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Sample records for factors governing glutamatergic

  1. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

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    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.

  3. The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

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    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.

  4. Environmental Factors Influencing Corporate Governance

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    Araniyar C. Isukul

    2015-05-01

    Full Text Available With the enthronement of democratic governance in Nigeria, there is the expectation that democracy would strengthen political institutions, regulatory institutions, and governance effectively, and by so doing, create an enabling environment for good corporate governance practices to thrive. This research uses data from World Bank Governance indicators for three countries, Nigeria, South Africa, and Egypt, and examines how institutional quality has changed from 1996 to 2012. The research methodology used in investigating this research is a cross-country research analysis. The findings of this research reveal that the adoption of democratic institutions has not significantly increased the institutional quality of political and regulatory institutions in Nigeria. On the contrary, there has been an increasing trend of political instability and violence; however, there appears to be significant improvement in freedom of the press, democracy has allowed pressed freedom to thrive.

  5. Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

    Science.gov (United States)

    Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

    2015-01-01

    Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF

  6. Factors Affecting the Productivity of Government Workers

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    Jerry P. Haenisch

    2012-01-01

    Full Text Available While there have been a variety of studies concerning government worker motivation and productivity, few, if any, studies have focused specifically on state government workers’ perceptions about what factors affect their productivity. With more than 5 million workers employed by state governments in the United States, any improvement in state workplace productivity could have significant financial and service impact for society. In this study, state government workers identified those factors perceived as most affecting their workplace productivity. Data were collected through a survey offered to state government workers in the state of Wyoming. Factor analysis was used to derive key productivity factors from survey responses. The results indicate that state government workers appreciate having freedom and autonomy, like their jobs and the sense of achievement, and welcome teamwork, but feel limited by poor supervision and management, poor communications, and insufficient budgets and staffing. To improve productivity, the workers would eliminate bureaucracy, supervise better, and improve communication.

  7. Glutamatergic System and Schizophrenia

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    Osman Ozdemir

    2016-12-01

    Full Text Available Glutamate is the major excitatory neurotransmitter in the brain. It has a role several cognitive functions including learning, memory and perception. Glutamatergic neurotransmission is also involved in regulating neuronal migration, synaptogenesis, and the pruning neurons. Glutamatergic exci-totoxicity has been implicated in various neuropsychiatric disorders. Accumulating evidence suggests that glutamatergic dysfunction may contribute to the pathogenesis of schizophrenia. The N-methyl-D-aspartic acid (NMDA receptor antagonists such as phencyclidine and ketamine can cause both the positive and negative symptoms psychotic symptoms in normal humans, and worsen these symptoms in persons with schizophrenia. Hence, it has been hypotesized that schizophrenia may be associated with decreased NMDA-receptor activity. According to the hypothesis, NMDA reseptor hypofunction can lead to decreased inhibition of glutamatergic neurons and excessive glutamate release. Finally, the reduction of gray matter in several brain regions seen in patients with schizophrenia has been suggested to be the result of neurotoxicity mediated by NMDA receptors. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(4.000: 394-405

  8. 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.

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    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.

  9. Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice.

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    Morioka, Norimitsu; Zhang, Fang Fang; Nakamura, Yoki; Kitamura, Tomoya; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2015-10-01

    Spinal cord astrocytes are critical in the maintenance of neuropathic pain. Connexin 43 (Cx43) expressed on spinal dorsal horn astrocytes modulates synaptic neurotransmission, but its role in nociceptive transduction has yet to be fully elaborated. In mice, Cx43 is mainly expressed in astrocytes, not neurons or microglia, in the spinal dorsal horn. Hind paw mechanical hypersensitivity was observed beginning 3days after partial sciatic nerve ligation (PSNL), but a persistent downregulation of astrocytic Cx43 in ipsilateral lumbar spinal dorsal horn was not observed until 7days post-PSNL, suggesting that Cx43 downregulation mediates the maintenance and not the initiation of nerve injury-induced hypersensitivity. Downregulation of Cx43 expression by intrathecal treatment with Cx43 siRNA also induced mechanical hypersensitivity. Conversely, restoring Cx43 by an adenovirus vector expressing Cx43 (Ad-Cx43) ameliorated PSNL-induced mechanical hypersensitivity. The sensitized state following PSNL is likely maintained by dysfunctional glutamatergic neurotransmission, as Cx43 siRNA-induced mechanical hypersensitivity was attenuated with intrathecal treatment of glutamate receptor antagonists MK801 and CNQX, but not neurokinin-1 receptor antagonist CP96345 or the Ca(2+) channel subunit α2δ1 blocker gabapentin. The source of this dysfunctional glutamatergic neurotransmission is likely decreased clearance of glutamate from the synapse rather than increased glutamate release into the synapse. Astrocytic expression of glutamate transporter GLT-1, but not GLAST, and activity of glutamate transport were markedly decreased in mice intrathecally injected with Cx43-targeting siRNA but not non-targeting siRNA. Glutamate release from spinal synaptosomes prepared from mice treated with either Cx43-targeting siRNA or non-targeting siRNA was unchanged. Intrathecal injection of Ad-Cx43 in PSNL mice restored astrocytic GLT-1 expression. The cytokine tumor necrosis factor (TNF) has been

  10. Institutional factors, government policies and appropriate technologies.

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    Watanabe, S

    1980-01-01

    Traditionally the use of inappropriate technologies in the developing countries has been explained by the existence of factor price distortions, e.g. the price of labor being artificially raised by labor legislation, and the price of capital being reduced by subsidies and unrealistic exchange rates. In reality the technological choice is often determined by economic conditions and the local sociocultural/political conditions. The institutional framework of the country may discourage the appropriate technology. The obstacles can be overcome when the following conditions are met: 1) a national consensus about the need for development efforts and importance of policy goals; 2) promising market prospects and/or an effective marketing system; and, 3) sufficient industrial competition in both home and international markets. Institutional problems come from the generation and diffusion of technologies from the supply side which are introduced to people who do not see the need for them. More emphasis on the marketing side ususally results in application of correct technology, especially where governments fund research and development projects and formulate their plans on the basis of a concrete investment or production plan and a clear idea about the target market. Land reforms and agricultural price policies are needed as well as the establishment of an efficient national administrative network.

  11. A Structural Equation Model (SEM of Governing Factors Influencing the Implementation of T-Government

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    Sameer Alshetewi

    2015-11-01

    Full Text Available Governments around the world have invested significant sums of money on Information and Communication Technology (ICT to improve the efficiency and effectiveness of services been provided to their citizens. However, they have not achieved the desired results because of the lack of interoperability between different government entities. Therefore, many governments have started shifting away from the original concept of e-Government towards a much more transformational approach that encompasses the entire relationship between different government departments and users of public services, which can be termed as transformational government (t- Government. In this paper, a model is proposed for governing factors that impact the implementation of t-Government such as strategy, leadership, stakeholders, citizen centricity and funding in the context of Saudi Arabia. Five constructs are hypothesised to be related to the implementation of t-Government. To clarify the relationships among these constructs, a structural equation model (SEM is utilised to examine the model fit with the five hypotheses. The results show that there are positive and significant relationships among the constructs such as the relationships between strategy and t-Government; the relationships between stakeholders and t-Government; the relationships between leadership and t-Government. This study also showed an insignificant relationship between citizens’ centricity and t-Government and also an insignificant relationship between funding and t-Government. document is a “live” template and already defines the components of your paper [title, text, heads, etc.] in its style sheet.

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

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    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.

  13. Discovering Citizens Reaction Toward E-Government: Factors in E-Government Adoption

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    Mohammad Kamel Alomari

    2014-10-01

    Full Text Available E-government has been considered as one approach for changing the face of government in the eyes of the citizenry. Therefore, citizens’ socialization in relation to their engagement with e-government should be explored. This study argues that citizens played a significant role in determining the success of an e-government project in the Middle Eastern country of Jordan. This paper aims to provide insight and evaluation into the factors that could influence e-government’s effective functioning in the Jordanian social community through its interaction with citizens. The study collected data from 356 Jordanian citizens via a survey, to ascertain their understanding of 10 factors that may influence their intention to use e-government services. To investigate the adoption of e-government services in depth, two departments in Jordan were selected: the Jordanian Government’s Income and Sales Tax Department (ISTD and its Driver and Vehicle Licenses Department (DVDL. The factor analysis technique was used to identify the main factors related to e-government services’ adoption. The results indicated that trust in the internet, website design, religious beliefs, internet and computer skill confidence, word of mouth, resistance to change, perceived usefulness, relative advantage and complexity are the main factors that should be considered when addressing the topic of e-government services’ adoption in Jordan. This study is different from most existing studies on e-government adoption as it empirically investigated the impact of word of mouth (WOM, wasta (favoritism, and resistance to change on e-government adoption. This study highlights the importance of considering the social cohesion of the Jordanian community when exploring factors related to e-government adoption.

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

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    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.

  15. Critical Factors In Data Governance For Learning Analytics

    OpenAIRE

    Elouazizi, Noureddine

    2014-01-01

     This paper identifies some of the main challenges of data governance modeling in the context of learning analytics for higher education institutions, and discusses the critical factors for designing data governance models for learning analytics. It identifies three fundamental common challenges that cut across any learning analytics data governance model, viz., the ownership of the learning analytics data sets, its interpretation and the enacting of decision-making on the basis of this learn...

  16. Critical Factors in Data Governance for Learning Analytics

    Science.gov (United States)

    Elouazizi, Noureddine

    2014-01-01

    This paper identifies some of the main challenges of data governance modelling in the context of learning analytics for higher education institutions, and discusses the critical factors for designing data governance models for learning analytics. It identifies three fundamental common challenges that cut across any learning analytics data…

  17. Teacher Governance Factors and Social Cohesion: Insights from Pakistan

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    Halai, Anjum; Durrani, Naureen

    2016-01-01

    This paper explores teacher governance factors, particularly recruitment and deployment of teachers, in relation to inequalities and social cohesion. Pakistan introduced major reforms in education in the post 9/11 context of escalating conflict. These include a merit and needs-based policy on teacher recruitment to eliminate corruption in…

  18. Teacher Governance Factors and Social Cohesion: Insights from Pakistan

    Science.gov (United States)

    Halai, Anjum; Durrani, Naureen

    2016-01-01

    This paper explores teacher governance factors, particularly recruitment and deployment of teachers, in relation to inequalities and social cohesion. Pakistan introduced major reforms in education in the post 9/11 context of escalating conflict. These include a merit and needs-based policy on teacher recruitment to eliminate corruption in…

  19. Significant Factors Determining E-government Adoption in Selangor, Malaysia

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    Siti Hajar Mohd Idris

    2016-06-01

    Full Text Available Studies have shown that low adoption rate among citizens has been hindering the optimization of e-Government services especially in developing countries. Hence, one of the critical measures that has to be undertaken is to identify and overcome possible barriers to further facilitate a higher rate of adoption. A multistage stratified sampling was used in this study to collect data from 1000 respondents, both user and non-user residing in the state of Selangor, Malaysia. This state was chosen as to provide a better understanding of low adoption when issues of basic facilities have been successfully overcome. An exploratory factor analysis was performed to identify latent constructs and seven key factors were identified. A multiple regression model was subsequently used to analyze significant factors in determining the willingness to use e-Government services. The determinants are language barrier, educational level, secure, format, easy to use, enjoyable, reliable, visual appeal and infrastructure. The result shows significant variables that act as barriers to adoption are reliable, enjoyable, easy to use, secure, and language used. The constraints pointed out in the open ended questions mainly focus on the issue of accessibility, ease of use and awareness. Overcoming these obstacles is therefore crucial in order to enhance the usage of e-Government services which consequently will improve the quality of public administration in Malaysia.

  20. What Governs Lorentz Factors of Jet Components in Blazars?

    Indian Academy of Sciences (India)

    Xinwu Cao; Bo Chai; Ming Zhou; Minfeng Gu

    2014-09-01

    We use a sample of radio-loud Active Galactic Nuclei (AGNs) with measured black hole masses to explore the jet formation mechanisms in these sources. We find a significant correlation between black hole mass and the bulk Lorentz factor of the jet components for this sample, while no significant correlation is present between the bulk Lorentz factor and the Eddington ratio. Recent investigations suggested that the most super-massive black holes in elliptical galaxies have on average higher spins than the black holes in spiral galaxies. The correlation between black hole mass and bulk Lorentz factor of the jet components found in this work implies that the motion velocity of the jet components is probably governed by the black hole spin. The faster moving jets are magnetically accelerated by the magnetic fields threading the horizon of more rapidly rotating black holes.

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

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    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.

  2. An Exploratory study of proposed factors to Adopt e-government Services

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    Sulaiman A. Alateyah

    2013-12-01

    Full Text Available this paper discusses e-government, in particular the challenges that face adoption of e-government in Saudi Arabia. In this research we define e-government as a matrix of stakeholders: governments to governments, governments to business and governments to citizens, using information and communications technology to deliver and consume services. e-government services still face many challenges in their implementation and general adoption in many countries including Saudi Arabia. In addition, the background and the discussion identify the influential factors that affect the citizens’ intention to adopt e-government services in Saudi Arabia. Consequently, these factors have been defined and categorized followed by an exploratory study to examine the importance of these factors. Therefore, this research has identified factors that determine if the citizen will adopt e-government services and thereby aiding governments in accessing what is required to increase adoption.

  3. Factors governing formation of todorokite at atmospheric pressure

    Institute of Scientific and Technical Information of China (English)

    CUI; Haojie; FENG; Xionghan; LIU; Fan; TAN; Wenfeng; HE; Ji

    2005-01-01

    Todorokite commonly occurs in Earth surface environments. The factors governing formation of todorokite, such as reaction temperature, metal ions, dissolved O2 and pH, were investigated in this paper. Results showed that the forming rate of todorokite and its crystallinity decreased with falling reaction temperature, and the effect of temperature was more significant than that of other parameters. Nature of metal ions in the interlayer of buserite precursor and the structure of the buserite precursor obviously affected buserite transformation into todorokite. Weak bonding between the metal ions and MnO6 layer of buserite was favorable to todorokite formation. The rate of todorokite formation was promoted at a lower temperature with appropriate bubbling of O2. The pH in the system slightly influenced the todorokite formation, and todorokite could also be formed in a weak alkali medium or in a slightly acidic medium. Aged buserite precursor more easily form todorokite than the unaged one.

  4. Lean government: critical success factors for XBRL-based business-to-government reporting

    NARCIS (Netherlands)

    Bharosa, N.; De Winne, C.P.I.; Van Wijk, R.; Janssen, M.F.W.H.A.

    2012-01-01

    Lean government is all about doing better with less through the use of ICT and the realisation of process improvements. The recently introduced eXtensible Business Reporting Language (XBRL) has shown some initial success in realising lean government. Once data is stored in XBRL format, businesses ca

  5. Cannabinoids: Glutamatergic Transmission and Kynurenines.

    Science.gov (United States)

    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.

  6. TEACHER GOVERNANCE FACTORS AND SOCIAL COHESION: INSIGHTS FROM PAKISTAN

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    Anjum Halai

    2016-12-01

    Full Text Available This paper explores teacher governance factors, particularly recruitment and deployment of teachers, in relation to inequalities and social cohesion. Pakistan introduced major reforms in education in the post 9/11 context of escalating conflict. These include a merit and needs-based policy on teacher recruitment to eliminate corruption in recruitment and improve equity on the basis of gender, language, ethnicity, religion, and special needs. A 4Rs framework of redistribution, recognition, representation and reconciliation was employed to analyse data gathered from: interviews with teacher educators, policy makers and development partners, and focus group discussions with and questionnaires completed by pre- and in-service teachers. The study concluded that teacher recruitment was driven by concerns of quality with weakly implemented largely quantitative measures of inclusion. Socio-politically grounded measures would be required for a diverse teaching force. Alongside, policies and procedures for the transfer of teachers would need to be streamlined so that teachers deployed to schools in marginalised areas serve there for a specified period of time.

  7. The anemia of prematurity. Factors governing the erythropoietin response.

    Science.gov (United States)

    Stockman, J A; Garcia, J F; Oski, F A

    1977-03-24

    We performed sequential studies in 45 premature infants (birth weights less than 1500 g) from 7 to 120 days of age to determine factors governing the erythropoietin response to a declining hemoglobin concentration. The hemoglobin level and the plasma erythropoietin showed a significant inverse correlation (r = 0.50, P less than 0.001), as did, even more strikingly, the plasma erythropoietin response and the infants' oxygen-unloading capacity (r = 0.55, P less than 0.001). In infants with "right-shifted" oxygen-hemoglobin dissociation curves (hemoglobin F less than 30 per cent) hemoglobin levels fell 2 to 3 g per deciliter lower than those in infants with "left-shifted" curves (hemoglobin F greater than 60 per cent) before comparable erythropoietin responses occurred. It appears that premature infants respond appropriately to alterations in oxygen unloading capacity and that the position of the oxygen-hemoglobin dissociation curve and not the hemoglobin concentration alone has a major role in modulated erythropoiesis.

  8. Factors governing the deep ventilation of the Red Sea

    KAUST Repository

    Papadopoulos, Vassilis P.

    2015-11-19

    A variety of data based on hydrographic measurements, satellite observations, reanalysis databases, and meteorological observations are used to explore the interannual variability and factors governing the deep water formation in the northern Red Sea. Historical and recent hydrographic data consistently indicate that the ventilation of the near-bottom layer in the Red Sea is a robust feature of the thermohaline circulation. Dense water capable to reach the bottom layers of the Red Sea can be regularly produced mostly inside the Gulfs of Aqaba and Suez. Occasionally, during colder than usual winters, deep water formation may also take place over coastal areas in the northernmost end of the open Red Sea just outside the Gulfs of Aqaba and Suez. However, the origin as well as the amount of deep waters exhibit considerable interannual variability depending not only on atmospheric forcing but also on the water circulation over the northern Red Sea. Analysis of several recent winters shows that the strength of the cyclonic gyre prevailing in the northernmost part of the basin can effectively influence the sea surface temperature (SST) and intensify or moderate the winter surface cooling. Upwelling associated with periods of persistent gyre circulation lowers the SST over the northernmost part of the Red Sea and can produce colder than normal winter SST even without extreme heat loss by the sea surface. In addition, the occasional persistence of the cyclonic gyre feeds the surface layers of the northern Red Sea with nutrients, considerably increasing the phytoplankton biomass.

  9. Central cholinesterase inhibition enhances glutamatergic synaptic transmission.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Success Factors Contributing to eGovernment Adoption in Saudi Arabia: G2C approach

    OpenAIRE

    Abunadi, Ibrahim; Sanzogni, Louis; Sandhu, Kuldeep; Woods, Peter

    2012-01-01

    Saudi Arabia is predetermined to implement eGovernment and provide world-class government services to citizens by 2010. However, this initiative will be meaningless if the people did not adopt these electronic services. Therefore, the purpose of this study is to determine success factors that will facilitate the adoption of eGovernment in Saudi Arabia. The results of the literature review have been deployed into surveys with Saudi eGovernment users. The discussion of the analysis from results...

  12. 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.

  13. The Critical Factors Affecting e-Government Adoption in Indonesia: A Conceptual Framework

    Directory of Open Access Journals (Sweden)

    Deden Witarsyah

    2017-02-01

    Full Text Available Electronic government (E-government is the use of information and communication technology by the government to increase the service to citizens. E-government also could be applied on the legislative and judicative to improve internal efficiency of democratic governance. However, technological, governing and social issues have to treat carefully in order to adopt these phenomena. This study aims to find critical factor that influence e-government adoption. Furthermore, comprehensive analysis base on the bibliometric technic on various resources has been chosen to guide this work.  Several dependent variables such as information quality, trust, and system quality also considered relevant were integrated with the unified theory of acceptance and use of technology (UTAUT constructs as examining variables affecting the adoption of e-government. Finally, this study found a formulation of the conceptual framework on the basis of existing experience and their relationship.

  14. Factor Analysis 01- Healthcare Service Quality In Medan Government Hospital

    OpenAIRE

    Lubis, Arlina Nurbaity; Lumbanraja, Prihatin; Lubis, Rahmawaty; Hasibuan, Beby Kendida

    2016-01-01

    Service sector increases rapidly especially in Indonesia. This can be seen from the distribution of the percentage of Product Domestic Bruto (PDB) based on job vacancy showing that the service sector contribution approaches 50%. One of the service/care industries with rapid growth is healthcare service. It can be seen from the government plan year 2015-2016 to do healthcare reinforcement. Generally, healthcare is identically related to hospital. A hospital is a professional healthcare institu...

  15. 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...

  16. Factors governing the textural development of Skaergaard gabbros: A review

    Science.gov (United States)

    McBirney, Alexander R.

    2009-07-01

    Recent work has shown that the nomenclature and earlier interpretations of "cumulates" no longer provide an adequate conceptual framework for understanding basic plutonic rocks. Most of the rocks have undergone extensive recrystallization and no longer preserve their original textures, compositions, or modal proportions. Depending on the conditions governing these metasomatic changes, they can produce a wide variety of effects. We still have much to learn, but with the abundant evidence available in well-studies bodies like the Skaergaard Intrusion it should be possible to reach a better understanding of the late-stage processes that have had such pervasive effects on mafic layered intrusions.

  17. 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.

  18. IMPACT FACTORS IN ASSIMILATION AND OPERATIONALIZATION OF THE CONCEPT OF E-GOVERNMENT

    OpenAIRE

    Florentina NEAMTU; Bogdan NICHIFOR

    2013-01-01

    Governments around the world are making significant efforts towards assimilation and operationalization of e-governance. These efforts are not only focused on the digitization process itself, but also on a broader reorganization process of public services and participation processes based on new information technologies. This paper presents in a synthetic manner, contributory factors and barriers in the process of assimilation and operationalization of e-governance platforms in the practice o...

  19. 41 CFR 109-40.112 - Transportation factors in the location of Government facilities.

    Science.gov (United States)

    2010-07-01

    ... in the location of Government facilities. 109-40.112 Section 109-40.112 Public Contracts and Property... 40.1-General Provision § 109-40.112 Transportation factors in the location of Government facilities... prior to the selection of new site locations and during the planning and construction phases in the...

  20. Glutamatergic Transmission: A Matter of Three.

    Science.gov (United States)

    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.

  1. Trachoma Prevalence and Risk Factors in Eight Local Government ...

    African Journals Online (AJOL)

    2010 and July 2011 using a two-stage sampling with probability proportional to size. ... control were used in planning the survey, while the risk factors assessment was based on ... Chi‑square analysis shows access to latrine, knowledge of trachoma as a disease, and ... design effect of 4; and a nonresponse of 10% to cover.

  2. Key factors governing alkaline pretreatment of waste activated sludge

    Institute of Scientific and Technical Information of China (English)

    Xianli Shi; Li Deng; Fangfang Sun; Jieyu Liang; Xu Deng

    2015-01-01

    Alkaline pretreatment is an effective technology to disintegrate sewage sludge, where alkali dosage and sludge concentration are two important factors. pH value or alkali concentration is usually adjusted in order to deter-mine a proper dosage of alkali. Our work has found that this is not a good strategy. A new parameter, the ratio of alkali to sludge (Ra/s), is more sensitive in controlling the alkali dosage. The sludge concentration Cs and reten-tion time t are two other important factors to consider. The validity of these arguments is confirmed with model-ing and experiments. The individual effect of Ra/s, Cs and t was studied separately. Then the combined effect of these three factors was evaluated. The sludge disintegration degree of 44.7%was achieved with the optimized factors. Furthermore, an alkaline-microwave combined pretreatment process was carried out under these optimized conditions. A high disintegration degree of 62.3%was achieved while the energy consumption of microwave was much lower than previously reported.

  3. 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.

  4. Factors governing water condensation in the Martian atmosphere

    Science.gov (United States)

    Colburn, David S.; Pollack, J. B.; Haberle, Robert M.

    1988-01-01

    Modeling results are presented suggesting a diurnal condensation cycle at high altitudes at some seasons and latitudes. In a previous paper, the use of atmospheric optical depth measurements at the Viking lander site to show diurnal variability of water condensation at different seasons of the Mars year was described. Factors influencing the amount of condensation include latitude, season, atmospheric dust content and water vapor content at the observation site. A one-dimensional radiative-convective model is used herein based on the diabatic heating routines under development for the Mars General Circulation Model. The model predicts atmospheric temperature profiles at any latitude, season, time of day and dust load. From these profiles and an estimate of the water vapor, one can estimate the maximum occurring at an early morning hour (AM) and the minimum in the late afternoon (PM). Measured variations in the atmospheric optical density between AM and PM measurements were interpreted as differences in AM and PM condensation.

  5. Factors governing sustainable groundwater pumping near a river

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Hubbard, S.S.; Finsterle, S.

    2011-01-15

    The objective of this paper is to provide new insights into processes affecting riverbank filtration (RBF). We consider a system with an inflatable dam installed for enhancing water production from downstream collector wells. Using a numerical model, we investigate the impact of groundwater pumping and dam operation on the hydrodynamics in the aquifer and water production. We focus our study on two processes that potentially limit water production of an RBF system: the development of an unsaturated zone and riverbed clogging. We quantify river clogging by calibrating a time-dependent riverbed permeability function based on knowledge of pumping rate, river stage, and temperature. The dynamics of the estimated riverbed permeability reflects clogging and scouring mechanisms. Our results indicate that (1) riverbed permeability is the dominant factor affecting infiltration needed for sustainable RBF production; (2) dam operation can influence pumping efficiency and prevent the development of an unsaturated zone beneath the riverbed only under conditions of sufficient riverbed permeability; (3) slow river velocity, caused by dam raising during summer months, may lead to sedimentation and deposition of fine-grained material within the riverbed, which may clog the riverbed, limiting recharge to the collector wells and contributing to the development of an unsaturated zone beneath the riverbed; and (4) higher river flow velocities, caused by dam lowering during winter storms, scour the riverbed an thus increase its permeability. These insights can be used as the basis for developing sustainable water management of a RBF system.

  6. Factors governing risk of cougar attacks on humans

    Science.gov (United States)

    Mattson, David; Logan, Kenneth; Sweanor, Linda

    2011-01-01

    Since the 1980s wildlife managers in the United States and Canada have expressed increasing concern about the physical threat posed by cougars (Puma concolor) to humans. We developed a conceptual framework and analyzed 386 human–cougar encounters (29 fatal attacks, 171 instances of nonfatal contact, and 186 close-threatening encounters) to provide information relevant to public safety. We conceived of human injury and death as the outcome of 4 transitions affected by different suites of factors: (1) a human encountering a cougar: (2) given an encounter, odds that the cougar would be aggressive; (3) given aggression, odds that the cougar would attack; and (4) given an attack, odds that the human would die. We developed multivariable logistic regression models to explain variation in odds at transitions three and four using variables pertaining to characteristics of involved people and cougars. Young (≤ 2.5 years) or unhealthy (by weight, condition, or disease) cougars were more likely than any others to be involved in close (typically females were more likely than males to attack, and of attacking animals, adults were more likely than juveniles to kill the victim (32% versus 9% fatality, respectively). During close encounters, victims who used a weapon killed the involved cougar in 82% of cases. Other mitigating behaviors (e.g., yelling, backing away, throwing objects, increasing stature) also substantially lessened odds of attack. People who were moving quickly or erratically when an encounter happened (running, playing, skiing, snowshoeing, biking, ATV-riding) were more likely to be attacked and killed compared to people who were less active (25% versus 8% fatality). Children (≤ 10 years) were more likely than single adults to be attacked, but intervention by people of any age reduced odds of a child’s death by 4.6×. Overall, cougar attacks on people in Canada and the United States were rare (currently 4 to 6/year) compared to attacks by large felids and

  7. Factors Affecting Project Governance Of Arusha Archdiocesan Food Security And Livelihood Project In Monduli District Tanzania.

    Directory of Open Access Journals (Sweden)

    Kisame Deogratious

    2015-06-01

    Full Text Available Abstract This research project dealt with the factors affecting governance of Food security and livelihood projects a case study of the Food security and livelihood project that was implemented by AAIDRO in Monduli district and included 60 respondents all together. The specific objectives of this study intended to access the Leadership styles that are being used in project governance. The findings of the study indicated that 91.7 of the respondents were in favor of their leaders project governance styles it was portrayed that participative leadership style was being used by the leaders for project governance. Based on a sample of 60 project members this study had confirmed that a project leaders leadership roles like mentor facilitator innovator and coordinator are important in influencing project governance effectiveness which includes team mission goal achievement and empowerment open and honest communication

  8. Factors in the Transfer of Governance-Facilitation Skills within Farmers' Marketing Organizations in Uganda

    Science.gov (United States)

    Miiro, Richard F.; Mazur, Robert E.; Matsiko, Frank B.

    2012-01-01

    Purpose: Training transfer has been examined for formal industrial and service organizations in developed countries but rarely for rural organizations in sub-Saharan Africa. This study sought to identify transfer system factors that best explain the transfer of governance-facilitation skills provided to leaders of farmers' marketing organizations…

  9. Exclusion Factors in Latin American Higher Education: A Preliminary Analyze From University Governing Board Perspective

    Science.gov (United States)

    Castro, Diego; Rodríguez-Gómez, David; Gairín, Joaquín

    2017-01-01

    Access to higher education has increased substantially in Latin America, but inequalities in access to and completion of higher education still remain. In this regard, identifying vulnerable groups and exclusion factors is a priority in Latin America's university systems. The aim of this article is to understand in depth governing board…

  10. Factors in the Transfer of Governance-Facilitation Skills within Farmers' Marketing Organizations in Uganda

    Science.gov (United States)

    Miiro, Richard F.; Mazur, Robert E.; Matsiko, Frank B.

    2012-01-01

    Purpose: Training transfer has been examined for formal industrial and service organizations in developed countries but rarely for rural organizations in sub-Saharan Africa. This study sought to identify transfer system factors that best explain the transfer of governance-facilitation skills provided to leaders of farmers' marketing organizations…

  11. Factors Influencing Adaptive Marine Governance in a Developing Country Context: a Case Study of Southern Kenya

    Directory of Open Access Journals (Sweden)

    Louisa S. Evans

    2011-06-01

    Full Text Available Adaptive governance can be conceptualized as distinct phases of: 1 understanding environmental change; 2 using this understanding to inform decision making; and 3 acting on decisions in a manner that sustains resilience of desirable system states. Using this analytical framework, we explore governance in practice in two case studies in Kenya, that reflect the "messiness" of contemporary coastal governance in many developing country contexts. Findings suggest that adaptive marine governance is unlikely to be a smooth process of learning, knowledge sharing, and responding. There are institutional, sociocultural, and political factors, past and present, that influence each phase of both local and state decision making. New local institutions related to fisher associations and Beach Management Units influence learning and knowledge sharing in ways contrary to those expected of institutions that enable collaborative fisheries management. Similarly, state decision making is relatively uninformed by the diverse knowledge systems available in the coastal zone, despite the rhetoric of participation. Historical relations and modes of working continue to play a significant role in mediating the potential for adaptive governance in the future. The case studies are illustrative and point to a number of institutional and political issues that would need to be addressed in processes of governance reform towards more adaptive management in developing country contexts.

  12. Factors Affecting Governance In Catholic Church Run Educational Institutions In Arusha Archdiocese Tanzania

    Directory of Open Access Journals (Sweden)

    Philip Adoka Okisai

    2015-06-01

    Full Text Available Abstract Governance is an important aspect in the day to day operations of schools and achievement of school goals and attaining development in any part of the world and indeed in Tanzania. The main purpose of this study was to examine the factors affecting governance in catholic run educational institutions in Arusha Tanzania. The study specifically aimed to investigate the effect of policy frameworks monitoring and evaluation and organizational structure in governance in catholic run educational institutions. During the study primary data collection was done using questionnaires and personal interviews. Both simple random and purposive samplings were used to obtain data. The findings of the study indicated that most catholic run educational institutions are aware of the factors of governance which were being investigated. The majority of the leaders were in favor of good governance in their institutions which is characterized by transparency and accountability. This research shows that the presence of good policies brings about guidance and direction in the institution which in place enhances accountability and effectiveness in the part of those in leadership position. The study recommends that the Institutions should endeavor through staff development programs to induct new staff members in the institution to have a harmonious understanding of institutional policy framework and to achieve the set institutional goals.

  13. Success and failure factors for e-government projects: A case from Egypt

    Directory of Open Access Journals (Sweden)

    Hatem Elkadi

    2013-07-01

    Full Text Available E-government implementations in developing countries still face difficulties, leading to a large failure ratio. This is too high a cost for developing countries. Analysis of the reasons behind success and failure of e-government projects is still an interesting domain of investigation. Several approaches were advanced and success and failure factors have been stipulated, but factors pertinent to Public Administration have yet to be investigated and analyzed. This work builds on the results of earlier research, analyzing the factors behind the change in performance of the different sites of a specific project, reasons of their original success, and the relapse of one site. It reviews in detail the factors advanced by previous works and integrates for the first time the results obtained by 3 different research methodologies. It clarifies the causality between different factors presumed to individually affect the e-government implementations, thus enabling the disambiguation between the main and secondary less effective causes of failure. The success and failure factors significance and relative importance are identified, revealing the recommended track of action for the set-back remedy.

  14. SUCCESS FACTORS FOR E-LIVESTOCK: AN E-GOVERNMENT INITIATIVE

    Directory of Open Access Journals (Sweden)

    Arief Ramadhan

    2013-01-01

    Full Text Available E-Government system has been developed in various countries. Currently, e-Government specifically appears in various paradigms, such as e-Procurement, e-Voting. Lastly, has emerged a new paradigm in e-Government, called e-Livestock. Therefore, in this study, we will propose and discuss about several success factors for e-Livestock in Indonesia. We will take into account four previous researches that are related to this research. Based on four previous researches, we compose first round questionnaire that consists of 65 suggested success factors. We also compose second round questionnaire that consists of 14 suggested success factors. We combine and analyzed the result of both questionnaires, so that we get 62 success factors for e-Livestock in Indonesia. We propose that in practice, to make their initiative success, all of the 62 success factors that resulted from this research have to exist and be accommodated by all parties that involved in the e-Livestock initiative in Indonesia.

  15. Governance Regime Factors Conducive to Innovation Uptake in Urban Water Management: Experiences from Europe

    Directory of Open Access Journals (Sweden)

    Josselin Rouillard

    2016-10-01

    Full Text Available Innovative ways to manage the urban water cycle are required to deal with an ageing drinking and waste water infrastructure and new societal imperatives. This paper examines the influence of water governance in enabling transformations and technological innovation uptake in urban water management. A governance assessment framework is developed and applied in three case-studies, examining different scales and types of innovations used to tackle challenges in European urban water management. The methodology combines documentary analysis and interviews to reconstruct historical storylines of the shift in the water governance of urban water management for each site. The research provides detailed empirical observations on the factors conducive to innovation uptake at the local level. Critical governance factors such as commitment to compromise, the necessity to build political support, and the role of “entrepreneurs” and coalitions are highlighted. The paper also explores the role of discursive strategies and partnership design, as well as that of regulative, economic and communicative instruments, in creating barriers and opportunities to initiate and secure change. A number of recommendations targeted at innovators and water managers are presented in the conclusion.

  16. 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.

  17. 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.

  18. A Framework For Linking Process Factors To Organisational Performance In A Government Department

    OpenAIRE

    Chengedzai Mafini; David Rabolane Isaac Pooe

    2014-01-01

    Organisational performance in the public sector in South Africa remains an issue of concern, due to the fact that most government departments continue to perform below the expected standard. This presented an impetus to conduct research on organisational performance in the sector on a continuous basis, in order to find current solutions. In this study, the relationship between organisational performance and four organisational process factors; namely, organisational structure, change, teamwor...

  19. Investigating antecedent factors to job performance: Contemporary evidence from government supply management professionals

    Directory of Open Access Journals (Sweden)

    Chengedzai Mafini

    2015-02-01

    Full Text Available Purpose: The purpose of the study was to investigate the influence of transformational leadership, organisational citizenship behaviour and quality of work life on job performance amongst supply management professionals employed by the South African government.Rationale: The depressed job performance of supply management professionals in the South African government presents an impetus to generate new empirical information on the subject in order to find solutions.Methodology: A quantitative survey approach was followed using a sample of 264 supply management professionals employed in the South African government and were based in Gauteng Province. A Confirmatory Factor Analysis (CFA was conducted to assess psychometric properties of the measurement instrument. Hypotheses were tested using Structural Equation Modelling (SEM.Findings: Transformational leadership had positive and significant relationships with organisational citizenship behaviour and quality of work life. Quality of work life exerted a greater influence of job performance than organisational citizenship behaviour.Value of research: The study provides current evidence of the influence of transformational leadership on organisational citizenship behaviour and quality of work life, as well as the influence of organisational citizenship behaviour and quality of work life on job performance amongst supply management professionals.Conclusion: Transformational leadership has a positive influence on organisational citizenship behaviour and quality of work life amongst supply management professionals in the government. Both organisational citizenship behaviour and quality of work life exerta positive influence on the job performance of supply management professionals in the government. Future studies should be extended to other professional cohorts in both the private and the government sectors.

