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Sample records for circuitry regulating phasic

  1. Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

    Directory of Open Access Journals (Sweden)

    Christelle Anaclet

    Full Text Available BACKGROUND: Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS. METHODOLOGY/PRINCIPAL FINDINGS: To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS. CONCLUSIONS/SIGNIFICANCE: These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2

  2. Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders

    Science.gov (United States)

    Wilcox, Claire E.; Pommy, Jessica M.; Adinoff, Bryon

    2016-01-01

    Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders

  3. Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders.

    Science.gov (United States)

    Wilcox, Claire E; Pommy, Jessica M; Adinoff, Bryon

    2016-04-01

    Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders

  4. Phytochemical regulation of Fyn and AMPK signaling circuitry.

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    Lee, Chan Gyu; Koo, Ja Hyun; Kim, Sang Geon

    2015-12-01

    During the past decades, phytochemical terpenoids, polyphenols, lignans, flavonoids, and alkaloids have been identified as antioxidative and cytoprotective agents. Adenosine monophosphate-activated protein kinase (AMPK) is a kinase that controls redox-state and oxidative stress in the cell, and serves as a key molecule regulating energy metabolism. Many phytochemicals directly or indirectly alter the AMPK pathway in distinct manners, exerting catabolic metabolism. Some of them are considered promising in the treatment of metabolic diseases such as type II diabetes, obesity, and hyperlipidemia. Another important kinase that regulates energy metabolism is Fyn kinase, a member of the Src family kinases that plays a role in various cellular responses such as insulin signaling, cell growth, oxidative stress and apoptosis. Phytochemical inhibition of Fyn leads to AMPK-mediated protection of the cell in association with increased antioxidative capacity and mitochondrial biogenesis. The kinases may work together to form a signaling circuitry for the homeostasis of energy conservation and expenditure, and may serve as targets of phytochemicals. This review is intended as a compilation of recent advancements in the pharmacological research of phytochemicals targeting Fyn and AMPK circuitry, providing information for the prevention and treatment of metabolic diseases and the accompanying tissue injuries. PMID:25951818

  5. Ghrelin regulates phasic dopamine and nucleus accumbens signaling evoked by food-predictive stimuli

    OpenAIRE

    Cone, Jackson J; Roitman, Jamie D.; Roitman, Mitchell F.

    2015-01-01

    Environmental stimuli that signal food availability hold powerful sway over motivated behavior and promote feeding, in part, by activating the mesolimbic system. These food-predictive cues evoke brief (phasic) changes in nucleus accumbens (NAc) dopamine concentration and in the activity of individual NAc neurons. Phasic fluctuations in mesolimbic signaling have been directly linked to goal-directed behaviors, including behaviors elicited by food-predictive cues. Food-seeking behavior is also ...

  6. Unraveling a new circuitry for sleep regulation in Parkinson's disease.

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    Targa, Adriano D S; Rodrigues, Lais S; Noseda, Ana Carolina D; Aurich, Mariana F; Andersen, Monica L; Tufik, Sergio; da Cunha, Cláudio; Lima, Marcelo M S

    2016-09-01

    Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation. Then, we administrated a dopaminergic D2 receptor agonist, antagonist or vehicle directly in the striatum. After a period of 24 h of sleep-wake recording, we observed that the ibotenic acid infusion in the pedunculopontine tegmental nucleus blocked the so-called sleep rebound effect mediated by REM sleep deprivation, which was reversed by striatal D2 receptors activation. Rotenone infusion in the substantia nigra pars compacta also blocked the sleep rebound, however, striatal D2 receptors activation did not reverse it. In addition, rotenone administration decreased the time spent in NREM sleep, which was corroborated by positive correlations between dopamine levels in both substantia nigra pars compacta and striatum and the time spent in NREM sleep. These findings suggest a new circuitry for sleep regulation in Parkinson's disease, involving the triad composed by pedunculopontine nucleus, substantia nigra pars compacta and striatum, evidencing a potential therapeutic target for the sleep disturbances associated to this pathology. PMID:27091486

