiffin, Charlotte Jane; Hasselder, Alison

    Nursing has become an all-graduate profession; as such, student nurses must develop their skills of critical analysis. The need to develop critical analytical thinking has been identified as the single most important skill in undergraduate education and reaching the academic requirements of level six study. In degree-level healthcare programmes, students are frequently asked to complete a structured critical appraisal of research. This paper examines how critical appraisal activities can be an opportunity for students to develop transferable critical thinking skills. Critical appraisal teaches objectivity, reflection, logic and discipline, which encourage students to think critically in both theory and practice.

  17. Analysis of broadcasting satellite service feeder link power control and polarization

    Science.gov (United States)

    Sullivan, T. M.

    1982-01-01

    Statistical analyses of carrier to interference power ratios (C/Is) were performed in assessing 17.5 GHz feeder links using (1) fixed power and power control, and (2) orthogonal linear and orthogonal circular polarizations. The analysis methods and attenuation/depolarization data base were based on CCIR findings to the greatest possible extent. Feeder links using adaptive power control were found to neither cause or suffer significant C/I degradation relative to that for fixed power feeder links having similar or less stringent availability objectives. The C/Is for sharing between orthogonal linearly polarized feeder links were found to be significantly higher than those for circular polarization only in links to nominally colocated satellites from nominally colocated Earth stations in high attenuation environments.

  18. Mass spectrometric analysis of O-linked oligosaccharides from various recombinant expression systems.

    Science.gov (United States)

    Kenny, Diarmuid T; Gaunitz, Stefan; Hayes, Catherine A; Gustafsson, Anki; Sjöblom, Magnus; Holgersson, Jan; Karlsson, Niclas G

    2013-01-01

    Analysis of O-linked glycosylation is one of the main challenges during structural validation of recombinant glycoproteins. With methods available for N-linked glycosylation in regard to oligosaccharide analysis as well as glycopeptide mapping, there are still challenges for O-linked glycan analysis. Here, we present mass spectrometric methodology for O-linked oligosaccharides released by reductive β-elimination. Using LC-MS and LC-MS(2) with graphitized carbon columns, oligosaccharides are analyzed without derivatization. This approach provides a high-throughput method for screening during clonal selection, as well as product structure verification, without impairing sequencing ability. The protocols are exemplified by analysis of glycoproteins from mammalian cell cultures (CHO cells) as well as insect cells and yeast. The data shows that the method can be successfully applied to both neutral and acidic O-linked oligosaccharides, where sialic acid, hexuronic acid, and sulfate are common substituents. Further characterization of O-glycans can be achieved using permethylation. Permethylation of O-linked oligosaccharides followed by direct infusion into the mass spectrometer provide information about oligosaccharide composition, and subsequent MS (n) experiments can be carried out to elucidate oligosaccharide structure including linkage information and sequence.

  19. Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

    Science.gov (United States)

    Rodríguez-Muñoz, Rafael; Cárdenas-Aguayo, María Del Carmen; Alemán, Víctor; Osorio, Beatriz; Chávez-González, Oscar; Rendon, Alvaro; Martínez-Rojas, Dalila; Meraz-Ríos, Marco Antonio

    2015-01-01

    The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f), during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV). By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60%) and multipolar Glutamatergic (≤40%) neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC): dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively), in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles) of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures.

  20. Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

    Directory of Open Access Journals (Sweden)

    Rafael Rodríguez-Muñoz

    Full Text Available The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f, during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV. By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60% and multipolar Glutamatergic (≤40% neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC: dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively, in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures.

  1. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Walls, Anne B; Schousboe, Arne

    2009-01-01

    The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present...... in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important...... for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d...

  2. Genetic deletion of NR3A accelerates glutamatergic synapse maturation.

    Directory of Open Access Journals (Sweden)

    Maile A Henson

    Full Text Available Glutamatergic synapse maturation is critically dependent upon activation of NMDA-type glutamate receptors (NMDARs; however, the contributions of NR3A subunit-containing NMDARs to this process have only begun to be considered. Here we characterized the expression of NR3A in the developing mouse forebrain and examined the consequences of NR3A deletion on excitatory synapse maturation. We found that NR3A is expressed in many subcellular compartments, and during early development, NR3A subunits are particularly concentrated in the postsynaptic density (PSD. NR3A levels dramatically decline with age and are no longer enriched at PSDs in juveniles and adults. Genetic deletion of NR3A accelerates glutamatergic synaptic transmission, as measured by AMPAR-mediated postsynaptic currents recorded in hippocampal CA1. Consistent with the functional observations, we observed that the deletion of NR3A accelerated the expression of the glutamate receptor subunits NR1, NR2A, and GluR1 in the PSD in postnatal day (P 8 mice. These data support the idea that glutamate receptors concentrate at synapses earlier in NR3A-knockout (NR3A-KO mice. The precocious maturation of both AMPAR function and glutamate receptor expression are transient in NR3A-KO mice, as AMPAR currents and glutamate receptor protein levels are similar in NR3A-KO and wildtype mice by P16, an age when endogenous NR3A levels are normally declining. Taken together, our data support a model whereby NR3A negatively regulates the developmental stabilization of glutamate receptors involved in excitatory neurotransmission, synaptogenesis, and spine growth.

  3. Investigation of synapse formation and function in a glutamatergic-GABAergic two-neuron microcircuit.

    Science.gov (United States)

    Chang, Chia-Ling; Trimbuch, Thorsten; Chao, Hsiao-Tuan; Jordan, Julia-Christine; Herman, Melissa A; Rosenmund, Christian

    2014-01-15

    Neural circuits are composed of mainly glutamatergic and GABAergic neurons, which communicate through synaptic connections. Many factors instruct the formation and function of these synapses; however, it is difficult to dissect the contribution of intrinsic cell programs from that of extrinsic environmental effects in an intact network. Here, we perform paired recordings from two-neuron microculture preparations of mouse hippocampal glutamatergic and GABAergic neurons to investigate how synaptic input and output of these two principal cells develop. In our reduced preparation, we found that glutamatergic neurons showed no change in synaptic output or input regardless of partner neuron cell type or neuronal activity level. In contrast, we found that glutamatergic input caused the GABAergic neuron to modify its output by way of an increase in synapse formation and a decrease in synaptic release efficiency. These findings are consistent with aspects of GABAergic synapse maturation observed in many brain regions. In addition, changes in GABAergic output are cell wide and not target-cell specific. We also found that glutamatergic neuronal activity determined the AMPA receptor properties of synapses on the partner GABAergic neuron. All modifications of GABAergic input and output required activity of the glutamatergic neuron. Because our system has reduced extrinsic factors, the changes we saw in the GABAergic neuron due to glutamatergic input may reflect initiation of maturation programs that underlie the formation and function of in vivo neural circuits.

  4. Improved Stability Analysis of Nonlinear Networked Control Systems over Multiple Communication Links

    OpenAIRE

    Delavar, Rahim; Tavassoli, Babak; Beheshti, Mohammad Taghi Hamidi

    2015-01-01

    In this paper, we consider a nonlinear networked control system (NCS) in which controllers, sensors and actuators are connected via several communication links. In each link, networking effects such as the transmission delay, packet loss, sampling jitter and data packet miss-ordering are captured by time-varying delays. Stability analysis is carried out based on the Lyapunov Krasovskii method to obtain a condition for stability of the nonlinear NCS in the form of linear matrix inequality (LMI...

  5. Mass spectrometric analysis of a UV-cross-linked protein-DNA complex: tryptophans 54 and 88 of E. coli SSB cross-link to DNA

    DEFF Research Database (Denmark)

    Steen, H; Petersen, J; Mann, M

    2001-01-01

    Protein-nucleic acid complexes are commonly studied by photochemical cross-linking. UV-induced cross-linking of protein to nucleic acid may be followed by structural analysis of the conjugated protein to localize the cross-linked amino acids and thereby identify the nucleic acid binding site. Mass...... spectrometry is becoming increasingly popular for characterization of purified peptide-nucleic acid heteroconjugates derived from UV cross-linked protein-nucleic acid complexes. The efficiency of mass spectrometry-based methods is, however, hampered by the contrasting physico-chemical properties of nucleic....... coli single-stranded DNA binding protein (SSB) that was UV-cross-linked to a 5-iodouracil containing DNA oligomer. Two methods were optimized to circumvent the need for standard liquid chromatography and gel electrophoresis, thereby dramatically increasing the overall sensitivity of the analysis...

  6. Digging in to Link Analysis Researches in Iran and all around the World: a Review Article

    Directory of Open Access Journals (Sweden)

    Fatemeh Nooshinfard

    2011-10-01

    Full Text Available Increasing websites quantity, specially scientific websites, there were many researches with concern of link analysis using webometrics by librarian and other scholars in different academic majors around the world. The purpose of this article was link analysis of all link analysis related papers from the beginning to February 19th 2009. The research based on Weiner, Amick, and Lee searching model in 2008, this study included 96 refereed papers extracted from international databases like Springer, Proquest, Sage, Emerald, IEEE, Science Direct and national databases such as Magiran and SID. These papers were studied focusing on their different parts like authors, affiliated organizations, purpose, methods, tools, keywords, date of publishing, publication, indexing databases and their suggestions. Moreover, analyzing those papers and studying any related models were the other purposes of the current article. The findings have been categorized and analyses in ten different sections.

  7. AODV routing overhead analysis based on link failure probability in MANET

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qin-juan; WU Mu-qing; ZHEN Yan; SHANG Cui-li

    2010-01-01

    This article puts forward an Ad-hoc on-demand distance vector routing(AODV)routing overhead analysis method in mobile Ad-hoc network(MANET).Although multiple routing protocols have been proposed to improve the performance,scarcely any paper analyzed the routing overhead caused by routing setup and maintenance processes in mathematical way.Routing overhead consumes part of network resources and limits the supported traffic in the network.For on-demand routing protocols like AODV,the routing overhead depends on the link failure probability to a great extent.This article analyzes the collision probability caused by hidden-node problem and the impact on link failure probability.In chain and rectangle scenarios,it presents a mathematical analysis of the theoretical routing overhead of AODV protocol based on link failure probability.Simulations on OPNET 14.5platform match well with the theoretical derivation which confirms the effectiveness of the analysis method.

  8. Theoretical and experimental analysis of inverter fed induction motor system under DC link capacitor failure

    Directory of Open Access Journals (Sweden)

    Hadeed A. Sher

    2017-04-01

    Full Text Available In this paper theoretical and experimental analysis of an AC–DC–AC inverter under DC link capacitor failure is presented. The failure study conducted for this paper is the open circuit of the DC link capacitor. The presented analysis incorporates the results for both single and three phase AC input. It has been observed that the higher ripple frequency provides better ride through capability for this fault. Furthermore, the effects of this fault on electrical characteristics of AC–DC–AC inverter and mechanical properties of the induction motor are also presented. Moreover, the effect of pulsating torque as a result of an open circuited DC link capacitor is also taken into consideration. Theoretical analysis is supported by computer aided simulation as well as with a real time experimental prototype.

  9. Analysis of the dynamic stress of planar flexible-links parallel robots

    Institute of Scientific and Technical Information of China (English)

    DU Zhaocai; YU Yueqing; YANG Jianxin

    2007-01-01

    This paper presents a method for the dynamic stress analysis of planar parallel robots with flexible links and a rigid moving platform.The finite element-based dynamic model of flexible parallel robots is proposed.The relation between elastic deformations and elastic displacements of the flexible links is investigated,considering the coupling effects of elastic motion and rigid motion.The elastic deformations of links are calculated.Considering the effects of bendingshearing strain and tensile-compression strain,the dynamic stress of the links and its position are derived by using the Kineto-Elastodynamics theory and the Timoshenko beam theory.Due to the flexibility of the links,the dynamic stresses are well illustrated through numerical simulation.Compared with the results of the finite element software SAMCEF,the numerical simulation results show the good coherence and advantages of the analysis method.The dynamic stress analysis is demonstrated to have a significant impact on the analysis,design and control of flexible parallel robots.

  10. Link Prediction in Criminal Networks: A Tool for Criminal Intelligence Analysis.

    Science.gov (United States)

    Berlusconi, Giulia; Calderoni, Francesco; Parolini, Nicola; Verani, Marco; Piccardi, Carlo

    2016-01-01

    The problem of link prediction has recently received increasing attention from scholars in network science. In social network analysis, one of its aims is to recover missing links, namely connections among actors which are likely to exist but have not been reported because data are incomplete or subject to various types of uncertainty. In the field of criminal investigations, problems of incomplete information are encountered almost by definition, given the obvious anti-detection strategies set up by criminals and the limited investigative resources. In this paper, we work on a specific dataset obtained from a real investigation, and we propose a strategy to identify missing links in a criminal network on the basis of the topological analysis of the links classified as marginal, i.e. removed during the investigation procedure. The main assumption is that missing links should have opposite features with respect to marginal ones. Measures of node similarity turn out to provide the best characterization in this sense. The inspection of the judicial source documents confirms that the predicted links, in most instances, do relate actors with large likelihood of co-participation in illicit activities.

  11. Challenges and Capacity Analysis of 100 Gbps Optical Fibre Wireless Links in 75-110 GHz Band

    DEFF Research Database (Denmark)

    Dogadaev, Anton Konstantinovich; Tafur Monroy, Idelfonso

    2011-01-01

    We report on the capacity analysis of hybrid optical fiber-wireless links operating at 75-110 GHz band. We provide link design guidelines towards achieving 100 Gbps data transmission using M-ary modulation formats.......We report on the capacity analysis of hybrid optical fiber-wireless links operating at 75-110 GHz band. We provide link design guidelines towards achieving 100 Gbps data transmission using M-ary modulation formats....

  12. Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Jose L Serrano-Velez

    2014-06-01

    Full Text Available Dye-coupling, whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35, and freeze-fracture replica immunogold labeling (FRIL reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish.To study gap junctions’ role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in 50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment.Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions’ role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.

  13. Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals.

    Science.gov (United States)

    Yuen, Eunice Y; Zhong, Ping; Li, Xiangning; Wei, Jing; Yan, Zhen

    2013-09-06

    The prefrontal cortex (PFC), a key brain region for cognitive and emotional processes, is highly regulated by dopaminergic inputs. The dopamine D4 receptor, which is enriched in PFC, has been implicated in mental disorders, such as attention deficit-hyperactivity disorder and schizophrenia. Recently we have found homeostatic regulation of AMPA receptor-mediated synaptic transmission in PFC pyramidal neurons by the D4 receptor, providing a potential mechanism for D4 in stabilizing cortical excitability. Because stress is tightly linked to adaptive and maladaptive changes associated with mental health and disorders, we examined the synaptic actions of D4 in stressed rats. We found that neural excitability was elevated by acute stress and dampened by repeated stress. D4 activation produced a potent reduction of excitatory transmission in acutely stressed animals and a marked increase of excitatory transmission in repeatedly stressed animals. These effects of D4 targeted GluA2-lacking AMPA receptors and relied on the bi-directional regulation of calcium/calmodulin kinase II activity. The restoration of PFC glutamatergic transmission in stress conditions may enable D4 receptors to serve as a synaptic stabilizer in normal and pathological conditions.

  14. Dynamic Analysis and Control of Lightweight Manipulators with Flexible Parallel Link Mechanisms. Ph.D. Thesis

    Science.gov (United States)

    Lee, Jeh Won

    1990-01-01

    The objective is the theoretical analysis and the experimental verification of dynamics and control of a two link flexible manipulator with a flexible parallel link mechanism. Nonlinear equations of motion of the lightweight manipulator are derived by the Lagrangian method in symbolic form to better understand the structure of the dynamic model. The resulting equation of motion have a structure which is useful to reduce the number of terms calculated, to check correctness, or to extend the model to higher order. A manipulator with a flexible parallel link mechanism is a constrained dynamic system whose equations are sensitive to numerical integration error. This constrained system is solved using singular value decomposition of the constraint Jacobian matrix. Elastic motion is expressed by the assumed mode method. Mode shape functions of each link are chosen using the load interfaced component mode synthesis. The discrepancies between the analytical model and the experiment are explained using a simplified and a detailed finite element model.

  15. Avoiding Aliasing in Allan Variance: an Application to Fiber Link Data Analysis

    CERN Document Server

    Calosso, Claudio E; Micalizio, Salvatore

    2015-01-01

    Optical fiber links are known as the most performing tools to transfer ultrastable frequency reference signals. However, these signals are affected by phase noise up to bandwidths of several kilohertz and a careful data processing strategy is required to properly estimate the uncertainty. This aspect is often overlooked and a number of approaches have been proposed to implicitly deal with it. Here, we face this issue in terms of aliasing and show how typical tools of signal analysis can be adapted to the evaluation of optical fiber links performance. In this way, it is possible to use the Allan variance as estimator of stability and there is no need to introduce other estimators. The general rules we derive can be extended to all optical links. As an example, we apply this method to the experimental data we obtained on a 1284 km coherent optical link for frequency dissemination, which we realized in Italy.

  16. Design and Analysis for the Y-axis linking Part of PCB Drilling Machine

    Directory of Open Access Journals (Sweden)

    Feida Ma

    2013-04-01

    Full Text Available Aiming at the problem of the printed circuit board (PCB Y axis linking part, we establish the 3D three-dimension model by using the Solidworks software , analysis the structure of the linking part and making appropriate solutions according to its works process and machining process. Finally, we use finite element method to analysis with COSMOSwork software to find the priory solution, improve the R&D speed, reduce processing costs and provide a reliable basis for the machine tool structure optimization design.

  17. Sonic hedgehog and retinoic Acid induce bone marrow-derived stem cells to differentiate into glutamatergic neural cells.

    Science.gov (United States)

    Yu, Zhenhai; Wu, Shixing; Liu, Zhen; Lin, Haiyan; Chen, Lei; Yuan, Xinli; Zhang, Zhiying; Liu, Fang; Zhang, Chuansen

    2015-01-01

    Studies have showed that transplanted stem cells in the inner ear won't regenerate to replace the damaged sensory hair cells. They can spontaneously differentiate into mesenchymal cells and fibrocytes in the damaged inner ear. Only mature sensory cells of MSCs-derived possess the great potency for cell transplantation in the treatment of sensorineural hearing loss. So, we try to establish an efficient generation of the glutamatergic sensory neural phenotype for the cell transplantation of the hearing loss. We isolated MSCs from femoral and tibial bones according to their adherence to culture dishes. After purification, proliferation, and passaged, cells became homogeneous in appearance, showing more uniformity and grew in a monolayer with a typical spindle-shape morphology. The cell surface markers were assessed using FACS to characterize the isolated cells. For neural induction to harvest the glutamatergic sensory neurons, passage 3 MSCs were incubated with preinduced medium for 24 hr, and neural-induced medium for an additional 14 days. The cells exhibit a typical neural shape. RT-PCR analysis indicated that the mRNA levels of the neural cell marker nestin, Tau, MAP-2, β-tubulin III, GluR-3, and GluR-4 were higher compared with primary MSCs. Immunohistochemistry and western-blotting proofed that nestin, MAP-2, β-tubulin III, and GluR-4 proteins indeed exhibit their expression difference in the induced cells compared to the MSCs. We show an efficient protocol by the combined applications of Sonic Hedgehog (Shh) and Retinoic Acid (RA) to induce MSCs to differentiate into the glutamatergic sensory neuron which were identified from the morphological, biochemical, and molecular characteristics.

  18. Mapping a decade of linked data progress through co-word analysis

    Directory of Open Access Journals (Sweden)

    Massoomeh Niknia

    2015-12-01

    Full Text Available Linked data describes a method of publishing structured data which it can be interlinked and become more effective through semantic queries. This enables data from different sources to be connected and queried. It builds upon standard web technologies such as HTTP, RDF and URIs. This method helps human readers to share information in a way that can be read automatically by computers. Regarding the importance of Linked data, the main aim of this article is visualizing scientific mapping of linked data to show its progress through one decade. The scientometric study employs hierarchical cluster analysis, strategic diagrams and network analysis to map and visualize the linked data landscape of the "Scopus" publications through the use of co-word analysis. The study quantifies and describes the thematic evolution of the field based on a total of 717 Scopus articles and their associated 19977 keywords published between 1970s and 2014. According to the results the thematic visualization and the clusters show most concepts concentrated around computer related terms, such as big data; cloud computing semantic data; semantic technologies; semantic web; artificial intelligence; computer programming; semantic search, etc. In addition, we found that in recent years after librarians and information scientists doing researches in linked data on the behalf of computer scientist the “user” studies became important.

  19. Subpopulations of neurokinin 1 receptor-expressing neurons in the rat lateral amygdala display a differential pattern of innervation from distinct glutamatergic afferents

    OpenAIRE

    Sreepathi, H.K.; Ferraguti, F.

    2012-01-01

    Substance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. Immunofluorescence analysis of the co-expression of NK1 with calciu...

  20. Analysis of Harmonics Suppression by Active Damping Control on Multi Slim DC-link Drives

    DEFF Research Database (Denmark)

    Yang, Feng; Máthé, Lászlo; Lu, Kaiyuan;

    2016-01-01

    Compared with conventional dc-link drive, slim dc-link drive is expected to achieve lower cost and longer life time. However, harmonics distortion problem may occur in such drive systems. This paper proposes to use an active damping control method to suppress the harmonic distortion...... with the benefit of low cost and also low loss. A new analysis method, based on the frequency domain impedance model, is presented to explore the mechanism of harmonics suppression. Also, a general method is presented to build the impedance model of a PMSM drive system using Field Oriented Control (FOC) method....... Some design issues, including power levels, current control bandwidth and harmonic interaction, are discussed when the drive system is fed by a weak grid. Case studies on a two-drive system composed by two slim dc-link drive units are provided to verify the proposed analysis method....

  1. Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons.

    Science.gov (United States)

    Jeong, Seok-Gwon; Choi, In-Sun; Cho, Jin-Hwa; Jang, Il-Sung

    2013-12-01

    Although muscarinic acetylcholine (mACh) receptors are expressed in trigeminal ganglia, it is still unknown whether mACh receptors modulate glutamatergic transmission from primary afferents onto medullary dorsal horn neurons. In this study, we have addressed the cholinergic modulation of primary afferent glutamatergic transmission using a conventional whole cell patch clamp technique. Glutamatergic excitatory postsynaptic currents (EPSCs) were evoked from primary afferents by electrical stimulation of trigeminal tract and monosynaptic EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices. Muscarine and ACh reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, muscarine reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that muscarine acts presynaptically to decrease the probability of glutamate release onto medullary dorsal horn neurons. The muscarine-induced decrease of glutamatergic EPSCs was significantly occluded by methoctramine or AF-DX116, M2 receptor antagonists, but not pirenzepine, J104129 and MT-3, selective M1, M3 and M4 receptor antagonists. The muscarine-induced decrease of glutamatergic EPSCs was highly dependent on the extracellular Ca2+ concentration. Physostigmine and clinically available acetylcholinesterase inhibitors, such as rivastigmine and donepezil, significantly shifted the concentration-inhibition relationship of ACh for glutamatergic EPSCs. These results suggest that muscarine acts on presynaptic M2 receptors to inhibit glutamatergic transmission by reducing the Ca2+ influx into primary afferent terminals, and that M2 receptor agonists and acetylcholinesterase inhibitors could be, at least, potential targets to reduce nociceptive transmission from orofacial tissues.

  2. Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases.

    Science.gov (United States)

    Gardoni, Fabrizio; Bellone, Camilla

    2015-01-01

    Dopamine (DA) plays a major role in motor and cognitive functions as well as in reward processing by regulating glutamatergic inputs. In particular in the striatum the release of DA rapidly influences synaptic transmission modulating both AMPA and NMDA receptors. Several neurodegenerative and neuropsychiatric disorders, including Parkinson, Huntington and addiction-related diseases, manifest a dysregulation of glutamate and DA signaling. Here, we will focus our attention on the mechanisms underlying the modulation of the glutamatergic transmission by DA in striatal circuits.

  3. Dynamic analysis and control of lightweight manipulators with flexible parallel link mechanisms

    Science.gov (United States)

    Lee, Jeh Won

    1991-01-01

    The flexible parallel link mechanism is designed for increased rigidity to sustain the buckling when it carries a heavy payload. Compared to a one link flexible manipulator, a two link flexible manipulator, especially the flexible parallel mechanism, has more complicated characteristics in dynamics and control. The objective of this research is the theoretical analysis and the experimental verification of dynamics and control of a two link flexible manipulator with a flexible parallel link mechanism. Nonlinear equations of motion of the lightweight manipulator are derived by the Lagrangian method in symbolic form to better understand the structure of the dynamic model. A manipulator with a flexible parallel link mechanism is a constrained dynamic system whose equations are sensitive to numerical integration error. This constrained system is solved using singular value decomposition of the constraint Jacobian matrix. The discrepancies between the analytical model and the experiment are explained using a simplified and a detailed finite element model. The step response of the analytical model and the TREETOPS model match each other well. The nonlinear dynamics is studied using a sinusoidal excitation. The actuator dynamic effect on a flexible robot was investigated. The effects are explained by the root loci and the Bode plot theoretically and experimentally. For the base performance for the advanced control scheme, a simple decoupled feedback scheme is applied.

  4. VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons

    Science.gov (United States)

    Qi, Jia; Zhang, Shiliang; Wang, Hui-Ling; Barker, David J.; Miranda-Barrientos, Jorge; Morales, Marisela

    2016-01-01

    The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens-glutamatergic pathway remains unknown. Here, we report that nAcc photoactivation of mesoaccumbens-glutamatergic fibers promotes aversion. Although we found that these mesoaccumbens-glutamate-fibers lack GABA, the aversion evoked by their photoactivation depends on glutamate and GABA receptor signaling, and not on dopamine receptor signaling. We found that mesoaccumbens-glutamatergic-fibers establish multiple asymmetric synapses on single parvalbumin-GABAergic interneurons, and that nAcc photoactivation of these fibers drives AMPA-mediated cellular firing of parvalbumin-GABAergic interneurons. These parvalbumin-GABAergic-interneurons, in turn, inhibit nAcc medium spiny output neurons, as such, controlling inhibitory neurotransmission within nAcc. The mesoaccumbens-glutamatergic pathway is the first glutamatergic input to nAcc shown to mediate aversion, instead of reward, and the first pathway shown to establish excitatory synapses on nAcc parvalbumin-GABAergic interneurons. PMID:27019014

  5. Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems.

    Science.gov (United States)

    Köles, László; Kató, Erzsébet; Hanuska, Adrienn; Zádori, Zoltán S; Al-Khrasani, Mahmoud; Zelles, Tibor; Rubini, Patrizia; Illes, Peter

    2016-03-01

    Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning.

  6. The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

    Science.gov (United States)

    Christensen, G B; Knight, S; Camp, N J

    2009-11-01

    We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

  7. NEURO FUZZY LINK BASED CLASSIFIER FOR THE ANALYSIS OF BEHAVIOR MODELS IN SOCIAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Indira Priya Ponnuvel

    2014-01-01

    Full Text Available In this study, a new link based classifier using neuro fuzzy logic has been proposed for analyzing the social behavior based on Weblog dataset. In this system, data are processed using a multistage structure. This system provides a diagnosis using a neuro fuzzy link based classifier that analyses the user’s behavior to specific diagnostic categories based on their cluster category in social networks. It uses random walks method to organize the labels. Since the links present in the social network graph frequently represent relationships among the users with respect to social contacts and behaviours, this work observes the links of the graph in order to identify the relationships represented in the graph between the users of the social network based on some new social network metrics and the past behaviour of the users. This work is useful to provide connection between consolidated features of users based on network data and also using the traditional metrics used in the analysis of social network users. From the experiments conducted in this research work, it is observed that the proposed work provides better classification accuracy due to the application of neuro fuzzy classification method in link analysis.

  8. Glutamatergic neurons are present in the rat ventral tegmental area

    Science.gov (United States)

    Yamaguchi, Tsuyoshi; Sheen, Whitney; Morales, Marisela

    2010-01-01

    The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or γ-amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed that additional cell types, such as those that express the neurotransmitter glutamate may also be present in this area. Thus, by using in situ hybridization histochemistry we investigated whether transcripts encoded by genes for the two vesicular glutamate transporters, VGluT1 or VGluT2, were expressed in the VTA. We found that VGluT2 mRNA but not VGluT1 mRNA is expressed in the VTA. Neurons expressing VGluT2 mRNA were differentially distributed throughout the rostro-caudal and medio-lateral aspects of the VTA, with the highest concentration detected in rostro-medial areas. Phenotypic characterization with double in situ hybridization of these neurons indicated that they rarely co–expressed mRNAs for tyrosine hydroxylase (TH, marker for DAergic neurons) or glutamic acid decarboxylase (GAD, marker for GABAergic neurons). Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non-DAergic and non-GABAergic. PMID:17241272

  9. Separating the Effect of Independent Interference Sources with Rayleigh Faded Signal Link: Outage Analysis and Applications

    CERN Document Server

    Kahlon, Arshdeep S; Periyalwar, Shalini; Yanikomeroglu, Halim

    2012-01-01

    We show that, for independent interfering sources and a signal link with exponentially distributed received power, the total probability of outage can be decomposed as a simple expression of the outages from the individual interfering sources. We give a mathematical proof of this result, and discuss some immediate implications, showing how it results in important simplifications to statistical outage analysis. We also discuss its application to two active topics of study: spectrum sharing, and sum of interference powers (e.g., lognormal) analysis.

  10. Stability Analysis of DC-link Voltage Control on Autonomous Micro Hydro Power Plant System

    Directory of Open Access Journals (Sweden)

    Feri Yusivar

    2014-12-01

    Full Text Available Micro Hydro Power Plant has become one of the interesting topics to be researched nowadays. This paper deals with the stability analysis on control system of excitation voltage in Micro Hydro Power Plant. The control of this voltage can be achieved by controlling the Permanent Magnet Synchronous Machine (PMSM with particular algorithm so the voltage on the DC-link part of the system can be controlled. Without knowing the exact specification of system parameters, the system will be most likely unstable. The DC-link control system is modeled, simulated, and mathematically analyzed so the parameter specification for the stable system can be obtained.

  11. Global Stability Analysis for an Internet Congestion Control Model with a Time-Varying Link Capacity

    CERN Document Server

    Rezaie, B; Analoui, M; Khorsandi, S

    2009-01-01

    In this paper, a global stability analysis is given for a rate-based congestion control system modeled by a nonlinear delayed differential equation. The model determines the dynamics of a single-source single-link network, with a time-varying capacity of link and a fixed communication delay. We obtain a sufficient delay-independent conditions on system parameters under which global asymptotic stability of the system is guarantied. The proof is based on an extension of Lyapunov-Krasovskii theorem for a class of nonlinear time-delay systems. The numerical simulations for a typical scenario justify the theoretical results.

  12. Short Circuit Ratio analysis of multi-infeed HVDC system with a VSC-HVDC link

    DEFF Research Database (Denmark)

    Liu, Yan; Chen, Zhe

    2011-01-01

    As an important indicator of system stability, Short Circuit Ratio (SCR) is commonly used in power system analysis. For systems include HVDC link connection, the Effective SCR (ESCR) is mostly applied to indicate the strength of HVDC infeed bus. The contribution of VSC-HVDC link to multi......-infeed HVDC system stability has been analyzed a lot but the study on ESCR of this kind of system is still insufficient. This paper presents a calculation method for ESCR of the hybrid multi infeed HVDC system based on a simple two-infeed HVDC system model. The equivalent circuit of this system under short...

  13. D-serine and serine racemase are associated with PSD-95 and glutamatergic synapse stability

    Directory of Open Access Journals (Sweden)

    Hong eLin

    2016-02-01

    Full Text Available D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs, synthesized by serine racemase (SR through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking alpha7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1, in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5 and 7-chlorokynurenic acid (7-CK, a specific antagonist at the glycine site of NMDARs

  14. Can Mismatch Negativity Be Linked to Synaptic Processes? A Glutamatergic Approach to Deviance Detection

    Science.gov (United States)

    Strelnikov, Kuzma

    2007-01-01

    This article aims to provide a theoretical framework to elucidate the neurophysiological underpinnings of deviance detection as reflected by mismatch negativity. A six-step model of the information processing necessary for deviance detection is proposed. In this model, predictive coding of learned regularities is realized by means of long-term…

  15. Sensory Input-Dependent Changes in Glutamatergic Neurotransmission- Related Genes and Proteins in the Adult Rat Trigeminal Ganglion

    Science.gov (United States)

    Fernández-Montoya, Julia; Buendia, Izaskun; Martin, Yasmina B.; Egea, Javier; Negredo, Pilar; Avendaño, Carlos

    2016-01-01

    Experience-dependent plasticity induces lasting changes in the structure of synapses, dendrites, and axons at both molecular and anatomical levels. Whilst relatively well studied in the cortex, little is known about the molecular changes underlying experience-dependent plasticity at peripheral levels of the sensory pathways. Given the importance of glutamatergic neurotransmission in the somatosensory system and its involvement in plasticity, in the present study, we investigated gene and protein expression of glutamate receptor subunits and associated molecules in the trigeminal ganglion (TG) of young adult rats. Microarray analysis of naïve rat TG revealed significant differences in the expression of genes, coding for various glutamate receptor subunits and proteins involved in clustering and stabilization of AMPA receptors, between left and right ganglion. Long-term exposure to sensory-enriched environment increased this left–right asymmetry in gene expression. Conversely, unilateral whisker trimming on the right side almost eliminated the mentioned asymmetries. The above manipulations also induced side-specific changes in the protein levels of glutamate receptor subunits. Our results show that sustained changes in sensory input induce modifications in glutamatergic transmission-related gene expression in the TG, thus supporting a role for this early sensory-processing node in experience-dependent plasticity. PMID:27965535

  16. Disclosure-Protected Inference with Linked Microdata Using a Remote Analysis Server

    Directory of Open Access Journals (Sweden)

    Chipperfield James O.

    2014-03-01

    Full Text Available Large amounts of microdata are collected by data custodians in the form of censuses and administrative records. Often, data custodians will collect different information on the same individual. Many important questions can be answered by linking microdata collected by different data custodians. For this reason, there is very strong demand from analysts, within government, business, and universities, for linked microdata. However, many data custodians are legally obliged to ensure the risk of disclosing information about a person or organisation is acceptably low. Different authors have considered the problem of how to facilitate reliable statistical inference from analysis of linked microdata while ensuring that the risk of disclosure is acceptably low. This article considers the problem from the perspective of an Integrating Authority that, by definition, is trusted to link the microdata and to facilitate analysts’ access to the linked microdata via a remote server, which allows analysts to fit models and view the statistical output without being able to observe the underlying linked microdata. One disclosure risk that must be managed by an Integrating Authority is that one data custodian may use the microdata it supplied to the Integrating Authority and statistical output released from the remote server to disclose information about a person or organisation that was supplied by the other data custodian. This article considers analysis of only binary variables. The utility and disclosure risk of the proposed method are investigated both in a simulation and using a real example. This article shows that some popular protections against disclosure (dropping records, rounding regression coefficients or imposing restrictions on model selection can be ineffective in the above setting.

  17. AC Versus DC Link Comparison Based on Power Flow Analysis of a Multimachine Power System

    Directory of Open Access Journals (Sweden)

    Mohammed Abdeljalil DJEHAF

    2014-02-01

    Full Text Available Deregulation and privatization is posing new challenges on high voltage transmission and on distributions systems as well. An increasingly liberalized market will encourage trading opportunities to be identified and developed. High voltage power electronics, such as HVDC (High Voltage Direct Current and FACTS (Flexible AC Transmission Systems provide the necessary features to avoid technical problems in heavily loaded power systems; HVDC offers most advantages: it can be used for system interconnection and for control of power flow as well. The major benefit of HVDC is its incorporated ability for fault-current blocking, which is not possible with synchronous AC links. In addition, HVDC can effectively support the surrounding AC systems in case of transient fault conditions and it serves as firewall against cascading disturbances. This paper presents a comparison between HVDC link and an HVAC link in a 29 Bus multimachine system, based on load flow analysis using Newton-Raphson method for the AC link case, and sequential method for the HVDC link case.

  18. Phenotype and genotype analysis of a Chinese family with prelingual X-linked hereditary hearing impairment

    Institute of Scientific and Technical Information of China (English)

    HAN Bing; CHENG Jing; YANG Shu-zhi; CAO Ju-yang; SHEN Wei-dong; JI Fei; KANG Dong-yang; ZHANG Xin; DAI Pu; YUAN Hui-jun

    2009-01-01

    Background X-linked hearing impairment is clinically and genetically a heterogeneous disease.Although many disorders manifest with hearing loss,a limited number of sex-linked loci and only one gene (POU3F4) have been shown to be implicated in X-linked non-syndromic hearing impairment.In the present study,we have performed a clinical and genetic analysis of a Chinese family with X-linked non-syndromic hearing loss,with emphasis on audiological findings and genomic mapping.Methods The clinical features of Family JX01 were evaluated by physical and audiometric examination in eighteen family members.Mutation screening of POU3F4 was identified by polymerase chain reaction (PCR) amplification and sequencing.Molecular evaluation consisted of X-chromosome wide genotyping by microsatellite makers (STR),followed by analyzing using MLINK computer program.Results Five affected males demonstrated bilateral,symmetrical sensorineural and profound hearing loss.The hearing impairment started prelingual.The female carriers did not have any complain of hearing loss,however,two of them were tested with milder loss with high frequency.No causative mutations in POU3F4 gene were detected by DNA sequencing.Linkage analysis indicated that the responsible gene was linked to locus DXS1227 (maximum lod score=2.04 at θ=0).Conclusions The affected males in Family JX01 have profound prelingual sensorineural hearing impairment,In addition,two female carriers showed mild to moderate hearing losses.However,none of females complained of any hearing loss.Analysis of hereditary deafness in this family mapped most compatibly to the Xq27.2.

  19. Kynurenines and Glutamate: Multiple Links and Therapeutic Implications.

    Science.gov (United States)

    Schwarcz, R

    2016-01-01

    Glutamate is firmly established as the major excitatory neurotransmitter in the mammalian brain and is actively involved in most aspects of neurophysiology. Moreover, glutamatergic impairments are associated with a wide variety of dysfunctional states, and both hypo- and hyperfunction of glutamate have been plausibly linked to the pathophysiology of neurological and psychiatric diseases. Metabolites of the kynurenine pathway (KP), the major catabolic route of the essential amino acid tryptophan, influence glutamatergic activity in several distinct ways. This includes direct effects of these "kynurenines" on ionotropic and metabotropic glutamate receptors or vesicular glutamate transport, and indirect effects, which are initiated by actions at various other recognition sites. In addition, some KP metabolites affect glutamatergic functions by generating or scavenging highly reactive free radicals. This review summarizes these phenomena and discusses implications for brain physiology and pathology.

  20. Stability Analysis of DC-link Voltage Control on Autonomous Micro Hydro Power Plant System

    OpenAIRE

    Feri Yusivar; M. Shanizal; A. Subiantoro; Gunawan, R

    2014-01-01

    Micro Hydro Power Plant has become one of the interesting topics to be researched nowadays. This paper deals with the stability analysis on control system of excitation voltage in Micro Hydro Power Plant. The control of this voltage can be achieved by controlling the Permanent Magnet Synchronous Machine (PMSM) with particular algorithm so the voltage on the DC-link part of the system can be controlled. Without knowing the exact specification of system parameters, the system will be most likel...

  1. Lexical Link Analysis (LLA) Application: Improving Web Service to Defense Acquisition Visibility Environment (DAVE)

    Science.gov (United States)

    2015-05-01

    1 LEXICAL LINK ANALYSIS (LLA) APPLICATION: IMPROVING WEB SERVICE TO DEFENSE ACQUISITION VISIBILITY ENVIRONMENT(DAVE) May 13-14, 2015 Dr. Ying...Improving Web Service to Defense Acquisition Visibility Environment (DAVE) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...to install the LLA/CLA/SSA system as a web service in the Defense Acquisition Visibility Environment (DAVE) test bed via the AT&L eBusiness Center

  2. Divergent Modulation of Nociception by Glutamatergic and GABAergic Neuronal Subpopulations in the Periaqueductal Gray

    Science.gov (United States)

    Grajales-Reyes, Jose G.; Copits, Bryan A.; O’Brien, Daniel E.; Trigg, Sarah L.; Gomez, Adrian M.

    2017-01-01

    Abstract The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis. Here, we demonstrate the different contributions of genetically defined glutamatergic and GABAergic vlPAG neurons in nociceptive processing by employing cell type-specific chemogenetic approaches in mice. Global chemogenetic manipulation of vlPAG neuronal activity suggests that vlPAG neural circuits exert tonic suppression of nociception, consistent with previous pharmacological and electrophysiological studies. However, selective modulation of GABAergic or glutamatergic neurons demonstrates an inverse regulation of nociceptive behaviors by these cell populations. Selective chemogenetic activation of glutamatergic neurons, or inhibition of GABAergic neurons, in vlPAG suppresses nociception. In contrast, inhibition of glutamatergic neurons, or activation of GABAergic neurons, in vlPAG facilitates nociception. Our findings provide direct experimental support for a model in which excitatory and inhibitory neurons in the PAG bidirectionally modulate nociception. PMID:28374016

  3. Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2013-07-01

    Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission.

  4. Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.

    Science.gov (United States)

    Llansola, Marta; Montoliu, Carmina; Agusti, Ana; Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Gomez-Gimenez, Belen; Malaguarnera, Michele; Dadsetan, Sherry; Belghiti, Majedeline; Garcia-Garcia, Raquel; Balzano, Tiziano; Taoro, Lucas; Felipo, Vicente

    2015-09-01

    The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neurotransmission. We will summarize some examples of the (1) interplay between glutamatergic and GABAergic neurotransmission alterations in different areas in the basal ganglia-thalamus-cortex circuit in the motor alterations in minimal hepatic encephalopathy (MHE); (2) interplay between glutamatergic and GABAergic neurotransmission alterations in cerebellum in the impairment of cognitive function in MHE through altered function of the glutamate-nitric oxide-cGMP pathway. We will also comment the therapeutic implications of the above studies and the utility of modulators of glutamate and GABA receptors to restore cognitive and motor function in rats with hyperammonemia and hepatic encephalopathy.

  5. Morphological changes of glutamatergic synapses in animal models of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2015-09-01

    Full Text Available The striatum and the subthalamic nucleus are the main entry doors for extrinsic inputs to reach the basal ganglia circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and subthalamic nucleus of animal models of Parkinson’s disease, and that these changes may contribute to aberrant network neuronal activity in the basal ganglia-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and subthalamic nucleus in models of Parkinson’s disease. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the basal ganglia circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in Parkinson’s disease will be examined.

  6. Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum.

    Science.gov (United States)

    Higley, Michael J; Gittis, Aryn H; Oldenburg, Ian A; Balthasar, Nina; Seal, Rebecca P; Edwards, Robert H; Lowell, Bradford B; Kreitzer, Anatol C; Sabatini, Bernardo L

    2011-04-22

    The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.

  7. Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum.

    Directory of Open Access Journals (Sweden)

    Michael J Higley

    Full Text Available The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs express the Type-3 vesicular glutamate transporter (VGluT3, although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.

  8. Autocrine glutamatergic transmission for the regulation of embryonal carcinoma stem cells.

    Science.gov (United States)

    Teng, Lin; Lei, Hui-Min; Sun, Fan; An, Shi-Min; Tang, Ya-Bin; Meng, Shuang; Wang, Cong-Hui; Shen, Ying; Chen, Hong-Zhuan; Zhu, Liang

    2016-08-02

    Glutamate behaves as the principal excitatory neurotransmitter in the vertebrate central nervous system and recently demonstrates intercellular signaling activities in periphery cancer cells. How the glutamatergic transmission is organized and operated in cancer stem cells remains undefined. We have identified a glutamatergic transmission circuit in embryonal carcinoma stem cells. The circuit is organized and operated in an autocrine mechanism and suppresses the cell proliferation and motility. Biological analyses determined a repertoire of glutamatergic transmission components, glutaminase, vesicular glutamate transporter, glutamate NMDA receptor, and cell membrane excitatory amino-acid transporter, for glutamate biosynthesis, package for secretion, reaction, and reuptake in mouse and human embryonal carcinoma stem cells. The glutamatergic components were also identified in mouse transplanted teratocarcinoma and in human primary teratocarcinoma tissues. Released glutamate acting as the signal was directly quantified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Genetic and pharmacological abolishment of the endogenously released glutamate-induced tonic activation of the NMDA receptors increased the cell proliferation and motility. The finding suggests that embryonal carcinoma stem cells can be actively regulated by establishing a glutamatergic autocrine/paracrine niche via releasing and responding to the transmitter.

  9. Morphological changes of glutamatergic synapses in animal models of Parkinson's disease.

    Science.gov (United States)

    Villalba, Rosa M; Mathai, Abraham; Smith, Yoland

    2015-01-01

    The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson's disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

  10. Release probability of hippocampal glutamatergic terminals scales with the size of the active zone.

    Science.gov (United States)

    Holderith, Noemi; Lorincz, Andrea; Katona, Gergely; Rózsa, Balázs; Kulik, Akos; Watanabe, Masahiko; Nusser, Zoltan

    2012-06-10

    Cortical synapses have structural, molecular and functional heterogeneity; our knowledge regarding the relationship between their ultrastructural and functional parameters is still fragmented. Here we asked how the neurotransmitter release probability and presynaptic [Ca(2+)] transients relate to the ultrastructure of rat hippocampal glutamatergic axon terminals. Two-photon Ca(2+) imaging-derived optical quantal analysis and correlated electron microscopic reconstructions revealed a tight correlation between the release probability and the active-zone area. Peak amplitude of [Ca(2+)] transients in single boutons also positively correlated with the active-zone area. Freeze-fracture immunogold labeling revealed that the voltage-gated calcium channel subunit Cav2.1 and the presynaptic protein Rim1/2 are confined to the active zone and their numbers scale linearly with the active-zone area. Gold particles labeling Cav2.1 were nonrandomly distributed in the active zones. Our results demonstrate that the numbers of several active-zone proteins, including presynaptic calcium channels, as well as the number of docked vesicles and the release probability, scale linearly with the active-zone area.

  11. Notch1 regulates hippocampal plasticity through interaction with the Reelin pathway, glutamatergic transmission and CREB signaling

    Directory of Open Access Journals (Sweden)

    Emanuele eBrai

    2015-11-01

    Full Text Available Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the establishment of memory in mice. We observe that Notch1 is a postsynaptic receptor with functional interactions with the Reelin receptor, ApoER2, and the ionotropic receptor, NMDAR. Targeted loss of Notch1 in the hippocampal CA fields affects Reelin signaling by influencing Dab1 expression and impairs the synaptic potentiation achieved through Reelin stimulation. Further analysis indicates that loss of Notch1 affects the expression and composition of the NMDAR but not AMPAR. Glutamatergic signaling is further compromised through downregulation of CamKII and its secondary and tertiary messengers resulting in reduced CREB signaling. Our results identify Notch1 as an important regulator of mechanisms involved in synaptic plasticity and memory formation. These findings emphasize the possible involvement of this signaling receptor in dementia.

  12. Simulation of postsynaptic glutamate receptors reveals critical features of glutamatergic transmission.

    Directory of Open Access Journals (Sweden)

    Renaud Greget

    Full Text Available Activation of several subtypes of glutamate receptors contributes to changes in postsynaptic calcium concentration at hippocampal synapses, resulting in various types of changes in synaptic strength. Thus, while activation of NMDA receptors has been shown to be critical for long-term potentiation (LTP and long term depression (LTD of synaptic transmission, activation of metabotropic glutamate receptors (mGluRs has been linked to either LTP or LTD. While it is generally admitted that dynamic changes in postsynaptic calcium concentration represent the critical elements to determine the direction and amplitude of the changes in synaptic strength, it has been difficult to quantitatively estimate the relative contribution of the different types of glutamate receptors to these changes under different experimental conditions. Here we present a detailed model of a postsynaptic glutamatergic synapse that incorporates ionotropic and mGluR type I receptors, and we use this model to determine the role of the different receptors to the dynamics of postsynaptic calcium with different patterns of presynaptic activation. Our modeling framework includes glutamate vesicular release and diffusion in the cleft and a glutamate transporter that modulates extracellular glutamate concentration. Our results indicate that the contribution of mGluRs to changes in postsynaptic calcium concentration is minimal under basal stimulation conditions and becomes apparent only at high frequency of stimulation. Furthermore, the location of mGluRs in the postsynaptic membrane is also a critical factor, as activation of distant receptors contributes significantly less to calcium dynamics than more centrally located ones. These results confirm the important role of glutamate transporters and of the localization of mGluRs in postsynaptic sites in their signaling properties, and further strengthen the notion that mGluR activation significantly contributes to postsynaptic calcium

  13. Curved Track Analysis of FSO Link for Ground-to-Train Communications

    Directory of Open Access Journals (Sweden)

    R. Paudel

    2014-04-01

    Full Text Available In this work, a free space optical (FSO link for the ground-to-train (G2T-FSO communications is proposed. Analytical analysis is carried out for the curved rail tracks. We show that the transmitter divergence angle, the transmit power and the size of the concentration lens need to increase for the curved section of the rail track compared to the straight track. We derive the analytical expression for the received power level based on the link geometry for the case of the curved track In the worst case scenario when the curvature radius is 120 m, the transmit power at the optical base station (BS needs to increase by over 2 dB when the concentration lens radius is increased by 5 times. Analyses also show that the received power along the track increases with the curvature radius for the same transmit power and receiver optics illustrating the effect due to link geometry. Additionally, the signal-to-noise ratio (SNR and the bit error rate (BER performance of the system for the curved track with different curvature radii is analysed at data rates of 10 Mbps and 100 Mbps for an additive white Gaussian noise (AWGN channel showing a good agreement between the theoretical and the simulated BER. Finally, effect of scintillations on the G2T-FSO link performance is discussed.

  14. On-line topical importance estimation: an effective focused crawling algorithm combining link and content analysis

    Institute of Scientific and Technical Information of China (English)

    Can WANG; Zi-yu GUAN; Chun CHEN; Jia-jun BU; Jun-feng WANG; Huai-zhong LIN

    2009-01-01

    Focused crawling is an important technique for topical resource discovery on the Web. The key issue in focusedcrawling is to prioritize uncrawled uniform resource locators (URLs) in the frontier to focus the crawling on relevant pages.Traditional focused crawlers mainly rely on content analysis. Link-based techniques are not effectively exploited despite their usefulness. In this paper, we propose a new frontier prioritizing algorithm, namely the on-line topical importance estimation (OTIE) algorithm. OTIE combines link-and content-based analysis to evaluate the priority of an uncrawled URL in the frontier. We performed real crawling experiments over 30 topics selected from the Open Directory Project (ODP) and compared harvest rate and target recall of the four crawling algorithms: breadth-first, link-context-prediction, on-line page importance computation (OPlC) and our OTIE. Experimental results showed that OTIE significantly outperforms the other three algorithms on the average target recall while maintaining an acceptable harvest rate. Moreover, OTIE is much faster than the traditional focused crawling algorithm.

  15. Link Winds: A visual data analysis system and its application to the atmospheric ozone depletion problem

    Science.gov (United States)

    Jacobson, Allan S.; Berkin, Andrew L.

    1995-01-01

    The Linked Windows Interactive Data System (LinkWinds) is a prototype visual data exploration system resulting from a NASA Jet Propulsion Laboratory (JPL) program of research into the application of graphical methods for rapidly accessing, displaying, and analyzing large multi variate multidisciplinary data sets. Running under UNIX it is an integrated multi-application executing environment using a data-linking paradigm to dynamically interconnect and control multiple windows containing a variety of displays and manipulators. This paradigm, resulting in a system similar to a graphical spreadsheet, is not only a powerful method for organizing large amounts of data for analysis, but leads to a highly intuitive, easy-to-learn user interface. It provides great flexibility in rapidly interacting with large masses of complex data to detect trends, correlations, and anomalies. The system, containing an expanding suite of non-domain-specific applications, provides for the ingestion of a variety of data base formats and hard -copy output of all displays. Remote networked workstations running LinkWinds may be interconnected, providing a multiuser science environment (MUSE) for collaborative data exploration by a distributed science team. The system is being developed in close collaboration with investigators in a variety of science disciplines using both archived and real-time data. It is currently being used to support the Microwave Limb Sounder (MLS) in orbit aboard the Upper Atmosphere Research Satellite (UARS). This paper describes the application of LinkWinds to this data to rapidly detect features, such as the ozone hole configuration, and to analyze correlations between chemical constituents of the atmosphere.

  16. Cumulative t-link threshold models for the genetic analysis of calving ease scores

    Directory of Open Access Journals (Sweden)

    Tempelman Robert J

    2003-09-01

    Full Text Available Abstract In this study, a hierarchical threshold mixed model based on a cumulative t-link specification for the analysis of ordinal data or more, specifically, calving ease scores, was developed. The validation of this model and the Markov chain Monte Carlo (MCMC algorithm was carried out on simulated data from normally and t4 (i.e. a t-distribution with four degrees of freedom distributed populations using the deviance information criterion (DIC and a pseudo Bayes factor (PBF measure to validate recently proposed model choice criteria. The simulation study indicated that although inference on the degrees of freedom parameter is possible, MCMC mixing was problematic. Nevertheless, the DIC and PBF were validated to be satisfactory measures of model fit to data. A sire and maternal grandsire cumulative t-link model was applied to a calving ease dataset from 8847 Italian Piemontese first parity dams. The cumulative t-link model was shown to lead to posterior means of direct and maternal heritabilities (0.40 ± 0.06, 0.11 ± 0.04 and a direct maternal genetic correlation (-0.58 ± 0.15 that were not different from the corresponding posterior means of the heritabilities (0.42 ± 0.07, 0.14 ± 0.04 and the genetic correlation (-0.55 ± 0.14 inferred under the conventional cumulative probit link threshold model. Furthermore, the correlation (> 0.99 between posterior means of sire progeny merit from the two models suggested no meaningful rerankings. Nevertheless, the cumulative t-link model was decisively chosen as the better fitting model for this calving ease data using DIC and PBF.

  17. Activation of α7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses.

    Science.gov (United States)

    Wang, Xulong; Lippi, Giordano; Carlson, David M; Berg, Darwin K

    2013-12-01

    Astrocytes, an abundant form of glia, are known to promote and modulate synaptic signaling between neurons. They also express α7-containing nicotinic acetylcholine receptors (α7-nAChRs), but the functional relevance of these receptors is unknown. We show here that stimulation of α7-nAChRs on astrocytes releases components that induce hippocampal neurons to acquire more α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors post-synaptically at glutamatergic synapses. The increase is specific in that no change is seen in synaptic NMDA receptor clusters or other markers for glutamatergic synapses, or in markers for GABAergic synapses. Moreover, the increases in AMPA receptors on the neuron surface are accompanied by increases in the frequency of spontaneous miniature synaptic currents mediated by the receptors and increases in the ratio of evoked synaptic currents mediated by AMPA versus NMDA receptors. This suggests that stimulating α7-nAChRs on astrocytes can convert 'silent' glutamatergic synapses to functional status. Astrocyte-derived thrombospondin is necessary but not sufficient for the effect, while tumor necrosis factor-α is sufficient but not necessary. The results identify astrocyte α7-nAChRs as a novel pathway through which nicotinic cholinergic signaling can promote the development of glutamatergic networks, recruiting AMPA receptors to post-synaptic sites and rendering the synapses more functional. We find that activation of nicotinic receptors on astrocytes releases a component that specifically recruits AMPA receptors to glutamatergic synapses. The recruitment appears to occur preferentially at what may be 'silent synapses', that is, synapses that have all the components required for glutamatergic transmission (including NMDA receptors) but lack sufficient AMPA receptors to generate a response. The results are unexpected and open up new possibilities for mechanisms underlying network formation and synaptic plasticity.