  20. Governance Factors Affecting Community Participation In Public Development Projects In Meru District In Arusha In Tanzania

    Directory of Open Access Journals (Sweden)

    Jackson Estomih Muro

    2015-06-01

    Full Text Available ABSTRACT The purpose of this study was to have a fresh look at the local governance status through exploring governance factors affecting community participation in public development projects. The study also has investigated the actors and factors shaping participation as well as causes for non-participation. For the purpose of the study six wards within two divisions of Poli and Mbuguni and Meru district headquarters were selected. In the wards a total of 80 respondents from among the community members were interviewed through a structured questionnaire. Others were Village chairman Village Executive Officers Ward Executive Officers and Councilors were also interviewed and involved in the FGD. Data were analyzed using SPSS. Simple descriptive statistics and cross tabulation and figures were used in the analysis. The analysis showed that the communities were participated in the public development projects and people were participating through financial material and labor contribution to the public development projects. The analysis also showed that the government supported the ongoing public development projects including through provision of fund and expertise. The study showed the benefit of community participation in the development projects or programs like ownership of the projects and enjoying the benefits accrued from the projects. The study also indicated that there is significant change in terms of governance as influencers of community participation in public development projects. Despite the fortunes study showed some challenges found in wards and villages being the incidence of corruptions and misuse of public resources which were mentioned to slow community participation in public development projects. It was therefore concluded that adhering to the good governance principles contribute positively towards community participation in public development projects.

  1. Research on the Influencing Factors of Rural Low-carbon Economic Development and Government Regulation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    This paper analyses the main factors causing sluggish development of rural low-carbon economy in China as follows:the rural energy structure is irrational;the infrastructure and technology are relatively backward;system of laws,regulations and policy is not sound;fund-raising mechanism develops slowly;farmers’ low-carbon awareness and ability are limited.On the basis of these unfavorable factors,from the perspective of government regulation,feasible strategies are put forward in line with the actual situation of rural low-carbon economic development in China.

  2. Paradoxical upregulation of glutamatergic presynaptic boutons during mild cognitive impairment.

    Science.gov (United States)

    Bell, Karen F S; Bennett, David A; Cuello, A Claudio

    2007-10-03

    Synaptic integrity is now recognized as a central component of Alzheimer's disease. Surprisingly, however, the structural status of glutamatergic synapses in Alzheimer's disease is unclear, despite the fact that glutamate is the major excitatory transmitter of the CNS and has key roles in excitotoxicity and long-term potentiation. The identification of specific markers of glutamatergic neurons now allows an assessment of the structural involvement of the glutamatergic system across progressive stages of the Alzheimer's pathology, an opportunity not afforded by previously used neurochemical approaches. Glutamatergic presynaptic bouton density and dystrophic neurite abundance were quantified in midfrontal gyrus brain tissue from subjects with no cognitive impairment, mild cognitive impairment, or mild- or severe-stage Alzheimer's disease. Our study demonstrates a striking pathology-dependent pattern of glutamatergic synaptic remodeling with disease progression. Subjects with mild cognitive impairment display a paradoxical elevation in glutamatergic presynaptic bouton density, a situation akin to that observed in the cholinergic system, which then depletes and drops with disease progression. This pattern of synaptic remodeling mirrors our previous findings in transgenic animal models and is of major relevance to current transmitter-based therapeutics.

  3. 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.

  4. Factors Influencing Electronic Government Adoption Perspectives Of Less Frequent Internet Users Of Pakistan

    Directory of Open Access Journals (Sweden)

    Farooq Alam Khan

    2015-01-01

    Full Text Available Abstract Much literature on electronic government services research could be found on adoptability issues from government and service providers point of view. Many studies have looked into adoptability factors from user perspectives and majority captured adoptability perspectives of frequent Internet users the ones who use Internet applications for more than 10 hours a week. On the contrary the perspectives of majority of Pakistani users which use Internet applications for less than 10 hours per week are never inquired. This paper tries to fill this gap by looking into electronic government adoptability perspectives and expectations of such Internet users of Pakistan which are much greater in numbers than others. An amended UTAUT model with all its moderators is used in this study and the results demonstrate that performance level ease of effort and social influence strongly effect behavioral intention of users in using electronic government services in Pakistan. The individuals behavioral intention along with presence of appropriate facilitating conditions triggers use behavior of users. The results show that only gender moderates majority of UTAUT relationships and accordingly a modified UTAUT model is presented. The paper provides certain insights for people making policies and academicians for performing further research while it stresses for service proliferation with special attention towards female population.

  5. 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.

  6. Assessing social capacity and vulnerability of private households to natural hazards - integrating psychological and governance factors

    Science.gov (United States)

    Werg, J.; Grothmann, T.; Schmidt, P.

    2013-06-01

    People are unequally affected by extreme weather events in terms of mortality, morbidity and financial losses; this is the case not only for developing, but also for industrialized countries. Previous research has established indicators for identifying who is particularly vulnerable and why, focusing on socio-demographic factors such as income, age, gender, health and minority status. However, these factors can only partly explain the large disparities in the extent to which people are affected by natural hazards. Moreover, these factors are usually not alterable in the short to medium term, which limits their usefulness for strategies of reducing social vulnerability and building social capacity. Based on a literature review and an expert survey, we propose an approach for refining assessments of social vulnerability and building social capacity by integrating psychological and governance factors.

  7. Retention factors of management staff in the maintenance phase of their careers in local government

    Directory of Open Access Journals (Sweden)

    Mervin Munsamy

    2009-04-01

    Full Text Available Organisations require an employer value proposition (EVP to attract and retain people in management. This study was undertaken to understand the key retention factors that influence experienced management employees, in the maintenance phase of their careers, to remain employed at a local government organisation. Retention factors inform the organisation’s EVP. A qualitative, empirical-analytical research paradigm with a modernist approach was adopted. Data were obtained through purposive sampling (n = 10 by way of semi-structured interviews. A theoretical framework was used against which data could be deducted and compared. Sixteen key factors were identified, of which Job Aligned with Personal Meaning or Passion emerged as the strongest retention factor among the study’s participants.

  8. Analysis of the financial factors governing the profitability of lunar helium-3

    Science.gov (United States)

    Kulcinski, G. L.; Thompson, H.; Ott, S.

    1989-01-01

    Financial factors influencing the profitability of the mining and utilization of lunar helium-3 are examined. The analysis addressed the following questions: (1) which financial factors have the greatest leverage on the profitability of He-3; (2) over what range can these factors be varied to keep the He-3 option profitable; and (3) what ultimate effect could this energy source have on the price of electricity for U.S. consumers. Two complementary methods of analysis were used in the assessment: rate of return on incremental investment required and reduction revenue requirements (total cost to customers) achieved. Some of the factors addressed include energy demand, power generation costs with and without fusion, profitability for D-He(3) fusion, annual capital and operating costs, launch mass and costs, He-3 price, and government funding. Specific conclusions are made with respect to each of the companies considered: utilities, lunar mining company, and integrated energy company.

  9. Beyond job security and money: driving factors of motivation for government doctors in India

    Science.gov (United States)

    2014-01-01

    Background Despite many efforts from government to address the shortage of medical officers (MOs) in rural areas, rural health centres continue to suffer from severe shortage of MOs. Lack of motivation to join and continue service in rural areas is a major reason for such shortage. In the present study, we aimed to assess and rank the driving factors of motivation important for in-service MOs in their current job. Methods The study participants included ninety two in-service government MOs from three states in India. The study participants were required to rank 14 factors of motivation important for them in their current job. The factors for the study were selected using Herzberg’s two-factor theory of motivation and the data were collected using an instrument that has an established reliability and validity. Test of Kendall’s coefficient of concordance (W) was carried out to assess the agreement in ranks assigned by participants to various motivation factors. Next, we studied the distributions of ranks of different motivating factors using standard descriptive statistics and box plots, which gave us interesting insights into the strength of agreement of the MOs in assigning ranks to various factors. And finally to assess whether MOs are more intrinsically motivated or extrinsically motivated, we used Kolmogorov-Smirnov test. Results The (W) test indicated statistically significant (P factors than to extrinsic factors. The study results indicate that job security was the most important factor related to motivation, closely followed by interesting work and respect and recognition. Among the top five preferred factors, three were intrinsic factors indicating a great importance given by MOs to factors beyond money and job security. Conclusion To address the issue of motivation, the health departments need to pay close attention to devising management strategies that address not only extrinsic but also intrinsic factors of motivation. The study results may be

  10. Beyond job security and money: driving factors of motivation for government doctors in India.

    Science.gov (United States)

    Purohit, Bhaskar; Bandyopadhyay, Tathagata

    2014-02-21

    Despite many efforts from government to address the shortage of medical officers (MOs) in rural areas, rural health centres continue to suffer from severe shortage of MOs. Lack of motivation to join and continue service in rural areas is a major reason for such shortage. In the present study, we aimed to assess and rank the driving factors of motivation important for in-service MOs in their current job. The study participants included ninety two in-service government MOs from three states in India. The study participants were required to rank 14 factors of motivation important for them in their current job. The factors for the study were selected using Herzberg's two-factor theory of motivation and the data were collected using an instrument that has an established reliability and validity. Test of Kendall's coefficient of concordance (W) was carried out to assess the agreement in ranks assigned by participants to various motivation factors. Next, we studied the distributions of ranks of different motivating factors using standard descriptive statistics and box plots, which gave us interesting insights into the strength of agreement of the MOs in assigning ranks to various factors. And finally to assess whether MOs are more intrinsically motivated or extrinsically motivated, we used Kolmogorov-Smirnov test. The (W) test indicated statistically significant (P motivational importance to intrinsic factors than to extrinsic factors. The study results indicate that job security was the most important factor related to motivation, closely followed by interesting work and respect and recognition. Among the top five preferred factors, three were intrinsic factors indicating a great importance given by MOs to factors beyond money and job security. To address the issue of motivation, the health departments need to pay close attention to devising management strategies that address not only extrinsic but also intrinsic factors of motivation. The study results may be useful

  11. Preliminary Investigation Of Emirati Women Entrepreneurship In The UAE Motivating Factors Challenges And Government Initiatives

    Directory of Open Access Journals (Sweden)

    Mohammad Rehan Shahnawaz

    2015-08-01

    Full Text Available Abstract Purpose The purpose of this research is to conduct an in depth preliminary investigation of the Emirati Women Entrepreneurship in the UAE in terms of the factors motivating the Emirati women to engage in the entrepreneurial activities challenges and issues faced by them in that process and initiatives taken by the government of UAE in overcoming those challenges and in encouraging promoting and safeguarding their interests. Methodology This research is an exploratory one due to the fact that the topic of the research strongly requires an in depth analysis or investigation of the underlying motivating factors challenges and issues and the government initiatives taken on behalf of Emirati women entrepreneurs. The research has used qualitative content analysis technique in which the existing literature secondary data on women and Emirati women entrepreneurship was gathered and discussed to serve the purpose of the research such as from other published researches internet searches and books. DiscussionsFindings The research explored an array of factors motivating the Emirati women towards entrepreneurship and the challenges and issues they come across in that process. The motivating factors were divided into positive and negative factors with main emphasis on the positive factors. Among the positive motivating factors were the Emiratization change in the organizational culture and beliefs relaxation of social and cultural structures inde-pendence and self-improvement and development. The negative motivating factors were the necessity unacceptable working conditions inflexible work hours wage gap between males and females and job frustrations. The major challenges and issues they usually come across are traditions cultural religious and social restrictions lack of managerial experience and basic business knowledge low self-confidence and determination male prejudice stereotyping and preconception minimal networking gender based promotional

  12. 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.

  13. Significant factors for enabling knowledge sharing between government agencies within South Africa

    Directory of Open Access Journals (Sweden)

    Avain Mannie

    2013-07-01

    Full Text Available Background: Globally, organisations have recognised the strategic importance of knowledge management (KM and are increasingly focusing efforts on practices to foster the creation, sharing and integration of knowledge.Objectives: This study aimed to validate the significant factors that influence the effectiveness of KM between government agencies in South Africa. The commonly identified pillars of KM in the extant literature served as a primary framework in establishing these factors.Method: Data were gathered using an electronic survey made available to different national government agencies within the security cluster. Responses were analysed using structural equation modelling.Main findings: Existing literature highlighted organisational culture, learning organisation, collaboration, subject matter experts and trust as being determinants for knowledge management. The first two were identified as the most significant factors for knowledge sharing to succeed.Conclusion: Whilst there is universal consent as to the strategic importance of KM, actionable implementation of knowledge sharing initiatives appears to be lacking. This study emphasised the fact that leaders must instil a knowledge sharing culture either through employee performance contracts or methods such as the balanced score card. The study also showed that it is imperative for leaders to acknowledge that KM is a multi-faceted discipline that offers strategic advantages. Leaders of developing countries should note that they are on a developmental journey. This requires their organisations to be learning organisations, which necessitates a change in the organisational culture and knowledge interventions through their academies of learning.

  14. A REPLICATED ASSESSMENT OF THE CRITICAL SUCCESS FACTORS FOR THE ADOPTION OF MOBILE GOVERNMENT SERVICES: THE CASE OF JORDAN

    Directory of Open Access Journals (Sweden)

    Yousef Elsheikh

    2016-08-01

    Full Text Available Previous research indicates that there is a failure in the adoption of e-government services to citizens as planned in the context of developing countries. Obstacles behind this failure are varied, including sociocultural, economic and technical obstacles. But with recent advances in mobile technologies as well as the pervasive penetration of mobile phones, governments in developing countries including Jordan have been able to overcome most of these obstacles through the so-called mobile government (or m-government. This has provided an alternative channel for governments to improve the interaction with their citizens, as well as the quality of services provided to them. Accordingly, the exploration of the factors that affect the adoption of m-government services would reduce the gap between government strategies and policies relating to the development of m-government services on the one hand, and the perceptions of citizens on the other hand, allowing for a better understanding of citizens' needs and priorities that must be taken into account by the governments in order to ensure the success of such services on a large scale. This research is based on a re-evaluation of the empirical results of a comprehensive study conducted by Susanto and Goodwin (2010, which concludes that there are fifteen factors that are likely to affect citizens in 25 countries around the world to adopt SMS-based e-government services, but in the context of a different country in the Arab world, namely Jordan.

  15. Pesticides in stream sediment and aquatic biota: distribution, trends, and governing factors

    Science.gov (United States)

    Nowell, Lisa H.; Capel, Peter D.

    1999-01-01

    More than 20 years after the ban of DDT and other organochlorine pesticides, pesticides continue to be detected in air, rain, soil, surface water, bed sediment, and aquatic and terrestrial biota throughout the world. Recent research suggests that low levels of some of these pesticides may have the potential to affect the development, reproduction, and behavior of fish and wildlife, and possibly humans. Pesticides in Stream Sediment and Aquatic Biota: Distribution, Trends, and Governing Factors assesses the occurrence and behavior of pesticides in bed sediment and aquatic biota-the two major compartments of the hydrologic system where organochlorine pesticides are most likely to accumulate. This book collects, for the first time, results from several hundred monitoring studies and field experiments, ranging in scope from individual sites to the entire nation. Comprehensive tables provide concise summaries of study locations, pesticides analyzed, and study outcomes. Comprehensive and extensively illustrated, Pesticides in Stream Sediment and Aquatic Biota: Distribution, Trends, and Governing Factors evaluates the sources, environmental fate, geographic distribution, and long-term trends of pesticides in bed sediment and aquatic biota. The book focuses on organochlorine pesticides, but also assesses the potential for currently used pesticides to be found in bed sediment and aquatic biota. Topics covered in depth include the effect of land use on pesticide occurrence, mechanisms of pesticide uptake and accumulation by aquatic biota, and the environmental significance of observed levels of pesticides in stream sediment and aquatic biota.

  16. Contextual Factors Affecting E-Government Strategy Implementation and Its Impact on Public Sector Performance in Kenya

    Directory of Open Access Journals (Sweden)

    Dr. James Gathungu

    2013-06-01

    Full Text Available This paper assesses the contextual factors affecting the implementation of e-government strategy and its impact on the performance of the public sector in Kenya using the Wing Lam, (2005 E-government Integration Model. Electronic government (E-government is viewed in this study as the utilization of Information Communication Technologies (ICTs to transform the efficiency, effectiveness, transparency and accountability of exchanges within government, between government and citizens and businesses locally and abroad; and to empower citizens through access and use of information. Although e-government is a rapidly growing concept in both developing and developed countries very few e-government initiatives progress to maturity. Different countries are faced with different contextual circumstances and environments in the realization of e-government initiatives. This study attempts to address the gap between theory and rhetoric about the potential of e-government and the reality of its application on the ground in Kenya. The study attempts to analyze the philosophy, theories and paradigms of e-government. The development of the commercial concept as a new paradigm in public administration replacing the traditional bureaucratic systems of government is highlighted in the study. A detailed conceptual discussion anchors the study on the Wing Lam, (2005 E-government Integration Model (EGI basing it on the Kenyan perspective. The study also reviews relevant e-government studies from an international, regional and local perspective anchoring the study on the configuration school of management thought. These discussions are used to develop new insights in view of the emerging issues and their relevance to the public sector in Kenya.

  17. Contextual Factors Affecting E-Government Strategy Implementation and Its Impact on Public Sector Performance in Kenya

    Directory of Open Access Journals (Sweden)

    Dr. James Gathungu

    2013-06-01

    Full Text Available This paper assesses the contextual factors affecting the implementation of e-government strategy and its impact on the performance of the public sector in Kenya using the Wing Lam, (2005 E-government Integration Model. Electronic government (E-government is viewed in this study as the utilization of Information Communication Technologies (ICTs to transform the efficiency, effectiveness, transparency and accountability of exchanges within government, between government and citizens and businesses locally and abroad; and to empower citizens through access and use of information. Although e-government is a rapidly growing concept in both developing and developed countries very few e-government initiatives progress to maturity. Different countries are faced with different contextual circumstances and environments in the realization of e-government initiatives. This study attempts to address the gap between theory and rhetoric about the potential of e-government and the reality of its application on the ground in Kenya. The study attempts to analyze the philosophy, theories and paradigms of e-government. The development of the commercial concept as a new paradigm in public administration replacing the traditional bureaucratic systems of government is highlighted in the study. A detailed conceptual discussion anchors the study on the Wing Lam, (2005 E-government Integration Model (EGI basing it on the Kenyan perspective. The study also reviews relevant e-government studies from an international, regional and local perspective anchoring the study on the configuration school of management thought. These discussions are used to develop new insights in view of the emerging issues and their relevance to the public sector in Kenya.  

  18. Processes and their explanatory factors governing distribution of organic phosphorous pools in lake sediments.

    Science.gov (United States)

    Lü, Changwei; He, Jiang; Zuo, Le; Vogt, Rolf D; Zhu, Liang; Zhou, Bin; Mohr, Christian W; Guan, Rui; Wang, Weiying; Yan, Daohao

    2016-02-01

    The amount of organic phosphorus (OP) and its distribution among different pools in lake sediments depends on biotic and abiotic processes driving the OP fractionation. Key environmental factors governing these transformations processes between OP fractionations in sediments were studied on the basis of geochemical characteristics of OP pools in relation to environmental factors in the sediments. The results illustrate that the factors influencing the accumulation or depletion of different OP pools were intrinsically dependent on the composition of the deposited organic matter (OM). During the mineralization of the OM the microorganisms excrete the enzyme alkaline phosphatase, accelerating the OP hydrolysis, and thereby setting the grounds for the bacterially-mediated oxidation of OM. There are two main degradation products of the labile OP pool (LOP) and the moderately labile OP pool (MLOP): Either the OP is transformed to a dissolved organic or inorganic P form, and thereby released to water column, or OP is transformed to a non-labile OP pool and stored in the sediments. A comparative study showed that oxy-hydroxides of iron (Fe) and aluminum (Al) only played an important role in influencing OP fractionation in Lake Wuliangsuhai, while the complexation reactions of OP with calcium ions and sorption to its minerals are key factors governing the OP fractionation in the two alkaline lakes. It is worth noting that a significant correlation between the Fe-P pool and the pools of LOP and MLOP indicates that the degradation of the rather labile OP pools are highly dependent on the iron redox reaction.

  19. The status of vaccine availability and associated factors in Tshwane government clinics

    Directory of Open Access Journals (Sweden)

    Ntombenhle Judith Ngcobo

    2017-06-01

    Full Text Available Background. Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA is no exception, as there are indications of vaccine stock-outs in clinics. Objective. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. Methods. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA. Results. A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Conclusion. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should

  20. The status of vaccine availability and associated factors in Tshwane government clinics.

    Science.gov (United States)

    Ngcobo, Ntombenhle Judith; Kamupira, Mercy G

    2017-05-24

    Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA) is no exception, as there are indications of vaccine stock-outs in clinics. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA). A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should be restructured and overhauled with the use of advances in technology

  1. A Review on Critical Success Factors of Governance towards Sustainable Campus Operations

    Science.gov (United States)

    Halid Abdullah, Abd; Razman, Ruzaimah; Muslim, Rahmat

    2017-08-01

    Campus Sustainability is an effort that integrates environmentally sustainable practices into institutional practices. A successful transition to a sustainable campus requires the involvement of the university community; the administration, academics departments (faculty and students), researchers and he local community. Our research seeks to identify Critical Success Factors (CSFs) of university governance that contribute to the success in implementing Sustainable Campus Operation (SCO) initiatives. The common CSFs have been identified from 22 published and unpublished articles, conference proceedings, university reports, books, and website documents. The CSFs are mapped and ranked based on the frequency of the identified CSFs. 23 CSFs of SCO have been identified through this research. This research revealed that the CSF that contributes the highest frequency as indicated by most researchers is “developing network with external parties for gaining consensus and commitment”. By identifying these CSFs, this research will help assist universities in successfully plan and implement their SCO initiatives.

  2. Critical parameters governing energy density of Li-storage cathode materials unraveled by confirmatory factor analysis

    Science.gov (United States)

    Sohn, Kee-Sun; Han, Su Cheol; Park, Woon Bae; Pyo, Myoungho

    2016-03-01

    Despite extensive effort during the past few decades, a comprehensive understanding of the key variables governing the electrochemical properties of cathode materials in Li-ion batteries is still far from complete. To elucidate the critical parameters affecting energy density (ED) and capacity (Q) retention in layer and spinel cathodes, we data-mine the existing experimental data via confirmatory factor analysis (CFA) based on a structural equation model (SEM), which is a proven, versatile tool in understanding complex problems in the social science. The data sets are composed of 18 and 15 parameters extracted from 38 layer and 33 spinel compounds, respectively. CFA reveals the irrelevance of Q retention to all the parameters we adopt, but it also reveals the sensitive variations of ED with specific parameters. We validate the usefulness of CFA in material science and pinpointed critical parameters for high-ED cathodes, hoping to suggest a new insight in materials design.

  3. 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

  4. GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A2A Receptors

    Science.gov (United States)

    Gomes, Catarina A.R.V.; Simões, Patrícia F.; Canas, Paula M.; Quiroz, César; Sebastião, Ana M.; Ferré, Sergi; Cunha, Rodrigo A.; Ribeiro, Joaquim A.

    2009-01-01

    Glial cell line-derived neurotrophic factor (GDNF) affords neuroprotection in Parkinson’s disease in accordance with its ability to bolster nigrostriatal innervation. We previously found that GDNF facilitates dopamine release in a manner dependent on adenosine A2A receptor activation. Since motor dysfunction also involves modifications of striatal glutamatergic innervation, we now tested if GDNF and its receptor system, Ret (rearranged during transfection) and GFRα1 (GDNF family receptor alpha 1) controlled the cortico-striatal glutamatergic pathway in an A2A receptor-dependent manner. GDNF (10 ng/ml) enhanced (by ≈13%) glutamate release from rat striatal nerve endings, an effect potentiated (up to ≈ 30%) by the A2A receptor agonist CGS 21680 (10 nM) and prevented by the A2A receptor antagonist, SCH 58261 (50 nM). Triple immunocytochemical studies revealed that Ret and GFRα1 were located in 50% of rat striatal glutamatergic terminals (immunopositive for vesicular glutamate transporters-1/2), where they were found to be co-located with A2A receptors. Activation of the glutamatergic system upon in vivo electrical stimulation of the rat cortico-striatal input induced striatal Ret phosphoprylation that was prevented by pre-treatment with the A2A receptor antagonist, MSX-3 (3 mg/kg). The results provide the first functional and morphological evidence that GDNF controls cortico-striatal glutamatergic pathways in a manner largely dependent on the co-activation of adenosine A2A receptors. PMID:19141075

  5. What factors are most influential in governing stemflow production from plantation-grown teak trees?

    Science.gov (United States)

    Tanaka, Nobuaki; Levia, Delphis; Igarashi, Yasunori; Yoshifuji, Natsuko; Tanaka, Katsunori; Tantasirin, Chatchai; Nanko, Kazuki; Suzuki, Masakazu; Kumagai, Tomo'omi

    2017-01-01

    Stemflow (SF) has been recognized as an important process delivering water to spatially localized areas of the forest floor. Based on almost six years of daily SF data from nine teak trees in a Thai plantation, together with detailed above-canopy meteorological data and daily leaf area index (LAI) data, this study sought to better understand how specific biotic and abiotic factors affect both individual and stand-scale SF production from teak trees. Specifically, the factors affecting stemflow funneling ratio (SFFR) at individual and stand scales were analyzed and compared by means of boosted regression tree (BRT) analysis. The largest variation of SFFR among individual teak trees was observed in the leafed state. For trees taller than average, the BRT analysis revealed that vapor pressure deficit during rain was the most influential factor affecting SFFR. Vapor pressure deficit had a negative influence on SFFR, implying significant control of evaporative demand during rain. In contrast, for trees shorter than the average, rain duration (RD) was the most influential variable, having a positive correlation with SFFR. The stand-scale BRT analysis for all nine teak trees demonstrated that RD was the most influential factor affecting SFFR (exerting positive influence) but that an array of other factors (both abiotic and biotic) played intricate and complex roles in governing SFFR. The effect of LAI on SFFR was complicated and varied greatly among individual teak trees. It is possible that spatially heterogeneous flowpaths of intercepted water inside the teak canopy, which could be a product of the large-sized mature leaves of teak, may account for the tree-to-tree variation in the responses of SFFR to changing LAI. Although our study focused on teak trees, the demonstrated physically-based mechanistic explanations of stemflow production could apply to other even-aged deciduous forests and monospecific plantations.

  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. 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

  8. 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.

  9. 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 ...

  10. Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

    Science.gov (United States)

    van Huijstee, Aile N.; Mansvelder, Huibert D.

    2015-01-01

    Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine (DA) system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behavior, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA). This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC), with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioral symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodeling of PFC glutamatergic circuits can persist into adulthood, causing a lasting vulnerability to relapse. We will discuss how these neurobiological changes produced by drugs of abuse may provide novel targets for potential treatment strategies for addiction. PMID:25653591

  11. 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.

  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. 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.

  14. Factors Influencing the Selection of the Systems Integration Organizational Model Type for Planning and Implementing Government High-Technology Programs

    Science.gov (United States)

    Thomas, Leann; Utley, Dawn

    2006-01-01

    While there has been extensive research in defining project organizational structures for traditional projects, little research exists to support high technology government project s organizational structure definition. High-Technology Government projects differ from traditional projects in that they are non-profit, span across Government-Industry organizations, typically require significant integration effort, and are strongly susceptible to a volatile external environment. Systems Integration implementation has been identified as a major contributor to both project success and failure. The literature research bridges program management organizational planning, systems integration, organizational theory, and independent project reports, in order to assess Systems Integration (SI) organizational structure selection for improving the high-technology government project s probability of success. This paper will describe the methodology used to 1) Identify and assess SI organizational structures and their success rate, and 2) Identify key factors to be used in the selection of these SI organizational structures during the acquisition strategy process.

  15. Trans-acting factors governing acetylcholinesterase mRNA metabolism in neurons

    Directory of Open Access Journals (Sweden)

    Lucas M. Bronicki

    2012-03-01

    Full Text Available The most characterized function of acetylcholinesterase (AChE is to terminate cholinergic signaling at neuron-neuron and neuro-muscular synapses. In addition, AChE is causally or casually implicated in neuronal development, stress-response, cognition and neurodegenerative diseases. Given the importance of AChE, many studies have focused on identifying the molecular mechanisms that govern its expression. Despite these efforts, post-transcriptional control of AChE mRNA expression is still relatively unclear. Here, we review the trans-acting factors and cis-acting elements that are known to control AChE pre-mRNA splicing, mature mRNA stability and translation. Moreover, since the Hu/ELAV family of RNA-binding proteins (RBPs have emerged in recent years as ‘master’ post-transcriptional regulators, we discuss the possibility that predominantly neuronal ELAVs (nELAVs play multiple roles in regulating splicing, stability, localization and translation of AChE mRNA.

  16. Peak Stress Intensity Factor Governs Crack Propagation Velocity In Crosslinked UHMWPE

    Science.gov (United States)

    Sirimamilla, P. Abhiram; Furmanski, Jevan; Rimnac, Clare

    2013-01-01

    Ultra high molecular weight polyethylene (UHMWPE) has been successfully used as a bearing material in total joint replacement components. However, these bearing materials can fail as a result of in vivo static and cyclic loads. Crack propagation behavior in this material has been considered using the Paris relationship which relates fatigue crack growth rate, da/dN (mm/cycle) versus the stress intensity factor range, ΔK (Kmax-Kmin, MPa√m). However, recent work suggests that the crack propagation velocity of conventional UHMWPE is driven by the peak stress intensity (Kmax), not ΔK. The hypothesis of this study is that the crack propagation velocity of highly crosslinked and remelted UHMWPE is also driven by the peak stress intensity, Kmax, during cyclic loading, rather than by ΔK. To test this hypothesis, two highly crosslinked (65 kGy and 100 kGy) and remelted UHMWPE materials were examined. Frequency, waveform and R-ratio were varied between test conditions to determine the governing factor for fatigue crack propagation. It was found that the crack propagation velocity in crosslinked UHMWPE is also driven by Kmax and not ΔK, and is dependent on loading waveform and frequency in a predictable quasi-static manner. The current study supports that crack growth in crosslinked UHMWPE materials, even under cyclic loading conditions, can be described by a relationship between the velocity of crack growth, da/dt and the peak stress intensity, Kmax. The findings suggest that stable crack propagation can occur as a result of static loading only and this should be taken into consideration in design of UHMWPE total joint replacement components. PMID:23165898

  17. Peak stress intensity factor governs crack propagation velocity in crosslinked ultrahigh-molecular-weight polyethylene.

    Science.gov (United States)

    Sirimamilla, Abhiram; Furmanski, Jevan; Rimnac, Clare

    2013-04-01

    Ultrahigh-molecular-weight polyethylene (UHMWPE) has been successfully used as a bearing material in total joint replacement components. However, these bearing materials can fail as a result of in vivo static and cyclic loads. Crack propagation behavior in this material has been considered using the Paris relationship which relates fatigue crack growth rate, da/dN (mm/cycle) versus the stress intensity factor range, ΔK (Kmax - Kmin , MPa√m). However, recent work suggests that the crack propagation velocity of conventional UHMWPE is driven by the peak stress intensity (Kmax ), not ΔK. The hypothesis of this study is that the crack propagation velocity of highly crosslinked and remelted UHMWPE is also driven by the peak stress intensity, Kmax , during cyclic loading. To test this hypothesis, two highly crosslinked (65 kGy and 100 kGy) and remelted UHMWPE materials were examined. Frequency, waveform, and R-ratio were varied between test conditions to determine the governing factor for fatigue crack propagation. It was found that the crack propagation velocity in crosslinked UHMWPE is also driven by Kmax and not ΔK, and is dependent on loading waveform and frequency in a predictable quasistatic manner. This study supports that crack growth in crosslinked UHMWPE materials, even under cyclic loading conditions, can be described by a relationship between the velocity of crack growth, da/dt and the peak stress intensity, Kmax . The findings suggest that stable crack propagation can occur as a result of static loading only and this should be taken into consideration in design of UHMWPE total joint replacement components.

  18. Crepuscular flight activity of an invasive insect governed by interacting abiotic factors.

    Directory of Open Access Journals (Sweden)

    Yigen Chen

    Full Text Available Seasonal and diurnal flight patterns of the invasive walnut twig beetle, Pityophthorus juglandis, were assessed between 2011 and 2014 in northern California, USA in the context of the effects of ambient temperature, light intensity, wind speed, and barometric pressure. Pityophthorus juglandis generally initiated flight in late January and continued until late November. This seasonal flight could be divided approximately into three phases (emergence: January-March; primary flight: May-July; and secondary flight: September-October. The seasonal flight response to the male-produced aggregation pheromone was consistently female-biased (mean of 58.9% females. Diurnal flight followed a bimodal pattern with a minor peak in mid-morning and a major peak at dusk (76.4% caught between 1800 and 2200 h. The primarily crepuscular flight activity had a Gaussian relationship with ambient temperature and barometric pressure but a negative exponential relationship with increasing light intensity and wind speed. A model selection procedure indicated that the four abiotic factors collectively and interactively governed P. juglandis diurnal flight. For both sexes, flight peaked under the following second-order interactions among the factors when: 1 temperature between was 25 and 30 °C and light intensity was less than 2000 lux; 2 temperature was between 25 and 35 °C and barometric pressure was between 752 and 762 mba (and declined otherwise; 3 barometric pressure was between 755 and 761 mba and light intensity was less than 2000 lux (and declined otherwise; and 4 temperature was ca. 30 °C and wind speed was ca. 2 km/h. Thus, crepuscular flight activity of this insect can be best explained by the coincidence of moderately high temperature, low light intensity, moderate wind speed, and low to moderate barometric pressure. The new knowledge provides physical and temporal guidelines for the application of semiochemical-based control techniques as part of an IPM

  19. Crepuscular Flight Activity of an Invasive Insect Governed by Interacting Abiotic Factors

    Science.gov (United States)

    Chen, Yigen; Seybold, Steven J.

    2014-01-01

    Seasonal and diurnal flight patterns of the invasive walnut twig beetle, Pityophthorus juglandis, were assessed between 2011 and 2014 in northern California, USA in the context of the effects of ambient temperature, light intensity, wind speed, and barometric pressure. Pityophthorus juglandis generally initiated flight in late January and continued until late November. This seasonal flight could be divided approximately into three phases (emergence: January–March; primary flight: May–July; and secondary flight: September–October). The seasonal flight response to the male-produced aggregation pheromone was consistently female-biased (mean of 58.9% females). Diurnal flight followed a bimodal pattern with a minor peak in mid-morning and a major peak at dusk (76.4% caught between 1800 and 2200 h). The primarily crepuscular flight activity had a Gaussian relationship with ambient temperature and barometric pressure but a negative exponential relationship with increasing light intensity and wind speed. A model selection procedure indicated that the four abiotic factors collectively and interactively governed P. juglandis diurnal flight. For both sexes, flight peaked under the following second-order interactions among the factors when: 1) temperature between was 25 and 30°C and light intensity was less than 2000 lux; 2) temperature was between 25 and 35°C and barometric pressure was between 752 and 762 mba (and declined otherwise); 3) barometric pressure was between 755 and 761 mba and light intensity was less than 2000 lux (and declined otherwise); and 4) temperature was ca. 30°C and wind speed was ca. 2 km/h. Thus, crepuscular flight activity of this insect can be best explained by the coincidence of moderately high temperature, low light intensity, moderate wind speed, and low to moderate barometric pressure. The new knowledge provides physical and temporal guidelines for the application of semiochemical-based control techniques as part of an IPM program for

  20. Change Management as a Critical Success Factor in e-Government Implementation

    Directory of Open Access Journals (Sweden)

    Janja Nograšek

    2011-01-01

    Full Text Available Change management in e-government implementation is a very complex issue. E-government services are frequently distributed over different IT systems and organizations. There are also events from outside the public administration that cause changes such as government policies and legislation, public-private partnership, etc., and finally a huge resistance to change exists in public administration proverbial. Another problem is that the e-government is predominantly seen only as a technology mission and not as an organizational transformation issue. Those are probably the main reasons that the existing literature about change management in e-government is still missing at large. There are articles dealing with some aspects of changes affected by the new technology implementation, however, there is no comprehensive framework that would identify changes that have to be managed in e-government implementation. Therefore, the main aim of the paper is to identify a comprehensive set of changes that have to be considered in e-government implementation and the role of leadership in such processes. Finally, the paper proposes a conceptual model of change management in e-government implementation.