  18. Ergodic Capacity Analysis of Free-Space Optical Links with Nonzero Boresight Pointing Errors

    KAUST Repository

    Ansari, Imran Shafique

    2015-04-01

    A unified capacity analysis of a free-space optical (FSO) link that accounts for nonzero boresight pointing errors and both types of detection techniques (i.e. intensity modulation/ direct detection as well as heterodyne detection) is addressed in this work. More specifically, an exact closed-form expression for the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system is presented in terms of well-known elementary functions. Capitalizing on these new moments expressions, we present approximate and simple closedform results for the ergodic capacity at high and low SNR regimes. All the presented results are verified via computer-based Monte-Carlo simulations.

  19. Performance Analysis of FSO Links over Unified Gamma-Gamma Turbulence Channels

    KAUST Repository

    Ansari, Imran Shafique

    2015-05-01

    In this work, we present a unified performance analysis of a free-space optical (FSO) link that accounts for pointing errors and both types of detection techniques (i.e. intensity modulation/direct detection as well as heterodyne detection). We, then, present unified exact closed-form expressions for various statistical characteristics of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system. We capitalize on these unified results to offer unified exact closed-form expressions for various performance metrics. Additionally, we derive the asymptotic results for all the expressions derived earlier in the high SNR regime in terms of simple elementary functions. We also derive new asymptotic expressions for the ergodic capacity in the low as well as high SNR regimes in terms of simple elementary functions via utilizing moments. All the presented results are verified via computer-based Monte-Carlo simulations. © 2015 IEEE.

  20. Linking experimental results, biological networks and sequence analysis methods using Ontologies and Generalised Data Structures.

    Science.gov (United States)

    Koehler, Jacob; Rawlings, Chris; Verrier, Paul; Mitchell, Rowan; Skusa, Andre; Ruegg, Alexander; Philippi, Stephan

    2005-01-01

    The structure of a closely integrated data warehouse is described that is designed to link different types and varying numbers of biological networks, sequence analysis methods and experimental results such as those coming from microarrays. The data schema is inspired by a combination of graph based methods and generalised data structures and makes use of ontologies and meta-data. The core idea is to consider and store biological networks as graphs, and to use generalised data structures (GDS) for the storage of further relevant information. This is possible because many biological networks can be stored as graphs: protein interactions, signal transduction networks, metabolic pathways, gene regulatory networks etc. Nodes in biological graphs represent entities such as promoters, proteins, genes and transcripts whereas the edges of such graphs specify how the nodes are related. The semantics of the nodes and edges are defined using ontologies of node and relation types. Besides generic attributes that most biological entities possess (name, attribute description), further information is stored using generalised data structures. By directly linking to underlying sequences (exons, introns, promoters, amino acid sequences) in a systematic way, close interoperability to sequence analysis methods can be achieved. This approach allows us to store, query and update a wide variety of biological information in a way that is semantically compact without requiring changes at the database schema level when new kinds of biological information is added. We describe how this datawarehouse is being implemented by extending the text-mining framework ONDEX to link, support and complement different bioinformatics applications and research activities such as microarray analysis, sequence analysis and modelling/simulation of biological systems. The system is developed under the GPL license and can be downloaded from http://sourceforge.net/projects/ondex/

  1. The Profitability of the Strategy Linking Fundamental, Portfolio and Technical Analysis on the Polish Capital Market

    Directory of Open Access Journals (Sweden)

    Flotyński Marcin

    2016-12-01

    Full Text Available In the article, several methods of taking investment decisions are described: a fundamental, portfolio, and technical analysis. They constitute different approaches which are convenient for different types of investors with various expectations and time horizons of their investments. The simultaneous combination of these three analyses is not popular. The aim of this study is to test the effectiveness of simultaneous use of a fundamental analysis, portfolio analysis, and technical analysis for shares quoted on the Warsaw Stock Exchange (WSE in 2000–2007. The research hypothesis is advanced that the concurrent-linked application of a fundamental, portfolio, and technical analysis brings better results than the separate use of these analyses. Models of capital market, such as CAPM and APT, have been used, as well as P/E ratio, Return on Equity (RoE, Relative Strength Index (RSI, and Exponential Moving Average (EMA. The combination of a financial analysis, technical indicators, and models of the capital market in order to invest on the stock exchange is author’s own method. In general, the survey has been carried out on the grounds of quantitative methods (financial analysis, regression model, and multi regression model and a comparative analysis. The results of the research have been used to create diversified portfolios on the WSE. It occurs that the concurrent use of the three analyses brings the highest rate of return of a portfolio.

  2. Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior.

    Science.gov (United States)

    Hutchison, M A; Gu, X; Adrover, M F; Lee, M R; Hnasko, T S; Alvarez, V A; Lu, W

    2017-02-14

    Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Molecular Psychiatry advance online publication, 14 February 2017; doi:10.1038/mp.2017.7.

  3. Linking Advanced Visualization and MATLAB for the Analysis of 3D Gene Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Ruebel, Oliver; Keranen, Soile V.E.; Biggin, Mark; Knowles, David W.; Weber, Gunther H.; Hagen, Hans; Hamann, Bernd; Bethel, E. Wes

    2011-03-30

    Three-dimensional gene expression PointCloud data generated by the Berkeley Drosophila Transcription Network Project (BDTNP) provides quantitative information about the spatial and temporal expression of genes in early Drosophila embryos at cellular resolution. The BDTNP team visualizes and analyzes Point-Cloud data using the software application PointCloudXplore (PCX). To maximize the impact of novel, complex data sets, such as PointClouds, the data needs to be accessible to biologists and comprehensible to developers of analysis functions. We address this challenge by linking PCX and Matlab via a dedicated interface, thereby providing biologists seamless access to advanced data analysis functions and giving bioinformatics researchers the opportunity to integrate their analysis directly into the visualization application. To demonstrate the usefulness of this approach, we computationally model parts of the expression pattern of the gene even skipped using a genetic algorithm implemented in Matlab and integrated into PCX via our Matlab interface.

  4. Detection and Analysis of Twitter Trending Topics via LinkAnomaly Detection

    Directory of Open Access Journals (Sweden)

    Chandan M G

    2015-04-01

    Full Text Available This paper involves two approaches for finding the trending topics in social networks that is key-based approach and link-based approach. In conventional key-based approach for topics detection have mainly focus on frequencies of (textual words. We propose a link-based approach which focuses on posts reflected in the mentioning behavior of hundreds users. The anomaly detection in the twitter data set is carried out by retrieving the trend topics from the twitter in a sequential manner by using some API and corresponding user for training, then computed anomaly score is aggregated from different users. Further the aggregated anomaly score will be feed into change-point analysis or burst detection at the pinpoint, in order to detect the emerging topics. We have used the real time twitter account, so results are vary according to the tweet trends made. The experiment shows that proposed link-based approach performs even better than the keyword-based approach.

  5. Analysis of the preliminary optical links between ARTEMIS and the Optical Ground Station

    Science.gov (United States)

    Reyes Garcia-Talavera, Marcos; Chueca, Sergio; Alonso, Angel; Viera, Teodora; Sodnik, Zoran

    2002-12-01

    In the frame of the SILEX project, the European Space Agency (ESA) has put into orbit two Laser Communication Terminals, to establish an experimental free space optical communication link between a GEO satellite (ARTEMIS) and a LEO satellite (SPOT IV), to relay earth observation data. In order to perform In Orbit Testing (IOT) of these, and other, optical communications systems, ESA and the Instituto de Astrofisica de Canarias (IAC) reached an agreement for building the Optical Ground Station (OGS), in the Teide Observatory of the IAC. With ARTEMIS placed in a circular parking orbit at about 31000 kilometres, its optical payload has been preliminary tested with the OGS. First results and analysis are presented on the space-to-ground bi-directional link, including pointing acquisition and tracking performance, Bit-Error Rate (BER) and transmitted beam divergence effects related with atmospheric models and predictions. Future plans include deeper optical bi-directional communication tests of OGS, not only with ARTEMIS but also with OSCAR-40 (downlink) and SMART-1 (up-link) satellites, in order to do a full characterisation of the performances of laser beam propagation through atmospheric turbulence and a comparison with theoretical predictions.

  6. Local Control of Extracellular Dopamine Levels in the Medial Nucleus Accumbens by a Glutamatergic Projection from the Infralimbic Cortex.

    Science.gov (United States)

    Quiroz, César; Orrú, Marco; Rea, William; Ciudad-Roberts, Andrés; Yepes, Gabriel; Britt, Jonathan P; Ferré, Sergi

    2016-01-20

    It is generally assumed that infralimbic cortex (ILC) and prelimbic cortex, two adjacent areas of the medial prefrontal cortex (mPFC) in rodents, provide selective excitatory glutamatergic inputs to the nucleus accumbens (NAc) shell and core, respectively. It is also generally believed that mPFC influences the extracellular levels of dopamine in the NAc primarily by an excitatory collateral to the ventral tegmental area (VTA). In the present study, we first established the existence of a selective functional connection between ILC and the posteromedial portions of the VTA (pmVTA) and the mNAc shell (pmNAc shell), by measuring striatal neuronal activation (immunohistochemical analysis of ERK1/2 phosphorylation) and glutamate release (in vivo microdialysis) upon ILC electrical stimulation. A novel optogenetic-microdialysis approach allowed the measurement of extracellular concentrations of glutamate and dopamine in the pmNAc shell upon local light-induced stimulation of glutamatergic terminals from ILC. Cortical electrical and local optogenetic stimulation produced significant increases in the extracellular concentrations of glutamate and dopamine in the pmNAc shell. Local blockade of glutamate release by perfusion of an adenosine A2A receptor antagonist in the pmNAc shell blocked the dopamine release induced by local optogenetic stimulation but only partially antagonized dopamine release induced by cortical electrical stimulation. The results demonstrate that ILC excitatory afferents directly modulate the extracellular concentration of dopamine in the pmNAc shell, but also support the involvement of an indirect mechanism of dopamine control, through a concomitant ILC-mediated activation of the pmVTA. Significance statement: We established the existence of a functional connection between the infralimbic cortex (ILC) and the posteromedial portions of the ventral tegmental area (pmVTA) and the medial nucleus acumbens shell (pmNAc shell). A novel optogenetic

  7. Design verification and performance analysis of Serial AXI Links in Broadcom System-on-Chip

    OpenAIRE

    Sarai, Simran Kaur

    2014-01-01

    Design verification is an essential step in the development of any product. Also referred to as qualification testing, design verification ensures that the product as designed is the same as the product as intended. In this project, design verification and performance analysis of Thin Advanced Extensible Interface Links (T-AXI) is conducted on a Broadcom’s SoC (System on Chip). T-AXI is a Broadcom’s proprietary bus that interfaces all the subsystems on the System-onchip (SoC) to the system me...

  8. In search for peripheral markers for epilepsy and ALS - focus on glutamatergic signaling in blood cells

    NARCIS (Netherlands)

    Bos, Willemina Minke

    2005-01-01

    This thesis describes the research that was undertaken to find peripheral markers for epilepsy and ALS. Changes in the glutamatergic system and excitotoxicity are suggested to play a role in the pathogenesis of epilepsy and amyotrophic lateral sclerosis (ALS) (chapter 1) and therefore research was f

  9. GABA(A) receptor-mediated presynaptic inhibition on glutamatergic transmission.

    Science.gov (United States)

    Yamamoto, Sokatsu; Yoshimura, Megumu; Shin, Min-Chul; Wakita, Masahito; Nonaka, Kiku; Akaike, Norio

    2011-01-15

    We investigated the functional roles of presynaptic GABA(A) receptors on excitatory nerve terminals in contributing to spontaneous and action potential-evoked glutamatergic transmission to rat hippocampal CA3 pyramidal neurons. Single CA3 neurons were mechanically isolated with adherent nerve terminals, namely the 'synaptic bouton preparation', and spontaneous glutamatergic excitatory synaptic potentials (sEPSCs) and EPSCs evoked by focal electrical stimuli of a single presynaptic glutamatergic boutons (eEPSCs) were recorded using conventional whole-cell patch recordings. Selective activation of presynaptic GABA(A) receptors on these excitatory nerve terminals by muscimol, markedly facilitated sEPSCs frequency but inhibited eEPSC amplitude. The facilitation of sEPSC frequency was completely occluded by GABA(A) receptor-Cl⁻ channel blockers bicuculline or penicillin (PN). PN itself concentration-dependently inhibited the GABA(A) receptor response induced by bath application of muscimol, but had no effect on the glutamate receptor response. In addition, pretreatment with a blocker of the Na(+), K(+), 2Cl⁻ co-transporter type 1 (NKCC-1), bumetanide, prevented the muscimol-induced inhibition of eEPSCs. The results indicate that activation of presynaptic GABA(A) receptors directly depolarizes glutamatergic excitatory nerve terminals and thereby differentially modulates sEPSCs and eEPSCs.

  10. Molecular genetic analysis of X-linked hypogammaglobulinemia and isolated growth hormone deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, D.M.; Kurman, C.C.; Staudt, L.M. [Univ. of Brescia (Italy)] [and others

    1995-09-01

    In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) was described. XLA/GHD patients have reduced serum levels of Ig and normal cell-mediated immunity, and thus resemble patients with Bruton`s X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations and deletions in the Bruton`s tyrosine kinase gene (BTK) are responsible for Bruton`s XLA. We investigated BTK gene expression in an XLA/GHD patient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to BTK. BTK mRNA was normal in size and abundance, and the mRNA sequence was normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Thus, at the molecular level, XLA/GHD is a different disease entity from Bruton`s XLA. These results suggest that undescribed genes critical for B cell development and growth hormone production exist on the X chromosome. 17 refs., 4 figs.

  11. Genetic analysis of X-linked hybrid sterility in the house mouse.

    Science.gov (United States)

    Storchová, Radka; Gregorová, Sona; Buckiová, Daniela; Kyselová, Vendula; Divina, Petr; Forejt, Jirí

    2004-07-01

    Hybrid sterility is a common postzygotic reproductive isolation mechanism that appears in the early stages of speciation of various organisms. Mus musculus musculus and Mus musculus domesticus represent two recently separated mouse subspecies particularly suitable for genetic studies of hybrid sterility. Here we show that the introgression of Chr X of M. m. musculus origin (PWD/Ph inbred strain, henceforth PWD) into the genetic background of the C57BL/6J (henceforth B6) inbred strain (predominantly of M. m. domesticus origin) causes male sterility. The X-linked hybrid sterility is associated with reduced testes weight, lower sperm count, and morphological abnormalities of sperm heads. The analysis of recombinant Chr Xs in sterile and fertile males as well as quantitative trait locus (QTL) analysis of several fertility parameters revealed an oligogenic nature of the X-linked hybrid sterility. The Hstx1 locus responsible for male sterility was mapped near DXMit119 in the central part of Chr X. To ensure full sterility, the PWD allele of Hstx1 has to be supported with the PWD allelic form of loci in at least one proximal and/or one distal region of Chr X. Mapping and cloning of Hstx1 and other genes responsible for sterility of B6-X PWD Y B6 males could help to elucidate the special role of Chr X in hybrid sterility and consequently in speciation.

  12. Feasibility Analysis Of Free Space Earth To Satellite Optical Link In Tropical Region

    Directory of Open Access Journals (Sweden)

    Norhanis Aida M. Nor

    2012-01-01

    Full Text Available Free Space Optics (FSO becomes a great attention because of the chances in transmitting data up to 2.5Gbps. There are a lot of advantages offered by FSO such as easily deployment with saving time and cost and no electromagnetic interference. In spite of the advantages, FSO has an uncontrolled drawback which is highly sensitive to atmospheric phenomena because uses air as tranmission medium. Current studies and researches are only focusing on FSO terrestrial link with short path length and based on data from temperate region. Therefore, this paper is aiming to provide feasibility analysis of FSO link from earth to satellite especially Low Earth Orbit (LEO based on atmospheric data in tropical region. The analysis will include the losses from geometrical attenuation, absorption, scintillation, haze attenuation, and rain attenuation. ABSTRAK: Ruang Bebas Optik (Free Space Optics (FSO mendapat perhatian kerana kebolehannya memancarkan data pada kelajuan tinggi. Di sebalik kelebihannya, FSO amat sensitif terhadap fenomena atmosfera kerana ia menggunakan udara sebagai perantara transmisi. Penyelidikan dan kajian terkini hanya memfokus kepada jalinan darat FSO dengan kepanjangan jarak pendek dan bergantung kepada kawasan tenang.  Oleh itu, kertas ini menyasarkan untuk memberikan analisis kebolehlaksanaan  jalinan FSO dari bumi ke satelit terutamanya Orbit Rendah Bumi (Low Earth Orbit (LEO bergantung kepada data atmosfera di kawasan tropika. Analisa termasuklah kehilangannya akibat pengecilan geometri, penyerapan, kelipan, pelemahan jerebu dan pelemahan hujan.KEYWORDS:  feasibility; Free Space Optics; availability; atmospheric attenuation; beam divergence angle; elevation angle

  13. Linking trading ratio with TMDL (total maximum daily load) allocation matrix and uncertainty analysis.

    Science.gov (United States)

    Zhang, H X

    2008-01-01

    An innovative approach for total maximum daily load (TMDL) allocation and implementation is the watershed-based pollutant trading. Given the inherent scientific uncertainty for the tradeoffs between point and nonpoint sources, setting of trading ratios can be a contentious issue and was already listed as an obstacle by several pollutant trading programs. One of the fundamental reasons that a trading ratio is often set higher (e.g. greater than 2) is to allow for uncertainty in the level of control needed to attain water quality standards, and to provide a buffer in case traded reductions are less effective than expected. However, most of the available studies did not provide an approach to explicitly address the determination of trading ratio. Uncertainty analysis has rarely been linked to determination of trading ratio.This paper presents a practical methodology in estimating "equivalent trading ratio (ETR)" and links uncertainty analysis with trading ratio determination from TMDL allocation process. Determination of ETR can provide a preliminary evaluation of "tradeoffs" between various combination of point and nonpoint source control strategies on ambient water quality improvement. A greater portion of NPS load reduction in overall TMDL load reduction generally correlates with greater uncertainty and thus requires greater trading ratio. The rigorous quantification of trading ratio will enhance the scientific basis and thus public perception for more informed decision in overall watershed-based pollutant trading program.

  14. Network analysis of physics discussion forums and links to course success

    Science.gov (United States)

    Traxler, Adrienne; Gavrin, Andrew; Lindell, Rebecca

    2017-01-01

    Large introductory science courses tend to isolate students, with negative consequences for long-term retention in college. Many active learning courses build collaboration and community among students as an explicit goal, and social network analysis has been used to track the development and beneficial effects of these collaborations. Here we supplement such work by conducting network analysis of online course discussion forums in two semesters of an introductory physics class. Online forums provide a tool for engaging students with each other outside of class, and offer new opportunities to commuter or non-traditional students with limited on-campus time. We look for correlations between position in the forum network (centrality) and final course grades. Preliminary investigation has shown weak correlations in the very dense full-semester network, so we will consider reduced ''backbone'' networks that highlight the most consistent links between students. Future work and implications for instruction will also be discussed.

  15. Automated Assignment of MS/MS Cleavable Cross-Links in Protein 3D-Structure Analysis

    Science.gov (United States)

    Götze, Michael; Pettelkau, Jens; Fritzsche, Romy; Ihling, Christian H.; Schäfer, Mathias; Sinz, Andrea

    2015-01-01

    CID-MS/MS cleavable cross-linkers hold an enormous potential for an automated analysis of cross-linked products, which is essential for conducting structural proteomics studies. The created characteristic fragment ion patterns can easily be used for an automated assignment and discrimination of cross-linked products. To date, there are only a few software solutions available that make use of these properties, but none allows for an automated analysis of cleavable cross-linked products. The MeroX software fills this gap and presents a powerful tool for protein 3D-structure analysis in combination with MS/MS cleavable cross-linkers. We show that MeroX allows an automatic screening of characteristic fragment ions, considering static and variable peptide modifications, and effectively scores different types of cross-links. No manual input is required for a correct assignment of cross-links and false discovery rates are calculated. The self-explanatory graphical user interface of MeroX provides easy access for an automated cross-link search platform that is compatible with commonly used data file formats, enabling analysis of data originating from different instruments. The combination of an MS/MS cleavable cross-linker with a dedicated software tool for data analysis provides an automated workflow for 3D-structure analysis of proteins. MeroX is available at www.StavroX.com .

  16. Subregional Expression of Hippocampal Glutamatergic and GABAergic Genes in F344 Rats with Social Isolation after Weaning.

    Science.gov (United States)

    Iwata, Hisaya; Yamamuro, Yutaka

    2016-02-01

    Many studies have shown that postweaning social isolation (pwSI) alters various behavioral phenotypes, including hippocampusdependent tasks. Here, we report the comprehensive analysis of the expression of glutamatergic and GABAergic neurotransmissionrelated genes in the distinct hippocampal subregions of pwSI rats. Male F344 rats (age, 4 wk) experienced either pwSI or group housing (controls). At 7 wk of age, the hippocampus of each rat was removed and laser-microdissected into the CA1 and CA3 layers of pyramidal cells and the granule cell layer of the dentate gyrus. Subsequently, the expression of glutamatergic- and GABAergic- related genes was analyzed by quantitative RT-PCR. In the CA1 and CA3 pyramidal cell layers, 18 of 24 glutamate receptor subunit genes were at least 1.5-fold increased in expression after pwSI. In particular, the expression of several N-methyl-D-aspartate and kainate receptors (for example, Grin2a in CA1, Grik4 in CA3) was significantly increased after pwSI. In contrast, pwSI tended to decrease the expression of GABAA receptor subunit genes, and Gabra1, Gabra2, Gabra4, Gabra5, Gabrb2, Gabrg1, and Gabrg2 were all significantly decreased in expression compared with the levels in the group-housed rats. These results indicate a subregion- specific increase of glutamate receptors and reduction of GABAA receptors, suggesting that the hippocampal circuits of pwSI rats may be in more excitable states than those of group-housed rats.

  17. Hipótese glutamatérgica da esquizofrenia Glutamatergic hypothesis of schizophrenia

    Directory of Open Access Journals (Sweden)

    Rodrigo A Bressan

    2003-09-01

    Full Text Available A esquizofrenia é um transtorno psiquiátrico devastador cuja fisiopatologia ainda está para ser esclarecida. Apesar de uma disfunção dopaminérgica estar bem estabelecida na esquizofrenia, há uma série de evidências sugerindo o envolvimento do sistema glutamatérgico na fisiopatologia do transtorno. Este artigo faz uma breve revisão de alguns aspectos básicos do funcionamento dos receptores glutamatérgicos com ênfase nos receptores N-metil-D-aspartato (NMDA. Apresenta evidências científicas sugerindo uma disfunção do sistema glutamatérgico na esquizofrenia (hipofunção de receptores NMDA. E discute as interações entre os sistemas dopaminérgico e glutamatérgico; mais especificamente como os estados hiperdopaminérgicos encontrados na esquizofrenia podem estar associados a uma alteração glutamatérgica.Schizophrenia is a devastating psychiatric disorder whose pathophysiology has not been fully clarified yet. Although dopamine dysfunction in schizophrenia is unequivocal, there are many evidences suggesting the involvement of the glutamatergic system. This paper briefly describes some basic knowledge regarding the functioning of the glutamatergic receptors with emphasis on the N-methyl-D-aspartate (NMDA receptors. Presents evidence for glutamatergic dysfunction in schizophrenia, more specifically NMDA receptor hypofunction. Finaly the paper discusses the interaction between the dopaminergic and the glutamatergic systems; in special how hyperdopaminergic state found in schizophrenia can be associated to glutamatergic dysfunctions.

  18. Multiple roles for mammalian target of rapamycin signaling in both glutamatergic and GABAergic synaptic transmission.

    Science.gov (United States)

    Weston, Matthew C; Chen, Hongmei; Swann, John W

    2012-08-15

    The mammalian target of rapamycin (mTOR) signaling pathway in neurons integrates a variety of extracellular signals to produce appropriate translational responses. mTOR signaling is hyperactive in neurological syndromes in both humans and mouse models that are characterized by epilepsy, autism, and cognitive disturbances. In addition, rapamycin, a clinically important immunosuppressant, is a specific and potent inhibitor of mTOR signaling. While mTOR is known to regulate growth and synaptic plasticity of glutamatergic neurons, its effects on basic parameters of synaptic transmission are less well studied, and its role in regulating GABAergic transmission is unexplored. We therefore performed an electrophysiological and morphological comparison of glutamatergic and GABAergic neurons in which mTOR signaling was either increased by loss of the repressor Pten or decreased by treatment with rapamycin. We found that hyperactive mTOR signaling increased evoked synaptic responses in both glutamatergic and GABAergic neurons by ∼50%, due to an increase in the number of synaptic vesicles available for release, the number of synapses formed, and the miniature event size. Prolonged (72 h) rapamycin treatment prevented these abnormalities and also decreased synaptic transmission in wild-type glutamatergic, but not GABAergic, neurons. Further analyses suggested that hyperactivation of the mTOR pathway also impairs presynaptic function, possibly by interfering with vesicle fusion. Despite this presynaptic impairment, the net effect of Pten loss is enhanced synaptic transmission in both GABAergic and glutamatergic neurons, which has numerous implications, depending on where in the brain mutations of an mTOR suppressor gene occur.

  19. Mutational analysis of Btk, the defective gene in X-linked agammaglobulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Conley, M.E.; Fitch-Hilgenberg, M.E.; Rohrer, J. [St. Jude Children`s Research Hospital, Memphis, TN (United States)

    1994-09-01

    Recent studies have shown that X-linked agammaglobulinemia (XLA), a disorder of B cell development, is due to mutations in an scr-like cytoplasmic tyrosine kinase, Btk. Thus far, mutations in this gene have been identified by sequencing of cDNA. To permit the detection of mutations in genomic DNA, we determined the structure of Btk and identified 19 exons in 37 kb of DNA. PCR primers were designed to amplify each exon with its splice sites. Two overlapping PCR products were employed for exons longer than 230 base pairs. Single strand conformation polymorphism (SSCP) analysis was used to screen genomic DNA from 30 unrelated families presumed to carry a mutation in Btk. It was possible to amplify DNA in every reaction from every patient. None of the DNA samples demonstrated more than one aberrant SSCP pattern. Twenty three mutations were detected in 25 families. Seven point mutations resulting in amino acid substitutions were seen. An additional 7 base pair substitutions gave rise to premature stop codons. Two splice defects were noted. Small insertions or deletions, all resulting in frameshifts and premature stop codons were seen in eight patients. One patient had an A to G transition in the ATG start codon. Two mutations, both at CpG dinucleotides, were seen in more than one family. Haplotype analysis, using CA repeats closely linked to Btk, demonstrated that the mutations in these families arose independently. We conclude from these studies that the mutations in Btk in patients with XLA are highly variable. Large deletions are uncommon, although small 1 to 4 bp insertions or deletions constitute as many as one third of the mutations. Further analysis of patients with amino acid substitutions will permit structure/function correlations.

  20. Performance Analysis of Free-Space Optical Links Over Malaga (M) Turbulence Channels with Pointing Errors

    KAUST Repository

    Ansari, Imran Shafique

    2015-08-12

    In this work, we present a unified performance analysis of a free-space optical (FSO) link that accounts for pointing errors and both types of detection techniques (i.e. intensity modulation/direct detection (IM/DD) as well as heterodyne detection). More specifically, we present unified exact closedform expressions for the cumulative distribution function, the probability density function, the moment generating function, and the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system, all in terms of the Meijer’s G function except for the moments that is in terms of simple elementary functions. We then capitalize on these unified results to offer unified exact closed-form expressions for various performance metrics of FSO link transmission systems, such as, the outage probability, the scintillation index (SI), the average error rate for binary and M-ary modulation schemes, and the ergodic capacity (except for IM/DD technique, where we present closed-form lower bound results), all in terms of Meijer’s G functions except for the SI that is in terms of simple elementary functions. Additionally, we derive the asymptotic results for all the expressions derived earlier in terms of Meijer’s G function in the high SNR regime in terms of simple elementary functions via an asymptotic expansion of the Meijer’s G function. We also derive new asymptotic expressions for the ergodic capacity in the low as well as high SNR regimes in terms of simple elementary functions via utilizing moments. All the presented results are verified via computer-based Monte-Carlo simulations.

  1. Innervation by a GABAergic neuron depresses spontaneous release in glutamatergic neurons and unveils the clamping phenotype of synaptotagmin-1.

    Science.gov (United States)

    Wierda, Keimpe D B; Sørensen, Jakob B

    2014-02-01

    The role of spontaneously occurring release events in glutamatergic and GABAergic neurons and their regulation is intensely debated. To study the interdependence of glutamatergic and GABAergic spontaneous release, we compared reciprocally connected "mixed" glutamatergic/GABAergic neuronal pairs from mice cultured on astrocyte islands with "homotypic" glutamatergic or GABAergic pairs and autaptic neurons. We measured mEPSC and mIPSC frequencies simultaneously from both neurons. Neuronal pairs formed both interneuronal synaptic and autaptic connections indiscriminately. We find that whereas mEPSC and mIPSC frequencies did not deviate between autaptic and synaptic connections, the frequency of mEPSCs in mixed pairs was strongly depressed compared with either autaptic neurons or glutamatergic pairs. Simultaneous imaging of synapses, or comparison to evoked release amplitudes, showed that this decrease was not caused by fewer active synapses. The mEPSC frequency was negatively correlated with the mIPSC frequency, indicating interdependence. Moreover, the reduction in mEPSC frequency was abolished when established pairs were exposed to bicuculline for 3 d, but not by long-term incubation with tetrodotoxin, indicating that spontaneous GABA release downregulates mEPSC frequency. Further investigations showed that knockout of synaptotagmin-1 did not affect mEPSC frequencies in either glutamatergic autaptic neurons or in glutamatergic pairs. However, in mixed glutamatergic/GABAergic pairs, mEPSC frequencies were increased by a factor of four in the synaptotagmin-1-null neurons, which is in line with data obtained from mixed cultures. The effect persisted after incubation with BAPTA-AM. We conclude that spontaneous GABA release exerts control over mEPSC release, and GABAergic innervation of glutamatergic neurons unveils the unclamping phenotype of the synaptotagmin-1-null neurons.

  2. Highly efficient codec based on significance-linked connected-component analysis of wavelet coefficients

    Science.gov (United States)

    Chai, Bing-Bing; Vass, Jozsef; Zhuang, Xinhua

    1997-04-01

    Recent success in wavelet coding is mainly attributed to the recognition of importance of data organization. There has been several very competitive wavelet codecs developed, namely, Shapiro's Embedded Zerotree Wavelets (EZW), Servetto et. al.'s Morphological Representation of Wavelet Data (MRWD), and Said and Pearlman's Set Partitioning in Hierarchical Trees (SPIHT). In this paper, we propose a new image compression algorithm called Significant-Linked Connected Component Analysis (SLCCA) of wavelet coefficients. SLCCA exploits both within-subband clustering of significant coefficients and cross-subband dependency in significant fields. A so-called significant link between connected components is designed to reduce the positional overhead of MRWD. In addition, the significant coefficients' magnitude are encoded in bit plane order to match the probability model of the adaptive arithmetic coder. Experiments show that SLCCA outperforms both EZW and MRWD, and is tied with SPIHT. Furthermore, it is observed that SLCCA generally has the best performance on images with large portion of texture. When applied to fingerprint image compression, it outperforms FBI's wavelet scalar quantization by about 1 dB.

  3. Molecular analysis of sex chromosome-linked mutants in the silkworm Bombyx mori

    Indian Academy of Sciences (India)

    Tsuguru Fujii; Hiroaki Abe; Toru Shimada

    2010-09-01

    In Bombyx mori, the W chromosome determines the female sex. A few W chromosome-linked mutations that cause masculinization of the female genitalia have been found. In female antennae of a recently isolated mutant, both female-type and male-type Bmdsx mRNAs were expressed, and BmOr1 (bombykol receptor) and BmOr3 (bombykal receptor), which are predominantly expressed in the antennae of male moths, were expressed about 50 times more abundantly in the antennae of mutant females than in those of normal females. These mutants are valuable resources for the molecular analysis of the sex-determination system. Besides the Fem gene, the quantitative egg size-determining gene Esd is thought to be present on the W chromosome, based on the observation that ZWW triploid moths produce larger eggs than ZZW triploids. The most recently updated B. mori genome assembly comprises 20.5 Mb of Z chromosome sequence. Using these sequence data, responsible genes or candidate genes for four Z-linked mutants have been reported. The od (distinct oily) and spli (soft and pliable) are caused by mutation in BmBLOS2 and Bmacj6, respectively. Bmap is a candidate gene for $V_g$ (vestigial). Similarly, Bmprm is a candidate gene for Md (muscle dystrophy), causing abnormal development of indirect flight muscle.

  4. Power-Aware Routing and Network Design with Bundled Links: Solutions and Analysis

    Directory of Open Access Journals (Sweden)

    Rosario G. Garroppo

    2013-01-01

    Full Text Available The paper deeply analyzes a novel network-wide power management problem, called Power-Aware Routing and Network Design with Bundled Links (PARND-BL, which is able to take into account both the relationship between the power consumption and the traffic throughput of the nodes and to power off both the chassis and even the single Physical Interface Card (PIC composing each link. The solutions of the PARND-BL model have been analyzed by taking into account different aspects associated with the actual applicability in real network scenarios: (i the time for obtaining the solution, (ii the deployed network topology and the resulting topology provided by the solution, (iii the power behavior of the network elements, (iv the traffic load, (v the QoS requirement, and (vi the number of paths to route each traffic demand. Among the most interesting and novel results, our analysis shows that the strategy of minimizing the number of powered-on network elements through the traffic consolidation does not always produce power savings, and the solution of this kind of problems, in some cases, can lead to spliting a single traffic demand into a high number of paths.

  5. Analysis of Link Formation, Persistence and Dissolution in NetSense Data

    CERN Document Server

    Bahulkar, Ashwin; Lizardo, Omar; Dong, Yuxiao; Yang, Yang; Chawla, Nitesh V

    2016-01-01

    We study a unique behavioral network data set (based on periodic surveys and on electronic logs of dyadic contact via smartphones) collected at the University of Notre Dame.The participants are a sample of members of the entering class of freshmen in the fall of 2011 whose opinions on a wide variety of political and social issues and activities on campus were regularly recorded - at the beginning and end of each semester - for the first three years of their residence on campus. We create a communication activity network implied by call and text data, and a friendship network based on surveys. Both networks are limited to students participating in the NetSense surveys. We aim at finding student traits and activities on which agreements correlate well with formation and persistence of links while disagreements are highly correlated with non-existence or dissolution of links in the two social networks that we created. Using statistical analysis and machine learning, we observe several traits and activities displ...

  6. Transmission Performance Analysis of Digital Wire and Wireless Optical Links in Local and Wide Areas Optical Networks

    CERN Document Server

    Mohamed, Abd El Naser A; Rashed, Ahmed Nabih Zaki; Nabawy, Amina E M El

    2009-01-01

    In the present paper, the transmission performance analysis of digital wire and wireless optical links in local and wide areas optical networks have been modeled and parametrically investigated over wide range of the affecting parameters. Moreover, we have analyzed the basic equations of the comparative study of the performance of digital fiber optic links with wire and wireless optical links. The development of optical wireless communication systems is accelerating as a high cost effective to wire fiber optic links. The optical wireless technology is used mostly in wide bandwidth data transmission applications. Finally, we have investigated the maximum transmission distance and data transmission bit rates that can be achieved within digital wire and wireless optical links for local and wide areas optical network applications.

  7. Micro Chemical (Elemental Analysis of Leucas aspera (Willd Link Employing SEM-EDAX

    Directory of Open Access Journals (Sweden)

    Sunkara Yashvanth

    2013-01-01

    Full Text Available The plant, Leucas aspera (Willd Link is well known for its varied medicinal uses. Present study deals with its micro chemical (elemental characterization using Energy Dispersive X-ray Analysis (EDAX detector fitted to Scanning Electron Microscope. The plant has very interesting morphology. Crystals of varied shape and inclusions/exudates were noticed within and on the leaf & stem surfaces. Various plant parts analysed were, stem surface, stem sections, stem inclusions, blebs on stem hairs, crystals of varied shape, root sections, abaxial and adaxial surfaces, flower, seed and seed caruncle. Lot of variation in elemental composition was observed in various plant parts. Major elements detected were Carbon, Oxygen, Calcium, Silica, and Aluminum. Other elements found were Iron, Sodium, potassium, Phosphorus and Chlorine.

  8. Personality and personal projects: linking big five and PAC units of analysis.

    Science.gov (United States)

    Little, B R; Lecci, L; Watkinson, B

    1992-06-01

    This article examines the relationships between classical trait units as represented by the five-factor model (e.g., Digman, 1990) and personal action construct (PAC) units as measured by Personal Projects Analysis (Little, 1983). One hundred and forty-seven students were administered the NEO Personality Inventory (Costa & McCrae, 1985) and two components of Personal Projects methodology during their first term in university. Neuroticism and Conscientiousness were related to problematic and positive project systems, respectively, with these effects generalizing across the academic and interpersonal project domains. Extraversion and Agreeableness were also associated with positive evaluations of personal projects, particularly in the interpersonal domain. Openness was distinctively linked with project initiation and value congruency. We suggest theoretical and applied implications of using PAC methods to expand and refine the classical trait research agenda.

  9. Numerical analysis of thermal distortion of the mirror in space-to-ground laser communication links

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-feng; ZHANG Bai-lei; LIN Mi; QI Li-mei

    2005-01-01

    The thermal distortion of an optical reflector surface due to the changing sunlight in a space environment will cause shift and spreading of its reflected focus and thereby influence the performance of space-to-ground laser communication links. Based on the characteristics of a low orbit satellite, the normal shift of a plan mirror caused by thermal distortion is analyzed with the software of the ANSYS of finite element analysis. A general expression of the transmitted beam from a distorted reflector surface and a counting formula for the shifts of the focus center before and after thermal distortion are deduced. The result of simulation shows that the magnitude order of the normal shift of the antenna mirror surface can be as high as tens of μrad.The worse the mirror thermal distortion is, the larger the shift of the received focus center is. And the change of the shifts does not obey a linear rule.

  10. Molecular Infectious Disease Epidemiology: Survival Analysis and Algorithms Linking Phylogenies to Transmission Trees.

    Science.gov (United States)

    Kenah, Eben; Britton, Tom; Halloran, M Elizabeth; Longini, Ira M

    2016-04-01

    Recent work has attempted to use whole-genome sequence data from pathogens to reconstruct the transmission trees linking infectors and infectees in outbreaks. However, transmission trees from one outbreak do not generalize to future outbreaks. Reconstruction of transmission trees is most useful to public health if it leads to generalizable scientific insights about disease transmission. In a survival analysis framework, estimation of transmission parameters is based on sums or averages over the possible transmission trees. A phylogeny can increase the precision of these estimates by providing partial information about who infected whom. The leaves of the phylogeny represent sampled pathogens, which have known hosts. The interior nodes represent common ancestors of sampled pathogens, which have unknown hosts. Starting from assumptions about disease biology and epidemiologic study design, we prove that there is a one-to-one correspondence between the possible assignments of interior node hosts and the transmission trees simultaneously consistent with the phylogeny and the epidemiologic data on person, place, and time. We develop algorithms to enumerate these transmission trees and show these can be used to calculate likelihoods that incorporate both epidemiologic data and a phylogeny. A simulation study confirms that this leads to more efficient estimates of hazard ratios for infectiousness and baseline hazards of infectious contact, and we use these methods to analyze data from a foot-and-mouth disease virus outbreak in the United Kingdom in 2001. These results demonstrate the importance of data on individuals who escape infection, which is often overlooked. The combination of survival analysis and algorithms linking phylogenies to transmission trees is a rigorous but flexible statistical foundation for molecular infectious disease epidemiology.

  11. Performance Analysis of a Free Space Optics Link with Multiple Transmitters/Receivers

    Directory of Open Access Journals (Sweden)

    Nur Haedzerin Md Noor

    2012-04-01

    Full Text Available ABSTRACT:  Multiple transmitters/receivers (TX/RX are used to improve the quality of Free Space Optics (FSO communication systems. With the current needs of this technology for longer distance communication, the qualitative analysis of the system has become essential. In this work, the received power level (PR and bit error rate (BER are considered to influence the FSO link performance. The relationship between the two parameters are investigated and analysed. Furthermore, the received power for various numbers of TXs and RXs are experimentally measured and compared with the values obtained from theoretical calculations. The first part of the work deals with the theoretical calculation and simulation designs of multiple laser beams based on the commercial FSO used in actual sites. The second part describes the practical work and analysis of the system’s performance.ABSTRAK: Pemancar/penerima berganda (TX/RX digunakan bagi meningkatkan kualiti sistem komunikasi Ruang Optik Bebas (FSO. Analisis kualitatif ke atas sistemnya adalah penting bagi keperluan semasa teknologi ini untuk jarak jauh. Di dalam kajian ini, aras kuasa penerima (PR dan kadar ralat bit (BER telah diambilkira bagi menentukan prestasi rangkaian FSO. Hubungan di antara kedua-dua parameter telah dikaji dan dianalisis. Seterusnya, kuasa penerima untuk pelbagai nombor TXs dan RXs diukur secara eksperimen dan dibandingkan dengan nilai teori yang dikira. Bahagian pertama skop kajian berkaitan dengan pengiraan teori dan rekabentuk simulasi sinaran laser berdasarkan FSO komersial di lapangan. Bahagian kedua kajian adalah kerja lapangan dan analisis prestasi sistem.KEY WORDS:  Free Space Optics (FSO link; Multiple TX/RX FSO; bit error rate (BER; eye diagram.

  12. A didactical structural model – linking analysis of teaching and analysis of educational media

    DEFF Research Database (Denmark)

    Graf, Stefan Ting

    2009-01-01

    1. Gap between general didactics and textbook/media research There seems to be a gap between general didactics (theory of teaching) and research in textbooks or educational media in general at least in the Nordic and German speaking countries. General didactic and their models seem to underestimate...... for teaching if the research or the analysis does not have an integrated concept of teaching? Concrete concepts of teaching could be very challenging for research serving both teacher education and media production. As a radical example for such a challenge I will present and discuss the concept of “Lehrkunst...

  13. Purification and SAXS analysis of the integrin linked kinase, PINCH, parvin (IPP heterotrimeric complex.

    Directory of Open Access Journals (Sweden)

    Amy L Stiegler

    Full Text Available The heterotrimeric protein complex containing the integrin linked kinase (ILK, parvin, and PINCH proteins, termed the IPP complex, is an essential component of focal adhesions, where it interacts with many proteins to mediate signaling from integrin adhesion receptors. Here we conduct a biochemical and structural analysis of the minimal IPP complex, comprising full-length human ILK, the LIM1 domain of PINCH1, and the CH2 domain of α-parvin. We provide a detailed purification protocol for IPP and show that the purified IPP complex is stable and monodisperse in solution. Using small-angle X-ray scattering (SAXS, we also conduct the first structural characterization of IPP, which reveals an elongated shape with dimensions 120×60×40 Å. Flexibility analysis using the ensemble optimization method (EOM is consistent with an IPP complex structure with limited flexibility, raising the possibility that inter-domain interactions exist. However, our studies suggest that the inter-domain linker in ILK is accessible and we detect no inter-domain contacts by gel filtration analysis. This study provides a structural foundation to understand the conformational restraints that govern the IPP complex.

  14. Using Aoristic Analysis to Link Remote and Ground-Level Phenological Observations

    Science.gov (United States)

    Henebry, G. M.

    2013-12-01

    Phenology is about observing events in time and space. With the advent of publically accessible geospatial datastreams and easy to use mapping software, specifying where an event occurs is much less of a challenge than it was just two decades ago. In contrast, specifying when an event occurs remains a nontrivial function of a population of organismal responses, sampling interval, compositing period, and reporting precision. I explore how aoristic analysis can be used to analyzing spatiotemporal events for which the location is known to acceptable levels of precision but for which temporal coordinates are poorly specified or only partially bounded. Aoristic analysis was developed in the late 1990s in the field of quantitative criminology to leverage temporally imprecise geospatial data of crime reports. Here I demonstrate how aoristic analysis can be used to link remotely sensed observations of land surface phenology to ground-level observations of organismal phenophase transitions. Explicit representation of the windows of temporal uncertainty with aoristic weights enables cross-validation exercises and forecasting efforts to avoid false precision.

  15. Stability analysis and dynamic response of a DC-link module with a series voltage compensator

    DEFF Research Database (Denmark)

    Wang, Huai; Liu, Wenchao; Chung, Henry

    2013-01-01

    A DC-link module composed of a reduced value of DC-link capacitor and a series voltage compensator has been proposed. The voltage compensator processes the ripple voltage on the DC link and reactive power only, which can be implemented by low-voltage devices. The overall energy storage of the DC...

  16. Subpopulations of neurokinin 1 receptor-expressing neurons in the rat lateral amygdala display a differential pattern of innervation from distinct glutamatergic afferents

    Science.gov (United States)

    Sreepathi, H.K.; Ferraguti, F.

    2012-01-01

    Substance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. Immunofluorescence analysis of the co-expression of NK1 with calcium binding proteins in LA revealed that ∼35% of NK1-containing neurons co-expressed parvalbumin (PV), whereas no co-localization was detected in the basal amygdaloid nucleus. We also show that neurons expressing NK1 receptors in LA did not contain detectable levels of calcium/calmodulin kinase IIα, thus suggesting that NK1 receptors are expressed by interneurons. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, we found that in LA ∼75% of glutamatergic synapses onto NK1-expressing neurons were labeled for the vesicular glutamate transporter 1 indicating that they most likely are of cortical, hippocampal, or intrinsic origin. The remaining ∼25% were immunoreactive for the vesicular glutamate transporter 2 (VGluT2), and may then originate from subcortical areas. On the other hand, we could not detect VGluT2-containing inputs onto NK1/PV immunopositive neurons. Our data add to previous localization studies by describing an unexpected variation between LA and basal nucleus of the amygdala (BA) in the neurochemical phenotype of NK1-expressing neurons and reveal the relative source of glutamatergic inputs that may activate these neurons, which in turn regulate fear and anxiety responses. PMID:22210508

  17. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: A review of magnetic resonance spectroscopy studies

    NARCIS (Netherlands)

    Naaijen, J.; Lithgoe, D.J.; Amiri, H.; Buitelaar, J.; Glennon, J.C.

    2015-01-01

    Compulsivity and impulsivity are cross-disorder traits observed in autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Aberrant fronto-striatal glutamatergic signalling is core to the understanding of compulsive and impulsive diso

  18. MARKAL-MACRO: A linked model for energy-economy analysis

    Energy Technology Data Exchange (ETDEWEB)

    Manne, A.S. (Stanford Univ., CA (United States)); Wene, C.O. (Brookhaven National Lab., Upton, NY (United States) Chalmers Univ. of Tech., Goeteborg (Sweden))

    1992-02-01

    MARKAL-MACRO is an experiment in model linkage for energy and economy analysis. This new tool is intended as an improvement over existing methods for energy strategy assessment. It is designed specifically for estimating the costs and analyzing the technologies proposed for reducing environmental risks such as global climate change or regional air pollution. The greenhouse gas debate illustrates the usefulness of linked energy-economy models. A central issue is the coupling between economic growth, the level of energy demands, and the development of an energy system to supply these demands. The debate is often connected with alternative modeling approaches. The competing philosophies may be labeled top-down macroeconomic'' and bottom-up engineering'' perspectives. MARKAL is a systems engineering (physical process) analysis built on the concept of a Reference Energy System (RES). MARKAL is solved by means of dynamic linear programming. In most applications, the end use demands are fixed, and an economically efficient solution is obtained by minimizing the present value of energy system's costs throughout the planning horizon. MACRO is a macroeconomic model with an aggregated view of long-term economic growth. The basis input factors of production are capital, labor and individual forms of energy. MACRO is solved by nonlinear optimization.

  19. Analysis of the Tunnel Boring Machine Advancement on the Bologna-Florence Railway Link

    Directory of Open Access Journals (Sweden)

    M. Cardu

    2009-01-01

    Full Text Available Problem statement: The high-velocity railway link between Bologna and Firenze (Italy is today under construction and several tunnels have to be excavated for this purpose, some of these using TBMs. A small diameter tunnel, named Cunicolo ginori, was realized by TBM parallel to a large railway tunnel (Vaglia, at the distance of only 35 m. Approach: The Vaglia tunnel had been excavated by conventional methods and provided, thanks to a detailed survey and a systematic geotechnical monitoring (rock quality evaluation and convergence measurements the characterization data of the crossed rock mass; moreover the TBM performance data in Cunicolo ginori were continuously monitored. A tunnel stretch, 587 m long, was recorded and the analysis of the data from both surveys allowed to correlate the geomechanical parameters of the rock-mass to the TBM performances (net advancement rate, thrust, specific energy. Results: Based on this large amount of data a new system to predict the net TBM advancement rate for a tunnel in rock masses of known geological and geomechanical characteristics was then developed. Also the Utilization Coefficient (CU can be correlated to the rock quality Indices: The net advance rate and the utilization coefficient provide a mean to foresee the gross advancement rate and to evaluate the suitability of a machine for the excavation of a tunnel. Conclusion: In this study, an analysis had been carried out on about 587 m of a service tunnel, excavated by a TBM in a flysch formation.

  20. MARKAL-MACRO: A linked model for energy-economy analysis

    Energy Technology Data Exchange (ETDEWEB)

    Manne, A.S. [Stanford Univ., CA (United States); Wene, C.O. [Brookhaven National Lab., Upton, NY (United States)]|[Chalmers Univ. of Tech., Goeteborg (Sweden)

    1992-02-01

    MARKAL-MACRO is an experiment in model linkage for energy and economy analysis. This new tool is intended as an improvement over existing methods for energy strategy assessment. It is designed specifically for estimating the costs and analyzing the technologies proposed for reducing environmental risks such as global climate change or regional air pollution. The greenhouse gas debate illustrates the usefulness of linked energy-economy models. A central issue is the coupling between economic growth, the level of energy demands, and the development of an energy system to supply these demands. The debate is often connected with alternative modeling approaches. The competing philosophies may be labeled ``top-down macroeconomic`` and ``bottom-up engineering`` perspectives. MARKAL is a systems engineering (physical process) analysis built on the concept of a Reference Energy System (RES). MARKAL is solved by means of dynamic linear programming. In most applications, the end use demands are fixed, and an economically efficient solution is obtained by minimizing the present value of energy system`s costs throughout the planning horizon. MACRO is a macroeconomic model with an aggregated view of long-term economic growth. The basis input factors of production are capital, labor and individual forms of energy. MACRO is solved by nonlinear optimization.

  1. Inositol 1,4,5-Triphosphate Drives Glutamatergic and Cholinergic Inhibition Selectively in Spiny Projection Neurons in the Striatum

    OpenAIRE

    Clements, Michael A; Swapna, Immani; Morikawa, Hitoshi

    2013-01-01

    The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this stud...

  2. Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors.

    Science.gov (United States)

    Martín-García, Elena; Bourgoin, Lucie; Cathala, Adeline; Kasanetz, Fernando; Mondesir, Miguel; Gutiérrez-Rodriguez, Ana; Reguero, Leire; Fiancette, Jean-François; Grandes, Pedro; Spampinato, Umberto; Maldonado, Rafael; Piazza, Pier Vincenzo; Marsicano, Giovanni; Deroche-Gamonet, Véronique

    2016-08-01

    The type 1 cannabinoid receptor (CB1) modulates numerous neurobehavioral processes and is therefore explored as a target for the treatment of several mental and neurological diseases. However, previous studies have investigated CB1 by targeting it globally, regardless of its two main neuronal localizations on glutamatergic and GABAergic neurons. In the context of cocaine addiction this lack of selectivity is critical since glutamatergic and GABAergic neuronal transmission is involved in different aspects of the disease. To determine whether CB1 exerts different control on cocaine seeking according to its two main neuronal localizations, we used mutant mice with deleted CB1 in cortical glutamatergic neurons (Glu-CB1) or in forebrain GABAergic neurons (GABA-CB1). In Glu-CB1, gene deletion concerns the dorsal telencephalon, including neocortex, paleocortex, archicortex, hippocampal formation and the cortical portions of the amygdala. In GABA-CB1, it concerns several cortical and non-cortical areas including the dorsal striatum, nucleus accumbens, thalamic, and hypothalamic nuclei. We tested complementary components of cocaine self-administration, separating the influence of primary and conditioned effects. Mechanisms underlying each phenotype were explored using in vivo microdialysis and ex vivo electrophysiology. We show that CB1 expression in forebrain GABAergic neurons controls mouse sensitivity to cocaine, while CB1 expression in cortical glutamatergic neurons controls associative learning processes. In accordance, in the nucleus accumbens, GABA-CB1 receptors control cocaine-induced dopamine release and Glu-CB1 receptors control AMPAR/NMDAR ratio; a marker of synaptic plasticity. Our findings demonstrate a critical distinction of the altered balance of Glu-CB1 and GABA-CB1 activity that could participate in the vulnerability to cocaine abuse and addiction. Moreover, these novel insights advance our understanding of CB1 neuropathophysiology.

  3. Prenatal betamethasone does not affect glutamatergic or GABAergic neurogenesis in preterm newborns.

    Science.gov (United States)

    Vose, L R; Vinukonda, G; Diamond, D; Korumilli, R; Hu, F; Zia, M T K; Hevner, R; Ballabh, P

    2014-06-13

    Prenatal glucocorticoids (GCs) are routinely used for pregnant women in preterm labor to prevent respiratory distress syndrome and intraventricular hemorrhage in premature infants. However, the effect of antenatal GCs on neurogenesis in preterm neonates remains elusive. Herein, we hypothesized that prenatal GCs might suppress both glutamatergic and GABAergic neurogenesis in preterm rabbits and that this treatment would induce distinct changes in the expression of transcription factors regulating these developmental events. To test our hypotheses, we treated pregnant rabbits with betamethasone at E27 and E28, delivered the pups at E29 (term=32d), and assessed neurogenesis at birth and postnatal day 3. We quantified radial glia (Sox2(+)) and intermediate progenitor cells (Tbr2(+)) in the dorsal cortical subventricular zone to assess glutamatergic neuronal progenitors, and counted Nkx2.1(+) and Dlx2(+) cells in the ganglionic eminence to evaluate GABAergic neurogenesis. In addition, we assayed transcription factors regulating neurogenesis. We found that prenatal GCs did not affect the densities of radial glia and intermediate progenitors of glutamatergic or GABAergic neurons. The number of GABA(+) interneurons in the ganglionic eminence was similar between the prenatal GC-treated pups compared to untreated controls. Moreover, the mRNA expression of transcription factors, including Pax6, Ngn1/2, Emx1/2, Insm1, Dlx1, Nkx2.1, and Gsh2, were comparable between the two groups. However, there was a transient elevation in Mash1 protein in betamethasone-treated pups relative to controls at birth. These data suggest that prenatal GC treatment does not significantly impact the balance of glutamatergic and GABAergic neurogenesis in premature infants.