  1. 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...

  2. Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission

    DEFF Research Database (Denmark)

    Schousboe, A; Sarup, A; Bak, L K

    2004-01-01

    The fine tuning of both glutamatergic and GABAergic neurotransmission is to a large extent dependent upon optimal function of astrocytic transport processes. Thus, glutamate transport in astrocytes is mandatory to maintain extrasynaptic glutamate levels sufficiently low to prevent excitotoxic...... neuronal damage. In GABA synapses hyperactivity of astroglial GABA uptake may lead to diminished GABAergic inhibitory activity resulting in seizures. As a consequence of this the expression and functional activity of astrocytic glutamate and GABA transport is regulated in a number of ways...

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

    Science.gov (United States)

    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.

  4. 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.

  5. Factors explaining adoption and implementation processes for web accessibility standards within eGovernment systems and organizations

    NARCIS (Netherlands)

    Velleman, Eric M.; Nahuis, Inge; Geest, van der Thea

    2015-01-01

    Local government organizations such as municipalities often seem unable to fully adopt or implement web accessibility standards even if they are actively pursuing it. Based on existing adoption models, this study identifies factors in five categories that influence the adoption and implementation of

  6. Governance factors in the identification of global conservation priorities for mammals.

    Science.gov (United States)

    Eklund, Johanna; Arponen, Anni; Visconti, Piero; Cabeza, Mar

    2011-09-27

    Global conservation priorities have often been identified based on the combination of species richness and threat information. With the development of the field of systematic conservation planning, more attention has been given to conservation costs. This leads to prioritizing developing countries, where costs are generally low and biodiversity is high. But many of these countries have poor governance, which may result in ineffective conservation or in larger costs than initially expected. We explore how the consideration of governance affects the selection of global conservation priorities for the world's mammals in a complementarity-based conservation prioritization. We use data on Control of Corruption (Worldwide Governance Indicators project) as an indicator of governance effectiveness, and gross domestic product per capita as an indicator of cost. We show that, while core areas with high levels of endemism are always selected as important regardless of governance and cost values, there are clear regional differences in selected sites when biodiversity, cost or governance are taken into account separately. Overall, the analysis supports the concentration of conservation efforts in most of the regions generally considered of high priority, but stresses the need for different conservation approaches in different continents owing to spatial patterns of governance and economic development.

  7. Governance factors in the identification of global conservation priorities for mammals

    Science.gov (United States)

    Eklund, Johanna; Arponen, Anni; Visconti, Piero; Cabeza, Mar

    2011-01-01

    Global conservation priorities have often been identified based on the combination of species richness and threat information. With the development of the field of systematic conservation planning, more attention has been given to conservation costs. This leads to prioritizing developing countries, where costs are generally low and biodiversity is high. But many of these countries have poor governance, which may result in ineffective conservation or in larger costs than initially expected. We explore how the consideration of governance affects the selection of global conservation priorities for the world's mammals in a complementarity-based conservation prioritization. We use data on Control of Corruption (Worldwide Governance Indicators project) as an indicator of governance effectiveness, and gross domestic product per capita as an indicator of cost. We show that, while core areas with high levels of endemism are always selected as important regardless of governance and cost values, there are clear regional differences in selected sites when biodiversity, cost or governance are taken into account separately. Overall, the analysis supports the concentration of conservation efforts in most of the regions generally considered of high priority, but stresses the need for different conservation approaches in different continents owing to spatial patterns of governance and economic development. PMID:21844045

  8. Methane oxidation potential of boreal landfill cover materials: The governing factors and enhancement by nutrient manipulation.

    Science.gov (United States)

    Maanoja, Susanna T; Rintala, Jukka A

    2015-12-01

    Methanotrophs inhabiting landfill covers are in a crucial role in mitigating CH4 emissions, but the characteristics of the cover material or ambient temperature do not always enable the maximal CH4 oxidation potential (MOP). This study aimed at identifying the factors governing MOPs of different materials used for constructing biocovers and other cover structures. We also tested whether the activity of methanotrophs could be enhanced at cold temperature (4 and 12°C) by improving the nutrient content (NO3(-), PO4(3-), trace elements) of the cover material. Compost samples from biocovers designed to support CH4 oxidation were exhibiting the highest MOPs (4.16 μmol CH4 g dw(-1) h(-1)), but also the soil samples collected from other cover structures were oxidising CH4 (0.41 μmol CH4 g dw(-1) h(-1)). The best predictors for the MOPs were the NO3(-) content and activity of heterotrophic bacteria at 72.8%, which were higher in the compost samples than in the soil samples. The depletion of NO3(-) from the landfill cover material limiting the activity of methanotrophs could not be confirmed by the nutrient manipulation assay at 4°C as the addition of nitrogen decreased the MOPs from 0.090 μmol CH4 g dw(-1) h(-1) to 0.096 μmol CH4 g dw(-1)h(-1)) suggesting that this was attributable to stimulation of the enzymatic activity of the psychrotolerant methanotrophs.

  9. Factors Governing the Performance of Bauxite for Fluoride Remediation of Groundwater.

    Science.gov (United States)

    Cherukumilli, Katya; Delaire, Caroline; Amrose, Susan; Gadgil, Ashok J

    2017-02-21

    Globally, 200 million people drink groundwater contaminated with fluoride concentrations exceeding the World Health Organization's recommended level (WHO-MCL = 1.5 mg F(-)/L). This study investigates the use of minimally processed (dried/milled) bauxite ore as an inexpensive adsorbent for remediating fluoride-contaminated groundwater in resource-constrained areas. Adsorption experiments in synthetic groundwater using bauxites from Guinea, Ghana, U.S., and India as single-use batch dispersive media demonstrated that doses of ∼10-23 g/L could effectively remediate 10 mg F(-)/L. To elucidate factors governing fluoride removal, bauxites were characterized using X-ray fluorescence, X-ray diffraction, gas-sorption analysis, and adsorption isotherms/envelopes. All ores contained gibbsite, had comparable surface areas (∼14-17 m(2)/g), had similar intrinsic affinities and capacities for fluoride, and did not leach harmful ions into product water. Fluoride uptake on bauxite -primarily through ion-exchange- was strongly pH-dependent, with highest removal occurring at pH 5.0-6.0. Dissolution of CaCO3, present in trace amounts in India bauxite, significantly hindered fluoride removal by increasing solution pH. We also showed that fluoride remediation with the best-performing Guinea bauxite was ∼23-33 times less expensive than with activated alumina. Overall, our results suggest that bauxite could be an affordable fluoride-remediation adsorbent with the potential to improve access to drinking water for millions living in developing countries.

  10. Cross-country differences in economic governance : Culture as a major explanatory factor

    NARCIS (Netherlands)

    Semenov, R.

    2000-01-01

    Mechanisms through which economic agents coordinate their activities differ dramatically across nations. These differences largely persist despite an increasing internationalization of economies. This thesis investigates the causes of differences in organ ation of industrial finance, in governance

  11. Exploring the success, failure and factors influencing M-government implementation in developing countries

    CSIR Research Space (South Africa)

    Ogunleye, OS

    2014-05-01

    Full Text Available The proliferation of mobile technologies and mobile phones has presented an opportunity for Government in the developing countries to utilize Mobile Information and Communication Technologies (M-ICT) to help facilitate daily administration...

  12. E-GOVERNMENT: A DRIVING FACTOR FOR STIMULATING INNOVATION PERFORMANCE IN ROMANIA?

    Directory of Open Access Journals (Sweden)

    Coculescu Cristina

    2011-07-01

    Full Text Available The development of public services is one of the priorities on the agendas of all policies, both national and European. One of the most recent concerns of the European Commission, as shown in the 2010 Innobarometer, is to find ways and develop strategies to support the innovation in the public administration sector, in the context of the continuously changing economic background. In this paper, we'll investigate the relationship between e-Government, and the overall innovation performance at national level, for some European Union countries. e-Government is already a known concept, widespread in the world, promoting the implementation of information and communication technologies in the public administration, in order to provide better public services to citizens and businesses. A main component of the e-Government concept is the 'counter reform', aimed to streamlining administrative act quickly in order to respond to the demands of citizens, businesses and government structures. Innovation in e-Government will be measured with two Eurostat indicators e-Government on-line availability and e-Government usage by individuals while for the overall innovation performance we'll use a composite indicator the Summary Innovation Index (SII - from the Innovation Union Scoreboard (IUS. In Romania, even if the values of these indicators are not at the level of other EU countries, we can say that the situation has improved and electronic public services are being used increasingly often. The study also includes a comparison between two modest innovators: Romania and Bulgaria. Regarding the overall innovation performance, according to the 2010 Innovation Union Scoreboard ranking, Romania is the leader of the modest innovators countries, overcoming Latvia, Bulgaria and Lithuania. However, in the field of e-Government our country has major shortcomings. Romania has registered a significant progress in the years after the EU integration, followed by a setback in

  13. Organizational growth of SMEs in Serbia: Governance as a built-in limiting growth factor

    OpenAIRE

    Janićijević Nebojša; Bogićević-Milikić Biljana

    2010-01-01

    The aim of the study is to investigate the characteristics of governance structures in three Serbian medium-sized enterprises and, particularly, whether the corporate governance influences organizational growth prospects of these firms. The results suggest that in all the companies owners held a tight personal control over all activities, not being willing to delegate any authority to professional managers. This unwillingness of owners to delegate authority actually presents the main barrier ...

  14. Investigating antecedent factors to job performance: Contemporary evidence from government supply management professionals

    OpenAIRE

    Chengedzai Mafini

    2015-01-01

    Purpose: The purpose of the study was to investigate the influence of transformational leadership, organisational citizenship behaviour and quality of work life on job performance amongst supply management professionals employed by the South African government.Rationale: The depressed job performance of supply management professionals in the South African government presents an impetus to generate new empirical information on the subject in order to find solutions.Methodology: A quantitative ...

  15. 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

  16. 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'.

  17. Soil transmitted helminths and associated factors among schoolchildren in government and private primary school in Jimma Town, Southwest Ethiopia.

    Science.gov (United States)

    Debalke, Serkadis; Worku, Amare; Jahur, Nejat; Mekonnen, Zeleke

    2013-11-01

    Soil transmitted helminth infections are among the most common human infections. They are distributed throughout the world with high prevalence rates in tropical and sub-tropical countries mainly because of lack of adequate sanitary facilities, inappropriate waste disposal systems, lack of safe water supply, and low socio-economic status. A comparative cross sectional study was conducted from December 2011 to June 2012 to determine and assess the prevalence of soil transmitted helminths and their associated factors among government and private primary school children. Stool samples were collected from 369 randomly selected children and examined microscopically for eggs of soil transmitted helminth following McMaster techniques. Soil samples were collected from different parts of the school compound and microscopic examination was performed for eggs of the helminths using sodium nitrate flotation technique. The overall prevalence rate of soil transmitted helminth infections in private and government schools was 20.9% and 53.5% respectively. T. trichiura was the most common soil transmitted helminth in both schools while hookworm infections were identified in government school students only. Type of school and sex were significantly associated with soil transmitted helminth. Soil contamination rate of the school compounds was 11.25% with predominant parasites of A. lumbricoides. Higher prevalence of soil transmitted helminth infection was found among government school students. Thus, more focus, on personal hygiene and sanitary facilities, should be given to children going to government schools.

  18. [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.

  19. Critical success factors for governing farmer-managed public goods in rural areas in the Netherlands

    NARCIS (Netherlands)

    Blom-Zandstra, Greet; Korevaar, Hein; Stuiver, Marian; Groot, Annemarie

    2016-01-01

    Multifunctional land use has become a widely supported pathway for Europe's countryside. Brussels and the national governments stimulate farmers to integrate primary production with non-agricultural practices from which they can also benefit. In favour of this development different stakeholders a

  20. Influence of Psychosocial Factors on Aging among the Aged in Ihitte-Uboma Local Government Area of Imo State, Nigeria

    Directory of Open Access Journals (Sweden)

    Ojukwu M.O.

    2016-10-01

    Full Text Available The major aim of this study was to examine influence of psychosocial factors on aging among the aged in Ihitte Uboma Local Government Area of Imo State, Nigeria. Ex-post facto or casual comparative research design was adopted for the study. Two hundred and twenty-five (225 old people were selected through random sampling for the study. Self-constructed instrument entitled “Influence of Psychosocial factors on aging in Ihitte Uboma LGA” was used to collect data. Two research questions and two hypotheses guided the study. Mean and t-test analysis were used to analyze the data collected for the study. Major findings revealed that lack of security, inadequate care giver, poverty, migration of kids and family members to the urban areas, lack of health facilities and care are the major psychosocial factors affecting aging in the LGA. In all these it was also revealed that women were more influenced by these psychosocial factors than their men counterpart. It was also revealed that self-concept has significant influence on the ageing process of the aged in the area. Based on the findings it was recommended that government should provide adequate security in the villages, as well as provision of adequate healthcare and facilities. Keywords: Influence, Psychosocial factors, aged, aging process and Ihitte Uboma

  1. 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.

  2. Assessing social capacity and vulnerability of private households to natural hazards – integrating psychological and governance factors

    Directory of Open Access Journals (Sweden)

    J. Werg

    2013-06-01

    Full Text Available People are unequally affected by extreme weather events in terms of mortality, morbidity and financial losses; this is the case not only for developing, but also for industrialized countries. Previous research has established indicators for identifying who is particularly vulnerable and why, focusing on socio-demographic factors such as income, age, gender, health and minority status. However, these factors can only partly explain the large disparities in the extent to which people are affected by natural hazards. Moreover, these factors are usually not alterable in the short to medium term, which limits their usefulness for strategies of reducing social vulnerability and building social capacity. Based on a literature review and an expert survey, we propose an approach for refining assessments of social vulnerability and building social capacity by integrating psychological and governance factors.

  3. 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

    volume quantified [2]. Distribution of glutamatergic synaptic terminals was evaluated with immunohistochemistry. Asymmetric-glutamatergic synapses were identified and the size of readilyreleasable pool and reserve-pool of vesicles estimated, through serial section electron microscopy. Extension of post...

  4. SOCIO-ECONOMIC FACTORS AFFECTING GROUNDNUT PRODUCTION IN SABONGARI LOCAL GOVERNMENT OF KADUNA STATE, NIGERIA

    Directory of Open Access Journals (Sweden)

    Ibrahim Usman

    2013-07-01

    Full Text Available Groundnut an important oil seed crop provides significant sources of cash through the sales of seed, cakes, oil and haulms. Groundnut plays an important role in the diets of rural populations. Groundnut pod yields from farmer’s field are low, averaging about 800 kg per ha, less than one-third the potential yield of 3000 kg per ha. This large gap is of concern and in view of this, the study was carried out to assess the socio economic characteristics of groundnut farmers, determine the level of profitability of groundnut production, the resource use efficiency as well as to find out problems encountered in groundnut production in Sabon-gari local government area. Seventy-nine farmers involved in groundnut production were randomly selected from the various farms located within the local government area. Data were collected using primary and secondary sources. To examine the profitability of groundnut production, the gross margin and cost benefit analysis were carried out. The result of the study shows that experienced farmers are less involved in groundnut production and most groundnut farmers are engaged in other form of businesses. The cost, availability, and lack of technical knowledge of inputs requirements are responsible for poor use of the inputs. Labour, fertilizer, seed and herbicides are all over utilized except insecticide which is underutilized. Among the problems encountered in groundnut production in the study are lacks of capital and extension services. These two problems accounted for over 78% of the problem of groundnut in the study area. It is therefore recommended that government and research institutes should strengthen extension services to deliver improved technologies to the farmers. Farmers are also advised to source for loans through cooperatives, banks and other available sources at low charges and the procedure for loan should be made simple to enable farmers’ access loans so that groundnut production can be improved.

  5. 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.

  6. [A study of factors related to Korean physicians' trust in the government: on the target for board members of physicians' associations].

    Science.gov (United States)

    Lee, Sunhee; Yang, Gunmo; Seo, Juhyun; Kim, Juhye

    2010-09-01

    This study aims to investigate the factors related to Korean physicians' trust in the government. We used structured questionnaires that were composed of multidimensional scales for each of the various categories. The recognition levels of trust of the government by Korean physicians were not high, and they ranged from 3.6 to 4.8 for ten scales. The factors related to trust in the government were categorized into seven factors on the basis of a factor analysis. On the regression analysis, a positive relationship was found between "the individual propensity to trust" and trust in the government, while a negative relationship was found between "the recognition level regarding the government as an authoritarian power" and trust in the government. "Confidence about participation in the policy process" as internal efficacy and "belief in governmental ability and motivation toward public demand" as external efficacy also showed a strong positive relationship with trust in the government. From these results, we can draw the conclusion that making efforts to improve the recognition level of trust in the government among physicians is an important policy task. To increase the trust level, participation of physicians in the policy process in various ways and open communication between the physicians'associations and the government should be facilitated.

  7. Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies.

    Science.gov (United States)

    Xu, Wei; Boehm, Garth; Zheng, Qiang

    2016-01-01

    Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution.

  8. Factors Contributing To The Sustainability Of 5S Programmes In Government Hospitals In Regional Director Of Health Services Area Kurunegala

    Directory of Open Access Journals (Sweden)

    Dr. K.W.C.U.K Kendangamuwa

    2015-03-01

    Full Text Available Abstract Introduction 5S is the stepping stone for many quality improvement concepts and its roots date back to 16th century. When successfully implemented 5S gives many benefits to the organization as well as its stakeholders. Though 5S itself has a tool to sustain most of the organizations find it difficult to sustain the 5S practice over the time. Therefore the objective of this study was to find out the factors contributing to sustainability of 5S programmes in Government Hospitals in RDHS area Kurunegala. Methodology This study was a descriptive cross sectional study with two components. First component was to identify the 5S sustaining hospitals from not sustaining hospitals by validated evaluation sheet. Second component was to determine the factors contributing to sustainability of 5S programmes in selected study setting. Self-administrated questionnaire was used for this purpose. Total study population was 543 employees of all the categories of hospital staff. Calculated sample size was 422 and 375 were responded to the questionnaire giving response rate of 88.9. Results The study revealed that the implemented 5S programmes were sustaining in eight hospitals out of ten i.e. sustaining rate was 80. When it considered the degree of sustainability 50 of the selected hospitals reported more than 70 sustainability. This was considered as favourable trend in government health sector in healthcare quality point of view. Ten factors were studied as contributing factors for the 5S sustainability. Socio- demographic factors were also considered. Those ten factors were top management commitment leadership of the organization commitment of middle amp frontline managers commitment amp satisfaction of employees training amp changing attitude of employees motivation of employees organizational culture group cohesiveness community participation and customer satisfaction. Study revealed that organizational leadership customer satisfaction community

  9. The effect of UTAUT2 moderator factors on citizens’ intention to adopt e-government: the case of two SADC countries

    Directory of Open Access Journals (Sweden)

    Willard Munyoka

    2017-03-01

    Full Text Available E-government is widely believed to play a significant role in improving the public service delivery system in developing countries. Yet, its adoption and utilization amongst citizens remain a subject of concern amongst government policy makers. This study aims to investigate moderating factors that influence citizens’ decisions to adopt and utilize e-government services in the SADC region. The study adopts the extended UTAUT2 model as a theoretical underpinning, backed by recent literature on e-government adoption to advance and test an e-government adoption model. Empirical quantitative data for validating the proposed model was collected from 247 participants using self-administered questionnaires. In analyzing the empirical data, five moderating demographic factors affecting citizens’ behavioral intention to adopt e-government services were tested and confirmed. The study found that only four moderating factors (age, level of education, the location of residence, and vernacular language positively influenced citizens’ intention to adopt e-government. The study concludes by drawing attention to insights on moderating factors affecting e-government adoption, thereby casting more light to success factors and gray areas for failed adoption.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. Study of Core Competency Elements and Factors Affecting Performance Efficiency of Government Teachers in Northeastern Thailand

    Science.gov (United States)

    Chansirisira, Pacharawit

    2012-01-01

    The research aimed to investigate the core competency elements and the factors affecting the performance efficiency of the civil service teachers in the northeastern region, Thailand. The research procedure consisted of two steps. In the first step, the data were collected using a questionnaire with the reliability (Cronbach's Alpha) of 0.90. The…

  16. The network of cytokines, receptors and transcription factors governing the development of dendritic cell subsets

    OpenAIRE

    Sathe, Priyanka; Wu, Li

    2011-01-01

    The pathways leading to the development of different dendritic cell (DC) subsets have long been unclear. In recent years, a number of precursors on the route to DC development, both under steady state and inflammatory conditions, have been described, and the nature of these pathways is becoming clearer. In addition, the development of various knockout mouse models and an in vitro system modelling DC development have revealed the role of numerous cytokines and transcription factors that influe...

  17. Reported Pain During Labour - A Qualitative Study of Influencing Factors among Parturient During Confinement in Private or Government Hospital.

    Science.gov (United States)

    Parthasarathy, S; Ravishankar, M; Hemanthkumar, V R

    2016-03-01

    Labour pain is distressing and it produces undue side effects both to the mother and the baby. The incidence is high in developing countries like India where the awareness about labour analgesia is still lacking. It is to find out the incidence of labour pain and the influence of various described factors on pain with a comparison between patients admitted in a government set up with a private set up in a south Indian semi-urban area. Two hundred continuous uneventful normal deliveries each in a Government (group G) and a private hospital (group P) were enrolled for the study. The reported pain during labour was noted 6-7 hours after delivery by interacting with the patient. The factors like age of the mother, sex and weight of the baby, literacy, socioeconomic status, the use of oxytocics and analgesia were evaluated. The incidence of severe pain was more in group G (43.5%) than group P (12%). There was no analgesic intervention in 68.5% in group G while it was 13.5% (27/200) in group P. Even among these 27 patients who did not receive analgesics, only three parturients reported severe pain. Even administration of analgesics in a Government set up did not decrease pain to a significant extent. There were richer and more literate patients in group P. Booked cases were less in group G. Logistic regression analyses to find out factors which influenced pain in either group was used. Gravida, analgesic intervention and admission in a Govt. hospital influenced the pain experience of the parturient. There was minimal antenatal preparation in both the groups. There were no post partum complications. Mothers suffered from labour pain to a significant extent and there is an urgent need for awareness about labour analgesia. Primigravida, admission in a Govt. set up and analgesic interventions were the factors which influenced pain than others. Patients admitted in Govt. hospitals suffered more pain with less analgesic intervention possibly due to illiteracy. The increased

  18. Reported Pain During Labour – A Qualitative Study of Influencing Factors among Parturient During Confinement in Private or Government Hospital

    Science.gov (United States)

    Ravishankar, M.; Hemanthkumar, V.R.

    2016-01-01

    Introduction Labour pain is distressing and it produces undue side effects both to the mother and the baby. The incidence is high in developing countries like India where the awareness about labour analgesia is still lacking. Aim It is to find out the incidence of labour pain and the influence of various described factors on pain with a comparison between patients admitted in a government set up with a private set up in a south Indian semi-urban area. Materials and Methods Two hundred continuous uneventful normal deliveries each in a Government (group G) and a private hospital (group P) were enrolled for the study. The reported pain during labour was noted 6-7 hours after delivery by interacting with the patient. The factors like age of the mother, sex and weight of the baby, literacy, socioeconomic status, the use of oxytocics and analgesia were evaluated. Results The incidence of severe pain was more in group G (43.5%) than group P (12%). There was no analgesic intervention in 68.5% in group G while it was 13.5% (27/200) in group P. Even among these 27 patients who did not receive analgesics, only three parturients reported severe pain. Even administration of analgesics in a Government set up did not decrease pain to a significant extent. There were richer and more literate patients in group P. Booked cases were less in group G. Logistic regression analyses to find out factors which influenced pain in either group was used. Gravida, analgesic intervention and admission in a Govt. hospital influenced the pain experience of the parturient. There was minimal antenatal preparation in both the groups. There were no post partum complications. Conclusion Mothers suffered from labour pain to a significant extent and there is an urgent need for awareness about labour analgesia. Primigravida, admission in a Govt. set up and analgesic interventions were the factors which influenced pain than others. Patients admitted in Govt. hospitals suffered more pain with less analgesic

  19. Lateral gas transport in soil adjacent to an old landfill: factors governing gas migration

    DEFF Research Database (Denmark)

    Christophersen, Mette; Kjeldsen, Peter

    2001-01-01

    migration of landfill gas was a very dynamic system and the concentrations of LFG at a specific place and depth changed dramatically within a very short time. The experiments showed that change in barometric pressure was an important factor affecting gas migration at the Skellingsted landfill in Denmark.......Field experiments investigating lateral gas transport in soil adjacent to an old landfill in Denmark during a one-year period were conducted. A significant seasonal variation, with low concentrations of methane and high concentrations of carbon dioxide in the summer, caused by methane oxidation...

  20. Several developmental and morphogenetic factors govern the evolution of stomatal patterning in land plants.

    Science.gov (United States)

    Rudall, Paula J; Hilton, Jason; Bateman, Richard M

    2013-11-01

    We evaluate stomatal development in terms of its primary morphogenetic factors and place it in a phylogenetic context, including clarification of the contrasting specialist terms that are used by different sets of researchers. The genetic and structural bases for stomatal development are well conserved and increasingly well understood in extant taxa, but many phylogenetically crucial plant lineages are known only from fossils, in which it is problematic to infer development. For example, specialized lateral subsidiary cells that occur adjacent to the guard cells in some taxa can be derived either from the same cell lineage as the guard cells or from an adjacent cell file. A potentially key factor in land-plant evolution is the presence (mesogenous type) or absence (perigenous type) of at least one asymmetric division in the cell lineage leading to the guard-mother cell. However, the question whether perigenous or mesogenous development is ancestral in land plants cannot yet be answered definitively based on existing data. Establishment of 'fossil fingerprints' as developmental markers is critical for understanding the evolution of stomatal patterning. Long cell-short cell alternation in the developing leaf epidermis indicates that the stomata are derived from an asymmetric mitosis. Other potential developmental markers include nonrandom stomatal orientation and a range of variation in relative sizes of epidermal cells. Records of occasional giant stomata in fossil bennettites could indicate development of a similar type to early-divergent angiosperms. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  1. Ecological factors governing the distribution of soil microfungi in some forest soils of Pachmarhi Hills, India

    Directory of Open Access Journals (Sweden)

    Shashi Chauhan

    2014-02-01

    Full Text Available An ecological study of the microfungi occurring in the various forest soils of Pachmarhi Hills, India has been carried-out by the soil plate technique. Soil samples from 5 different forest communities viz., moist deciduous forest dominated by tree ferns, Diospyros forest, Terminalia forest, Shorea forest and scrub forest dominated by Acacia and Dalbergia sp. were collected during October, 1983. Some physico-chemical characteristics of the soil were analysed and their role in distribution of fungi in 5 soil types was studied and discussed. 43 fungal species were isolated, of which Asperigillus niger I and Penicillium janthinellum occurred in all the 5 soil types. Statistically, none of the edaphic factors showed positive significant correlation with the number of fungi.

  2. Resilience dysregulation in major depressive disorder: focus on glutamatergic imbalance and microglial activation.

    Science.gov (United States)

    Réus, Gislaine Z; de Moura, Airam B; Silva, Ritele H; Resende, Wilson R; Quevedo, João

    2017-06-30

    Many studies have been shown an important role of glutamatergic system as well microglial activation in the pathophysiology of major depressive disorder (MDD). Experimental and clinical data suggest that attenuation of N-methyl-D-aspartate (NMDA) receptor function exerts antidepressant effects. Glutamatergic system is involved with memory establishment and function, and it regulates plasticity in the brain. Microglial cells play pivotal role to the brain functions; however, under chronic inflammation status microglial could be turn activated and increase the pro-inflammatory cytokines. In humans most resistant to the development of psychiatric disorders, including MDD, are observed a greater degree of resilience resulting from stress. Less resilience is associated with neuroendocrine and neuroinflammatory markers, as well as with glutamatergic system dysregulation. Thus, this review we highlighted findings from literature identifying the function of glutamatergic system, microglial activation and inflammation in resilience. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. E-government factors to reduce administrative and finance corruption in Arab countries: Case study Iraqi oil sector

    Science.gov (United States)

    Mohammed, M. A.; Eman, Y.; Hussein, A. H.; Hasson, A. R.

    2015-12-01

    Arab countries face the corruption issues in its several public organizations. The corruption in these countries is considered as the main challenge. The oil sector is one of the public sectors that have huge level of corruption. However, the Iraqi economy had become dependable on oil sector daring the last three decades, and on the contrary, of what other oil countries did. The capital is considered as one of the essential factor for economic development. The revenues of oil exports will stay the essential source for economic development in Iraq in the future in order to reduce being dependable on oil. Since the beginning of the 3rd thousands, the world witnessed great rise in the demand on oil, but the Iraqi exports of crude oil come to be less than its similarities in the seventeenths of last century. So our oil sector is still in need of deep study. This study focuses on technological technique that can make huge decrease for corruption in oil sector in Iraq. However, e-government is considered as the best techniques that can decrease the corruption. Thus, this study bases on challenges that effect on build successful e-government project in Iraqi oil industry.

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Identifying the factors governing attitude towards the e-Agriservice among dairy farmers in Maharashtra, India

    Directory of Open Access Journals (Sweden)

    Sagar Kisan Wadkar

    2016-01-01

    Full Text Available Information and communication technology (ICT projects have a great potential to revolutionise the information delivery system by bridging the gap between farmers and extension personnel. aAQUA (Almost All Questions Answered portal was launched by the Developmental Informatics Laboratory (DIL at Indian Institute of Technology (IIT Mumbai, Maharashtra, India in 2003 as an information providing system to deliver technology options and tailored information for the problems and queries raised by Indian dairy farmers. To measure the effectiveness of this service the attitudinal dimensions of the users of aAQUA e-Agriservice were investigated using a 22 item scale. A simple random sampling technique was used to select 120 dairy farmers from which data were collected and subjected to factor analysis to identify the underlying constructs in this research. From the attitude items, four components were extracted and named as the pessimistic, utility, technical and efficacy perspective, which influenced the development of varied level of attitudinal inclination towards the e-Agriservice. These components explained 64.40 per cent of variation in the attitude of the users towards the aAQUA e-Agriservice. This study provides a framework for technically efficient service provision that might help to reduce the pessimistic attitude of target population to adopt e-Agriservice in their farming system. The results should also be helpful for researchers, academics, ICT based service providers and policy makers to consider these perspectives while planning and implementing ICT projects.

  8. A longitudinal causal relationship among cardiovascular risk factors in the employees of the government savings bank.

    Science.gov (United States)

    Temcharoen, Paradee; Vorapongsathorn, Thavatchai; Pradipasen, Mandhana; Sritara, Piyamitr

    2002-08-01

    A longitudinal structural causal model was generated to examine the causal relationship among determinants which were composed of four personal factors, stress, four health behaviors, and BMI on five physiological risks for cardiovascular disease: SBP, DBP, FBS, TC and HDL-C in 1,019 bank employees, within a five-year interval. A fourteen-item food frequency questionnaire for assessing eating habits and the Health Opinion Survey for the stress test were included in the self-administered questionnaires. Weight, height and blood pressure were measured and blood samples were collected for blood chemical analysis. Data analysis by LISREL showed that the determinants in the proposed model explained as much as 96 per cent variation in physiological risks for CVD (R2 = 0.96, relative chi-square = 1.92, RMSEA = 0.03, GFI = 0.96 and AGFI = 0.95). The findings also indicated that current physiological status was affected by their status of age, education, health behaviors, BMI and physiological status 5 years ago.

  9. Factors governing the form of the relation between muscle force and the EMG: a simulation study.

    Science.gov (United States)

    Zhou, Ping; Rymer, William Zev

    2004-11-01

    The dependence of the form of the EMG-force relation on key motoneuron and muscle properties was explored using a simulation approach. Surface EMG signals and isometric forces were simulated using existing motoneuron pool, muscle force, and surface EMG models, based primarily on reported properties of the first dorsal interosseous (FDI) muscle in humans. Our simulation results indicate that the relation between electrical and mechanical properties of the individual motor unit level plays the dominant role in determining the overall EMG amplitude-force relation of the muscle, while the underlying motor unit firing rate strategy appears to be a less important factor. However, different motor unit firing rate strategies result in substantially different relations between counts of the numbers of motoneuron discharges and the isometric force. Our simulation results also show that EMG amplitude (estimated as the average rectified value) increases as a result of synchronous discharges of different motor units within the pool, but the magnitude of this increase is determined primarily by the action potential duration of the synchronized motor units. Furthermore, when the EMG effects are normalized to their maximum levels, motor unit synchrony does not exert significant effects on the form of the EMG-force relation, provided that the synchrony level is held similar at different excitation levels.

  10. The Aspergillus fumigatus Transcription Factor Ace2 Governs Pigment Production, Conidiation and Virulence

    Science.gov (United States)

    Ejzykowicz, Daniele E.; Cunha, Marcel M.; Rozental, Sonia; Solis, Norma V.; Gravelat, Fabrice N.; Sheppard, Donald C.; Filler, Scott G.

    2009-01-01

    Summary Aspergillus fumigatus causes serious and frequently fatal infections in immunocompromised patients. To investigate the regulation of virulence of this fungus, we constructed and analyzed an A. fumigatus mutant that lacked the transcription factor Ace2, which influences virulence in other fungi. The Δace2 mutant had dysmorphic conidiophores, reduced conidia production, and abnormal conidial cell wall architecture. This mutant produced an orange pigment when grown on solid media, although its conidia had normal pigmentation. Conidia of the Δace2 mutant were larger and had accelerated germination. The resulting germlings were resistant to hydrogen peroxide, but not other stressors. Non-neutropenic mice that were immunosuppressed with cortisone acetate and infected with the Δace2 mutant had accelerated mortality, greater pulmonary fungal burden, and increased pulmonary inflammatory responses compared to mice infected with the wild-type or Δace2∷ace2 complemented strains. The Δace2 mutant had reduced ppoC, ecm33, and ags3 mRNA expression. It is known that A. fumigatus mutants with absent or reduced expression of these genes have increased virulence in mice, as well as other phenotypic similarities to the Δace2 mutant. Therefore, reduced expression of these genes likely contributes to the increased virulence of the Δace2 mutant. PMID:19220748

  11. Spatially distributed influence of agro-environmental factors governing nitrate fate and transport in an irrigated stream-aquifer system

    Science.gov (United States)

    Bailey, R. T.; Ahmadi, M.; Gates, T. K.; Arabi, M.

    2015-12-01

    Elevated levels of nitrate (NO3) in groundwater systems pose a serious risk to human populations and natural ecosystems. As part of an effort to remediate NO3 contamination in irrigated stream-aquifer systems, this study elucidates agricultural and environmental parameters and processes that govern NO3 fate and transport at the regional (500 km2), local (50 km2), and field scales (humus decomposition also dominate or partially dominate in other locations. Each factor, with the exception of O2 reduction rate, is the dominating influence on NO3 groundwater concentration at one or more locations within the study area. Results can be used to determine critical processes and key management actions for future data collection and remediation strategies, with efforts able to be focused on localized areas.

  12. 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.

  13. 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

  14. 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

  15. Collaborative Governance of Protected Areas: Success Factors and Prospects for Hin Nam No National Protected Area, Central Laos

    Directory of Open Access Journals (Sweden)

    Mirjam de Koning

    2017-01-01

    Full Text Available Collaborative governance of protected areas has emerged as a response to failures of, and ethical concerns about, centralised environmental governance. This paper assesses the governance of the Hin Nam No National Protected Area in central Laos to identify the conditions that support successful collaborative governance. Our analysis is based on the argument that collaborative governance is more likely to be successful under conditions that provide incentives for community engagement, formal mechanisms for power sharing, local ownership of resources, downward accountability, mechanisms for building trust, and an adaptive approach to performance assessment and improvement. We show that collaborative governance in Hin Nam No demonstrates the potential for a more decentralised and democratic system of governance based on customary rights, but requires ongoing political will to consolidate and sustain these arrangements. The findings of this study contribute to the growing literature on collaborative governance of protected areas in Asia and elsewhere.

  16. 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

  17. Prevalence of Sexual Harassment and its Associated Factors among Registered Nurses Working in Government Hospitals in Melaka State, Malaysia.

    Science.gov (United States)

    Suhaila, O; Rampal, K G

    2012-10-01

    This study focuses on sexual harassment, a form of psycological hazard that female registered nurses face throughout their day to day routine. The objective of this study is to find the prevalence of sexual harassment among female registered nurses working in government hospitals in Melaka, Malaysia and factors affecting them. This is a cross sectional study conducted on 455 female registered nurses who have worked more than one year in the present 3 government hospitals in Melaka, Malaysia. A validated and pre tested questionnaires were given for the respondents to answer. Before respondents answer the questionaires, they are required to read the definition and the forms of sexual harassment provided. This is to help them to understand the correct definition and forms of sexual harassment that they could have experienced. The researcher is available during the distribution of the questionnaires and the respondents are free to ask the researcher anything that they do not understand about it. The results of this study show that the prevalence of sexual harassment among these nurses was 51.2% with the past one year incidence recorded at 22.8%. The most common forms of sexual harassment were verbal (46.6% ), visual (24.8% ), psycological (20.9%), physical (20.7%) and non -verbal (16.7% ). The study showed that 74.7% of the victims suffered from psychological effects brought upon by their encounter with various types of sexual harrasement at work. The study also found that the victims' self-perception of their physicality was a contributing factor to the prevalance of this situation. Those who were pretty, with attractive body figure, a friendly character and easy going had a higher prevalence of sexual harassment in the workplace. Meanwhile, those who were strict, and those who had a fierce character were not prone to sexual harassment. The prevalence of sexual harassment among registered nurses in the workplace found in this study was high and self-perception profile

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

    Science.gov (United States)

    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.

  19. Factor Configurations with Governance as Conditions for Low HIV/AIDS Prevalence in HIV/AIDS Recipient Countries: Fuzzy-set Analysis.

    Science.gov (United States)

    Lee, Hwa-Young; Yang, Bong-Min; Kang, Minah

    2015-11-01

    This paper aims to investigate whether good governance of a recipient country is a necessary condition and what combinations of factors including governance factor are sufficient for low prevalence of HIV/AIDS in HIV/AIDS aid recipient countries during the period of 2002-2010. For this, Fuzzy-set Qualitative Comparative Analysis (QCA) was used. Nine potential attributes for a causal configuration for low HIV/AIDS prevalence were identified through a review of previous studies. For each factor, full membership, full non-membership, and crossover point were specified using both author's knowledge and statistical information of the variables. Calibration and conversion to a fuzzy-set score were conducted using Fs/QCA 2.0 and probabilistic tests for necessary and sufficiency were performed by STATA 11. The result suggested that governance is the necessary condition for low prevalence of HIV/AIDS in a recipient country. From sufficiency test, two pathways were resulted. The low level of governance can lead to low level of HIV/AIDS prevalence when it is combined with other favorable factors, especially, low economic inequality, high economic development and high health expenditure. However, strengthening governance is a more practical measure to keep low prevalence of HIV/AIDS because it is hard to achieve both economic development and economic quality. This study highlights that a comprehensive policy measure is the key for achieving low prevalence of HIV/AIDS in recipient country.

  20. 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

  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.

  2. Early Life Stress and Sleep Restriction as Risk Factors in PTSD: An Integrative Pre-Clinical Approach

    Science.gov (United States)

    2014-04-01

    that CCK increases glutamatergic transmission in the DG (Sinton, 1988; Gabriel et al., 1996; Deng et al., 2010) as well as long-term potentiation (LTP...patterns of selected GABAergic and Glutamatergic factors in the ventral and dorsal hippocampus and in the BLA One-way ANOVA followed by post hoc...Table 2: Effects of an Exposure to Juvenile Stress, UWT and UWT reminder. Protein expression of GABAergic and glutamatergic factors was assessed in the

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Possible environmental factors underlying amphibian decline in eastern Puerto Rico: Analysis of U.S. government data archives

    Science.gov (United States)

    Stallard, R.F.

    2001-01-01

    The past three decades have seen major declines in populations of several species of amphibians at high elevations in eastern Puerto Rico, a region unique in the humid tropics because of the degree of environmental monitoring that has taken place through the efforts of U.S. government agencies. I examined changes in environmental conditions by examining time-series data sets that extend back at least into the 1980s, a period when frog populations were declining. The data include forest cover; annual mean, minimum, and maximum daily temperature; annual rainfall; rain and stream chemistry; and atmospheric-dust transport. I examined satellite imagery and air-chemistry samples from a single National Aeronautics and Space Administration aircraft flight across the Caribbean showing patches of pollutants, described as thin sheets or lenses, in the lower troposphere. The main source of these pollutants appeared to be fires from land clearing and deforestation, primarily in Africa. Some pollutant concentrations were high and, in the case of ozone, approached health limits set for urban air. Urban pollution impinging on Puerto Rico, dust generation from Africa (potential soil pathogens), and tropical forest burning (gaseous pollutants) have all increased during the last three decades, overlapping the timing of amphibian declines in eastern Puerto Rico. None of the data sets pointed directly to changes so extreme that they might be considered a direct lethal cause of amphibian declines in Puerto Rico. More experimental research is required to link any of these environmental factors to this problem.

  12. On Factors Influencing the Process of Government Innovation in Foreign Countries%国外政府创新过程中的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    李兆友; 董健

    2014-01-01

    政府创新研究应当加强本体性关怀与过程性关怀。从政府创新本体视阈审思,政府创新本质上是一种多种影响因素之间相互作用的过程。这些影响因素在政府创新不同阶段所释放出不同的功能,总结各种影响因素在政府创新过程中的积极作用与负面障碍,以此实现政府创新成功经验与失效成因的理性观照,从而在政府创新的一般性规律与政府创新的运行现实之间建立起真实的关系。%The research of government innovation should pay more attention to the subject and the process of innovation. From the perspective of innovating subject, government innovation is a process of interactions among a variety of factors. However, nowadays, the study of the factors that influence government innovation is in lack of in-depth macroscopic classifications and microscopic interpretations in foreign countries. In this paper, we take political factors, governmental factors and social factors as the objects of our research, discuss their functions in the process of government innovation and describe their positive and negative effects. Our purpose is to engage in a rational reflection on the successes and failures in the process of government innovation, and establish real connections between the general patterns and the practical realities in the process of government innovation.

  13. Statistical study to identify the key factors governing ground water recharge in the watersheds of the arid Central Asia.

    Science.gov (United States)

    Zhu, Binq-Qi; Wang, Yue-Ling

    2016-01-01

    Understanding the source and recharge of ground waters is of great significance to our knowledge in hydrological cycles in arid environments over the world. Northern Xinjiang in northwestern China is a significant repository of information relating to the hydrological evolution and climatic changes in central Asia. In this study, two multivariate statistical techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to assess the ground water recharge and its governing factors, with the principal idea of exploring the above techniques to utilize all available hydrogeochemical variables in the quality assessment, which are not considered in the conventional techniques like Stiff and Piper diagrams. Q-mode HCA and R-mode PCA were combined to partition the water samples into seven major water clusters (C1-C7) and three principal components (PC1-PC3, PC1 salinity, PC2 hydroclimate, PC3 contaminant). The water samples C1 + C4 were classified as recharge area waters (Ca-HCO3 water), C2 + C3 as transitional zone waters (Ca-Mg-HCO3-SO4 water), and C5 + C6 + C7 as discharge area waters (Na-SO4 water). Based on the Q-mode PCA scores, three groups of geochemical processes influencing recharge regimes were identified: geogenic (i.e., caused by natural geochemical processes), geomorphoclimatic (caused by topography and climate), and anthropogenic (caused by ground water contamination). It is proposed that differences in recharge mechanism and ground water evolution, and possible bedrock composition difference, are responsible for the chemical genesis of these waters. These will continue to influence the geochemistry of the northern Xinjiang drainage system for a long time due to its steady tectonics and arid climate. This study proved that the chemistry differentiation of ground water can effectively support the identification of ground water recharge and evolution patterns.

  14. 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

    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 m......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...

  15. 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.

  16. Theorizing governance

    NARCIS (Netherlands)

    Gupta, J.; Verrest, H.; Jaffe, R.; Gupta, J.; Pfeffer, K.; Verrest, H.; Ros-Tonen, M.

    2015-01-01

    This chapter presents an overview of governance theories and discusses the emergence of governance as an analytical and a normative tool. It reviews theories that conceptualize the relations between different governance actors, including debates on interactive and hybrid governance, and presents

  17. Interactive governance

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob; Peters, B. Guy

    Governance has become one of the most commonly used concepts in contemporary political science. It is, however, often used to mean a variety of different things. This book helps to clarify this conceptual muddle by concentrating on one variety of governance-interactive governance. The authors argue...... that although the state may remain important for many aspects of governing, interactions between state and society represent an important, and perhaps increasingly important, dimension of governance. These interactions may be with social actors such as networks, with market actors or with other governments......, but all these forms represent means of governing involving mixtures of state action with the actions of other entities.This book explores thoroughly this meaning of governance, and links it to broader questions of governance. In the process of explicating this dimension of governance the authors also...

  18. 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

  19. 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

  20. 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.

  1. Effects of 3 weeks GMP oral administration on glutamatergic parameters in mice neocortex.

    Science.gov (United States)

    Ganzella, Marcelo; Moreira, Julia Dubois; Almeida, Roberto Farina; Böhmer, Ana Elisa; Saute, Jonas Alex Morales; Holmseth, Silvia; Souza, Diogo Onofre

    2012-03-01

    Overstimulation of the glutamatergic system (excitotoxicity) is involved in various acute and chronic brain diseases. Several studies support the hypothesis that guanosine-5'-monophosphate (GMP) can modulate glutamatergic neurotransmission. The aim of this study was to evaluate the effects of chronically administered GMP on brain cortical glutamatergic parameters in mice. Additionally, we investigated the neuroprotective potential of the GMP treatment submitting cortical brain slices to oxygen and glucose deprivation (OGD). Moreover, measurements of the cerebrospinal fluid (CSF) purine levels were performed after the treatment. Mice received an oral administration of saline or GMP during 3 weeks. GMP significantly decreases the cortical brain glutamate binding and uptake. Accordingly, GMP reduced the immunocontent of the glutamate receptors subunits, NR2A/B and GluR1 (NMDA and AMPA receptors, respectively) and glutamate transporters EAAC1 and GLT1. GMP treatment significantly reduced the immunocontent of PSD-95 while did not affect the content of Snap 25, GLAST and GFAP. Moreover, GMP treatment increased the resistance of neocortex to OGD insult. The chronic GMP administration increased the CSF levels of GMP and its metabolites. Altogether, these findings suggest a potential modulatory role of GMP on neocortex glutamatergic system by promoting functional and plastic changes associated to more resistance of mice neocortex against an in vitro excitotoxicity event.

  2. Kölliker-Fuse GABAergic and glutamatergic neurons project to distinct targets.

    Science.gov (United States)

    Geerling, Joel C; Yokota, Shigefumi; Rukhadze, Irma; Roe, Dan; Chamberlin, Nancy L

    2017-06-01

    The Kölliker-Fuse nucleus (KF) is known primarily for its respiratory function as the "pneumotaxic center" or "pontine respiratory group." Considered part of the parabrachial (PB) complex, KF contains glutamatergic neurons that project to respiratory-related targets in the medulla and spinal cord (Yokota, Oka, Tsumori, Nakamura, & Yasui, 2007). Here we describe an unexpected population of neurons in the caudal KF and adjacent lateral crescent subnucleus (PBlc), which are γ-aminobutyric acid (GABA)ergic and have an entirely different pattern of projections than glutamatergic KF neurons. First, immunofluorescence, in situ hybridization, and Cre-reporter labeling revealed that many of these GABAergic neurons express FoxP2 in both rats and mice. Next, using Cre-dependent axonal tracing in Vgat-IRES-Cre and Vglut2-IRES-Cre mice, we identified different projection patterns from GABAergic and glutamatergic neurons in this region. GABAergic neurons in KF and PBlc project heavily and almost exclusively to trigeminal sensory nuclei, with minimal projections to cardiorespiratory nuclei in the brainstem, and none to the spinal cord. In contrast, glutamatergic KF neurons project heavily to the autonomic, respiratory, and motor regions of the medulla and spinal cord previously identified as efferent targets mediating KF cardiorespiratory effects. These findings identify a novel, GABAergic subpopulation of KF/PB neurons with a distinct efferent projection pattern targeting the brainstem trigeminal sensory system. Rather than regulating breathing, we propose that these neurons influence vibrissal sensorimotor function. © 2017 Wiley Periodicals, Inc.

  3. "Wind of change": the role of human centered healthcare factors in the implementation of clinical governance in an Italian University teaching hospital.

    Science.gov (United States)

    Specchia, Maria Lucia; de Belvis, Antonio Giulio; Parente, Paolo; Avolio, Maria; Ricciardi, Walter; Damiani, Gianfranco

    2016-01-01

    Clinical governance (CG) is an approach to quality improvement in healthcare aimed at achieving a patient-centered health care system. The main objective of this study was to highlight human centered healthcare latent factors underlying the results of a CG assessment performed in the teaching hospital "A. Gemelli" of Rome, Italy. CG implementation levels were assessed through OPTIGOV© (OPTimizing healthcare GOVernance), a CG scorecard methodology. In order to identify the variables generating latent factors that can influence the governance of the Hospital, the multiple correspondence analysis (MCA) was applied. The application of OPTIGOV© showed a good CG implementation level in the Gemelli Hospital. By applying MCA, the variables aggregated so as to define 3 latent factors (F1: assessment for people oriented improvement strategy; F2: assessment for people targeted management; F3: tracking for timely accountable people) explaining as a whole 82.68% of the total variance and respectively 48.09% (F1), 24.95% (F2) and 9.64% (F3). The heuristic interpretation of the three latent factors could bring back to the concept of humanization in healthcare. This study shows that in the teaching hospital "A. Gemelli" humanization in healthcare is the driver of health care quality improvement.

  4. 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.

  5. 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.

  6. Variation at Local Government Level in the Support for Families of Severely Disabled Children and the Factors that Affect It

    Science.gov (United States)

    Forsyth, Rob; McNally, Richard; James, Peter; Crossland, Kevin; Woolley, Mark; Colver, Allan

    2010-01-01

    Aim: The aim of this study was to examine geographical variability in the support for families caring for children with severe disabilities as well as the relationships between this variability and local government social and educational performance indicators. Method: Data were collected from a cross-sectional, self-completed postal survey of the…

  7. The Factors of Local Energy Transition in the Seoul Metropolitan Government: The Case of Mini-PV Plants

    Directory of Open Access Journals (Sweden)

    Jae-Seung Lee

    2017-03-01

    Full Text Available As a way of enhancing urban sustainability, Seoul Special City, the capital of South Korea, has shown strong enthusiasm for urban energy transition by tackling climate change and expanding renewable energy. The Seoul Metropolitan Government (SMG has adopted the “One Less Nuclear Power Plant (OLNPP” strategy since April 2012 and specific policy measures, including a mini-photovoltaic (PV plant program, were introduced to facilitate the energy transition. However, varying degrees of success were achieved by 25 district-level local governments (Gu with mini-PV plant programs. This study explored the reason why those local governments showed different levels of performance despite the strong will of municipal government (SMG to implement urban energy transitions through the mini-PV plant program. The tested hypotheses were based on capacity, political context, public awareness and geographical diffusion. The findings indicated that institutional capacity, financial dependence, political orientation and public perception had positively affected the performance of mini-PV plant installation at each district level. Especially, the political will of each district mayor played an important role in the implementation of the policy.

  8. Factors Influencing Low Level of Women Participation in Literacy Programme in Maiha Local Government Area of Adamawa State

    Science.gov (United States)

    Daniel, Aminchi

    2015-01-01

    This study was designed to determine the extent to which poverty, gender stereotype, socio-cultural belief and lack of awareness influence low level of women participation in literacy programme in Maiha Local Government Area of Adamawa State. Survey designed was adopted for the study and a sample consisting of three hundred (300) women who were…

  9. Factors influencing current interests and motivations of local governments to supply carbon offset credits from urban forestry

    Science.gov (United States)

    N. Poudyal; J. Siry; M. Bowker

    2009-01-01

    This study conducted a nationwide survey of municipal governments in the United States to assess their motivations, willingness, and technical as well as managerial capacities of cities to store carbon and sell carbon offsets. The analysis reveals that cities are fairly interested in selling carbon offsets and their interest in carbon trading is driven by the degree of...

  10. Interactive governance

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob; Peters, B. Guy

    that although the state may remain important for many aspects of governing, interactions between state and society represent an important, and perhaps increasingly important, dimension of governance. These interactions may be with social actors such as networks, with market actors or with other governments...... explore some of the more fundamental questions about governance theory. For example, although governance is talked about a great deal political science has done relatively little about how to measure this concept. Likewise, the term multi-level governance has become widely used but its important...

  11. Interactive Governance

    DEFF Research Database (Denmark)

    Bang, Henrik

    2016-01-01

    Governance analysis has exploded in recent years, and it has become nearly impossible to tell what difference the concept and practice of governance makes from those of government and state. In addition governance analysis has been placed more and more in the shadow of the new institutionalisms and...... and growth. However, interactive governance is not a property or effect of institutions; nor does it apply solely to those individuals who seek success above everything else. It is connective more than individualistic or collectivistic in nature; and it manifests a governability capacity which...

  12. Corporate Governance and Shareholder Litigation

    OpenAIRE

    Kalchev, Georgi

    2009-01-01

    The probability for shareholder litigation is studied and how corporate governance characteristics and other factors explain it. Shareholder litigation results from failure of corporate governance. Thus a better quality of corporate governance is hypothesized to decrease the litigation probability. Corporate governance index is constructed based on principal components. It is found to be a significant predictor of shareholder litigation.

  13. Herdsmen and Livestock Farmers’ Perception, Attitudes and Risk Factors towards Zoonotic Diseases in Awka North and South Local Government Areas, Southeastern Nigeria

    OpenAIRE

    2016-01-01

    A cross-sectional survey utilizing semi-structured questionnaires was used to study the herdsmen and livestock farmers’ perception, attitudes and risk factors towards zoonotic diseases in Awka North and South Local Government Area. Data obtained were analyzed using chi-square on SPSS (Version 15.0) at a significance level of p < 0.05 to determine possible associations between variables and perceptions of zoonotic diseases. Out of the 384 respondents, 214 (55.7%) had heard about zoonotic disea...

  14. Governing education

    NARCIS (Netherlands)

    Ria Bronneman-Helmers

    2011-01-01

    Governing education. Trends in Dutch education policy 1990-2010 The Dutch government is responsible for e a cohesive and properly functioning education system. This report discusses the way in which the government fulfilled that responsibility in the period 1990-2010.  The study is

  15. Occurrence factors of large vacant lots in central districts and their utilization by local governments in Japan

    Directory of Open Access Journals (Sweden)

    Takeshi Kobayashi

    2016-12-01

    Full Text Available In Japan, local cities experience a number of problems related to deterioration of residential environment, quality of public service, and vitalization of commercial land. Specifically, the presence of large vacant lots behind sizable stores, office buildings, hospitals, and factories devitalize urban activity and its landscape. Many local cities are seeking to actualize a sustainable compact city with an integrated population, commerce, traffic and other public services in ways that promote a low carbon and energy-conserving society. Against the backdrop of these issues, this study examines the occurrence of large vacant lots and their utilization by local governments in Japan based on a questionnaire and field survey. It highlights several cases in which a large vacant lot is used to forward the development of a compact city by a local government.

  16. Dysfunctional astrocytic and synaptic regulation of hypothalamic glutamatergic transmission in a mouse model of early-life adversity: relevance to neurosteroids and programming of the stress response.

    Science.gov (United States)

    Gunn, Benjamin G; Cunningham, Linda; Cooper, Michelle A; Corteen, Nicole L; Seifi, Mohsen; Swinny, Jerome D; Lambert, Jeremy J; Belelli, Delia

    2013-12-11

    Adverse early-life experiences, such as poor maternal care, program an abnormal stress response that may involve an altered balance between excitatory and inhibitory signals. Here, we explored how early-life stress (ELS) affects excitatory and inhibitory transmission in corticotrophin-releasing factor (CRF)-expressing dorsal-medial (mpd) neurons of the neonatal mouse hypothalamus. We report that ELS associates with enhanced excitatory glutamatergic transmission that is manifested as an increased frequency of synaptic events and increased extrasynaptic conductance, with the latter associated with dysfunctional astrocytic regulation of glutamate levels. The neurosteroid 5α-pregnan-3α-ol-20-one (5α3α-THPROG) is an endogenous, positive modulator of GABAA receptors (GABAARs) that is abundant during brain development and rises rapidly during acute stress, thereby enhancing inhibition to curtail stress-induced activation of the hypothalamic-pituitary-adrenocortical axis. In control mpd neurons, 5α3α-THPROG potently suppressed neuronal discharge, but this action was greatly compromised by prior ELS exposure. This neurosteroid insensitivity did not primarily result from perturbations of GABAergic inhibition, but rather arose functionally from the increased excitatory drive onto mpd neurons. Previous reports indicated that mice (dams) lacking the GABAAR δ subunit (δ(0/0)) exhibit altered maternal behavior. Intriguingly, δ(0/0) offspring showed some hallmarks of abnormal maternal care that were further exacerbated by ELS. Moreover, in common with ELS, mpd neurons of δ(0/0) pups exhibited increased synaptic and extrasynaptic glutamatergic transmission and consequently a blunted neurosteroid suppression of neuronal firing. This study reveals that increased synaptic and tonic glutamatergic transmission may be a common maladaptation to ELS, leading to enhanced excitation of CRF-releasing neurons, and identifies neurosteroids as putative early regulators of the stress

  17. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Menard, Claude

    2014-01-01

    Plural governance is a form of governance where a firm both makes and buys similar goods or services. Despite a widespread use of plural governance there are no transaction cost models of how plural governance affects performance. This paper reviews the literature about plural forms and proposes...... a model relating transaction cost and resource-based variables to the cost of the plural form. The model is then used to analyze when the plural form is efficient compared to alternative governance structures. We also use the model to discuss the strength of three plural form synergies....

  18. Program governance

    CERN Document Server

    Khan, Muhammad Ehsan

    2014-01-01

    FOUNDATION OF GOVERNANCEGovernanceDefining GovernanceGovernance at Multiple LevelsSummaryReferencesTransaction Cost EconomicsTransactions-Core Elements and Attributes     Behavioral Assumptions     Governance Structure AttributesHazards of Concern     Incomplete Contracting     Bilateral Dependency and Fundamental Transformation     Adaptation or MaladaptationLinking Governance, Governance Structures, and ContractsThe Impact of Asset Specificity and Behavioral Assumptions on ContractsAp

  19. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Menard, Claude

    2014-01-01

    Plural governance is a form of governance where a firm both makes and buys similar goods or services. Despite a widespread use of plural governance there are no transaction cost models of how plural governance affects performance. This paper reviews the literature about plural forms and proposes...... a model relating transaction cost and resource-based variables to the cost of the plural form. The model is then used to analyze when the plural form is efficient compared to alternative governance structures. We also use the model to discuss the strength of three plural form synergies....

  20. 我国证券公司治理绩效的因子分析%Factor Analysis of the Governance Performance of Securities Companies in China

    Institute of Scientific and Technical Information of China (English)

    陈毅

    2014-01-01

    证券公司是资本市场最重要的行为主体之一,我国证券公司虽已建立了董事会、监事会、独立董事等现代公司治理框架,但在实际运作中其职能行使上存在许多不规范的地方。2008年金融危机告诫我们,不仅需要提高证券公司的风险防范机制,更需要建立完善的公司治理结构,促使证券公司风险防范机制作用顺利发挥。通过因子分析法将证券公司内部治理变量综合成为四个因子,即规模激励因子、结构因子、监管因子和独立性因子,进而分析内部治理因子对证券公司经营绩效的影响。%The Securities firms is one of the most important actor in the capital market. Though securities firms in China have established a modern Corporate governance framework with the board of directors,the board of supervisors,independent directors,but there are many irregularities in the exercise of their functions.The financial crisis in 2008 warned us that securi-ties firms should not only improve the risk prevention mechanisms,but also need to establish sound corporate governance structure to ensure the risk prevention mechanism plays its supposed role.With a factor analysis of internal corporate governance,variables are categorized into four factors,namely the motivation and scale factor,the structure factor,the regulatory factor and the independent factors,and the effect of the internal governance factors on the performance of securities companies are analyzed.

  1. Internet Governance

    Directory of Open Access Journals (Sweden)

    Pedro Veiga

    2010-01-01

    Full Text Available It has now become quite obvious that the Internet has brought significant changes to our society and a break on how we lived before its emergence. It is still too early to assess the impact on society of the new services at our disposal, such as the capacity to communicate faster and cheaper on a global scale, access information and, perhaps more importantly, to produce and disseminate information in a way that is accessible to all.It is clear that the advent of the Information Society implies changes in our society that constitute a point of no return. However, contrary to what happened when we entered the Industrial Age about three centuries ago, when the changing process was slow and led by older individuals, these days the entrance into the Information Society is taking place rapidly and the decisive players are younger people. The global nature of the Internet, the possibility of producing and distributing any type of content in digital form at almost zero cost, as well as the vast number of people who use the web, have highlighted the need for new forms of intervention in a sector where there are many types of players. It is in this context that the problem of Internet Governance becomes a very current issue, inasmuch as one feels the need to guarantee a diversity of rights and duties, which may appear difficult to reconcile.This paper presents a brief overview of the main players and initiatives which, in the field of Internet Governance, have tried to contribute to turning this network into a factor for social development and democraticity on a global scale.

  2. The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube.

    Science.gov (United States)

    Hanotel, Julie; Bessodes, Nathalie; Thélie, Aurore; Hedderich, Marie; Parain, Karine; Van Driessche, Benoit; Brandão, Karina De Oliveira; Kricha, Sadia; Jorgensen, Mette C; Grapin-Botton, Anne; Serup, Palle; Van Lint, Carine; Perron, Muriel; Pieler, Tomas; Henningfeld, Kristine A; Bellefroid, Eric J

    2014-02-15

    The basic helix-loop-helix (bHLH) transcriptional activator Ptf1a determines inhibitory GABAergic over excitatory glutamatergic neuronal cell fate in progenitors of the vertebrate dorsal spinal cord, cerebellum and retina. In an in situ hybridization expression survey of PR domain containing genes encoding putative chromatin-remodeling zinc finger transcription factors in Xenopus embryos, we identified Prdm13 as a histone methyltransferase belonging to the Ptf1a synexpression group. Gain and loss of Ptf1a function analyses in both frog and mice indicates that Prdm13 is positively regulated by Ptf1a and likely constitutes a direct transcriptional target. We also showed that this regulation requires the formation of the Ptf1a-Rbp-j complex. Prdm13 knockdown in Xenopus embryos and in Ptf1a overexpressing ectodermal explants lead to an upregulation of Tlx3/Hox11L2, which specifies a glutamatergic lineage and a reduction of the GABAergic neuronal marker Pax2. It also leads to an upregulation of Prdm13 transcription, suggesting an autonegative regulation. Conversely, in animal caps, Prdm13 blocks the ability of the bHLH factor Neurog2 to activate Tlx3. Additional gain of function experiments in the chick neural tube confirm that Prdm13 suppresses Tlx3(+)/glutamatergic and induces Pax2(+)/GABAergic neuronal fate. Thus, Prdm13 is a novel crucial component of the Ptf1a regulatory pathway that, by modulating the transcriptional activity of bHLH factors such as Neurog2, controls the balance between GABAergic and glutamatergic neuronal fate in the dorsal and caudal part of the vertebrate neural tube.

  3. 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

  4. 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...

  5. Analysis of Factors that Influence the Willingness to Pay for Irrigation Water in the Kurdistan Regional Government, Iraq

    Directory of Open Access Journals (Sweden)

    Rezhen Harun

    2015-07-01

    Full Text Available Water availability has become a problem in many countries of the world. Water scarcity can be economic or physical. Agricultural water use accounts for about three quarters of total global consumption; in many developing countries, irrigation represents over 90% of the water used. The purpose of this paper is to explore the willingness to pay for irrigation water among the farmers from the boundaries governed by the Kurdistan Regional Government (KRG. During the field study, 236 farmers from KRG were interviewed. The collected data were analyzed for each of the precipitation zones of the area (secured (A and non-secured rainfed (B. The contingent valuation method was used to determine the willingness to pay for irrigation water. The following possible independent variables influencing farmers’ decisions were considered: the bid amounts; evaluation scale of the water deficit; source of water for irrigation; cultivated area; education and age of respondents; main agricultural activity. In Zone A, the median willingness to pay of the farmers that used ground water for irrigation is 20.28 USD/10 m3, and for the farmers that use other sources of water, the willingness to pay is 11.49 USD/10 m3. The median willingness to pay in Zone B is 18.56/10 m3.

  6. 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.

  7. 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.

  8. 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.

  9. Routine health information system utilization and factors associated thereof among health workers at government health institutions in East Gojjam Zone, Northwest Ethiopia.

    Science.gov (United States)

    Shiferaw, Atsede Mazengia; Zegeye, Dessalegn Tegabu; Assefa, Solomon; Yenit, Melaku Kindie

    2017-08-07

    Using reliable information from routine health information systems over time is an important aid to improving health outcomes, tackling disparities, enhancing efficiency, and encouraging innovation. In Ethiopia, routine health information utilization for enhancing performance is poor among health workers, especially at the peripheral levels of health facilities. Therefore, this study aimed to assess routine health information system utilization and associated factors among health workers at government health institutions in East Gojjam Zone, Northwest Ethiopia. An institution based cross-sectional study was conducted at government health institutions of East Gojjam Zone, Northwest Ethiopia from April to May, 2013. A total of 668 health workers were selected from government health institutions, using the cluster sampling technique. Data collected using a standard structured and self-administered questionnaire and an observational checklist were cleaned, coded, and entered into Epi-info version 3.5.3, and transferred into SPSS version 20 for further statistical analysis. Variables with a p-value of less than 0.05 at multiple logistic regression analysis were considered statistically significant factors for the utilization of routine health information systems. The study revealed that 45.8% of the health workers had a good level of routine health information utilization. HMIS training [AOR = 2.72, 95% CI: 1.60, 4.62], good data analysis skills [AOR = 6.40, 95%CI: 3.93, 10.37], supervision [AOR = 2.60, 95% CI: 1.42, 4.75], regular feedback [AOR = 2.20, 95% CI: 1.38, 3.51], and favorable attitude towards health information utilization [AOR = 2.85, 95% CI: 1.78, 4.54] were found significantly associated with a good level of routine health information utilization. More than half of the health workers working at government health institutions of East Gojjam were poor health information users compared with the findings of others studies. HMIS training, data

  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. 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.

  17. Apoptosis of glutamatergic neurons fails to trigger a neurogenic response in the adult neocortex.

    Science.gov (United States)

    Diaz, Frank; McKeehan, Nicholas; Kang, Wenfei; Hébert, Jean M

    2013-04-10

    Adult neurogenesis is actively studied in part because of the potential to manipulate endogenous neural stem and progenitor cells for tissue repair. Although constitutive generation of neurons in the adult rodent olfactory bulb and hippocampal dentate gyrus is widely accepted and stroke-induced generation of striatal inhibitory neurons consistently observed, evidence supporting the generation of neurons in the neocortex after neuronal loss remains slim. Nevertheless, a few studies suggested that targeted apoptosis of neocortical glutamatergic neurons could trigger the generation of new ones in the adult brain. In light of such studies, we tested whether apoptosis of glutamatergic cortical neurons using two novel transgenic approaches in mice, an inducible Caspase-8 protein and an inducible diphtheria toxin gene, results in new neurons. After a thorough analysis, no new neurons were detected in the neocortex. Interestingly, an increase in the expression of the neuroblast marker DCX was observed in both models, in some cases in cells with morphologies previously associated with poststroke neuroblasts, but DCX(+) cells coexpressed the oligodendrocyte precursor marker Olig2, suggesting caution when using DCX as a marker for neuroblasts after injury. Given that the adult neocortex lacks an innate potential to regenerate lost glutamatergic neurons, future strategies should concentrate on manipulating the differentiation potential of endogenous or exogenous precursor cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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.

  1. Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer's disease.

    Science.gov (United States)

    Vazin, Tandis; Ball, K Aurelia; Lu, Hui; Park, Hyungju; Ataeijannati, Yasaman; Head-Gordon, Teresa; Poo, Mu-ming; Schaffer, David V

    2014-02-01

    Alzheimer's disease (AD) is among the most prevalent forms of dementia affecting the aging population, and pharmacological therapies to date have not been successful in preventing disease progression. Future therapeutic efforts may benefit from the development of models that enable basic investigation of early disease pathology. In particular, disease-relevant models based on human pluripotent stem cells (hPSCs) may be promising approaches to assess the impact of neurotoxic agents in AD on specific neuronal populations and thereby facilitate the development of novel interventions to avert early disease mechanisms. We implemented an efficient paradigm to convert hPSCs into enriched populations of cortical glutamatergic neurons emerging from dorsal forebrain neural progenitors, aided by modulating Sonic hedgehog (Shh) signaling. Since AD is generally known to be toxic to glutamatergic circuits, we exposed glutamatergic neurons derived from hESCs to an oligomeric pre-fibrillar forms of Aβ known as "globulomers", which have shown strong correlation with the level of cognitive deficits in AD. Administration of such Aβ oligomers yielded signs of the disease, including cell culture age-dependent binding of Aβ and cell death in the glutamatergic populations. Furthermore, consistent with previous findings in postmortem human AD brain, Aβ-induced toxicity was selective for glutamatergic rather than GABAeric neurons present in our cultures. This in vitro model of cortical glutamatergic neurons thus offers a system for future mechanistic investigation and therapeutic development for AD pathology using human cell types specifically affected by this disease. © 2013.

  2. 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.

  3. The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube

    DEFF Research Database (Denmark)

    Hanotel, Julie; Bessodes, Nathalie; Thélie, Aurore

    2014-01-01

    The basic helix-loop-helix (bHLH) transcriptional activator Ptf1a determines inhibitory GABAergic over excitatory glutamatergic neuronal cell fate in progenitors of the vertebrate dorsal spinal cord, cerebellum and retina. In an in situ hybridization expression survey of PR domain containing gene...... and glutamatergic neuronal fate in the dorsal and caudal part of the vertebrate neural tube....... and a reduction of the GABAergic neuronal marker Pax2. It also leads to an upregulation of Prdm13 transcription, suggesting an autonegative regulation. Conversely, in animal caps, Prdm13 blocks the ability of the bHLH factor Neurog2 to activate Tlx3. Additional gain of function experiments in the chick neural...... tube confirm that Prdm13 suppresses Tlx3(+)/glutamatergic and induces Pax2(+)/GABAergic neuronal fate. Thus, Prdm13 is a novel crucial component of the Ptf1a regulatory pathway that, by modulating the transcriptional activity of bHLH factors such as Neurog2, controls the balance between GABAergic...

  4. Variation at local government level in the support for families of severely disabled children and the factors that affect it.