  4. High abundance of BDNF within glutamatergic presynapses of cultured hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Thomas eAndreska

    2014-04-01

    Full Text Available In the mammalian brain, the neurotrophin brain-derived neurotrophic factor (BDNF has emerged as a key factor for synaptic refinement, plasticity and learning. Although BDNF-induced signaling cascades are well known, the spatial aspects of the synaptic BDNF localization remained unclear. Recent data provide strong evidence for an exclusive presynaptic location and anterograde secretion of endogenous BDNF at synapses of the hippocampal circuit. In contrast, various studies using BDNF overexpression in cultured hippocampal neurons support the idea that postsynaptic synapses and other dendritic structures are the preferential sites of BDNF localization and release. In this study we used rigorously tested anti-BDNF antibodies and achieved a dense labeling of endogenous BDNF close to synapses. Confocal microscopy showed natural BDNF close to many, but not all glutamatergic synapses, while neither GABAergic synapses nor postsynaptic structures carried a typical synaptic BDNF label. To visualize the BDNF distribution within the fine structure of synapses, we implemented super resolution fluorescence imaging by direct stochastic optical reconstruction microscopy (dSTORM. Two-color dSTORM images of neurites were acquired with a spatial resolution of ~20 nm. At this resolution, the synaptic scaffold proteins Bassoon and Homer exhibit hallmarks of mature synapses and form juxtaposed bars, separated by a synaptic cleft. BDNF imaging signals form granule-like clusters with a mean size of ~60 nm and are preferentially found within the fine structure of the glutamatergic presynapse. Individual glutamatergic presynapses carried up to 90% of the synaptic BDNF immunoreactivity, and only a minor fraction of BDNF molecules was found close to the postsynaptic bars. Our data proof that hippocampal neurons are able to enrich and store high amounts of BDNF in small granules within the mature glutamatergic presynapse, at a principle site of synaptic plasticity.

  5. Salsolinol facilitates glutamatergic transmission to dopamine neurons in the posterior ventral tegmental area of rats.

    Directory of Open Access Journals (Sweden)

    Guiqin Xie

    Full Text Available Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D(1 receptors (D(1Rs. In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D(1Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D(1R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D(1Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol.

  6. Salsolinol facilitates glutamatergic transmission to dopamine neurons in the posterior ventral tegmental area of rats.

    Science.gov (United States)

    Xie, Guiqin; Ye, Jiang-Hong

    2012-01-01

    Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA) partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D(1) receptors (D(1)Rs). In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D(1)Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D(1)R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D(1)Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol.

  7. Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect.

    Science.gov (United States)

    Yuan, Kejing; Sheng, Huan; Song, Jiaojiao; Yang, Li; Cui, Dongyang; Ma, Qianqian; Zhang, Wen; Lai, Bin; Chen, Ming; Zheng, Ping

    2016-08-22

    Drug addiction is a chronic brain disorder characterized by the compulsive repeated use of drugs. The reinforcing effect of repeated use of drugs on reward plays an important role in morphine-induced addictive behaviors. The nucleus accumbens (NAc) is an important site where morphine treatment produces its reinforcing effect on reward. However, how morphine treatment produces its reinforcing effect on reward in the NAc remains to be clarified. In the present study, we studied the influence of morphine treatment on the effects of DA and observed whether morphine treatment could directly change glutamatergic synaptic transmission in the NAc. We also explored the functional significance of morphine-induced potentiation of glutamatergic synaptic transmission in the NAc at behavioral level. Our results show that (1) morphine treatment removes the inhibitory effect of DA on glutamatergic input onto NAc neurons; (2) morphine treatment potentiates glutamatergic input onto NAc neurons, especially the one from the basolateral amygdala (BLA) to the NAc; (3) blockade of glutamatergic synaptic transmission in the NAc or ablation of projection neurons from BLA to NAc significantly decreases morphine treatment-induced increase in locomotor activity. These results suggest that morphine treatment enhances glutamatergic input onto neurons of the NAc via both disinhibitory and stimulating effect and therefore increases locomotor activity.

  8. Synaptic plasticity in glutamatergic and GABAergic neurotransmission following chronic memantine treatment in an in vitro model of limbic epileptogenesis.

    Science.gov (United States)

    He, Shuijin; Bausch, Suzanne B

    2014-02-01

    Chronic N-methyl-D-aspartate receptor (NMDAR) blockade with high affinity competitive and uncompetitive antagonists can lead to seizure exacerbation, presumably due to an imbalance in glutamatergic and GABAergic transmission. Acute administration of the moderate affinity NMDAR antagonist memantine in vivo has been associated with pro- and anticonvulsive properties. Chronic treatment with memantine can exacerbate seizures. Therefore, we hypothesized that chronic memantine treatment would increase glutamatergic and decrease GABAergic transmission, similar to high affinity competitive and uncompetitive antagonists. To test this hypothesis, organotypic hippocampal slice culture were treated for 17-21 days with memantine and then subjected to electrophysiological recordings. Whole-cell recordings from dentate granule cells revealed that chronic memantine treatment slightly, but significantly increased sEPSC frequency, mEPSC amplitude and mEPSC charge transfer, consistent with minimally increased glutamatergic transmission. Chronic memantine treatment also increased both sIPSC and mIPSC frequency and amplitude, suggestive of increased GABAergic transmission. Results suggest that a simple imbalance between glutamatergic and GABAergic neurotransmission may not underlie memantine's ictogenic properties. That said, glutamatergic and GABAergic transmission were assayed independently of one another in the current study. More complex interactions between glutamatergic and GABAergic transmission may prevail under conditions of intact circuitry.

  9. Enhanced ability of TRPV1 channels in regulating glutamatergic transmission after repeated morphine exposure in the nucleus accumbens of rat.

    Science.gov (United States)

    Zhang, Haitao; Jia, Dong; Wang, Yuan; Qu, Liang; Wang, Xuelian; Song, Jian; Heng, Lijun; Gao, Guodong

    2017-04-01

    Glutamatergic projections to nucleus accumbens (NAc) drive drug-seeking behaviors during opioids withdrawal. Modulating glutamatergic neurotransmission provides a novel pharmacotherapeutic avenue for treatment of opioids dependence. Great deals of researches have verified that transient receptor potential vanilloid 1 (TRPV1) channels alters synaptic transmitter release and regulate neural plasticity. In the present study, whole-cell patch clamp recordings were adopted to examine the activity of TRPV1 Channels in regulating glutamate-mediated excitatory postsynaptic currents (EPSCs) in NAc of rat during morphine withdrawal for 3days and 3weeks. The data showed that the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and the amplitudes of evoked excitatory postsynaptic currents (eEPSCs) were increased during morphine withdrawal after applied with capsaicin (TRPV1 agonist). Capsaicin decreased the paired pulse ratio (PPR) and increased sEPSCs frequency but not their amplitudes suggesting a presynaptic locus of action during morphine withdrawal. All these effects were fully blocked by the TRPV1 antagonist Capsazepine. Additionally, In the presence of AM251 (CB1 receptor antagonist), depolarization-induced release of endogenous cannabinoids activated TRPV1 channels to enhance glutamatergic neurotransmission during morphine withdrawal. The functional enhancement of TRPV1 Channels in facilitating glutamatergic transmission was not recorded in dorsal striatum. Our findings demonstrate the ability of TRPV1 in regulating excitatory glutamatergic transmission is enhanced during morphine withdrawal in NAc, which would deepen our understanding of glutamatergic modulation during opioids withdrawal.

  10. Hypoxia-induced hypothermia mediated by the glutamatergic transmission in the lateral preoptic area.

    Science.gov (United States)

    Osaka, T

    2012-12-13

    Hypoxia evokes a regulated decrease in the body core temperature, which response is mediated, at least in part, by noradrenaline (NA) and nitric oxide (NO) in the rostromedial preoptic area (POA) of the hypothalamus. In the accompanying paper, it was shown that glutamatergic activation of the lateral POA also evokes hypothermic responses. Here, I tested the hypothesis that the glutamatergic transmission in the lateral POA is critically involved in the neural mechanism of hypoxia-induced hypothermia. Hypoxic ventilation (10% O(2)-90% N(2), 5 min) as well as a single microinjection of NA (50 pmol) or the NO donor sodium nitroprusside (8.4 nmol) into the rostromedial POA evoked an increase in the tail skin temperature and a decrease in the colonic temperature in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. All of these responses were greatly attenuated by pretreatment with multiple microinjections of kynurenic acid (10 nmol, four locations), a nonselective glutamate receptor antagonist, but not by those with saline solution, in the bilateral rostral and central parts of the lateral POA. These results suggest that the NA- and NO-sensitive structure in the rostromedial POA activated the glutamatergic transmission in the lateral POA to mediate hypoxia-induced hypothermia.

  11. The role of the glutamatergic system in the patogenesis and treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Karina Łukasik

    2010-10-01

    Full Text Available The lack of satisfactory results of alcohol dependence treatment has necessitated the search for new directions of studies. One of them is connected with glutamatergic transmission. The influence of alcohol on this transmission is very complex and relates to changes including at the molecular level. However, the diversity of glutamatergic receptors creates a new possibility of modulation of its activity. It leads to decrease of alcohol reward abilities, prolongs abstinence time and reduces the incidence of acute alcohol intoxication in alcohol addicts. The use of acamprosate – a glutamatergic transmission modulator drug – and naltrexone (an opioid receptor antagonist improves therapy effectiveness of acamprosate alone. Satisfactory results were achieved in the studies of topiramate – an antagonist of AMPA and KA receptors. Its effectiveness was proved in clinical studies. Topiramate reduced alcohol craving and prolonged abstinence time, which decreased the probability of relapse. There are promising preclinical results of groups I and II metabotropic receptor antagonists. However, further studies are necessary to elucidate precisely their role in alcohol dependence.

  12. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

    Science.gov (United States)

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

    2016-07-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.

  13. M4 mAChR-mediated modulation of glutamatergic transmission at corticostriatal synapses.

    Science.gov (United States)

    Pancani, Tristano; Bolarinwa, Caroline; Smith, Yoland; Lindsley, Craig W; Conn, P Jeffrey; Xiang, Zixiu

    2014-04-16

    The striatum is the main input station of the basal ganglia and is extensively involved in the modulation of motivated behavior. The information conveyed to this subcortical structure through glutamatergic projections from the cerebral cortex and thalamus is processed by the activity of several striatal neuromodulatory systems including the cholinergic system. Acetylcholine potently modulates glutamate signaling in the striatum via activation of muscarinic receptors (mAChRs). It is, however, unclear which mAChR subtype is responsible for this modulatory effect. Here, by using electrophysiological, optogenetic, and immunoelectron microscopic approaches in conjunction with a novel, highly selective M4 positive allosteric modulator VU0152100 (ML108) and M4 knockout mice, we show that M4 is a major mAChR subtype mediating the cholinergic inhibition of corticostriatal glutamatergic input on both striatonigral and striatopallidal medium spiny neurons (MSNs). This effect is due to activation of presynaptic M4 receptors, which, in turn, leads to a decrease in glutamate release from corticostriatal terminals. The findings of the present study raise the interesting possibility that M4 mAChR could be a novel therapeutic target for the treatment of neurological and neuropsychiatric disorders involving hyper-glutamatergic transmission at corticostriatal synapses.

  14. Upregulation of glutamatergic transmission in anterior cingulate cortex in the diabetic rats with neuropathic pain.

    Science.gov (United States)

    Li, Weifang; Wang, Peng; Li, Hua

    2014-05-07

    Peripheral neuropathic pain is a common complication in the diabetic patients, and the underlying central mechanism remains unclear. Forebrain anterior cingulate cortex (ACC) is critically involved in the supraspinal perception of physical and affective components of noxious stimulus and pain modulation. Excitatory glutamatergic transmission in the ACC extensively contributed to the maintenance of negative affective component of chronic pain. The present study examined the adaptation of glutamatergic transmission in the ACC in rats with diabetic neuropathic pain. Injection with streptozotocin (STZ) induced hyperglycemia, thermal hyperalgesia and mechanical allodynia in the rats. In these rats, significant enhanced basal glutamatergic transmission was observed in the ACC neurons. The increased presynaptic glutamate release and enhanced conductance of postsynaptic glutamate receptors were also observed in the ACC neurons of these modeled rats. Increased phosphorylation of PKMζ, but not the expression of total PKMζ, was also observed in the ACC. Microinjection of PKMζ inhibitor ZIP into ACC attenuated the upregulation of glutamate transmission and painful behaviors in STZ-injected rats. These results revealed a substantial central sensitization in the ACC neurons in the rodents with diabetic neuropathic pain, which may partially underlie the negative affective components of patients with diabetic neuropathic pain.

  15. Effects of Etomidate on GABAergic and Glutamatergic Transmission in Rat Thalamocortical Slices.

    Science.gov (United States)

    Fu, Bao; Wang, Yuan; Yang, Hao; Yu, Tian

    2016-12-01

    Although accumulative evidence indicates that the thalamocortical system is an important target for general anesthetics, the underlying mechanisms of anesthetic action on thalamocortical neurotransmission are not fully understood. The aim of the study is to explore the action of etomidate on glutamatergic and GABAergic transmission in rat thalamocortical slices by using whole cell patch-clamp recording. We found that etomidate mainly prolonged the decay time of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs), without changing the frequency. Furthermore, etomidate not only prolonged the decay time of miniature inhibitory postsynaptic currents (mIPSCs) but also increased the amplitude. On the other hand, etomidate significantly decreased the frequency of spontaneous glutamatergic excitatory postsynaptic currents (sEPSCs), without altering the amplitude or decay time in the absence of bicuculline. When GABAA receptors were blocked using bicuculline, the effects of etomidate on sEPSCs were mostly eliminated. These results suggest that etomidate enhances GABAergic transmission mainly through postsynaptic mechanism in thalamocortical neuronal network. Etomidate attenuates glutamatergic transmission predominantly through presynaptic action and requires presynaptic GABAA receptors involvement.

  16. Baicalein ameliorated the upregulation of striatal glutamatergic transmission in the mice model of Parkinson's disease.

    Science.gov (United States)

    Xue, Xinhong; Liu, Hong; Qi, Lifeng; Li, Xueli; Guo, Cunju; Gong, Dianrong; Qu, Huaiqian

    2014-04-01

    Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by a loss of projecting dopaminergic neurons in the substantia nigra and diminished dopamine level in the striatum. Dopaminergic deficit consequently leads to the alterations of striatal basal glutamatergic synaptic transmission and plasticity in the medium spiny neurons. The cytokines and neurotoxins released from the reactive immune cells induced the loss of the projecting dopaminergic neurons in the substantia nigra, which triggering the pathogenesis of PD. The present study investigated the effect of treatment with baicalein (5,6,7-trihydroxyflavone) on the central cytokine synthesis, striatal glutamatergic transmission, and behavioral performance in the rotarod task in the mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with baicalein significantly attenuated the upregulation of striatal basal glutamatergic strength by decreasing the presynaptic glutamate release and recovering the insertion of postsynaptic glutamate receptor subunit GluR1 induced by MPTP. It also significantly improved the behavioral performance in the rotarod task in the mice injected with MPTP. Treatment with baicalein decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1β) in the substantia nigra and striatum in the mice injected with MPTP. These results indicated that baicalein might serve as novel approach for the treatment of the patients with PD.

  17. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition.

    Science.gov (United States)

    Wei, J; Yuen, E Y; Liu, W; Li, X; Zhong, P; Karatsoreos, I N; McEwen, B S; Yan, Z

    2014-05-01

    Converging evidence suggests that females and males show different responses to stress; however, little is known about the mechanism underlying the sexually dimorphic effects of stress. In this study, we found that young female rats exposed to 1 week of repeated restraint stress show no negative effects on temporal order recognition memory (TORM), a cognitive process controlled by the prefrontal cortex (PFC), which was contrary to the impairment in TORM observed in stressed males. Concomitantly, normal glutamatergic transmission and glutamate receptor surface expression in PFC pyramidal neurons were found in repeatedly stressed females, in contrast to the significant reduction seen in stressed males. The detrimental effects of repeated stress on TORM and glutamate receptors were unmasked in stressed females when estrogen receptors were inhibited or knocked down in PFC, and were prevented in stressed males with the administration of estradiol. Blocking aromatase, the enzyme for the biosynthesis of estrogen, revealed the stress-induced glutamatergic deficits and memory impairment in females, and the level of aromatase was significantly higher in the PFC of females than in males. These results suggest that estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and PFC-dependent cognition, which may underlie the stress resilience of females.

  18. Linking dynamic phenotyping with metabolite analysis to study natural variation in drought responses of Brachypodium distachyon

    Directory of Open Access Journals (Sweden)

    Lorraine H.C. Fisher

    2016-11-01

    Full Text Available Drought is an important environmental stress limiting the productivity of major crops worldwide. Understanding drought tolerance and possible mechanisms for improving drought resistance is therefore a prerequisite to develop drought-tolerant crops that produce significant yields with reduced amounts of water. Brachypodium distachyon (Brachypodium is a key model species for cereals, forage grasses and energy grasses. In this study, initial screening of a Brachypodium germplasm collection consisting of 138 different ecotypes exposed to progressive drought, highlighted the natural variation in morphology, biomass accumulation and responses to drought stress. A core set of ten ecotypes, classified as being either tolerant, susceptible or intermediate, in response to drought stress, were exposed to mild or severe (respectively 15% and 0% soil water content drought stress and phenomic parameters linked to growth and colour changes were assessed. When exposed to severe drought stress, phenotypic data and metabolite profiling combined with multivariate analysis revealed a remarkable consistency in separating the selected ecotypes into their different pre-defined drought tolerance groups. Increases in several metabolites, including for the phytohormones jasmonic acid and salicylic acid, and TCA-cycle intermediates, were positively correlated with biomass yield and with reduced yellow pixel counts; suggestive of delayed senescence, both key target traits for crop improvement to drought stress. While metabolite analysis also separated ecotypes into the distinct tolerance groupings after exposure to mild drought stress, similar analysis of the phenotypic data failed to do so, confirming the value of metabolomics to investigate early responses to drought stress. The results highlight the potential of combining the analyses of phenotypic and metabolic responses to identify key mechanisms and markers associated with drought tolerance in both the Brachypodium

  19. Analysis of protein-nucleic acid interactions by photochemical cross-linking and mass spectrometry

    DEFF Research Database (Denmark)

    Steen, Hanno; Jensen, Ole Nørregaard

    2002-01-01

    Photochemical cross-linking is a commonly used method for studying the molecular details of protein-nucleic acid interactions. Photochemical cross-linking aids in defining nucleic acid binding sites of proteins via subsequent identification of cross-linked protein domains and amino acid residues....... Mass spectrometry (MS) has emerged as a sensitive and efficient analytical technique for determination of such cross-linking sites in proteins. The present review of the field describes a number of MS-based approaches for the characterization of cross-linked protein-nucleic acid complexes...... and for sequencing of peptide-nucleic acid heteroconjugates. The combination of photochemical cross-linking and MS provides a fast screening method to gain insights into the overall structure and formation of protein-oligonucleotide complexes. Because the analytical methods are continuously refined and protein...

  20. ANALYSIS OF EXCHANGE RATE LINKED SUBSIDIES FOR NON-PRICE EXPORT PROMOTION: THE CASE OF COTTON

    OpenAIRE

    Paudel, Laxmi; Adhikari, Murali; Houston, Jack E.; Kinnucan, Henry W.

    2002-01-01

    An equilibrium displacement framework was developed to evaluate the effect of exchange rate linked subsidies for non-price export promotion for US cotton. Study results show that an increase in promotion expenditure increased the dollar value and producer welfare of cotton growers. The gross gain to the domestic cotton producers from the exchange-rate linked subsidy scheme was positive. These evidences support exchange rate linked subsidies for US cotton export promotion.

  1. Transcriptional evidence for the role of chronic venlafaxine treatment in neurotrophic signaling and neuroplasticity including also Glutamatergic [corrected] - and insulin-mediated neuronal processes.

    Directory of Open Access Journals (Sweden)

    Viola Tamási

    Full Text Available Venlafaxine (VLX, a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD. Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration.Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment.Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2. Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3, glutamatergic transmission (Gria3, Grin2b and Grin2a, neuroplasticity (Camk2g/b, Cd47, synaptogenesis (Epha5a, Gad2 and cognitive processes (Clstn2. Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1. Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1, a mechanism that has recently been linked to neuroprotection, learning and memory.Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in

  2. An Exploratory Study of Spectroscopic Glutamatergic Correlates of Cortical Excitability in Depressed Adolescents

    Directory of Open Access Journals (Sweden)

    Charles P. Lewis

    2016-11-01

    Full Text Available Introduction: Transcranial magnetic stimulation (TMS research has suggested dysfunction in cortical glutamatergic systems in depression, while proton magnetic resonance spectroscopy (1H-MRS studies have demonstrated deficits in concentrations of glutamatergic metabolites in depressed individuals in several cortical regions, including the anterior cingulate cortex (ACC. However, few studies have combined TMS and MRS methods to examine relationships between glutamatergic neurochemistry and excitatory and inhibitory neural functions, and none have utilized TMS-MRS methodology in clinical populations or in youth. This exploratory study aimed to examine relationships between TMS measures of cortical excitability and inhibition and concentrations of glutamatergic metabolites as measured by 1H-MRS in depressed adolescents. Methods: Twenty-four children and adolescents (aged 11-18 years with depressive symptoms underwent TMS testing, which included measures of the resting motor threshold (RMT, cortical silent period (CSP, short-interval intracortical inhibition (SICI, and intracortical facilitation (ICF. Fourteen participants from the same sample also completed 1H-MRS in a 3 T MRI scanner after TMS testing. Glutamate + glutamine (Glx concentrations were measured in medial ACC and left primary motor cortex voxels with a TE-optimized PRESS sequence. Metabolite concentrations were corrected for cerebrospinal fluid after tissue segmentation. Pearson product-moment and Spearman rank-order correlations were calculated to assess relationships between TMS measures and Glx. Results: In the left primary motor cortex voxel, Glx had a significant positive correlation with the RMT. In the medial ACC voxel, Glx had significant positive correlations with ICF at the 10-ms and 20-ms ISIs.Conclusions: These preliminary data implicate glutamate in cortical excitatory processes measured by TMS. Limitations included small sample size, lack of healthy control comparators

  3. A multi-platform linking code for fuel burnup and radiotoxicity analysis

    Science.gov (United States)

    Cunha, R.; Pereira, C.; Veloso, M. A. F.; Cardoso, F.; Costa, A. L.

    2014-02-01

    A linking code between ORIGEN2.1 and MCNP has been developed at the Departamento de Engenharia Nuclear/UFMG to calculate coupled neutronic/isotopic results for nuclear systems and to produce a large number of criticality, burnup and radiotoxicity results. In its previous version, it evaluated the isotopic composition evolution in a Heat Pipe Power System model as well as the radiotoxicity and radioactivity during lifetime cycles. In the new version, the code presents features such as multi-platform execution and automatic results analysis. Improvements made in the code allow it to perform simulations in a simpler and faster way without compromising accuracy. Initially, the code generates a new input for MCNP based on the decisions of the user. After that, MCNP is run and data, such as recoverable energy per prompt fission neutron, reaction rates and keff, are automatically extracted from the output and used to calculate neutron flux and cross sections. These data are then used to construct new ORIGEN inputs, one for each cell in the core. Each new input is run on ORIGEN and generates outputs that represent the complete isotopic composition of the core on that time step. The results show good agreement between GB (Coupled Neutronic/Isotopic code) and Monteburns (Automated, Multi-Step Monte Carlo Burnup Code System), developed by the Los Alamos National Laboratory.

  4. Genetic mapping of X-linked ocular albinism: Linkage analysis in a large Newfoundland kindred

    Energy Technology Data Exchange (ETDEWEB)

    Charles, S.J.; Moore, A.T.; Barton, D.E.; Yates, J.R.W. (Addenbrooke' s Hospital, Cambridge (United Kingdom)); Green, J.S. (Memorial Univ. of Newfoundland, St. John' s (Canada))

    1993-04-01

    Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Z[sub max] = 21.96 at [theta] = 0.01, confidence interval (CI) 0.0005--0.05) and linkage to DXS85 (782; Z[sub max] = 17.60 at [theta] = 0.07, CI = 0.03--0.13) and DXS237 (GMGX9; Z[sub max] = 15.20 at [theta] = 0.08, CI = 0.03--0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10[sup 10]:1 over other locations for the disease locus. 11 refs., 1 fig., 1 tab.

  5. Further Developments in the Communication Link and Error Analysis (CLEAN) Simulator

    Science.gov (United States)

    Ebel, William J.; Ingels, Frank M.

    1995-01-01

    During the period 1 July 1993 - 30 June 1994, significant developments to the Communication Link and Error ANalysis (CLEAN) simulator were completed. Many of these were reported in the Semi-Annual report dated December 1993 which has been included in this report in Appendix A. Since December 1993, a number of additional modules have been added involving Unit-Memory Convolutional codes (UMC). These are: (1) Unit-Memory Convolutional Encoder module (UMCEncd); (2) Hard decision Unit-Memory Convolutional Decoder using the Viterbi decoding algorithm (VitUMC); and (3) a number of utility modules designed to investigate the performance of LTMC's such as LTMC column distance function (UMCdc), UMC free distance function (UMCdfree), UMC row distance function (UMCdr), and UMC Transformation (UMCTrans). The study of UMC's was driven, in part, by the desire to investigate high-rate convolutional codes which are better suited as inner codes for a concatenated coding scheme. A number of high-rate LTMC's were found which are good candidates for inner codes. Besides the further developments of the simulation, a study was performed to construct a table of the best known Unit-Memory Convolutional codes. Finally, a preliminary study of the usefulness of the Periodic Convolutional Interleaver (PCI) was completed and documented in a Technical note dated March 17, 1994. This technical note has also been included in this final report.

  6. Corneal collagen cross-linking in keratoconus: A systematic review and meta-analysis

    Science.gov (United States)

    Chunyu, Tian; Xiujun, Peng; Zhengjun, Fan; Xia, Zhang; Feihu, Zhou

    2014-01-01

    The aim of this study was to determine the effectiveness of corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus (KC). Some of the published literature, including a few small, randomized controlled trials (RCTs), demonstrated good results after CXL, but large RCTs with long-term follow-up to establish a cause-effect relationship are lacking. Using PubMed, EMBASE, and the Cochrane Library database, we searched for relevant studies published between October 2007 and March 2014. A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify the effectiveness of CXL for treating KC. The primary outcome parameters included uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refraction, corneal topography, and corneal thickness at baseline and at 1, 3, 6, 12, and 18 months after CXL. A total of 1171 participants (1557 eyes) were enrolled in this meta-analysis. CXL may be effective in halting the progress of KC for at least 12 months under certain conditions. However, further research from randomized trials is needed to confirm our findings. PMID:25007895

  7. MALDI analysis of proteins after extraction from dissolvable ethylene glycol diacrylate cross-linked polyacrylamide gels.

    Science.gov (United States)

    Papasotiriou, Dimitrios G; Markoutsa, Stavroula; Gorka, Jan; Schleiff, Enrico; Karas, Michael; Meyer, Bjoern

    2013-09-01

    Although the extraction of intact proteins from polyacrylamide gels followed by mass spectrometric molecular mass determination has been shown to be efficient, there is room for alternative approaches. Our study evaluates ethylene glycol diacrylate, a cleavable cross-linking agent used for a new type of dissolvable gels. It attains an ester linkage that can be hydrolyzed in alkali conditions. The separation performance of the new gel system was tested by 1D and 2D SDS-PAGE using the outer chloroplast envelope of Pisum sativum as well as a soluble protein fraction of human lymphocytes, respectively. Gel spot staining (CBB), dissolving, and extracting were conducted using a custom-developed workflow. It includes protein extraction with an ammonia-SDS buffer followed by methanol treatment to remove acrylamide filaments. Necessary purification for MALDI-TOF analysis was implemented using methanol-chloroform precipitation and perfusion HPLC. Both cleaning procedures were applied to several standard proteins of different molecular weight as well as 'real' biological samples (8-75 kDa). The protein amounts, which had to be loaded on the gel to detect a peak in MALDI-TOF MS, were in the range of 0.1 to 5 μg, and the required amount increased with increasing mass.

  8. Analysis of voltage modulation based active damping techniques for small DC-link drive system

    DEFF Research Database (Denmark)

    Wang, Dong; Lu, Kaiyuan; Rasmussen, Peter Omand;

    2015-01-01

    Small DC-link drive system, built with film capacitor in the DC link, may have the advantages of longer lifetime and the possibility to achieve a more compact design of capacitor bank at medium and high power rates. However, it exhibits instability problem, especially when it is fed by a soft grid...

  9. Multilayer interparticle linking hybrid MOF-199 for noninvasive enrichment and analysis of plant hormone ethylene.

    Science.gov (United States)

    Zhang, Zhuomin; Huang, Yichun; Ding, Weiwei; Li, Gongke

    2014-04-01

    Ethylene, an important plant hormone, is of utmost importance during many developmental processes of plants. However, the efficient enrichment and analysis of trace ethylene still remains a challenge. A simple and mild multilayer interparticle linking strategy was proposed to fabricate a novel hybrid MOF-199 enrichment coating. Strong chemical interparticle linkages throughout the coating improved the durability and reproducibility of hybrid MOF-199 coating dramatically. This coating performed a significant extraction superiority of ethylene over commonly used commercial coatings, attributed to the multiple interactions including "molecular sieving effect", hydrogen bonding, open metal site interaction, and π-π affinity. The hybridization of multiwalled carbon nanotubes (MWCNTs) with MOF-199 further improved the enrichment capability and also acted as a hydrophobic "shield" to prevent the open metal sites of MOF-199 from being occupied by water molecules, which effectively improved the moisture-resistant property of MOF-199/CNTs coating. Finally, this novel enrichment method was successfully applied for the noninvasive analysis of trace ethylene, methanol, and ethanol from fruit samples with relatively high humidity. The low detection limit was 0.016 μg/L for ethylene. It was satisfactory that trace ethylene could be actually detected from fruit samples by this noninvasive method. Good recoveries of spiked grape, wampee, blueberry, and durian husk samples were obtained in the range of 90.0-114%, 79.4-88.6%, 78.5-86.8%, and 85.2-105% with the corresponding relative standard deviations of 4.8-9.8%, 6.9-8.9%, 3.8-8.1%, and 9.3-10.5% (n = 3), respectively.

  10. Linking cases of illegal shootings of the endangered California condor using stable lead isotope analysis

    Energy Technology Data Exchange (ETDEWEB)

    Finkelstein, Myra E., E-mail: myraf@ucsc.edu [Microbiology and Environmental Toxicology Department, University of California, Santa Cruz, CA 95064 (United States); Kuspa, Zeka E. [Microbiology and Environmental Toxicology Department, University of California, Santa Cruz, CA 95064 (United States); Welch, Alacia [National Park Service, Pinnacles National Park, 5000 Highway 146, Paicines, CA 95043 (United States); Eng, Curtis; Clark, Michael [Los Angeles Zoo and Botanical Gardens, 5333 Zoo Drive, Los Angeles, CA 90027 (United States); Burnett, Joseph [Ventana Wildlife Society, 19045 Portola Dr. Ste. F-1, Salinas, CA 93908 (United States); Smith, Donald R. [Microbiology and Environmental Toxicology Department, University of California, Santa Cruz, CA 95064 (United States)

    2014-10-15

    Lead poisoning is preventing the recovery of the critically endangered California condor (Gymnogyps californianus) and lead isotope analyses have demonstrated that ingestion of spent lead ammunition is the principal source of lead poisoning in condors. Over an 8 month period in 2009, three lead-poisoned condors were independently presented with birdshot embedded in their tissues, evidencing they had been shot. No information connecting these illegal shooting events existed and the timing of the shooting(s) was unknown. Using lead concentration and stable lead isotope analyses of feathers, blood, and recovered birdshot, we observed that: i) lead isotope ratios of embedded shot from all three birds were measurably indistinguishable from each other, suggesting a common source; ii) lead exposure histories re-constructed from feather analysis suggested that the shooting(s) occurred within the same timeframe; and iii) two of the three condors were lead poisoned from a lead source isotopically indistinguishable from the embedded birdshot, implicating ingestion of this type of birdshot as the source of poisoning. One of the condors was subsequently lead poisoned the following year from ingestion of a lead buckshot (blood lead 556 µg/dL), illustrating that ingested shot possess a substantially greater lead poisoning risk compared to embedded shot retained in tissue (blood lead ∼20 µg/dL). To our knowledge, this is the first study to use lead isotopes as a tool to retrospectively link wildlife shooting events. - Highlights: • We conducted a case-based analysis of illegal shootings of California condors. • Blood and feather Pb isotopes were used to reconstruct the illegal shooting events. • Embedded birdshot from the three condors had the same Pb isotope ratios. • Feather and blood Pb isotopes indicated that the condors were shot in a common event. • Ingested shot causes substantially greater lead exposure compared to embedded shot.

  11. Monoclonal Antibody-Based Enzyme Linked Immunosorbent Assay for the Analysis of Jasmonates in Plants

    Institute of Scientific and Technical Information of China (English)

    Aixing Deng; Weiming Tan; Suping He; Wei Liu; Tiegui Nan; Zhaohu Li; Baomin Wang; Qing X.Li

    2008-01-01

    Methyl jasmonate (MeJA) and its free-acid form,jasmonic acid (JA) are naturally occurring plant growth regulators widely distributed in higher plants.In order to improve the sensitivity for the analysis of MeJA at low levels in small amounts of plant samples,a monoclonal antibody (MAb) (designated as MAb 3E5D7C4B6) against MeJA was derived from a JAbovine serum albumin (BSA) conjugate as an immunogen.The antibody belongs to the IgG1 subclass with a κ type light chain and has a dissociation constant of approximately 6.07 x 10-9 M.MAb3E5D7C4B6 is very specific to MeJA.It was used to develop a direct competitive enzyme-linked immunosorbent assay (dcELISA),conventional and simplified indirect competitive ELISAs (icELISA).JA was derivatized into MeJA for the ELISA analysis.The IC50 value and detection range for MeJA were,respectively,34 and 4-257 ng/mL by the conventional icELISA,21 and 3-226 ng/mL by the simplified icELISA and 5.0 and 0.7-97.0 ng/mL by the dcELISA.The dcELISA was more sensitive than either the conventional or simplified icELISA.The assays were used to measure the content of jasmonates as MeJA in tobacco leaves under drought stress or inoculated with tobacco mosaic virus and tomato leaves inoculated with tomato mosaic virus or Lirioinyza sativae Blanchard as compared with the corresponding healthy leaves.The increased jasmonates content indicated its role in response to the drought stress and pathogens.

  12. Analytical and Experimental Analysis of a Free Link in Contact with a Granular Medium

    Directory of Open Access Journals (Sweden)

    Dan B. Marghitu

    2013-01-01

    Full Text Available In this study, the experimental and the simulation results for a planar free link impacting a granular medium are analyzed. The resistance force of the granular medium on the body from the moment of the impact until the body stops is very important. Horizontal and vertical static resistance forces developed by theoretical and empirical approaches are considered. The penetrating depth of the impacting end of the free link increases with the increase of the initial impacting velocity. We define the stopping time as the time interval from the moment of impact until the vertical velocity of the link end is zero. The stopping time of the end decreases as the initial velocity increases. The faster the end of the link impacts the surface of the granular medium, the sooner it will come to a stop. This phenomenon involves how rapidly a free link strikes the granular medium and how it slows down upon contact.

  13. An analysis of single-index model with monotonic link function

    Institute of Scientific and Technical Information of China (English)

    ZHU Li-ping; YANG Xiao-yan; YU Zhou; LIU Xiang-rong

    2008-01-01

    The single-index model with monotonic link function is investigated. Firstly,it is showed that the link function h(·) can be viewed by a graphic method. That is,the plot with the fitted response y on the horizontal axis and the observed y on the vertical axis can be used to visualize the link function. It is pointed out that this graphic approach is also applicable even when the link function is not monotonic. Note that many existing nonparametric smoothers can also be used to assess h(·). Therefore,the I-spline approximation of the link function via maximizing the covariance function with a penalty function is investigated in the present work.The consistency of the criterion is constructed. A small simulation is carried out to evidence the efficiency of the approach proposed in the paper.

  14. Dissociation of CA3 pyramidal cells with attached, functional, identified mossy fiber and interneuronal boutons for studying glutamatergic and GABAergic synaptic transmission.

    Science.gov (United States)

    Beltrán, Jesús Q; Reyes, Sebastián; Pérez-Guzmán, José A; Elías-Viñas, David; Gutiérrez, Rafael

    2012-07-15

    Pyramidal cells of CA3 area receive glutamatergic signals from the mossy fibers (MFs), perforant path and collaterals of other pyramidal cells, as well as GABAergic inputs from interneurons. In hippocampal slices, an extracellular stimulation electrode is often used to activate the MFs, with the disadvantage of possibly activating fibers other than MFs. We set-up a preparation that allows the analysis of the glutamatergic input from identified, giant MF boutons as well as of GABAergic inputs from boutons of interneurons on single CA3 pyramidal cells. Mossy fiber boutons were labeled by exposing hippocampal slices to a zinc-reactive fluorescent dye, or by injecting a fluorescent dye in the granule cell layer and allowing its transport along the MFs to their terminals in CA3 area. After conducting an enzyme-free, mechanical dissociation of CA3 area, we obtained pyramidal cells containing fluorescent, giant MF boutons attached to their apical dendrites, as well as boutons of interneuronal origin. Whole cell recordings were then performed, whereby synaptic responses could be evoked by selective stimulation of the identified boutons. The synaptic currents evoked by stimulation of MF boutons, unlike those evoked by stimulation of interneuronal boutons, underwent strong frequency potentiation and were depressed by activation of metabotropic glutamate receptors, which are characteristics of transmission of MF origin. Combination of fluorophores can be used to label different tracts/boutons allowing the study of the different characteristics of neurotransmitter release from a variety of sources on single target cells.

  15. The establishment of GABAergic and glutamatergic synapses on CA1 pyramidal neurons is sequential and correlates with the development of the apical dendrite.

    Science.gov (United States)

    Tyzio, R; Represa, A; Jorquera, I; Ben-Ari, Y; Gozlan, H; Aniksztejn, L

    1999-12-01

    We have performed a morphofunctional analysis of CA1 pyramidal neurons at birth to examine the sequence of formation of GABAergic and glutamatergic postsynaptic currents (PSCs) and to determine their relation to the dendritic arborization of pyramidal neurons. We report that at birth pyramidal neurons are heterogeneous. Three stages of development can be identified: (1) the majority of the neurons (80%) have small somata, an anlage of apical dendrite, and neither spontaneous nor evoked PSCs; (2) 10% of the neurons have a small apical dendrite restricted to the stratum radiatum and PSCs mediated only by GABA(A) receptors; and (3) 10% of the neurons have an apical dendrite that reaches the stratum lacunosum moleculare and PSCs mediated both by GABA(A) and glutamate receptors. These three groups of pyramidal neurons can be differentiated by their capacitance (C(m) = 17.9 +/- 0.8; 30.2 +/- 1.6; 43.2 +/- 3.0 pF, respectively). At birth, the synaptic markers synapsin-1 and synaptophysin labeling are present in dendritic layers but not in the stratum pyramidale, suggesting that GABAergic peridendritic synapses are established before perisomatic ones. The present observations demonstrate that GABAergic and glutamatergic synapses are established sequentially with GABAergic synapses being established first most likely on the apical dendrites of the principal neurons. We propose that different sets of conditions are required for the establishment of functional GABA and glutamate synapses, the latter necessitating more developed neurons that have apical dendrites that reach the lacunosum moleculare region.

  16. DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling.

    Science.gov (United States)

    Martin, P-M; Stanley, R E; Ross, A P; Freitas, A E; Moyer, C E; Brumback, A C; Iafrati, J; Stapornwongkul, K S; Dominguez, S; Kivimäe, S; Mulligan, K A; Pirooznia, M; McCombie, W R; Potash, J B; Zandi, P P; Purcell, S M; Sanders, S J; Zuo, Y; Sohal, V S; Cheyette, B N R

    2016-10-18

    Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/β-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/β-catenin pathway.Molecular Psychiatry advance online publication, 18 October 2016; doi:10.1038/mp.2016.184.

  17. DNA interstrand cross-links of an antitumor trinuclear platinum(II) complex: thermodynamic analysis and chemical probing.

    Science.gov (United States)

    Malina, Jaroslav; Farrell, Nicholas P; Brabec, Viktor

    2011-06-06

    The trinuclear platinum compound [{trans-PtCl(NH(3))(2)}(2)(μ-trans-Pt(NH(3))(2){NH(2)(CH(2))(6)NH(2)}(2))](4+) (BBR3464) belongs to the polynuclear class of platinum-based anticancer agents. These agents form in DNA long-range (Pt,Pt) interstrand cross-links, whose role in the antitumor effects of BBR3464 predominates. Our results show for the first time that the interstrand cross-links formed by BBR3464 between two guanine bases in opposite strands separated by two base pairs (1,4-interstrand cross-links) exist as two distinct conformers, which are not interconvertible, not only if these cross-links are formed in the 5'-5', but also in the less-usual 3'-3' direction. Analysis of the conformers by differential scanning calorimetry, chemical probes of DNA conformation, and minor groove binder Hoechst 33258 demonstrate that each of the four conformers affects DNA in a distinctly different way and adopts a different conformation. The results also support the thesis that the molecule of antitumor BBR3464 when forming DNA interstrand cross-links may adopt different global structures, including different configurations of the linker chain of BBR3464 in the minor groove of DNA. Our findings suggest that the multiple DNA interstrand cross-links available to BBR3464 may all contribute substantially to its cytotoxicity.

  18. Web Service Based Approach to Link Heterogeneous Climate-Energy-Economy Models for Climate Change Mitigation Analysis

    NARCIS (Netherlands)

    Belete, Getachew F.; Voinov, Alexey; Bulavskaya, Tatyana; Niamir, Leila; Dhavala, Kishore

    2016-01-01

    Climate change mitigation analysis requires understanding the causes and identifying the possible alternative actions that could be taken. We linked heterogeneous models that focus on climate, energy, and economy for the purpose of climate change mitigation. The models were originally developed to s

  19. Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Deschenes, S.M.; Puck, J.M.; Dutra, A.S. [Univ. of Pennsylvania School of Medicine and Children`s Hospital of Philadelphia, PA (United States)] [and others

    1994-09-01

    Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly (TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly (CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the {gamma} chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification. 35 refs., 4 figs., 1 tab.

  20. Vibro-acoustic modelling of aircraft double-walls with structural links using Statistical Energy Analysis

    Science.gov (United States)

    Campolina, Bruno L.

    The prediction of aircraft interior noise involves the vibroacoustic modelling of the fuselage with noise control treatments. This structure is composed of a stiffened metallic or composite panel, lined with a thermal and acoustic insulation layer (glass wool), and structurally connected via vibration isolators to a commercial lining panel (trim). The goal of this work aims at tailoring the noise control treatments taking design constraints such as weight and space optimization into account. For this purpose, a representative aircraft double-wall is modelled using the Statistical Energy Analysis (SEA) method. Laboratory excitations such as diffuse acoustic field and point force are addressed and trends are derived for applications under in-flight conditions, considering turbulent boundary layer excitation. The effect of the porous layer compression is firstly addressed. In aeronautical applications, compression can result from the installation of equipment and cables. It is studied analytically and experimentally, using a single panel and a fibrous uniformly compressed over 100% of its surface. When compression increases, a degradation of the transmission loss up to 5 dB for a 50% compression of the porous thickness is observed mainly in the mid-frequency range (around 800 Hz). However, for realistic cases, the effect should be reduced since the compression rate is lower and compression occurs locally. Then the transmission through structural connections between panels is addressed using a four-pole approach that links the force-velocity pair at each side of the connection. The modelling integrates experimental dynamic stiffness of isolators, derived using an adapted test rig. The structural transmission is then experimentally validated and included in the double-wall SEA model as an equivalent coupling loss factor (CLF) between panels. The tested structures being flat, only axial transmission is addressed. Finally, the dominant sound transmission paths are

  1. Forward-Link Performance Analysis in CDMA Distributed Antenna Systems with Imperfect Channel Estimation

    Institute of Scientific and Technical Information of China (English)

    CHEN Peng; WU Wei-ling

    2005-01-01

    The impact of imperfect channel estimation on the forward-link performance in CDMA distributed antenna systems in multi-path fading environment is investigated.A detailed analytical model based on a hybrid signal combining method is presented and exact outage probability expression is derived.The investigation shows that the effect of imperfect channel estimates varies with system load.Furthermore,if simulcasting is employed,macro-diversity can decrease the sensitivity of forward-link to channel estimation errors and increase the forward-link outage performance,which is contrary to the conclusion drawn based on the ideal channel estimation assumption.

  2. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes.

    Directory of Open Access Journals (Sweden)

    Peter Hevezi

    Full Text Available Efforts to unravel the mechanisms underlying taste sensation (gustation have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM procured fungiform (FG and circumvallate (CV taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology.

  3. Frames as visual links between paintings and the museum environment: An analysis of statistical image properties

    Directory of Open Access Journals (Sweden)

    Christoph eRedies

    2013-11-01

    Full Text Available Frames provide a visual link between artworks and their surround. We asked how image properties change as an observer zooms out from viewing a painting alone, to viewing the painting with its frame and, finally, the framed painting in its museum environment (museum scene. To address this question, we determined three higher-order image properties that are based on histograms of oriented luminance gradients. First, complexity was measured as the sum of the strengths of all gradients in the image. Second, we determined the self-similarity of histograms of the orientated gradients at different levels of spatial analysis. Third, we analyzed how much gradient strength varied across orientations (anisotropy. Results were obtained for three art museums that exhibited paintings from three major periods of Western art. In all three museums, the mean complexity of the frames was higher than that of the paintings or the museum scenes. Frames thus provide a barrier of complexity between the paintings and their exterior. By contrast, self-similarity and anisotropy values of images of framed paintings were intermediate between the images of the paintings and the museum scenes, i.e., the frames provided a transition between the paintings and their surround. We also observed differences between the three museums that may reflect modified frame usage in different art periods. For example, frames in the museum for 20th century art tended to be smaller and less complex than in the two other two museums that exhibit paintings from earlier art periods (13th-18th century and 19th century, respectively. Finally, we found that the three properties did not depend on the type of reproduction of the paintings (photographs in museums, scans from books or images from the Google Art Project. To the best of our knowledge, this study is the first to investigate the relation between frames and paintings by measuring physically defined, higher-order image properties.

  4. Gene expression analysis approach to establish possible links between Parkinson's disease, cancer and cardiovascular diseases.

    Science.gov (United States)

    Karim, Sajjad; Mirza, Zeenat; Kamal, Mohammad A; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2014-01-01

    Non-communicable chronic diseases have been apparently established as threat to human health, and are currently the world's main killer. Cardiovascular diseases (CVD), cancer, diabetes and neurodegenerative diseases are collectively amounting to more than 60% of non-communicable disease burden across world. Tremendous advancements in healthcare enabled us to fight several health problems primarily infectious diseases. However, this increased longevity where in many cases an individual suffers from several such chronic diseases simultaneously, making treatment complex. Finding whether diseases can coexist in an individual by chance or there exists a possible association between them is vital. Our goal is to establish possible existing link among CVD, cancer and Parkinson's disease (PD) for better understanding of the associated molecular network. In this study, we integrated multiple dataset retrieved from the National Centre for Biotechnology Information's Gene Expression Omnibus database, and took a systems-biology approach to compare and distinguish the molecular network associated with PD, cancer and CVD. We identified 230, 308 and 1619 differentially expressed genes for CVD, cancer and PD dataset respectively using cut off p value2. We integrated these data with known pathways using Ingenuity Pathway Analysis tool and found following common pathways associated with all three diseases to be most affected; epithelial adherens junction signaling, remodelling of epithelial adherens junctions, role of BRCA1 in DNA damage response, sphingomyelin metabolism, 3- phosphoinositide biosynthesis, acute myeloid leukemia signaling, type I diabetes mellitus signaling, agrin interactions at neuromuscular junction, role of IL-17A in arthritis, and antigen presentation pathways. In conclusion, CVD, cancer and PD appear tightly associated at molecular level.

  5. Requirements analysis and design for implementation of a satellite link for a local area computer network

    OpenAIRE

    Lorentzen, Richard B.

    1991-01-01

    Approved for public release; distribution is unlimited The purpose of this thesis is to provide naval computer students with a basic knowledge on Very Small Aperture Terminal (VSAT) satellite technology and to define the hardware and software requirements at the interface between a VSAT and a Local Area Network (LAN). By restricting a computer network to terrestrial links, a vast amount of knowledge is not accessed because either the terrestrial links can't access the information or the...

  6. Analysis of glycation induced protein cross-linking inhibitory effects of some antidiabetic plants and spices

    OpenAIRE

    Perera, Handunge Kumudu Irani; Handuwalage, Charith Sandaruwan

    2015-01-01

    Background Protein cross-linking which occurs towards the latter part of protein glycation is implicated in the development of chronic diabetic complications. Glycation induced protein cross-linking inhibitory effects of nine antidiabetic plants and three spices were evaluated in this study using a novel, simple, electrophoresis based method. Methods Methanol extracts of thirteen plants including nine antidiabetic plants and three spices were used. Lysozyme and fructose were incubated at 37 °...

  7. Characterization of the Raptor/4E-BP1 interaction by chemical cross-linking coupled with mass spectrometry analysis.

    Science.gov (United States)

    Coffman, Kimberly; Yang, Bing; Lu, Jie; Tetlow, Ashley L; Pelliccio, Emelia; Lu, Shan; Guo, Da-Chuan; Tang, Chun; Dong, Meng-Qiu; Tamanoi, Fuyuhiko

    2014-02-21

    mTORC1 plays critical roles in the regulation of protein synthesis, growth, and proliferation in response to nutrients, growth factors, and energy conditions. One of the substrates of mTORC1 is 4E-BP1, whose phosphorylation by mTORC1 reverses its inhibitory action on eIF4E, resulting in the promotion of protein synthesis. Raptor in mTOR complex 1 is believed to recruit 4E-BP1, facilitating phosphorylation of 4E-BP1 by the kinase mTOR. We applied chemical cross-linking coupled with mass spectrometry analysis to gain insight into interactions between mTORC1 and 4E-BP1. Using the cross-linking reagent bis[sulfosuccinimidyl] suberate, we showed that Raptor can be cross-linked with 4E-BP1. Mass spectrometric analysis of cross-linked Raptor-4E-BP1 led to the identification of several cross-linked peptide pairs. Compilation of these peptides revealed that the most N-terminal Raptor N-terminal conserved domain (in particular residues from 89 to 180) of Raptor is the major site of interaction with 4E-BP1. On 4E-BP1, we found that cross-links with Raptor were clustered in the central region (amino acid residues 56-72) we call RCR (Raptor cross-linking region). Intramolecular cross-links of Raptor suggest the presence of two structured regions of Raptor: one in the N-terminal region and the other in the C-terminal region. In support of the idea that the Raptor N-terminal conserved domain and the 4E-BP1 central region are closely located, we found that peptides that encompass the RCR of 4E-BP1 inhibit cross-linking and interaction of 4E-BP1 with Raptor. Furthermore, mutations of residues in the RCR decrease the ability of 4E-BP1 to serve as a substrate for mTORC1 in vitro and in vivo.

  8. Analysis of a Combined Antenna Arrays and Reverse-Link Synchronous DS-CDMA System over Multipath Rician Fading Channels

    Directory of Open Access Journals (Sweden)

    Kim Yong-Seok

    2005-01-01

    Full Text Available We present the BER analysis of antenna array (AA receiver in reverse-link asynchronous multipath Rician channels and analyze the performance of an improved AA system which applies a reverse-link synchronous transmission technique (RLSTT in order to effectively make a better estimation of covariance matrices at a beamformer-RAKE receiver. In this work, we provide a comprehensive analysis of user capacity which reflects several important factors such as the ratio of the specular component power to the Rayleigh fading power, the shape of multipath intensity profile, and the number of antennas. Theoretical analysis demonstrates that for the case of a strong specular path's power or for a high decay factor, the employment of RLSTT along with AA has the potential of improving the achievable capacity by an order of magnitude.

  9. M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission.

    Science.gov (United States)

    Sun, Jianli; Kapur, Jaideep

    2012-08-15

    Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M-type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M-type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN-A-343, increased the frequency of mEPSCs, but did not alter their amplitude. The M-channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M-channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium-free external medium. Blocking P/Q- and N-type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M-channels increases presynaptic calcium-dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M-channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN-A-343 and XE991; these effects were consistent with the closure of M-channels. Muscarinic activation inhibits M-channels in CA3 pyramidal neurons and its efferents – Schaffer collateral, which causes the depolarization, activates voltage-gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons.

  10. Multi-walled carbon nanotube inhibits CA1 glutamatergic synaptic transmission in rat's hippocampal slices.

    Science.gov (United States)

    Chen, Ting; Yang, Jiajia; Zhang, Hui; Ren, Guogang; Yang, Zhuo; Zhang, Tao

    2014-09-17

    The purpose of the study was to investigate the neurotoxic effect of multi-walled carbon nanotubes (MWCNTs) on the properties of glutamatergic synaptic transmission in rat's hippocampal slices using whole-cell patch clamp technique. The amplitude and frequency of excitatory postsynaptic current (EPSC) were accessed on the hippocampal pyramidal neurons. The alterations of glutamatergic synaptic transmission in CA3-CA1 were examined by measuring both the amplitude of evoked excitatory postsynaptic current (eEPSC) and paired-pulse ratio (PPR). The data showed that the amplitude of either spontaneous excitatory postsynaptic current (sEPSC) or miniature excitatory postsynaptic current (mEPSC) was significantly inhibited by 1 μg/mL MWCNTs. However, it was found that there was a trend of different change on the frequency index. When 1 μg/mL MWCNTs was applied, there were a decreased frequency of mEPSC and an increased frequency of sEPSC, which might be due to the effect of action potential. Furthermore, the amplitudes of eEPSC at CA3-CA1 synapses were remarkably decreased. And the mean amplitude of AMPAR-mediated eEPSC was significantly reduced as well. Meanwhile, a majority of PPRs data were greater than one. There were no significant differences of PPRs between control and MWCNTs states, but an increased trend of paired-pulse facilitation was found. These results suggested that MWCNT markedly inhibited hippocampal CA1 glutamatergic synaptic transmission in vitro, which provided new insights into the MWCNT toxicology on CNS at cellular level.