    Science.gov (United States)

    Forsyth, Rob; McNally, Richard; James, Peter; Crossland, Kevin; Woolley, Mark; Colver, Allan

    2010-11-01

    The aim of this study was to examine geographical variability in the support for families caring for children with severe disabilities as well as the relationships between this variability and local government social and educational performance indicators. Data were collected from a cross-sectional, self-completed postal survey of the families of 5862 children and young people (aged 0-24 y, mean 10 y 7 mo; 68% male) with severe disabilities resulting in a variety of impairments (21% with autism spectrum disorders, 16% with learning disabilities,* 13% with emotional and behavioural difficulties, and 13% with cerebral palsy [CP]). Data on the severity of intrinsic impairment were assessed using the Health Utilities Index, and the need for support was assessed from the results of a novel parent-completed questionnaire, the European Child Environment Questionnaire (ECEQ). These responses were related to data published by local authorities on educational and social policy. Higher levels of unmet need and lack of support, as reported by parents of children and young people with severe disabilities, are associated with greater impairment but not with socioeconomic deprivation. After controlling for impairment and diagnosis, variation at local government level is of the order of 1 to 1.5 ECEQ standard deviation scores. The best- and the worst-performing local authorities--in terms of the averages of the 'support' scores reported by their surveyed residents--cluster in urban areas. For children with CP, a positive correlation was found between the reported unmet educational support requirements in each local authority area and rates of mainstream school placement for children with special educational needs. This indicates that the placement of children with disabilities into mainstream schools is associated with reported unmet need (r=0.60; p=0.01). In the case of children with autism spectrum diagnoses, the provision of additional basic educational support in mainstream

  5. On the factors governing water vapor turbulence mixing in the convective boundary layer over land: Concept and data analysis technique using ground-based lidar measurements

    Energy Technology Data Exchange (ETDEWEB)

    Pal, Sandip, E-mail: sup252@PSU.EDU

    2016-06-01

    The convective boundary layer (CBL) turbulence is the key process for exchanging heat, momentum, moisture and trace gases between the earth's surface and the lower part of the troposphere. The turbulence parameterization of the CBL is a challenging but important component in numerical models. In particular, correct estimation of CBL turbulence features, parameterization, and the determination of the contribution of eddy diffusivity are important for simulating convection initiation, and the dispersion of health hazardous air pollutants and Greenhouse gases. In general, measurements of higher-order moments of water vapor mixing ratio (q) variability yield unique estimates of turbulence in the CBL. Using the high-resolution lidar-derived profiles of q variance, third-order moment, and skewness and analyzing concurrent profiles of vertical velocity, potential temperature, horizontal wind and time series of near-surface measurements of surface flux and meteorological parameters, a conceptual framework based on bottom up approach is proposed here for the first time for a robust characterization of the turbulent structure of CBL over land so that our understanding on the processes governing CBL q turbulence could be improved. Finally, principal component analyses will be applied on the lidar-derived long-term data sets of q turbulence statistics to identify the meteorological factors and the dominant physical mechanisms governing the CBL turbulence features. - Highlights: • Lidar based study for CBL turbulence features • Water vapor and aerosol turbulence profiles • Processes governing boundary layer turbulence profiles using lidars.

  6. 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

  7. Experimentalist governance

    NARCIS (Netherlands)

    Sabel, C.F.; Zeitlin, J.; Levi-Faur, D.

    2012-01-01

    A secular rise in volatility and uncertainty is overwhelming the capacities of conventional hierarchical governance and ‘command-and-control’ regulation in many settings. One significant response is the emergence of a novel, ‘experimentalist’ form of governance that establishes deliberately

  8. Remaking Governance.

    Science.gov (United States)

    Carver, John

    2000-01-01

    The Policy Governance model's philosophical foundations lie in Rousseau's social contract, Greenleaf's servant-leadership, and modern management theory. Policy Governance stresses primacy of the owner-representative role; full-board authority; superintendents as chief executive officers; authoritative prescription of "ends," bounded freedom for…

  9. Corporate Governance

    OpenAIRE

    International Finance Corporation; UN Global Compact

    2017-01-01

    Corporate citizenship - a commitment to ethical behavior in business strategy, operations, and culture - has been on the periphery of corporate governance and board leadership, linked mainly to corporate reputation. However, in today’s globalized and interconnected world, investors, creditors, and other stakeholders have come to recognize that environmental, social, and governance responsi...

  10. Factors associated with support for smoke-free policies among government workers in Six Chinese cities: a cross-sectional study.

    Science.gov (United States)

    Kegler, Michelle C; Hua, Xinwei; Solomon, Madeleine; Wu, Yiqun; Zheng, Pin Pin; Eriksen, Michael

    2014-11-04

    A certain level of public support for smoke-free environments is a prerequisite for adoption and enforcement of policies and can be used as an indicator of readiness for legislative action. This study assessed support for comprehensive smoke-free policies in a range of settings such as hotels and colleges among government workers in China and identified factors associated with support for smoke-free policies. Understanding the extent to which government workers, a large segment of the working population in China, report a smoke-free workplace and support for smoke-free policies may be important indicators of readiness for strengthened policies given their role in formulating, implementing and enforcing regulations. Data were from an evaluation of the Tobacco Free Cities initiative of Emory University's Global Health Institute-China Tobacco Control Partnership. Self-administered surveys were completed by 6,646 workers in 160 government agencies in six Chinese cities. Multivariate logistic regression was used to identify factors associated with support for smoke-free worksites, bars, hotels, and colleges. Over half (54.6%) of participants were male. A large percentage of the male workers smoked (45.9%,) whereas very few women did (1.9%). Fewer than 50% of government workers reported smoke-free policies at work, with 19.0% reporting that smoking is allowed anywhere. Support for smoke-free policies was generally very high, with the lowest levels of support for smoke-free bars (79.0%) and hotels (82.3%), higher levels of support for restaurants (90.0%) and worksites (93.0%), and above 95% support for hospitals, schools, colleges, public transportation and religious settings. Knowledge of the harmfulness of secondhand smoke was positively associated with support for smoke-free policies. Stricter worksite smoking policies were associated with support for smoke-free workplaces and bars, but not hotels and colleges. Women and nonsmokers were more supportive of smoke

  11. Evaluating the Governing Factors of Variability in Nocturnal Boundary Layer Height Based on Elastic Lidar in Wuhan.

    Science.gov (United States)

    Wang, Wei; Mao, Feiyue; Gong, Wei; Pan, Zengxin; Du, Lin

    2016-11-01

    The atmospheric boundary layer (ABL), an atmospheric region near the Earth's surface, is affected by surface forcing and is important for studying air quality, climate, and weather forecasts. In this study, long-term urban nocturnal boundary layers (NBLs) were estimated by an elastic backscatter light detection and ranging (LiDAR) with various methods in Wuhan (30.5° N, 114.4° E), a city in Central China. This study aims to explore two ABL research topics: (1) the relationship between NBL height (NBLH) and near-surface parameters (e.g., sensible heat flux, temperature, wind speed, and relative humidity) to elucidate meteorological processes governing NBL variability; and (2) the influence of NBLH variations in surface particulate matter (PM) in Wuhan. We analyzed the nocturnal ABL-dilution/ABL-accumulation effect on surface particle concentration by using a typical case. A long-term analysis was then performed from 5 December 2012-17 June 2016. Results reveal that the seasonal averages of nocturnal (from 20:00 to 05:00 next day, Chinese standard time) NBLHs are 386 ± 161 m in spring, 473 ± 154 m in summer, 383 ± 137 m in autumn, and 309 ± 94 m in winter. The seasonal variations in NBLH, AOD, and PM2.5 display a deep (shallow) seasonal mean NBL, consistent with a small (larger) seasonal mean PM2.5 near the surface. Seasonal variability of NBLH is partly linearly correlated with sensible heat flux at the surface (R = 0.72). Linear regression analyses between NBLH and other parameters show the following: (1) the positive correlation (R = 0.68) between NBLH and surface temperature indicates high (low) NBLH corresponding to warm (cool) conditions; (2) the slight positive correlation (R = 0.52) between NBLH and surface relative humidity in Wuhan; and (3) the weak positive correlation (R = 0.38) between NBLH and wind speed inside the NBL may imply that the latter is not an important direct driver that governs the seasonal variability of NBLH.

  12. Factors Affecting Student Success in Distance Learning Courses at a Local California Community College: Joint Governance Perspectives

    Science.gov (United States)

    Gonzalez, Luis A.

    2012-01-01

    The purpose of this study was to explore the perspectives of staff and faculty regarding factors affecting student success in distance learning at a California community college (CCC). Participants were members of the leadership group known as the distance learning committee. Data were collected through in-depth interviews using open-ended…

  13. Factors Affecting Student Success in Distance Learning Courses at a Local California Community College: Joint Governance Perspectives

    Science.gov (United States)

    Gonzalez, Luis A.

    2012-01-01

    The purpose of this study was to explore the perspectives of staff and faculty regarding factors affecting student success in distance learning at a California community college (CCC). Participants were members of the leadership group known as the distance learning committee. Data were collected through in-depth interviews using open-ended…

  14. A new corporate governance

    Directory of Open Access Journals (Sweden)

    Ion Bucur

    2015-12-01

    Full Text Available The issue of corporate governance has become increasingly important as globalisation has begun to accelerate and the economic and financial turmoil have intensified. Post-crisis context has imposed the need to expand the prospects for analysis over governance and companies, as well as the need to identify new ways of administration and resource management. From this perspective, the author aims to highlight the conditions, factors and events that have generated profound changes within the business environment, while the analysis is focusing on contemporary changes in the systems of corporate governance and economic mutations, especially in terms of the companies. The establishment of new governance rules is demanding a theoretical approach based on new methodological requirements which are needed to reform theoretical foundations and to promote creative and effective shapes and governance systems.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Diet is a major factor governing the fecal butyrate-producing community structure across Mammalia, Aves and Reptilia.

    Science.gov (United States)

    Vital, Marius; Gao, Jiarong; Rizzo, Mike; Harrison, Tara; Tiedje, James M

    2015-03-17

    Butyrate-producing bacteria have an important role in maintaining host health. They are well studied in human and medically associated animal models; however, much less is known for other Vertebrata. We investigated the butyrate-producing community in hindgut-fermenting Mammalia (n = 38), Aves (n = 8) and Reptilia (n = 8) using a gene-targeted pyrosequencing approach of the terminal genes of the main butyrate-synthesis pathways, namely butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). Most animals exhibit high gene abundances, and clear diet-specific signatures were detected with but genes significantly enriched in omnivores and herbivores compared with carnivores. But dominated the butyrate-producing community in these two groups, whereas buk was more abundant in many carnivorous animals. Clustering of protein sequences (5% cutoff) of the combined communities (but and buk) placed carnivores apart from other diet groups, except for noncarnivorous Carnivora, which clustered together with carnivores. The majority of clusters (but: 5141 and buk: 2924) did not show close relation to any reference sequences from public databases (identity <90%) demonstrating a large 'unknown diversity'. Each diet group had abundant signature taxa, where buk genes linked to Clostridium perfringens dominated in carnivores and but genes associated with Ruminococcaceae bacterium D16 were specific for herbivores and omnivores. Whereas 16S rRNA gene analysis showed similar overall patterns, it was unable to reveal communities at the same depth and resolution as the functional gene-targeted approach. This study demonstrates that butyrate producers are abundant across vertebrates exhibiting great functional redundancy and that diet is the primary determinant governing the composition of the butyrate-producing guild.

  17. Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food-Restricted Rats: Involvement of CB1 Receptors.

    Science.gov (United States)

    Talani, Giuseppe; Licheri, Valentina; Biggio, Francesca; Locci, Valentina; Mostallino, Maria Cristina; Secci, Pietro Paolo; Melis, Valentina; Dazzi, Laura; Carta, Gianfranca; Banni, Sebastiano; Biggio, Giovanni; Sanna, Enrico

    2016-04-01

    The endogenous endocannabinoid system has a crucial role in regulating appetite and feeding behavior in mammals, as well as working memory and reward mechanisms. In order to elucidate the possible role of cannabinoid type-1 receptors (CB1Rs) in the regulation of hippocampal plasticity in animals exposed to food restriction (FR), we limited the availability of food to a 2-h daily period for 3 weeks in Sprague-Dawley rats. FR rats showed a higher long-term potentiation at hippocampal CA1 excitatory synapses with a parallel increase in glutamate release when compared with animals fed ad libitum. FR rats showed a significant increase in the long-term spatial memory determined by Barnes maze. FR was also associated with a decreased inhibitory effect of the CB1R agonist win55,212-2 on glutamatergic field excitatory postsynaptic potentials, together with a decrease in hippocampal CB1R protein expression. In addition, hippocampal brain-derived neurotrophic factor protein levels and mushroom dendritic spine density were significantly enhanced in FR rats. Altogether, our data suggest that alterations of hippocampal CB1R expression and function in FR rats are associated with dendritic spine remodeling and functional potentiation of CA1 excitatory synapses, and these findings are consistent with increasing evidence supporting the idea that FR may improve cognitive functions.

  18. 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

  19. Explanatory factors for the use of the financial report in decision-making: Evidence from Local Government in Portugal

    Directory of Open Access Journals (Sweden)

    Sónia Paula S. Nogueira

    2016-07-01

    Two important implications of this study are the following: first, professional bodies and the financial situation in the country; while stimulating informational needs by internal users in the public sector they determine the usefulness they offer to financial reporting for decision-making. Second, the lack of knowledge of the accounting information system, especially by local politicians, is a hindering factor of the usefulness given to financial reporting for internal decision-making. Nowadays, when many countries are considering reforms of public sector accounting in line with the International Public Sector Accounting Standards (IPSAS, supposedly increasing the sophistication, the level of information and usefulness of financial reporting, such factors must be taken into account.

  20. Experimentalist governance

    OpenAIRE

    Sabel, C.F.; Zeitlin, J; D Levi-Faur

    2012-01-01

    A secular rise in volatility and uncertainty is overwhelming the capacities of conventional hierarchical governance and ‘command-and-control’ regulation in many settings. One significant response is the emergence of a novel, ‘experimentalist’ form of governance that establishes deliberately provisional frameworks for action and elaborates and revises these in light of recursive review of efforts to implement them in various contexts. Robust examples can be found in the United States and the E...

  1. Organizational governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Klein, Peter G.

    This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory, and the ......This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory...

  2. Corporate Governance

    Directory of Open Access Journals (Sweden)

    Dragoș-Mihail Daghie

    2011-05-01

    Full Text Available The purpose of this study is to analyze and understand the recently introduced form of managementof a company limited by shares. The Law no. 441/2006, which fundamentally amended Company Law,created this form of controlling the company, the corporate governance, but the legislation does not explicitlydefine what it wants to achieve through this instrument. This topic is recent in research as the theme ofgerman-roman commercial law systems (in French corporate governance system was introduced in 1966 andin Romania in 2006 but in terms of Anglo-Saxon law, the topic has been addressed years since 1776 (AdamSmith: The Wealth of Nations The concept of corporate governance would like, as a result, to establish somerules that companies must comply in order to achieve effective governance, transparent and beneficial forboth shareholders and for the minority. Corporate governance is a key element with an aim at improvingefficiency and economic growth in full accordance with the increase of investors’ confidence. Corporategovernance assumes a series of relationship between the company management, leadership, shareholders andthe other people concerned. Also corporate governance provides for that structure by means of which thecompany’s targets are set out and the means to achieve them and also the manner how to monitor such.

  3. A study on Surgical Site Infections (SSI and associated factors in a government tertiary care teaching hospital in Mysore, Karnataka

    Directory of Open Access Journals (Sweden)

    Naveen Kikkeri Hanumantha Setty

    2014-04-01

    Full Text Available Background: Surgical site infections (SSI are the most common nosocomial infection and frequently cause morbidity and mortality among inpatients of hospitals. The incidence varies from hospital to hospital. Several factors affect the development of SSI. Objectives: To study the incidence of and to identify the risk factors for Surgical Site Infections in the surgical wards of K.R.Hospital, Mysore. Materials and Methods: Study Period: July to August 2007 Study Subjects: One hundred and eighty patients who underwent various surgeries in the General Surgery department of K.R. Hospital Mysore. A predesigned and pretested proforma was used to collect the data. Surgical sites were examined and graded. Culture and sensitivity testing was done on infected wounds. Data was analyzed using SPSS 13 software. Results: Among 180 patients 39 (21.66% developed surgical site infections (SSI. Of 39 SSIs 20 were grade 3 and 19 were grade 4 infections. SSIs were found more commonly among the aged, males, underweight and overweight, anaemics, diabetics, hypertensives, patients with longer pre operative waiting time, with multiple blood transfusions and without antibiotic prophylaxis. Age, Sex, BMI, Diabetes mellitus, Blood transfusion and pre operative waiting had univariate statistical significance. Gender, extreme BMI, Diabetes mellitus and Blood transfusion remained independent predictors of surgical site infection in multivariate analysis. Most of the SSIs yielded multiple organisms and Staphylococcus aureus was the predominant. Resistance to tetracycline was most common. Conclusion: The incidence of SSI is high. Gender, extremes of BMI, diabetes mellitus and blood transfusion are the important risk factors for it.

  4. 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.

  5. 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.

  6. 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.

  7. A study of several factors governing the fatigue limits of austempered ductile cast iron with various microstructures

    Science.gov (United States)

    Kim, Jinhak; Kim, Sangtae; Kim, Mingun

    2000-06-01

    The effects the leading factors bearing on fatigue limits were investigated with three kinds of ductile iron specimens various microstructures. As a result of examination, the fatigue limits in relationship to hardness and tensile strength, the expected higher improvement for fatigue limits in the case of the high strength specimens that experienced austempering treatment are not observed in comparison with the specimens treated with stress relief treatment. The estimated maximum defect size is one of the important parameters in predicting and evaluating fatigue limits for three different heat-treated ductile cast irons. Also, a quantitative relationship can be established between the fatigue limit and maximum defect size. Moreover, it is possible to explain the difference in fatigue limits in the three ductile cast irons by application of the rates of non-propagating crack which connects the adjacent graphite nodules before it stops.

  8. An Empirical Analysis of Government Administrative Strategy: From the Governance, Competence and Relationship Perspectives

    National Research Council Canada - National Science Library

    Chiou Chi-Ho

    2013-01-01

      Employing the governance, competence and relationship perspectives, this article discusses what factors will enhance a government's administrative efficiency and effectiveness, and how to improve...

  9. Good Governance

    Directory of Open Access Journals (Sweden)

    S de la Harpe

    2008-08-01

    Full Text Available This issue of the Potchefstroom Electronic Law Journal (PELJ is entirely dedicated to the concept of good governance. It is the outcome of the first Summer/Winter school on Good Governance which was held at North-West University, Potchefstroom (SA in January 2006 and at Tilburg University, Tilburg (NL in January 2007. This Summer/Winter school has now become a yearly event with a bi-annual theme. Academic staff from both universities collaborate in teaching this course. Students from the two universities who participate in the Summer/Winter school have the unique possibility to deepen their knowledge on a particular subject while enjoying a cross-cultural learning environment. The subject of good governance was not selected by chance but was chosen because of its impact in many fields and the many ways in which the concept is used. It was time for a deeper insight into this multiple role of the concept of good governance. The contributions to this journal are the analytical outcome of the research done in preparation for the lectures given during the Summer/Winter school. As the contributions directly apply the good governance concept to various specific fields of expertise, this introduction will be used to give a short reflection on the concept as such.

  10. On the factors governing water vapor turbulence mixing in the convective boundary layer over land: Concept and data analysis technique using ground-based lidar measurements.

    Science.gov (United States)

    Pal, Sandip

    2016-06-01

    The convective boundary layer (CBL) turbulence is the key process for exchanging heat, momentum, moisture and trace gases between the earth's surface and the lower part of the troposphere. The turbulence parameterization of the CBL is a challenging but important component in numerical models. In particular, correct estimation of CBL turbulence features, parameterization, and the determination of the contribution of eddy diffusivity are important for simulating convection initiation, and the dispersion of health hazardous air pollutants and Greenhouse gases. In general, measurements of higher-order moments of water vapor mixing ratio (q) variability yield unique estimates of turbulence in the CBL. Using the high-resolution lidar-derived profiles of q variance, third-order moment, and skewness and analyzing concurrent profiles of vertical velocity, potential temperature, horizontal wind and time series of near-surface measurements of surface flux and meteorological parameters, a conceptual framework based on bottom up approach is proposed here for the first time for a robust characterization of the turbulent structure of CBL over land so that our understanding on the processes governing CBL q turbulence could be improved. Finally, principal component analyses will be applied on the lidar-derived long-term data sets of q turbulence statistics to identify the meteorological factors and the dominant physical mechanisms governing the CBL turbulence features.

  11. Stakeholder Governance

    DEFF Research Database (Denmark)

    Flak, Leif Skiftenes; Rose, Jeremy

    2005-01-01

    The e-government field, like most young fields, lacks a strong body of well-developed theory. One strategy for coping with theoretical immaturity is to import and adapt theories from other, more mature fields. This study reviews Stakeholder Theory (ST) and investigates its potential in relation...... to e-Government. Originally a management theory, stakeholder theory advocates addressing the concerns of all stakeholders in a firm, as opposed to concentration on the interests of senior managers and stockholders. Apart from the original profit focus, there is no serious conceptual mismatch between...... stakeholder theory and government’s objective of providing policy and services for citizens and organizations – society’s stakeholders. Potential problems with adapting a management theory to a government setting are discussed. The paper further discusses how information technology impacts a stakeholder model...

  12. Stakeholder Governance

    DEFF Research Database (Denmark)

    Flak, Leif Skiftenes; Rose, Jeremy

    2005-01-01

    The e-government field, like most young fields, lacks a strong body of well-developed theory. One strategy for coping with theoretical immaturity is to import and adapt theories from other, more mature fields. This study reviews Stakeholder Theory (ST) and investigates its potential in relation...... to e-Government. Originally a management theory, stakeholder theory advocates addressing the concerns of all stakeholders in a firm, as opposed to concentration on the interests of senior managers and stockholders. Apart from the original profit focus, there is no serious conceptual mismatch between...... stakeholder theory and government’s objective of providing policy and services for citizens and organizations – society’s stakeholders. Potential problems with adapting a management theory to a government setting are discussed. The paper further discusses how information technology impacts a stakeholder model...

  13. Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract.

    Science.gov (United States)

    Shankar, Jyoti; Solis, Norma V; Mounaud, Stephanie; Szpakowski, Sebastian; Liu, Hong; Losada, Liliana; Nierman, William C; Filler, Scott G

    2015-02-03

    Receipt of broad-spectrum antibiotics enhances Candida albicans colonization of the GI tract, a risk factor for haematogenously-disseminated candidiasis. To understand how antibiotics influence C. albicans colonization, we treated mice orally with vancomycin or a combination of penicillin, streptomycin, and gentamicin (PSG) and then inoculated them with C. albicans by gavage. Only PSG treatment resulted in sustained, high-level GI colonization with C. albicans. Furthermore, PSG reduced bacterial diversity in the colon much more than vancomycin. Both antibiotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-γ mRNA levels in the terminal ileum but had limited effect on the GI fungal microbiome. Through a series of models that employed Bayesian model averaging, we investigated the associations between antibiotic treatment, GI microbiota, and host immune response and their collective impact on C. albicans colonization. Our analysis revealed that bacterial genera were typically associated with either C. albicans colonization or altered cytokine expression but not with both. The only exception was Veillonella, which was associated with both increased C. albicans colonization and reduced IL-21 expression. Overall, antibiotic-induced changes in the bacterial microbiome were much more consistent determinants of C. albicans colonization than either the GI fungal microbiota or the GI immune response.

  14. Regulation of Insulin-Like Growth Factor Signaling by Yap Governs Cardiomyocyte Proliferation and Embryonic Heart Size

    Science.gov (United States)

    Xin, Mei; Kim, Yuri; Sutherland, Lillian B.; Qi, Xiaoxia; McAnally, John; Schwartz, Robert J.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.

    2012-01-01

    The Hippo signaling pathway regulates growth of the heart and other tissues. Hippo pathway kinases influence the activity of various targets, including the transcriptional coactivator Yap, but the specific role of Yap in heart growth has not been investigated. We show that Yap is necessary and sufficient for embryonic cardiac growth in mice. Deletion of Yap in the embryonic mouse heart impeded cardiomyocyte proliferation, causing myocardial hypoplasia and lethality at embryonic stage 10.5. Conversely, forced expression of a constitutively active form of Yap in the embryonic heart increased cardiomyocyte number and heart size. Yap activated the insulin-like growth factor (IGF) signaling pathway in cardiomyocytes, resulting in inactivation of glycogen synthase kinase 3β, which led to increased abundance of β-catenin, a positive regulator of cardiac growth. Our results point to Yap as a critical downstream effector of the Hippo pathway in the control of cardiomyocyte proliferation and a nexus for coupling the IGF, Wnt, and Hippo signaling pathways with the developmental program for heart growth. PMID:22028467

  15. 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.

  16. Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation.

    Science.gov (United States)

    Fanger, G R; Vaillancourt, R R; Heasley, L E; Montmayeur, J P; Johnson, G L; Maue, R A

    1997-01-01

    The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) beta receptors with mutations that eliminate activation of specific signalling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel alpha-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na+ channels while leaving the induction of type II alpha-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC gamma, GAP, and Syp abolished the induction of type II alpha-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na+ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na+ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.

  17. Prevalence, intensity of infection and risk factors of urinary schistosomiasis in pre-school and school aged children in Guma Local Government Area, Nigeria

    Institute of Scientific and Technical Information of China (English)

    EU Amuta; RS Houmsou

    2014-01-01

    Objective: To determine the prevalence and intensity of infection and the risk factors associated with urinary schistosomiasis in pre-school and school aged children in Guma Local Government Area of Benue State, Nigeria. Methods: Urine filtration technique using polycarbonate membrane filters was employed to process urine specimens and to determine presence of Schistosoma haematobium eggs in urine. Questionnaires were also administered to children to collect information on socio-demographic data and water-contact activities. Results: An overall prevalence of 55.0% (165/300) was recorded out of the 300 urine samples examined. Prevalence of infection varied between 36.0%-64.0% with a significant difference (χ2= 11.59, P=0.041) between the different communities visited. Males were more infected (60.6%, 103/170) than females (47.7%, 62/130) with a significant difference (χ2= 4.95, P=0.026). The age-related prevalence showed higher prevalence (70.5%, 36/52) in the 11-15 year old children than that in the 1-5 year old ones (44.9%, 53/118). A significant difference was observed in the prevalence between the age groups (χ2=10.56, P=0.014). The prevalence of light intensity of infection (1-49 eggs/10 mL of urine) (86.6%) was significantly higher than that of heavy intensity of infection (≥50 eggs/10 mL of urine) (13.3%) in the area (t=16.48, P=0.000). Water contact activities of the children revealed that children that were involved in irrigation and those that went swimming in water bodies were observed to be at higher risk of becoming infected with urinary schistosomiasis in the area with odd ratios (risk factors) of 2.756 (1.334-5.693) and 2.366 (1.131-4.948) respectively at P<0.05 level. Conclusions: The study revealed the hyperendemicity of urinary schistosomiasis in the pre-school and school aged children in Guma Local Government Area. It is therefore recommended that praziquantel should be administered to children in the area and systematic epidemiological

  18. 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.

  19. Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice.

    Science.gov (United States)

    Kroeger, Daniel; Ferrari, Loris L; Petit, Gaetan; Mahoney, Carrie E; Fuller, Patrick M; Arrigoni, Elda; Scammell, Thomas E

    2017-02-01

    The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states. More than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep-wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our

  20. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2012-01-01

    of knowledge, belief and opinions in which engineering is immersed. Thus the overall objective is explorative. By investigating the language, practices and techniques by which engineering is governed the chapter sets out to point to the presumptions, stipulations and ‘limits’ of the dominant discourses...

  1. Military Government

    Science.gov (United States)

    1949-07-01

    Public finance -------------------~·---------------------22 Civilian protection -------------------------------------23 Public health and sanitation...22. PUBLIC. ~INANCE.~q. Basic "planning data for public finance in- clude-- (1) ·rrax·ation systems: - .(2)- ~ethods of_tpaking appropriations.- ( 3...Probable ·adequacy- of public funds. (.4) Administrative .. _ organization for_ public finance sections. b. Military government -staff sections

  2. Government Organizations

    DEFF Research Database (Denmark)

    Krause Hansen, Hans; Salskov-Iversen, Dorte

    2017-01-01

    , with clearly defined boundaries between the public and private; and in terms of polycentrism, where power and authority are seen as dispersed among state and nonstate organizations, including business and civil society organizations. Globalization and new media technologies imply changes in the relationship...... democracy and the public sphere; and discourse approaches to studying the intersections of government, organizational change, and information and communication technology....

  3. Electronic Government

    DEFF Research Database (Denmark)

    Wimmer, Maria A.; Traunmüller, Roland; Grönlund, Åke

    This book constitutes the refereed proceedings of the 4th International Conference on Electronic Government, EGOV 2005, held in Copenhagen, Denmark, in August 2005. The 30 revised papers presented were carefully reviewed and selected from numerous submissions, and assess the state-of-the-art in e...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Glutamatergic synapse protein composition of wild-type mice is sensitive to in utero MTHFR genotype and the timing of neonatal vigabatrin exposure.

    Science.gov (United States)

    Zuckerman, Chava; Blumkin, Elinor; Melamed, Osnat; Golan, Hava M

    2015-10-01

    The enzyme methylenetetrahydrofolate-reductase (MTHFR) is part of the homocysteine and folate metabolic pathways. In utero, Mthfr-deficient environment has been reported as a risk factor for neurodevelopmental disorders such as autism and neural tube defects. Neonatal disruption of the GABAergic system is also associated with behavioral outcomes. The interaction between Mthfr deficiency and neonatal exposure to the GABA-potentiating drug vigabatrin (GVG) in mice alters anxiety, memory, and social behavior in a gender-dependent manner. In addition, a gender-dependent enhancement of proteins implicated in excitatory synapse plasticity in the cerebral cortex was shown. Here we show that in utero MTHFR deficiency is sufficient to alter the levels of glutamate receptor subunits GluR1, GluR2, and NR2B in the cerebral cortex and hippocampus of adult offspring with a WT genotype. In addition, FMRP1, CAMKII α and γ, and NLG1 levels in WT offspring were vulnerable to the in utero genotype. These effects depend on brain region and the cellular compartment tested. The effect of in utero MTHFR deficiency varies with the age of neonatal GVG exposure to modify GluR1, NR2A, reelin, CAMKII α, and NLG1 levels. These changes in molecular composition of the glutamatergic synapse were associated with increased anxiety-like behavior. Complex, multifactorial disorders of the nervous system show significant association with several genetic and environmental factors. Our data exemplify the contribution of an in utero MTHFR-deficient environment and early exposure to an antiepileptic drug to the basal composition of the glutamatergic synapses. The robust effect is expected to alter synapse function and plasticity and the cortico-hippocampal circuitry. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  11. Small government or big government?

    Directory of Open Access Journals (Sweden)

    MATEO SPAHO

    2015-03-01

    Full Text Available Since the beginning of the twentieth century, economists and philosophers were polarizedon their positions beyond the role that the government should have in the economy. On one hand John Maynard Keynes represented, within the optics of market economy, a position where the state should intervene in the economy to maintain the aggregate demand and the employment in the country, without hesitation in creating budget deficits and public debt expansion. This approach happens especially in the moments when the domestic economy and global economic trends show a weak growth or a recession. This means a heavy interference inthe economy, with higher income but with high expenditure to GDP too. On the other side, Liberals and Neoliberalsled by Friedrich Hayek advocated a withdrawal of the government from economic activity not just in moments of economic growth but also during the crisis, believing that the market has self-regulating mechanisms within itself. The government, as a result will have a smaller dimension with lower income and also low expenditures compared to the GDP of the country. We took the South-Eastern Europe countries distinguishing those with a "Big Government" or countries with "Small Government". There are analyzed the economic performances during the global crisis (2007-2014. In which countries the public debt grew less? Which country managed to attract more investments and which were the countries that preserved the purchasing power of their consumers? We shall see if during the economic crisis in Eastern Europe the Great Government or the Liberal and "Small" one has been the most successful the model.

  12. 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

  13. Governing factors in resurgence of prostitution and whoring and legal countermeasures%浅议卖淫嫖娼沉渣泛起的主要因素及法律对策

    Institute of Scientific and Technical Information of China (English)

    曹育明

    1997-01-01

    In the early period after liberation,prostitution and whoring in China were condemned and brougt under control by the Party and government,and vanished eventually.Recently,however,owing to various complicate causes,the activities of prostitution and whoring have revived and spread quickly over vast regions,Corrupting public morals and inducing svevere problems of public security.The rigorous suppression and sanction by the government yield limited results.This paper deals with the governing factors in resurgence of prostitution and whoring and the relevant legal problems so as to arouse the concern and stimulate the study by the legal circles.

  14. Prevalence of Antenatal Depression and Associated Risk Factors among Pregnant Women Attending Antenatal Clinics in Abeokuta North Local Government Area, Nigeria.

    Science.gov (United States)

    Thompson, Okechukwu; Ajayi, IkeOluwapo

    2016-01-01

    Objective. The prevalence of antenatal depression (AD) and associated risk factors among pregnant women attending antenatal clinics in Abeokuta North Local Government Area, Nigeria, was determined. Methods. A descriptive cross-sectional survey was conducted, interviewing 314 pregnant women selected by multistage sampling technique from among those attending antenatal clinics. Information was collected using structured questionnaire and a screening tool, Edinburgh Postnatal Depression Scale (EPDS), to assess probable depression. Results. The prevalence of antenatal depression was 24.5%. There were significant associations between antenatal depression and attending public health facility (P = 0.000), young maternal age (P = 0.012), single marital status (P = 0.010), not having formal education (P = 0.022), large family size (P = 0.029), planned pregnancy (P = 0.014), coexisting medical conditions (P = 0.034), history of previous caesarian section (P = 0.032), drinking alcohol during pregnancy (P = 0.004), and gender based abuse (P = 0.001). On health seeking behaviour for antenatal depression among depressed pregnant women, most, 68.9%, consulted their husbands about their symptoms; 57.3% took the decision to get treatment from doctors, and 52% sought prayer in the church. Conclusion. Antenatal depression is prevalent in this study population. Interventions to address its risk factors should be carried out and physicians should suspect depression in pregnant women reporting alcohol use and gender abuse.

  15. Mobilizing Government

    DEFF Research Database (Denmark)

    Wang, Cancan; Medaglia, Rony; Jensen, Tina Blegind

    2016-01-01

    The nature of inter-organizational collaboration between government and other stakeholders is rapidly changing with the introduction of open social media (OSM) platforms. Characterized by a high degree of informality as well as a blurred personal/professional nature, OSM can potentially introduce...... changes and tensions in the well-established routines of the public sector. This paper aims at shedding light on such changes, presenting findings from a study on the use of an OSM platform, WeChat, in an interorganizational collaboration project between government, university, and industry stakeholders...... in the four dimensions of time, task, team, and transition. Specifically, we report on new collaboration procedures that are characterized by an ad-hoc and non-linear management of time; a sense of shared commitment to the accomplishment of tasks; a serendipitous recruitment of team members based on expertise...

  16. Identification of key factors governing chemistry in groundwater near the water course recharged by reclaimed water at Miyun County, Northern China

    Institute of Scientific and Technical Information of China (English)

    Yilei Yu; Xianfang Song; Yinghua Zhang; Fandong Zheng; Ji Liang; Dongmei Han; Ying Ma

    2013-01-01

    Reclaimed water was successfully used to recover the dry Chaobai River in Northern China,but groundwater may be polluted.To ensure groundwater protection,it is therefore critical to identify the governing factors of groundwater chemistry.Samples of reclaimed water,river and groundwater were collected monthly at Chaobai River from January to September in 2010.Fifteen water parameters were analyzed.Two kinds of reclaimed water were different in type (Na-Ca-Mg-C1-HCO3 or Na-Ca-Cl-HCO3) and concentration of nitrogen.The ionic concentration and type in river were similar to reclaimed water.Some shallow wells near the river bed had the same type (Na-Ca-Mg-Cl-HCO3) and high concentration as reclaimed water,but others were consistent with the deep wells (Ca-Mg-HCO3).Using cluster analysis,the 9 months were divided into two periods (dry and wet seasons),and all samples were grouped into several spatial clusters,indicating different controlling mechanisms.Principal component analysis and conventional ionic plots showed that calcium,magnesium and bicarbonate were controlled by water-rock interaction in all deep and some shallow wells.This included the dissolution of calcite and carbonate weathering.Sodium,potassium,chloride and sulfate in river and some shallow wells recharged by river were governed by evaporation crystallization and mixing of reclaimed water.But groundwater chemistry was not controlled by precipitation.During the infiltration of reclaimed water,cation exchange took place between (sodium,potassium) and (calcium,magnesium).Nitrification and denitrification both happened in most shallow groundwater,but only denitrification in deep groundwater.

  17. Organizational governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Klein, Peter G.

    This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory......, and the incomplete-contracts or property-rights approach. We distill the main unifying characteristics of these streams, survey each stream, and offer some critical commentary and suggestions for moving forward....

  18. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Hansen, Jesper Rosenberg; Villadsen, Anders Ryom

    We suggest that both making and buying the same product or service has several effects on market performance. A model is developed and tested by use of 170 answers gathered from the Danish municipalities. The results support the hypotheses that both making and buying: (1) moderates the negative r...... on how the plurality is measured. The results indicate that internal production may facilitate effective governance of the relationships with suppliers. Implications for research on firm boundaries and for practice are also discussed....

  19. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Hansen, Jesper Rosenberg; Villadsen, Anders Ryom

    We suggest that both making and buying the same product or service has several effects on market performance. A model is developed and tested by use of 170 answers gathered from the Danish municipalities. The results support the hypotheses that both making and buying: (1) moderates the negative r...... on how the plurality is measured. The results indicate that internal production may facilitate effective governance of the relationships with suppliers. Implications for research on firm boundaries and for practice are also discussed....

  20. CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Dan Alexandru SITARU

    2009-10-01

    Full Text Available The work is aimed to examine the issues “corporate governance” involves, with the goal set to clarify the meanings of such notion, and to provide an overall image of the positive effects arising implementing the corporate governance principles. The first section includes a series of definitions for the purpose of explaining and outlining the concept of “corporate governance”, subsequently giving a definition that appears adequate to us, from the legal standpoint pre eminently. The second section has for purpose to state the corporate governance Principles, and briefly examine the same. Its purpose also includes concretely illustrating the efficient operation methods for a “corporation”, as well as the main dilemmas, and the existing solutions for the same within the internal structure of a joint stock company to adopt, and subject itself to, such principles. Finally, the last section of the work underlines the corporate governance importance, and states the goals to be attained for purposes of securing effective, balanced, and not in the last place profitable management.

  1. Risk factors for visual impairment and blindness amongst black adult diabetis receiving treatment at Government healthcare facilitis in Mopani District, Limpopo province, South Africa

    Directory of Open Access Journals (Sweden)

    Raymond G. Mabaso

    2014-01-01

    Full Text Available Background: Diabetes mellitus (DM is a common systemic disease amongst Black South Africans. It may lead to diabetic retinopathy (DR, a common cause of visual impairment (VI and blindness. DR may signifiantly increase the prevalence of VI and blindness.Aim: To assess risk factors for VI and blindness amongst a black diabetic South African population aged ≥ 40 years.Setting: The study was conducted in seven Government healthcare facilities (two hospitals, four clinics and one health centre in Mopani District, Limpopo province, South Africa.Methods: This was a cross-sectional health facility-based quantitative study. Structured interviews were used to obtain information, which included sociodemographic profie, knowledge about DM and its ocular complications, presence of hypertension and accessibility to health facilities. Subsequently participants were examined for VI and blindness using an autorefractor, pinhole disc, ophthalmoscope and logMAR visual acuity chart. Anthropometric measurements (height, weight and waist were also taken. Associations between 31 risk factors and VI as well as blindness were statistically examined.Results: Participants (N = 225 included 161 women and 64 men aged 40–90 years (mean 61.5 ± 10.49 years; 41.3% of them had VI and 3.6% were blind. Cataracts (76.8% and DR (7.1% were the common causes of compensated VI and blindness. Risk factors that were associated with VI and blindness were age, monthly income, compliance with losing weight and physical activity.Conclusion: Findings suggest that lifestyle intervention and appropriate eyecare programmes may reduce VI and blindness in this population.

  2. Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear.

    Science.gov (United States)

    Zhu, Xiao-Na; Liu, Xian-Dong; Zhuang, Hanyi; Henkemeyer, Mark; Yang, Jing-Yu; Xu, Nan-Jie

    2016-09-28

    The amygdala serves as emotional center to mediate innate fear behaviors that are reflected through neuronal responses to environmental aversive cues. However, the molecular mechanism underlying the initial neuron responses is poorly understood. In this study, we monitored the innate defensive responses to aversive stimuli of either elevated plus maze or predator odor in juvenile mice and found that glutamatergic neurons were activated in amygdala. Loss of EphB2, a receptor tyrosine kinase expressed in amygdala neurons, suppressed the reactions and led to defects in spine morphogenesis and fear behaviors. We further found a coupling of spinogenesis with these threat cues induced neuron activation in developing amygdala that was controlled by EphB2. A constitutively active form of EphB2 was sufficient to rescue the behavioral and morphological defects caused by ablation of ephrin-B3, a brain-enriched ligand to EphB2. These data suggest that kinase-dependent EphB2 intracellular signaling plays a major role for innate fear responses during the critical developing period, in which spinogenesis in amygdala glutamatergic neurons was involved. Generation of innate fear responses to threat as an evolutionally conserved brain feature relies on development of functional neural circuit in amygdala, but the molecular mechanism remains largely unknown. We here identify that EphB2 receptor tyrosine kinase, which is specifically expressed in glutamatergic neurons, is required for the innate fear responses in the neonatal brain. We further reveal that EphB2 mediates coordination of spinogenesis and neuron activation in amygdala during the critical period for the innate fear. EphB2 catalytic activity plays a major role for the behavior upon EphB-ephrin-B3 binding and transnucleus neuronal connections. Our work thus indicates an essential synaptic molecular signaling within amygdala that controls synapse development and helps bring about innate fear emotions in the postnatal

  3. Development of Glutamatergic Proteins in Human Visual Cortex across the Lifespan.

    Science.gov (United States)

    Siu, Caitlin R; Beshara, Simon P; Jones, David G; Murphy, Kathryn M

    2017-06-21

    Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan.SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most

  4. High yield derivation of enriched glutamatergic neurons from suspension-cultured mouse ESCs for neurotoxicology research

    Directory of Open Access Journals (Sweden)

    Hubbard Kyle S

    2012-10-01

    Full Text Available Abstract Background Recently, there has been a strong emphasis on identifying an in vitro model for neurotoxicity research that combines the biological relevance of primary neurons with the scalability, reproducibility and genetic tractability of continuous cell lines. Derived neurons should be homotypic, exhibit neuron-specific gene expression and morphology, form functioning synapses and consistently respond to neurotoxins in a fashion indistinguishable from primary neurons. However, efficient methods to produce neuronal populations that are suitable alternatives to primary neurons have not been available. Methods With the objective of developing a more facile, robust and efficient method to generate enriched glutamatergic neuronal cultures, we evaluated the neurogenic capacity of three mouse embryonic stem cell (ESC lines (R1, C57BL/6 and D3 adapted to feeder-independent suspension culture. Neurogenesis and neuronal maturation were characterized as a function of time in culture using immunological, genomic, morphological and functional metrics. The functional responses of ESNs to neurotropic toxins with distinctly different targets and mechanisms of toxicity, such as glutamate, α-latrotoxin (LTX, and botulinum neurotoxin (BoNT, were also evaluated. Results Suspension-adapted ESCs expressed markers of pluripotency through at least 30 passages, and differentiation produced 97×106 neural progenitor cells (NPCs per 10-cm dish. Greater than 99% of embryonic stem cell-derived neurons (ESNs expressed neuron-specific markers by 96 h after plating and rapidly developed complex axodendritic arbors and appropriate compartmentalization of neurotypic proteins. Expression profiling demonstrated the presence of transcripts necessary for neuronal function and confirmed that ESN populations were predominantly glutamatergic. Furthermore, ESNs were functionally receptive to all toxins with sensitivities and responses consistent with primary neurons

  5. Counting Vesicular Release Events Reveals Binomial Release Statistics at Single Glutamatergic Synapses.

    Science.gov (United States)

    Malagon, Gerardo; Miki, Takafumi; Llano, Isabel; Neher, Erwin; Marty, Alain

    2016-04-06

    Many central glutamatergic synapses contain a single presynaptic active zone and a single postsynaptic density. However, the basic functional properties of such "simple synapses" remain unclear. One important step toward understanding simple synapse function is to analyze the number of synaptic vesicles released in such structures per action potential, but this goal has remained elusive until now. Here, we describe procedures that allow reliable vesicular release counting at simple synapses between parallel fibers and molecular layer interneurons of rat cerebellar slices. Our analysis involves local extracellular stimulation of single parallel fibers and deconvolution of resulting EPSCs using quantal signals as template. We observed a reduction of quantal amplitudes (amplitude occlusion) in pairs of consecutive EPSCs due to receptor saturation. This effect is larger (62%) than previously reported and primarily reflects receptor activation rather than desensitization. In addition to activation-driven amplitude occlusion, each EPSC reduces amplitudes of subsequent events by an estimated 3% due to cumulative desensitization. Vesicular release counts at simple synapses follow binomial statistics with a maximum that varies from 2 to 10 among experiments. This maximum presumably reflects the number of docking sites at a given synapse. These results show striking similarities, as well as significant quantitative differences, with respect to previous results at simple GABAergic synapses. It is generally accepted that the output signal of individual central synapses saturates at high release probability, but it remains unclear whether the source of saturation is presynaptic, postsynaptic, or both presynaptic and postsynaptic. To clarify this and other issues concerning the function of synapses, we have developed new recording and analysis methods at single central glutamatergic synapses. We find that individual release events engage a high proportion of postsynaptic

  6. 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.

  7. 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.

  8. 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

  9. Problems of Revenue Generation in Local Government ...

    African Journals Online (AJOL)

    user

    2013-07-07

    Jul 7, 2013 ... financial problems hindering local governments in Nigeria, most especially .... Borrowing from State Government and financial institutions. f. Local government share of value added tax (VAT). .... Thus, tax evasion ... factors responsible for Local Government poor revenue .... 3 Issue 3 P.54 on internet. Orewa ...

  10. Modulation of the NMDA Receptor Through Secreted Soluble Factors.

    Science.gov (United States)

    Cerpa, Waldo; Ramos-Fernández, Eva; Inestrosa, Nibaldo C

    2016-01-01

    Synaptic activity is a critical determinant in the formation and development of excitatory synapses in the central nervous system (CNS). The excitatory current is produced and regulated by several ionotropic receptors, including those that respond to glutamate. These channels are in turn regulated through several secreted factors that function as synaptic organizers. Specifically, Wnt, brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF), and transforming growth factor (TGF) particularly regulate the N-methyl-D-aspartate receptor (NMDAR) glutamatergic channel. These factors likely regulate early embryonic development and directly control key proteins in the function of important glutamatergic channels. Here, we review the secreted molecules that participate in synaptic organization and discuss the cell signaling behind of this fine regulation. Additionally, we discuss how these factors are dysregulated in some neuropathologies associated with glutamatergic synaptic transmission in the CNS.

  11. 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.

  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. 主权财富基金规模的实际表征:经济要素抑或政府行为%Factors of Sovereign Wealth Funds' Asset Size:Economic Factors or Government Behavior

    Institute of Scientific and Technical Information of China (English)

    戴利研

    2011-01-01

    Based on reviewing the literatures, this paper analyzes the influencing factors of a country's Sovereign Wealth Funds' asset size. The analysis on the macroeconomy, political policy and fund governance show that a country's total reserves, energy exports, total savings, per capita GDP, voice and accountability, political stability and fund's structure, governance, accountability and transparency, as well as fund's duration all significantly impact on Sovereign Wealth Funds' asset size. Nevertheless, a country's government effectiveness, regulatory quality, rule of law, control of corruption and fund' s behavior have no significant effect on fund' s asset size.%在综述已有文献的基础上,对影响一国主权财富基金规模的因素进行实证研究。对宏观经济、政治以及基金治理三个方面的分析表明,一国的总储备、能源出口、总储蓄、人均GDP、话语权和问责制、政治稳定程度以及基金的结构、管理、问责制和透明度、建立的时间长度等因素对主权财富基金的规模具有显著影响;而一国的政府效率、监管质量、法制环境、腐败控制以及基金的投资行为等因素对主权财富基金规模的影响不显著。

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Cannabinoid Type 1 Receptors Transiently Silence Glutamatergic Nerve Terminals of Cultured Cerebellar Granule Cells

    Science.gov (United States)

    Ramírez-Franco, Jorge; Bartolomé-Martín, David; Alonso, Beatris; Torres, Magdalena; Sánchez-Prieto, José

    2014-01-01

    Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1α protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals. PMID:24533119

  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. 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.

  4. Toluene inhalation in adolescent rats reduces flexible behaviour in adulthood and alters glutamatergic and GABAergic signalling.

    Science.gov (United States)

    Furlong, Teri M; Duncan, Jhodie R; Corbit, Laura H; Rae, Caroline D; Rowlands, Benjamin D; Maher, Anthony D; Nasrallah, Fatima A; Milligan, Carol J; Petrou, Steven; Lawrence, Andrew J; Balleine, Bernard W

    2016-12-01

    Toluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long-term impact remains limited. Here, we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABAergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABAergic profile. Similarly, in vitro electrophysiology in Xenopus oocytes found that acute toluene exposure reduced NMDA receptor signalling. Finally, in an adolescent rodent model of chronic intermittent exposure to toluene (10 000 ppm), we found that, while toluene exposure did not affect initial learning, it induced a deficit in updating that learning when response-outcome relationships were reversed or degraded in an instrumental conditioning paradigm. There were also group differences when more effort was required to obtain the reward; toluene-exposed animals were less sensitive to progressive ratio schedules and to delayed discounting. These behavioural deficits were accompanied by changes in subunit expression of both NMDA and GABA receptors in adulthood, up to 10 weeks after the final exposure to toluene in the hippocampus, prefrontal cortex and ventromedial striatum; regions with recognized roles in behavioural flexibility and decision-making. Collectively, our data suggest that exposure to toluene is sufficient to induce adaptive changes in glutamatergic and GABAergic systems and in adaptive behaviour that may underlie the deficits observed following adolescent inhalant abuse, including susceptibility to further drug-use. © 2016 International Society for Neurochemistry.

  5. Interaction of PGHS-2 and glutamatergic mechanisms controlling the ovine fetal hypothalamus-pituitary-adrenal axis.

    Science.gov (United States)

    Knutson, Nathan; Wood, Charles E

    2010-07-01

    Prostaglandins, generated within the fetal brain, are integral components of the mechanism controlling the fetal hypothalamus-pituitary-adrenal (HPA) axis. Previous studies in this laboratory demonstrated that prostaglandin G/H synthase isozyme 2 (PGHS-2) inhibition reduces the fetal HPA axis response to cerebral hypoperfusion, blocks the preparturient rise in fetal plasma ACTH concentration, and delays parturition. We also discovered that blockade of N-methyl-d-aspartate (NMDA) receptors reduces the fetal ACTH response to cerebral hypoperfusion. The present study was designed to test the hypothesis that PGHS-2 action and the downstream effect of HPA axis stimulation are stimulated by NMDA-mediated glutamatergic neurotransmission. Chronically catheterized late-gestation fetal sheep (n = 8) were injected with NMDA (1 mg iv). All responded with increases in fetal plasma ACTH and cortisol concentrations. Pretreatment with resveratrol (100 mg iv, n = 5), a specific inhibitor of PGHS-1, did not alter the magnitude of the HPA axis response to NMDA. Pretreatment with nimesulide (10 mg iv, n = 6), a specific inhibitor of PGHS-2, significantly reduced the HPA axis response to NMDA. To further explore this interaction, we injected NMDA in six chronically catheterized fetal sheep that were chronically infused with nimesulide (n = 6) at a rate of 1 mg/day into the lateral cerebral ventricle for 5-7 days. In this group, there was no significant ACTH response to NMDA. Finally, we tested whether the HPA axis response to prostaglandin E(2) (PGE(2)) is mediated by NMDA receptors. Seven chronically catheterized late-gestation fetal sheep were injected with 100 ng of PGE(2), which significantly increased fetal plasma ACTH and cortisol concentrations. Pretreatment with ketamine (10 mg iv), an NMDA antagonist, did not alter the ACTH or cortisol response to PGE(2). We conclude that generation of prostanoids via the action of PGHS-2 in the fetal brain augments the fetal HPA axis response

  6. 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.

  7. 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.

  8. A comparative study of factors influencing decisions on desired family size among married men and women in Bokkos, a rural local government area in Plateau state.

    Science.gov (United States)

    Kahansim, Makshwar L; Hadejia, Idris S; Sambo, Mohammed N

    2013-03-01

    The total fertility rate of Nigerian women has remained high at 5.7. This is even higher for women in rural areas. Men and women in rural areas desire more children than those in urban areas. This study was aimed at describing and comparing the factors that influence family size decisions among men and women in Bokkos, a rural Local Government Area in Plateau state, Nigeria. A cross sectional descriptive comparative study was used. Data was collected using structured interviewer administered questionnaires. Seventy two percent of women and 83.6% of men who desire to have 1-4 children had at least a secondary school education. Close to seventy percent of both men and women would have fewer children if they are certain of their survival to adulthood. Over 50% of the respondents believe that the husbands should have the final say on family size decisions. Preference for male children influences decisions on family size among men and women in the study population.

  9. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2011-01-01

    Abstract: Most people agree that our world faces daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel...... dominant perspectives in challenge perception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping...... of engineering education and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter...

  10. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2012-01-01

    Most people agree that our world face daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel dominant...... perspectives in challenge per-ception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping of engineering education...... and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter strives to elicit the bodies...

  11. Governing Warfare

    DEFF Research Database (Denmark)

    Harste, Gorm

      It would seem as though warfare has gotten out of control, not only in Iraq and Afghanistan, but also in Central Africa. The paper outlines the strategic history of politically controlled warfare since the early Enlightenment. The argument is that control is implausible. The idea of control has...... the risks of lacking unity and displays the organisational trap to the fatal political myth of controlled warfare: Does it come from the military organisation system itself, from political ideologies of goal-rational governance, or from the chameleonic logic of wars?  ...... administration. While organisation systems continue to make some kind of political control possible, this is not the case in relation to wars. The organisation system is the in-between that should mediatise politics and war but is not functionally equivalent to just and unjust wars. The paper investigates...

  12. 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

  13. Terminal Uranium(V/VI) Nitride Activation of Carbon Dioxide and Carbon Disulfide: Factors Governing Diverse and Well-Defined Cleavage and Redox Reactions.

    Science.gov (United States)

    Cleaves, Peter A; Kefalidis, Christos E; Gardner, Benedict M; Tuna, Floriana; McInnes, Eric J L; Lewis, William; Maron, Laurent; Liddle, Stephen T

    2017-02-24

    The reactivity of terminal uranium(V/VI) nitrides with CE2 (E=O, S) is presented. Well-defined C=E cleavage followed by zero-, one-, and two-electron redox events is observed. The uranium(V) nitride [U(Tren(TIPS) )(N)][K(B15C5)2 ] (1, Tren(TIPS) =N(CH2 CH2 NSiiPr3 )3 ; B15C5=benzo-15-crown-5) reacts with CO2 to give [U(Tren(TIPS) )(O)(NCO)][K(B15C5)2 ] (3), whereas the uranium(VI) nitride [U(Tren(TIPS) )(N)] (2) reacts with CO2 to give isolable [U(Tren(TIPS) )(O)(NCO)] (4); complex 4 rapidly decomposes to known [U(Tren(TIPS) )(O)] (5) with concomitant formation of N2 and CO proposed, with the latter trapped as a vanadocene adduct. In contrast, 1 reacts with CS2 to give [U(Tren(TIPS) )(κ(2) -CS3 )][K(B15C5)2 ] (6), 2, and [K(B15C5)2 ][NCS] (7), whereas 2 reacts with CS2 to give [U(Tren(TIPS) )(NCS)] (8) and "S", with the latter trapped as Ph3 PS. Calculated reaction profiles reveal outer-sphere reactivity for uranium(V) but inner-sphere mechanisms for uranium(VI); despite the wide divergence of products the initial activation of CE2 follows mechanistically related pathways, providing insight into the factors of uranium oxidation state, chalcogen, and NCE groups that govern the subsequent divergent redox reactions that include common one-electron reactions and a less-common two-electron redox event. Caution, we suggest, is warranted when utilising CS2 as a reactivity surrogate for CO2 .

  14. Corporate Governance Communication

    OpenAIRE

    Gnecchi, Flavio

    2006-01-01

    The recognised critical importance of corporate governance, and the attention that it is paid today, can be ascribed to several factors: sensational financial scandals (and the repercussions they have had for securities and financial markets), the exponential development of stock option policies, the information asymmetry that can be noted in practically every company, The different requests for information of the various categories of stakeholders, combine to strengthen the decision to adopt...

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction.

    Science.gov (United States)

    Manto, Mario; Dalmau, Josep; Didelot, Adrien; Rogemond, Véronique; Honnorat, Jérôme

    2010-11-26

    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. 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. 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. 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.

  2. 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.

  3. Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat.

    Directory of Open Access Journals (Sweden)

    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

  4. Peculiarities of Corporate Governance Methodology

    Directory of Open Access Journals (Sweden)

    Victoria Vladimirovna Prokhorova

    2016-04-01

    Full Text Available This work is devoted to the study of the quality and identification of priorities of institutional investors in corporate governance in Russia. The authors conclude that the main task of the corporate governance system is to create favorable conditions for broad attraction of foreign investments in Russian companies and to increase the role of shareholders in strategic management. At present, the companies from developed countries achieve higher economic performance through the introduction of modern methods of corporate governance. The adoption of the new Code of Corporate Governance in the Russian Federation in 2014 will create an opportunity to improve the efficiency of Russian companies and to conduct their activities in accordance with international standards through the introduction of modern corporate governance practices, including ensuring transparency of activities for investors. At the same time, despite significant improvements in corporate governance practices of Russian companies, the level of its quality in comparison with foreign countries remains low. The article highlights both positive and negative trends in the Russian practice of corporate governance. One of the effective corporate governance methods is to ensure feedback between Russian companies and institutional investors. The article presents the results of a survey of opinions of investors that allow to identify the main factors of corporate governance that motivate them to take investment decisions on the Russian market.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  13. Nicotinic modulation of glutamatergic synaptic transmission in region CA3 of the hippocampus.

    Science.gov (United States)

    Giocomo, Lisa M; Hasselmo, Michael E

    2005-09-01

    Cholinergic modulation of synaptic transmission in the hippocampus appears to be involved in learning, memory and attentional processes. In brain slice preparations of hippocampal region CA3, we have explored the effect of nicotine on the afferent connections of stratum lacunosum moleculare (SLM) vs. the intrinsic connections of stratum radiatum (SR). Nicotine application had a lamina-selective effect, causing changes in synaptic transmission only in SLM. The nicotinic effect in SLM was characterized by a transient decrease in synaptic potential size followed by a longer period of enhancement of synaptic transmission. The effect was blocked by gamma-aminobutyric acid (GABA)ergic antagonists, indicating the role of GABAergic interneurons in the observed nicotinic effect. The biphasic nature of the nicotinic effect could be due to a difference in receptor subtypes, as supported by the effects of the nicotinic antagonists mecamylamine and methyllycaconitine. Nicotinic modulation of glutamatergic synaptic transmission could complement muscarinic suppression of intrinsic connections, amplifying incoming information and providing a physiological mechanism for the memory-enhancing effect of nicotine.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    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.

  1. Identification of the factors that govern the ability of therapeutic antibodies to provide postchallenge protection against botulinum toxin: a model for assessing postchallenge efficacy of medical countermeasures against agents of bioterrorism and biological warfare.

    Science.gov (United States)

    Al-Saleem, Fetweh H; Nasser, Zidoon; Olson, Rebecca M; Cao, Linsen; Simpson, Lance L

    2011-08-01

    Therapeutic antibodies are one of the major classes of medical countermeasures that can provide protection against potential bioweapons such as botulinum toxin. Although a broad array of antibodies are being evaluated for their ability to neutralize the toxin, there is little information that defines the circumstances under which these antibodies can be used. In the present study, an effort was made to quantify the temporal factors that govern therapeutic antibody use in a postchallenge scenario. Experiments were done involving inhalation administration of toxin to mice, intravenous administration to mice, and direct application to murine phrenic nerve-hemidiaphragm preparations. As part of this study, several pharmacokinetic characteristics of botulinum toxin and neutralizing antibodies were measured. The core observation that emerged from the work was that the window of opportunity within which postchallenge administration of antibodies exerted a beneficial effect increased as the challenge dose of toxin decreased. The critical factor in establishing the window of opportunity was the amount of time needed for fractional redistribution of a neuroparalytic quantum of toxin from the extraneuronal space to the intraneuronal space. This redistribution event was a dose-dependent phenomenon. It is likely that the approach used to identify the factors that govern postchallenge efficacy of antibodies against botulinum toxin can be used to assess the factors that govern postchallenge efficacy of medical countermeasures against any agent of bioterrorism or biological warfare.

  2. Corporate Governance and Corporate Creditworthiness

    Directory of Open Access Journals (Sweden)

    Dror Parnes

    2011-12-01

    Full Text Available We examine the relation between corporate governance and bankruptcy risk as an underlying force affecting a bond’s yield. The level of corporate governance is captured by the G-index, along with the explicit groups of governance provisions. We estimate bankruptcy risk by Z-score, by cash-flow-score, by O-score, through Merton structural model default probabilities, and by S&P credit ratings. After addressing endogeneity and while controlling for firm-specific factors, based on the four objective methodologies we find that corporate governance is inversely related to bankruptcy risk. Yet, rating agencies take a mixed approach towards this association likely because of the conflicting impact of different governance provisions.

  3. Corporate governance cycles during transition

    DEFF Research Database (Denmark)

    Mygind, Niels; Demina, Natalia; Gregoric, Aleksandra

    2004-01-01

    -nancial system. To provide simple hypothesis tests, we use Russian enterprise data for 1995-2003 and Slovenian data covering 1998-2003. In spite of differences in institutional development, con-cerning privatization and development of corporate governance institutions, we find that govern-ance cycles are broadly......Ownership is determined by firm specific factors and the environment. Firms change over their life-cycle. The governance cycle - here defined as changes in identity of the dominant owner and own-ership concentration - is marked by key phases including start-up, growth, and possibly a restructur...... of ownership on managers, external domestic and foreign owners. JEL-codes: G3, J5, P2, P3 - Keywords: corporate governance, life-cycle, privatization, ownership change, transition economies, Russia and Slovenia....

  4. Governability in Contemporary Mexico

    Directory of Open Access Journals (Sweden)

    Leonardo Curzio Gutiérrez

    1998-04-01

    Full Text Available Given the difficulties to establish a concept of governability and the frequent ideological usage of the term, it is much more operative to turn to the principle of governability, in the broad sense, which supports itself on five pillars: the political legitimacy of the government, the governmental efficiency to attend to the demands of society, the existence of shared social project, the agreement with the principle special interest groups, and international viability. The analysis of the structure and relevance of these five points during the long period of political transition that Mexico underwent between 1988 and 1997 shows how it was possible for this country to play off certain factors against each other in order to secure governability and safeguard against the consequences of any resultant imbalances. Between 1998-1993, the government of Salinas de Gotari based itself on the viability of a neoliberal project within an international context, and on this projectís attention to domestic demands as well as on the governmentís pact with elites. Institutional integration and legitimacy made up, then, for a process of discreet liberalization and the lack of democratic electoral commitment, which culminated in the PRI’s 1994 elections victory.The assassination of Colosia, though, and the appearance of the EZLN and the subsequent crisis surrounding the peso’s devaluation that accompanied Ernesto Zedilloís rise to power soon led to the collapse of those pillars of support. Crowning the process of the silenttransition were the elections of 1997, which makes it possible to say that in Mexico today there are now smooth elections, but that reform of the State is still unresolved —a subject that includes the reduction of the president’s competence. Seen in the short term, the most direct threats to Mexico’s governability will come as a result of the lack of attention to those demands of society’s underprivileged and the ill

  5. Shall I Tell You Where I Live and Who I Am? Factors Influencing the Behavioral Intention to Disclose Personal Data for Online Government Transactions

    NARCIS (Netherlands)

    Beldad, Ardion Daroca; van der Geest, Thea; de Jong, Menno D.T.; Steehouder, M.F.

    2012-01-01

    The success of an online transaction with a government organization depends on citizen's willingness to share personal data relevant for the transaction. However, disclosing personal data online is oftentimes considered risky. It has been substantiated in a number of empirical studies that

  6. Planning local E-government

    NARCIS (Netherlands)

    Vriens, D.J.; Achterbergh, J.M.I.M.

    2004-01-01

    User requirements, organizational change, government regulations, and politics are all factors that any organization embarking on a systems development project must take into consideration. These factors, plus that of general societal trends, have an even greater significance for governmental IT org

  7. Governance and Investment of Public Pension Assets : Practitioners' Perspectives

    OpenAIRE

    2011-01-01

    The impact of good governance on investment management and performance is immense. Several key factors contribute to good governance within pension funds, appropriate governance structures; well-defined accountabilities, policies, and procedures; and suitable processes for the selection and operation of governing bodies and managing institutions. Not surprisingly, good governance requires ...

  8. 当前我国电子政务信息安全中不良因素及防范对策%On the Negative Factors of China's E-government Information Security and the Current Preventive Measures

    Institute of Scientific and Technical Information of China (English)

    罗玮琛; 吴靖琳

    2014-01-01

    E-government is a government of ice to realize the inevitable development trend of the future, with the continuous improvement of the socio-economic construction, China's current e-government construction is constantly in-depth information on the development and construction of them, and some of the factors associated with this security has become a cause in emerging at ention and urgent problem. This article also our current e-government information security in a number of adverse factors were analyzed, and put forward some corresponding preventive measures in order to bring the reference value, to ensure the safety of China's e-government information, stable and rapid development.%电子政务是政府实现未来办公的必然发展趋势,随着我国社会经济建设的不断完善,当前我国电子政务信息建设也在不断的深入发展与建设当中,而伴随于此出现的一些安全因素已经成为引起人们关注并且亟待解决的问题。本文也就我国当前电子政务信息安全中一些不良因素进行了分析,并且提出了一些对应的防范对策,以期可以带来参考价值,确保我国电子政务信息的安全、稳定、快速发展。

  9. Government and governance strategies in medical tourism

    NARCIS (Netherlands)

    Ormond, M.E.; Mainil, T.

    2015-01-01

    This chapter provides an overview of current government and governance strategies relative to medical tourism development and management around the world. Most studies on medical tourism have privileged national governments as key actors in medical tourism regulation and, in some cases, even

  10. Engineering governance: introducing a governance meta framework.

    NARCIS (Netherlands)

    Brand, N.; Beens, B.; Vuuregge, E.; Batenburg, R.

    2011-01-01

    There is a need for a framework that depicts strategic choices within an organisation with regard to potential governance structures. The governance meta framework provides the necessary structure in the current developments of governance. Performance as well as conformance are embedded in this fram

  11. Dynamics of glutamatergic signaling in the mushroom body of young adult Drosophila

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. 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.

  14. Blockade of glutamatergic transmission in the primate basolateral amygdala suppresses active behavior without altering social interaction.

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    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

  15. 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.

  16. 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.

  17. Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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.

  1. Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal separation distress in mouse pups

    Science.gov (United States)

    Takahashi, Aki.; Yap, Jasmine. J.; Bohager, Dawnya Zitzman; Faccidomo, Sara; Clayton, Terry; Cook, James. M.

    2009-01-01

    Introduction Dysregulation of GABAergic inhibition and glutamatergic excitation has been implicated in exaggerated anxiety. Mouse pups emit distress-like ultrasonic vocalizations (USVs) when they are separated from their dam/siblings, and this behavior is reduced by benzodiazepines (BZs) which modulate GABAergic inhibition. The roles of glutamate receptors on USVs remain to be investigated. Materials and methods We examined the roles of glutamate receptor subtypes on mouse pup USVs using N-methyl-D-aspartate (NMDA) receptor antagonists with different affinities [dizocilpine (MK-801), memantine, and neramexane] and group II metabotropic glutamate receptor agonist (LY-379268) and antagonist (LY-341495). These effects were compared with classic BZs: flunitrazepam, bromazepam, and chlordiazepoxide. To assess the role of GABAA receptor subunits on USVs, drugs that have preferential actions at different GABAA-α subunits (L-838417 and QH-ii-066) were tested. Seven-day-old CFW mouse pups were separated from their dam and littermates and placed individually on a 19°C test platform for 4 min. Grid crossings and body rolls were measured in addition to USVs. Results Dizocilpine dose-dependently reduced USVs, whereas memantine and neramexane showed biphasic effects and enhanced USVs at low to moderate doses. The NMDA receptor antagonists increased locomotion. LY-379268 reduced USVs but also suppressed locomotion. All BZs reduced USVs and increased motor incoordination. Neither L-838417 nor QH-ii-066 changed USVs, but both induced motor incoordination. Conclusion Low-affinity NMDA receptor antagonists, but not the high-affinity antagonist, enhanced mouse pup distress calls, which may be reflective of an anxiety-like state. BZs reduced USVs but also induced motor incoordination, possibly mediated by the α5 subunit containing GABAA receptors. PMID:19099296

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

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    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

  3. Business Climate and Good Governance

    Directory of Open Access Journals (Sweden)

    Besmira Manaj

    2015-03-01

    Full Text Available This paper consists of three factors, namely: Good Governance, Business Climate and Corruption. How they affect the development product of Albania, not only as a concept, and a principle but mostly as a sensitive aspect in the integration process. There are some interpretations of this concept, but I intend to analyze the key factors and actors, their cooperation and concrete production in society. Improving governance is necessary to have an integrated long term strategy based upon a continuous cooperation between institutions and citizens. But in developing countries like Albania there are some important questions such as: How can we measure the improvement of Good Governance through policies? Has Good Governance indicated an effective way for the sustainable development? (Meisel, 2008, 6. These question give us the orientation to reflect about the process of development, social economic political behavior and how this multidimensional is transformed in product of good governance. The business cycle is strongly connected with many aspects of political-, social-, juridical aspects and good governance. Despite attempts to draft law regulations, the level of corruption and informality in Albania continues to be a major obstacle. The credibility level in the implementation of law is an indicator that affects democratization and institutional integration. At present, different reports of international institutions, define Albania as the country with the highest level of Corruption in the Balkans, which is a key factor influencing business. The ways with

  4. 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.

  5. Voluntary Environmental Governance Arrangements

    NARCIS (Netherlands)

    van der Heijden, J.

    2012-01-01

    Voluntary environmental governance arrangements have focal attention in studies on environmental policy, regulation and governance. The four major debates in the contemporary literature on voluntary environmental governance arrangements are studied. The literature falls short of sufficiently

  6. Developing digital forensic governance

    CSIR Research Space (South Africa)

    Grobler, M

    2010-03-01

    Full Text Available This paper presents a Digital Forensic (DF) governance framework and its mapping on the SANS ISO/IEC 38500:2009 Corporate governance of information technology structure. DF governance assists organisations in guiding the management team...

  7. Voluntary Environmental Governance Arrangements

    NARCIS (Netherlands)

    van der Heijden, J.

    2012-01-01

    Voluntary environmental governance arrangements have focal attention in studies on environmental policy, regulation and governance. The four major debates in the contemporary literature on voluntary environmental governance arrangements are studied. The literature falls short of sufficiently specify

  8. VT Certified Local Governments

    Data.gov (United States)

    Vermont Center for Geographic Information — Vermont established its Certified Local Government (CLG) program in 1985 to better help local governments integrate historic preservation concerns with planning and...

  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. An analysis of the dispute process regarding high-level nuclear waste repository siting in Toyo-cho, Japan: Decisive factors in the dispute and roles of the governments and experts

    Energy Technology Data Exchange (ETDEWEB)

    Komatsuzaki, Shunsaku; Horii, Hideyuki (Dept. of Civil Engineering, Univ. of Tokyo (Japan)); Saigo, Takahiro (Mitsubishi Research Institute, Inc. (Japan))

    2010-09-15

    The siting policy of HLW repository in Japan was 'application-based' until 2007 and Toyo-cho is the only municipality which applied for the Literature Survey. In Toyo-cho, however, a serious antagonism among citizens occurred and the application was withdrawn after the mayor was replaced by election. Our detailed analysis of the process based on the methods of political science and psychology shows five decisive factors: 1) opposing activists both in the town and from outside successfully changed citizens' perceptions of HLW by rhetorical expressions, 2) the mayor lacks careful actions and effective policy adviser, 3) NUMO, an organization which runs HLW projects, didn't effectively coordinate Toyo-cho and stakeholders, 4) the municipal government and council exercised very limited influences on the dispute despite their political authority, and 5) the existence of grant adversely influenced the citizens since it causes criticism that Toyo-cho applies a repository for grant. We finally conclude that the substantial problems, caused by the five decisive factors, were the propagation of enthusiastic opposition and the lack of peaceful deliberation based on local governance. In order to avoid enthusiastic opposition and to realize responsible decision making, or negotiation, we suggest that A) active and prompt response of experts, especially political/administrative ones, to radical opposing activities, B) solution to the adverse influence of the grant by the government's agenda

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Spatial relationships between GABAergic and glutamatergic synapses on the dendrites of distinct types of mouse retinal ganglion cells across development.