  11. Glutamatergic deficits and parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia

    Directory of Open Access Journals (Sweden)

    Kelley JF

    2009-11-01

    Full Text Available Abstract Background We have previously reported that the expression of the messenger ribonucleic acid (mRNA for the NR2A subunit of the N-methyl-D-aspartate (NMDA class of glutamate receptor was decreased in a subset of inhibitory interneurons in the cerebral cortex in schizophrenia. In this study, we sought to determine whether a deficit in the expression of NR2A mRNA was present in the subset of interneurons that contain the calcium buffer parvalbumin (PV and whether this deficit was associated with a reduction in glutamatergic inputs in the prefrontal cortex (PFC in schizophrenia. Methods We examined the expression of NR2A mRNA, labeled with a 35S-tagged riboprobe, in neurons that expressed PV mRNA, visualized with a digoxigenin-labeled riboprobe via an immunoperoxidase reaction, in twenty schizophrenia and twenty matched normal control subjects. We also immunohistochemically labeled the glutamatergic axon terminals with an antibody against vGluT1. Results The density of the PV neurons that expressed NR2A mRNA was significantly decreased by 48-50% in layers 3 and 4 in the subjects with schizophrenia, but the cellular expression of NR2A mRNA in the PV neurons that exhibited a detectable level of this transcript was unchanged. In addition, the density of vGluT1-immunoreactive boutons was significantly decreased by 79% in layer 3, but was unchanged in layer 5 of the PFC in schizophrenia. Conclusion These findings suggest that glutamatergic neurotransmission via NR2A-containing NMDA receptors on PV neurons in the PFC may be deficient in schizophrenia. This may disinhibit the postsynaptic excitatory circuits, contributing to neuronal injury, aberrant information flow and PFC functional deficits in schizophrenia.

  12. Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons.

    Science.gov (United States)

    Gill, Luther C; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

    2016-06-01

    Cervical spinal cord injury (SCI) interrupts descending neural drive to phrenic motoneurons causing diaphragm muscle (DIAm) paralysis. Recent studies using a well-established model of SCI, unilateral spinal hemisection of the C2 segment of the cervical spinal cord (SH), provide novel information regarding the molecular and cellular mechanisms of functional recovery after SCI. Over time post-SH, gradual recovery of rhythmic ipsilateral DIAm activity occurs. Recovery of ipsilateral DIAm electromyogram (EMG) activity following SH is enhanced by increasing brain-derived neurotrophic factor (BDNF) in the region of the phrenic motoneuron pool. Delivery of exogenous BDNF either via intrathecal infusion or via mesenchymal stem cells engineered to release BDNF similarly enhance recovery. Conversely, recovery after SH is blunted by quenching endogenous BDNF with the fusion-protein TrkB-Fc in the region of the phrenic motoneuron pool or by selective inhibition of TrkB kinase activity using a chemical-genetic approach in TrkB(F616A) mice. Furthermore, the importance of BDNF signaling via TrkB receptors at phrenic motoneurons is highlighted by the blunting of recovery by siRNA-mediated downregulation of TrkB receptor expression in phrenic motoneurons and by the enhancement of recovery evident following virally-induced increases in TrkB expression specifically in phrenic motoneurons. BDNF/TrkB signaling regulates synaptic plasticity in various neuronal systems, including glutamatergic pathways. Glutamatergic neurotransmission constitutes the main inspiratory-related, excitatory drive to motoneurons, and following SH, spontaneous neuroplasticity is associated with increased expression of ionotropic N-methyl-d-aspartate (NMDA) receptors in phrenic motoneurons. Evidence for the role of BDNF/TrkB and glutamatergic signaling in recovery of DIAm activity following cervical SCI is reviewed.

  13. Genome analysis methods - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available [ Credits ] BLAST Search Image Search Home About Archive Update History Contact us PGDBj Registered...ear Year of genome analysis Sequencing method Sequencing method Read counts Read counts Covered genome region Covered...otation method Number of predicted genes Number of predicted genes Genome database Genome database informati... License Update History of This Database Site Policy | Contact Us Genome analysis... methods - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive ...

  14. Time Development of Early Social Networks: Link analysis and group dynamics

    CERN Document Server

    Bruun, Jesper

    2013-01-01

    Empirical data on early network history are rare. Students beginning their studies at a university with no or few prior connections to each other offer a unique opportunity to investigate the formation and early development of social networks. During a nine week introductory physics course, first year physics students were asked to identify those with whom they communicated about problem solving in physics during the preceding week. We use these students' self reports to produce time dependent student interaction networks. These networks have also been investigated to elucidate possible effects of gender and students' final course grade. Changes in the weekly number of links are investigated to show that while roughly half of all links change from week to week, students also reestablish a growing number of links as they progress through their first weeks of study. To investigate how students group, Infomap is used to establish groups. Further, student group flow is examined using alluvial diagrams, showing th...

  15. Area Analysis for On-chip Routers with Different Data-link Widths

    Institute of Scientific and Technical Information of China (English)

    ZHANG Min; LUO Feng-guang; FENG Yong-hua; HU Jia

    2006-01-01

    Compared with the traditional and inter-chip networks, on-chip networks (NoCs) have enormous wire resources which can be traded for improving other performance requirements. This means that much wider data links can be used for NoCs. This paper focuses on the area costs for on-chip routers under four different data-link widths: 8 bits, 16 bits, 128 bits, and 256 bits. Firstly, a virtual-channel based on-chip router is introduced. Secondly, the components of the router are implemented by Verilog HDL models and synthesized by Quartus II 4.0 in a FPGA device. Finally, the area costs are analyzed. It can be seen from the results that data-link width has great influence on area costs of buffers and crossbar while has no influence on area costs of arbiter.

  16. Genipin Cross-Linked Polymeric Alginate-Chitosan Microcapsules for Oral Delivery: In-Vitro Analysis

    Directory of Open Access Journals (Sweden)

    Hongmei Chen

    2009-01-01

    Full Text Available We have previously reported the preparation of the genipin cross-linked alginate-chitosan (GCAC microcapsules composed of an alginate core with a genipin cross-linked chitosan membrane. This paper is the further investigation on their structural and physical characteristics. Results showed that the GCAC microcapsules had a smooth and dense surface and a networked interior. Cross-linking by genipin substantially reduced swelling and physical disintegration of microcapsules induced by nongelling ions and calcium sequestrants. Strong resistance to mechanical shear forces and enzymatic degradation was observed. Furthermore, the GCAC membranes were permeable to bovine serum albumin and maintained a molecular weight cutoff at 70 KD, analogous to the widely studied alginate-chitosan, and alginate-poly-L-lysine-alginate microcapsules. The release features and the tolerance of the GCAC microcapsules in the stimulated gastrointestinal environment were also investigated. This GCAC microcapsule formulation offers significant potential as a delivery vehicle for many biomedical applications.

  17. ANALYSIS OF LINK STATE RESOURCE RESERVATION PROTOCOL FOR CONGESTION MANAGEMENT IN SMART WEB HOTSPOT ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    Anulika Okoye Joy1

    2016-06-01

    Full Text Available With the wide spread of WiFi hotspots, concentrated traffic workload on Smart Web (SW can slow down the network performance. This paper presents a congestion management strategy considering real time activities in today’s smart web. With the SW context, cooperative packet recovery using resource reservation procedure for TCP flows was adapted for mitigating packet losses. This is to maintain data consistency between various access points of smart web hotspot. Using a real world scenario, it was confirmed that generic TCP cannot handle traffic congestion in a SW hotspot network. With TCP in scalable workload environments, continuous packet drops at the event of congestion remains obvious. This is unacceptable for mission critical domains. An enhanced Link State Resource Reservation Protocol (LSRSVP which serves as dynamic feedback mechanism in smart web hotspots is presented. The contextual behaviour was contrasted with the generic TCP model. For the LS-RSVP, a simulation experiment for TCP connection between servers at the remote core layer and the access layer was carried out while using selected benchmark metrics. From the results, under realistic workloads, a steady-state throughput response was achieved by TCP LS-RSVP to about 3650Bits/secs compared with generic TCP plots in a previous study. Considering network service availability, this was found to be dependent on fault-tolerance of the hotspot network. From study, a high peak threshold of 0.009 (i.e. 90% was observed. This shows fairly acceptable service availability behaviour compared with the existing TCP schemes. For packet drop effects, an analysis on the network behaviour with respect to the LS-RSVP yielded a drop response of about 0.000106 bits/sec which is much lower compared with the case with generic TCP with over 0.38 bits/sec. The latency profile of average FTP download response was found to be 0.030secs, but with that of FTP pload response, this yielded about 0.028 sec. The

  18. Linkage analysis and physical mapping near the gene for x-linked agammaglobulinemia at Xq22

    Energy Technology Data Exchange (ETDEWEB)

    Parolini, O.; Lassiter, G.L.; Henry, M.J.; Conley, M.E. (Univ. of Tennessee College of Medicine, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Hejtmancik, J.F. (National Inst. of Health, Bethesda, MD (United States)); Allen, R.C.; Belmont, J.W. (Baylor College of Medicine, Houston, TX (United States)); Barker, D.F. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    The gene for x-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the prob p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, and 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segman of DNA within which the gene for SLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DCS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XL)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel. Our studies also limit the segment of DNA within which the XLA gene must lie to the 3- to 4-cM distance between DCS442 and DXS94 and they identify and orient polymorphisms that can be used in genetic counseling not only for XLA but also for Pelizaeus-Merzbacher disease (PLP deficiency), Alport syndrome (COL4A5 deficiency), and Fabry disease ([alpha]-galactosidase A difficiency). 31 refs., 5 figs., 2 tabs.

  19. Analysis of fog effects on terrestrial Free Space optical communication links

    KAUST Repository

    Esmail, Maged Abdullah

    2016-07-26

    In this paper, we consider and examine fog measurement data, coming from several locations in Europe and USA, and attempt to derive a unified model for fog attenuation in free space optics (FSO) communication links. We evaluate and compare the performance of our proposed model to that of many well-known alternative models. We found that our proposed model, achieves an average RMSE that outperforms them by more than 9 dB. Furthermore, we have studied the performance of the FSO system using different performance metrics such as signal-to-noise (SNR) ratio, bit error rate (BER), and channel capacity. Our results show that FSO is a short range technology. Therefore, FSO is expected to find its place in future networks that will have small cell size, i.e., <1 km diameter. Moreover, our investigation shows that under dense fog, it is difficult to maintain a communications link because of the high signal attenuation, which requires switching the communications to RF backup. Our results show that increasing the transmitted power will improve the system performance under light fog. However, under heavy fog, the effect is minor. To enhance the system performance under low visibility range, multi-hop link is used which can enhance the power budget by using short segments links. Using 22 dBm transmitted power, we obtained BER=10-3 over 1 km link length with 600 m visibility range which corresponds to light fog. However, under lower visibility range equals 40 m that corresponds to dense fog, we obtained the same BER but over 200 m link length. © 2016 IEEE.

  20. Performance Analysis of a JTIDS/Link-16-type Waveform Transmitted over Slow, Flat Nakagami Fading Channels in the Presence of Narrowband Interference

    Science.gov (United States)

    2008-12-01

    ANALYSIS OF A JTIDS/LINK-16-TYPE WAVEFORM TRANSMITTED OVER SLOW, FLAT NAKAGAMI FADING CHANNELS IN THE PRESENCE OF NARROWBAND INTERFERENCE by...Performance Analysis of a JTIDS/Link-16-type Waveform Transmitted over Slow, Flat Nakagami Fading Channels in the Presence of Narrowband Interference 6...performance of a JTIDS/Link-16-type waveform in both additive white Gaussian noise (AWGN) and narrowband interference transmitted over a slow, flat Nakagami

  1. DYNAMIC ANALYSIS OF FLEXIBLE-LINK AND FLEXIBLE-JOINT ROBOTS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ding-guo; ZHOU Sheng-feng

    2006-01-01

    The dynamic modeling and simulation of an N-flexible-link and N-flexiblejoint robot is reported. Each flexible joint is modeled as a linearly elastic torsional spring and the approach of assumed modes is adopted to describe the deformation of the flexiblelink. The complete governing equations of motion of the flexible-link-joint robots are derived via Kane's method. An illustrative example is given to validate the algorithm presented and to show the effects of flexibility on the dynamics of robots.

  2. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

    Science.gov (United States)

    Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

    2014-02-01

    Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized.

  3. Performance Analysis of a Link-16/JTIDS Compatible Waveform With Noncoherent Detection, Diversity and Side Information

    Science.gov (United States)

    2009-09-01

    Narrowband Waveform over Slow, Flat Nakagami Fading Channels,” Proc. IEEE MILCOM, November 2008. [13] Bernard Sklar, Digital Communications...JTIDS.Link-16-type Waveform Transmitted over Nakagami Fading Channels with Pulsed-Noise Interference,” Proc. IEEE Military Commun. Conf., 2008

  4. Linking Adverbials in First-Year Korean University EFL Learners' Writing: A Corpus-Informed Analysis

    Science.gov (United States)

    Ha, Myung-Jeong

    2016-01-01

    This study examines the frequency and usage patterns of linking adverbials in Korean students' essay writing in comparison with native English writing. The learner corpus used in the present study is composed of 105 essays that were produced by first-year university students in Korea. The control corpus was taken from the American LOCNESS…

  5. Neuroticism, a central link between somatic and psychiatric morbidity : path analysis of prospective data

    NARCIS (Netherlands)

    Neeleman, J; Bijl, R; Ormel, J

    2004-01-01

    Background. Neuroticism and somatic complaints are linked, and the aim of this study is to disentangle which mechanisms may be responsible for this association. Method. In a stratified sample of 7076 adults (18-65 years), neuroticism, 22 self-reported chronic somatic conditions and five broad CIDI-d

  6. Analysis of Analog Photonic Links Employing Multiple-Channel (Arrayed) Receivers

    Science.gov (United States)

    2008-11-07

    Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Gain and Noise Penalty Characterization of Commercial EDFAs ...EXCESS NOISE ARIS- ING FROM INCORPORATION OF AN EDFA . . . . . . . . . . . . . . . . . . . . . . . . 25 iii I EXECUTIVE SUMMARY Analog photonic links...photocurrent, optical amplifiers – predominantly erbium-doped fiber amplifiers ( EDFAs ) – have been readily incorporated into a variety of systems. It is

  7. Integration and Analysis of Neighbor Discovery and Link Quality Estimation in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Marjan Radi

    2014-01-01

    Full Text Available Network connectivity and link quality information are the fundamental requirements of wireless sensor network protocols to perform their desired functionality. Most of the existing discovery protocols have only focused on the neighbor discovery problem, while a few number of them provide an integrated neighbor search and link estimation. As these protocols require a careful parameter adjustment before network deployment, they cannot provide scalable and accurate network initialization in large-scale dense wireless sensor networks with random topology. Furthermore, performance of these protocols has not entirely been evaluated yet. In this paper, we perform a comprehensive simulation study on the efficiency of employing adaptive protocols compared to the existing nonadaptive protocols for initializing sensor networks with random topology. In this regard, we propose adaptive network initialization protocols which integrate the initial neighbor discovery with link quality estimation process to initialize large-scale dense wireless sensor networks without requiring any parameter adjustment before network deployment. To the best of our knowledge, this work is the first attempt to provide a detailed simulation study on the performance of integrated neighbor discovery and link quality estimation protocols for initializing sensor networks. This study can help system designers to determine the most appropriate approach for different applications.

  8. Analysis of a generic model for a bottleneck link in an integrated services communications network

    NARCIS (Netherlands)

    Al-Begain, K.; Heindl, A.; Telek, M.; Litjens, R.; Boucherie, R.J.

    2007-01-01

    We develop and analyse a generic model for performance evaluation, parameter optimisation and dimensioning of a bottleneck link in an integrated services communications network. Possible application areas include ip, atm and gsm/gprs networks. The model enables analytical evaluation for a scenario o

  9. Beliefs and Ideologies Linked with Approval of Corporal Punishment: A Content Analysis of Online Comments

    Science.gov (United States)

    Taylor, C. A.; Al-Hiyari, R.; Lee, S. J.; Priebe, A.; Guerrero, L. W.; Bales, A.

    2016-01-01

    This study employs a novel strategy for identifying points of resistance to education efforts aimed at reducing rates of child physical abuse and use of corporal punishment (CP). We analyzed online comments (n = 581) generated in response to media coverage of a study linking CP with increased child aggression. Most comments (71%) reflected…

  10. A New Realistic Evaluation Analysis Method: Linked Coding of Context, Mechanism, and Outcome Relationships

    Science.gov (United States)

    Jackson, Suzanne F.; Kolla, Gillian

    2012-01-01

    In attempting to use a realistic evaluation approach to explore the role of Community Parents in early parenting programs in Toronto, a novel technique was developed to analyze the links between contexts (C), mechanisms (M) and outcomes (O) directly from experienced practitioner interviews. Rather than coding the interviews into themes in terms of…

  11. Revisiting the Gun Ownership and Violence Link; a multi- level analysis of victimisation survey data.

    NARCIS (Netherlands)

    van Kesteren, J.N.

    2014-01-01

    The link between gun ownership victimisation by violent crime remains one of the most contested issues in criminology. Some authors claim that high gun availability facilitates serious violence. Others claim that gun ownership prevents crime. This article revisits these issues using individual and a

  12. Integration and analysis of neighbor discovery and link quality estimation in wireless sensor networks.

    Science.gov (United States)

    Radi, Marjan; Dezfouli, Behnam; Abu Bakar, Kamalrulnizam; Abd Razak, Shukor

    2014-01-01

    Network connectivity and link quality information are the fundamental requirements of wireless sensor network protocols to perform their desired functionality. Most of the existing discovery protocols have only focused on the neighbor discovery problem, while a few number of them provide an integrated neighbor search and link estimation. As these protocols require a careful parameter adjustment before network deployment, they cannot provide scalable and accurate network initialization in large-scale dense wireless sensor networks with random topology. Furthermore, performance of these protocols has not entirely been evaluated yet. In this paper, we perform a comprehensive simulation study on the efficiency of employing adaptive protocols compared to the existing nonadaptive protocols for initializing sensor networks with random topology. In this regard, we propose adaptive network initialization protocols which integrate the initial neighbor discovery with link quality estimation process to initialize large-scale dense wireless sensor networks without requiring any parameter adjustment before network deployment. To the best of our knowledge, this work is the first attempt to provide a detailed simulation study on the performance of integrated neighbor discovery and link quality estimation protocols for initializing sensor networks. This study can help system designers to determine the most appropriate approach for different applications.

  13. Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring.

    Science.gov (United States)

    Kim, Ki Chan; Lee, Dong-Keun; Go, Hyo Sang; Kim, Pitna; Choi, Chang Soon; Kim, Ji-Woon; Jeon, Se Jin; Song, Mi-Ryoung; Shin, Chan Young

    2014-02-01

    Imbalance in excitatory/inhibitory signal in the brain has been proposed as one of the main pathological features in autism spectrum disorders, although the underlying cellular and molecular mechanism is unclear yet. Because excitatory/inhibitory imbalance can be induced by aberration in glutamatergic/GABAergic neuronal differentiation, we investigated the mechanism of dysregulated neuronal differentiation between excitatory and inhibitory neurons in the embryonic and postnatal brain of prenatally valproic acid-exposed rat offspring, which is often used as an animal model of autism spectrum disorders. Transcription factor Pax6, implicated in glutamatergic neuronal differentiation, was transiently increased in embryonic cortex by valproate exposure, which resulted in the increased expression of glutamatergic proteins in postnatal brain of offspring. Chromatin immunoprecipitation showed increased acetylated histone binding on Pax6 promoter region, which may underlie the transcriptional up-regulation of Pax6. Other histone deacetylase (HDAC) inhibitors including TSA and SB but not valpromide, which is devoid of HDAC inhibitor activity, induced Pax6 up-regulation. Silencing Pax6 expression in cultured rat primary neural progenitor cells demonstrated that up-regulation of Pax6 plays an essential role in valproate-induced glutamatergic differentiation. Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a lesser extent with MPEP treatment, reversed the impaired social behaviors and seizure susceptibility of prenatally valproate-exposed offspring. Together, environmental factors may contribute to the imbalance in excitatory/inhibitory neuronal activity in autistic brain by altering expression of transcription factors governing glutamatergic/GABAergic differentiation during fetal neural development, in conjunction with the genetic preload.

  14. The role of glutamatergic and GABAergic systems on serotonin- induced feeding behavior in chicken.

    Science.gov (United States)

    Mortezaei, Sepideh Seyedali; Zendehdel, Morteza; Babapour, Vahab; Hasani, Keyvan

    2013-12-01

    It has been reported that serotonin can modulate glutamate and GABA release in central nervous system (CNS). The present study was designed to examine the role of glutamatergic and GABAergic systems on serotonin- induced feeding behavior in chickens. In Experiment 1 intracerebroventricular (ICV) injection of MK- 801(NMDA receptor antagonist, 15 nmol) performed followed by serotonin (10 μg). In experiments 2, 3, 4, 5, 6 and 7 prior to serotonin injection, chickens received CNQX (AMPA/kainate receptor antagonist, 390 nmol), AIDA (mGluR1 antagonist, 2 nmol), LY341495 (mGluR2 antagonist, 150 nmol), UBP1112 (mGluR3 antagonist, 2 nmol), picrotoxin (GABA A receptor antagonist, 0.5 μg), CGP54626 (GABAB receptor antagonist, 20 ng) respectively. Cumulative food intake was determined at 3 h post injection. The results of this study showed that the hypophagic effect of serotonin was significantly attenuated by pretreatment with MK- 801 and CNQX (p 0.05). Also, the inhibitory effect of serotonin on food intake was amplified by picrotoxin (p 0.05). These results suggest that serotonin as a modulator probably interacts with glutamatergic (via NMDA and AMPA/Kainate receptors) and GABAergic (via GABAA receptor) systems on feeding behavior in chicken.

  15. The effect of α7 nicotinic receptor activation on glutamatergic transmission in the hippocampus.

    Science.gov (United States)

    Cheng, Qing; Yakel, Jerrel L

    2015-10-15

    Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and mediate both synaptic and perisynaptic activities of endogenous cholinergic inputs and pharmacological actions of exogenous compounds (e.g., nicotine and choline). Behavioral studies indicate that nicotine improves such cognitive functions as learning and memory, however the cellular mechanism of these actions remains elusive. With help from newly developed biosensors and optogenetic tools, recent studies provide new insights on signaling mechanisms involved in the activation of nAChRs. Here we will review α7 nAChR's action in the tri-synaptic pathway in the hippocampus. The effects of α7 nAChR activation via either exogenous compounds or endogenous cholinergic innervation are detailed for spontaneous and evoked glutamatergic synaptic transmission and synaptic plasticity, as well as the underlying signaling mechanisms. In summary, α7 nAChRs trigger intracellular calcium rise and calcium-dependent signaling pathways to enhance glutamate release and induce glutamatergic synaptic plasticity.

  16. Melatonin receptor activation increases glutamatergic synaptic transmission in the rat medial lateral habenula.

    Science.gov (United States)

    Evely, Katherine M; Hudson, Randall L; Dubocovich, Margarita L; Haj-Dahmane, Samir

    2016-05-01

    Melatonin (MLT) is secreted from the pineal gland and mediates its physiological effects through activation of two G protein-coupled receptors, MT1 and MT2 . These receptors are expressed in several brain areas, including the habenular complex, a pair of nuclei that relay information from forebrain to midbrain and modulate a plethora of behaviors, including sleep, mood, and pain. However, so far, the precise mechanisms by which MLT control the function of habenula neurons remain unknown. Using whole cell recordings from male rat brain slices, we examined the effects of MLT on the excitability of medial lateral habenula (MLHb) neurons. We found that MLT had no significant effects on the intrinsic excitability of MLHb neurons, but profoundly increased the amplitude of glutamate-mediated evoked excitatory post-synaptic currents (EPSC). The increase in strength of glutamate synapses onto MLHb neurons was mediated by an increase in glutamate release. The MLT-induced increase in glutamatergic synaptic transmission was blocked by the competitive MT1 /MT2 receptor antagonist luzindole (LUZ). These results unravel a potential cellular mechanism by which MLT receptor activation enhances the excitability of MLHb neurons. The MLT-mediated control of glutamatergic inputs to the MLHb may play a key role in the modulation of various behaviors controlled by the habenular complex.

  17. Impaired glutamatergic and GABAergic transmission by amitraz in primary hippocampal cells.

    Science.gov (United States)

    Del Pino, Javier; Frejo, María Teresa; Baselga, María José Anadon; Moyano, Paula; Díaz, María Jesús

    2015-01-01

    Amitraz is a formamidine pesticide that has been reported to be a neurotoxic compound that induces convulsions among other effects. Excitatory and inhibitory neurotransmission is mediated mainly by glutamate and GABA, respectively, so their alteration could be responsible for induction of seizures. In this regard, amitraz α2 adrenergic agonist action, which has been suggested as likely responsible for this effect, could alter these neurotransmitter systems and lead to seizure induction. Moreover, other amitraz mechanisms such as histamine H1 receptor inhibition could be involved. To confirm if amitraz disrupts glutamatergic/GABAergic transmission by these mechanisms, we evaluated, in primary hippocampal neurons, the effect of amitraz (0.01 μM to 100 μM) with or without the α2 adrenergic antagonist idazoxan (1 μM) and/or the H1 receptor agonist n-methylhistaprodifen (30 μM) co-treatment on 4-aminobutyrate aminotransferase, glutamate decarboxylase 65 (GAD 65), succinate-semialdehyde dehydrogenase and glutaminase gene expression and on glutamate and GABA levels after 24h treatment. We observed that amitraz disrupts glutaminase and GAD 65 gene expression, altering glutamatergic and GABAergic transmission. These effects were mediated partially by H1 and α2 receptors suggesting that other mechanisms could be involved. These data could help explain the mechanism by which amitraz induces seizures and provide a therapeutic strategy to protect against this effect in case of poisoning.

  18. Glutamatergic motoneurons in the stomatogastric ganglion of the mantis shrimp Squilla oratoria.

    Science.gov (United States)

    Chiba, C; Tazaki, K

    1992-07-01

    1. Transmitters of motoneurons in the stomatogastric ganglion (STG) of Squilla were identified by analyzing the excitatory neuromuscular properties of muscles in the posterior cardiac plate (pcp) and pyloric regions. 2. Bath and iontophoretic applications of glutamate produce depolarizations in these muscles. The pharmacological experiments and desensitization of the junctional receptors elucidate the glutamatergic nature of the excitatory junctional potentials (EJPs) evoked in the constrictor and dilator muscles. The reversal potentials for the excitatory junctional current (EJC) and for the glutamate-induced current are almost the same. 3. Some types of dilator muscle show sensitivity to both glutamate and acetylcholine (ACh) exogenously applied. The pharmacological evidence and desensitization of the junctional receptors indicate the glutamatergic nature of neuromuscular junctions in these dually sensitive muscles. The reversal potentials for the EJC and for the ACh-induced current are not identical. 4. Glutamate is a candidate as an excitatory neuro-transmitter at the neuromuscular junctions which the STG motoneurons named PCP, PY, PD, LA and VC make with the identified muscles. Kainic and quisqualic acids which act on glutamate receptors are potent excitants of these muscles. Extrajunctional receptors to ACh are present in two types of the muscle innervated by LA and VC. 5. Neurotransmitters used by the STG motoneurons of stomatopods are compared to those of decapods.

  19. Targeting the Glutamatergic System to Treat Pathological Gambling: Current Evidence and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Mauro Pettorruso

    2014-01-01

    Full Text Available Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.

  20. Scandinavian links

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

    centres, one joins more thinly populated regions, and the last one links peripheral areas. Two of them (The Great Belt Link and the Oresund Link) have been constructed and are in full operation. The third (the Fehmarnbelt Link) has been decided 2008 on bilateral government level. The three links...

  1. Deletion of Shank1 has minimal effects on the molecular composition and function of glutamatergic afferent postsynapses in the mouse inner ear

    NARCIS (Netherlands)

    Braude, Jeremy P.; Vijayakumar, Sarath; Baumgarner, Katherine; Laurine, Rebecca; Jones, Timothy A.; Jones, Sherri M.; Pyott, Sonja J.

    2015-01-01

    Shank proteins (1-3) are considered the master organizers of glutamatergic postsynaptic densities in the central nervous system, and the genetic deletion of either Shank1, 2, or 3 results in altered composition, form, and strength of glutamatergic postsynapses. To investigate the contribution of Sha

  2. Plant DB link - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available [ Credits ] BLAST Search Image Search Home About Archive Update History Contact us PGDBj Registered... Description Download License Update History of This Database Site Policy | Contact Us Plant DB link - PGDBj Registered

  3. [A Method for Protein Photo-cross-linking in Living Cells Facilitating Analysis of Physiological Interactions of Proteins].

    Science.gov (United States)

    Hino, Nobumasa

    2015-01-01

    In living cells, most proteins form complexes with other proteins to exert their functions. Since protein functions are regulated in response to changes in the cellular environment, the components of the complexes can vary; therefore, proteins often interact in a weak and transient manner. To capture such labile protein interactions, we have developed a method for photo-cross-linking of proteins directly interacting in mammalian cells; this method involves expansion of the genetic code and site-specific incorporation of photoreactive amino acids into proteins. Upon cross-linking, protein complexes are stabilized by a covalent bond and can be readily isolated from cell extracts without the problems usually associated with simple affinity purification methods such as co-immunoprecipitation. Photo-cross-linkers have another benefit: they react exclusively with molecules within a range defined by the linker length. This property becomes useful for determining the binding interface of two proteins because the linkers can be introduced in a site-directed manner with our method. In this review, we first describe the expansion of the genetic code of mammalian cells for the incorporation of non-natural amino acids into proteins. Then, we introduce our recent applications and developments of the cross-linking method: identification of intracellular binding partners of the signaling protein growth factor receptor binding protein 2; analysis of the binding between membrane proteins on the cell surface; and a novel photoreactive amino acid that enables wide-ranging photo-cross-linking.

  4. A Contrastive Analysis of the Links of Textuality in Abstracts Written by Persian and English Writers in Clinical Psychology Journals

    Directory of Open Access Journals (Sweden)

    Abbas Mehrabi Boshrabadi

    2014-07-01

    Full Text Available It is generally agreed today that lexical cohesion is one of the fundamental elements of the text texture achieved through lexical semantic relations dominating the arrangement of propositional units in a text. Accordingly, this study sought to compare and contrast the textual links or lexical cohesive devices enlisted in the psychological abstracts written by Persian and English writers. To this end, 40 abstracts from Persian and English articles, 20 in each language, published in clinical psychology journals were randomly selected. The framework serving as tertium comprationis for analyzing lexical cohesion markers was derived from Halliday and Hasan’s (1976 model [Halliday, M. A. K., & Hasan, R. (1976. Cohesion in English. London: Longman]. A frequency count analysis was employed to gauge the number of occurrences of cohesive links in the selected corpus. The results revealed that lexical links of synonymy and repetition were more frequent than other cohesive devices in both English and Persian abstracts.Keywords: Links of textuality, Lexical cohesive devices, Synonymy, Repetition, Clinical psychology journal abstracts

  5. The link in Linking

    Science.gov (United States)

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  6. Advancements in mass spectrometry for biological samples: Protein chemical cross-linking and metabolite analysis of plant tissues

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Adam [Iowa State Univ., Ames, IA (United States)

    2015-01-01

    This thesis presents work on advancements and applications of methodology for the analysis of biological samples using mass spectrometry. Included in this work are improvements to chemical cross-linking mass spectrometry (CXMS) for the study of protein structures and mass spectrometry imaging and quantitative analysis to study plant metabolites. Applications include using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to further explore metabolic heterogeneity in plant tissues and chemical interactions at the interface between plants and pests. Additional work was focused on developing liquid chromatography-mass spectrometry (LC-MS) methods to investigate metabolites associated with plant-pest interactions.

  7. Effects of enterprise technology on supply chain collaboration: analysis of China-linked supply chain

    Science.gov (United States)

    Li, Ling

    2012-02-01

    Supply chain collaboration has received increasing attention from scholars and practitioners in recent years. However, our understanding of how enterprise information technology facilitates supply chain collaboration is still very limited, especially with regard to Chinese enterprise ownerships such as state-owned firms, joint-venture firms and local village-owned firms. This paper extends the theory established in enterprise information technology (IT) and supply chain collaboration literature and relates it with coordination in China-linked supply chain. Drawing upon an empirical study from 177 Chinese companies, we provide three major findings: (i) uncovered the importance of leveraging enterprise IT through supply chain collaboration; (ii) identified the relationship between enterprise ownership and enterprise technology use and supply chain collaboration in China-linked supply chain and (iii) illustrated effects of supply chain collaborative activities on operational and market performance.

  8. Optimization and small-amplitude analysis of Purcell's three-link microswimmer model

    Science.gov (United States)

    Wiezel, O.; Or, Y.

    2016-08-01

    This work studies the motion of Purcell's three-link microswimmer in viscous flow, by using perturbation expansion of its dynamics under small-amplitude strokes. Explicit leading-order expressions and next-order correction terms for the displacement of the swimmer are obtained for the cases of a square or circular gait in the plane of joint angles. The correction terms demonstrate the reversal in movement direction for large stroke amplitudes, which has previously only been shown numerically. In addition, asymptotic expressions for Lighthill's energetic efficiency are obtained for both gaits. These approximations enable calculating optimal stroke amplitudes and swimmer's geometry (i.e. ratio of links' lengths) for maximizing either net displacement or Lighthill's efficiency.

  9. Optimization and small-amplitude analysis of Purcell's three-link microswimmer model

    CERN Document Server

    Wiezel, Oren

    2016-01-01

    This work studies the motion of Purcell's three-link microswimmer in viscous flow, by using perturbation expansion of its dynamics under small-amplitude strokes. Leading-order expressions and next-order correction terms for the displacement of the swimmer are obtained for the cases of a square or circular gait in the plane of joint angles. The correction terms demonstrate the reversal in movement direction for large stroke amplitudes, which has previously only been shown numerically. In addition, asymptotic expressions for Lighthill's energetic efficiency are obtained for both gaits. These approximations enable calculating optimal stroke amplitudes and swimmer's geometry (i.e. ratio of links' lengths) for maximizing either the displacement or Lighthill's efficiency.

  10. Analysis of Tactical Data Links used by the Department of Defense

    Science.gov (United States)

    1977-03-01

    Imagery AIDATS CEFLY LANCER wide band ICNS wide band COMPASS BRIGHT 2. PLSS Command JTIDS 3. PLSS GB Guidance WCCM narrow band PMACS narrow band ICNS...narrow band 4. PLSS Sensor AIDATS CEFLY LANCER wide band ICNS wide band COMPASS BRIGHT 5. RMCS Command JTIDS WCCM narrow band PMACS narrow band ICNS...expendable. Narrow-bandwidth data links that have these characteristics and should be considered for this applica- tion are: WALLEYE, WCCM, PMACS

  11. THE LINK BETWEEN GLOBALISATION, ECONOMIC GROWTH AND EDUCATION: AN ANALYSIS IN THE CASE OF ROMANIA

    Directory of Open Access Journals (Sweden)

    Stela Dima

    2014-12-01

    Full Text Available The paper tries to offer empirical evidence on the link between economic growth, globalisation phenomenon and education level of population in the Romanian economy. Using time series for 1990-2011 in a regression model, we found a positive validated correlation between globalisation and economic growth, globalisation and education and, economic growth and education. For globalisation measurement the KOF index of globalisation was used.

  12. Link Performance Analysis for a Proposed Future Architecture of the Air Force Satellite Control Network

    Science.gov (United States)

    2011-12-01

    stations are selected from the online database provided by STK and generic spacecraft orbits were defined using STK’s orbit modeler. STK automatically...shipped to each RTS and then installed on the system. Or the software update can be uploaded to an online database connected to the world wide web and...Dynamic System - A Divide and Conquer Approach. Espoo, Finland: IEEE. Cuevas, E. G., & Rehwinkel, C. A. SPOCS : A System to Measure Satellite Link

  13. A COMPARATIVE ANALYSIS BETWEEN UNIT-LINKED LIFE INSURANCE AND OTHER ALTERNATIVE INVESTMENTS

    OpenAIRE

    CRISTINA CIUMAS; DIANA-MARIA CHIS

    2015-01-01

    The unit-linked life insurance has two important components: protection and investment. The protection component refers to the insured sum in case of the occurrence of insured risks and the investment component refers to the policyholder’s account that represents the present value of the units from the chosen investment funds.These financial products invest most of the premium paid by the insured person in the funds managed by the insurance company or an external administrator and the lower p...

  14. A COMPARATIVE ANALYSIS BETWEEN UNIT-LINKED LIFE INSURANCE AND OTHER ALTERNATIVE INVESTMENTS

    OpenAIRE

    CRISTINA CIUMAS; DIANA-MARIA CHIS

    2015-01-01

    The unit-linked life insurance has two important components: protection and investment. The protection component refers to the insured sum in case of the occurrence of insured risks and the investment component refers to the policyholder’s account that represents the present value of the units from the chosen investment funds.These financial products invest most of the premium paid by the insured person in the funds managed by the insurance company or an external administrator and...

  15. Energy-delay bounds analysis in wireless multi-hop networks with unreliable radio links

    CERN Document Server

    Zhang, Ruifeng; Jaffrès-Runser, Katia

    2008-01-01

    Energy efficiency and transmission delay are very important parameters for wireless multi-hop networks. Previous works that study energy efficiency and delay are based on the assumption of reliable links. However, the unreliability of the channel is inevitable in wireless multi-hop networks. This paper investigates the trade-off between the energy consumption and the end-to-end delay of multi-hop communications in a wireless network using an unreliable link model. It provides a closed form expression of the lower bound on the energy-delay trade-off for different channel models (AWGN, Raleigh flat fading and Nakagami block-fading) in a linear network. These analytical results are also verified in 2-dimensional Poisson networks using simulations. The main contribution of this work is the use of a probabilistic link model to define the energy efficiency of the system and capture the energy-delay trade-offs. Hence, it provides a more realistic lower bound on both the energy efficiency and the energy-delay trade-o...

  16. A COMPARATIVE ANALYSIS BETWEEN UNIT-LINKED LIFE INSURANCE AND OTHER ALTERNATIVE INVESTMENTS

    Directory of Open Access Journals (Sweden)

    CRISTINA CIUMAS

    2015-07-01

    Full Text Available The unit-linked life insurance has two important components: protection and investment. The protection component refers to the insured sum in case of the occurrence of insured risks and the investment component refers to the policyholder’s account that represents the present value of the units from the chosen investment funds.These financial products invest most of the premium paid by the insured person in the funds managed by the insurance company or an external administrator and the lower part of the premium is intended to cover the insured risk (death, disability, etc. An important component of the activity carried out by the insurance companies is the investment of the premiums paid by policyholders in various types of assets, in order to obtain higher yields than those guaranteed by the insurance contracts, while providing the necessary liquidity for the payment of insurance claims in case of occurrence of the assumed risks. This research contributes to the existing literature regarding the study of investment alternatives, with an exclusive focus on the investment in unit-linked life insurance. A special place in this study is the presentation of investments in unit-linked insurance versus other types of financial investments: deposits, treasury bills, shares (BET, currency (EURO and gold.

  17. LTE Link Budget Study and Analysis%LTE链路预算研究及分析

    Institute of Scientific and Technical Information of China (English)

    黄芷辛; 冯健; 麦磊鑫

    2013-01-01

    Link budget is fundamental for wireless network planning, significant for the estimation of network coverage capacity as well as network construction cost. In this paper, the method and major parameters affected of LTE link budget are studied, the typical values of key parameters are given, and the impact on link budget and coverage ability under different scenes and duplex mode is analyzed and summarized.%  链路预算是无线网络规划的基础环节,对网络覆盖能力和建设成本的估算具有十分重要的意义。重点对LTE链路预算的方式及主要参数进行研究,给出了关键参数的典型取值,并分析总结不同的场景或双工方式对链路预算及覆盖能力的影响。

  18. Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons.

    Science.gov (United States)

    Gajewska-Woźniak, Olga; Grycz, Kamil; Czarkowska-Bauch, Julita; Skup, Małgorzata

    2016-01-01

    The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG). LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF) using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models of injury is a

  19. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA. [Human Reliability Analysis (HRA)

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-01-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  20. Xlink Analyzer: software for analysis and visualization of cross-linking data in the context of three-dimensional structures.

    Science.gov (United States)

    Kosinski, Jan; von Appen, Alexander; Ori, Alessandro; Karius, Kai; Müller, Christoph W; Beck, Martin

    2015-03-01

    Structural characterization of large multi-subunit protein complexes often requires integrating various experimental techniques. Cross-linking mass spectrometry (XL-MS) identifies proximal protein residues and thus is increasingly used to map protein interactions and determine the relative orientation of subunits within the structure of protein complexes. To fully adapt XL-MS as a structure characterization technique, we developed Xlink Analyzer, a software tool for visualization and analysis of XL-MS data in the context of the three-dimensional structures. Xlink Analyzer enables automatic visualization of cross-links, identifies cross-links violating spatial restraints, calculates violation statistics, maps chemically modified surfaces, and allows interactive manipulations that facilitate analysis of XL-MS data and aid designing new experiments. We demonstrate these features by mapping interaction sites within RNA polymerase I and the Rvb1/2 complex. Xlink Analyzer is implemented as a plugin to UCSF Chimera, a standard structural biology software tool, and thus enables seamless integration of XL-MS data with, e.g. fitting of X-ray structures to EM maps. Xlink Analyzer is available for download at http://www.beck.embl.de/XlinkAnalyzer.html.

  1. Performance Analysis of Industrial Network CC-LINK IE%工业以太网CC-LINK IE的性能分析

    Institute of Scientific and Technical Information of China (English)

    周丽娟

    2013-01-01

    The industrial Ethernet CC-LINK IE, based on Gigabit Ethernet, has released two major products control network and field network, providing seamless communication between upper-level information systems and lower-level field systems.CC-LINK IE makes not much difference in data capacity and transmission speed with Gigabit Ethernet, and breaks through the problem of time delay which exists in traditional industrial networks. In addition, its wiring design allows double ring topology to ensure the network can work normally even if one station in the loop happens to malfunction, largely improves the reliability. This text will analyze the advantages and disadvantages of CC-LINK IE and other industrial networks. Finally the interrelated application case is recited.%  基于以太网的整合网络CC-LINK IE系列推出的控制网络与现场网络,实现了从上位信息系统到下位现场系统的无缝协作.CC-LINK IE在数据容量与传输速度方面都与商用以太网相差无几,又很大程度上突破了传统工业以太网的延时性.除此之外,CC-LINK IE采用双环路的网络结构,任何一个站出现故障都不会干扰整个网络的数据交换,很大程度上提高了可靠性.本文比较了CC-LINK IE与其他工业以太网的优缺点,最后提出有关应用案例.

  2. Non-Invasive Parameter Identification in Rotordynamics via Fluid Film Bearings: Linking Active Lubrication and Operational Modal Analysis

    DEFF Research Database (Denmark)

    Santos, Ilmar; Svendsen, Peter Kjær

    2016-01-01

    of this paper is to show experimentally that the knowledge about the several transfer functions can be bypassed by using output-only identification techniques. The manuscript links controllable (active) lubrication techniques with operational modal analysis, allowing for in-situ parameter identification...... in rotordynamics, i.e. estimation of damping ratio and natural frequencies.The experimental analysis is carried out on a rigid rotor level system supported by one single pair of pads. The estimation of damping and natural frequencies is performed using classical experimental modal analysis (EMA) and operational...... modal analysis (OMA). Very good agreements between the two experimental approaches are found. Maximum values of the main input parameters, namely servovalve voltage and radial injection pressure, are experimentally found with the objective of defining ranges of non-invasive perturbation forces....

  3. Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders.

    Science.gov (United States)

    Karim, Sajjad; Kamal, Mohammad A; Iqbal, Zafar; Ansari, Shakeel A; Rasool, Mahmood; Al-Qahtani, Mohammed H; Damanhouri, Gazi; Mirza, Zeenat

    2016-01-01

    Schizophrenia, a psychological disorder with enormous societal impact, is a result of abnormalities in gene expression and dysregulation of the immune response in the brain. Few studies have been conducted to understand its etiology, however, the exact molecular mechanism largely remains unknown, though some poorly understood theories abound. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis. We retrieved genome-wide mRNA expression data and clinico-pathological information from five independent studies of schizophrenic patients from Gene Expression Omnibus database. We continued further with three studies having common platform. Our result showed a total of 527 differentially expressed genes of which 314 are up regulated and 213 are down regulated. After adjusting the sources of variation, we carried out pathway and gene ontology analysis, and observed alteration of 14-3-3-mediated signaling, γ-aminobutyric acid receptor signaling, role of nuclear factor of activated T-cells in regulation of the immune response, G beta gamma signaling, dopamine- and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 feedback in cAMP signaling, complement system, axonal guidance signaling, dendritic cell maturation, cAMP response element-binding protein signaling in neurons and interleukin-1 signaling pathways and networks. Conclusively, our global gene expression pathway and gene set enrichment analysis studies suggest disruption of many common pathways and processes, which links schizophrenia to immune and central nervous system. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis.

  4. Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles

    NARCIS (Netherlands)

    Banks, R.W.; Cahusac, P.M.; Graca, A.; Kain, N.; Shenton, F.; Singh, P.; Nja, A.; Simon, A.; Watson, S.; Slater, C.R.; Bewick, G.S.

    2013-01-01

    Abstract Our aim in the present study was to determine whether a glutamatergic modulatory system involving synaptic-like vesicles (SLVs) is present in the lanceolate ending of the mouse and rat hair follicle and, if so, to assess its similarity to that of the rat muscle spindle annulospiral ending w

  5. Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice.

    Science.gov (United States)

    Song, Mingke; Yu, Shan Ping; Mohamad, Osama; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Jiang, Michael Qize; Wei, Ling

    2017-02-01

    Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Whether SVZ neurogenesis can be upregulated by specific neuronal activity in vivo and promote functional recovery after stroke is largely unknown. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we tested the hypothesis that glutamatergic activation in the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain. In transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity in the striatum triggered glutamate release into SVZ region, evoked membrane currents, Ca(2+) influx and increased proliferation of SVZ neuroblasts, mediated by AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic stroke, optogenetic stimuli to the striatum started 5days after stroke for 8days not only promoted cell proliferation but also the migration of SVZ neuroblasts into the peri-infarct cortex with increased neuronal differentiation and improved long-term functional recovery. These data provide the first morphological and functional evidence showing a unique striatum-SVZ neuronal regulation via a semi-phasic synaptic mechanism that can boost neurogenic cascades and stroke recovery. The benefits from stimulating endogenous glutamatergic activity suggest a novel regenerative strategy after ischemic stroke and other brain injuries.

  6. Metabotropic glutamate and GABA receptors modulate cellular excitability and glutamatergic transmission in chicken cochlear nucleus angularis neurons.

    Science.gov (United States)

    Shi, Wei; Lu, Yong

    2017-03-01

    Neurons in the avian cochlear nucleus angularis (NA) receive glutamatergic input from the auditory nerve, and GABAergic input from the superior olivary nucleus. Physiologically heterogeneous, NA neurons perform multiple functions including encoding sound intensity information. Using in vitro whole-cell patch recordings from acute brain slices and immunohistochemistry staining, we investigated neuromodulation mediated by metabotropic glutamate and GABA receptors (mGluRs and GABABRs) in NA neurons. Based on their intrinsic firing patterns in response to somatic current injections, NA neurons were classified into onset, damped, and tonic cells. Pharmacological activation of group II mGluRs, group III mGluRs, and GABABRs, by their respective agonists, suppressed the cellular excitability of non-onset firing NA neurons. Each of these agonists inhibited the glutamatergic transmission in NA neurons, in a cell type-independent manner. The frequency but not the amplitude of spontaneous release of glutamate was reduced by each of these agonists, suggesting that the modulation of the glutamatergic transmission was via presynaptic actions. Interestingly, activation of group I mGluRs increased cellular excitability and suppressed glutamatergic transmission in non-onset neurons. These results elaborate that auditory processing in NA neurons is subject to neuromodulation mediated by metabotropic receptors activated by native neurotransmitters released at NA.

  7. N-linked glycosylation in Archaea: a structural, functional, and genetic analysis.

    Science.gov (United States)

    Jarrell, Ken F; Ding, Yan; Meyer, Benjamin H; Albers, Sonja-Verena; Kaminski, Lina; Eichler, Jerry

    2014-06-01

    N-glycosylation of proteins is one of the most prevalent posttranslational modifications in nature. Accordingly, a pathway with shared commonalities is found in all three domains of life. While excellent model systems have been developed for studying N-glycosylation in both Eukarya and Bacteria, an understanding of this process in Archaea was hampered until recently by a lack of effective molecular tools. However, within the last decade, impressive advances in the study of the archaeal version of this important pathway have been made for halophiles, methanogens, and thermoacidophiles, combining glycan structural information obtained by mass spectrometry with bioinformatic, genetic, biochemical, and enzymatic data. These studies reveal both features shared with the eukaryal and bacterial domains and novel archaeon-specific aspects. Unique features of N-glycosylation in Archaea include the presence of unusual dolichol lipid carriers, the use of a variety of linking sugars that connect the glycan to proteins, the presence of novel sugars as glycan constituents, the presence of two very different N-linked glycans attached to the same protein, and the ability to vary the N-glycan composition under different growth conditions. These advances are the focus of this review, with an emphasis on N-glycosylation pathways in Haloferax, Methanococcus, and Sulfolobus.

  8. Time Transfer by Laser Link: Data analysis and validation to the ps level

    Science.gov (United States)

    Exertier, Pierre; Samain, E.; Martin, N.; Courde, C.; Laas-Bourez, M.; Foussard, C.; Guillemot, Ph.

    2014-12-01

    The Time Transfer by Laser Link (T2L2) is a very high resolution time transfer technique based on the recording of arrival times of laser pulses at the satellite. T2L2 was designed to achieve time stability in the range of 1 ps over 1000 s and an accuracy better than 100 ps. The project is in operation onboard the Jason-2 satellite since June 2008. The principle is based on the Satellite Laser Ranging (SLR) technology; it uses the input of 20-25 SLR stations of the international laser network which participate in the tracking. This paper focuses on the data reduction process which was developed specifically to transform the raw information given by both space instrument and ground network: first to identify the triplets (ground and onboard epochs and time of flight of the laser pulse), second to estimate a usable product in terms of ground-to-space time transfer (including instrumental corrections), and thirdly to produce synchronization between any pair of remote ground clocks. In describing the validation of time synchronizations, the paper opens a way for monitoring the time difference between ultra-stable clocks thanks to a laser link at a few ps level for Common View passes. It highlights however that without accurately characterizing the onboard oscillator of Jason-2 and knowing the unavailability of time calibrations of SLR stations generally, time transfer over intercontinental distances remain difficult to be accurately estimated.

  9. Scintillation analysis of multiple-input single-output underwater optical links.

    Science.gov (United States)

    Gökçe, Muhsİn Caner; Baykal, Yahya

    2016-08-01

    Multiple-input single-output (MISO) techniques are employed in underwater wireless optical communication (UWOC) links to mitigate the degrading effects of oceanic turbulence. In this paper, we consider a MISO UWOC system which consists of a laser beam array as transmitter and a point detector as receiver. Our aim is to find the scintillation index at the detector in order to quantify the system performance. For this purpose, the average intensity and the average of the square of the intensity are derived in underwater turbulence by using the extended Huygens-Fresnel principle. The scintillation index and the average bit-error-rate (⟨BER⟩) formulas presented in this paper depend on the oceanic turbulence parameters, such as the rate of dissipation of the mean-squared temperature, rate of dissipation of kinetic energy per unit mass of fluid, Kolmogorov microscale, and the ratio of temperature to salinity contributions to the refractive index spectrum, the link length, and the wavelength. Recently, we have derived an equivalent structure constant of atmospheric turbulence and expressed it in terms of the oceanic turbulence parameters [Appl. Opt.55, 1228 (2016)APOPAI0003-693510.1364/AO.55.001228]. In the formulation in this paper, this equivalent structure constant is utilized, which enables us to employ the existing similar formulation valid in atmospheric turbulence.

  10. Simulink models for performance analysis of high speed DQPSK modulated optical link

    Science.gov (United States)

    Sharan, Lucky; Rupanshi, Chaubey, V. K.

    2016-03-01

    This paper attempts to present the design approach for development of simulation models to study and analyze the transmission of 10 Gbps DQPSK signal over a single channel Peer to Peer link using Matlab Simulink. The simulation model considers the different optical components used in link design with their behavior represented initially by theoretical interpretation, including the transmitter topology, Mach Zehnder Modulator(MZM) module and, the propagation model for optical fibers etc. thus allowing scope for direct realization in experimental configurations. It provides the flexibility to incorporate the various photonic components as either user-defined or fixed and, can also be enhanced or removed from the model as per the design requirements. We describe the detailed operation and need of every component model and its representation in Simulink blocksets. Moreover the developed model can be extended in future to support Dense Wavelength Division Multiplexing (DWDM) system, thereby allowing high speed transmission with N × 40 Gbps systems. The various compensation techniques and their influence on system performance can be easily investigated by using such models.

  11. {sup 15}N/{sup 14}N isotopic ratio and statistical analysis: an efficient way of linking seized Ecstasy tablets

    Energy Technology Data Exchange (ETDEWEB)

    Palhol, Fabien; Lamoureux, Catherine; Chabrillat, Martine; Naulet, Norbert

    2004-05-10

    In this study, the {sup 15}N/{sup 14}N isotopic ratios of 106 samples of 3,4-methylenedioxymethamphetamine (MDMA) extracted from Ecstasy tablets are presented. These ratios, measured using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS), show a large discrimination between samples with a range of {delta}{sup 15}N values between -17 and +19%o, depending on the precursors and the method used in clandestine laboratories. Thus, {delta}{sup 15}N values can be used in a statistical analysis carried out in order to link Ecstasy tablets prepared with the same precursors and synthetic pathway. The similarity index obtained after principal component analysis and hierarchical cluster analysis appears to be an efficient way to group tablets seized in different places.

  12. Activation of both Group I and Group II metabotropic glutamatergic receptors suppress retinogeniculate transmission.

    Science.gov (United States)

    Lam, Y-W; Sherman, S M

    2013-07-09

    Relay cells of dorsal lateral geniculate nucleus (LGN) receive a Class 1 glutamatergic input from the retina and a Class 2 input from cortical layer 6. Among the properties of Class 2 synapses is the ability to activate metabotropic glutamate receptors (mGluRs), and mGluR activation is known to affect thalamocortical transmission via regulating retinogeniculate and thalamocortical synapses. Using brain slices, we studied the effects of Group I (dihydroxyphenylglycine) and Group II ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine) mGluR agonists on retinogeniculate synapses. We showed that both agonists inhibit retinogeniculate excitatory postsynaptic currents (EPSCs) through presynaptic mechanisms, and their effects are additive and independent. We also found high-frequency stimulation of the layer 6 corticothalamic input produced a similar suppression of retinogeniculate EPSCs, suggesting layer 6 projection to LGN as a plausible source of activating these presynaptic mGluRs.

  13. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... intermediates, were upregulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 upregulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two nonproducing mutants, restricted to a sub...