    Directory of Open Access Journals (Sweden)

    Adam Bleckert

    Full Text Available Neuronal output requires a concerted balance between excitatory and inhibitory (I/E input. Like other circuits, inhibitory synaptogenesis in the retina precedes excitatory synaptogenesis. How then do neurons attain their mature balance of I/E ratios despite temporal offset in synaptogenesis? To directly compare the development of glutamatergic and GABAergic synapses onto the same cell, we biolistically transfected retinal ganglion cells (RGCs with PSD95CFP, a marker of glutamatergic postsynaptic sites, in transgenic Thy1-YFPγ2 mice in which GABAA receptors are fluorescently tagged. We mapped YFPγ2 and PSD95CFP puncta distributions on three RGC types at postnatal day P12, shortly before eye opening, and at P21 when robust light responses in RGCs are present. The mature IGABA/E ratios varied among ON-Sustained (S A-type, OFF-S A-type, and bistratified direction selective (DS RGCs. These ratios were attained at different rates, before eye-opening for ON-S and OFF-S A-type, and after eye-opening for DS RGCs. At both ages examined, the IGABA/E ratio was uniform across the arbors of the three RGC types. Furthermore, measurements of the distances between neighboring PSD95CFP and YFPγ2 puncta on RGC dendrites indicate that their local relationship is established early in development, and cannot be predicted by random organization. These close spatial associations between glutamatergic and GABAergic postsynaptic sites appear to represent local synaptic arrangements revealed by correlative light and EM reconstructions of a single RGC's dendrites. Thus, although RGC types have different IGABA/E ratios and establish these ratios at separate rates, the local relationship between excitatory and inhibitory inputs appear similarly constrained across the RGC types studied.

  17. 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.

  18. Mechanisms involved in systemic nicotine-induced glutamatergic synaptic plasticity on dopamine neurons in the ventral tegmental area.

    Science.gov (United States)

    Gao, Ming; Jin, Yu; Yang, Kechun; Zhang, Die; Lukas, Ronald J; Wu, Jie

    2010-10-13

    Systemic exposure to nicotine induces glutamatergic synaptic plasticity on dopamine (DA) neurons in the ventral tegmental area (VTA), but mechanisms are largely unknown. Here, we report that single, systemic exposure in rats to nicotine (0.17 mg/kg free base) increases the ratio of DA neuronal currents mediated by AMPA relative to NMDA receptors (AMPA/NMDA ratio) assessed 24 h later, based on slice-patch recording. The AMPA/NMDA ratio increase is evident within 1 h and lasts for at least 72 h after nicotine exposure (and up to 8 d after repeated nicotine administration). This effect cannot be prevented by systemic injection of either α7-nAChR (nicotinic ACh receptor)-selective [methyllycaconitine (MLA)] or β2*-nAChR-selective [mecamylamine (MEC)] antagonists but is prevented by coinjection of MLA and MEC. In either nAChR α7 or β2 subunit knock-out mice, systemic exposure to nicotine still increases the AMPA/NMDA ratio. Preinjection in rats of a NMDA receptor antagonist MK-801((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), but neither DA receptor antagonists [SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) plus haloperidol] nor a calcineurin inhibitor (cyclosporine), prevents the nicotine-induced increase in AMPA/NMDA ratio. After systemic exposure to nicotine, glutamatergic (but not GABAergic) transmission onto rat VTA DA neuronal inputs is enhanced. Correspondingly, DA neuronal firing measured 24 h after nicotine exposure using extracellular single-unit recording in vivo is significantly faster, and there is conversion of silent to active DA neurons. Collectively, these findings demonstrate that systemic nicotine acting via either α7- or β2*-nAChRs increases presynaptic and postsynaptic glutamatergic function, and consequently initiates glutamatergic synaptic plasticity, which may be an important, early neuronal adaptation in nicotine reward and reinforcement.

  19. Prefrontal beta2 subunit-containing and alpha7 nicotinic acetylcholine receptors differentially control glutamatergic and cholinergic signaling.

    Science.gov (United States)

    Parikh, Vinay; Ji, Jinzhao; Decker, Michael W; Sarter, Martin

    2010-03-03

    One-second-long increases in prefrontal cholinergic activity ("transients") were demonstrated previously to be necessary for the incorporation of cues into ongoing cognitive processes ("cue detection"). Nicotine and, more robustly, selective agonists at alpha4beta2* nicotinic acetylcholine receptors (nAChRs) enhance cue detection and attentional performance by augmenting prefrontal cholinergic activity. The present experiments determined the role of beta2-containing and alpha7 nAChRs in the generation of prefrontal cholinergic and glutamatergic transients in vivo. Transients were evoked by nicotine, the alpha4beta2* nAChR agonist ABT-089 [2-methyl-3-(2-(S)-pyrrolindinylmethoxy) pyridine dihydrochloride], or the alpha7 nAChR agonist A-582941 [2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole]. Transients were recorded in mice lacking beta2 or alpha7 nAChRs and in rats after removal of thalamic glutamatergic or midbrain dopaminergic inputs to prefrontal cortex. The main results indicate that stimulation of alpha4beta2* nAChRs evokes glutamate release and that the presence of thalamic afferents is necessary for the generation of cholinergic transients. ABT-089-evoked transients were completely abolished in mice lacking beta2* nAChRs. The amplitude, but not the decay rate, of nicotine-evoked transients was reduced by beta2* knock-out. Conversely, in mice lacking the alpha7 nAChR, the decay rate, but not the amplitude, of nicotine-evoked cholinergic and glutamatergic transients was attenuated. Substantiating the role of alpha7 nAChR in controlling the duration of release events, stimulation of alpha7 nAChR produced cholinergic transients that lasted 10- to 15-fold longer than those evoked by nicotine. alpha7 nAChR-evoked cholinergic transients are mediated in part by dopaminergic activity. Prefrontal alpha4beta2* nAChRs play a key role in evoking and facilitating the transient glutamatergic-cholinergic interactions that are necessary for cue detection

  20. 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...

  1. Spatially-distributed influence of agro-environmental factors governing nitrate fate and transport in an irrigated stream-aquifer system

    Directory of Open Access Journals (Sweden)

    R. T. Bailey

    2015-02-01

    Full Text Available Elevated levels of nitrate (NO3 in groundwater systems pose a serious risk to human populations and natural ecosystems. As part of an effort to remediate NO3 contamination in irrigated stream-aquifer systems, this study elucidates agricultural and environmental parameters and processes that govern NO3 fate and transport at the regional (500 km2, local (50 km2, and field scales (2. Specifically, the revised Morris sensitivity analysis method was applied to a finite-difference nitrogen cycling and reactive transport model of a regional-scale study site in the Lower Arkansas River Valley in southeastern Colorado. The method was used to rank the influence of anthropogenic activities and natural chemical processes on NO3 groundwater concentration, NO3 mass leaching, and NO3 mass loading to the Arkansas River from the aquifer. Sensitivity indices were computed for the entire study area in aggregate as well as each canal command area, crop type, and individual grid cells. Results suggest that fertilizer loading, crop uptake, and heterotrophic denitrification govern NO3 fate and transport for the majority of the study area, while canal NO3 concentration and rates of autotrophic denitrification, nitrification, and humus decomposition dominate or partially dominate in several canal command areas. Also, NO3 leaching and groundwater concentration in adjacent cultivated fields often are governed by different processes and mass inputs/outputs. Results can be used to determine critical processes and key management actions for future data collection and remediation strategies, with efforts able to be focused on localized areas.

  2. PRACTICE OF GOOD GOVERNANCE AND CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Bălăceanu Cristina

    2010-12-01

    Full Text Available Corporate governance reforms are occurring in countries around the globe and potentially impacting the population of the entire planet. In developing countries, such reforms occur in a larger context that is primarily defined by previous attempts at promoting “development” and recent processes of economic globalization. In this context, corporate governance reforms (in combination with the liberalising reforms associated with economic globalization, in effect represent a new development strategy for third world countries. The most basic questions that arise with respect to this situation are what the prospects for this new development model are and whether alternatives should be considered. Keywords: governance, corporate governance, economic globalization, development.

  3. 公共危机中政府公信力的内部影响因素和提升策略%Internal Factors and Enhancement of Government's Public Trust in Public Crisis

    Institute of Scientific and Technical Information of China (English)

    闰丙金

    2012-01-01

    Our society is in a special historical period of profound transformation;All aspects of the crises revealed such as people's lives and property is threatened and the further development is restricted.The public trust of government will be shaped in the process of public crisis management though government plays the main role of management in the proceeding.Too many factors influence the public trust of government. The present research explore the impact factor of pre-control mechanisms ;information disclosure mechanism and legal system building;and bureaucratic workforces and discuss the theory of modern government's public trust. Com- bination the factors discussed above;we argue that public trust of government can be enhanced in public crisis by establishing the mechanism of alert;sound basement of laws system;as well as improving the transparence of official information and the capacities of civil servants.%我国社会正处在深刻转型的特殊历史时期,方方面面的危机事件时有发生,人民的生命、财产受到了威胁,社会的进一步发展受到了制约。政府作为公共危机管理的主体,在危机管理过程中其公信力也会有所变化。公共危机中影响政府公信力的因素很多,本文主要从危机预控机制、信息公开机制、法制建设等方面探究政府公信力的影响因素,阐释政府公信力的现代理论基础。结合上述影响因素,从建立危机预控机制、建全相关法律法规和加强信息公开等方面入手,寻求提升政府公信力的相关对策。

  4. Partnering to proceed: scaling up adolescent sexual reproductive health programmes in Tanzania. Operational research into the factors that influenced local government uptake and implementation

    Directory of Open Access Journals (Sweden)

    Andrew Bahati

    2010-05-01

    Full Text Available Abstract Background Little is known about how to implement promising small-scale projects to reduce reproductive ill health and HIV vulnerability in young people on a large scale. This evaluation documents and explains how a partnership between a non-governmental organization (NGO and local government authorities (LGAs influenced the LGA-led scale-up of an innovative NGO programme in the wider context of a new national multisectoral AIDS strategy. Methods Four rounds of semi-structured interviews with 82 key informants, 8 group discussions with 49 district trainers and supervisors (DTS, 8 participatory workshops involving 52 DTS, and participant observations of 80% of LGA-led and 100% of NGO-led meetings were conducted, to ascertain views on project components, flow of communication and decision-making and amount of time DTS utilized undertaking project activities. Results Despite a successful ten-fold scale-up of intervention activities in three years, full integration into LGA systems did not materialize. LGAs contributed significant human resources but limited finances; the NGO retained control over finances and decision-making and LGAs largely continued to view activities as NGO driven. Embedding of technical assistants (TAs in the LGAs contributed to capacity building among district implementers, but may paradoxically have hindered project integration, because TAs were unable to effectively transition from an implementing to a facilitating role. Operation of NGO administration and financial mechanisms also hindered integration into district systems. Conclusions Sustainable intervention scale-up requires operational, financial and psychological integration into local government mechanisms. This must include substantial time for district systems to try out implementation with only minimal NGO support and modest output targets. It must therefore go beyond the typical three- to four-year project cycles. Scale-up of NGO pilot projects of this

  5. Data governance implementation concept

    OpenAIRE

    Ullrichová, Jana

    2016-01-01

    This master´s thesis discusses concept of implementation for data governance. The theoretical part of this thesis is about data governance. It explains why data are important for company, describes definitoons of data governance, its history, its components, its principles and processes and fitting in company. Theoretical part is amended with examples of data governance failures and banking specifics. The main goal of this thesis is to create a concept for implementing data governance and its...

  6. Gene expression related to serotonergic and glutamatergic neurotransmission is altered in the flinders sensitive line rat model of depression: Effect of ketamine.

    Science.gov (United States)

    Du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Sanchez, Connie; Wegener, Gregers; Elfving, Betina

    2017-01-01

    Major depressive disorder (MDD) is associated with dysfunctional serotonergic and glutamatergic neurotransmission, and the genetic animal model of depression Flinders Sensitive Line (FSL) rats display alterations in these systems relatively to their control strain Flinders Resistant Line (FRL). However, changes on transcript level related to serotonergic and glutamatergic signaling have only been sparsely studied in this model. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has fast-onset antidepressant properties, and recent data implicate serotonergic neurotransmission in ketamine's antidepressant-like activities in rodents. Here, we investigated the transcript levels of 40 genes involved in serotonergic and glutamatergic neurotransmission in FSL and FRL rats in response to a single dose of ketamine (15 mg/kg; 90 min prior to euthanization). Using real-time quantitative polymerase chain reaction, we studied the effect of ketamine in the hippocampus, whereas strain differences were investigated in both hippocampus and frontal cortex. The expression of genes involved in serotonergic and glutamatergic neurotransmission were unaffected by a single dose of ketamine in the hippocampus. Relative to FRL rats, FSL rats displayed enhanced hippocampal transcript levels of 5-ht2c , and P11, whereas the expression was reduced for 5-ht2a , Nr2a, and Mglur2. In the frontal cortex, we found higher transcript levels of 5-ht2c and Mglur2, whereas the expression of 5-ht2a was reduced in FSL rats. Thus, ketamine is not associated with hippocampal alterations in serotonergic or glutamatergic genes at 90 min after an antidepressant dose. Furthermore, FSL rats display serotonergic and glutamatergic abnormalities on gene expression level that partly may resemble findings in MDD patients. © 2016 Wiley Periodicals, Inc.

  7. Discharge Profiles across the Sleep–Waking Cycle of Identified Cholinergic, GABAergic, and Glutamatergic Neurons in the Pontomesencephalic Tegmentum of the Rat

    Science.gov (United States)

    Boucetta, Soufiane; Cissé, Youssouf; Mainville, Lynda; Morales, Marisela

    2014-01-01

    Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping–waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep–wake states, cortical activity, and muscle tone. We found that all cholinergic neurons were maximally active during W and PS in positive correlation with fast (γ) cortical activity, as “W/PS-max active neurons.” Like cholinergic neurons, many GABAergic and glutamatergic neurons were also “W/PS-max active.” Other GABAergic and glutamatergic neurons were “PS-max active,” being minimally active during W and maximally active during PS in negative correlation with muscle tone. Conversely, some glutamatergic neurons were “W-max active,” being maximally active during W and minimally active during PS in positive correlation with muscle tone. Through different discharge profiles, the cholinergic, GABAergic, and glutamatergic neurons of the LDT, SubLDT, and MPPT thus appear to play distinct roles in promoting W and PS with cortical activation, PS with muscle atonia, or W with muscle tone. PMID:24672016

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Leisure, Government and Governance: A Swedish Perspective

    Science.gov (United States)

    Lindstrom, Lisbeth

    2011-01-01

    The leisure sector has witnessed a tremendous expansion since 1960. The purpose of this article is to analyse the decisions and goals of Swedish government policy during the period 1962 to 2005. The empirical analysis covers government Propositions and governmental investigations. The fields covered are sports, culture, exercise, tourism and…

  18. Sustainable Food Governance by Governments and Markets

    NARCIS (Netherlands)

    Oosterveer, P.J.M.

    2015-01-01

    The environmental consequences of the increasing global seafood production and consumption are substantial and drive a search for providing more adequate governance responses. In recent years, market-based approaches to sustainable seafood governance have gained considerable traction. Born in part

  19. 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...

  20. An Empirical Study on the Factors Influencing the E-government APP Adopted by the Public%公众采纳政务 APP 影响因素及实证研究

    Institute of Scientific and Technical Information of China (English)

    赵玉攀; 杨兰蓉

    2015-01-01

    The production of APP, to adapt to the needs of government reform, provides a multi-channel government service mode. Key to the success of the project lies in the public for its degree of adoption, at the same time, the APP is different from the traditional e-gov-ernment, therefore, it is of great value to study the factors influencing the public adoption of e-government APP. Based on the existing lit-erature and on the basis of the model, the article selected the interaction, mobility, situation, critical quality, perceived ease of use, per-ceived usefulness and perceived encouragement factor to build public adoption of e-government APP model. Through the data analysis car-ried out on the model, the article studied the relationship between the various factors, and drew the final conclusion.%政务 APP 的产生,适应了政府改革的需要,提供了多渠道、多途径的政务服务模式。政府项目的成败关键在于公众对于其采纳的程度,同时政务 APP 有别于传统的电子政务,因此,对公众采纳政务 APP 的影响因素进行研究具有重要价值。在已有的文献和模型基础上,选取互动性、移动性、情景感、临界质量、感知易用性、感知有用性以及感知鼓励等因素构建公众采纳政务 APP 的模型,通过数据对模型进行分析,研究各个因素之间的关系,最终得出结论。

  1. Salient factors in the low utilization of PICS bags (triple-bagging in Nasarawa local government area of Kano state, Nigeria

    Directory of Open Access Journals (Sweden)

    A.J. Adegbola

    2013-03-01

    Full Text Available Thepaper asserts that cowpea is a major nutritional legume in West Africa and thatthe grain experiences great losses at postharvest stages especially at storage.It posits that hermetic storage which the PICS is one of have proved to be avery successful storage option for cowpea storage without the use of agrochemicals but that there are daunting problems with its utilization. The studyrevealed among others that having outlets where the PICS can be bought(29%,making the PICS cheaper (45%, convince grain merchants that the PICS is more effective than regular storagebags(19%, and lastly forcing it on grain merchants by government would lead to more usage of the PICS (7%. Basedon the opinion of the cowpea merchants it was recommended that the sellingprice of the PICS be reviewed downwards, and that there should be a massiveenlightenment campaign for the use of the PICS; advantages of the PICS overregular bags and how to use the PICS should be demonstrated in all grainmarkets in the region by extension bodies both public and private.

  2. Why Mobile Government isn’t successful (yet)

    DEFF Research Database (Denmark)

    Ohme, Jakob; Seifert, Claudia; Renatus, Rebecca

    Mobile Government as a subset of E-Government is part of the Open Government approach of leading countries, like Germany. Since adoption rates among the citizens are still low this study tries to answer the question, what factors concerning the relationship of the government and its citizens migh...

  3. The Fasting-induced Adipose Factor/Angiopoietin-like Protein 4 Is Physically Associated with Lipoproteins and Governs Plasma Lipid Levels and Adiposity

    NARCIS (Netherlands)

    Mandard, S.J.; Zandbergen, F.J.; Straten, van E.; Wahli, W.; Kuipers, F.; Müller, M.R.; Kersten, A.H.

    2006-01-01

    Proteins secreted from adipose tissue are increasingly recognized to play an important role in the regulation of glucose metabolism. However, much less is known about their effect on lipid metabolism. The fasting-induced adipose factor (FIAF/angiopoietin-like protein 4/peroxisome

  4. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity

    NARCIS (Netherlands)

    Mandard, S; Zandbergen, F; van Straten, E; Wahli, W; Kuipers, F; Muller, M; Kersten, S

    2006-01-01

    Proteins secreted from adipose tissue are increasingly recognized to play an important role in the regulation of glucose metabolism. However, muchless is known about their effect on lipid metabolism. The fasting-induced adipose factor (FIAF/angiopoietin-like protein 4/peroxisome

  5. Factors Influencing the Use of Information and Communication Technology (ICT) in Teaching and Learning Computer Studies in Ohaukwu Local Government Area of Ebonyi State-Nigeria

    Science.gov (United States)

    Agbo, Igwe Sylvester

    2015-01-01

    Research studies in the past years show that Information and Communication Technology is an effective means for boasting educational opportunities, but most teachers neither use this technology as an instructional delivery system nor integrate technology into their curriculum. Studies reveal a number of factors influencing teachers' decisions to…

  6. Transformative environmental governance

    Science.gov (United States)

    Chaffin, Brian C.; Garmestani, Ahjond S.; Gunderson, Lance H.; Harm Benson, Melinda; Angeler, David G.; Arnold, Craig Anthony (Tony); Cosens, Barbara; Kundis Craig, Robin; Ruhl, J.B.; Allen, Craig R.

    2016-01-01

    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to alternative, more desirable, or more functional regimes by altering the structures and processes that define the system. Transformative governance is rooted in ecological theories to explain cross-scale dynamics in complex systems, as well as social theories of change, innovation, and technological transformation. Similar to adaptive governance, transformative governance involves a broad set of governance components, but requires additional capacity to foster new social-ecological regimes including increased risk tolerance, significant systemic investment, and restructured economies and power relations. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds.

  7. Government and Business

    DEFF Research Database (Denmark)

    Campbell, John L.

    2015-01-01

    There is a vast literature about the relationships between government and business in advanced capitalist societies.......There is a vast literature about the relationships between government and business in advanced capitalist societies....

  8. Nordic Corporate Governance Revisited

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2016-01-01

    This paper reviews the key elements of the Nordic governance model, which include a distinct legal system, high governance ratings and low levels of corruption. Other characteristics include concentrated ownership, foundation ownership, semi two-tier board structures, employee representation...

  9. Governance in Health - The Need for Exchange and Evidence Comment on "Governance, Government, and the Search for New Provider Models".

    Science.gov (United States)

    Chanturidze, Tata; Obermann, Konrad

    2016-05-17

    Governance in health is cited as one of the key factors in balancing the concerns of the government and public sector with the interests of civil society/private players, but often remains poorly described and operationalized. Richard Saltman and Antonio Duran look at two aspects in the search for new provider models in a context of health markets signalling liberalisation: (i) the role of the government to balance public and private interests and responsibilities in delivering care through modernised governance arrangements, and (ii) the finding that operational complexities may hinder well-designed provider governance models, unless governance reflects country-specific realities. This commentary builds on the discussion by Saltman and Duran, and argues that the concept of governance needs to be clearly defined and operationalized in order to be helpful for policy debate as well as for the development of an applicable framework for performance improvement. It provides a working definition of governance and includes a reflection on the prevailing cultural norms in an organization or society upon which any governance needs to be build. It proposes to explore whether the "evidence-based governance" concept can be introduced to generate knowledge about innovative and effective governance models, and concludes that studies similar to the one by Saltman and Duran can inform this debate.

  10. Metropolitan Governance Reforms: The Case of Seoul Metropolitan Government

    Directory of Open Access Journals (Sweden)

    Nicholas Snyder

    2016-02-01

    Full Text Available Seoul is transforming into a global city that is competitive with many of the most notable cities in the world such as Tokyo, New York, and London. Seoul's metropolitan governance structure is uniquely suited to the Korean peninsula and has been able to be dynamic in order to adapt to political changes the country has experienced. This article examines the initiatives behind metropolitan governance reforms in Seoul and the factors that play an important role in influencing the current governance structure. The Seoul Metropolitan Government (SMG is set on improving the lives of citizens and ensuring they are happy with their city through transparency, accountability, efficiency, and effectiveness of government among other things. This region has become a strong contributor to the economic growth of the county and helped to create opportunities to attract and retain businesses, implement innovative investment projects and develop a talented workforce. Amongst other reasons, Seoul's solid fiscal system has allowed the city to build the necessary organizational capacity for SMG as well. Additionally, Seoul citizens enjoy a good quality of life because of the educational options, employment opportunities, housing spaces, leisure activities, and cultural experiences found in the city. There are still some challenges ahead but Seoul realizes the importance of civic participation for capacity building and sustainability. One of Seoul's strategies to promoting sustainable living within the city is its ability to engage the public. By promoting citizen participation and feedback, Seoul feels that it will gain new perceptivities during the policy decision-making process. The city's current governance methods continue to succeed because the leaders at SMG understand what is essential to executing successful governance reform: citizens.

  11. Metropolitan Governance Reforms: The Case of Seoul Metropolitan Government

    Directory of Open Access Journals (Sweden)

    Nicholas Snyder

    2012-10-01

    Full Text Available Seoul is transforming into a global city that is competitive with many of the most notable cities in the world such as Tokyo, New York, and London. Seoul’s metropolitan governance structure is uniquely suited to the Korean peninsula and has been able to be dynamic in order to adapt to political changes the country has experienced. This article examines the initiatives behind metropolitan governance reforms in Seoul and the factors that play an important role in influencing the current governance structure. The Seoul Metropolitan Government (SMG is set on improving the lives of citizens and ensuring they are happy with their city through transparency, accountability, efficiency, and effectiveness of government among other things. This region has become a strong contributor to the economic growth of the county and helped to create opportunities to attract and retain businesses, implement innovative investment projects and develop a talented workforce. Amongst other reasons, Seoul’s solid fiscal system has allowed the city to build the necessary organizational capacity for SMG as well. Additionally, Seoul citizens enjoy a good quality of life because of the educational options, employment opportunities, housing spaces, leisure activities, and cultural experiences found in the city. There are still some challenges ahead but Seoul realizes the importance of civic participation for capacity building and sustainability. One of Seoul’s strategies to promoting sustainable living within the city is its ability to engage the public. By promoting citizen participation and feedback, Seoul feels that it will gain new perceptivities during the policy decision-making process. The city’s current governance methods continue to succeed because the leaders at SMG understand what is essential to executing successful governance reform: citizens.

  12. 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

  13. Distinct Localization of SNAP47 Protein in GABAergic and Glutamatergic Neurons in the Mouse and the Rat Hippocampus.

    Science.gov (United States)

    Münster-Wandowski, Agnieszka; Heilmann, Heike; Bolduan, Felix; Trimbuch, Thorsten; Yanagawa, Yuchio; Vida, Imre

    2017-01-01

    Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member of the SNAP family, which does not contribute directly to exocytosis and synaptic vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread expression in nervous tissue, but little is known about its cellular and subcellular localization in hippocampal neurons. Therefore, in the present study we applied multiple-immunofluorescence labeling, immuno-electron microscopy and in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and rat hippocampus. While the immunofluorescence signal for SNAP47 showed a widespread distribution in both mouse and rat, the labeling pattern was complementary in the two species: in the mouse the immunolabeling was higher over the CA3 stratum radiatum, oriens and cell body layer. In contrast, in the rat the labeling was stronger over the CA1 neuropil and in the CA3 stratum lucidum. Furthermore, in the mouse high somatic labeling for SNAP47 was observed in GABAergic interneurons (INs). On the contrary, in the rat, while most INs were positive, they blended in with the high neuropil labeling. ISH confirmed the high expression of SNAP47 RNA in INs in the mouse. Co-staining for SNAP47 and pre- and postsynaptic markers in the rat revealed a strong co-localization postsynaptically with PSD95 in dendritic spines of pyramidal cells and, to a lesser extent, presynaptically, with ZnT3 and vesicular glutamate transporter 1 (VGLUT1) in glutamatergic terminals such as mossy fiber (MF) boutons. Ultrastructural analysis confirmed the pre- and postsynaptic localization at glutamatergic synapses. Furthermore, in the mouse hippocampus SNAP47 was found to be localized at low levels to dendritic shafts and axon terminals of putative INs forming symmetric synapses, indicating that this protein could be trafficked to both post- and presynaptic sites in both

  14. 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.

  15. 非政府组织的知识创新:需求、影响因素与路径%Knowledge Innovation of Non-Government Organization:Demands,Influencing Factors and Routes

    Institute of Scientific and Technical Information of China (English)

    裴乐

    2014-01-01

    在信息化浪潮下,知识的急速增长为组织发展带来了前所未有的机遇和挑战。知识因自身的独特性,不同于传统资源,有助于弥补非政府组织在资源配置和占有中的劣势。内外需求促使非政府组织准确分析知识、环境、组织因素,有效开展知识管理与创新,全面提升知识素质与能力。非政府组织可以从知识战略、组织学习、流程与机制、知识网络等方面,系统地实施知识创新活动,培养独特的核心知识,形成强大的竞争力,以更好的服务在社会转型和治理变革中实现价值。%Under the tide of informationization,the rapid growth of knowledge brings opportunities and challenges to organizations that did not exist before. The knowledge is different from traditional resources for its uniqueness, which helps remedy the disadvantages of non-government organizations in resources allocation and occupation. Demands from inside and outside impel non-government organizations to analyze factors of knowledge,environ-ment and organizations precisely,to develop knowledge management and innovation effectively,and to promote knowledge quality and ability totally. From aspects of knowledge strategy,organizing to learn,procedure,mecha-nism and knowledge network,non-government organizations can implement knowledge innovation activity system-atically to form unique core knowledge and powerful competence. Then,non-government organizations will realize value in social transformation and governance change by providing better and more services.

  16. Big Bad Governance.

    Science.gov (United States)

    Richardson, James T.

    1999-01-01

    Argues that the Association of Governing Boards of Universities and Colleges' statement on governance calls for more centralized authority, rejecting both the principles and the practice of shared governance and diminishing the role of faculty. Suggests that the association revise its statement to include a better understanding of how academe…

  17. Transformative environmental governance

    Science.gov (United States)

    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to ...

  18. Global water governance

    NARCIS (Netherlands)

    Gupta, J.; Falkner, R.

    2013-01-01

    Although (fresh) water challenges are primarily local in nature, globalization has led to feedback effects that make many water challenges global in nature. This chapter examines global water governance. It discusses four phases of water governance, argues that water governance is dispersed and

  19. Global water governance

    NARCIS (Netherlands)

    Gupta, J.; Falkner, R.

    2013-01-01

    Although (fresh) water challenges are primarily local in nature, globalization has led to feedback effects that make many water challenges global in nature. This chapter examines global water governance. It discusses four phases of water governance, argues that water governance is dispersed and inco

  20. Project governance: selected South African government experiments

    Directory of Open Access Journals (Sweden)

    G. van der Walt

    2008-07-01

    Full Text Available Some form of accountability and power structure binds all organisations. Such structures are typically referred to as the “governance” structure of the organisation. In organisations that have relatively mature project applications and methodologies in place, governance mechanisms are established on more permanent bases. With its focus on performance, results and outcomes, project governance establishes decision-making structures, as well as accountability and responsibility mechanisms in public institutions to oversee projects. As government institutions increasingly place emphasis on project applications for policy implementation and service delivery initiatives, mechanisms or structures should be established to facilitate clear interfaces between the permanent organisation and the temporary project organisation. Such mechanisms or structures should enhance the governance of projects, that is, the strategic alignment of projects, the decentralisation of decision- making powers, rapid resource allocation, and the participation of external stakeholders. The purpose of this article is to explore the concept “project governance”, and to highlight examples of project governance as applied in selected government departments in provincial and national spheres. This would enable the establishment of best practice examples and assist to develop benchmarks for effective project applications for service delivery improvement.

  1. Selective factors governing in vitro β-carotene bioaccessibility: negative influence of low filtration cutoffs and alterations by emulsifiers and food matrices.

    Science.gov (United States)

    Corte-Real, Joana; Richling, Elke; Hoffmann, Lucien; Bohn, Torsten

    2014-12-01

    Because of their putative health benefits, the biological fate of carotenoids after digestion has been met with much interest, and ex vivo methods using carotenoid standards to study their digestion and further metabolism have been developed. In the absence of a complex food matrix, that is, when studying isolated carotenoids, protocol conditions of gastrointestinal digestion models have to be adjusted. In this investigation, we hypothesized that certain selected factors would significantly influence the bioaccessibility of β-carotene in vitro. The factors considered included (i) type of lipid matrix employed (milk, cream, or oil), (ii) presence/absence of emulsifiers (e.g. lecithin and taurocholate), (iii) addition of a gastric lipase, and (iv) final filtration (20 or 200 nm) of the digesta. Adding an emulsifier mixture (10 mg lecithin + 50 mg monoolein + 5 mg oleic acid) enhanced β-carotene bioaccessibility 3 times (P emulsifier and matrix should be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Oestradiol Regulates Neuropeptide Y Release and Gene Coupling with the GABAergic and Glutamatergic Synapses in the Adult Female Rat Dentate Gyrus.

    Science.gov (United States)

    Velíšková, J; Iacobas, D; Iacobas, S; Sidyelyeva, G; Chachua, T; Velíšek, L

    2015-12-01

    Neuropeptide Y (NPY) is an endogenous modulator of neuronal activity affecting both GABAergic and glutamatergic transmission. Previously, we found that oestradiol modifies the number of NPY immunoreactive neurones in the hippocampal dentate gyrus. In the present study, we investigated which oestrogen receptor type is responsible for these changes in the number of NPY-positive neurones. Furthermore, we determined the effects of oestrogen receptor activation on NPY release. Finally, we examined the contribution of oestrogen toward the remodelling of the GABAergic and glutamatergic gene networks in terms of coupling with Npy gene expression in ovariectomised rats. We found that activation of either oestrogen receptor type (ERα or ERβ) increases the number of NPY-immunopositive neurones and enhances NPY release in the dentate gyrus. We also found that, compared to oestrogen-lacking ovariectomised rats, oestrogen replacement increases the probability of synergistic/antagonistic coupling between the Npy and GABAergic synapse genes, whereas the glutamatergic synapse genes are less likely to be coupled with Npy under similar conditions. The data together suggest that oestrogens play a critical role in the regulation of NPY system activity and are also involved in the coupling/uncoupling of the Npy gene with the GABAergic and glutamatergic synapses in the female rat dentate gyrus. © 2015 British Society for Neuroendocrinology.

  3. 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.

  4. 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…

  5. Corticolimbic hyper-response to emotion and glutamatergic function in people with high schizotypy : a multimodal fMRI-MRS study

    NARCIS (Netherlands)

    Modinos, G; McLaughlin, A; Egerton, A; McMullen, K; Kumari, V; Barker, G J; Keysers, C; Williams, S C R

    2017-01-01

    Animal models and human neuroimaging studies suggest that altered levels of glutamatergic metabolites within a corticolimbic circuit have a major role in the pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate dysfunction could lead to amygdala hyper-response to

  6. 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.

  7. 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…

  8. Factors Governing the Differences in the Degree to Which Preschool Learning Institutions are Prepared to Adopt the Federal State Educational Standard

    Directory of Open Access Journals (Sweden)

    Tatyana Afanaseva

    2015-03-01

    Full Text Available This article briefly describes the methodology and results of an empirical study into the preparedness of preschool learning institutions to adopt the Federal State Educational Standard (FSES, which was conducted as part of developing a theoretical model and tools for streamlining the mechanism of their development. The author identifies factors that determine the differences in the degree to which such institutions are prepared to introduce the FSES and establishes the extent of their impact.

  9. Energy value as a factor of agroforestry wood species selectivity in Akinyele and Ido local government areas of Oyo State, Nigeria

    Energy Technology Data Exchange (ETDEWEB)

    Erakhrumen, A.A. [Department of Forest Resources Management, University of Ibadan, Ibadan (Nigeria)

    2009-10-15

    Wood usage for cooking and heating is still very relevant in most developing countries especially those of sub-Saharan Africa and many parts of Asia. Therefore, sustainable means of generating it for this and other purposes are necessary bearing in mind the influence of indigenous knowledge/users' perspective on any production method regarding success and sustenance. In conformity with this view, questionnaires were administered on 240 respondents in 8 rural communities of Akinyele and Ido Local Government Areas (LGAs) of Oyo State, Nigeria, to elicit information on species that can be used as fuelwood, preferred by the respondents for incorporation into and/or retention in agroforestry plots, out of which 179 (i.e. 75% of the total number of questionnaires administered) were successfully retrieved for statistical analyses. Twelve woody species namely: Annona senegalensis, Anogeissus leiocarpus, Bridelia ferruginea, Daniellia oliveri, Detarium microcarpum, Gardenia ternifolia, Hymenocardia acida, Lophira lanceolata, Parkia biglobosa, Terminalia avicennioides, Triplochiton scleroxylon and Vitellaria paradoxa were prioritized on the basis of respondents' preference using a ranking pattern. Friedman chi-square analysis showed that there was no significant difference (p < 0.05) in the ranking pattern of the respondents from the two LGAs. The mean net calorific values (NCV) of the 12 species were found to be 17.71, 18.63, 18.04, 16.03, 17.67, 18.46, 19.00, 21.68, 19.63, 18.25, 14.65, and 19.47 MJ kg{sup -1} respectively. The result of a two-way analysis of variance indicated a significant variation (p < 0.05) in NCV data for all the species pooled together but not for each species except for D. oliveri with a follow-up test using Fisher's Least Significant Difference. The Pearson's moment correlation analysis gave positive coefficient values (r = 0.868 and 0.874, p < 0.05) between NCV and the cumulative ranking values in Akinyele and Ido LGAs

  10. Local Government Structure and Capacities in Europe

    NARCIS (Netherlands)

    Nemec, J.; Vries, M.S. de

    2015-01-01

    This article argues that the local government capacities and local government performance in Europe clearly rank this continent to the most developed world areas from the point of local democracy. The background factors explaining this situation have a multidimensional character and one can identify

  11. Local Government Structure and Capacities in Europe

    NARCIS (Netherlands)

    Nemec, J.; Vries, M.S. de

    2015-01-01

    This article argues that the local government capacities and local government performance in Europe clearly rank this continent to the most developed world areas from the point of local democracy. The background factors explaining this situation have a multidimensional character and one can identify

  12. Entrenching Good Government Reforms

    OpenAIRE

    Tushnet, Mark V.

    2011-01-01

    Those concerned with enumerated powers, the Tenth Amendment, and limited governance have many questions about current trends in U.S. governance: Has the federal government grown too large? Is it doing too much? Has it transgressed lawful limits? Is the federal‐state relationship out of balance? Assuming that the federal government has gotten too large, what can you do about it? Or, more generally, what can you do if you think that the federal government is too big, or too small, or is doin...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

    Science.gov (United States)

    Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

    2015-10-21

    Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

  1. 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.

  2. 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

  3. Late postnatal shifts of parvalbumin and nitric oxide synthase expression within the GABAergic and glutamatergic phenotypes of inferior colliculus neurons.

    Science.gov (United States)

    Fujimoto, Hisataka; Konno, Kotaro; Watanabe, Masahiko; Jinno, Shozo

    2017-03-01

    The inferior colliculus (IC) is partitioned into three subdivisions: the dorsal and lateral cortices (DC and LC) and the central nucleus (ICC), and serves as an integration center of auditory information. Recent studies indicate that a certain population of IC neurons may represent the non-GABAergic phenotype, while they express well-established cortical/hippocampal GABAergic neuron markers. In this study we used the optical disector to investigate the phenotype of IC neurons expressing parvalbumin (PV) and/or nitric oxide synthase (NOS) in C57BL/6J mice during the late postnatal period. Four major types of IC neurons were defined by the presence (+) or absence (-) of PV, NOS, and glutamic acid decarboxylase 67 (GAD67): PV(+) /NOS(-) /GAD67(+) , PV(+) /NOS(+) /GAD67(+) , PV(+) /NOS(-) /GAD67(-) , and PV(-) /NOS(+) /GAD67(-) . Fluorescent in situ hybridization for vesicular glutamate transporter 2 mRNA indicated that almost all GAD67(-) IC neurons represented the glutamatergic phenotype. The numerical densities (NDs) of total GAD67(+) IC neurons remained unchanged in all subdivisions. The NDs of PV(+) /NOS(-) /GAD67(+) neurons and PV(-) /NOS(+) /GAD67(-) neurons were reduced with age in the ICC, while they remained unchanged in the DC and LC. By contrast, the NDs of PV(+) /NOS(+) /GAD67(+) neurons and PV(+) /NOS(-) /GAD67(-) neurons were increased with age in the ICC, although there were no changes in the DC and LC. The cell body size of GAD67(+) IC neurons did not vary according to the expression of PV with or without NOS. The present findings indicate that the expression of PV and NOS may shift with age within the GABAergic and glutamatergic phenotypes of IC neurons during the late postnatal period. J. Comp. Neurol. 525:868-884, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Hard and Soft Governance

    DEFF Research Database (Denmark)

    Moos, Lejf

    2009-01-01

    and discusses governance forms at several levels. The first layer is the global: the methods of 'soft governance' that are being utilised by transnational agencies. The second layer is the national and local: the shift in national and local governance seen in many countries, but here demonstrated in the case......The governance and leadership at transnational, national and school level seem to be converging into a number of isomorphic forms as we see a tendency towards substituting 'hard' forms of governance, that are legally binding, with 'soft' forms based on persuasion and advice. This article analyses...... of Denmark, and finally the third layer: the leadership used in Danish schools. The use of 'soft governance' is shifting the focus of governance and leadership from decisions towards influence and power and thus shifting the focus of the processes from the decision-making itself towards more focus...

  5. Governance and organizational theory

    Directory of Open Access Journals (Sweden)

    Carlos E. Quintero Castellanos

    2017-07-01

    Full Text Available The objective of this essay is to propose a way to link the theoretical body that has been weaved around governance and organizational theory. For this, a critical exposition is done about what is the theoretical core of governance, the opportunity areas are identified for the link of this theory with organizational theory. The essay concludes with a proposal for the organizational analysis of administrations in governance. The essay addresses with five sections. The first one is the introduction. In the second one, I present a synthesis of the governance in its current use. In the next one are presented the work lines of the good governance. In the fourth part, I show the organizational and managerial limits in the governance theory. The last part develops the harmonization proposal for the governance and organizational theories.

  6. Enacting Governance through Strategy

    DEFF Research Database (Denmark)

    Brandtner, Christof; Höllerer, Markus A.; Meyer, Renate E.

    2017-01-01

    Over the past two decades, research has emphasised a shift from city government to urban governance. Such a shift brings about its very own challenges, namely governance gaps, uncertain configurations in governance and a limited capacity to act. In this paper, we argue that the concurrent rise...... of strategy documents in city administration addresses these challenges. Our central claim is that strategy documents can be understood as a distinct discursive device through which local governments enact aspired governance configurations. We illustrate our argument empirically using two prominent examples...... that, while showing similar features and characteristics, are anchored in different administrative traditions and institutional frameworks: the city administrations of Sydney, Australia, and Vienna, Austria. The contribution of the paper is to show how strategy documents enact governance configurations...

  7. Does the UK government's teenage pregnancy strategy deal with the correct risk factors? Findings from a secondary analysis of data from a randomised trial of sex education and their implications for policy.

    Science.gov (United States)

    Allen, E; Bonell, C; Strange, V; Copas, A; Stephenson, J; Johnson, A M; Oakley, A

    2007-01-01

    Much of the UK government's 1999 report on teenage pregnancy was by necessity based on rather old or non-longitudinal research. To examine the associations between risk factors identified in the report and pregnancy at or before age 16 years among young women and partners of young men using the more recent data. Socioeconomic disadvantage, being born to a teenage mother, expectation of being a teenage parent, low educational expectations and various other behaviours are potential risk factors for teenage pregnancy, as suggested by unadjusted analyses. Those who cited school as providing information on sex had a reduced risk of pregnancy at or before age 16 years, as did girls reporting easy communication with parent or guardian at baseline. Various measures of low sexual health knowledge were not associated, in either adjusted or unadjusted analyses, with increased risk of pregnancy at or before age 16 years among boys or girls. A focus on many of the risk factors identified in the 1999 report is supported herein. It is suggested that knowledge may not be an important determinant, but that relationships with parents and school, as well as expectations for the future, may have important influences on teenage pregnancy. The analysis also provides new insights into risk factors for pregnancies among the partners of young men.

  8. Corporate governance and government owned corporations in Queensland

    National Research Council Canada - National Science Library

    MCDONOUGH, Darryl D

    1998-01-01

    ...) - principles of corporate governance applicable to government owned corporations - history of corporatisation - objectives and features of the Government Owned Corporations Act 1993 - categorisation...

  9. Governance challenges in Tanzania's environmental impact ...

    African Journals Online (AJOL)

    EJIRO

    African Journal of Environmental Science and Technology Vol. 5(2), pp. ... include sociological and psychological factors, that influences accountability actions by environmental agencies ... Key words: Accountability, governance, effectiveness awareness, courage. ... only professional ethics for environmental assessments.

  10. Prevalence of traumatic dental injuries and role of incisal overjet and inadequate lip coverage as risk factors among 4-15 years old government school children in Baddi-Barotiwala Area, Himachal Pradesh, India.

    Science.gov (United States)

    Gupta, Shipra; Kumar-Jindal, Sanjeev; Bansal, Mohit; Singla, Anshu

    2011-11-01

    To assess the prevalence of traumatic dental injuries (TDI) in school children in Baddi- Barotiwala, Himachal Pradesh, India. A cross-sectional survey was carried out in Government schools among 1059 government school children aged 4- 15 years. The study was conducted from October 2009 to March 2010 during the school hours. The demographic detail was carried on a structured questionnaire. The data regarding the traumatic injuries was recorded using modified Ellis' classification. Prevalence of TDI was found to be 4.15 %. 95.45% of the injuries were to the maxillary anterior teeth. Maxillary central incisor was the most common tooth to be affected due to trauma (54.5 %). Enamel with dentin fracture with pulp exposure was the main type of TDI (43.1%). The majority of TDIs were untreated (97.7 %). Falls (54.5%) were found to be the main cause. Over jet over 3 mm and inadequate lip coverage were found to be important contributing factors for TDIs. The present study revealed a relatively low prevalence of dental trauma, but still this figure represents a large number of children. Therefore, educational programs are to be initiated for the community regarding causes, prevention and treatment of traumatic dental injuries. It is crucial to generate considerable efforts to implement health promotion strategies to reverse the observed trends and to provide treatment to TDIs to prevent their biologic and psychological consequences.

  11. The Economy Governing During Globalization Era

    Directory of Open Access Journals (Sweden)

    Ion Bucur

    2006-07-01

    Full Text Available World and national economie governing is an essential premise of the political stability and democratic evolution. In this study are approached theoretical and practical aspects of the economie governing. Theoretical acquisitions in this field highlit multiple perspectives of approaching and difficulties to characterize this complex and multisized fenomenon. A possible theory of governing the economy needs to use some concepts and mechanisms particular to more scientific fields (political science, economy, cibernetics, the theory of systems and others. The dinamic character and the instability of the present system of governing imposed the analysis of the factors and conditions which have generated the crises of the national and world economic governing. In this context, there are indentified the forms of manifesting the instability (lack of legitimacy, transpa¬rence and democratic responsability, and also the direction of necessary action to implement an efficient and responsable economic governing.

  12. The Economy Governing During Globalization Era

    Directory of Open Access Journals (Sweden)

    Ion Bucur

    2006-09-01

    Full Text Available World and national economie governing is an essential premise of the political stability and democratic evolution. In this study are approached theoretical and practical aspects of the economie governing. Theoretical acquisitions in this field highlit multiple perspectives of approaching and difficulties to characterize this complex and multisized fenomenon. A possible theory of governing the economy needs to use some concepts and mechanisms particular to more scientific fields (political science, economy, cibernetics, the theory of systems and others. The dinamic character and the instability of the present system of governing imposed the analysis of the factors and conditions which have generated the crises of the national and world economic governing. In this context, there are indentified the forms of manifesting the instability (lack of legitimacy, transpa¬rence and democratic responsability, and also the direction of necessary action to implement an efficient and responsable economic governing.

  13. Local Government Structure and Capacities in Europe

    OpenAIRE

    Nemec, J.; Vries, M.S. de

    2015-01-01

    This article argues that the local government capacities and local government performance in Europe clearly rank this continent to the most developed world areas from the point of local democracy. The background factors explaining this situation have a multidimensional character and one can identify as core positive factors the relative economic wealth, high human development, the long historical tradition of the subsidiarity principle in most parts of Europe, and the regulatory function of t...

  14. New Role for an Old Rule: N-end Rule-Mediated Degradation of Ethylene Responsive Factor Proteins Governs Low Oxygen Response in Plants

    Institute of Scientific and Technical Information of China (English)

    Francesco Licausi; Chiara Pucciariello; Pierdomenico Perata

    2013-01-01

    The N-end rule pathway regulates protein degradation,which depends on exposed N-terminal sequences in prokaryotes and eukaryotes.In plants,conserved and specific enzymes stimulate selective proteolysis.Although a number of developmental and growth phenotypes have been reported for mutants in the N-end rule,its function has remained unrelated to specific physiological pathways.The first report of the direct involvement of the N-end rule in stress responses focused on hypoxic signaling and how the oxygen-dependent oxidation of cystein promotes the N-end rule-mediated degradation of ethylene responsive factor (ERF)-Ⅶ proteins,the master regulators of anaerobic responses.It has been suggested that plants have evolved specific mechanisms to tune ERF-Ⅶ availability in the nucleus.In this review,we speculate that ERF-Ⅶ proteins are reversibly protected from degradation via membrane sequestration.The oxidative response in plants subjected to anoxic conditions suggests that reactive oxygen and nitrogen species (reactive oxygen species and reactive nitrogen species) may interact or interfere with the N-end rule pathway-mediated response to hypoxia.

  15. Experimental study of the factors governing the Staebler-Wronski photodegradation effect in a-Si:H solar cells. Final technical report, July 7, 1994--January 15, 1998

    Energy Technology Data Exchange (ETDEWEB)

    Han, D [Univ. of North Carolina, Chapel Hill, NC (United States)

    1998-05-01

    This report describes continuing studies on electroluminescence (EL), field profile, and hydrogen microstructure by the University of North Carolina, Chapel Hill, during the third year and the extension period. Based on systematic studies of the EL, the authors developed a complete model to explain the unique features of the EL as dispersive-transport-controlled, non-geminate recombinant processes. This model can explain the main features of the EL, not only in hydrogenated amorphous silicon (a-Si:H), but also in other types of trap-rich materials. By employing the forward current and EL temperature-dependence studies, information of both the localized tail states and the deep defect states in real solar-cell structures were obtained concomitantly, which is crucial for the device performance. The authors measured the internal electric field profile in p-i-n and n-i-p cells by a null-current method; they studied the structure of the hydrogen clusters in hot-wire a-Si:H films, both theoretically and experimentally, and show a clear evidence of improved structural order in hot-wire a-Si:H, which is an important factor leading to more stable materials. To link the film microstructure to the metastability, the authors also started the film stress measurements.

  16. Corporate Governance and Pension Fund Performance

    Directory of Open Access Journals (Sweden)

    Oskar Kowalewski

    2012-03-01

    Full Text Available This study provides new evidence on the impact of governance on the performance of privately defined contribution pension plans. Using a hand collected data set on governance factors, the study shows that the external and internal governance mechanisms in pension plans are weak. One explanation for this weakness is the potential conflict between the pension beneficiaries and the fund’s owner, which depends on who bears the investment risk in the pension plan. Hence, different governance factors are found to be important for pension fund return on invested assets and also for its economic performance. Consequently, the overall policy conclusion is that more focus should be put on the governance of the pension funds, taking into account the different interests of the beneficiaries and owners as it may determine their performance.

  17. Electronic Governance: Myth or Opportunity for Nigerian Public Administration?

    Directory of Open Access Journals (Sweden)

    Jacob Olufemi Fatile

    2012-09-01

    Full Text Available Information and Communication Technologies (ICTs have changed the process of governance in the world. To manage government affairs for the benefits of citizens, governments have adopted e-governance technologies in service delivery. The objectives of this study are to provide a comprehensive review of e-governance in order to give it a sound framework, assess the levels of e-governance implementation, and evaluate critical success factors of e-governance implementation. The analysis of the impact of e-governance in service provision Nigeria is also provided. It notes that Nigeria is facing a number of challenges in the introduction of e-Governance. Given the importance of the successful implementation of electronic governance services and from a practical perspective, the paper suggests that government should take a positive position towards the factors which will bring about effective and efficient e-governance in Nigeria. Government should declare access to ICT services as fundamental human right of every Nigerian and to establish a timetable and guarantee enabling environment for attracting the right level of investments. The paper concludes that there is a lot of hope on the potential of e-governance to transform the internal efficiency of government and the relationship of government with citizens.

  18. CORPORATE GOVERNANCE IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Ciprian Apostol

    2015-09-01

    Full Text Available The objective of the research was focused on measuring the performance level of corporate governance in Romania. This is carried out by evaluating the importance level given to the principles of corporate governance in the Romanian economy, while the practices of transparency and dissemination of companies’ information in the selected sample were monitored. To achieve the objectives of the study, we need to examine the Corporate Governance Code of the Bucharest Stock Exchange. Sample companies were selected and their information from the “Comply or Explain” Statements was analyzed.The research method is a non-participating observation—based on the information from the “Comply or Explain” Statement to determine whether companies are applying corporate governance and transparency elements. The research results highlight the progress of Romanian companies in the process of exercising to the principles of corporate governance, becoming internationally recognized, and integrating into the Corporate Governance Code of the Bucharest Stock Exchange.

  19. Trust in Government: A Note from Nigeria

    Directory of Open Access Journals (Sweden)

    Iroghama Paul Iroghama

    2012-06-01

    Full Text Available The relationship between trust in government and factors that accounts for Nigerians citizen trust in their government has been of interest due a dearth of literature on such issue. This study is an attempt to bridge the gap from a public policy perspective. One of the measures usually used in the literature to measure trust or distrust in government is perception of corruption, but there are other yardsticks with which to measure determinant of trust in government, such as economic performance or political participation. This study used a micro-level analysis of public opinion survey data (question by question to ascertain empirical linkages of political trust within Nigeria. To this end, Afrobarometer survey Round Four conducted in 2008 was used for the analyses. Descriptive statistics provide background information on the sample, while multivariate logistic regression using SPSS were used to model the citizens’ trust for government in Nigeria. This study revealed that political trust or trust in governments in Nigeria stems from a number of factors. These are economy performance, media, interest in public affairs, religious membership, political participation, interpersonal trust, lack of basic needs, and management of corruption. Furthermore, the variables that influence trust in government the most are interpersonal trust and government management of corruption issue. Those that reported interpersonal trust also reported that they have trust for the government. While those that believe the governments are fighting or managing corruption nicely have a tendency to trust in the government. Although this study does not claim to provide all the answer on political trust or trust in governments in Nigeria, its attempt is to bridge gap in the literature on the topic and to assist future research in the area, as nothing exist on the topic as the moment. It is hope the subject will forms a basis upon which further analytical work on political

  20. Factors Governing P-Glycoprotein-Mediated Drug-Drug Interactions at the Blood-Brain Barrier Measured with Positron Emission Tomography.

    Science.gov (United States)

    Wanek, Thomas; Römermann, Kerstin; Mairinger, Severin; Stanek, Johann; Sauberer, Michael; Filip, Thomas; Traxl, Alexander; Kuntner, Claudia; Pahnke, Jens; Bauer, Florian; Erker, Thomas; Löscher, Wolfgang; Müller, Markus; Langer, Oliver

    2015-09-01

    The adenosine triphosphate-binding cassette transporter P-glycoprotein (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distribution of many drugs. ABCB1 may be involved in drug-drug interactions (DDIs) at the BBB, which may lead to changes in brain distribution and central nervous system side effects of drugs. Positron emission tomography (PET) with the ABCB1 substrates (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide and the ABCB1 inhibitor tariquidar has allowed direct comparison of ABCB1-mediated DDIs at the rodent and human BBB. In this work we evaluated different factors which could influence the magnitude of the interaction between tariquidar and (R)-[(11)C]verapamil or [(11)C]-N-desmethyl-loperamide at the BBB and thereby contribute to previously observed species differences between rodents and humans. We performed in vitro transport experiments with [(3)H]verapamil and [(3)H]-N-desmethyl-loperamide in ABCB1 and Abcb1a overexpressing cell lines. Moreover we conducted in vivo PET experiments and biodistribution studies with (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide in wild-type mice without and with tariquidar pretreatment and in homozygous Abcb1a/1b((-/-)) and heterozygous Abcb1a/1b((+/-)) mice. We found no differences for in vitro transport of [(3)H]verapamil and [(3)H]-N-desmethyl-loperamide by ABCB1 and Abcb1a and its inhibition by tariquidar. [(3)H]-N-Desmethyl-loperamide was transported with a 5 to 9 times higher transport ratio than [(3)H]verapamil in ABCB1- and Abcb1a-transfected cells. In vivo, brain radioactivity concentrations were lower for [(11)C]-N-desmethyl-loperamide than for (R)-[(11)C]verapamil. Both radiotracers showed tariquidar dose dependent increases in brain distribution with tariquidar half-maximum inhibitory concentrations (IC50) of 1052 nM (95% confidence interval CI: 930-1189) for (R)-[(11)C]verapamil and 1329 nM (95% CI: 980-1801) for [(11)C]-N-desmethyl-loperamide. In homozygous Abcb1a/1b

  1. Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan.

    Science.gov (United States)

    Riaz, Haris; Riaz, Talha; Khan, Muhammad Ubaid; Aziz, Sina; Ullah, Faizan; Rehman, Anis; Zafar, Qandeel; Kazi, Abdul Nafey

    2011-08-11

    Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required. The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis.Of the seventy-nine patients included in the study, 46 (58.2%) were males while 33 (41.8%) were females. The mean age was 10.8 (± 4.5) years with the dominant age group (46.2%) being 10 to 14 years. In 62 (78.8%) cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2%) cases with monthly house hold income significant factor to the use of therapy. The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients.Conflicts of Interest: None.

  2. Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan

    Directory of Open Access Journals (Sweden)

    Rehman Anis

    2011-08-01

    Full Text Available Abstract Background Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required. Findings The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis. Of the seventy-nine patients included in the study, 46 (58.2% were males while 33 (41.8% were females. The mean age was 10.8 (± 4.5 years with the dominant age group (46.2% being 10 to 14 years. In 62 (78.8% cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2% cases with monthly house hold income significant factor to the use of therapy. Conclusions The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients. Conflicts of Interest: None

  3. Key factors governing uncertainty in the response to sunshade geoengineering from a comparison of the GeoMIP ensemble and a perturbed parameter ensemble

    Science.gov (United States)

    Irvine, Peter J.; Boucher, Olivier; Kravitz, Ben; Alterskjær, Kari; Cole, Jason N. S.; Ji, Duoying; Jones, Andy; Lunt, Daniel J.; Moore, John C.; Muri, Helene; Niemeier, Ulrike; Robock, Alan; Singh, Balwinder; Tilmes, Simone; Watanabe, Shingo; Yang, Shuting; Yoon, Jin-Ho

    2014-07-01

    Climate model studies of the consequences of solar geoengineering are central to evaluating whether such approaches may help to reduce the harmful impacts of global warming. In this study we compare the sunshade solar geoengineering response of a perturbed parameter ensemble (PPE) of the Hadley Centre Coupled Model version 3 (HadCM3) with a multimodel ensemble (MME) by analyzing the G1 experiment from the Geoengineering Model Intercomparison Project (GeoMIP). The PPE only perturbed a small number of parameters and shares a common structure with the unperturbed HadCM3 model, and so the additional weight the PPE adds to the robustness of the common climate response features in the MME is minor. However, analysis of the PPE indicates some of the factors that drive the spread within the MME. We isolate the role of global mean temperature biases for both ensembles and find that these biases have little effect on the ensemble spread in the hydrological response but do reduce the spread in surface air temperature response, particularly at high latitudes. We investigate the role of the preindustrial climatology and find that biases here are likely a key source of ensemble spread at the zonal and grid cell level. The role of vegetation, and its response to elevated CO2 concentrations through the CO2 physiological effect and changes in plant productivity, is also investigated and proves to have a substantial effect on the terrestrial hydrological response to solar geoengineering and to be a major source of variation within the GeoMIP ensemble.

  4. Exploring Knowledge Governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahoney, Joseph T

    Knowledge governance is characterized as a distinctive research subject, the understanding of which cuts across diverse fields in management. In particular, it represents an intersection of knowledge management, strategic management, and theories of the firm. Knowledge governance considers how...... deployment of governance mechanisms influences knowledge processes: sharing, retaining, and creating knowledge. We survey the papers in this volume of the special issue, and discuss the remaining research challenges....

  5. Governing through standards

    DEFF Research Database (Denmark)

    Brøgger, Katja

    2014-01-01

    This abstract adresses the ways in which new education standards have become integral to new modes of education governance. The paper explores the role of standards for accelerating the shift from national to transnational governance in higher education. Drawing on the case of higher education...... development in Scandinavia, the paper focuses on the unintended effects of the new international standards. The Bologna process was reframed and recontextualized in ways that undermined the very system it was set out to transform and govern....

  6. Governance and Socioeconomic Performance

    OpenAIRE

    Vītola, A; Šenfelde, M

    2012-01-01

    There are wide discussions on the causes of the differences in the economic performance. Recent studies have stressed out the crucial role of institutions – formal and informal constraints that shape human interaction. The aim of this article is to evaluate the influence of governance – traditions and institutions by which authority in a country is exercised –on the socioeconomic development. To measure the level of governance we used World Bank’s Worldwide Governance Indicators and such indi...

  7. Civil Society and Governance

    DEFF Research Database (Denmark)

    Hulgård, Lars

    An illustration of how important the relationship is between civil society anbd governance. A short historic journey with four snapshots of times and situations that have provided interesting evidence about the connection between civil society and governance. My goal for the short historic journey...... is to make clear and hopefully even verify that providing knowledge about the impact of civil society and citizens’ participation on governance is one of the most urgent research tasks in the current period of time....

  8. Civil Society and Governance

    DEFF Research Database (Denmark)

    Hulgård, Lars

    An illustration of how important the relationship is between civil society anbd governance. A short historic journey with four snapshots of times and situations that have provided interesting evidence about the connection between civil society and governance. My goal for the short historic journey...... is to make clear and hopefully even verify that providing knowledge about the impact of civil society and citizens’ participation on governance is one of the most urgent research tasks in the current period of time....

  9. Governability in Contemporary Mexico

    OpenAIRE

    Leonardo Curzio Gutiérrez

    1998-01-01

    Given the difficulties to establish a concept of governability and the frequent ideological usage of the term, it is much more operative to turn to the principle of governability, in the broad sense, which supports itself on five pillars: the political legitimacy of the government, the governmental efficiency to attend to the demands of society, the existence of shared social project, the agreement with the principle special interest groups, and international viability. The analysis of the st...

  10. Energy Efficiency Governance: Handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This handbook has been written to assist EE practitioners, government officials and stakeholders to establish effective EE governance structures for their country. The handbook provides readers with relevant information in an accessible format that will help develop comprehensive and effective governance mechanisms. For each of the specific topics dealt with (see Figure 1 in the Handbook), the IEA offers guidelines for addressing issues, or directs readers to examples of how such issues have been dealt with by specific countries.

  11. Implementing a new governance model.

    Science.gov (United States)

    Stanley-Clarke, Nicky; Sanders, Jackie; Munford, Robyn

    2016-05-16

    Purpose - The purpose of this paper is to discuss the lessons learnt from the process of implementing a new model of governance within Living Well, a New Zealand statutory mental health agency. Design/methodology/approach - It presents the findings from an organisational case study that involved qualitative interviews, meeting observations and document analysis. Archetype theory provided the analytical framework for the research enabling an analysis of both the formal structures and informal value systems that influenced the implementation of the governance model. Findings - The research found that the move to a new governance model did not proceed as planned. It highlighted the importance of staff commitment, the complexity of adopting a new philosophical approach and the undue influence of key personalities as key determining factors in the implementation process. The findings suggest that planners and managers within statutory mental health agencies need to consider the implications of any proposed governance change on existing roles and relationships, thinking strategically about how to secure professional commitment to change. Practical implications - There are ongoing pressures within statutory mental health agencies to improve the efficiency and effectiveness of organisational structures and systems. This paper has implications for how planners and managers think about the process of implementing new governance models within the statutory mental health environment in order to increase the likelihood of sustaining and embedding new approaches to service delivery. Originality/value - The paper presents insights into the process of implementing new governance models within a statutory mental health agency in New Zealand that has relevance for other jurisdictions.

  12. Corporate governance in Malaysia

    National Research Council Canada - National Science Library

    SINGAM, Kamini

    2003-01-01

    ... governance in Malaysia - the ownership structure, composition and operation of Malaysian companies in Malaysia - the nature of shareholder control and protection made available in the Malaysian corporate...

  13. The Socio-Demographic and Clinical Factors Associated with Quality of Life among Patients with Haematological Cancer in a Large Government Hospital in Malaysia.

    Science.gov (United States)

    Priscilla, Das; Hamidin, Awang; Azhar, Md Zain; Noorjan, Kon; Salmiah, Md Said; Bahariah, Khalid

    2011-07-01

    socio-demographic factors and clinical diagnoses. Efforts should be made to improve the overall quality of life of these patients.

  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. Learning Democratic Global Governance.

    Science.gov (United States)

    Haavelsrud, Magnus

    1996-01-01

    Outlines a model process of developing knowledge from within different groups and cultures to allow more equitable participation of all world societies in the definition of global governance. Reviews concepts relevant to education's contributions toward learning and creating democratic global governance. Discusses the educational utility of…

  16. Global Governance, Educational Change

    Science.gov (United States)

    Mundy, Karen

    2007-01-01

    In the last half decade, a rising literature has focused on the idea that processes of economic, political and social globalization require analysis in terms of governance at the global level. It is argued in this article that emerging forms of global governance have produced significant challenges to conventional conceptions of international…

  17. The governance of adaptation

    NARCIS (Netherlands)

    Huitema, Dave; Adger, William Neil; Berkhout, Frans; Massey, Eric; Mazmanian, Daniel; Munaretto, Stefania; Plummer, Ryan; Termeer, Katrien

    2016-01-01

    The governance of climate adaptation involves the collective efforts of multiple societal actors to address problems, or to reap the benefits, associated with impacts of climate change. Governing involves the creation of institutions, rules and organizations, and the selection of normative princi

  18. Using IT Governance

    Science.gov (United States)

    Brobst, Jan; Council, Chip

    2005-01-01

    The discussion in this article is intended to provide an examination of why top management, IT management, and internal auditors should be interested in IT governance. Some aspects of IT management will be described including implementation, auditing, availability, security, and alignment. One governance framework, COBIT, will be utilized as a…

  19. Educational Governance in Denmark

    Science.gov (United States)

    Moos, Lejf

    2014-01-01

    Denmark has entered global competition by expanding collaboration with European countries, which is profoundly impacting the public sector and school governance. Relations between the state and institutions are transforming from traditional democratic, public-sector models of governance into new forms characterized as corporate and market-driven…

  20. Sizing the government

    NARCIS (Netherlands)

    de Witte, K.; Moesen, W.

    2009-01-01

    Is there such a thing as an optimal government size? We investigate by the non-parametric Data Envelopment Analysis (DEA) the so-called `Armey curve' which claims an inverted U-shaped relationship between government size and economic performance. The DEA scores are linked to control variables as ini

  1. Sizing the government

    NARCIS (Netherlands)

    de Witte, K.; Moesen, W.

    2010-01-01

    Is there such a thing as an optimal government size? We investigate the so-called Armey curve, which claims an inverted U-shaped relationship between government size and economic performance, using non-parametric Data Envelopment Analysis (DEA). The DEA scores are linked to control variables, such a

  2. Educational Governance in Denmark

    Science.gov (United States)

    Moos, Lejf

    2014-01-01

    Denmark has entered global competition by expanding collaboration with European countries, which is profoundly impacting the public sector and school governance. Relations between the state and institutions are transforming from traditional democratic, public-sector models of governance into new forms characterized as corporate and market-driven…

  3. Improve Governance for Charters

    Science.gov (United States)

    Finn, Chester E., Jr.; Manno, Bruno V.; Wright, Brandon L.

    2017-01-01

    With 25 years of experience, the charter sector has had enough time to experience a host of unanticipated and unresolved problems related to the complex ways in which charter school governance relates to school leadership. The time has come for the sector to revisit some fundamental decisions about how charter schools and networks are governed,…

  4. Why Governments Intervene

    DEFF Research Database (Denmark)

    Knudsen, Jette Steen; Brown, Dana

    2015-01-01

    to promote international competitiveness of domestic businesses. Both sets of explanations see governments as driving CSR policies to meet particular national government goals. Support is found for the thesis that CSR policies are often related to international competitiveness, yet our findings suggest...

  5. Innovation in Governance

    NARCIS (Netherlands)

    Assche, van Kristof; Beunen, R.; Barba Lata, I.V.; Duineveld, M.

    2015-01-01

    In this chapter we develop a theoretical framework, deriving from the social systems theory of Niklas Luhmann and Evolutionary Governance Theory, to grasp the paradoxes of current notions of innovation in governance, and to outline an alternative approach. A renewed reflection on innovation we deem

  6. The Knowledge Governance Approach

    DEFF Research Database (Denmark)

    Foss, Nicolai

    2005-01-01

    An attempt is made to characterize a `knowledge governance approach' as a distinctive, emerging field that cuts across the fields of knowledge management, organisation studies, strategy and human resource management. Knowledge governance is taken up with how the deployment of administrative...... represents various challenges to more `closed' social science disciplines, notably economics....

  7. Policy Governance Revisited.

    Science.gov (United States)

    Price, William J.

    2001-01-01

    An administrator trainer/former superintendent's experience suggests that corporate governance models don't fit the reality of school governance in many districts. Elected board members define their roles differently than their business counterparts and derive little or no monetary benefit from public service. The "new breed" resemble…

  8. China and Global Governance

    Institute of Scientific and Technical Information of China (English)

    Wang Zaibang

    2007-01-01

    To enhance global governance has become more urgent with rapid development of globalization in the post-Cold War years. China has benefited from the process of globalization and hence should make greater contribution to the global governance in the future.

  9. Hard and Soft Governance

    DEFF Research Database (Denmark)

    Moos, Lejf

    2009-01-01

    The governance and leadership at transnational, national and school level seem to be converging into a number of isomorphic forms as we see a tendency towards substituting 'hard' forms of governance, that are legally binding, with 'soft' forms based on persuasion and advice. This article analyses...

  10. The governance of adaptation

    NARCIS (Netherlands)

    Huitema, Dave; Adger, William Neil; Berkhout, Frans; Massey, Eric; Mazmanian, Daniel; Munaretto, Stefania; Plummer, Ryan; Termeer, Katrien

    2016-01-01

    The governance of climate adaptation involves the collective efforts of multiple societal actors to address problems, or to reap the benefits, associated with impacts of climate change. Governing involves the creation of institutions, rules and organizations, and the selection of normative

  11. Instruments of Transformative Governance

    DEFF Research Database (Denmark)

    Borrás, Susana

    production and distribution channels. PDPs aim at overcoming current market and government failures by pooling resources in the attempt to solve this global social challenge. Thus, PDPs are a case of instruments of transformative research and innovation, operating in a transnational governance context...

  12. The Iraqi Governing Council

    Science.gov (United States)

    Social Education, 2004

    2004-01-01

    This article provides the details of the chronological events surrounding the establishment of a Governing Council in Iraq in July 2003 by the United States, acting as the leader of the Coalition Provisional Authority (CPA) that administers Iraq. The following topics are discussed in the article: (1) The Composition of the Governing Council; (2)…

  13. Partnerships and Governance

    DEFF Research Database (Denmark)

    Damgaard, Bodil

    Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark.......Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark....

  14. Privacy and Open Government

    Directory of Open Access Journals (Sweden)

    Teresa Scassa

    2014-06-01

    Full Text Available The public-oriented goals of the open government movement promise increased transparency and accountability of governments, enhanced citizen engagement and participation, improved service delivery, economic development and the stimulation of innovation. In part, these goals are to be achieved by making more and more government information public in reusable formats and under open licences. This paper identifies three broad privacy challenges raised by open government. The first is how to balance privacy with transparency and accountability in the context of “public” personal information. The second challenge flows from the disruption of traditional approaches to privacy based on a collapse of the distinctions between public and private sector actors. The third challenge is that of the potential for open government data—even if anonymized—to contribute to the big data environment in which citizens and their activities are increasingly monitored and profiled.

  15. Making Government Liquid

    DEFF Research Database (Denmark)

    du Gay, Paul; Millo, Yuval; Tuck, Penelope

    2012-01-01

    - an assemblage. We argue that understanding such assemblages-their emergence, activity, and, frequently, their failures-opens a window on analysing the nature of contemporary forms of financialised governance as a technosocial system. In so doing we suggest that the governance devices approach can off er a way......The financialised character of contemporary rationalities of public governance has been the subject of increased attention within a range of disciplinary and interdisciplinary fields. With this paper we propose a particular analytical framework, focused on the notion of 'governance devices......', for understanding the processes that underpin financialised governance and, more fundamentally, maintain the connections between markets and politics. Deploying three distinct cases, we indicate that these devices transcend divisions between the actor and the device and create a diff erent form of agency...

  16. Energy Efficiency Governance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    The purpose of this report is to help EE practitioners, government officials and stakeholders to establish the most effective EE governance structures, given their specific country context. It also aims to provide readers with relevant and accessible information to support the development of comprehensive and effective governance mechanisms. The International Energy Agency (IEA) conducted a global review of many elements of EE governance,including legal frameworks, institutional frameworks, funding mechanisms, co-ordination mechanisms and accountability arrangements, such as evaluation and oversight. The research tools included a survey of over 500 EE experts in 110 countries, follow-up interviews of over 120 experts in 27 countries and extensive desk study and literature searches on good EE governance.

  17. THEORIES OF CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Sorin Nicolae BORLEA

    2013-03-01

    Full Text Available This study attempts to provide a theoretical framework for the corporate governance debate. The review of various corporate governance theories enhances the major objective of corporate governance which is maximizing the value for shareholders by ensuring good social and environment performances. The theories of corporate governance are rooted in agency theory with the theory of moral hazard’s implications, further developing within stewardship theory and stakeholder theory and evolving at resource dependence theory, transaction cost theory and political theory. Later, to these theories was added ethics theory, information asymmetry theory or the theory of efficient markets. These theories are defined based on the causes and effects of variables such as: the configuration of the board of directors, audit committee, independence of managers, the role of top management and their social relations beyond the legal regulatory framework. Effective corporate governance requires applying a combination

  18. Governance, Trus