  14. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    Directory of Open Access Journals (Sweden)

    Caroline eMenard

    2014-05-01

    Full Text Available The LOU/C/Jall (LOU rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn, an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non obese aging

  15. Analysis of Cell Planning and Link Budgeting in WiMAX Communication

    Directory of Open Access Journals (Sweden)

    Md. Masud Hasan

    2012-05-01

    Full Text Available This thesis is related with the WiMAX (Worldwide Interoperatibility for Microwave Access technology. Today, different types of cellular networks are actively working on the radio links. For instance, the Global System for Mobile Communication (GSM is being used in nearly all of the countries of the world and currently it has around three billion users all over the world. Universal Mobile Telecommunication System (UMTS is currently deployed in many countries and it is providing increased data rates, coverage and mobility as compared to GSM. Wireless Local Area Networks (WLAN are very famous when we have a small area and none real time services. Worldwide Interoperability for Microwave Access (WiMAX is a new technology and it is in deployment phase. In all these cellular technologies, we have very limited resources and we have to make best use of them by proper management. Radio Resource Management (RRM is a control mechanism for the overall system which is being used to manage radio resources in the air interface inside a cellular network. The main objective is to utilize the available spectral resources as efficiently as possible. Our aim is to use them in the best possible way to maximize the performance and spectral efficiency in such a way that we have maximum number of users in our network and Quality of Service (QoS is up to the mark. In a cellular communication system, a service area or a geographical region is divided into a number of cells and each cell is served by an infrastructure element called the base station which works through a radio interface. The frequency license fees, real estate, distribution network and maintenance are the issues which dominates the cost for deploying a cellular network. In RRM, we control parameters like Radio Frequency (RF planning, link budgeting, modulation schemes, channel access schemes etc. RF planning includes cell planning, coverage of the network and capacity of the network. Our main focus in

  16. Design and Performance Analysis of a C Band Micro-strip Patch Feed Reflector Antenna and Link Budget Optimization

    Directory of Open Access Journals (Sweden)

    Sanjida Sharmin Mohona

    2015-02-01

    Full Text Available This paper deals with the design and performance analysis of a very small size, low-cost, lowprofile, high gain and high directivity C Band Micro strip Patch Feed Reflector Antenna considering the link budget optimization. The proposed antenna system has a gain of -4.45dB, directivity of 7.062dBi, return loss of - 16.817327dB at 5.532 GHz and -15.998dB at 6.532GHz, Voltage Standing Wave Ratio (VSWR of 1.338 at 5.5302GHz and 1.3766 at 6.5309 GHz, at C band it operates in two regions with bandwidth of 184MHz (5.4431 to 5.6275GHz and 422MHz (6.3356 to 6.7576 GHz. The resonant frequencies of the antenna are 5.532GHzand 6.532GHz. The proposed antenna system can be used for C-band like satellite communications transmissions, VSAT, Wi-Fi, weather radar systems, medical applications and other wireless systems. The antenna system is designed and simulated in the CST Microwave Studio. Link budget optimization is performed in order to analyze the critical factors in the transmission chain and to optimize the performance characteristics. The link budget determines what size antenna is to use, power requirements and in general, the overall customer satisfaction.

  17. A multi-level analysis of the EU linking directive process: the controversial connection between EU and global climate policy

    Energy Technology Data Exchange (ETDEWEB)

    Flaam, Karoline Haegstad

    2007-10-15

    Despite initial scepticism in the EU towards the Kyoto Protocol's project mechanisms (the CDM and JI), the 'Linking Directive' was adopted in October 2004, connecting the EU emissions trading scheme with the project mechanisms. Not only was the Linking Directive settled remarkably quickly, the decision-making process also left a more liberal text, with fewer restrictions on the use of the project mechanisms, as compared to the initial directive proposal. This report examines possible explanations to this puzzle, evaluating whether Member State preferences, EU institutions or external influence from the climate regime best can contribute to understanding the process. On the basis of the analysis of written sources stemming from the decision-making process, as well as seven in-depth interviews, the report finds that Member State preferences were the main driver in the Linking Directive process. This gives support to the intergovernmentalist mantra, that Member States are the main decision-makers in the EU. It also challenges much recent research claiming that EU policy-making is increasingly being taken out of the hands of the nation-state and into supranational actors such as the Commission and the European Parliament. (author). 41 refs., figs., tabs

  18. Glutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence

    Directory of Open Access Journals (Sweden)

    Edouard ePearlstein

    2015-05-01

    Full Text Available The spontaneous activity pattern of adult dopaminergic (DA neurons of the substantia nigra pars compacta (SNc results from interactions between intrinsic membrane conductances and afferent inputs. In adult SNc DA neurons, low-frequency tonic background activity is generated by intrinsic pacemaker mechanisms, whereas burst generation depends on intact synaptic inputs in particular the glutamatergic ones. Tonic DA release in the striatum during pacemaking is required to maintain motor activity, and burst firing evokes phasic DA release, necessary for cue-dependent learning tasks. However, it is still unknown how the firing properties of SNc DA neurons mature during postnatal development before reaching the adult state. We studied the postnatal developmental profile of spontaneous and evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs in SNc DA neurons in brain slices from immature (postnatal days P4-10 and young adult (P30-50 tyrosine hydroxylase (TH-GFP mice. We found that somato-dendritic fields of SNc DA neurons are already mature at P4-10. In contrast, spontaneous glutamatergic EPSCs show a developmental sequence. Spontaneous NMDA EPSCs in particular are larger and more frequent in immature SNc DA neurons than in young adult ones and have a bursty pattern. They are mediated by GluN2B and GluN2D subunit-containing NMDA receptors. The latter generate long-lasting, DQP1105-sensitive, spontaneous EPSCs, which are transiently recorded during this early period. Due to high NMDA activity, immature SNc DA neurons generate large and long lasting NMDA receptor-dependent (APV-sensitive bursts in response to the stimulation of the subthalamic nucleus. We conclude that the transient high NMDA activity allows calcium influx into the dendrites of developing SNc DA neurons.

  19. Differential presynaptic actions of pyrethroid insecticides on glutamatergic and GABAergic neurons in the hippocampus.

    Science.gov (United States)

    Hossain, Muhammad Mubarak; Suzuki, Tadahiko; Unno, Toshihiro; Komori, Seiichi; Kobayashi, Haruo

    2008-01-14

    This study was designed to investigate the effects of several pyrethroids on the extracellular level of glutamate and gamma-aminobutyric acid (GABA) in the hippocampus of rats measured using microdialysis following systemic (i.p.) administration. Pyrethroids, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II), were found to have differential effects on glutamatergic and GABAergic neurons in the hippocampus. Allethrin had an interesting dual effect, increasing glutamate release with low doses (10 and 20mg/kg) to about 175-150% and decreasing glutamate release with high dose (60 mg/kg) to about 50% of baseline. Cyhalothrin (10, 20 and 60 mg/kg) inhibited the release of glutamate dose-dependently to about 60-30% of baseline. The extracellular level of GABA was decreased to about 50% of baseline by 10 and 20mg/kg allethrin. The high dose of allethrin (60 mg/kg) and all doses of cyhalothrin (10, 20 and 60 mg/kg) increased the extracellular level of GABA while decreasing the level of glutamate. Deltamethrin dose-dependently increased extracellular glutamate levels to about 190-275% of baseline while decreasing the level of GABA. Local infusion of TTX (1 microM), a Na(+) channel blocker, completely prevented the effect of allethrin (10, 20 and 60 mg/kg), cyhalothrin (20 and 60 mg/kg) and deltamethrin (20mg/kg) on glutamate and GABA release, but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on glutamate release was completely prevented by local infusion of nimodipine (10 microM), an L-type Ca(2+) channel blocker. Collectively, results from this study suggest that the excitatory glutamatergic neurons in the hippocampus are modulated by inhibitory GABA-releasing interneurons and that other mechanisms, beside sodium channels, may be involved with the neurotoxic action of pyrethroids.

  20. Glutamatergic mechanisms associated with stress-induced amygdala excitability and anxiety-related behavior.

    Science.gov (United States)

    Masneuf, Sophie; Lowery-Gionta, Emily; Colacicco, Giovanni; Pleil, Kristen E; Li, Chia; Crowley, Nicole; Flynn, Shaun; Holmes, Andrew; Kash, Thomas

    2014-10-01

    The neural factors underlying individual differences in susceptibility to chronic stress remain poorly understood. Preclinical studies demonstrate that mouse strains vary greatly in anxiety-related responses to chronic stress in a manner paralleled by differential stress-induced changes in glutamatergic signaling in the basolateral amygdala (BLA). Previous work has also shown that alterations in the amygdala gene expression of the GluN1 NMDA and the GluK1 kainate receptors are associated with stress-induced alterations in anxiety-like behavior in the C57BL/6J mouse strain. Using in vivo behavioral pharmacological and ex vivo physiological approaches, the aim of the current study was to further elucidate changes in glutamate neurotransmission in the BLA caused by stress and to test the functional roles of GluN1 and GluK1 in mediating stress-related changes in behavior. Results showed that stress-induced alterations in anxiety-like behavior (light/dark exploration test) were absent following bilateral infusion of the GluK1 agonist ATPA into the BLA. Intra-BLA infusion of the competitive NMDA antagonist AP5 produced a generalized behavioral disinhibition/locomotor hyperactivity, irrespective of stress. Slice electrophysiological recordings showed that ATPA augmented BLA GABAergic neurotransmission and that stress increased the amplitude of network-dependent spontaneous excitatory postsynaptic currents and amplitude of GABAergic miniature inhibitory postsynaptic currents in BLA. These findings could indicate stress-induced BLA glutamatergic neuronal network hyperexcitability and a compensatory increase in GABAergic neurotransmission, suggesting that GluK1 agonism augmented GABAergic inhibition to prevent behavioral sequelae of stress. Current data could have implications for developing novel therapeutic approaches, including GluK1 agonists, for stress-related anxiety disorders.

  1. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    Directory of Open Access Journals (Sweden)

    Nicole Purrier

    Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

  2. Recovery of network-driven glutamatergic activity in rat hippocampal neurons during chronic glutamate receptor blockade.

    Science.gov (United States)

    Leininger, Eric; Belousov, Andrei B

    2009-01-28

    Previous studies indicated that a long-term decrease in the activity of ionotropic glutamate receptors induces cholinergic activity in rat and mouse hypothalamic neuronal cultures. Here we studied whether a prolonged inactivation of ionotropic glutamate receptors also induces cholinergic activity in hippocampal neurons. Receptor activity was chronically suppressed in rat hippocampal primary neuronal cultures with two proportionally increasing sets of concentrations of NMDA plus non-NMDA receptor antagonists: 100 microM/10 microM AP5/CNQX (1X cultures) and 200 microM/20 microM AP5/CNQX (2X cultures). Using calcium imaging we demonstrate that cholinergic activity does not develop in these cultures. Instead, network-driven glutamate-dependent activity, that normally is detected in hyper-excitable conditions, reappears in each culture group in the presence of these antagonists and can be reversibly suppressed by higher concentrations of AP5/CNQX. This activity is mediated by non-NMDA receptors and is modulated by NMDA receptors. Further, non-NMDA receptors, the general level of glutamate receptor activity and CaMK-dependent signaling are critical for development of this network-driven glutamatergic activity in the presence of receptor antagonists. Using electrophysiology, western blotting and calcium imaging we show that some neuronal parameters are either reduced or not affected by chronic glutamate receptor blockade. However, other parameters (including neuronal excitability, mEPSC frequency, and expression of GluR1, NR1 and betaCaMKII) become up-regulated and, in some cases, proportionally between the non-treated, 1X and 2X cultures. Our data suggest recovery of the network-driven glutamatergic activity after chronic glutamate receptor blockade. This recovery may represent a form of neuronal plasticity that compensates for the prolonged suppression of the activity of glutamate receptors.

  3. Methamphetamine modulates glutamatergic synaptic transmission in rat primary cultured hippocampal neurons.

    Science.gov (United States)

    Zhang, Shuzhuo; Jin, Yuelei; Liu, Xiaoyan; Yang, Lujia; Ge, Zhi juan; Wang, Hui; Li, Jin; Zheng, Jianquan

    2014-09-25

    Methamphetamine (METH) is a psychostimulant drug. Abuse of METH produces long-term behavioral changes including behavioral, sensitization, tolerance, and dependence. It induces neurotoxic effects in several areas of the brain via enhancing dopamine (DA) level abnormally, which may cause a secondary release of glutamate (GLU). However, repeated administration of METH still increases release of GLU even when dopamine content in tissue is significantly depleted. It implies that some other mechanisms are likely to involve in METH-induced GLU release. The goal of this study was to observe METH affected glutamatergic synaptic transmission in rat primary cultured hippocampal neurons and to explore the mechanism of METH modulated GLU release. Using whole-cell patch-clamp recordings, we found that METH (0.1-50.0μM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs). However, METH decreased the frequency of sEPSCs and mEPSCs at high concentration of 100μM. The postsynaptic NMDA receptor currents and P/Q-type calcium channel were not affected by the use of METH (10,100μM). METH did not present visible effect on N-type Ca(2+) channel current at the concentration lower than 50.0μM, but it was inhibited by use of METH at a 100μM. The effect of METH on glutamatergic synaptic transmission was not revered by pretreated with DA receptor antagonist SCH23390. These results suggest that METH directly modulated presynaptic GLU release at a different concentration, while dopaminergic system was not involved in METH modulated release of GLU in rat primary cultured hippocampal neurons.

  4. Presynaptic muscarinic M(2) receptors modulate glutamatergic transmission in the bed nucleus of the stria terminalis.

    Science.gov (United States)

    Guo, Ji-Dong; Hazra, Rimi; Dabrowska, Joanna; Muly, E Chris; Wess, Jürgen; Rainnie, Donald G

    2012-03-01

    The anterolateral cell group of the bed nucleus of the stria terminalis (BNST(ALG)) serves as an important relay station in stress circuitry. Limbic inputs to the BNST(ALG) are primarily glutamatergic and activity-dependent changes in this input have been implicated in abnormal behaviors associated with chronic stress and addiction. Significantly, local infusion of acetylcholine (ACh) receptor agonists into the BNST trigger stress-like cardiovascular responses, however, little is known about the effects of these agents on glutamatergic transmission in the BNST(ALG). Here, we show that glutamate- and ACh-containing fibers are found in close association in the BNST(ALG). Moreover, in the presence of the acetylcholinesterase inhibitor, eserine, endogenous ACh release evoked a long-lasting reduction of the amplitude of stimulus-evoked EPSCs. This effect was mimicked by exogenous application of the ACh analog, carbachol, which caused a reversible, dose-dependent, reduction of the evoked EPSC amplitude, and an increase in both the paired-pulse ratio and coefficient of variation, suggesting a presynaptic site of action. Uncoupling of postsynaptic G-proteins with intracellular GDP-β-S, or application of the nicotinic receptor antagonist, tubocurarine, failed to block the carbachol effect. In contrast, the carbachol effect was blocked by prior application of atropine or M(2) receptor-preferring antagonists, and was absent in M(2)/M(4) receptor knockout mice, suggesting that presynaptic M(2) receptors mediate the effect of ACh. Immunoelectron microscopy studies further revealed the presence of M(2) receptors on axon terminals that formed asymmetric synapses with BNST neurons. Our findings suggest that presynaptic M(2) receptors might be an important modulator of the stress circuit and hence a novel target for drug development.

  5. Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome.

    Science.gov (United States)

    Kaur, Gurjinder; Sharma, Ajay; Xu, Wenjin; Gerum, Scott; Alldred, Melissa J; Subbanna, Shivakumar; Basavarajappa, Balapal S; Pawlik, Monika; Ohno, Masuo; Ginsberg, Stephen D; Wilson, Donald A; Guilfoyle, David N; Levy, Efrat

    2014-04-09

    Trisomy 21, or Down's syndrome (DS), is the most common genetic cause of intellectual disability. Altered neurotransmission in the brains of DS patients leads to hippocampus-dependent learning and memory deficiency. Although genetic mouse models have provided important insights into the genes and mechanisms responsible for DS-specific changes, the molecular mechanisms leading to memory deficits are not clear. We investigated whether the segmental trisomy model of DS, Ts[Rb(12.1716)]2Cje (Ts2), exhibits hippocampal glutamatergic transmission abnormalities and whether these alterations cause behavioral deficits. Behavioral assays demonstrated that Ts2 mice display a deficit in nest building behavior, a measure of hippocampus-dependent nonlearned behavior, as well as dysfunctional hippocampus-dependent spatial memory tested in the object-placement and the Y-maze spontaneous alternation tasks. Magnetic resonance spectra measured in the hippocampi revealed a significantly lower glutamate concentration in Ts2 as compared with normal disomic (2N) littermates. The glutamate deficit accompanied hippocampal NMDA receptor1 (NMDA-R1) mRNA and protein expression level downregulation in Ts2 compared with 2N mice. In concert with these alterations, paired-pulse analyses suggested enhanced synaptic inhibition and/or lack of facilitation in the dentate gyrus of Ts2 compared with 2N mice. Ts2 mice also exhibited disrupted synaptic plasticity in slice recordings of the hippocampal CA1 region. Collectively, these findings imply that deficits in glutamate and NMDA-R1 may be responsible for impairments in synaptic plasticity in the hippocampus associated with behavioral dysfunctions in Ts2 mice. Thus, these findings suggest that glutamatergic deficits have a significant role in causing intellectual disabilities in DS.

  6. Effect of VGLUT inhibitors on glutamatergic synaptic transmission in the rodent hippocampus and prefrontal cortex.

    Science.gov (United States)

    Neale, S A; Copeland, C S; Salt, T E

    2014-07-01

    Vesicular glutamate transporters (VGLUTs) are known to be important in the uptake of glutamate into vesicles in the presynaptic terminal; thereby playing a role in synaptic function. VGLUT dysfunction has also been suggested in neurological and psychiatric disorders such as epilepsy and schizophrenia. A number of compounds have been identified as VGLUT inhibitors; however, little is known as to how these compounds affect synaptic transmission. We therefore investigated the effects of structurally unrelated VGLUT inhibitors on synaptic transmission in the rodent hippocampus and prefrontal cortex. In the CA1 and dentate gyrus regions of the in vitro slice preparation of mouse hippocampus, AMPA receptor-mediated field excitatory postsynaptic potentials (fEPSPs) were evoked in response to Schaffer collateral/commissural pathway stimulation. Application of the VGLUT inhibitors Rose Bengal (RB), Congo Red (CR) or Chicago Sky Blue 6B (CB) resulted in a concentration-related reduction of fEPSP amplitudes. RB (30μM) or CB (300μM) also depressed NMDA receptor-mediated responses in the CA1 region. The naturally occurring kynurenine Xanthurenic Acid (XA) is reported to be a VGLUT inhibitor. We found XA attenuated both AMPA and NMDA receptor-mediated synaptic transmission. The potency order of the VGLUT inhibitors was consistent with literature Ki values for VGLUT inhibition. Impaired glutamatergic neurotransmission is believed to contribute to schizophrenia, and VGLUTs have also been implicated in this disease. We therefore investigated the effect of VGLUT inhibition in the prefrontal cortex. Application of the VGLUT inhibitors RB or CB resulted in a concentration-dependent reduction in the amplitude of glutamate receptor-mediated fEPSPs recorded in layer V/VI in response to stimulation in the forceps minor. We conclude that VGLUT inhibitors can modulate glutamatergic synaptic transmission in the PFC and hippocampus. This could be important in the pathophysiology of nervous

  7. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    Science.gov (United States)

    Purrier, Nicole; Engeland, William C; Kofuji, Paulo

    2014-01-01

    Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

  8. Linking Automated Data Analysis and Visualization with Applications in Developmental Biology and High-Energy Physics

    Energy Technology Data Exchange (ETDEWEB)

    Ruebel, Oliver [Technical Univ. of Darmstadt (Germany)

    2009-11-20

    Knowledge discovery from large and complex collections of today's scientific datasets is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the increasing number of data dimensions and data objects is presenting tremendous challenges for data analysis and effective data exploration methods and tools. Researchers are overwhelmed with data and standard tools are often insufficient to enable effective data analysis and knowledge discovery. The main objective of this thesis is to provide important new capabilities to accelerate scientific knowledge discovery form large, complex, and multivariate scientific data. The research covered in this thesis addresses these scientific challenges using a combination of scientific visualization, information visualization, automated data analysis, and other enabling technologies, such as efficient data management. The effectiveness of the proposed analysis methods is demonstrated via applications in two distinct scientific research fields, namely developmental biology and high-energy physics.Advances in microscopy, image analysis, and embryo registration enable for the first time measurement of gene expression at cellular resolution for entire organisms. Analysis of high-dimensional spatial gene expression datasets is a challenging task. By integrating data clustering and visualization, analysis of complex, time-varying, spatial gene expression patterns and their formation becomes possible. The analysis framework MATLAB and the visualization have been integrated, making advanced analysis tools accessible to biologist and enabling bioinformatic researchers to directly integrate their analysis with the visualization. Laser wakefield particle accelerators (LWFAs) promise to be a new compact source of high-energy particles and radiation, with wide applications ranging from medicine to physics. To gain insight into the complex physical processes of particle

  9. Error Probability Analysis of Free-Space Optical Links with Different Channel Model under Turbulent Condition

    CERN Document Server

    Barua, Bobby; Islam, Md Rezwan

    2012-01-01

    Free space optics (FSO) is a promising solution for the need to very high data rate point-to point communication. FSO communication technology became popular due to its large bandwidth potential, unlicensed spectrum, excellent security and quick and inexpensive setup. Unfortunately, atmospheric turbulence-induced fading is one of the main impairments affecting FSO communications. To design a high performance communication link for the atmospheric FSO channel, it is of great importance to characterize the channel with proper model. In this paper, the modulation format is Q-ary PPM across lasers, with intensity modulation and ideal photodetectors are assumed to investigate the most efficient PDF models for FSO communication under turbulent condition. The performance results are evaluated in terms of symbol error probability (SEP) for different type of channel model and the simulation results confirm the analytical findings.

  10. Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.

    Science.gov (United States)

    Bulusu, Vinay; Prior, Nicole; Snaebjornsson, Marteinn T; Kuehne, Andreas; Sonnen, Katharina F; Kress, Jana; Stein, Frank; Schultz, Carsten; Sauer, Uwe; Aulehla, Alexander

    2017-02-27

    How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated metabolic changes during development of organogenesis-stage mouse embryos, focusing on the presomitic mesoderm (PSM). We measured glycolytic labeling kinetics from (13)C-glucose tracing experiments and detected elevated glycolysis in the posterior, more undifferentiated PSM. We found evidence that the spatial metabolic differences are functionally relevant during PSM development. To enable real-time quantification of a glycolytic metabolite with spatiotemporal resolution, we generated a pyruvate FRET-sensor reporter mouse line. We revealed dynamic changes in cytosolic pyruvate levels as cells transit toward a more anterior PSM state. Combined, our approach identifies a gradient of glycolytic activity across the PSM, and we provide evidence that these spatiotemporal metabolic changes are intrinsically linked to PSM development and differentiation.

  11. Experimental and Simulation Analysis for the Impact of a Two-Link Chain with Granular Matter

    Directory of Open Access Journals (Sweden)

    Eliza A. Banu

    2015-01-01

    Full Text Available The resistance force of the granular matter is modeled as a linear superposition of a static (quadratic depth-dependent resistance force and a dynamic (quadratic velocity-dependent frictional force. The impact is defined from the moment the end point of the system comes in contact with the granular matter surface until the vertical linear velocity of the end point is zero. The variables of interest are the final depth at the end of the penetration phase and the stopping time. The results for a two-link kinematic chain with two points of contact were compared to the results obtained by applying the resistance force formulation developed to corresponding CAD simulation models. The results revealed that the final displacement increases with initial velocity, while the stopping time decreases. The sensitivity to the initial velocity was studied and an improvement to the resistance force formulated as a result. A series of expressions are proposed for the resistance force coefficients.

  12. Synthesis and conformational analysis of novel trimeric maleimide cross-linking reagents.

    Science.gov (United States)

    Szczepanska, Agnieszka; Espartero, José Luis; Moreno-Vargas, Antonio J; Carmona, Ana T; Robina, Inmaculada; Remmert, Sarah; Parish, Carol

    2007-08-31

    Nine homotrifunctional cross-linking reagents are presented. Their synthesis and chemical properties as well as their characterization by classical mechanical conformational searching techniques is reported. Mixed Low Mode and Monte Carlo searching techniques were used to exhaustively sample the OPLS2005/GBSA(water) potential energy surface of trisubstituted cyclohexane and benzene derivatives of C3 symmetry. Geometric structure, molecular length, and hydrogen-bonding patterns were analyzed. Nonaromatic compounds exhibited exclusively chair conformations at low energies, with a preference for axial or equatorial arms depending upon the presence of additional ring substituent Me groups. Increasing chain length often resulted in overall shorter molecular length due to additional chain flexibility. These results were consistent with one- and two-dimensional temperature-dependent NMR studies.

  13. Linking renewable energy CDM projects and TGC schemes: An analysis of different options

    Energy Technology Data Exchange (ETDEWEB)

    Del Rio, Pablo [Department of Economics and Business, Facultad de Ciencias Juridicas y Sociales, Universidad de Castilla-La Mancha, C/ Cobertizo de S. Pedro Martir s/n., Toledo-45071 (Spain)]. E-mail: pablo.rio@uclm.es

    2006-11-15

    Renewable energy CDM (RE-CDM) projects encourage cost-effective GHG mitigation and enhanced sustainable development opportunities for the host countries. CERs from CDM projects include the value of the former benefits (i.e., 'climate change benefits'), whereas the second can be given value through the issuing and trading of tradable green certificates (TGCs). Countries could agree to trade these TGCs, leading to additional revenues for the investors in renewable energy projects and, therefore, further encouraging the deployment of CDM projects, currently facing significant barriers. However, the design of a combination of CDM projects and TGC schemes raises several conflicting issues and leads to trade-offs. This paper analyses these issues, identifies the alternatives that may exist to link TGC schemes with RE-CDM projects and analyses the impacts of those options on different variables and actors.

  14. On the Performance Analysis of Free-Space Optical Links under Generalized Turbulence and Misalignment Models

    KAUST Repository

    AlQuwaiee, Hessa

    2016-11-01

    One of the potential solutions to the radio frequency (RF) spectrum scarcity problem is optical wireless communications (OWC), which utilizes the unlicensed optical spectrum. Long-range outdoor OWC are usually referred to in the literature as free-space optical (FSO) communications. Unlike RF systems, FSO is immune to interference and multi-path fading. Also, the deployment of FSO systems is flexible and much faster than optical fibers. These attractive features make FSO applicable for broadband wireless transmission such as optical fiber backup, metropolitan area network, and last mile access. Although FSO communication is a promising technology, it is negatively affected by two physical phenomenon, namely, scintillation due to atmospheric turbulence and pointing errors. These two critical issues have prompted intensive research in the last decade. To quantify the effect of these two factors on FSO system performance, we need effective mathematical models. In this work, we propose and study a generalized pointing error model based on the Beckmann distribution. Then, we aim to generalize the FSO channel model to span all turbulence conditions from weak to strong while taking pointing errors into consideration. Since scintillation in FSO is analogous to the fading phenomena in RF, diversity has been proposed too to overcome the effect of irradiance fluctuations. Thus, several combining techniques of not necessarily independent dual-branch free-space optical links were investigated over both weak and strong turbulence channels in the presence of pointing errors. On another front, improving the performance, enhancing the capacity and reducing the delay of the communication link has been the motivation of any newly developed schemes, especially for backhauling. Recently, there has been a growing interest in practical systems to integrate RF and FSO technologies to solve the last mile bottleneck. As such, we also study in this thesis asymmetric an RF-FSO dual-hop relay

  15. Links between Bloom's Taxonomy and Gardener's Multiple Intelligences: The Issue of Textbook Analysis

    Science.gov (United States)

    Tabari, Mahmoud Abdi; Tabari, Iman Abdi

    2015-01-01

    The major thrust of this research was to investigate the cognitive aspect of the high school textbooks and interchange series, due to their extensive use, through content analysis based on Bloom's taxonomy and Gardner's Multiple Intelligences (MI). This study embraced two perspectives in a grid in order to broaden and deepen the analysis by…

  16. QTL list - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available [ Credits ] BLAST Search Image Search Home About Archive Update History Contact us PGDBj Registered...Policy | Contact Us QTL list - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive ...

  17. Preserving and maintaining vital Ecosystem Services: the importance of linking knowledge from Geosciences and social-ecological System analysis

    Science.gov (United States)

    Finger, David; Petursdottir, Thorunn

    2013-04-01

    Human kind has always been curios and motivated to understand and quantify environmental processes in order to predict and anticipate the evolution of vital ecosystem services. Even the very first civilizations used empirical correlations to predict outcomes of rains and subsequent harvest efficiencies. Along with the insights into the functioning of ecosystems, humans also became aware that their anthropogenic activities can have positive and negative impact on ecosystem services. In recent years, geosciences have brought forward new sophisticated observations and modeling tools, with the aim to improve predictions of ecological developments. At the same time, the added value of linking ecological factors to the surrounding social structure has received a growing acceptance among scientists. A social-ecological system approach brings in a holistic understanding of how these systems are inevitably interlinked and how their sustainability can be better maintained. We claim that the biggest challenge for geoscience in the coming decades will be to link these two disciplines in order to establish adequate strategies to preserve natural ecosystems and their services, parallel to their utilization. We will present various case studies from more than a decade of research, ranging from water quality in mountain lakes, climate change impacts on water availability and declining fishing yields in freshwaters and discuss how the studies outcomes could be given added value by interpreting them via social-ecological system analysis. For instance, sophisticated field investigations revealed that deep water mixing in lake Issyk-Kul, Kirgizstan, is intensively distributing pollutants in the entire lake. Although fishery is an important sector in the region, the local awareness of the importance of water quality is low. In Switzerland, strict water protection laws led to ologotrophication of alpine lakes, reducing fishing yields. While local fishermen argued that local fishery is

  18. Analysis of fourth-grade flat machines with movable close-cycle formed by the rods and two complex links

    Directory of Open Access Journals (Sweden)

    S.О. Koshel

    2016-09-01

    Full Text Available Complex multielement mechanisms are increasingly used in the technical equipment of consumer industry. The lack of a universal method of kinematic research of these mechanisms asserts the relevance of work on the kinematic analysis of multielement mechanisms. Aim: The aim of this research is to develop an algorithm kinetic research of velocities of the points that coincide with geometric centers kinematic pairs of structure group of the 4th class and 3rd order with movable close-cycle formed by connecting rod and two complex links. Materials and Methods: The graphic-analytical method of a kinematic research will be used to achieve the goals of research. Development of an algorithm is based on provisions of the theory of mechanisms and engines about property of high classes mechanisms to change its class depending on another possible initial mechanism chosen conditionally which comes to structure of the conducted structural groups of the mechanism links and provisions of theoretical mechanics relatively to instantaneous center of speeds. Results: Velocity vectors of points of Assur group links of the 4th class and 3rd order of the composite flat mechanism are determined by a graphic-analytical method, where the initial mechanism speeds that led to decrease of a class of the mechanism and allowed to investigate it. Unlike the known erroneous statements method which is applied to research the structural groups of the 3rd class, the offered algorithm of the kinematic analysis allows to investigate mechanisms of the 4th class without need to rebuild the plan which was constructed in a uncertain scale, with the subsequent calculation of the real scale parameter of provided plotting of a graph.

  19. Kinetic analysis of histamine release due to covalently linked IgE dimers

    Energy Technology Data Exchange (ETDEWEB)

    Dembo, M. (Los Alamos Scientific Lab., NM); Kagey-Sobotka, A.; Lichtenstein, L.M.; Goldstein, B.

    1982-01-01

    We present a kinetic model of histamine release from human basophils due to covalently linked IgE dimers. Comparison of theory with experiment shows that the model gives a good description of histamine release by IgE dimers and allows a number of the parameters of the model to be determined. Comparison with previous models of release by conventional antigens indicates that despite their covalent structure, IgE dimers are subject to the same laws governing inactivation as are antigen produced crosslinks. In addition, the kinetic equation which relates the rate of histamine release to the number of crosslinked Fc/sub e/ receptors per cell is the same for crosslinks formed by IgE dimers as for antigen induced crosslinks. Quantitative fitting of histamine release data also yields a value for the rate constant for crosslink formation by IgE dimer on the cell surface (r/sub x/ approx. = to 5 x 10/sup -10/ cm/sup 2//sec). This rate constant is remarkably high and indicates that the reaction is diffusion controlled.

  20. Analysis of the solid waste management practices in Chinhoyi: bridging the missing link

    Directory of Open Access Journals (Sweden)

    Ishumael SANGO

    2010-12-01

    Full Text Available Over the years, there has been noticeable and steady mismatch between urban population growth and capacity for managing the corresponding increases in solid wastes. The local community is greatly concerned because it is aware of the clear link between poorly managed waste and the potential for the spread of diseases. This study was carried out to examine the solid waste management practices in Chinhoyi urban area and assess the impacts on the environment and human health. The study combined quantitative and qualitative data collected through fieldwork, questionnaires, interviews and document reviews. The population of Chinhoyi stands at about 60 000 generating more than 100 tons of waste per day. Results of the study include high percentage of uncollected waste, high levels of health and safety related problems such as lacerations, contusions, strain/sprains, and illness as well as noticeable deterioration of facilities and the environment. Issues affecting the effective management of waste are discussed. Recommendations based on the sustainable principle of integrated solid waste management are suggested. Sustainability requires the system to be environmentally effective, economically affordable, and socially acceptable.

  1. A new measure based on degree distribution that links information theory and network graph analysis

    Science.gov (United States)

    2012-01-01

    Background Detailed connection maps of human and nonhuman brains are being generated with new technologies, and graph metrics have been instrumental in understanding the general organizational features of these structures. Neural networks appear to have small world properties: they have clustered regions, while maintaining integrative features such as short average pathlengths. Results We captured the structural characteristics of clustered networks with short average pathlengths through our own variable, System Difference (SD), which is computationally simple and calculable for larger graph systems. SD is a Jaccardian measure generated by averaging all of the differences in the connection patterns between any two nodes of a system. We calculated SD over large random samples of matrices and found that high SD matrices have a low average pathlength and a larger number of clustered structures. SD is a measure of degree distribution with high SD matrices maximizing entropic properties. Phi (Φ), an information theory metric that assesses a system’s capacity to integrate information, correlated well with SD - with SD explaining over 90% of the variance in systems above 11 nodes (tested for 4 to 13 nodes). However, newer versions of Φ do not correlate well with the SD metric. Conclusions The new network measure, SD, provides a link between high entropic structures and degree distributions as related to small world properties. PMID:22726594

  2. PDD CRAWLER: A FOCUSED WEB CRAWLER USING LINK AND CONTENT ANALYSIS FOR RELEVENCE PREDICTION

    Directory of Open Access Journals (Sweden)

    Prashant Dahiwale

    2014-11-01

    Full Text Available Majority of the computer or mobile phone enthusiasts make use of the web for searching activity. Web search engines are used for the searching; The results that the search engines get are provided to it by a software module known as the Web Crawler. The size of this web is increasing round-the-clock. The principal problem is to search this huge database for specific information. To state whether a web page is relevant to a search topic is a dilemma. This paper proposes a crawler called as “PDD crawler” which will follow both a link based as well as a content based approach. This crawler follows a completely new crawling strategy to compute the relevance of the page. It analyses the content of the page based on the information contained in various tags within the HTML source code and then computes the total weight of the page. The page with the highest weight, thus has the maximum content and highest relevance.

  3. Constraint Network Analysis (CNA): a Python software package for efficiently linking biomacromolecular structure, flexibility, (thermo-)stability, and function.

    Science.gov (United States)

    Pfleger, Christopher; Rathi, Prakash Chandra; Klein, Doris L; Radestock, Sebastian; Gohlke, Holger

    2013-04-22

    For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity analyses in that phase transition points ("melting points") and unfolding nuclei ("structural weak spots") are determined automatically. Furthermore, CNA robustly handles small-molecule ligands in general. Such advancements are important for applying rigidity analysis to data-driven protein engineering and for estimating the influence of ligand molecules on biomacromolecular stability. CNA maintains the efficiency of FIRST such that the analysis of a single protein structure takes a few seconds for systems of several hundred residues on a single core. These features make CNA an interesting tool for linking biomacromolecular structure, flexibility, (thermo-)stability, and function. CNA is available from http://cpclab.uni-duesseldorf.de/software for nonprofit organizations.

  4. Links between Bloom's Taxonomy and Gardener's Multiple Intelligences: The issue of Textbook Analysis

    Directory of Open Access Journals (Sweden)

    Mahmoud Abdi Tabari

    2015-02-01

    Full Text Available The major thrust of this research was to investigate the cognitive aspect of the high school textbooks and interchange series, due to their extensive use, through content analysis based on Bloom's taxonomy and Gardner's Multiple Intelligences (MI. This study embraced two perspectives in a grid in order to broaden and deepen the analysis by determining the numbers and the types of intelligences with respect to their learning objectives tapped in the textbooks and comparing them. Through codification of Bloom’s learning objectives and Gardner's MI, the results showed that there was a significant difference between the numbers of intelligences with respect to their learning objectives in the textbooks. However, the interchange series enjoyed a large number of the spatial and the interpersonal intelligences across eight levels of learning objectives, whereas they had the least number of the intrapersonal, the musical, and the bodily-kinesthetic intelligences across knowledge understanding and application levels. Keywords: learning objectives, multiple intelligences, textbook analysis

  5. Investigating the Link Between Climate and Leptospirosis in the Caribbean Using Wavelet Analysis.

    Science.gov (United States)

    Batchelor, T. W.; Amarakoon, D.; Taylor, M. A.; Stephenson, T.

    2009-05-01

    The Caribbean has shown changes in its climate (temperature and rainfall) as a result of urbanisation, population growth and industrialisation. The climatic changes have implications for the emergence and re- emergence of rodent-borne diseases such as leptospirosis. In this paper wavelet analysis is used to investigate the relationship between the incidence of leptospirosis in the Caribbean and climate variables such as temperature and precipitation. Wavelet analysis takes into account characteristics unique to climate and epidemiological data which other spectral techniques failed to do. The analysis reveals 2-3 year periodic signals in both the wavelet power spectrum and wavelet coherency. There is also a correlation between incidence of leptospirosis and late season Caribbean rainfall.

  6. Stability analysis of glutamic acid linked peptides coupled to NOTA through different chemical linkages.

    Science.gov (United States)

    Lang, Lixin; Ma, Ying; Kiesewetter, Dale O; Chen, Xiaoyuan

    2014-11-03

    Glutamic acid is a commonly used linker to form dimeric peptides with enhanced binding affinity than their corresponding monomeric counterparts. We have previously labeled NOTA-Bn-NCS-PEG3-E[c(RGDyK)]2 (NOTA-PRGD2) [1] with [(18)F]AlF and (68)Ga for imaging tumor angiogenesis. The p-SCN-Bn-NOTA was attached to E[c(RGDyK)]2 [2] through a mini-PEG with a thiourea linkage, and the product [1] was stable at radiolabeling condition of 100 °C and pH 4.0 acetate buffer. However, when the same p-SCN-Bn-NOTA was directly attached to the α-amine of E[c(RGDfK)]2 [3], the product NOTA-Bn-NCS-E[c(RGDfK)]2 [4] became unstable under similar conditions and the release of monomeric c(RGDfK) [5] was observed. The purpose of this work was to use HPLC and LC-MS to monitor the decomposition of glutamic acid linked dimeric peptides and their NOTA derivatives. A c(RGDyK) [6] and bombesin (BBN) [7] heterodimer c(RGDyK)-E-BBN [8], and a dimeric bombesin E(BBN)2 [9], both with a glutamic acid as the linker, along with a model compound PhSCN-E[c(RGDfK)] [10] were also studied. All the compounds were dissolved in 0.5 M pH 4.0 acetate buffer at the concentration of 1 mg/mL, and 0.1 mL of each sample was heated at 100 °C for 10 min and the more stable compounds were heated for another 30 min. The samples at both time points were analyzed with analytical HPLC to monitor the decomposition of the heated samples. The samples with decomposition were further analyzed by LC-MS to determine the mass of products from the decomposition for possible structure elucidation. After 10 min heating, the obvious release of c(RGDfK) [5] was observed for NOTA-Bn-NCS-E[c(RGDfK)]2 [4] and Ph-SCN-E[c(RGDfK)] [10]. Little or no release of monomers was observed for the remaining samples at this time point. After further heating, the release of monomers was clearly observed for E[c(RGDyK)]2 [2], E[c(RGDfK)]2 [3], c(RGDyK)-E-BBN [8], and E(BBN)2 [9]. No decomposition or little decomposition was observed for NOTA

  7. From Kindergarten readiness to fourth-grade assessment: longitudinal analysis with linked population data.

    Science.gov (United States)

    Lloyd, Jennifer E V; Hertzman, Clyde

    2009-01-01

    Early child development (ECD)--the development of physical, social-emotional, and language-cognitive capacities in the early years--is a foundation of health, well-being, learning, and behaviour across the life course. Consequently, the capacity to monitor ECD is an important facet of a modern society. This capacity is achieved by having in place an ongoing flow of high-quality information on the state of early child development, its determinants, and long-term developmental outcomes. Accordingly, there remains a considerable need for research that merges community-centred, longitudinal, and linked-data approaches to monitoring child development. The current paper addresses this need by introducing one method of summarising and quantifying the developmental trajectories of British Columbian children at the neighbourhood- or district-level: computing the Community Index of Child Development (CICD) for each geographic area. A simple index that describes change in children's developmental trajectories at the aggregate level, the CICD is computable because of our capacity to conduct individual-level linkage of two population data sets: the Early Development Instrument (EDI), a holistic measure of children's readiness for school which is administered at Kindergarten, and the British Columbia Ministry of Education's Foundation Skills Assessment (FSA), a Grade 4 measure of academic skills. In this paper, we demonstrate: (a) wide variation in the CICDs according to the children's district of residence in Kindergarten; (b) an association of the CICDs with an indicator of the socioeconomic character of the neighbourhoods; and (c) contrasting patterns of neighbourhood convergence and divergence in two different school districts--such that, in some areas, children from high vulnerability neighbourhoods tend to catch up between Kindergarten and Grade 4 whereas, in other areas, they tend to fall further behind.

  8. Adenosine A₂A receptors in striatal glutamatergic terminals and GABAergic neurons oppositely modulate psychostimulant action and DARPP-32 phosphorylation.

    Directory of Open Access Journals (Sweden)

    Hai-Ying Shen

    Full Text Available Adenosine A2A receptors (A2AR are located postsynaptically in striatopallidal GABAergic neurons, antagonizing dopamine D2 receptor functions, and are also located presynaptically at corticostriatal terminals, facilitating glutamate release. To address the hypothesis that these two A2AR populations differently control the action of psychostimulants, we characterized A2AR modulation of cocaine-induced effects at the level of DARPP-32 phosphorylation at Thr-34 and Thr-75, c-Fos expression, and psychomotor activity using two lines of cell-type selective A2AR knockout (KO mice with selective A2AR deletion in GABAergic neurons (striatum-A2AR-KO mice, or with A2AR deletion in both striatal GABAergic neurons and projecting cortical glutamatergic neurons (forebrain-A2AR-KO mice. We demonstrated that striatum-A2AR KO mice lacked A2ARs exclusively in striatal GABAergic terminals whereas forebrain-A2AR KO mice lacked A2ARs in both striatal GABAergic and glutamatergic terminals leading to a blunted A2AR-mediated facilitation of synaptosomal glutamate release. The inactivation of A2ARs in GABAergic neurons reduced striatal DARPP-32 phosphorylation at Thr-34 and increased its phosphorylation at Thr-75. Conversely, the additional deletion of corticostriatal glutamatergic A2ARs produced opposite effects on DARPP-32 phosphorylation at Thr-34 and Thr-75. This distinct modulation of DARPP-32 phosphorylation was associated with opposite responses to cocaine-induced striatal c-Fos expression and psychomotor activity in striatum-A2AR KO (enhanced and forebrain-A2AR KO mice (reduced. Thus, A2ARs in glutamatergic corticostriatal terminals and in GABAergic striatal neurons modulate the action of psychostimulants and DARPP-32 phosphorylation in opposite ways. We conclude that A2ARs in glutamatergic terminals prominently control the action of psychostimulants and define a novel mechanism by which A2ARs fine-tune striatal activity by integrating GABAergic, dopaminergic and

  9. Lexical Link Analysis Application: Improving Web Service to Acquisition Visibility Portal Phase II

    Science.gov (United States)

    2014-04-30

    Distributed Information and Systems Experimentation ( DISE ). Dr. Gallup has a multi-disciplinary science, engineering, and analysis background including...Experimentation ( DISE ) research group, since 2007. In 2009, he became involved with data mining research and its effect on Knowledge Management and defense

  10. Design and analysis of eccentrically braced steel frames with vertical links using shape memory alloys

    Science.gov (United States)

    Massah, Saeed Reza; Dorvar, Hosein

    2014-10-01

    In recent years, the philosophy behind traditional methods by which structures were designed to withstand natural disasters has gone through major changes. Shape memory alloys (SMAs) are characterized by their superelastic behavior, which enables them to recover their original shape after experiencing large deformations. This characteristic provides an ideal reversibility capacity that can be used in the passive control of buildings exposed to earthquakes. This article has attempted to identify the effects of changing the hysteretic characteristics of SMA materials when they are used as passive control systems in eccentric bracing frames. By evaluating the numerical analysis results obtained from the modeling of an experimental sample and the modeling of the proposed EBF system, the accuracy of the above-stated notion was confirmed. Moreover, the results that pertain to the nonlinear pushover analysis, time-history dynamic analysis and seismic damage analysis of eccentric steel bracing frames of 4-, 9- and 14-story structures indicate that the use of SMA superelastic materials, in addition to effectively improving their ductility, stiffness and lateral strength, provides an excellent reversibility capacity, which considerably reduces both the maximum relative displacement and the residual deformation in the structure.

  11. A multiplex network analysis of the Mexican banking system: link persistence, overlap, and waiting times

    NARCIS (Netherlands)

    Molina-Borboa, J.L.; Martínez-Jaramillo, S.; López-Gallo, F.; van der Leij, M.

    2015-01-01

    This paper analyzes the persistence and overlap of relationships between banks in a multiplex decomposition of the exposures network. Our analysis may be useful for researchers designing stress tests or models in which the behavior of banks is modeled explicitly. This has not been looked at previous

  12. Supply Chain Visibility with Linked Open Data for Supply Chain Risk Analysis

    NARCIS (Netherlands)

    Hofman, W.J.

    2011-01-01

    Current customs applications are declaration based to support the various customs procedures based on (inter)national laws and regulations. To be able to perform a proper supply chain risk analysis, customs requires to have all data in supply chains. The current declaration procedures are not suffic

  13. IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway.

    Directory of Open Access Journals (Sweden)

    Takashi Hayashi

    Full Text Available Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1 is associated with X-linked mental retardation and autism spectrum disorder. We found that IL1RAPL1 regulates synapse formation of cortical neurons. To investigate how IL1RAPL1 controls synapse formation, we here screened IL1RAPL1-interacting proteins by affinity chromatography and mass spectroscopy. IL1RAPL1 interacted with Mcf2-like (Mcf2l, a Rho guanine nucleotide exchange factor, through the cytoplasmic Toll/IL-1 receptor domain. Knockdown of endogenous Mcf2l and treatment with an inhibitor of Rho-associated protein kinase (ROCK, the downstream kinase of RhoA, suppressed IL1RAPL1-induced excitatory synapse formation of cortical neurons. Furthermore, we found that the expression of IL1RAPL1 affected the turnover of AMPA receptor subunits. Insertion of GluA1-containing AMPA receptors to the cell surface was decreased, whereas that of AMPA receptors composed of GluA2/3 was enhanced. Mcf2l knockdown and ROCK inhibitor treatment diminished the IL1RAPL1-induced changes of AMPA receptor subunit insertions. Our results suggest that Mcf2l-RhoA-ROCK signaling pathway mediates IL1RAPL1-dependent formation and stabilization of glutamatergic synapses of cortical neurons.

  14. ON AVERAGE CASE ANALYSIS THROUGH STATISTICAL BOUNDS : LINKING THEORY TO PRACTICE

    Directory of Open Access Journals (Sweden)

    Niraj Kumar Singh

    2013-02-01

    Full Text Available Theoretical analysis of algorithms involves counting of operations and a separate bound is provided for a specific operation type. Such a methodology is plagued with its inherent limitations. In this paper we argue as to why we should prefer weight based statistical bounds, which permit mixing of operations, instead as a robust approach. Empirical analysis is an important idea and should be used to supplement and compliment its existing theoretical counterpart as empirically we can work on weights (e.g. time of an operation can be taken as its weight. Not surprisingly, it should not only be taken as an opportunity so as to amend the mistakes already committed knowingly or unknowingly but also to tell a new story.

  15. High-throughput metabolic state analysis: The missing link in integrated functional genomics of yeasts

    DEFF Research Database (Denmark)

    Villas-Bôas, Silas Granato; Moxley, Joel. F; Åkesson, Mats Fredrik

    2005-01-01

    The lack of comparable metabolic state assays severely limits understanding the metabolic changes caused by genetic or environmental perturbations. The present study reports the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software that ach......The lack of comparable metabolic state assays severely limits understanding the metabolic changes caused by genetic or environmental perturbations. The present study reports the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software...... that achieve comparable throughput, effort and cost compared with DNA arrays. Our sample workup method enables simultaneous metabolite measurements throughout central carbon metabolism and amino acid biosynthesis, using a standard GC-MS platform that was optimized for this Purpose. As an implementation proof...

  16. Interlocking editorship. A network analysis of the links between economic journals

    CERN Document Server

    Baccini, Alberto; 10.1007/s11192-009-0053-7

    2011-01-01

    The exploratory analysis developed in this paper relies on the hypothesis that each editor possesses some power in the definition of the editorial policy of her journal. Consequently if the same scholar sits on the board of editors of two journals, those journals could have some common elements in their editorial policies. The proximity of the editorial policies of two scientific journals can be assessed by the number of common editors sitting on their boards. A database of all editors of ECONLIT journals is used. The structure of the network generated by interlocking editorship is explored by applying the instruments of network analysis. Evidences have been found of a compact network containing different components. This is interpreted as the result of a plurality of perspectives about the appropriate methods for the investigation of problems and the construction of theories within the domain of economics.

  17. Analysis of logistical support as the key link of military logistics

    Directory of Open Access Journals (Sweden)

    Артем Володимирович Зозуля

    2016-11-01

    Full Text Available The analysis of the specific logistic support in terms of military logistics is proposed in the article. Special attention is addressed to legal regulation of financial and business activity of military units in logistics processes. The special role of prime importance of the formation of the corresponding moral - psychological model of military personnel of military units and subunits are noted. The specifics of the formation of military logistics systems in current economic conditions is analyzed

  18. Lexical Link Analysis Application: Improving Web Service to Acquisition Visibility Portal Phase III

    Science.gov (United States)

    2015-04-30

    Experimentation ( DISE ) research group where he leads multidisciplinary studies ranging from leading the Analyst Capability Working Group for the U.S. Air...Information and Systems Experimentation ( DISE ). Dr. Gallup has a multidisciplinary science, engineering, and analysis background, including microbiology...4), 19–31. Retrieved from http://www.nps.edu/Academics/Schools/GSOIS/Departments/IS/ DISE /docs/improving- use-and-understanding-of-data-dod.pdf Zhou

  19. Dynamic Links between Exchange Rates and Stock Prices in Malaysia: An Asymmetric Cointegration analysis

    OpenAIRE

    ALI, Hamisu Sadi; Umar MUKHTAR; MANIAM, Ganthi Selvi

    2015-01-01

    Abstract. The present article used a monthly data and applied Enders and Siklos (2001) asymmetric cointegration analysis to examine the impact of exchange rates on stock prices in Malaysia for the period of 1999-2014. The result suggests that variables were cointegrated based on Engle-granger two step technique. Moving to threshold auto regressive (TAR) and momentumthreshold auto regressive (M-TAR) the finding reveals that based on the latter variables were asymmetrically cointegrated as null...

  20. Whole-Proteome Analysis of Twelve Species of Alphaproteobacteria Links Four Pathogens

    Directory of Open Access Journals (Sweden)

    Yunyun Zhou

    2013-11-01

    Full Text Available Thousands of whole-genome and whole-proteome sequences have been made available through advances in sequencing technology, and sequences of millions more organisms will become available in the coming years. This wealth of genetic information will provide numerous opportunities to enhance our understanding of these organisms including a greater understanding of relationships among species. Researchers have used 16S rRNA and other gene sequences to study the evolutionary origins of bacteria, but these strategies do not provide insight into the sharing of genes among bacteria via horizontal transfer. In this work we use an open source software program called pClust to cluster proteins from the complete proteomes of twelve species of Alphaproteobacteria and generate a dendrogram from the resulting orthologous protein clusters. We compare the results with dendrograms constructed using the 16S rRNA gene and multiple sequence alignment of seven housekeeping genes. Analysis of the whole proteomes of these pathogens grouped Rickettsia typhi with three other animal pathogens whereas conventional sequence analysis failed to group these pathogens together. We conclude that whole-proteome analysis can give insight into relationships among species beyond their phylogeny, perhaps reflecting the effects of horizontal gene transfer and potentially providing insight into the functions of shared genes by means of shared phenotypes.

  1. Microfluidic single-cell analysis links boundary environments and individual microbial phenotypes.

    Science.gov (United States)

    Dusny, Christian; Schmid, Andreas

    2015-06-01

    Life is based on the cell as the elementary replicative and self-sustaining biological unit. Each single cell constitutes an independent and highly dynamic system with a remarkable individuality in a multitude of physiological traits and responses to environmental fluctuations. However, with traditional population-based cultivation set-ups, it is not possible to decouple inherent stochastic processes and extracellular contributions to phenotypic individuality for two central reasons: the lack of environmental control and the occlusion of single-cell dynamics by the population average. With microfluidic single-cell analysis as a new cell assay format, these issues can now be addressed, enabling cultivation and time-resolved analysis of single cells in precisely manipulable extracellular environments beyond the bulk. In this article, we explore the interplay of cellular physiology and environment at a single-cell level. We review biological basics that govern the functional state of the cell and put them in context with physical fundamentals that shape the extracellular environment. Furthermore, the significance of single-cell growth rates as pivotal descriptors for global cellular physiology is discussed and highlighted by selected studies. These examples illustrate the unique opportunities of microfluidic single-cell cultivation in combination with growth rate analysis, addressing questions of fundamental bio(techno)logical interest.

  2. A Unified Performance Analysis of Free-Space Optical Links over Gamma-Gamma Turbulence Channels with Pointing Errors

    KAUST Repository

    Ansari, Imran Shafique

    2013-11-13

    In this work, we present a unified performance analysis of a free-space optical (FSO) link that accounts for pointing errors and both types of detection techniques (i.e. intensity modulation/direct detection as well as heterodyne detection). More specifically, we present unified exact closed-form expressions for the cumulative distribution function, the probability density function, the moment generating function, and the moments of the end-to-end signal-to-noise ratio (SNR) of a single link FSO transmission system, all in terms of the Meijer\\'s G function except for the moments that is in terms of simple elementary functions. We then capitalize on these unified results to offer unified exact closed-form expressions for various performance metrics of FSO link transmission systems, such as, the outage probability, the higher-order amount of fading (AF), the average error rate for binary and M-ary modulation schemes, and the ergodic capacity, all in terms of Meijer\\'s G functions except for the higher-order AF that is in terms of simple elementary functions. Additionally, we derive the asymptotic results for all the expressions derived earlier in terms of Meijer\\'s G function in the high SNR regime in terms of simple elementary functions via an asymptotic expansion of the Meijer\\'s G function. We also derive new asymptotic expressions for the ergodic capacity in the low as well as high SNR regimes in terms of simple elementary functions via utilizing moments. All the presented results are verified via computer-based Monte-Carlo simulations.

  3. A Topical Trajectory on Survival: an Analysis of Link-Making in a Sequence of Lessons on Evolution

    Science.gov (United States)

    Rocksén, Miranda; Olander, Clas

    2016-04-01

    This study explores the concept of link-making in relation to communicative strategies applied in the teaching and studying of biological evolution. The analysis focused on video recordings of 11 lessons on biological evolution conducted in a Swedish 9th grade class of students aged 15 years. It reveals how the teacher and students connected classroom conversations, the frequency of references to conversations in whole-class settings, and the development of a theme focusing on species survival and extinction. Detailed examples from the data illustrate how this theme developed from its initiation during the first lesson, through discussion and clarification, to its wrapping up during the last lesson. They further illustrate how students made sense of what the teacher said and wrote, and how the teacher postponed issues, explained and developed topics, provided opportunities for link-making, organised the class, motivated students, and checked their understanding. The study's methodological approach offers a way of including several time dimensions within research. Based on our findings, we conclude that the excerpts examined here did succeed in building `islands of coherence' in the co-construction of curricular content. Moreover, the topical trajectory in relation to species survival provided opportunities for constructing a `scientific story' in the classroom.

  4. Analysis and Optimization of Spiral Circular Inductive Coupling Link for Bio-Implanted Applications on Air and within Human Tissue

    Directory of Open Access Journals (Sweden)

    Saad Mutashar

    2014-06-01

    Full Text Available The use of wireless communication using inductive links to transfer data and power to implantable microsystems to stimulate and monitor nerves and muscles is increasing. This paper deals with the development of the theoretical analysis and optimization of an inductive link based on coupling and on spiral circular coil geometry. The coil dimensions offer 22 mm of mutual distance in air. However, at 6 mm of distance, the coils offer a power transmission efficiency of 80% in the optimum case and 73% in the worst case via low input impedance, whereas, transmission efficiency is 45% and 32%, respectively, via high input impedance. The simulations were performed in air and with two types of simulated human biological tissues such as dry and wet-skin using a depth of 6 mm. The performance results expound that the combined magnitude of the electric field components surrounding the external coil is approximately 98% of that in air, and for an internal coil, it is approximately 50%, respectively. It can be seen that the gain surrounding coils is almost constant and confirms the omnidirectional pattern associated with such loop antennas which reduces the effect of non-alignment between the two coils. The results also show that the specific absorption rate (SAR and power loss within the tissue are lower than that of the standard level. Thus, the tissue will not be damaged anymore.

  5. Ka-Band Link Study and Analysis for a Mars Hybrid RF/Optical Software Defined Radio

    Science.gov (United States)

    Zeleznikar, Daniel J.; Nappier, Jennifer M.; Downey, Joseph A.

    2014-01-01

    The integrated radio and optical communications (iROC) project at the NASA Glenn Research Center (GRC) is investigating the feasibility of a hybrid RF and optical communication subsystem for future deep space missions. The hybrid communications subsystem enables the advancement of optical communications while simultaneously mitigating the risk of infusion by combining an experimental optical transmitter and telescope with a reliable Ka-band RF transmitter and antenna. The iROC communications subsystem seeks to maximize the total data return over the course of a potential 2-year mission in Mars orbit beginning in 2021. Although optical communication by itself offers potential for greater data return over RF, the reliable Ka-band link is also being designed for high data return capability in this hybrid system. A daily analysis of the RF link budget over the 2-year span is performed to optimize and provide detailed estimates of the RF data return. In particular, the bandwidth dependence of these data return estimates is analyzed for candidate waveforms. In this effort, a data return modeling tool was created to analyze candidate RF modulation and coding schemes with respect to their spectral efficiency, amplifier output power back-off, required digital to analog conversion (DAC) sampling rates, and support by ground receivers. A set of RF waveforms is recommended for use on the iROC platform.

  6. Analysis Linking the Tensor Structure to the Least-Squares Method.

    Science.gov (United States)

    1984-01-01

    7 A-A142 159 ANALYSIS LINKIN THE TENSOR STRUCTURE TO THE LEAST-SQUARES METHOD(U) NOVA UNIV OCEANOGRAPHIC CENTER DANIA FL G BLAHA JAN 84 AFGL-TR-84...Tienstra ([5], [6], [7]), Baarda (C81, [9], [10]), Kooimans ([11]) and a number of others (for example, the editors of [71). It would probably be more...institute, Technische Hogeschool, Delft, 1967 & 1970. 11. A. H. KOOIMANS : "Principles of the Calculus of Observations". Rapport Special, Neuvi me Congr

  7. Periodic analysis of solar activity and its link with the Arctic oscillation phenomenon

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Weizheng; Li, Chun; Du, Ling; Huang, Fei [Ocean University of China, 14-1' -601, 2117 Jinshui Road, Qingdao 266100 (China); Li, Yanfang, E-mail: quweizhe@ouc.edu.cn [Yantai Institute of Coastal Zone Research Chinese Academy of Sciences (China)

    2014-12-01

    Based on spectrum analysis, we provide the arithmetic expressions of the quasi 11 yr cycle, 110 yr century cycle of relative sunspot numbers, and quasi 22 yr cycle of solar magnetic field polarity. Based on a comparative analysis of the monthly average geopotential height, geopotential height anomaly, and temperature anomaly of the northern hemisphere at locations with an air pressure of 500 HPa during the positive and negative phases of AO (Arctic Oscillation), one can see that the abnormal warming period in the Arctic region corresponds to the negative phase of AO, while the anomalous cold period corresponds to its positive phase. This shows that the abnormal change in the Arctic region is an important factor in determining the anomalies of AO. In accordance with the analysis performed using the successive filtering method, one can see that the AO phenomenon occurring in January shows a clear quasi 88 yr century cycle and quasi 22 yr decadal cycle, which are closely related to solar activities. The results of our comparative analysis show that there is a close inverse relationship between the solar activities (especially the solar magnetic field index changes) and the changes in the 22 yr cycle of the AO occurring in January, and that the two trends are basically opposite of each other. That is to say, in most cases after the solar magnetic index MI rises from the lowest value, the solar magnetic field turns from north to south, and the high-energy particle flow entering the Earth's magnetosphere increases to heat the polar atmosphere, thus causing the AO to drop from the highest value; after the solar magnetic index MI drops from the highest value, the solar magnetic field turns from south to north, and the solar high-energy particle flow passes through the top of the Earth's magnetosphere rather than entering it to heat the polar atmosphere. Thus the polar temperature drops, causing the AO to rise from the lowest value. In summary, the variance

  8. Cover crops effect on farm benefits and nitrate leaching: linking economic and environmental analysis

    Science.gov (United States)

    Gabriel, José Luis; Vanclooster, Marnik; Garrido, Alberto; Quemada, Miguel

    2013-04-01

    Introducing cover crops interspersed with intensively fertilized crops in rotation has the potential to reduce nitrate leaching. However, despite the evident environmental services provided and the range of agronomic benefits documented in the literature, farmers' adoption of the technique is still limited because growing CC could lead to extra costs for the farm in three different forms: direct, indirect, and opportunity costs. Environmental studies are complex, and evaluating the indicators that are representative of the environmental impact of an agricultural system is a complicated task that is conducted by specialized groups and methodologies. Multidisciplinary studies may help to develop reliable approaches that would contribute to choosing the best agricultural strategies based on linking economic and environmental benefits. This study evaluates barley (Hordeum vulgare L., cv. Vanessa), vetch (Vicia villosa L., cv. Vereda) and rapeseed (Brassica napus L., cv. Licapo) as cover crops between maize, leaving the residue in the ground or selling it for animal feeding, and compares the economic and environmental results with respect to a typical maize-fallow rotation. Nitrate leaching for different weather conditions was calculated using the mechanistic-deterministic WAVE model, using the Richards equation parameterised with a conceptual model for the soil hydraulic properties for describing the water flow in the vadose zone, combined with field observed data. The economic impact was evaluated through stochastic (Monte-Carlo) simulation models of farms' profits using probability distribution functions of maize yield and cover crop biomass developed fitted with data collected from various field trials (during more than 5 years) and probability distribution functions of maize and different cover crop forage prices fitted from statistical sources. Stochastic dominance relationships are obtained to rank the most profitable strategies from a farm financial perspective

  9. Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain.

    Science.gov (United States)

    Satchell, Karla J F; Jones, Christopher J; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H

    2016-09-01

    Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates.

  10. Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis.

    Directory of Open Access Journals (Sweden)

    Clemens D Cohen

    Full Text Available BACKGROUND: Diabetic nephropathy (DN is a complex and chronic metabolic disease that evolves into a progressive fibrosing renal disorder. Effective transcriptomic profiling of slowly evolving disease processes such as DN can be problematic. The changes that occur are often subtle and can escape detection by conventional oligonucleotide DNA array analyses. METHODOLOGY/PRINCIPAL FINDINGS: We examined microdissected human renal tissue with or without DN using Affymetrix oligonucleotide microarrays (HG-U133A by standard Robust Multi-array Analysis (RMA. Subsequent gene ontology analysis by Database for Annotation, Visualization and Integrated Discovery (DAVID showed limited detection of biological processes previously identified as central mechanisms in the development of DN (e.g. inflammation and angiogenesis. This apparent lack of sensitivity may be associated with the gene-oriented averaging of oligonucleotide probe signals, as this includes signals from cross-hybridizing probes and gene annotation that is based on out of date genomic data. We then examined the same CEL file data using a different methodology to determine how well it could correlate transcriptomic data with observed biology. ChipInspector (CI is based on single probe analysis and de novo gene annotation that bypasses probe set definitions. Both methods, RMA and CI, used at default settings yielded comparable numbers of differentially regulated genes. However, when verified by RT-PCR, the single probe based analysis demonstrated reduced background noise with enhanced sensitivity and fewer false positives. CONCLUSIONS/SIGNIFICANCE: Using a single probe based analysis approach with de novo gene annotation allowed an improved representation of the biological processes linked to the development and progression of DN. The improved analysis was exemplified by the detection of Wnt signaling pathway activation in DN, a process not previously reported to be involved in this disease.

  11. Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles

    OpenAIRE

    Robert W Banks; Cahusac, Peter M. B.; Graca, Anna; Kain, Nakul; Shenton, Fiona; Singh, Paramjeet; Njå, Arild; Simon, Anna; Watson, Sonia; Slater, Clarke R; Bewick, Guy S.

    2013-01-01

    Our aim in the present study was to determine whether a glutamatergic modulatory system involving synaptic-like vesicles (SLVs) is present in the lanceolate ending of the mouse and rat hair follicle and, if so, to assess its similarity to that of the rat muscle spindle annulospiral ending we have described previously. Both types of endings are formed by the peripheral sensory terminals of primary mechanosensory dorsal root ganglion cells, so the presence of such a system in the lanceolate end...

  12. Inositol 1,4,5-triphosphate drives glutamatergic and cholinergic inhibition selectively in spiny projection neurons in the striatum.

    Science.gov (United States)

    Clements, Michael A; Swapna, Immani; Morikawa, Hitoshi

    2013-02-06

    The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this study, using mouse striatal slices, we show that glutamatergic and cholinergic inputs exert direct inhibitory regulation of SPN activity via activation of metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. While pressure ejection of the group I mGluR (mGluR1/5) agonist DHPG [(S)-3,5-dihydroxyphenylglycine] equally engages both mGluR1 and mGluR5 subtypes, the mGluR-dependent component of IPSCs elicited by intrastriatal electrical stimulation is almost exclusively mediated by the mGluR1 subtype. Ca(2+) release from intracellular stores specifically through inositol 1,4,5-triphospahte receptors (IP(3)Rs) and not ryanodine receptors (RyRs) mediates this form of inhibition by gating two types of Ca(2+)-activated K(+) channels (i.e., small-conductance SK channels and large-conductance BK channels). Conversely, spike-evoked Ca(2+) influx triggers Ca(2+) release solely through RyRs to generate SK-dependent slow afterhyperpolarizations, demonstrating functional segregation of IP(3)Rs and RyRs. Finally, IP(3)-induced Ca(2+) release is uniquely observed in SPNs and not in different types of interneurons in the striatum. These results demonstrate that IP(3)-mediated activation of SK and BK channels provides a robust mechanism for glutamatergic and cholinergic inputs to selectively suppress striatal output neuron activity.

  13. Non-Invasive Parameter Identification in Rotordynamics via Fluid Film Bearings: Linking Active Lubrication and Operational Modal Analysis

    DEFF Research Database (Denmark)

    Santos, Ilmar; Svendsen, Peter Kjær

    2017-01-01

    forces, resulting from a strong coupling between hydrodynamic, hydrostatic and controllable lubrication regimes, can be used either to control or to excite rotor lateral vibrations. If non-invasive forces are generated via lubricant fluid film, in situ parameter identification can be carried out......, enabling evaluation of the mechanical condition of the rotating machine. Using the lubricant fluid film as a non-invasive calibrated shaker is troublesome, once several transfer functions among mechanical, hydraulic and electronic components become necessary. In this framework the main original...... contribution of this paper is to show experimentally that the knowledge about the several transfer functions can be bypassed by using output-only identification techniques. The manuscript links controllable (active) lubrication techniques with operational modal analysis, allowing for in-situ parameter...

  14. Linking Material Flow Analysis with Resilience Using Rice: A Case Study in Global, Visual MFA of a Key Food Product

    Directory of Open Access Journals (Sweden)

    Michal Monit

    2016-01-01

    Full Text Available This article uses the rice price crisis of 2007–2008 to show how material flow analysis (MFA can be combined with resilience research. After presentation of fundamental information and methods, resilience-related concepts are illustrated using graphical methods and MFA data. Herfindahl-Hirschman Index (HHI and node-link diagrams are used to highlight potential vulnerability hotspots and show response to, recovery from disturbance and adaptation following a disruption of the global rice market. The methods presented are especially useful in rapid screening for potential impact of supply-side disruptions, such as export restrictions or poor harvests. The article concludes by discussing other potential applications of the chosen approach and stressing the importance of visual communication in dissemination of results and cross-pollination between disciplines. All the data used in this study is available online, as interactive visualizations, at: http://ricestudyvis.weebly.com.

  15. Creating community action plans for obesity prevention using the ANGELO (Analysis Grid for Elements Linked to Obesity) Framework

    DEFF Research Database (Denmark)

    Simmons, A; Mavoa, H M; Bell, A C

    2009-01-01

    prioritized, community-participatory action plans for obesity prevention projects in children and adolescents using the ANGELO (Analysis Grid for Elements Linked to Obesity) Framework. We combined stakeholder engagement processes, the ANGELO Framework (scans for environmental barriers, targeted behaviours......, gaps in skills and knowledge) and workshops with key stakeholders to create action plans for six diverse obesity prevention projects in Australia (n = 3), New Zealand, Fiji and Tonga from 2002 to 2005. Some sites included sociocultural contextual analyses in the environmental scans. Target groups were...... under-5-year-olds (Australia), 4-12-year-olds (Australia) and 13-18-year-olds (all four countries). Over 120 potential behavioural, knowledge, skill and environmental elements were identified for prioritization leading into each 2-day workshop. Many elements were common across the diverse cultural...

  16. Applications of Crown Ether Cross-Linked Chitosan for the Analysis of Lead and Cadmium in Environmental Water Samples

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new type of crown ether cross-linked chitosan was synthesized by the reaction of chitosan with 4,4'-dibromodibenzo-18-crown-6 (Br-DBC). Its token structure was analyzed with FT-IR and NMR and the adsorption behaviors for lead and cadmium in environmental water samples by FAAS were studied. In addition the best analysis conditions were discussed and the adsorption mechanism was explained. As the enrichment factor is above 100, both recoveries are 94%-106%, the detection limits of lead and cadmium are 0.5μg*L-1and 0.04 μg*L-1 and the relatively standard deviations of lead and cadmium are 3.1% and 2.8% respectively, this new method was successfully applied to the determination of environmental water samples. This method is fast and simple and it greatly enhances the determination ability of FAAS for lead and cadmium.

  17. Vacuum structure revealed by over-improved stout-link smearing compared with the overlap analysis for quenched QCD

    Energy Technology Data Exchange (ETDEWEB)

    Ilgenfritz, E.M.; Leinweber, D.; Moran, P. [Adelaide Univ., SA (AU). Special Research Centre for the Subatomic Structure of Matter (CSSM); Koller, K. [Muenchen Univ. (Germany). Sektion Physik; Schierholz, G. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Weinberg, V. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Freie Univ. Berlin (Germany). Inst. fuer Theoretische Physik

    2008-01-11

    A detailed comparison is made between the topological structure of quenched QCD as revealed by the recently proposed over-improved stout-link smearing in conjunction with an improved gluonic definition of the topological density on one hand and a similar analysis made possible by the overlap-fermionic topological charge density both with and without variable ultraviolet cutoff {lambda}{sub cut}. The matching is twofold, provided by fitting the density-density two-point functions on one hand and by a point-by-point fitting of the topological densities according to the two methods. We point out the similar cluster structure of the topological density for moderate smearing and 200 MeV<{lambda}{sub cut}<600 MeV, respectively. We demonstrate the relation of the gluonic topological density for extensive smearing to the location of the overlap zero modes and the lowest overlap non-zero mode as found for the unsmeared configurations. (orig.)

  18. PageRank, HITS and a unified framework for link analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Chris; He, Xiaofeng; Husbands, Parry; Zha, Hongyuan; Simon, Horst

    2001-10-01

    Two popular webpage ranking algorithms are HITS and PageRank. HITS emphasizes mutual reinforcement between authority and hub webpages, while PageRank emphasizes hyperlink weight normalization and web surfing based on random walk models. We systematically generalize/combine these concepts into a unified framework. The ranking framework contains a large algorithm space; HITS and PageRank are two extreme ends in this space. We study several normalized ranking algorithms which are intermediate between HITS and PageRank, and obtain closed-form solutions. We show that, to first order approximation, all ranking algorithms in this framework, including PageRank and HITS, lead to same ranking which is highly correlated with ranking by indegree. These results support the notion that in web resource ranking indegree and outdegree are of fundamental importance. Rankings of webgraphs of different sizes and queries are presented to illustrate our analysis.

  19. Linking Neighborhood Characteristics and Drug-Related Police Interventions: A Bayesian Spatial Analysis

    Directory of Open Access Journals (Sweden)

    Miriam Marco

    2017-02-01

    Full Text Available This paper aimed to analyze the spatial distribution of drug-related police interventions and the neighborhood characteristics influencing these spatial patterns. To this end, police officers ranked each census block group in Valencia, Spain (N = 552, providing an index of drug-related police interventions. Data from the City Statistics Office and observational variables were used to analyze neighborhood characteristics. Distance to the police station was used as the control variable. A Bayesian ecological analysis was performed with a spatial beta regression model. Results indicated that high physical decay, low socioeconomic status, and high immigrant concentration were associated with high levels of drug-related police interventions after adjustment for distance to the police station. Results illustrate the importance of a spatial approach to understanding crime.

  20. Analysis of Single-Mode Fiber Link Performance for Attenuation in Long-Haul Optical Networks

    Science.gov (United States)

    Kaur, Karamjit; Singh, Hardeep

    2017-03-01

    In the past decades, optical fiber has been widely used in communication system owing to low transmission losses, large information carrying capacity, small size, immunity to electrical interference and increased signal security. Focusing on increasing the network transmission capacity, control on the quality of transmission was the field that withdraws attention of research community. For this reason, fiber losses and their compensation remain the important design issue. In the present work, an effort is put in to design a system capable of doing error analysis of system for power losses taking place in the presence of attenuation effect. Attenuation is one of the important phenomena that determine the maximum possible distance between a transmitter and receiver or quantity and position of amplifiers and repeaters in optical networks. The mathematical model equations are obtained representing variation trends of bit error rate BER and Q-value with varying attenuation, which has been verified by different wavelength sources and network conditions.

  1. Analysis and Algorithm Simulation of Forward-link CDMA Signal Spectral Regrowth

    Institute of Scientific and Technical Information of China (English)

    LIN Mao-liu; XU Qing-hua

    2006-01-01

    Closed-form expressions for the spectral regrowth of CDMA signal passing through a nonlinear amplifier with a digitally modulated carrier are derived using the power series and statistical methods of high-order cumulant. The technique yields an analytical expression for the autocorrelation function of the output signal as a function of the statistics of the input signal transformed by a behavioral model of the amplifier. The third-order nonlinearity is expressed in terms of to include the memory effects of the circuit in-band and out-of-band reactance. The analysis is based on a time-domain model of the signal and the model is used to derive the power spectrum density and other statistical properties of the CDMA signal. Such analytical results are useful in finding optimal operating conditions of the power Amplifier.

  2. Analysis of the link between a definition of sustainability and the life cycle methodologies

    DEFF Research Database (Denmark)

    Jørgensen, Andreas; Herrmann, Ivan Tengbjerg; Bjørn, Anders

    2013-01-01

    , is presented and detailed to a level enabling an analysis of the relation to the impact categories at midpoint level considered in life cycle (LC) methodologies.The interpretation of the definition of sustainability as outlined in Our Common Future (WCED 1987) suggests that the assessment of a product......'s sustainability is about addressing the extent to which product life cycles affect poverty levels among the current generation, as well as changes in the level of natural, human and produced and social capital available for the future population. It is shown that the extent to which product life cycles affect...... poverty to some extent is covered by impact categories included in existing SLCA approaches. It is also found that the extent to which product life cycles affect natural capital is well covered by LCA, and human capital is covered by both LCA and SLCA but in different ways. Produced capital is not to any...

  3. LORICA - A new model for linking landscape and soil profile evolution: Development and sensitivity analysis

    Science.gov (United States)

    Temme, Arnaud J. A. M.; Vanwalleghem, Tom

    2016-05-01

    Soils and landscapes evolve in tandem. Landscape position is a strong determinant of vertical soil development, which has often been formalized in the catena concept. At the same time, soil properties are strong determinants of geomorphic processes such as overland erosion, landsliding and creep. We present a new soilscape evolution model; LORICA, to study these numerous interactions between soil and landscape development. The model is based on the existing landscape evolution model LAPSUS and the soil formation model MILESD. The model includes similar soil formation processes as MILESD, but the main novelties include the consideration of more layers and the dynamic adaption of the number of layers as a function of the soil profile's heterogeneity. New processes in the landscape evolution component include a negative feedback of vegetation and armouring and particle size selectivity of the erosion-deposition process. In order to quantify these different interactions, we present a full sensitivity analysis of the input parameters. First results show that the model successfully simulates various soil-landscape interactions, leading to outputs where the surface changes in the landscape clearly depend on soil development, and soil changes depend on landscape location. Sensitivity analysis of the model confirms that soil and landscape interact: variables controlling amount and position of fine clay have the largest effect on erosion, and erosion variables control among others the amount of chemical weathering. These results show the importance of particle size distribution, and especially processes controlling the presence of finer clay particles that are easily eroded, both for the resulting landscape form as for the resulting soil profiles. Further research will have to show whether this is specific to the boundary conditions of this study or a general phenomenon.

  4. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Directory of Open Access Journals (Sweden)

    Tejasvi S Niranjan

    Full Text Available X-linked Intellectual Disability (XLID is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  5. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Science.gov (United States)

    Niranjan, Tejasvi S; Skinner, Cindy; May, Melanie; Turner, Tychele; Rose, Rebecca; Stevenson, Roger; Schwartz, Charles E; Wang, Tao

    2015-01-01

    X-linked Intellectual Disability (XLID) is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome) in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families) using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  6. Unbalance of CB1 receptors expressed in GABAergic and glutamatergic neurons in a transgenic mouse model of Huntington's disease.

    Science.gov (United States)

    Chiodi, Valentina; Uchigashima, Motokazu; Beggiato, Sarah; Ferrante, Antonella; Armida, Monica; Martire, Alberto; Potenza, Rosa Luisa; Ferraro, Luca; Tanganelli, Sergio; Watanabe, Masahiko; Domenici, Maria Rosaria; Popoli, Patrizia

    2012-03-01

    Cannabinoid CB1 receptors (CB1Rs) are known to be downregulated in patients and in animal models of Huntington's disease (HD). However, the functional meaning of this reduction, if any, is still unclear. Here, the effects of the cannabinoid receptor agonist WIN 55,212-2 (WIN) were investigated on striatal synaptic transmission and on glutamate and GABA release in symptomatic R6/2 mice, a genetic model of HD. The expression levels of CB1Rs in glutamatergic and GABAergic synapses were also evaluated. We found that in R6/2 mice, WIN effects on synaptic transmission and glutamate release were significantly increased with respect to wild type mice. On the contrary, a decrease in WIN-induced reduction of GABA release was found in R6/2 versus WT mice. The expression of CB1Rs in GABAergic neurons was drastically reduced, while CB1Rs levels in glutamatergic neurons were unchanged. These results demonstrate that the expression and functionality of CB1Rs are differentially affected in GABAergic and glutamatergic neurons in R6/2 mice. As a result, the balance between CB1Rs expressed by the two neuronal populations and, thus, the net effect of CB1R stimulation, is profoundly altered in HD mice.

  7. The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum.

    Science.gov (United States)

    Jing, Deqiang; Lee, Francis S; Ninan, Ipe

    2017-01-01

    The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene disrupts the activity-dependent release of BDNF, which might underlie its involvement in several neuropsychiatric disorders. Consistent with the potential role of regulated release of BDNF in synaptic functions, earlier studies have demonstrated that the BDNF Val66Met polymorphism impairs NMDA receptor-mediated synaptic transmission and plasticity in the hippocampus, the medial prefrontal cortex and the central amygdala. However, it is unknown whether the BDNF Val66Met polymorphism affects synapses in the dorsal striatum, which depends on cortical afferents for BDNF. Electrophysiological experiments revealed an enhanced glutamatergic transmission in the dorsolateral striatum (DLS) of knock-in mice containing the variant polymorphism (BDNF(Met/Met)) compared to the wild-type (BDNF(Val/Val)) mice. This increase in glutamatergic transmission is mediated by a potentiation in glutamate release and NMDA receptor transmission in the medium spiny neurons without any alterations in non-NMDA receptor-mediated transmission. We also observed an impairment of synaptic plasticity, both long-term potentiation and depression in the DLS neurons, in BDNF(Met/Met) mice. Thus, the BDNF Val66Met polymorphism exerts an increase in glutamatergic transmission but impairs synaptic plasticity in the dorsal striatum, which might play a role in its effect on neuropsychiatric symptoms. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

  8. Activation of steroid-sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats.

    Science.gov (United States)

    Zamudio-Bulcock, Paula A; Everett, Julie; Harteneck, Christian; Valenzuela, C Fernando

    2011-11-01

    The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. In this study, we demonstrate the abundant expression of TRPM3 steroid-sensitive channels in the developing cerebellar cortex. We also show that TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje cells. We recently showed that PregS potentiates spontaneous glutamate release onto neonatal Purkinje cells during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3-like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.

  9. In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

    Directory of Open Access Journals (Sweden)

    Manto Mario

    2010-11-01

    Full Text Available Abstract Background A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown. Methods We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats. Results Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF. Conclusion These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder.

  10. Chemometric analysis reveals links in the formation of fragrant bio-molecules during agarwood (Aquilaria malaccensis) and fungal interactions

    Science.gov (United States)

    Sen, Supriyo; Dehingia, Madhusmita; Talukdar, Narayan Chandra; Khan, Mojibur

    2017-01-01

    Fragrant agarwood, arguably the costliest wood in the world, is formed by plant-fungal interactions in Aquilaria spp. However, very little is known about this fragrant outcome of interaction. Therefore, mimicking the ancient traditions of agarwood production in Assam (Northeast India), a chemometric assessment of the agarwood-fungus interaction was made by chemical profiling (GC-MS) coupled with statistical analysis (principal component, correlation network analysis) across three platforms, viz. callus, juvenile plants and resinous wood-chips with an associated Fusarium. In the study of callus-fungus interaction, increased accumulation of key aroma compounds such as pentatriacontane {fold change (log2FC) = 3.47)}, 17-pentatriacontene (log2FC = 2.95), tetradecane, 2-methyl- (log2FC = 1.10) over callus and activation of pathways related to defense and secondary metabolism indicated links to aroma production. Study on fungal interactions in juvenile plants and resinous wood-chips indicated formation of terpenoid precursors (e.g. farnesol, geranylgeraniol acetate) and agarwood sesquiterpenes (e.g. agarospirol, γ-eudesmol). Correlation network analysis revealed the possible regulation of sesquiterpene biosynthesis involving squalene. Also a direct role of fungus in aroma (e.g. dodecane, 4-methyl-, tetracosane) was highlighted. Appearance of fragrant molecules unknown to agarwood during interaction featured as a new possibility for future research. PMID:28290512

  11. Network inference analysis identifies an APRR2-like gene linked to pigment accumulation in tomato and pepper fruits.

    Science.gov (United States)

    Pan, Yu; Bradley, Glyn; Pyke, Kevin; Ball, Graham; Lu, Chungui; Fray, Rupert; Marshall, Alexandra; Jayasuta, Subhalai; Baxter, Charles; van Wijk, Rik; Boyden, Laurie; Cade, Rebecca; Chapman, Natalie H; Fraser, Paul D; Hodgman, Charlie; Seymour, Graham B

    2013-03-01

    Carotenoids represent some of the most important secondary metabolites in the human diet, and tomato (Solanum lycopersicum) is a rich source of these health-promoting compounds. In this work, a novel and fruit-related regulator of pigment accumulation in tomato has been identified by artificial neural network inference analysis and its function validated in transgenic plants. A tomato fruit gene regulatory network was generated using artificial neural network inference analysis and transcription factor gene expression profiles derived from fruits sampled at various points during development and ripening. One of the transcription factor gene expression profiles with a sequence related to an Arabidopsis (Arabidopsis thaliana) ARABIDOPSIS PSEUDO RESPONSE REGULATOR2-LIKE gene (APRR2-Like) was up-regulated at the breaker stage in wild-type tomato fruits and, when overexpressed in transgenic lines, increased plastid number, area, and pigment content, enhancing the levels of chlorophyll in immature unripe fruits and carotenoids in red ripe fruits. Analysis of the transcriptome of transgenic lines overexpressing the tomato APPR2-Like gene revealed up-regulation of several ripening-related genes in the overexpression lines, providing a link between the expression of this tomato gene and the ripening process. A putative ortholog of the tomato APPR2-Like gene in sweet pepper (Capsicum annuum) was associated with pigment accumulation in fruit tissues. We conclude that the function of this gene is conserved across taxa and that it encodes a protein that has an important role in ripening.

  12. Haplotype analysis of DNA microsatellites tightly linked to the locus of Usher syndrome type I on chromosome 11q

    Energy Technology Data Exchange (ETDEWEB)

    Korostishevsky, M.; Kalinsky, H.; Seroussi, E. [Sackler Faculty of Medicine, Ramat-Aviv (Israel)] [and other

    1994-09-01

    Usher syndrome type I (USHI), an autosomal recessive disorder associated with congenital sensorineural deafness and progressive visual loss, is closely linked to the D11S533 locus. The availability of 7 other polymorphic markers within few centimorgans spanning the disease locus allowed us to identify a unique and single haplotype among all carriers of USHI gene in the Samaritan kindred. Occurrence of recombination in this small chromosomal interval is rare, hindering the detection of the mitotic recombination events needed for analysis by traditional linkage methods. Attempts to order the eight loci by linkage disequilibrium models proved to be problematic. However, our haplotype analysis implied that recombinations which had arisen in past generations may be utilized in fine mapping of the USHI gene and in resolving the conflicting linkage maps previously obtained for this region. We have developed a simple algorithm for predicting the order of the microsatellites on the basis of haplotype resemblance. The following chromosomal map in which the USHI gene is closest to D11S533 (location score of 31.0 by multipoint analysis) is suggested: D11S916, GARP, D11S527, D11S533, OMP, D11S906, D11S911, D11S937. Physical mapping efforts are currently directed to verify and to detail the map of this chromosomal region.

  13. Inheritance Analysis and Identification of SSR Markers Linked to Late Blight Resistant Gene in Tomato

    Institute of Scientific and Technical Information of China (English)

    ZHU Hai-shan; WU Tao; ZHANG Zhen-xian

    2006-01-01

    Late blight caused by Phytophthora infestans is the most serious disease of tomato production in China. Studies on the genetics of resistance and identification of molecular markers are very useful for breeding late blight resistant varieties.The objective of this paper was to study the inheritance of late blight resistance and identify simple sequence repeat (SSR)markers associated with resistance allele in tomato (Lycopersicon esculentum Mill). The results came from an F2 progeny of 241 plants derived from a cross between 5# inbred line that is susceptible to late blight and a resistant accession CLN2037E. The late blight responses of F2 plants were tested by artificially inoculation of detached-leaflets in plate and natural infection assayed under greenhouse conditions. Both methods showed that the resistance is dominant and inherited as monogenic trait. Genetic mapping and linkage analysis showed that the late blight resistance gene Ph-ROL was located on chromosome 9 with a genetic distance of 5.7 cM to the SSR marker TOM236.

  14. Dynamic Links between Exchange Rates and Stock Prices in Malaysia: An Asymmetric Cointegration analysis

    Directory of Open Access Journals (Sweden)

    Hamisu Sadi ALI

    2015-09-01

    Full Text Available Abstract. The present article used a monthly data and applied Enders and Siklos (2001 asymmetric cointegration analysis to examine the impact of exchange rates on stock prices in Malaysia for the period of 1999-2014. The result suggests that variables were cointegrated based on Engle-granger two step technique. Moving to threshold auto regressive (TAR and momentumthreshold auto regressive (M-TAR the finding reveals that based on the latter variables were asymmetrically cointegrated as null hypothesis of no cointegration was rejected at 1% significance level based on Enders and Siklos (2001, while the former shows that variables do not have long-run relationship and the speed of adjustment is symmetric. This signifies that increase in the prices of shares in Malaysian stock market could lead to Malaysian Ringgit appreciation over other major global currencies. The stocks will become more expensive and discourage foreign investors’ participation in the market which inhibits the influx of stable foreign capital into Malaysian financial system. The implication is that regulators should ensure that adequate and efficient policies are put in place in order to keep the Ringgit exchange rates at optimal level so as to enhance the participation of foreign investors and improve market competitiveness.Keywords. Stock prices, Exchange rates, Asymmetric, Cointegration, Malaysia.JEL. F18, F21, F23, O47.

  15. Ammonia impairs glutamatergic communication in astroglial cells: protective role of resveratrol.

    Science.gov (United States)

    Bobermin, Larissa Daniele; Hansel, Gisele; Scherer, Emilene B S; Wyse, Angela T S; Souza, Diogo Onofre; Quincozes-Santos, André; Gonçalves, Carlos-Alberto

    2015-12-01

    Ammonia is a key toxin in the precipitation of hepatic encephalopathy (HE), a neuropsychiatric disorder associated with liver failure. In response to ammonia, various toxic events are triggered in astroglial cells, and alterations in brain glutamate communication are common. Resveratrol is a polyphenolic compound that has been extensively studied in pathological events because it presents several beneficial effects, including some in the central nervous system (CNS). We previously described that resveratrol is able to significantly modulate glial functioning and has a protective effect during ammonia challenge in vitro. In this study, we addressed the mechanisms by which resveratrol can protect C6 astroglial cells from glutamatergic alterations induced by ammonia. Resveratrol was able to prevent all the effects triggered by ammonia: (i) decrease in glutamate uptake activity and expression of the EAAC1 glutamate transporter, the main glutamate transporter present in C6 cells; (ii) increase of glutamate release, which was also dependent on the activation of the Na(+)-K(+)-Cl(-) co-transporter NKCC1; (iii) reduction in GS activity and intracellular GSH content; and (iv) impairment of Na(+)K(+)-ATPase activity. Interestingly, resveratrol, per se, also positively modulated the astroglial functions evaluated. Moreover, we demonstrated that heme oxygenase 1 (HO1), an enzyme that is part of the cellular defense system, mediated some of the effects of resveratrol. In conclusion, the mechanisms of the putative protective role of resveratrol against ammonia toxicity involve the modulation of pathways and molecules related to glutamate communication in astroglial cells.

  16. Key role of the dopamine D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission.

    Science.gov (United States)

    Bonaventura, Jordi; Quiroz, César; Cai, Ning-Sheng; Rubinstein, Marcelo; Tanda, Gianluigi; Ferré, Sergi

    2017-01-01

    Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD). When compared with the wild-type mouse D4 receptor, the expanded intracellular domain of the humanized D4 receptor conferred a gain of function, blunting methamphetamine-induced cortical activation and optogenetic and methamphetamine-induced corticostriatal glutamate release. The results demonstrate a key role of the D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission. Furthermore, these data imply that enhanced D4 receptor-mediated dopaminergic control of corticostriatal transmission constitutes a vulnerability factor of ADHD and other neuropsychiatric disorders.

  17. Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

    Science.gov (United States)

    Perea, Gertrudis; Gómez, Ricardo; Mederos, Sara; Covelo, Ana; Ballesteros, Jesús J; Schlosser, Laura; Hernández-Vivanco, Alicia; Martín-Fernández, Mario; Quintana, Ruth; Rayan, Abdelrahman; Díez, Adolfo; Fuenzalida, Marco; Agarwal, Amit; Bergles, Dwight E; Bettler, Bernhard; Manahan-Vaughan, Denise; Martín, Eduardo D; Kirchhoff, Frank; Araque, Alfonso

    2016-12-24

    Interneurons are critical for proper neural network function and can activate Ca(2+) signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

  18. The NG2 Protein Is Not Required for Glutamatergic Neuron-NG2 Cell Synaptic Signaling.

    Science.gov (United States)

    Passlick, Stefan; Trotter, Jacqueline; Seifert, Gerald; Steinhäuser, Christian; Jabs, Ronald

    2016-01-01

    NG2 glial cells (as from now NG2 cells) are unique in receiving synaptic input from neurons. However, the components regulating formation and maintenance of these neuron-glia synapses remain elusive. The transmembrane protein NG2 has been considered a potential mediator of synapse formation and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) clustering, because it contains 2 extracellular Laminin G/Neurexin/Sex Hormone-Binding Globulin domains, which in neurons are crucial for formation of transsynaptic neuroligin-neurexin complexes. NG2 is connected via Glutamate Receptor-Interacting Protein with GluA2/3-containing AMPARs, thereby possibly mediating receptor clustering in glial postsynaptic density. To elucidate the role of NG2 in neuron-glia communication, we investigated glutamatergic synaptic transmission in juvenile and aged hippocampal NG2 cells of heterozygous and homozygous NG2 knockout mice. Neuron-NG2 cell synapses readily formed in the absence of NG2. Short-term plasticity, synaptic connectivity, postsynaptic AMPAR current kinetics, and density were not affected by NG2 deletion. During development, an NG2-independent acceleration of AMPAR current kinetics and decreased synaptic connectivity were observed. Our results indicate that the lack of NG2 does not interfere with genesis and basic properties of neuron-glia synapses. In addition, we demonstrate frequent expression of neuroligins 1-3 in juvenile and aged NG2 cells, suggesting a role of these molecules in synapse formation between NG2 glia and neurons.

  19. Glutamatergic Mechanisms of Comorbidity Between Acute Stress and Cocaine Self-administration

    Science.gov (United States)

    Garcia-Keller, Constanza; Kupchik, Yonatan; Gipson, Cassandra D; Brown, Robyn M; Spencer, Sade; Bollati, Flavia; Esparza, Maria A; Roberts-Wolfe, Doug; Heinsbroek, Jasper; Bobadilla, Ana-Clara; Cancela, Liliana M; Kalivas, Peter W

    2015-01-01

    There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining if the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate mediated synaptic currents, and dendritic spine morphology. We also determined if acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport, and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders. PMID:26821978

  20. Nicotinic, glutamatergic and dopaminergic synaptic transmission and plasticity in the mesocorticolimbic system: focus on nicotine effects.

    Science.gov (United States)

    Pistillo, Francesco; Clementi, Francesco; Zoli, Michele; Gotti, Cecilia

    2015-01-01

    Cigarette smoking is currently the leading cause of preventable deaths and disability throughout the world, being responsible for about five million premature deaths/year. Unfortunately, fewer than 10% of tobacco users who try to stop smoking actually manage to do so. The main addictive agent delivered by cigarette smoke is nicotine, which induces psychostimulation and reward, and reduces stress and anxiety. The use of new technologies (including optogenetics) and the development of mouse models characterised by cell-specific deletions of receptor subtype genes or the expression of gain-of-function nAChR subunits has greatly increased our understanding of the molecular mechanisms and neural substrates of nicotine addiction first revealed by classic electrophysiological, neurochemical and behavioural approaches. It is now becoming clear that various aspects of nicotine dependence are mediated by close interactions of the glutamatergic, dopaminergic and γ-aminobutyric acidergic systems in the mesocorticolimbic system. This review is divided into two parts. The first provides an updated overview of the circuitry of the ventral tegmental area, ventral striatum and prefrontal cortex, the neurotransmitter receptor subtypes expressed in these areas, and their physiological role in the mesocorticolimbic system. The second will focus on the molecular, functional and behavioural mechanisms involved in the acute and chronic effects of nicotine on the mesocorticolimbic system.

  1. Key role of the dopamine D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission

    Science.gov (United States)

    Bonaventura, Jordi; Quiroz, César; Cai, Ning-Sheng; Rubinstein, Marcelo; Tanda, Gianluigi; Ferré, Sergi

    2017-01-01

    Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD). When compared with the wild-type mouse D4 receptor, the expanded intracellular domain of the humanized D4 receptor conferred a gain of function, blunting methamphetamine-induced cortical activation and optogenetic and methamphetamine-induced corticostriatal glutamate release. The results demonstrate a key role of the D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission. Furthermore, these data imply that enhanced D4 receptor–mediated dopaminergic control of corticostriatal transmission constitutes a vulnerability factor of ADHD and other neuropsychiatric disorders. PMID:28097219

  2. Specification of Region-Specific Neurons Including Forebrain Glutamatergic Neurons from Human Induced Pluripotent Stem Cells

    Science.gov (United States)

    Martins-Taylor, Kristen; Wang, Xiaofang; Zhang, Zheng; Park, Jung Woo; Zhan, Shuning; Kronenberg, Mark S.; Lichtler, Alexander; Liu, Hui-Xia; Chen, Fang-Ping; Yue, Lixia; Li, Xue-Jun; Xu, Ren-He

    2010-01-01

    Background Directed differentiation of human induced pluripotent stem cells (hiPSC) into functional, region-specific neural cells is a key step to realizing their therapeutic promise to treat various neural disorders, which awaits detailed elucidation. Methodology/Principal Findings We analyzed neural differentiation from various hiPSC lines generated by others and ourselves. Although heterogeneity in efficiency of neuroepithelial (NE) cell differentiation was observed among different hiPSC lines, the NE differentiation process resembles that from human embryonic stem cells (hESC) in morphology, timing, transcriptional profile, and requirement for FGF signaling. NE cells differentiated from hiPSC, like those from hESC, can also form rostral phenotypes by default, and form the midbrain or spinal progenitors upon caudalization by morphogens. The rostrocaudal neural progenitors can further mature to develop forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and spinal motor neurons, respectively. Typical ion channels and action potentials were recorded in the hiPSC-derived neurons. Conclusions/Significance Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of rostrocaudal neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders. PMID:20686615

  3. Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex.

    Science.gov (United States)

    Szegedi, Viktor; Paizs, Melinda; Csakvari, Eszter; Molnar, Gabor; Barzo, Pal; Tamas, Gabor; Lamsa, Karri

    2016-11-01

    In the human neocortex, single excitatory pyramidal cells can elicit very large glutamatergic EPSPs (VLEs) in inhibitory GABAergic interneurons capable of triggering their firing with short (3-5 ms) delay. Similar strong excitatory connections between two individual neurons have not been found in nonhuman cortices, suggesting that these synapses are specific to human interneurons. The VLEs are crucial for generating neocortical complex events, observed as single pyramidal cell spike-evoked discharge of cell assemblies in the frontal and temporal cortices. However, long-term plasticity of the VLE connections and how the plasticity modulates neocortical complex events has not been studied. Using triple and dual whole-cell recordings from synaptically connected human neocortical layers 2-3 neurons, we show that VLEs in fast-spiking GABAergic interneurons exhibit robust activity-induced long-term depression (LTD). The LTD by single pyramidal cell 40 Hz spike bursts is specific to connections with VLEs, requires group I metabotropic glutamate receptors, and has a presynaptic mechanism. The LTD of VLE connections alters suprathreshold activation of interneurons in the complex events suppressing the discharge of fast-spiking GABAergic cells. The VLEs triggering the complex events may contribute to cognitive processes in the human neocortex, and their long-term plasticity can alter the discharging cortical cell assemblies by learning.

  4. Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells.

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    Hui Zeng

    Full Text Available BACKGROUND: Directed differentiation of human induced pluripotent stem cells (hiPSC into functional, region-specific neural cells is a key step to realizing their therapeutic promise to treat various neural disorders, which awaits detailed elucidation. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed neural differentiation from various hiPSC lines generated by others and ourselves. Although heterogeneity in efficiency of neuroepithelial (NE cell differentiation was observed among different hiPSC lines, the NE differentiation process resembles that from human embryonic stem cells (hESC in morphology, timing, transcriptional profile, and requirement for FGF signaling. NE cells differentiated from hiPSC, like those from hESC, can also form rostral phenotypes by default, and form the midbrain or spinal progenitors upon caudalization by morphogens. The rostrocaudal neural progenitors can further mature to develop forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and spinal motor neurons, respectively. Typical ion channels and action potentials were recorded in the hiPSC-derived neurons. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of rostrocaudal neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders.

  5. Tangential migration of glutamatergic neurons and cortical patterning during development: Lessons from Cajal-Retzius cells.

    Science.gov (United States)

    Barber, Melissa; Pierani, Alessandra

    2016-08-01

    Tangential migration is a mode of cell movement, which in the developing cerebral cortex, is defined by displacement parallel to the ventricular surface and orthogonal to the radial glial fibers. This mode of long-range migration is a strategy by which distinct neuronal classes generated from spatially and molecularly distinct origins can integrate to form appropriate neural circuits within the cortical plate. While it was previously believed that only GABAergic cortical interneurons migrate tangentially from their origins in the subpallial ganglionic eminences to integrate in the cortical plate, it is now known that transient populations of glutamatergic neurons also adopt this mode of migration. These include Cajal-Retzius cells (CRs), subplate neurons (SPs), and cortical plate transient neurons (CPTs), which have crucial roles in orchestrating the radial and tangential development of the embryonic cerebral cortex in a noncell-autonomous manner. While CRs have been extensively studied, it is only in the last decade that the molecular mechanisms governing their tangential migration have begun to be elucidated. To date, the mechanisms of SPs and CPTs tangential migration remain unknown. We therefore review the known signaling pathways, which regulate parameters of CRs migration including their motility, contact-redistribution and adhesion to the pial surface, and discuss this in the context of how CR migration may regulate their signaling activity in a spatial and temporal manner. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 847-881, 2016.

  6. Synergistic regulation of glutamatergic transmission by serotonin and norepinephrine reuptake inhibitors in prefrontal cortical neurons.

    Science.gov (United States)

    Yuen, Eunice Y; Qin, Luye; Wei, Jing; Liu, Wenhua; Liu, Aiyi; Yan, Zhen

    2014-09-05

    The monoamine system in the prefrontal cortex has been implicated in various mental disorders and has been the major target of anxiolytics and antidepressants. Clinical studies show that serotonin and norepinephrine reuptake inhibitors (SNRIs) produce better therapeutic effects than single selective reuptake inhibitors, but the underlying mechanisms are largely unknown. Here, we found that low dose SNRIs, by acting on 5-HT(1A) and α2-adrenergic receptors, synergistically reduced AMPA receptor (AMPAR)-mediated excitatory postsynaptic currents and AMPAR surface expression in prefrontal cortex pyramidal neurons via a mechanism involving Rab5/dynamin-mediated endocytosis of AMPARs. The synergistic effect of SNRIs on AMPARs was blocked by inhibition of activator of G protein signaling 3, a G protein modulator that prevents reassociation of G(i) protein α subunit and prolongs the βγ-mediated signaling pathway. Moreover, the depression of AMPAR-mediated excitatory postsynaptic currents by SNRIs required p38 kinase activity, which was increased by 5-HT(1A) and α2-adrenergic receptor co-activation in an activator of G protein signaling 3-dependent manner. These results have revealed a potential mechanism for the synergy between the serotonin and norepinephrine systems in the regulation of glutamatergic transmission in cortical neurons.

  7. Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus.

    Science.gov (United States)

    Jiao, Hui-Feng; Sun, Xiang-Dong; Bates, Ryan; Xiong, Lei; Zhang, Lei; Liu, Fang; Li, Lei; Zhang, Hong-Sheng; Wang, Shun-Qi; Xiong, Ming-Tao; Patel, Mihir; Stranahan, Alexis M; Xiong, Wen-Cheng; Li, Bao-Ming; Mei, Lin

    2017-01-31

    Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction. Tmem108-deficient neurons form fewer and smaller spines, suggesting that Tmem108 is required for spine formation and maturation. In agreement, excitatory postsynaptic currents of DG granule neurons were decreased in Tmem108 mutant mice, indicating a hypofunction of glutamatergic activity. Further cell biological studies indicate that Tmem108 is necessary for surface expression of AMPA receptors. Tmem108-deficient mice display compromised sensorimotor gating and cognitive function. Together, these observations indicate that Tmem108 plays a critical role in regulating spine development and excitatory transmission in DG granule neurons. When Tmem108 is mutated, mice displayed excitatory/inhibitory imbalance and behavioral deficits relevant to schizophrenia, revealing potential pathophysiological mechanisms of schizophrenia.

  8. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.

    Science.gov (United States)

    Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

    2015-07-24

    One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

  9. Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks

    Science.gov (United States)

    Perea, Gertrudis; Gómez, Ricardo; Mederos, Sara; Covelo, Ana; Ballesteros, Jesús J; Schlosser, Laura; Hernández-Vivanco, Alicia; Martín-Fernández, Mario; Quintana, Ruth; Rayan, Abdelrahman; Díez, Adolfo; Fuenzalida, Marco; Agarwal, Amit; Bergles, Dwight E; Bettler, Bernhard; Manahan-Vaughan, Denise; Martín, Eduardo D; Kirchhoff, Frank; Araque, Alfonso

    2016-01-01

    Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay. DOI: http://dx.doi.org/10.7554/eLife.20362.001 PMID:28012274

  10. NotI jumping and linking clones as a tool for genome mapping and analysis of chromosome rearrangements in different tumors.

    Science.gov (United States)

    Zabarovsky, E R; Kashuba, V I; Gizatullin, R Z; Winberg, G; Zabarovska, V I; Erlandsson, R; Domninsky, D A; Bannikov, V M; Pokrovskaya, E; Kholodnyuk, I; Petrov, N; Zakharyev, V M; Kisselev, L L; Klein, G

    1996-01-01

    Long-range restriction site maps are of central importance for mapping the human genome. The use of clones from linking and jumping libraries for genome mapping offers a promising alternative to the laborious procedures used up until now. In the present review, this research field is analyzed with particular emphasis on the implementation of a shot-gun sequencing strategy for genome mapping and the use of NotI linking clones for analysis of rearrangements in tumors and tumor cell lines.

  11. Communication Links

    OpenAIRE

    2003-01-01

    This interactive tutorial helps learners to: Identify key upward, lateral, downward, and informal communication links in their organizations. , Reflect on the benefits, control, satisfaction, information filters, and feedback mechanism of various communication links in the organizations. OCL1000 Communicating Change in Complex Organizations

  12. Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat.

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    Sergio G Benitez

    Full Text Available In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc. Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67 and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C rats and rats submitted to Pc, hypoxia-ischemia (L and a combination of both treatments (PcL. We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult--showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization--were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ∼110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult

  13. Biogeochemical analysis of ancient Pacific Cod bone suggests Hg bioaccumulation was linked to paleo sea level rise and climate change

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    Maribeth S. Murray

    2015-02-01

    Full Text Available Deglaciation at the end of the Pleistocene initiated major changes in ocean circulation and distribution. Within a brief geological time, large areas of land were inundated by sea-level rise and today global sea level is 120 m above its minimum stand during the last glacial maximum. This was the era of modern sea shelf formation; climate change caused coastal plain flooding and created broad continental shelves with innumerable consequences to marine and terrestrial ecosystems and human populations. In Alaska, the Bering Sea nearly doubled in size and stretches of coastline to the south were flooded, with regional variability in the timing and extent of submergence. Here we suggest how past climate change and coastal flooding are linked to mercury bioaccumulation that could have had profound impacts on past human populations and that, under conditions of continued climate warming, may have future impacts. Biogeochemical analysis of total mercury (tHg and 13C/15N ratios in the bone collagen of archaeologically recovered Pacific Cod (Gadus macrocephalus bone shows high levels of tHg during early/mid-Holocene. This pattern cannot be linked to anthropogenic activity or to food web trophic changes, but may result from natural phenomena such as increases in productivity, carbon supply and coastal flooding driven by glacial melting and sea-level rise. The coastal flooding could have led to increased methylation of Hg in newly submerged terrestrial land and vegetation. Methylmercury is bioaccumulated through aquatic food webs with attendant consequences for the health of fish and their consumers, including people. This is the first study of tHg levels in a marine species from the Gulf of Alaska to provide a time series spanning nearly the entire Holocene and we propose that past coastal flooding resulting from climate change had the potential to input significant quantities of Hg into marine food webs and subsequently to human consumers.

  14. Dynamics of glutamatergic signaling in the mushroom body of young adult Drosophila

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    Grau Yves

    2010-04-01

    Full Text Available Abstract Background The mushroom bodies (MBs are paired brain centers located in the insect protocerebrum involved in olfactory learning and memory and other associative functions. Processes from the Kenyon cells (KCs, their intrinsic neurons, form the bulk of the MB's calyx, pedunculus and lobes. In young adult Drosophila, the last-born KCs extend their processes in the α/β lobes as a thin core (α/β cores that is embedded in the surrounding matrix of other mature KC processes. A high level of L-glutamate (Glu immunoreactivity is present in the α/β cores (α/βc of recently eclosed adult flies. In a Drosophila model of fragile X syndrome, the main cause of inherited mental retardation, treatment with metabotropic Glu receptor (mGluR antagonists can rescue memory deficits and MB structural defects. Results To address the role of Glu signaling in the development and maturation of the MB, we have compared the time course of Glu immunoreactivity with the expression of various glutamatergic markers at various times, that is, 1 hour, 1 day and 10 days after adult eclosion. We observed that last-born α/βc KCs in young adult as well as developing KCs in late larva and at various pupal stages transiently express high level of Glu immunoreactivity in Drosophila. One day after eclosion, the Glu level was already markedly reduced in the α/βc neurons. Glial cell processes expressing glutamine synthetase and the Glu transporter dEAAT1 were found to surround the Glu-expressing KCs in very young adults, subsequently enwrapping the α/β lobes to become distributed equally over the entire MB neuropil. The vesicular Glu transporter DVGluT was detected by immunostaining in processes that project within the MB lobes and pedunculus, but this transporter is apparently never expressed by the KCs themselves. The NMDA receptor subunit dNR1 is widely expressed in the MB neuropil just after eclosion, but was not detected in the α/βc neurons. In contrast, we

  15. In vivo and in vitro effects of multiple sclerosis immunomodulatory therapeutics on glutamatergic excitotoxicity.

    Science.gov (United States)

    Luchtman, Dirk; Gollan, René; Ellwardt, Erik; Birkenstock, Jérôme; Robohm, Kerstin; Siffrin, Volker; Zipp, Frauke

    2016-03-01

    In multiple sclerosis (MS), a candidate downstream mechanism for neuronal injury is glutamate (Glu)-induced excitotoxicity, leading to toxic increases in intraneuronal Ca(2+) . Here, we used in vivo two-photon imaging in the brain of TN-XXL transgenic Ca(2+) reporter mice to test whether promising oral MS therapeutics, namely fingolimod, dimethyl fumarate, and their respective metabolites fingolimod-phosphate and monomethyl fumarate, can protect neurons against acute glutamatergic excitotoxic damage. We also assessed whether these drugs can protect against excitotoxicity in vitro using primary cortical neurons, and whether they can directly inhibit Glu release from pathogenic T-helper 17 lymphocytes. In vivo, direct and acute (1 h) administration of 100 mM Glu to the brainstem resulted in a rapid and significant up-regulation in neuronal Ca(2+) signaling as well as morphological excitotoxic changes that were attenuated by the NMDA-receptor antagonist MK801. Direct CNS administration of MS drugs prior to Glu significantly delayed or reduced, but did not prevent the neuronal Ca(2+) increase or morphological changes. In vitro, prolonged (24 h) treatment of primary neurons with the fumarates significantly protected against neurotoxicity induced by Glu as well as NMDA, similar to MK801. Furthermore, monomethyl fumerate significantly reduced Glu release from pathogenic T-helper 17 lymphocytes. Overall, these data suggest that MS drugs may mediate neuroprotection via excitotoxicity modulating effects. Evidence suggests MS pathogenesis may involve neuronal excitotoxicity, induced by local release of glutamate. However, current MS drugs, including dimethyl fumerate (DMF) and fingolimod (FTY720) are largely anti-inflammatory and not yet fully tested for their neuroprotective potential. Here, we show that the drugs, in particular DMF metabolite monomethyl fumerate (MMF), protect neurons by excitotoxicity modulating effects. Th17, T-helper 17.

  16. Peptide and lipid modulation of glutamatergic afferent synaptic transmission in the solitary tract nucleus

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    Michael C. Andresen

    2013-01-01

    Full Text Available The brainstem nucleus of the solitary tract (NTS holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current (EPSC often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g. hypothalamus neuron sources. Presynaptic receptors for angiotensin (AT1, vasopressin (V1a, oxytocin (OT, opioid (MOR, ghrelin (GHSR1 and cholecystokinin (CCK differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 (TRPV1 and the cannabinoid receptor (CB1 that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

  17. Effects of propofol on GABAergic and glutamatergic transmission in isolated hippocampal single nerve-synapse preparations.

    Science.gov (United States)

    Wakita, Masahito; Kotani, Naoki; Nonaka, Kiku; Shin, Min-Chul; Akaike, Norio

    2013-10-15

    We evaluated the effects of propofol on synaptic transmission using a mechanically dissociated preparation of rat hippocampal CA3 neurons to allow assays of single bouton responses evoked from retained functional native nerve endings. We studied synaptic and extrasynaptic GABAA and glutamate receptor responses in a preparation in which experimental solutions rapidly accessed synaptic terminals. Whole-cell responses were evoked by bath application of GABA and glutamate. Synaptic inhibitory and excitatory postsynaptic currents (IPSC and EPSC) were measured as spontaneous and evoked postsynaptic responses. Evoked currents were elicited by focal electrical stimulation. Propofol (1-100 μM) enhanced extrasynaptic GABAA-receptor mediated responses but the increase at clinically relevant concentrations (1 μM) were minor. In contrast, 1 μM propofol significantly increased both the amplitude and frequency of spontaneous IPSCs (sIPSCs) and increased the amplitudes of evoked IPSCs (eIPSCs) while decreasing failure rates (Rf) and paired-pulse ratios (PPR). Decay times of sIPSCs and eIPSCs were significantly prolonged. Although propofol had no effect on extrasynaptic glutamate responses, only supra-clinical propofol concentrations (≥ 10 µM) increased the spontaneous EPSCs (sEPSCs, amplitudes and frequencies) but suppressed evoked EPSCs (eEPSCs decreased amplitudes with increased Rf and PPR). The decay phases of sEPSCs and eEPSCs were not changed. The propofol-induced changes in sEPSCs and eEPSCs resulted from presynaptic GABAA receptor-mediated depolarization, because these actions were blocked by bicuculline. These results suggest that propofol acts at presynaptic and postsynaptic GABAA receptors within GABAergic synapses, but also increases extrasynaptic GABA responses. Our results expand the locus of propofol actions to GABAergic and glutamatergic synapses.

  18. Blockade of glutamatergic transmission in the primate basolateral amygdala suppresses active behavior without altering social interaction.

    Science.gov (United States)

    Forcelli, Patrick A; Wellman, Laurie L; Malkova, Ludise

    2017-04-01

    The amygdala is an integrator of affective processing, and a key component of a network regulating social behavior. While decades of lesion studies in nonhuman primates have shown alterations in social interactions after amygdala damage, acute manipulations of the amygdala in primates have been underexplored. We recently reported (Wellman, Forcelli, Aguilar, & Malkova, 2016) that acute pharmacological inhibition of the basolateral complex of the amygdala (BLA) or the central nucleus of the amygdala increased affiliative social interactions in experimental dyads of macaques; this was achieved through microinjection of a GABA-A receptor agonist. Prior studies in rodents have shown similar effects achieved by blocking NMDA receptors or AMPA receptors within the BLA. Here, we sought to determine the role of these receptor systems in the primate BLA in the context of social behavior. In familiar dyads, we microinjected the NMDA receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP7) or the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) and observed behaviors and social interactions in the immediate postinjection period. In striking contrast with our prior report using GABA agonists, and in contrast with prior reports in rodents using glutamate antagonists, we found that neither NMDA nor AMPA blockade increase social interaction. Both treatments, however, were associated with decreases in locomotion and manipulation and increases in passive behavior. These data suggest that local blockade of glutamatergic neurotransmission in BLA is not the functional equivalent of local activation of GABAergic signaling, and raise interesting questions regarding the functional microcircuitry of the nonhuman primate amygdala in the context of social behavior. (PsycINFO Database Record

  19. Acute stress enhances the glutamatergic transmission onto basoamygdala neurons embedded in distinct microcircuits.

    Science.gov (United States)

    Song, Chen; Zhang, Wen-Hua; Wang, Xue-Hui; Zhang, Jun-Yu; Tian, Xiao-Li; Yin, Xiao-Ping; Pan, Bing-Xing

    2017-01-09

    Amygdala activation is known to be critical for the processing of stressful events in brain. Recent studies have shown that the projection neurons (PNs) in amygdala, although architecturally intermingled, are integrated into distinct microcircuits and thus play divergent roles in amygdala-related behaviors. It remains unknown how stress regulates the individual amygdala PNs embedded in distinct microcircuits. Here, by using retrograde tracing and electrophysiological recording in in vitro slices, we explored the modulation of acute immobilization stress (AIS) on the basoamygdala (BA) PNs projecting either to medial prefrontal cortex (mPFC) or elsewhere, which we designated as BA-mPFC and non-BA-mPFC PNs respectively. The results showed that in the control mice, both the excitatory and inhibitory postsynaptic currents (sEPSCs/sIPSCs) were comparable between these two subsets of BA PNs. The influences of AIS on sEPSCs and sIPSCs were overall similar between the two neuronal populations. It markedly increased the sEPSCs amplitude but left unaltered their frequency as well as the sIPSCs amplitude and frequency. Despite this, several differences emerged between the effects of AIS on the distribution of sEPSCs/sIPSCs frequency in these two groups of BA PNs. Similar changes were also observed in the sEPSCs/sIPSCs of the two PN populations from mice experiencing forced swimming stress. Their intrinsic excitability, on the other hand, was nearly unaltered following AIS. Our results thus suggest that acute stress recruit both BA-mPFC and non-BA-mPFC PNs mainly through enhancing the glutamatergic transmission they receive.

  20. Developmental changes in the acute ethanol sensitivity of glutamatergic and GABAergic transmission in the BNST.

    Science.gov (United States)

    Wills, T A; Kash, T L; Winder, D G

    2013-11-01

    Glutamatergic and GABAergic transmission undergo significant changes during adolescence. Receptors for both of these transmitters (NMDAR, and GABAA) are known to be key targets for the acute effects of ethanol in adults. The current study set out to investigate the acute effects of ethanol on both NMDAR-mediated excitatory transmission and GABAergic inhibitory transmission within the bed nucleus of the stria terminalis (BNST) across age. The BNST is an area of the brain implicated in the negative reinforcing properties associated with alcohol dependence, and the BNST plays a critical role in stress-induced relapse. Therefore, assessing the developmental regulation of ethanol sensitivity in this key brain region is important to understanding the progression of ethanol dependence. To do this, whole-cell recordings of isolated NMDAR-evoked excitatory postsynaptic currents (eEPSCs) or evoked GABAergic inhibitory postsynaptic currents (eIPSCs) were performed on BNST neurons in slices from 4- or 8-week-old male C57BL/6J mice. Ethanol (50 mm) produced greater inhibition of NMDAR-eEPSCs in adolescent mice than in adult mice. This enhanced sensitivity in adolescence was not a result of shifts in function of the GluN2B subunit of the NMDAR, measured by Ro25-6981 inhibition and decay kinetics measured across age. Adolescent mice also exhibited greater ethanol sensitivity of GABAergic transmission, as ethanol (50 mm) enhanced eIPSCs in the BNST of adolescent but not adult mice. Collectively, this work illustrates that a moderate dose of ethanol produces greater inhibition of transmission in the BNST (through greater excitatory inhibition and enhancement of inhibitory transmission) in adolescents compared to adults. Given the role of the BNST in alcohol dependence, these developmental changes in acute ethanol sensitivity could accelerate neuroadaptations that result from chronic ethanol use during the critical period of adolescence.

  1. Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn

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    Vaughan Christopher W

    2010-10-01

    Full Text Available Abstract Background There is anatomical and behavioural evidence that μ- and δ-opioid receptors modulate distinct nociceptive modalities within the superficial dorsal horn. The aim of the present study was to examine whether μ- and δ-opioid receptor activation differentially modulates TRP sensitive inputs to neurons within the superficial dorsal horn. To do this, whole cell patch clamp recordings were made from lamina I - II neurons in rat spinal cord slices in vitro to examine the effect of opioids on TRP agonist-enhanced glutamatergic spontaneous miniature excitatory postsynaptic currents (EPSCs. Results Under basal conditions the μ-opioid agonist DAMGO (3 μM reduced the rate of miniature EPSCs in 68% of neurons, while the δ- and κ-opioid agonists deltorphin-II (300 nM and U69593 (300 nM did so in 13 - 17% of neurons tested. The TRP agonists menthol (400 μM and icilin (100 μM both produced a Ca2+-dependent increase in miniature EPSC rate which was unaffected by the voltage dependent calcium channel (VDCC blocker Cd2+. The proportion of neurons in which deltorphin-II reduced the miniature EPSC rate was enhanced in the presence of icilin (83%, but not menthol (0%. By contrast, the proportion of DAMGO and U69593 responders was unaltered in the presence of menthol (57%, 0%, or icilin (57%, 17%. Conclusions These findings demonstrate that δ-opioid receptor activation selectively inhibits inputs activated by icilin, whereas μ-opioid receptor activation has a more widespread effect on synaptic inputs to neurons in the superficial dorsal horn. These findings suggest that δ-opioids may provide a novel analgesic approach for specific, TRPA1-like mediated pain modalities.

  2. Enhancement by citral of glutamatergic spontaneous excitatory transmission in adult rat substantia gelatinosa neurons.

    Science.gov (United States)

    Zhu, Lan; Fujita, Tsugumi; Jiang, Chang-Yu; Kumamoto, Eiichi

    2016-02-10

    Although citral, which is abundantly present in lemongrass, has various actions including antinociception, how citral affects synaptic transmission has not been examined as yet. Citral activates in heterologous cells transient receptor potential vanilloid-1, ankyrin-1, and melastatin-8 (TRPV1, TRPA1, and TRPM8, respectively) channels, the activation of which in the spinal lamina II [substantia gelatinosa (SG)] increases the spontaneous release of L-glutamate from nerve terminals. It remains to be examined what types of transient receptor potential channel in native neurons are activated by citral. With a focus on transient receptor potential activation, we examined the effect of citral on glutamatergic spontaneous excitatory transmission using the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. Bath-applied citral for 3 min increased the frequency of spontaneous excitatory postsynaptic current in a concentration-dependent manner (half-maximal effective concentration=0.58 mM), with a small increase in its amplitude. The spontaneous excitatory postsynaptic current frequency increase produced by citral was repeated at a time interval of 30 min, albeit this action recovered with a slow time course after washout. The presynaptic effect of citral was inhibited by TRPA1 antagonist HC-030031, but not by voltage-gated Na-channel blocker tetrodotoxin, TRPV1 antagonist capsazepine, and TRPM8 antagonist BCTC. It is concluded that citral increases spontaneous L-glutamate release in SG neurons by activating TRPA1 channels. Considering that the SG plays a pivotal role in modulating nociceptive transmission from the periphery, the citral activity could contribute toward at least a part of the modulation.

  3. Presynaptic α7 nicotinic acetylcholine receptors enhance hippocampal mossy fiber glutamatergic transmission via PKA activation.

    Science.gov (United States)

    Cheng, Qing; Yakel, Jerrel L

    2014-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and mediate both synaptic and perisynaptic activities of endogenous cholinergic inputs and pharmacological actions of exogenous compounds (e.g., nicotine and choline). Behavioral studies indicate that nicotine improves such cognitive functions as learning and memory. However, the mechanism of nicotine's action on cognitive function remains elusive. We performed patch-clamp recordings from hippocampal CA3 pyramidal neurons to determine the effect of nicotine on mossy fiber glutamatergic synaptic transmission. We found that nicotine in combination with NS1738, an α7 nAChR-positive allosteric modulator, strongly potentiated the amplitude of evoked EPSCs (eEPSCs), and reduced the EPSC paired-pulse ratio. The action of nicotine and NS1738 was mimicked by PNU-282987 (an α7 nAChR agonist), and was absent in α7 nAChR knock-out mice. These data indicate that activation of α7 nAChRs was both necessary and sufficient to enhance the amplitude of eEPSCs. BAPTA applied postsynaptically failed to block the action of nicotine and NS1738, suggesting again a presynaptic action of the α7 nAChRs. We also observed α7 nAChR-mediated calcium rises at mossy fiber giant terminals, indicating the presence of functional α7 nAChRs at presynaptic terminals. Furthermore, the addition of PNU-282987 enhanced action potential-dependent calcium transient at these terminals. Last, the potentiating effect of PNU-282987 on eEPSCs was abolished by inhibition of protein kinase A (PKA). Our findings indicate that activation of α7 nAChRs at presynaptic sites, via a mechanism involving PKA, plays a critical role in enhancing synaptic efficiency of hippocampal mossy fiber transmission.

  4. Comparative analysis of enzyme-linked immunosorbent assay and direct microscopy for the diagnosis of Giardia intestinalis in fecal samples

    Directory of Open Access Journals (Sweden)

    Shipra Singhal

    2015-01-01

    Full Text Available Context: Giardiasis is one of the most common nonviral infections causing diarrheal illness worldwide. In this prospective cross-sectional study, we evaluated the RIDASCREEN ® Giardia kit for detection of Giardia intestinalis in stool samples and compared the results with direct microscopy. Materials and methods: A total of 360 fecal samples were collected. They were then processed by wet film, iodine preparation and an enzyme-linked immunosorbent assay (ELISA kit to determine the presence of Giardia trophozoites and cysts. Statistical analysis was performed by sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. Results and Conclusion: Of the 360 cases, 17.2% samples were positive for Giardia by direct microscopy and 23.6% were found to be positive by ELISA (sensitivity ~97%, but specificity was ~92% only. Because of less specificity, we need to perform ELISA in congruence with direct microscopy, etc. Further studies need to be performed on a larger sample size using other molecular tests in order to get more accurate estimations.

  5. Does the Neighborhood Context Alter the Link between Youth's After-School Time Activities and Developmental Outcomes? A Multilevel Analysis

    Science.gov (United States)

    Fauth, Rebecca C.; Roth, Jodie L.; Brooks-Gunn, Jeanne

    2007-01-01

    This article examines links between different measures of after-school time activity participation (5 specific activities and breadth) on youth's developmental outcomes (anxiety/depression, delinquency, and substance use) over 6 years and whether these links are moderated by neighborhood-level variables. The sample (N = 1,315) of 9- and…

  6. Assessing brain structural associations with working memory related brain patterns in schizophrenia and healthy controls using linked independent component analysis

    Directory of Open Access Journals (Sweden)

    Christine Lycke Brandt

    2015-01-01

    Full Text Available Schizophrenia (SZ is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC. Utilizing linked independent component analysis (LICA, a data-driven multimodal analysis approach, we investigated structure–function associations in a large sample of SZ (n = 96 and HC (n = 142. We tested for associations between task-positive (fronto-parietal and task-negative (default-mode brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p < .05, corrected for multiple comparisons was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure–function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.

  7. PDF Weaving - Linking Inventory Data and Monte Carlo Uncertainty Analysis in the Study of how Disturbance Affects Forest Carbon Storage

    Science.gov (United States)

    Healey, S. P.; Patterson, P.; Garrard, C.

    2014-12-01

    Altered disturbance regimes are likely a primary mechanism by which a changing climate will affect storage of carbon in forested ecosystems. Accordingly, the National Forest System (NFS) has been mandated to assess the role of disturbance (harvests, fires, insects, etc.) on carbon storage in each of its planning units. We have developed a process which combines 1990-era maps of forest structure and composition with high-quality maps of subsequent disturbance type and magnitude to track the impact of disturbance on carbon storage. This process, called the Forest Carbon Management Framework (ForCaMF), uses the maps to apply empirically calibrated carbon dynamics built into a widely used management tool, the Forest Vegetation Simulator (FVS). While ForCaMF offers locally specific insights into the effect of historical or hypothetical disturbance trends on carbon storage, its dependence upon the interaction of several maps and a carbon model poses a complex challenge in terms of tracking uncertainty. Monte Carlo analysis is an attractive option for tracking the combined effects of error in several constituent inputs as they impact overall uncertainty. Monte Carlo methods iteratively simulate alternative values for each input and quantify how much outputs vary as a result. Variation of each input is controlled by a Probability Density Function (PDF). We introduce a technique called "PDF Weaving," which constructs PDFs that ensure that simulated uncertainty precisely aligns with uncertainty estimates that can be derived from inventory data. This hard link with inventory data (derived in this case from FIA - the US Forest Service Forest Inventory and Analysis program) both provides empirical calibration and establishes consistency with other types of assessments (e.g., habitat and water) for which NFS depends upon FIA data. Results from the NFS Northern Region will be used to illustrate PDF weaving and insights gained from ForCaMF about the role of disturbance in carbon

  8. Ruminant rhombencephalitis-associated Listeria monocytogenes alleles linked to a multilocus variable-number tandem-repeat analysis complex.

    Science.gov (United States)

    Balandyté, Lina; Brodard, Isabelle; Frey, Joachim; Oevermann, Anna; Abril, Carlos

    2011-12-01

    Listeria monocytogenes is among the most important food-borne pathogens and is well adapted to persist in the environment. To gain insight into the genetic relatedness and potential virulence of L. monocytogenes strains causing central nervous system (CNS) infections, we used multilocus variable-number tandem-repeat analysis (MLVA) to subtype 183 L. monocytogenes isolates, most from ruminant rhombencephalitis and some from human patients, food, and the environment. Allelic-profile-based comparisons grouped L. monocytogenes strains mainly into three clonal complexes and linked single-locus variants (SLVs). Clonal complex A essentially consisted of isolates from human and ruminant brain samples. All but one rhombencephalitis isolate from cattle were located in clonal complex A. In contrast, food and environmental isolates mainly clustered into clonal complex C, and none was classified as clonal complex A. Isolates of the two main clonal complexes (A and C) obtained by MLVA were analyzed by PCR for the presence of 11 virulence-associated genes (prfA, actA, inlA, inlB, inlC, inlD, inlE, inlF, inlG, inlJ, and inlC2H). Virulence gene analysis revealed significant differences in the actA, inlF, inlG, and inlJ allelic profiles between clinical isolates (complex A) and nonclinical isolates (complex C). The association of particular alleles of actA, inlF, and newly described alleles of inlJ with isolates from CNS infections (particularly rhombencephalitis) suggests that these virulence genes participate in neurovirulence of L. monocytogenes. The overall absence of inlG in clinical complex A and its presence in complex C isolates suggests that the InlG protein is more relevant for the survival of L. monocytogenes in the environment.

  9. Activation of mu opioid receptor inhibits the excitatory glutamatergic transmission in the anterior cingulate cortex of the rats with peripheral inflammation.

    Science.gov (United States)

    Zheng, Weihong

    2010-02-25

    Emerging evidence recently indicates that the anterior cingulate cortex is critically involved in the central processing and modulation of noxious stimulus, although the neuroadaptation in the anterior cingulate cortex has not been well documented in the conditions of chronic pain. Meanwhile, the cellular mechanism underlying opiate analgesia in the anterior cingulate cortex remains unclear. To address these issues, the present study was undertaken to explore the adaptation of excitatory glutamatergic transmission and mu opioid receptor-mediated modulation of glutamatergic transmission in the anterior cingulate cortex slices from the complete Freund's adjuvant (CFA)-inflamed rats. The results demonstrated that glutamatergic paired-pulse facilitation was decreased in the anterior cingulate cortex neurons from the CFA-inflamed rats, indicating an enhanced presynaptic glutamate release. In addition, activation of mu opioid receptor significantly inhibited the glutamatergic excitatory postsynaptic currents (EPSCs) in the anterior cingulate cortex neurons, which was attained through the suppression of presynaptic glutamate release. Taken together, these findings provided the evidence for the functional adaptation of central glutamatergic transmission induced by peripheral inflammation, and elucidated the cellular mechanism underlying opiate analgesia in the anterior cingulate cortex.

  10. Nuclear respiratory factor 1 co-regulates AMPA glutamate receptor subunit 2 and cytochrome c oxidase: tight coupling of glutamatergic transmission and energy metabolism in neurons.

    Science.gov (United States)

    Dhar, Shilpa S; Liang, Huan Ling; Wong-Riley, Margaret T T

    2009-03-01

    Neuronal activity, especially of the excitatory glutamatergic type, is highly dependent on energy from the oxidative pathway. We hypothesized that the coupling existed at the transcriptional level by having the same transcription factor to regulate a marker of energy metabolism, cytochrome c oxidase (COX) and an important subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors, GluR2 (Gria2). Nuclear respiratory factor 1 (NRF-1) was a viable candidate because it regulates all COX subunits and potentially activates Gria2. By means of in silico analysis, electrophoretic mobility shift and supershift, chromatin immunoprecipitation, and promoter mutational assays, we found that NRF-1 functionally bound to Gria2 promoter. Silencing of NRF-1 with small interference RNA prevented the depolarization-stimulated up-regulation of Gria2 and COX, and over-expression of NRF-1 rescued neurons from tetrodotoxin-induced down-regulation of Gria2 and COX transcripts. Thus, neuronal activity and energy metabolism are tightly coupled at the molecular level, and NRF-1 is a critical agent in this process.

  11. Extrinsic and local glutamatergic inputs of the rat hippocampal CA1 area differentially innervate pyramidal cells and interneurons.

    Science.gov (United States)

    Takács, Virág T; Klausberger, Thomas; Somogyi, Peter; Freund, Tamás F; Gulyás, Attila I

    2012-06-01

    The two main glutamatergic pathways to the CA1 area, the Schaffer collateral/commissural input and the entorhinal fibers, as well as the local axons of CA1 pyramidal cells innervate both pyramidal cells and interneurons. To determine whether these inputs differ in their weights of activating GABAergic circuits, we have studied the relative proportion of pyramidal cells and interneurons among their postsynaptic targets in serial electron microscopic sections. Local axons of CA1 pyramidal cells, intracellularly labeled in vitro or in vivo, innervated a relatively high proportion of interneuronal postsynaptic targets (65.9 and 53.8%, in vitro and in vivo, respectively) in stratum (str.) oriens and alveus. In contrast, axons of in vitro labeled CA3 pyramidal cells in str. oriens and str. radiatum of the CA1 area made synaptic junctions predominantly with pyramidal cell spines (92.9%). The postsynaptic targets of anterogradely labeled medial entorhinal cortical boutons in CA1 str. lacunosum-moleculare were primarily pyramidal neuron dendritic spines and shafts (90.8%). The alvear group of the entorhinal afferents, traversing str. oriens, str. pyramidale, and str. radiatum showed a higher preference for innervating GABAergic cells (21.3%), particularly in str. oriens/alveus. These data demonstrate that different glutamatergic pathways innervate CA1 GABAergic cells to different extents. The results suggest that the numerically smaller CA1 local axonal inputs together with the alvear part of the entorhinal input preferentially act on GABAergic interneurons in contrast to the CA3, or the entorhinal input in str. lacunosum-moleculare. The results highlight differences in the postsynaptic target selection of the feed-forward versus recurrent glutamatergic inputs to the CA1 and CA3 areas.

  12. Biphasic Effects of Cannabinoids in Anxiety Responses: CB1 and GABAB Receptors in the Balance of GABAergic and Glutamatergic Neurotransmission

    Science.gov (United States)

    Rey, Alejandro Aparisi; Purrio, Martin; Viveros, Maria-Paz; Lutz, Beat

    2012-01-01

    Biphasic effects of cannabinoids have been shown in processes such as feeding behavior, motor activity, motivational processes and anxiety responses. Using two different tests for the characterization of anxiety-related behavior (elevated plus-maze and holeboard), we first identified in wild-type C57BL/6N mice, two doses of the synthetic CB1 cannabinoid receptor agonist CP-55,940 with anxiolytic (1 μg/kg) and anxiogenic properties (50 μg/kg), respectively. To clarify the role of CB1 receptors in this biphasic effect, both doses were applied to two different conditional CB1 receptor knockout (KO) mouse lines, GABA-CB1-KO (CB1 receptor inactivation in forebrain GABAergic neurons) and Glu-CB1-KO (CB1 receptor inactivation in cortical glutamatergic neurons). We found that the anxiolytic-like effects of the low dose of cannabinoids are mediated via the CB1 receptor on cortical glutamatergic terminals, because this anxiolytic-like response was abrogated only in Glu-CB1-KO mice. On the contrary, the CB1 receptor on the GABAergic terminals is required to induce an anxiogenic-like effect under a high-dose treatment because of the fact that this effect was abolished specifically in GABA-CB1-KO mice. These experiments were carried out in both sexes, and no differences occurred with the doses tested in the mutant mice. Interestingly, the positive allosteric modulation of GABAB receptor with GS-39783 was found to largely abrogate the anxiogenic-like effect of the high dose of CP-55,940. Our results shed new light in further understanding the biphasic effects of cannabinoids at the molecular level and, importantly, pave the way for the development of novel anxiolytic cannabinoid drugs, which may have favorable effect profiles targeting the CB1 receptor on glutamatergic terminals. PMID:22850737

  13. Cholinergic modulation of non-N-methyl-D-aspartic acid glutamatergic transmission in the chick ventral lateral geniculate nucleus.

    Science.gov (United States)

    Guo, J-Z; Sorenson, E M; Chiappinelli, V A

    2010-03-17

    Neurotransmission between glutamatergic terminals of retinal ganglion cells and principal neurons of the ventral lateral geniculate nucleus (LGNv) was examined with patch clamp recordings in chick brain slices during electrical stimulation of the optic tract. Since muscarinic and nicotinic receptors are present in high densities in LGNv, the present study examined possible roles of both receptors in modulating retinogeniculate transmission. During whole-cell recordings from LGNv neurons, acetylcholine (ACh, 100 microM) caused an initial increase in amplitudes of optic tract-evoked non-N-methyl-D-aspartic acid (NMDA) glutamatergic postsynaptic currents (PSCs). This increase was unchanged when 1 microM atropine was present, indicating that this initial enhancement of PSCs was due entirely to activation of nicotinic receptors. However, during washout of ACh the amplitudes of evoked PSCs became significantly decreased by 40.4+/-5.0% for several minutes before recovering to their original amplitudes, an effect blocked by 1 microM atropine. Exogenously applied muscarine (10 microM) markedly depressed optic tract-evoked PSCs, and this decrease in amplitude was blocked by atropine. In a second set of experiments, we examined effects of releasing endogenous ACh prior to optic tract stimulation. This was accomplished by stimulation of the lateral portion of LGNv via a separate conditioning electrode. Following a brief train of low intensity conditioning stimuli, non-NMDA glutamatergic PSCs evoked by optic tract stimulation were potentiated. However, at higher conditioning stimulus intensities the PSCs were markedly decreased compared with control, and this decrease was partially blocked by atropine (1 microM). Neither ACh nor muscarine altered amplitudes of PSCs elicited by exogenously applied glutamate. Muscarine significantly reduced the frequency but not the amplitudes of miniature PSCs, consistent with a presynaptic location for muscarinic receptors mediating these

  14. Perifornical hypothalamic pathway to the adrenal gland: Role for glutamatergic transmission in the glucose counter-regulatory response.

    Science.gov (United States)

    Sabetghadam, A; Korim, W S; Verberne, A J M

    2017-03-01

    Adrenaline is an important counter-regulatory hormone that helps restore glucose homeostasis during hypoglycaemia. However, the neurocircuitry that connects the brain glucose sensors and the adrenal sympathetic outflow to the chromaffin cells is poorly understood. We used electrical microstimulation of the perifornical hypothalamus (PeH) and the rostral ventrolateral medulla (RVLM) combined with adrenal sympathetic nerve activity (ASNA) recording to examine the relationship between the RVLM, the PeH and ASNA. In urethane-anaesthetised male Sprague-Dawley rats, intermittent single pulse electrical stimulation of the rostroventrolateral medulla (RVLM) elicited an evoked ASNA response that consisted of early (60±3ms) and late peaks (135±4ms) of preganglionic and postganglionic activity. In contrast, RVLM stimulation evoked responses in lumbar sympathetic nerve activity that were almost entirely postganglionic. PeH stimulation also produced an evoked excitatory response consisting of both preganglionic and postganglionic excitatory peaks in ASNA. Both peaks in ASNA following RVLM stimulation were reduced by intrathecal kynurenic acid (KYN) injection. In addition, the ASNA response to systemic neuroglucoprivation induced by 2-deoxy-d-glucose was abolished by bilateral microinjection of KYN into the RVLM. This suggests that a glutamatergic pathway from the perifornical hypothalamus (PeH) relays in the RVLM to activate the adrenal SPN and so modulate ASNA. The main findings of this study are that (i) adrenal premotor neurons in the RVLM may be, at least in part, glutamatergic and (ii) that the input to these neurons that is activated during neuroglucoprivation is also glutamatergic.

  15. Melamine Alters Glutamatergic Synaptic Transmission of CA3-CA1 Synapses Presynaptically Through Autophagy Activation in the Rat Hippocampus.

    Science.gov (United States)

    Zhang, Hui; Wang, Hui; Xiao, Xi; Zhang, Tao

    2016-01-01

    Melamine is an industrial chemical that can cause central nervous system disorders including excitotoxicity and cognitive impairment. Its illegal use in powdered baby formula was the focus of a milk scandal in China in 2008. One of our previous studies showed that melamine impaired glutamatergic transmission in rat hippocampal CA1 pyramidal cells. However, the underlying mechanism of action of melamine is unclear, and it is unknown if the CA3-CA1 pathway is directly involved. In the present study, a whole-cell patch-clamp technique was employed to investigate the effect of melamine on the hippocampal CA3-CA1 pathway in vitro. Both the evoked excitatory postsynaptic current (eEPSC) and the paired-pulse ratio (PPR) were recorded. Furthermore, we examined whether autophagy was involved in glutamatergic transmission alterations induced by melamine. Our data showed that melamine significantly increased the amplitude of eEPSCs in a dose-dependent manner. Inhibition of the N-methyl-D-aspartic acid receptor did not prevent the increase in eEPSC amplitude. In addition, the PPR was remarkably decreased by a melamine concentration of 5 × 10(-5) g/mL. It was found that autophagy could be activated by melamine and an autophagy inhibitor, 3-MA, prevented the melamine-induced increase in eEPSC amplitude. Overall, our results show that melamine presynaptically alters glutamatergic synaptic transmission of hippocampal CA3-CA1 synapses in vitro and this is likely associated with autophagy alteration.

  16. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

    Directory of Open Access Journals (Sweden)

    Mawrin Christian

    2011-08-01

    Full Text Available Abstract Background Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described. Methods Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA glutamate receptor agonist quinolinic acid (QUIN in the subgenual anterior cingulate cortex (sACC, anterior midcingulate cortex (aMCC and pregenual anterior cingulate cortex (pACC of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5 was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects. Results Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003 and the aMCC (P = 0.015 compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558. Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD. Conclusions These results add a novel link to the immune hypothesis of depression by providing evidence for an upregulation of microglial QUIN in brain regions known to be responsive to infusion of NMDA antagonists such as ketamine. Further work in this area could lead to a greater understanding of the pathophysiology of depressive disorders and pave the way for novel NMDA receptor therapies or immune-modulating strategies.

  17. A PRACTICAL APPROACH TO THE DETECTION OF ANDROGEN RECEPTOR GENE-MUTATIONS AND PEDIGREE ANALYSIS IN FAMILIES WITH X-LINKED ANDROGEN INSENSITIVITY

    NARCIS (Netherlands)

    RISSTALPERS, C; HOOGENBOEZEM, T; SLEDDENS, HFBM; VERLEUNMOOIJMAN, MCT; DEGENHART, HJ; DROP, SLS; HALLEY, DJJ; Oosterwijk, Jan; HODGINS, MB; TRAPMAN, J; BRINKMANN, AO

    1994-01-01

    Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of th

  18. [A simple method to correct genetic distance between linked genes and a correction of calculating data in tetrad analysis in Neurospora crassa].

    Science.gov (United States)

    Li, You-Yong; Zhao, Yuan-Zeng

    2003-05-01

    The present paper is dealing with a simple method to correct the distance of linked genes in tetrad analysis in Neurospora crassa. It is suggested that the data of 4-thread double crossing over should be added in two single crossing over respectively in centromere maping when calculating crossover value of the two genes locating across the centromere.

  19. Five-Year Experience of Vitamin E-Diffused Highly Cross-Linked Polyethylene Wear in Total Hip Arthroplasty Assessed by Radiostereometric Analysis

    DEFF Research Database (Denmark)

    Nebergall, Audrey K; Troelsen, Anders; Rubash, Harry E;

    2016-01-01

    BACKGROUND: Vitamin E-diffused highly cross-linked polyethylene (VEPE) was developed to reduce oxidation without compromising mechanical strength. The purpose of this study was to evaluate VEPE in vivo using radiostereometric analysis (RSA) and patient-reported outcome measures (PROMs). METHODS: ...

  20. Download - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available [ Credits ] BLAST Search Image Search Home About Archive Update History Contact us PGDBj Registered...d 1 README README_e.html - 2 Registered plant list pgdbj_dna_marker_linkage_map_plant_species_list_en.zip (2...Policy | Contact Us Download - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive ...

  1. Stress-induced impairment of glutamatergic terminals ultrastructure: High vulnerability of medial prefrontal cortex and preventing action of desipramine

    DEFF Research Database (Denmark)

    Nava, N.; Popoli, M.; Musazzi, L.;

    2013-01-01

    mediators, glucocorticoids, on brain volume and dendritic remodeling, in both humans and rodents. Nevertheless, few is still known on the structural changes exerted by behavioral stress on the features of glutamatergic synapses as sites of neuronal communication. Indeed, in excitatory synapses synaptic...... communication is driven by neurotransmitter which is stored, within the presynaptic terminal, in morphologically distinct pools of vesicles, namely the readily-releasable pool of vesicles (RRP), docked to the active zone and ready for release, and the reserve pool of vesicles. When neurotransmitter is released...

  2. Innervation by a GABAergic neuron depresses spontaneous release in glutamatergic neurons and unveils the clamping phenotype of synaptotagmin-1

    DEFF Research Database (Denmark)

    Wierda, Keimpe D B; Sørensen, Jakob Balslev

    2014-01-01

    EPSC and mIPSC frequencies did not deviate between autaptic and synaptic connections, the frequency of mEPSCs in mixed pairs was strongly depressed compared with either autaptic neurons or glutamatergic pairs. Simultaneous imaging of synapses, or comparison to evoked release amplitudes, showed...... that this decrease was not caused by fewer active synapses. The mEPSC frequency was negatively correlated with the mIPSC frequency, indicating interdependence. Moreover, the reduction in mEPSC frequency was abolished when established pairs were exposed to bicuculline for 3 d, but not by long-term incubation...

  3. Co-word analysis: a study on the links and boundaries between information and knowledge management according to iranian press authors

    OpenAIRE

    Hamid Ahmadi; Morteza Kokabi

    2015-01-01

    Information and knowledge management has emerged as major tools for collecting and regulating available data to spread over an entire organ.The present study is to identify the links and boundaries between the two management systems. Co-word analysis method is obtained as research method since along with other scientometric techniques is a parameter for content analysis. Articles accepted for domestic journals and conferences constitute the population of this study. The current research findi...

  4. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation.

    Science.gov (United States)

    Song, Wan Seok; Nam, Mi Sun; Namgung, Byeol; Yoon, Sung-il

    2015-03-20

    Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis.

  5. Critical body residues linked to octanol-water partitioning, organism composition, and LC50 QSARs: meta-analysis and model.

    Science.gov (United States)

    Hendriks, A Jan; Traas, Theo P; Huijbregts, Mark A J

    2005-05-01

    To protect thousands of species from thousands of chemicals released in the environment, various risk assessment tools have been developed. Here, we link quantitative structure-activity relationships (QSARs) for response concentrations in water (LC50) to critical concentrations in organisms (C50) by a model for accumulation in lipid or non-lipid phases versus water Kpw. The model indicates that affinity for neutral body components such as storage fat yields steep Kpw-Kow relationships, whereas slopes for accumulation in polar phases such as proteins are gentle. This pattern is confirmed by LC50 QSARs for different modes of action, such as neutral versus polar narcotics and organochlorine versus organophosphor insecticides. LC50 QSARs were all between 0.00002 and 0.2Kow(-1). After calibrating the model with the intercepts and, for the first time also, with the slopes of the LC50 QSARs, critical concentrations in organisms C50 are calculated and compared to an independent validation data set. About 60% of the variability in lethal body burdens C50 is explained by the model. Explanations for differences between estimated and measured levels for 11 modes of action are discussed. In particular, relationships between the critical concentrations in organisms C50 and chemical (Kow) or species (lipid content) characteristics are specified and tested. The analysis combines different models proposed before and provides a substantial extension of the data set in comparison to previous work. Moreover, the concept is applied to species (e.g., plants, lean animals) and substances (e.g., specific modes of action) that were scarcely studied quantitatively so far.

  6. Human cell toxicogenomic analysis linking reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts.

    Science.gov (United States)

    Pals, Justin; Attene-Ramos, Matias S; Xia, Menghang; Wagner, Elizabeth D; Plewa, Michael J

    2013-01-01

    Chronic exposure to drinking water disinfection byproducts has been linked to adverse health risks. The monohaloacetic acids (monoHAAs) are generated as byproducts during the disinfection of drinking water and are cytotoxic, genotoxic, mutagenic, and teratogenic. Iodoacetic acid toxicity was mitigated by antioxidants, suggesting the involvement of oxidative stress. Other monoHAAs may share a similar mode of action. Each monoHAA generated a significant concentration-response increase in the expression of a β-lactamase reporter under the control of the antioxidant response element (ARE). The monoHAAs generated oxidative stress with a rank order of iodoacetic acid (IAA) > bromoacetic acid (BAA) ≫ chloroacetic acid (CAA); this rank order was observed with other toxicological end points. Toxicogenomic analysis was conducted with a nontransformed human intestinal epithelial cell line (FHs 74 Int). Exposure to the monoHAAs altered the transcription levels of multiple oxidative stress responsive genes, indicating that each exposure generated oxidative stress. The transcriptome profiles showed an increase in thioredoxin reductase 1 (TXNRD1) and sulfiredoxin (SRXN1), suggesting peroxiredoxin proteins had been oxidized during monoHAA exposures. Three possible sources of reactive oxygen species were identified, the hypohalous acid generating peroxidase enzymes lactoperoxidase (LPO) and myeloperoxidase (MPO), nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase 5 (NOX5), and PTGS2 (COX-2) mediated arachidonic acid metabolism. Each monoHAA exposure caused an increase in COX-2 mRNA levels. These data provide a functional association between monoHAA exposure and adverse health outcomes such as oxidative stress, inflammation, and cancer.

  7. Recombinase polymerase and enzyme-linked immunosorbent assay as a DNA amplification-detection strategy for food analysis

    Energy Technology Data Exchange (ETDEWEB)

    Santiago-Felipe, S.; Tortajada-Genaro, L.A.; Puchades, R.; Maquieira, A., E-mail: amaquieira@qim.upv.es

    2014-02-06

    Graphical abstract: -- Highlights: •Recombinase polymerase amplification is a powerful DNA method operating at 40 °C. •The combination RPA–ELISA gives excellent performances for high-throughput analysis. •Screening of food safety threats has been done using standard laboratory equipment. •Allergens, GMOs, bacteria, and fungi have been successfully determined. -- Abstract: Polymerase chain reaction in conjunction with enzyme-linked immunosorbent assay (PCR–ELISA) is a well-established technique that provides a suitable rapid, sensitive, and selective method for a broad range of applications. However, the need for precise rapid temperature cycling of PCR is an important drawback that can be overcome by employing isothermal amplification reactions such as recombinase polymerase amplification (RPA). The RPA–ELISA combination is proposed for amplification at a low, constant temperature (40 °C) in a short time (40 min), for the hybridisation of labelled products to specific 5′-biotinylated probes/streptavidin in coated microtiter plates at room temperature, and for detection by colorimetric immunoassay. RPA–ELISA was applied to screen common safety threats in foodstuffs, such as allergens (hazelnut, peanut, soybean, tomato, and maize), genetically modified organisms (P35S and TNOS), pathogenic bacteria (Salmonella sp. and Cronobacter sp.), and fungi (Fusarium sp.). Satisfactory sensitivity and reproducibility results were achieved for all the targets. The RPA–ELISA technique does away with thermocycling and provides a suitable sensitive, specific, and cost-effective method for routine applications, and proves particularly useful for resource-limited settings.

  8. Bit-error-rate performance analysis of self-heterodyne detected radio-over-fiber links using phase and intensity modulation

    DEFF Research Database (Denmark)

    Yin, Xiaoli; Yu, Xianbin; Tafur Monroy, Idelfonso

    2010-01-01

    We theoretically and experimentally investigate the performance of two self-heterodyne detected radio-over-fiber (RoF) links employing phase modulation (PM) and quadrature biased intensity modulation (IM), in term of bit-error-rate (BER) and optical signal-to-noise-ratio (OSNR). In both links, self......-heterodyne receivers perform down-conversion of radio frequency (RF) subcarrier signal. A theoretical model including noise analysis is constructed to calculate the Q factor and estimate the BER performance. Furthermore, we experimentally validate our prediction in the theoretical modeling. Both the experimental...

  9. VGLUT2-dependent glutamatergic transmission in primary afferents is required for intact nociception in both acute and persistent pain modalities.

    Science.gov (United States)

    Rogoz, Katarzyna; Lagerström, Malin C; Dufour, Sylvie; Kullander, Klas

    2012-07-01

    Glutamate is an essential transmitter in pain pathways. However, its broad usage in the central and peripheral nervous system prevents us from designing efficient glutamate-based pain therapies without causing harmful side effects. The discovery of vesicular glutamate transporters (VGLUT1-3) has been a crucial step in describing specific glutamatergic neuronal subpopulations and glutamate-dependent pain pathways. To assess the role of VGLUT2-mediated glutamatergic contribution to pain transmission from the entire primary sensory population, we crossed our Vglut2(f/f) line with the Ht-Pa-Cre line. Such Vglut2-deficient mice showed significantly decreased, but not completely absent, acute nociceptive responses. The animals were less prone to develop an inflammatory-related state of pain and were, in the partial sciatic nerve ligation chronic pain model, much less hypersensitive to mechanical stimuli and did not develop cold allodynia or heat hyperalgesia. To take advantage of this neuropathic pain-resistant model, we analyzed Vglut2-dependent transcriptional changes in the dorsal spinal cord after nerve injury, which revealed several novel candidate target genes potentially relevant for the development of neuropathic pain therapeutics. Taken together, we conclude that VGLUT2 is a major mediator of nociception in primary afferents, implying that glutamate is the key somatosensory neurotransmitter.

  10. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex.

    Science.gov (United States)

    Beshara, Simon; Beston, Brett R; Pinto, Joshua G A; Murphy, Kathryn M

    2015-01-01

    Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity.

  11. Pre-synaptic adenosine A2A receptors control cannabinoid CB1 receptor-mediated inhibition of striatal glutamatergic neurotransmission.

    Science.gov (United States)

    Martire, Alberto; Tebano, Maria Teresa; Chiodi, Valentina; Ferreira, Samira G; Cunha, Rodrigo A; Köfalvi, Attila; Popoli, Patrizia

    2011-01-01

    An interaction between adenosine A(2A) receptors (A(2A) Rs) and cannabinoid CB(1) receptors (CB(1) Rs) has been consistently reported to occur in the striatum, although the precise mechanisms are not completely understood. As both receptors control striatal glutamatergic transmission, we now probed the putative interaction between pre-synaptic CB(1) R and A(2A) R in the striatum. In extracellular field potentials recordings in corticostriatal slices from Wistar rats, A(2A) R activation by CGS21680 inhibited CB(1) R-mediated effects (depression of synaptic response and increase in paired-pulse facilitation). Moreover, in superfused rat striatal nerve terminals, A(2A) R activation prevented, while A(2A) R inhibition facilitated, the CB(1) R-mediated inhibition of 4-aminopyridine-evoked glutamate release. In summary, the present study provides converging neurochemical and electrophysiological support for the occurrence of a tight control of CB(1) R function by A(2A) Rs in glutamatergic terminals of the striatum. In view of the key role of glutamate to trigger the recruitment of striatal circuits, this pre-synaptic interaction between CB(1) R and A(2A) R may be of relevance for the pathogenesis and the treatment of neuropsychiatric disorders affecting the basal ganglia.

  12. Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity.

    Science.gov (United States)

    Moeller, Scott J; London, Edythe D; Northoff, Georg

    2016-02-01

    Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications.

  13. Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: relationships to resting-state functional connectivity

    Science.gov (United States)

    Moeller, Scott J.; London, Edythe D.; Northoff, Georg

    2015-01-01

    Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. PMID:26657968

  14. [Evidence on the key role of the metabotrobic glutamatergic receptors in the pathogenesis of schizophrenia: a "breakthrough" in pharmacological treatment].

    Science.gov (United States)

    Pannese, Rossella; Minichino, Amedeo; Pignatelli, Marco; Delle Chiaie, Roberto; Biondi, Massimo; Nicoletti, Ferdinando

    2012-01-01

    The metabotropic glutamate receptors (mGluRs) are expressed pre- and post synaptically throughout the nervous system where they serve as modulators of synaptic transmission and neuronal excitability. The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. This paper reviews the neurodevelopmental origin and genetic susceptibility of schizophrenia relevant to NMDA receptor neurotransmission, and discusses the relationship between NMDA hypofunction and different domains of symptom in schizophrenia as well as putative treatment modality for the disorder. mGlu receptors have been hypothesizes as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. Group II of mGlu receptors are of particular interest because of their unique distribution and the regulatory roles they have in neurotransmission. The glutamate hypothesis of schizophrenia predicts that agents that restore the balance in glutamatergic neurotransmission will ameliorate the symptomatology associated with this illness. Development of potent, efficacious, systemically active drugs will help to address the antipsychotic potential of these novel therapeutics. This review will discuss recent progress in elucidating the pharmacology and function of group II receptors in the context of current hypotheses on the pathophysiology of schizophrenia and the need for new and better antipsychotics.

  15. Ongoing intrinsic synchronous activity is required for the functional maturation of CA3-CA1 glutamatergic synapses.

    Science.gov (United States)

    Huupponen, Johanna; Molchanova, Svetlana M; Lauri, Sari E; Taira, Tomi

    2013-11-01

    Fine-tuning of synaptic connectivity during development is guided by intrinsic activity of the immature networks characteristically consisting of intermittent bursts of synchronous activity. However, the role of synchronous versus asynchronous activity in synapse maturation in the brain is unclear. Here, we have pharmacologically prevented generation of synchronous activity in the immature rat CA3-CA1 circuitry in a manner that preserves unitary activity. Long-term desynchronization of the network resulted in weakening of AMPA-receptor-mediated glutamatergic transmission in CA1 pyramidal cells. This weakening was dependent on protein phosphatases and mGluR activity, associated with an increase in the proportion of silent synapses and a decrease in the protein levels of GluA4 suggesting postsynaptic mechanisms of expression. The findings demonstrate that synchronous activity in the immature CA3-CA1 circuitry is critical for the induction and maintenance of glutamatergic synapses and underscores the importance of temporal activity patterns in shaping the synaptic circuitry during development.

  16. Glutamatergic inputs to the CVLM independent of the NTS promote tonic inhibition of sympathetic vasomotor tone in rats.

    Science.gov (United States)

    Mandel, Daniel A; Schreihofer, Ann M

    2008-10-01

    GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA. In addition, we evaluated whether altering central respiratory drive, a baroreceptor-independent regulator of CVLM neurons, influences glutamatergic inputs to the CVLM. Splanchnic SNA and AP were measured in chloralose-anesthetized, ventilated, paralyzed rats. The infusion of nitroprusside decreased AP below threshold for baroreceptor afferent firing (NTS by microinjection of the GABA(A) agonist muscimol did not further increase SNA. In contrast, after inhibition of the NTS, blockade of glutamatergic inputs to CVLM by microinjection of kynurenate increased SNA (274+/-54%; PNTS-mediated excitation of the CVLM. Furthermore, glutamate tonically activates the CVLM to reduce SNA independent of the NTS, and this excitatory input appears to be affected by the strength of central respiratory drive.

  17. Sensitivity analysis for critical control points determination and uncertainty analysis to link FSO and process criteria: application to Listeria monocytogenes in soft cheese made from pasteurized milk.

    Science.gov (United States)

    Lamboni, Matieyendou; Sanaa, Moez; Tenenhaus-Aziza, Fanny

    2014-04-01

    Microbiological food safety is an important economic and health issue in the context of globalization and presents food business operators with new challenges in providing safe foods. The hazard analysis and critical control point approach involve identifying the main steps in food processing and the physical and chemical parameters that have an impact on the safety of foods. In the risk-based approach, as defined in the Codex Alimentarius, controlling these parameters in such a way that the final products meet a food safety objective (FSO), fixed by the competent authorities, is a big challenge and of great interest to the food business operators. Process risk models, issued from the quantitative microbiological risk assessment framework, provide useful tools in this respect. We propose a methodology, called multivariate factor mapping (MFM), for establishing a link between process parameters and compliance with a FSO. For a stochastic and dynamic process risk model of Listeriamonocytogenes in soft cheese made from pasteurized milk with many uncertain inputs, multivariate sensitivity analysis and MFM are combined to (i) identify the critical control points (CCPs) for L.monocytogenes throughout the food chain and (ii) compute the critical limits of the most influential process parameters, located at the CCPs, with regard to the specific process implemented in the model. Due to certain forms of interaction among parameters, the results show some new possibilities for the management of microbiological hazards when a FSO is specified.

  18. Glutamatergic and GABAergic disturbances as markers of choice-of-treatment – part of Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II)

    DEFF Research Database (Denmark)

    Bojesen, Kirsten Borup; Jessen, Kasper; Rostrup, Egill;

    may be related to persistent high levels of glutamate, the main excitatory neurotransmitter in the brain. However, the relationship of glutamatergic disturbances to psychopathology and level of functioning is largely unknown. Aim The aim is to clarify the relationship between glutamatergic...... disturbances in the two interconnected brain areas anterior cingulate cortex and thalamus to psychopathology and level of functioning in 40 anti-psychotic naïve patients with schizophrenia before and after 6 weeks treatment with aripiprazol. Method Design: Prospective 6 week follow-up study of 40 antipsychotic...

  19. Cross-linking immunoprecipitation-MS (xIP-MS): Topological Analysis of Chromatin-associated Protein Complexes Using Single Affinity Purification.

    Science.gov (United States)

    Makowski, Matthew M; Willems, Esther; Jansen, Pascal W T C; Vermeulen, Michiel

    2016-03-01

    In recent years, cross-linking mass spectrometry has proven to be a robust and effective method of interrogating macromolecular protein complex topologies at peptide resolution. Traditionally, cross-linking mass spectrometry workflows have utilized homogenous complexes obtained through time-limiting reconstitution, tandem affinity purification, and conventional chromatography workflows. Here, we present cross-linking immunoprecipitation-MS (xIP-MS), a simple, rapid, and efficient method for structurally probing chromatin-associated protein complexes using small volumes of mammalian whole cell lysates, single affinity purification, and on-bead cross-linking followed by LC-MS/MS analysis. We first benchmarked xIP-MS using the structurally well-characterized phosphoribosyl pyrophosphate synthetase complex. We then applied xIP-MS to the chromatin-associated cohesin (SMC1A/3), XRCC5/6 (Ku70/86), and MCM complexes, and we provide novel structural and biological insights into their architectures and molecular function. Of note, we use xIP-MS to perform topological studies under cell cycle perturbations, showing that the xIP-MS protocol is sufficiently straightforward and efficient to allow comparative cross-linking experiments. This work, therefore, demonstrates that xIP-MS is a robust, flexible, and widely applicable methodology for interrogating chromatin-associated protein complex architectures.

  20. Analysis of the CAG repeat region of the androgen receptor gene in a kindred with X-linked spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Belsham, D D; Yee, W C; Greenberg, C R; Wrogemann, K

    1992-10-01

    Herein we describe a family with X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), an adult onset neuromuscular disease characterized by slow progression, predominant proximal and bulbar muscle weakness. One frequent association is the appearance of gynecomastia. This disorder was previously shown to be linked to the locus DXYS1 on the proximal long arm of the X chromosome. Recently, a report implicated a mutation at the N-terminus of the androgen receptor gene involving amplification of CAG repeats as the cause of X-linked SBMA. We studied this region of the androgen receptor in a kindred clinically suspected but not confirmed of having X-linked SBMA by the polymerase chain reaction (PCR) followed by Southern analysis and DNA sequencing. The mutated allele was found to have an increased number of 51 CAG repeats confirming the clinical diagnosis of SBMA. Normal individuals revealed 23 repeat numbers within the normal range, while another unrelated X-linked SBMA patient had an enlarged CAG repeat region. The carrier or disease status could be established or confirmed in 12 individuals of this family on the basis of detecting normal and disease alleles reflected by the number of CAG repeats.

  1. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational approaches. Methods: Mixed qualitative design: survey based on telephone interviews with health managers (n=72), personal and focus group interviews with health professionals (n=84) and pupils (n=108) from 18 school classes, and comparative case studies in five selected municipalities of various...... educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education...

  2. Population distribution of flexible molecules from maximum entropy analysis using different priors as background information: application to the Φ, Ψ-conformational space of the α-(1-->2)-linked mannose disaccharide present in N- and O-linked glycoproteins.

    Science.gov (United States)

    Säwén, Elin; Massad, Tariq; Landersjö, Clas; Damberg, Peter; Widmalm, Göran

    2010-08-21

    The conformational space available to the flexible molecule α-D-Manp-(1-->2)-α-D-Manp-OMe, a model for the α-(1-->2)-linked mannose disaccharide in N- or O-linked glycoproteins, is determined using experimental data and molecular simulation combined with a maximum entropy approach that leads to a converged population distribution utilizing different input information. A database survey of the Protein Data Bank where structures having the constituent disaccharide were retrieved resulted in an ensemble with >200 structures. Subsequent filtering removed erroneous structures and gave the database (DB) ensemble having three classes of mannose-containing compounds, viz., N- and O-linked structures, and ligands to proteins. A molecular dynamics (MD) simulation of the disaccharide revealed a two-state equilibrium with a major and a minor conformational state, i.e., the MD ensemble. These two different conformation ensembles of the disaccharide were compared to measured experimental spectroscopic data for the molecule in water solution. However, neither of the two populations were compatible with experimental data from optical rotation, NMR (1)H,(1)H cross-relaxation rates as well as homo- and heteronuclear (3)J couplings. The conformational distributions were subsequently used as background information to generate priors that were used in a maximum entropy analysis. The resulting posteriors, i.e., the population distributions after the application of the maximum entropy analysis, still showed notable deviations that were not anticipated based on the prior information. Therefore, reparameterization of homo- and heteronuclear Karplus relationships for the glycosidic torsion angles Φ and Ψ were carried out in which the importance of electronegative substituents on the coupling pathway was deemed essential resulting in four derived equations, two (3)J(COCC) and two (3)J(COCH) being different for the Φ and Ψ torsions, respectively. These Karplus relationships are denoted

  3. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Wan Seok; Nam, Mi Sun; Namgung, Byeol [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Yoon, Sung-il, E-mail: sungil@kangwon.ac.kr [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2015-03-20

    Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis. - Highlights: • cjPseH adopts a single-domain structure of a central β-sheet decorated by α-helices. • cjPseH features two continuously connected grooves on the protein surface. • Acetyl coenzyme A (AcCoA) binds into a deep groove of cjPseH in an ‘L’ shape. • The acetyl end of AcCoA points to a wide groove, a potential substrate-binding site.

  4. Links between tectonism and exhumation in the Spanish Pyrenees: Evidence from apatite fission track analysis and Ar fault dating

    Science.gov (United States)

    Rahl, J. M.; Haines, S. H.; van der Pluijm, B. A.

    2009-12-01

    Analytical, numerical, and mechanical models of orogenic wedges suggest that the structural and erosional evolution of mountain belts are tightly linked. For example, erosion in the core of a mountain belt may thin a wedge and drive out-of-sequence faulting to reestablish critical taper. To provide a field-based test of these ideas, we present new geochronologic constraints on the deformational and erosional history of the orogenic wedge exposed in the south-central Spanish Pyrenees. Apatite fission-track data from the syn-orogenic sediments of the Sierra de Sis conglomerate reveal generally invariant ages in strata deposited between about 42 and 27 Ma. These data, as well as track-length distributions indicative of rapid cooling, imply the bedrock in the core of the wedge that produced the sediment experienced fast exhumation that began by at least 48 Ma and continued until 42 Ma. Numerical modeling of the detrital data suggests the source region experienced a deceleration in erosion rate from about 1.0 mm/yr to less than 0.5 to 0.2 mm/yr. Published bedrock thermochronometric data collected from the interior of the belt indicate a renewed period of rapid erosional exhumation culminating around 32 Ma. The temporal changes in erosion recorded by thermochronology are correlated with the deformational history of the Pyrenean fold-thrust belt. We present new constraints on fault activity in the Pyrenean foreland through the direct dating of fault gouge by illite age analysis. New fault dates show that tectonic activity youngs towards the interior of the mountain belt, with fault slip correlating to periods of rapid erosion. The relatively outboard Boixols fault has an age of 71 ± 6.4 Ma, reflecting Cretaceous convergence that marks the onset of Pyrenean deformation. Slip on the more inboard Nogueres fault occurred later, at 56 ± 1.4 Ma, consistent with a period of rapid erosion that continued through about 45 Ma inferred from detrital fission-track data. After a long

  5. Fat Intake Is Not Linked to Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Chang Xu

    Full Text Available Since the late 1960s, the average global supply of fat has increased by 20 g per capita per day. While fat intake has been considered a potential risk factor for prostate cancer (Pca, the hypothesis from previous epidemiologic studies remained equivocal.Relevant cohort studies were identified through a literature search in PubMed, ScienceDirect and Wiley Online Library up to March 1, 2015. A systematic review and dose-response meta-analysis were used to assess the relationship between fat intake and the risk for Pca.We identified 14 cohort studies, which included 37,349 cases and a total of 751,030 participants. We found no evidence of a non-linear association between fat intake and the risk for Pca. Overall, the summarized relative risks for every 28.35 g increment a day was 0.99 (95%CI: 0.98, 1.01; P=0.94; n=13 for total fat intake, 1.00 (95%CI: 1.00, 1.00; P=0.72; n=9 for saturated fat, 0.99 (95%CI: 0.95, 1.03; P=0.55; n=7 for polyunsaturated fat, and 1.00 (95%CI: 0.95, 1.04; P=0.85; n=8 for monounsaturated fat. Additionally, there was no link to the risk for advanced stage Pca regarding total fat intake (RR=1.02, 95%CI: 0.96, 1.08; P=0.63; n=5, saturated fat (RR=0.96, 95%CI: 0.84, 1.11; P=0.61; n=6, polyunsaturated fat (RR=0.96, 95%CI: 0.79, 1.17; P=0.68; n=6, or monounsaturated fat (RR=0.96, 95%CI: 0.86, 1.07; P=0.42; n=6. Subgroup and sensitively analyses showed consistent results.Little evidence from published cohort studies supports the statement that total fat, saturated fat or unsaturated fat intake increases the risk for Pca or advanced stage Pca.

  6. A Theoretical Analysis of Sideband Harmonics on the Inverter DC-link Current for an Electric Railcar

    Science.gov (United States)

    Ogawa, Tomoyuki; Wakao, Shinji; Taufiq, Jat; Kondo, Keiichiro; Terauchi, Nobuo

    The harmonics of the return current may interfere with the signaling current along with the rails. In this paper, we present the theoretical studies of the return current harmonics in the inverter-controlled DC electric railcar, aiming at contributing future work to improve the compatibility with the signaling current. We theoretically derive sideband harmonics of the DC-link current. Then, in order to verify the theoretical study, we experimentally measure the harmonics and numerically simulate the harmonics. As a result, we concluded the theoretical DC-link current is enough accurate to be utilized for the future improvement of the inverter harmonics current.

  7. Performance analysis of active damped small DC-link capacitor based drive for unbalanced input voltage supply

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig

    2011-01-01

    A small DC-link capacitor based drive is presented in this paper. The drive shows negative impedance instability at operating points with high power load. A phase portrait is presented for input filter states which exhibit a limit cycle. When the drive is operated with unbalanced input supply...

  8. Critical body residues linked to octanol-water partitioning, organism composition, and LC50 QSARs: Meta-analysis and model

    NARCIS (Netherlands)

    Hendriks, A.J.; Traas, T.P.; Huijbregts, M.A.J.

    2005-01-01

    To protect thousands of species from thousands of chemicals released in the environment, various risk assessment tools have been developed. Here, we link quantitative structure-activity relationships (QSARs) for response concentrations in water (LC50) to critical concentrations in organisms (C-50) b

  9. Update History of This Database - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

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  11. Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth.

    Science.gov (United States)

    Masson, Justine; Darmon, Michèle; Conjard, Agnès; Chuhma, Nao; Ropert, Nicole; Thoby-Brisson, Muriel; Foutz, Arthur S; Parrot, Sandrine; Miller, Gretchen M; Jorisch, Renée; Polan, Jonathan; Hamon, Michel; Hen, René; Rayport, Stephen

    2006-04-26

    Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein, and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated, and died in the first postnatal day. No gross or microscopic defects were detected in peripheral organs or in the CNS. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activity-dependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that although alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and thus the mutation is associated with impaired respiratory function, abnormal goal-directed behavior, and neonatal demise.

  12. Non-Invasive Evaluation of the GABAergic/Glutamatergic System in Autistic Patients Observed by MEGA-Editing Proton MR Spectroscopy Using a Clinical 3 Tesla Instrument

    Science.gov (United States)

    Harada, Masafumi; Taki, Masako M.; Nose, Ayumi; Kubo, Hitoshi; Mori, Kenji; Nishitani, Hiromu; Matsuda, Tsuyoshi

    2011-01-01

    Amino acids related to neurotransmitters and the GABAergic/glutamatergic system were measured using a 3 T-MRI instrument in 12 patients with autism and 10 normal controls. All measurements were performed in the frontal lobe (FL) and lenticular nuclei (LN) using a conventional sequence for n-acetyl aspartate (NAA) and glutamate (Glu), and the…

  13. The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

    Directory of Open Access Journals (Sweden)

    Laurent Roybon

    Full Text Available Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1 is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced - the mitral cells - can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers.

  14. Cholinergic and glutamatergic transmission at synapses between pedunculopotine tegmental nucleus axonal terminals and A7 catecholamine cell group noradrenergic neurons in the rat.

    Science.gov (United States)

    Li, Meng-Jiyuan; Chang, Tien-Wei; Hung, Wei-Chen; Wu, Chieh-Yi; Luo, Yu-Cheng; Chang, Ting-Hsuan; Lin, Chingju; Yang, Chi-Sheng; Yang, Hsiu-Wen; Min, Ming-Yuan

    2016-11-01

    We characterized transmission from the pedunculopotine tegmental nucleus (PPTg), which contains cholinergic and glutamatergic neurons, at synapses with noradrenergic (NAergic) A7 neurons. Injection of an anterograde neuronal tracer, biotinylated-dextran amine, into the PPTg resulted in labeling of axonal terminals making synaptic connection with NAergic A7 neurons. Consistent with this, extracellular stimulation using a train of 10 pulses at 100 Hz evoked both fast and slow excitatory synaptic currents (EPSCs) that were blocked, respectively, by DNQX, a non-N-methyl-d-aspartate receptor blocker, or atropine, a cholinergic muscarinic receptor (mAChR) blocker. Interestingly, many spontaneous-like, but stimulation-dependent, EPSCs, were seen for up to one second after the end of stimulation and were blocked by DNQX and decreased by EGTA-AM, a membrane permeable form of EGTA, showing they are glutamatergic EPSCs causing by asynchronous release of vesicular quanta. Moreover, application of atropine or carbachol, an mAChR agonist, caused, respectively, an increase in the number of asynchronous EPSCs or a decrease in the frequency of miniature EPSCs, showing that mAChRs mediated presynaptic inhibition of glutamatergic transmission of the PPTg onto NAergic A7 neurons. In conclusion, our data show direct synaptic transmission of PPTg afferents onto pontine NAergic neurons that involves cooperation of cholinergic and glutamatergic transmission. This dual-transmitter transmission drives the firing rate of NAergic neurons, which may correlate with axonal and somatic/dendritic release of NA.

  15. Performance Analysis of Polarization Modulated DirectDetection Optical CDMA Systems over Turbulent FSO LinksModeled by the Gamma-Gamma Distribution

    Directory of Open Access Journals (Sweden)

    Fan Bai

    2015-01-01

    Full Text Available This paper proposes a theoretical study to characterize the transmission of optical code division multiple access (CDMA systems deploying polarization shift keying (PolSK over a free space optical (FSO link under the impact of atmospheric turbulence. In our analysis, a novel transceiver architecture for atmospheric OCDMA FSO systems based on polarization modulation with direct detection is proposed and discussed. A detailed analytical model for PolSK-OCDMA systems over a turbulent FSO link is provided. Further, we derive a closed-form bit error ratio (BER and outage probability expressions, taking into account the multiple-access interference (MAI, optical noise and the atmospheric turbulence effect on the FSO link modeled by the Gamma-Gamma distribution. Finally, the results of this study show the most significant parameters that degrade the transmission performance of the PolSK-OCDMA signal over FSO links and indicate that the proposed approach offers improved bit error ratio (BER performances compared to the on-off-keying (OOK modulation scheme in the presence of turbulence.

  16. Analysis of protein-RNA interactions in CRISPR proteins and effector complexes by UV-induced cross-linking and mass spectrometry.

    Science.gov (United States)

    Sharma, Kundan; Hrle, Ajla; Kramer, Katharina; Sachsenberg, Timo; Staals, Raymond H J; Randau, Lennart; Marchfelder, Anita; van der Oost, John; Kohlbacher, Oliver; Conti, Elena; Urlaub, Henning

    2015-11-01

    Ribonucleoprotein (RNP) complexes play important roles in the cell by mediating basic cellular processes, including gene expression and its regulation. Understanding the molecular details of these processes requires the identification and characterization of protein-RNA interactions. Over the years various approaches have been used to investigate these interactions, including computational analyses to look for RNA binding domains, gel-shift mobility assays on recombinant and mutant proteins as well as co-crystallization and NMR studies for structure elucidation. Here we report a more specialized and direct approach using UV-induced cross-linking coupled with mass spectrometry. This approach permits the identification of cross-linked peptides and RNA moieties and can also pin-point exact RNA contact sites within the protein. The power of this method is illustrated by the application to different single- and multi-subunit RNP complexes belonging to the prokaryotic adaptive immune system, CRISPR-Cas (CRISPR: clustered regularly interspaced short palindromic repeats; Cas: CRISPR associated). In particular, we identified the RNA-binding sites within three Cas7 protein homologs and mapped the cross-linking results to reveal structurally conserved Cas7 - RNA binding interfaces. These results demonstrate the strong potential of UV-induced cross-linking coupled with mass spectrometry analysis to identify RNA interaction sites on the RNA binding proteins.

  17. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Xiangdong Bu; Rotter, J.I. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  18. Genomewide association analysis for awn length linked to the seed shattering gene qSH1 in rice

    Indian Academy of Sciences (India)

    RISPER AUMA MAGWA; HU ZHAO; WEN YAO; WEIBO XIE; LIN YANG; YONGZHONG XING; XUFENG BAI

    2016-09-01

    Awn is one of the most important domesticated traits in rice (Oryza sativa). Understanding the genetic basis of awn length is important for grain harvest and production, because long awn length is disadvantageous for both grain harvest and milling. We investigated the awn length of 529 rice cultivars and performed a Genomewide association studies (GWAS) in the indica andjaponica subpopulations, and the whole population. In total, we found 17 loci associated with awn length. Of these loci, seven were linked to previously reported quantitative trait loci, and one was linked to the awn gene An-1 . Nine novel loci were repeatedly identified in different environments. One of the nine associations was identified in both the whole and japonica populations. Special interest was the detection of the most significant association SNP, sf0136352825, which was less than 95 kb from the seed shattering gene qSH1. These results may provide potentially favourable haplotypes for molecular breeding in rice.

  19. The Drosophila larval neuromuscular junction as a model for scaffold complexes at glutamatergic synapses: benefits and limitations.

    Science.gov (United States)

    Thomas, Ulrich; Kobler, Oliver; Gundelfinger, Eckart D

    2010-09-01

    Based on unbeatable genetic accessibility and relative simplicity, the Drosophila larval neuromuscular junction has become a widely used model system for studying functional and structural aspects of excitatory glutamatergic synapses. Membrane-associated guanylate kinase-like proteins (MAGUKs) are first-order scaffolding molecules enriched at many cellular junctions, including synapses, where they coordinate multiple binding partners, including cell adhesion molecules and ion channels. The enrichment of the prototypic MAGUK Discs-Large at larval NMJs apparently parallels the high abundance of its homologs at excitatory synapses in the mammalian central nervous system. Here, the authors review selected aspects of the long-standing work on Dlg at fly neuromuscular junctions, thereby scrutinizing its subcellular localization, function, and regulation with regard to corresponding aspects of MAGUKs in vertebrate neurons.

  20. Simulation and Analysis of Autonomous Time Synchronization Based on Asynchronism Two-way Inter-satellite Link

    Science.gov (United States)

    Fang, L.; Yang, X. H.; Sun, B. Q.; Qin, W. J.; Kong, Y.

    2013-09-01

    The measurement of the inter-satellite link is one of the key techniques in the autonomous operation of satellite navigation system. Based on the asynchronism inter-satellite two-way measurement mode in GPS constellation, the reduction formula of the inter-satellite time synchronization is built in this paper. Moreover, the corrective method of main systematic errors is proposed. Inter-satellite two-way time synchronization is simulated on the basis of IGS (International GNSS Service) precise ephemeris. The impacts of the epoch domestication of asynchronism inter-satellite link pseudo-range, the initial orbit, and the main systematic errors on satellite time synchronization are analyzed. Furthermore, the broadcast clock error of each satellite is calculated by the ``centralized'' inter-satellite autonomous time synchronization. Simulation results show that the epoch domestication of asynchronism inter-satellite link pseudo-range and the initial orbit have little impact on the satellite clock errors, and thus they needn't be taken into account. The errors caused by the relativistic effect and the asymmetry of path travel have large impact on the satellite clock errors. These should be corrected with theoretical formula. Compared with the IGS precise clock error, the root mean square of the broadcast clock error of each satellite is about 0.4 ns.

  1. INTER-SATELLITE LINKS ANALYSIS OF WALKER CONSTELLITE%Walker星座星间链路分析

    Institute of Scientific and Technical Information of China (English)

    杨霞; 李建成

    2012-01-01

    在分析Walker星座构型以及星间链路分类、频率和准则的基础上,研究了24/3/2构型Walker星座星间链路的构建方法和链路可见性,计算和分析了所建立星间链路的方位角、仰角和距离(AER).研究结果表明,Walker星座可建立多条星间链路.%With the developments of satellite, radio communication, and computer technology, autonomous operation of satellite navigation system becomes more and more important. Inter -satellite Link (ISL) is a key technology. The Walker constellation structure, and its categories, frequencies and rules of inter-satellite links are introduced. Besides, the construction method and visibility of inter-satellite links of Walker constellation are analyzed and then, the azimuth, elevation, and range are computed as well. Study shows that multiple ISLs can be built in Walker constellation.

  2. Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons.

    Science.gov (United States)

    Yamada, Mayumi; Seto, Yusuke; Taya, Shinichiro; Owa, Tomoo; Inoue, Yukiko U; Inoue, Takayoshi; Kawaguchi, Yoshiya; Nabeshima, Yo-Ichi; Hoshino, Mikio

    2014-04-01

    In the cerebellum, the bHLH transcription factors Ptf1a and Atoh1 are expressed in distinct neuroepithelial regions, the ventricular zone (VZ) and the rhombic lip (RL), and are required for producing GABAergic and glutamatergic neurons, respectively. However, it is unclear whether Ptf1a or Atoh1 is sufficient for specifying GABAergic or glutamatergic neuronal fates. To test this, we generated two novel knock-in mouse lines, Ptf1a(Atoh1) and Atoh1(Ptf1a), that are designed to express Atoh1 and Ptf1a ectopically in the VZ and RL, respectively. In Ptf1a(Atoh1) embryos, ectopically Atoh1-expressing VZ cells produced glutamatergic neurons, including granule cells and deep cerebellar nuclei neurons. Correspondingly, in Atoh1(Ptf1a) animals, ectopically Ptf1a-expressing RL cells produced GABAergic populations, such as Purkinje cells and GABAergic interneurons. Consistent results were also obtained from in utero electroporation of Ptf1a or Atoh1 into embryonic cerebella, suggesting that Ptf1a and Atoh1 are essential and sufficient for GABAergic versus glutamatergic specification in the neuroepithelium. Furthermore, birthdating analyses with BrdU in the knock-in mice or with electroporation studies showed that ectopically produced fate-changed neuronal types were generated at temporal schedules closely simulating those of the wild-type RL and VZ, suggesting that the VZ and RL share common temporal information. Observations of knock-in brains as well as electroporated brains revealed that Ptf1a and Atoh1 mutually negatively regulate their expression, probably contributing to formation of non-overlapping neuroepithelial domains. These findings suggest that Ptf1a and Atoh1 specify spatial identities of cerebellar neuron progenitors in the neuroepithelium, leading to appropriate production of GABAergic and glutamatergic neurons, respectively.

  3. Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: colocalization with GABAergic and glutamatergic markers.

    Science.gov (United States)

    Hrabovszky, Erik; Wittmann, Gábor; Kalló, Imre; Füzesi, Tamás; Fekete, Csaba; Liposits, Zsolt

    2012-04-01

    Type 1 cannabinoid receptor (CB1) is the principal mediator of retrograde endocannabinoid signaling in the brain. In this study, we addressed the topographic distribution and amino acid neurotransmitter phenotype of endocannabinoid-sensitive hypothalamic neurons in mice. The in situ hybridization detection of CB1 mRNA revealed high levels of expression in the medial septum (MS) and the diagonal band of Broca (DBB), moderate levels in the preoptic area and the hypothalamic lateroanterior (LA), paraventricular (Pa), ventromedial (VMH), lateral mammillary (LM), and ventral premammillary (PMV) nuclei, and low levels in many other hypothalamic regions including the suprachiasmatic (SCh) and arcuate (Arc) nuclei. This regional distribution pattern was compared with location of γ-aminobutyric acid (GABA)ergic and glutamatergic cell groups, as identified by the expression of glutamic acid decarboxylase 65 (GAD65) and type 2 vesicular glutamate transporter (VGLUT2) mRNAs, respectively. The MS, DBB, and preoptic area showed overlaps between GABAergic and CB1-expressing neurons, whereas hypothalamic sites with moderate CB1 signals, including the LA, Pa, VMH, LM, and PMV, were dominated by glutamatergic neurons. Low CB1 mRNA levels were also present in other glutamatergic and GABAergic regions. Dual-label in situ hybridization experiments confirmed the cellular co-expression of CB1 with both glutamatergic and GABAergic markers. In this report we provide a detailed anatomical map of hypothalamic glutamatergic and GABAergic systems whose neurotransmitter release is controlled by retrograde endocannabinoid signaling from hypothalamic and extrahypothalamic target neurons. This neuroanatomical information contributes to an understanding of the role that the endocannabinoid system plays in the regulation of endocrine and metabolic functions.

  4. Intracellular accumulation of amyloid-β (Aβ) protein plays a major role in Aβ-induced alterations of glutamatergic synaptic transmission and plasticity.

    Science.gov (United States)

    Ripoli, Cristian; Cocco, Sara; Li Puma, Domenica D; Piacentini, Roberto; Mastrodonato, Alessia; Scala, Federico; Puzzo, Daniela; D'Ascenzo, Marcello; Grassi, Claudio

    2014-09-17

    Intracellular accumulation of amyloid-β (Aβ) protein has been proposed as an early event in AD pathogenesis. In patients with mild cognitive impairment, intraneuronal Aβ immunoreactivity was found especially in brain regions critically involved in the cognitive deficits of AD. Although a large body of evidence demonstrates that Aβ42 accumulates intraneuronally ((in)Aβ), the action and the role of Aβ42 buildup on synaptic function have been poorly investigated. Here, we demonstrate that basal synaptic transmission and LTP were markedly depressed following Aβ42 injection into the neuron through the patch pipette. Control experiments performed with the reverse peptide (Aβ42-1) allowed us to exclude that the effects of (in)Aβ depended on changes in oncotic pressure. To further investigate (in)Aβ synaptotoxicity we used an Aβ variant harboring oxidized methionine in position 35 that does not cross the neuronal plasma membrane and is not uploaded from the extracellular space. This Aβ42 variant had no effects on synaptic transmission and plasticity when applied extracellularly, but induced synaptic depression and LTP inhibition after patch-pipette dialysis. Finally, the injection of an antibody raised against human Aβ42 (6E10) in CA1 pyramidal neurons of mouse hippocampal brain slices and autaptic microcultures did not, per se, significantly affect LTP and basal synaptic transmission, but it protected against the toxic effects of extracellular Aβ42. Collectively, these findings suggest that Aβ42-induced impairment of glutamatergic synaptic function depends on its internalization and intracellular accumulation thus paving the way to a systemic proteomic analysis of intracellular targets/partners of Aβ42.

  5. Mixed Electrical-Chemical Synapses in Adult Rat Hippocampus are Primarily Glutamatergic and Coupled by Connexin-36.

    Science.gov (United States)

    Hamzei-Sichani, Farid; Davidson, Kimberly G V; Yasumura, Thomas; Janssen, William G M; Wearne, Susan L; Hof, Patrick R; Traub, Roger D; Gutiérrez, Rafael; Ottersen, Ole P; Rash, John E

    2012-01-01

    Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for "mixed" (electrical/chemical) synapses on both principal cells and interneurons in adult rat hippocampus. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF) terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr), apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into weakly fixed CA3pyr was detected in MF axons that contacted four injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold labeling revealed diverse sizes and morphologies of connexin-36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328-1140 connexons), three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin-section images of a CA3pyr, but none were found by immunogold labeling, suggesting the rarity of GABAergic mixed synapses. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal neurons.

  6. Mixed electrical-chemical synapses in adult rat hippocampus are primarily glutamatergic and coupled by connexin-36

    Directory of Open Access Journals (Sweden)

    Farid eHamzei-Sichani

    2012-05-01

    Full Text Available Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in the mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for mixed (electrical/chemical synapses in adult rat hippocampus on both principal cells and interneurons. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr, apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into four weakly-fixed CA3pyr was detected in MF axons that contacted the injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold-labeling revealed diverse sizes and morphologies of connexin36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328-1140 connexons, three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin section images of a CA3pyr, but none found by immunogold-labeling were at GABAergic mixed synapses, suggesting their rarity. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal

  7. Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus.

    Science.gov (United States)

    Mangin, Jean-Marie; Kunze, Albrecht; Chittajallu, Ramesh; Gallo, Vittorio

    2008-07-23

    Several studies have provided evidence that NG2-expressing (NG2(+)) progenitor cells are anatomically associated to neurons in gray matter areas. By analyzing the spatial distribution of NG2(+) cells in the hilus of the mouse dentate gyrus, we demonstrate that NG2(+) cells are indeed closely associated to interneurons. To define whether this anatomical proximity reflected a specific physiological interaction, we performed patch-clamp recordings on hilar NG2(+) cells and interneurons between 3 and 21 postnatal days. We first observed that hilar NG2(+) cells exhibit spontaneous glutamatergic EPSCs (sEPSCs) whose frequency and amplitude increase during the first 3 postnatal weeks. At the same time, the rise time and decay time of sEPSCs significantly decreased, suggesting that glutamatergic synapses in NG2(+) cells undergo a maturation process that is reminiscent of what has been reported in neurons during the same time period. We also observed that hilar interneurons and associated NG2(+) cells are similarly integrated into the local network, receiving excitatory inputs from both granule cells and CA3 pyramidal neurons. By performing pair recordings, we found that bursts of activity induced by GABAergic antagonists were strongly synchronized between both cell types and that the amplitude of these bursts was positively correlated. Finally, by applying carbachol to increase EPSC activity, we observed that closely apposed cells were more likely to exhibit synchronized EPSCs than cells separated by >200 microm. The finding that NG2(+) cells are sensing patterns of activity arising in closely associated neurons suggests that NG2(+) cell function is finely regulated by the local network.

  8. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    Science.gov (United States)

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain.

  9. Expression of the System N transporter (SNAT5/SN2) during development indicates its plausible role in glutamatergic neurotransmission.

    Science.gov (United States)

    Rodríguez, Angelina; Ortega, Arturo; Berumen, Laura C; García-Alcocer, María G; Giménez, Cecilio; Zafra, Francisco

    2014-07-01

    Solute neutral amino acid transporter 5 (SNAT5/SN2) is a member of the System N family, expressed in glial cells in the adult brain, able to transport glutamine, histidine or glycine among other substrates. Its tight association with synapses and its electroneutral mode of operation that allows the bidirectional movement of substrates, supports the idea that this transporter participates in the function of the glutamine-glutamate cycle between neurons and glia. Moreover, SNAT5/SN2 might contribute to the regulation of glycine concentration in glutamatergic synapses and, therefore, to the functioning of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors. Ontogenic maturation of these synapses occurs postnatally through the coordinate expression of a large number of receptors, transporters, structural and regulatory proteins that ensure the correct operation of the excitatory pathways in the central nervous system. Since the temporal pattern of expression of SNAT5/SN2 is unknown, we analyzed it by immunoblot and immunohistochemical techniques. Results indicate that the expression of SNAT5/SN2 is triggered between the second and third postnatal week in the cerebral cortex, in parallel to the expression of the vesicular glutamate transporter vGLUT1 and the glial glutamate transporter GLT1/EAAT2. In the cerebellum, this process occurs about one week later than in the cerebral cortex. Immunohistochemical staining of cortical sections shows that from postnatal day 14 to adulthood the transporter was expressed exclusively in glial cells. Our results are consistent with the idea that SNAT5/SN2 expression is coordinated with that of other proteins necessary for the operation of glutamatergic synapses and reinforce the existence of a regulatory cross-talk between neurons and glia that orchestrates the building up of these synapses.

  10. Investigating glutamatergic mechanism in attention and impulse control using rats in a modified 5-choice serial reaction time task.

    Directory of Open Access Journals (Sweden)

    Abigail Benn

    Full Text Available The 5-choice serial reaction time task (5CSRTT has been widely used to study attention and impulse control in rodents. In order to mimic cognitive impairments in psychiatry, one approach has been to use acute administration of NMDA antagonists. This disruption in glutamatergic transmission leads to impairments in accuracy, omissions, and premature responses although findings have been inconsistent. In this study, we further investigated glutamatergic mechanisms using a novel version of the 5CSRTT, which we have previously shown to be more sensitive to cognitive enhancers. We first investigated the effects of systemic treatment with NMDA antagonists. We also carried out a preliminary investigation using targeted medial prefrontal cortex infusions of a NMDA antagonist (MK801, mGluR2/3 antagonist (LY341495, and mGluR7 negative allosteric modulator (MMPIP. Acute systemic administration of the different NMDA antagonists had no specific effects on accuracy. At higher doses PCP, ketamine, and memantine, increased omissions and affected other measures suggesting a general disruption in task performance. Only MK801 increased premature responses, and reduced omissions at lower doses suggesting stimulant like effects. None of the NMDA antagonists affected accuracy or any other measures when tested using a short stimulus challenge. Infusions of MK801 had no effect on accuracy but increased premature responses following infralimbic, but not prelimbic infusion. LY341495 had no effects in either brain region but a decrease in accuracy was observed following prelimbic infusion of MMPIP. Contrary to our hypothesis, disruptions to glutamate transmission using NMDA antagonists did not induce any clear deficits in accuracy in this modified version of the 5CSRTT. We also found that the profile of effects for MK801 differed from those observed with PCP, ketamine, and memantine. The effects of MK801 in the infralimbic cortex add to the literature indicating this brain

  11. Regulation of the ERK pathway in the dentate gyrus by in vivo dopamine D1 receptor stimulation requires glutamatergic transmission.

    Science.gov (United States)

    Gangarossa, Giuseppe; Valjent, Emmanuel

    2012-11-01

    Acute systemic administration of the dopamine D1/D5 receptors (D1Rs) agonist, SKF81297, activates the extracellular signal-regulated protein kinases (ERK) pathway selectively in the granule cells of the dentate gyrus. In this study, we examined the mechanisms involved in this regulation and investigated the molecular components that could promote ERK-dependent transcription and translation. SKF81297 induced phosphorylation of ERK and histone H3 required intact glutamatergic transmission. Blockade of glutamate release achieved by the mGluR2/3 agonist, LY354740 or the selective adenosine A1R agonist, CCPA as well as neurotoxic lesions of lateral entorhinal cortex reduced the ability of SKF81297 to induce ERK activation in the dentate gyrus. This activation required the combined stimulation of NR2B-containing NMDARs, mGluR1 and mGluR5. SKF81297 evoked phosphorylation of the ribosomal protein S6 (rpS6) selectively at the Ser235/236 site while the Ser240/244 site remains unchanged. The SKF81297 induced increased phosphorylation of rpS6 was dependent on PKC and ERK/p90RSK activation. Surprisingly, administration of D1Rs agonist suppressed mTORC1/p70S6K pathway suggesting an mTOR-independent regulation of rpS6 phosphorylation. Taken together, our results show that intact glutamatergic transmission plays a major role in the regulation of ERK-dependent phosphorylation of histone H3 and rpS6 observed in the mouse dentate gyrus after systemic administration of SKF81297.

  12. Analysis of bulked segregants to identify molecular markers linked with cocoon weight and cocoon shell weight in the silkworm Bombyx mori L

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two silkworm strains viz, B20 A (high cocoon shell ratio) and C.Nichi (low cocoon shell ratio) were sib mated for 10 generations to determine the homozygosis. Both bulked segregant analysis(BSA) and near isogenic lines (NIL) studies were done to identify the RFLP markers closely linked to cocoon shell parameters. Three hundred and fifty-two random clones were identified as the low copy number sequence and used for identification of Restriction Fragment Length Polymorphic (RFLP) marker linked to cocoon weight and cocoon shell character. In the bulk segregant analysis, DNA from the parents (B20 A, C.Nichi), F1 and F2 progeny of high shell ratio (HSR) and low shell ratio (LSR) were screened for hybridization with the random clones. Polymorphic banding pattern achieved through southern hybridization with different probes indicated the probable correlation of polymorphism with high and low cocoon shell character which are possible landmarks in identifying the putative marker(s) for the cocoon shell character. Out of the 100 probes tried with parents, F1, F2 and their bulks, 10 probes were found to be closely linked to cocoon shell characters.

  13. A Dutch family with hearing loss linked to the DFNA20/26 locus: longitudinal analysis of hearing impairment.

    NARCIS (Netherlands)

    Kemperman, M.H.; Leenheer, E. de; Huygen, P.L.M.; Wijk, E. van; Duijnhoven, G.C.F. van; Cremers, F.P.M.; Kremer, J.M.J.; Cremers, C.W.R.J.

    2004-01-01

    OBJECTIVES: To perform linkage analysis and to outline hearing loss characteristics in a family exhibiting a nonsyndromic, autosomal dominant type of progressive sensorineural hearing loss. DESIGN: Genetic analysis was performed using microsatellite markers. Audiometric data were collected and analy

  14. SLC6A15, a novel stress vulnerability candidate, modulates anxiety and depressive-like behavior: involvement of the glutamatergic system.

    Science.gov (United States)

    Santarelli, S; Wagner, K V; Labermaier, C; Uribe, A; Dournes, C; Balsevich, G; Hartmann, J; Masana, M; Holsboer, F; Chen, A; Müller, M B; Schmidt, M V

    2016-01-01

    Major depression is a multifactorial disease, involving both environmental and genetic risk factors. Recently, SLC6A15 - a neutral amino acid transporter mainly expressed in neurons - was proposed as a new candidate gene for major depression and stress vulnerability. Risk allele carriers for a single nucleotide polymorphism (SNP) in a SLC6A15 regulatory region display altered hippocampal volume, glutamate levels, and hypothalamus-pituitary-adrenal axis activity, all markers associated with major depression. Despite this genetic link between SLC6A15 and depression, its functional role with regard to the development and maintenance of depressive disorder is still unclear. The aim of the current study was therefore to characterize the role of mouse slc6a15 in modulating brain function and behavior, especially in relation to stress as a key risk factor for the development of mood disorders. We investigated the effects of slc6a15 manipulation using two mouse models, a conventional slc6a15 knock-out mouse line (SLC-KO) and a virus-mediated hippocampal slc6a15 overexpression (SLC-OE) model. Mice were tested under basal conditions and following chronic social stress. We found that SLC-KO animals displayed a similar behavioral profile to wild-type littermates (SLC-WT) under basal conditions. Interestingly, following chronic social stress SLC-KO animals showed lower levels of anxiety- and depressive-like behavior compared to stressed WT littermates. In support of these findings, SLC-OE animals displayed increased anxiety-like behavior already under basal condition. We also provide evidence that GluR1 expression in the dentate gyrus, but not GluR2 or NR1, are regulated by slc6a15 expression, and may contribute to the difference in stress responsiveness observed between SLC-KO and SLC-WT animals. Taken together, our data demonstrate that slc6a15 plays a role in modulating emotional behavior, possibly mediated by its impact on glutamatergic neurotransmission.

  15. Investigation on silver complexes of novel 1,2,3-triazole linked crown ethers by NMR analysis

    Indian Academy of Sciences (India)

    Piotr Seliger; Natalia Gutowska; Monika Stefaniak; Jarosław Romański

    2015-10-01

    The novel derivatives of 1,2,3-triazole linked crown ethers were investigated towards silver(I) ion coordination. The NMR measurements in deuterated methanol in different ratios of ligand and silver cation were studied. The experiments were performed in order to examine the way of binding Ag(I) ion by the selected ligands. The results are presented for complexes with the Ag:L stoichiometry 0.5:1, 1:1 and 2:1, respectively. Depending on the type of crown ether moiety incorporated into the macrocyclic skeleton, interesting differences in the mode of stepwise coordination of the ion were noticed.

  16. Analysis of QoS-Based Band Power Allocation for Broadband Multi-Cell Forward Link Environments

    Science.gov (United States)

    Son, Hyukmin; Lee, Sanghoon

    ICI (Inter-Cell Interference) mitigation schemes at the cell border are frequently dealt with as a special issue in 3GPP LTE (Long Term Evolution). However, few papers have analyzed the outage performance for the ICI mitigation schemes. In this paper, we propose a generalized cell planning scheme termed QBPA (Quality of Service based Band Power Allocation). Utilizing the QBPA scheme, we measure how much increase in channel capacity can be obtained through the flexible control of bandwidth and power in multi-cell forward-link environments. In addition, the feasible performance of the conventional schemes can be evaluated as long as those schemes are specific forms of the QBPA.

  17. Dancing links

    CERN Document Server

    Knuth, Donald E

    2009-01-01

    The author presents two tricks to accelerate depth-first search algorithms for a class of combinatorial puzzle problems, such as tiling a tray by a fixed set of polyominoes. The first trick is to implement each assumption of the search with reversible local operations on doubly linked lists. By this trick, every step of the search affects the data incrementally. The second trick is to add a ghost square that represents the identity of each polyomino. Thus puts the rule that each polyomino be used once on the same footing as the rule that each square be covered once. The coding simplifies to a more abstract form which is equivalent to 0-1 integer programming. More significantly for the total computation time, the search can naturally switch between placing a fixed polyomino or covering a fixed square at different stages, according to a combined heuristic. Finally the author reports excellent performance for his algorithm for some familiar puzzles. These include tiling a hexagon by 19 hexiamonds and the N queen...

  18. Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD

    Directory of Open Access Journals (Sweden)

    Rogaeva Ekaterina

    2006-12-01

    Full Text Available Abstract Background A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD has recently been ascribed to chromosome 9p. Methods We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2 and undertook mutational screening of candidate genes within this locus. Results Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X in the intraflagellar transport 74 (IFT74 gene in family 476 (F476, but no mutation was detected within IFT74 in family 2 (F2. While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420. An additional sequence variant (G58D was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. Conclusion Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families.

  19. Research about link clustering algorithmic based on tensor analysis%基于张量分析的链接聚类算法的研究

    Institute of Scientific and Technical Information of China (English)

    杨珺; 杨炳儒; 唐志刚

    2011-01-01

    Because the multi-link high-dimensional data clustering problem of complex information networks was difficult to handle, this paper proposed a novel link clustering algorithm MCHOOI based on higher order tensor analysis methods and modularity network analysis. Used modularity approach to analysis networks, used multi-dimensional tensor expressed in the form of complex multi-link data, used Tucker tensor decomposition method to reduce the dimensions of the data, the time and space complexity of the algorithm. The effectiveness and robustness of the algorithmic was tested in complex network environment.%为了解决复杂信息网络中多链接高维数据聚类难以处理且效率较低问题,提出了一种新颖的基于高阶张量分析方法和模块化网络分析方法相结合的链接聚类算法(modularity-clustering-HOOI,MCHOOI).利用模块化方法分析网络,利用张量的形式表示多维的复杂的多链接数据,利用Tucker张量分解的方法进行降维处理,有效地降低了算法的时间和空间复杂度,并在实际网络环境下,通过实验验证了算法的有效性和健壮性.

  20. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Teresa Milano

    2016-01-01

    Full Text Available The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average that is homologous to fold type-I pyridoxal 5′-phosphate (PLP dependent enzymes like aspartate aminotransferase (AAT. These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs. Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups.

  1. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    Science.gov (United States)

    Milano, Teresa

    2016-01-01

    The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH) architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average) that is homologous to fold type-I pyridoxal 5′-phosphate (PLP) dependent enzymes like aspartate aminotransferase (AAT). These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs). Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups. PMID:27446613

  2. Analysis of bulked segregants to identify molecular markers linked with cocoon weight and cocoon shell weight in the silkworm Bombyx mori L

    Institute of Scientific and Technical Information of China (English)

    SateeshKumar; 徐孟奎; 陈玉银; Ponnuvel,K.M; Datta,R.K

    2002-01-01

    Two silkworm strains viz, B20 A (high cocoon shell ratio) and C. Nichi (low cocoon shell ratio) were sib mated for 10 generations to determine the homozygoeis. Both bulked segregant analysis (BSA) and near isogenic lines (NIL) studies were done to identify the RFLP markers doaely linked to cocoon shell parameters. Three hundred and fifty-two random clones were identified as the low copy number 'sequeiace and used for identification of Restriction Fragment Length Polyrnorphic (RFLP) marker linked to cocoon weight and cocoon shell character. In the bulk aegregant analysia, DNA from the parents (B20 A, C.Nichi), Fl and F2 progeny of high shell ratio (HSR) and low shell ratio (LSR) were screened for hybridization with the random clones. Polymorphic banding pattern achieved through southern hybridization with different probes indicated the probable correlation of polymorphism with high and low cocoon shell character which are possible landmarks in identifying the putative marker(s) for the cocoon shell character. Out of the 100 probes tried with parents, Fl, F2 and their bulks 10 probes were found to be closely linked to cocoon shell characters.

  3. Thirteen-Year Evaluation of Highly Cross-Linked Polyethylene Articulating With Either 28-mm or 36-mm Femoral Heads Using Radiostereometric Analysis and Computerized Tomography

    DEFF Research Database (Denmark)

    Nebergall, Audrey K; Greene, Meridith E; Rubash, Harry

    2016-01-01

    radiograph, and CT follow-up. The 1-year and 13-year plain radiographs as well as the CT scans were analyzed for the presence of osteolysis. RESULTS: The 13-year mean ± standard error steady-state wear was 0.05 ± 0.02 mm with no significant increase over time or between the 2 head size groups. Two patients......BACKGROUND: The objective of this 13-year prospective evaluation of highly cross-linked ultra high molecular weight polyethylene (HXLPE) was to (1) assess the long-term wear of HXLPE articulating with 2 femoral head sizes using radiostereometric analysis (RSA) and to (2) determine if osteolysis...

  4. [A cross-level analysis of the links between service quality and disconfirmation of expectations and customer satisfaction].

    Science.gov (United States)

    Sánchez-Hernández, Rosa M; Martínez-Tur, Vicente; González-Morales, M Gloria; Ramos, José; Peiró, José M

    2009-08-01

    This article examines links between disconfirmation of expectations and functional and relational service quality perceived by employees and customer satisfaction. A total of 156 employees, who were working in 52 work units, participated in the research study. In addition, 517 customers who were assisted by these work units were surveyed. Using a cross-level approach, we used a random coefficient model to test the aforementioned relationships. A strong relationship between disconfirmation of expectations and customer satisfaction was observed. Also, the results confirmed that functional service quality maintains an additional and significant association with customer satisfaction. In contrast, there were no significant relationships between relational service quality and customer satisfaction. The article concludes with a discussion of these results.

  5. Separate norovirus outbreaks linked to one source of imported frozen raspberries by molecular analysis, Denmark, 2010–2011

    DEFF Research Database (Denmark)

    Müller, L.; Schultz, Anna Charlotte; Fonager, J.

    2015-01-01

    Norovirus outbreaks occur frequently in Denmark and it can be difficult to establish whether apparently independent outbreaks have the same origin. Here we report on six outbreaks linked to frozen raspberries, investigated separately over a period of 3 months. Norovirus from stools were sequence...... capsid P2 region. In one outbreak at a hospital canteen, frozen raspberries was associated with illness by cohort investigation (relative risk 6·1, 95% confidence interval 3·2–11). Bags of raspberries suspected to be the source were positive for genogroup I and II noroviruses, one typable virus...... was genotype GI.6 (capsid). These molecular investigations showed that the apparently independent outbreaks were the result of one contamination event of frozen raspberries. The contaminated raspberries originated from a single producer in Serbia and were originally not considered to belong to the same batch...

  6. Comparative genomics analysis of completely sequenced microbial genomes reveals the ubiquity of N-linked glycosylation in prokaryotes.

    Science.gov (United States)

    Kumar, Manjeet; Balaji, Petety V

    2011-05-01

    Glycosylation of proteins in prokaryotes has been known for the last few decades. Glycan structures and/or the glycosylation pathways have been experimentally characterized in only a small number of prokaryotes. Even this has become possible only during the last decade or so, primarily due to technological and methodological developments. Glycosylated proteins are diverse in their function and localization. Glycosylation has been shown to be associated with a wide range of biological phenomena. Characterization of the various types of glycans and the glycosylation machinery is critical to understand such processes. Such studies can help in the identification of novel targets for designing drugs, diagnostics, and engineering of therapeutic proteins. In view of this, the experimentally characterized pgl system of Campylobacter jejuni, responsible for N-linked glycosylation, has been used in this study to identify glycosylation loci in 865 prokaryotes whose genomes have been completely sequenced. Results from the present study show that only a small number of organisms have homologs for all the pgl enzymes and a few others have homologs for none of the pgl enzymes. Most of the organisms have homologs for only a subset of the pgl enzymes. There is no specific pattern for the presence or absence of pgl homologs vis-à-vis the 16S rRNA sequence-based phylogenetic tree. This may be due to differences in the glycan structures, high sequence divergence, horizontal gene transfer or non-orthologous gene displacement. Overall, the presence of homologs for pgl enzymes in a large number of organisms irrespective of their habitat, pathogenicity, energy generation mechanism, etc., hints towards the ubiquity of N-linked glycosylation in prokaryotes.

  7. Are learning strategies linked to academic performance among adolescents in two States in India? A tobit regression analysis.

    Science.gov (United States)

    Areepattamannil, Shaljan

    2014-01-01

    The results of the fourth cycle of the Program for International Student Assessment (PISA) revealed that an unacceptably large number of adolescent students in two states in India-Himachal Pradesh and Tamil Nadu-have failed to acquire basic skills in reading, mathematics, and science (Walker, 2011). Drawing on data from the PISA 2009 database and employing multivariate left-censored to bit regression as a data analytic strategy, the present study, therefore, examined whether or not the learning strategies-memorization, elaboration, and control strategies-of adolescent students in Himachal Pradesh (N = 1,616; Mean age = 15.81 years) and Tamil Nadu (N = 3,210; Mean age = 15.64 years) were linked to their performance on the PISA 2009 reading, mathematics, and science assessments. Tobit regression analyses, after accounting for student demographic characteristics, revealed that the self-reported use of control strategies was significantly positively associated with reading, mathematical, and scientific literacy of adolescents in Himachal Pradesh and Tamil Nadu. While the self-reported use of elaboration strategies was not significantly associated with reading literacy among adolescents in Himachal Pradesh and Tamil Nadu, it was significantly positively associated with mathematical literacy among adolescents in Himachal Pradesh and Tamil Nadu. Moreover, the self-reported use of elaboration strategies was significantly and positively linked to scientific literacy among adolescents in Himachal Pradesh alone. The self-reported use of memorization strategies was significantly negatively associated with reading, mathematical, and scientific literacy in Tamil Nadu, while it was significantly negatively associated with mathematical and scientific literacy alone in Himachal Pradesh. Implications of these findings are discussed.

  8. Functional analysis of seven genes linked to body mass index and adiposity by genome-wide association studies: a review.

    Science.gov (United States)

    Speakman, John R

    2013-01-01

    Genome-wide association studies (GWAS) have identified a total of about 40 single nucleotide polymorphisms (SNPs) that show significant linkage to body mass index, a widely utilised surrogate measure of adiposity. However, only 8 of these associations have been confirmed by follow-up GWAS using more sophisticated measures of adiposity (computed tomography). Among these 8, there is a SNP close to the gene FTO which has been the subject of considerable work to diagnose its function. The remaining 7 SNPs are adjacent to, or within, the genes NEGR1, TMEM18, ETV5, FLJ35779, LINGO2, SH2B1 and GIPR, most of which are less well studied than FTO, particularly in the context of obesity. This article reviews the available data on the functions of these genes, including information gleaned from studies in humans and animal models. At present, we have virtually no information on the putative mechanism associating the genes FLJ35779 and LINGO2 to obesity. All of these genes are expressed in the brain, and for 2 of them (SH2B1 and GIPR), a direct link to the appetite regulation system is known. SH2B1 is an enhancer of intracellular signalling in the JAK-STAT pathway, and GIPR is the receptor for an appetite-linked hormone (GIP) produced by the alimentary tract. NEGR1, ETV5 and SH2B1 all have suggested roles in neurite outgrowth, and hence SNPs adjacent to these genes may affect development of the energy balance circuitry. Although the genes have central patterns of gene expression, implying a central neuronal connection to energy balance, for at least 4 of them (NEGR1, TMEM18, SH2B1 and GIPR), there are also significant peripheral functions related to adipose tissue biology. These functions may contribute to their effects on the obese phenotype.

  9. Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway

    Directory of Open Access Journals (Sweden)

    Rask-Andersen Mathias

    2011-11-01

    Full Text Available Abstract Background The Fat mass and obesity gene (FTO has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI. However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression. Results We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2, cAMP-dependent protein kinase catalytic subunit beta (Prkacb, Brain derived neurotrophic factor (Bdnf, neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2, Signal transducer and activator of transcription 3 (Stat3, and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation. Conclusions Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ.

  10. Comparative analysis of protocadherin-11 X-linked expression among postnatal rodents, non-human primates, and songbirds suggests its possible involvement in brain evolution.

    Directory of Open Access Journals (Sweden)

    Eiji Matsunaga

    Full Text Available BACKGROUND: Protocadherin-11 is a cell adhesion molecule of the cadherin superfamily. Since, only in humans, its paralog is found on the Y chromosome, it is expected that protocadherin-11X/Y plays some role in human brain evolution or sex differences. Recently, a genetic mutation of protocadherin-11X/Y was reported to be associated with a language development disorder. Here, we compared the expression of protocadherin-11 X-linked in developing postnatal brains of mouse (rodent and common marmoset (non-human primate to explore its possible involvement in mammalian brain evolution. We also investigated its expression in the Bengalese finch (songbird to explore a possible function in animal vocalization and human language faculties. METHODOLOGY/PRINCIPAL FINDINGS: Protocadherin-11 X-linked was strongly expressed in the cerebral cortex, hippocampus, amygdala and brainstem. Comparative analysis between mice and marmosets revealed that in certain areas of marmoset brain, the expression was clearly enriched. In Bengalese finches, protocadherin-11 X-linked was expressed not only in nuclei of regions of the vocal production pathway and the tracheosyringeal hypoglossal nucleus, but also in areas homologous to the mammalian amygdala and hippocampus. In both marmosets and Bengalese finches, its expression in pallial vocal control areas was developmentally regulated, and no clear expression was seen in the dorsal striatum, indicating a similarity between songbirds and non-human primates. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the enriched expression of protocadherin-11 X-linked is involved in primate brain evolution and that some similarity exists between songbirds and primates regarding the neural basis for vocalization.

  11. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  12. Resective surgery for liver tumor:a multivariate analysis of causes and risk factors linked to postoperative complications

    Institute of Scientific and Technical Information of China (English)

    Enrico Benzoni; Dario Lorenzin; Umberto Baccarani; Gian Luigi Adani; Alessandro Favero; Alessandro Cojutti; Fabrizio Bresadola; Alessandro Uzzau

    2006-01-01

    BACKGROUND: In spite of accurate selection of patients eligible for resection, and although advances in surgical techniques and perioperative management have greatly contributed to reducing the rate of perioperative deaths, stress must be placed on reducing the postoperative complication rates reported to be still as high as 50%. This study was designed to analyze the causes and foreseeable risk factors linked to postoperative morbidity on the grounds of data derived from a single-center surgical population. METHODS: From September 1989 to March 2005, 287 consecutive patients, affected either with HCC or liver metastasis, had liver resection at our department. Among the HCC series we recorded 98 patients (73.2%) in Child-Pugh class A, 32 (23.8%) in class B and 4 in class C (3%). In 104 colorectal metastases, 71% were due to colon cancer, 25% rectal, 3% sigmoid, and 1% anorectal. In 49 non-colorectal metastases, 22.4% were derived from breast cancer, 63.2% gastrointestinal tumors (excluding colon) and 14.4%other cancers. We performed 80 wedge resections, 77 bisegmentectomies and/or left lobectomies, 74 segmentectomies, 22 major hepatectomies, 20 left hepatectomies, and 14 trisegmentectomies. RESULTS: The in-hospital mortality rate in this series was 4.5%, and the morbidity rate was 47.7%, because of pleural effusion (30%), hepatic abscess (25%), hepatic insufifciency (19%), ascites (10%), hemoperitoneum (10%), or biliary ifstula (6%). The variables associated with the technical aspects of the surgical procedure that were responsible for the complications were: a Pringle maneuver length more than 20 minutes (P=0.001);the type of liver resection procedure, including major hepatectomy (P=0.02), left hepatectomy (P=0.04), trisegmentectomy (P=0.04), bisegmentectomy and/or left lobectomy (P=0,04);and a blood transfusion of more than 600 ml (P=0.04). CONCLUSION: The evaluation of causes and foreseeable risk factors linked to postoperative morbidity during the planning of

  13. Role of a hippocampal SRC-family kinase-mediated glutamatergic mechanism in drug context-induced cocaine seeking.