  7. Corticostriatal circuitry in regulating diseases characterized by intrusive thinking.

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    Kalivas, Benjamin C; Kalivas, Peter W

    2016-03-01

    Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression. PMID:27069381

  8. Neuroanatomy of cardiac activity-regulating circuitry : A transneuronal retrograde viral labelling study in the rat

    NARCIS (Netherlands)

    TerHorst, GJ; Hautvast, RWM; DeJongste, MJL; Korf, J

    1996-01-01

    The anatomy of cardiac activity-regulating circuitry was studied with retrograde transneuronal viral labelling after pseudorabies virus injections into different parts of the rat heart. Transection of the spinal cord at Th1 was used to reveal selectively the parasympathetic neuronal networks. Virus-

  9. Regulation of dietary choice by the decision-making circuitry

    OpenAIRE

    Rangel, Antonio

    2013-01-01

    To advance our understanding of how the brain makes food decisions, it is essential to combine knowledge from two fields that have not yet been well integrated: the neuro-computational basis of decision-making and the homeostatic regulators of feeding. This Review integrates these two literatures from a neuro-computational perspective, with an emphasis in describing the variables computed by different neural systems and how they affect dietary choice. We highlight what is unique about feeding...

  10. Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

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    Elisa M. Nabel

    2013-11-01

    Full Text Available Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development –the preeminent model of experience-dependent critical period plasticity- actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins– endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  11. Effects of emotion regulation difficulties on the tonic and phasic cardiac autonomic response.

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    Guillaume Berna

    Full Text Available Emotion regulation theory aims to explain the interactions between individuals and the environment. In this context, Emotion Regulation Difficulties (ERD disrupt the physiological component of emotions through the autonomic nervous system and are involved in several psychopathological states.We were interested in comparing the influence of a film-elicited emotion procedure on the autonomic nervous system activity of two groups with different levels of emotion regulation difficulties.A total of 63 women (undergraduate students ranging from 18 to 27 (20.7 ± 1.99 years old were included. Using the upper and lower quartile of a questionnaire assessing the daily difficulties in regulating emotions, two groups, one with low (LERD and one with high (HERD levels of emotion regulation difficulties, were constituted and studied during a film-elicited emotion procedure. Cardiac vagal activity (HF-HRV was analyzed during three periods: baseline, film-elicited emotion, and recovery.The cardiovascular results showed a decrease in HF-HRV from baseline to elicitation for both groups. Then, from elicitation to recovery, HF-HRV increased for the LERD group, whereas a low HF-HRV level persisted for the HERD group.The HERD group exhibited inappropriate cardiac vagal recovery after a negative emotion elicitation had ended. Cardiac vagal tone took longer to return to its initial state in the HERD group than in the LERD group. Prolonged cardiac vagal suppression might constitute an early marker of emotion regulation difficulties leading to lower cardiac vagal tone.

  12. Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation.

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    Cansell, Celine; Luquet, Serge

    2016-01-01

    In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. PMID:26159487

  13. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

    OpenAIRE

    Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

    2013-01-01

    Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of ...

  14. Role of basal ganglia in sleep-wake regulation: neural circuitry and clinical significance

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    Ramalingam Vetrivelan

    2010-11-01

    Full Text Available Researchers over the last decade have made substantial progress towards understanding the roles of dopamine and the basal ganglia in the control of sleep-wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the basal ganglia (BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson’s disease in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine and modafinil may be linked to the ventral periaquductal grey (vPAG dopaminergic circuitry targeting the extra-BG sleep-wake network.

  15. Phasic Triplet Markov Chains.

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    El Yazid Boudaren, Mohamed; Monfrini, Emmanuel; Pieczynski, Wojciech; Aïssani, Amar

    2014-11-01

    Hidden Markov chains have been shown to be inadequate for data modeling under some complex conditions. In this work, we address the problem of statistical modeling of phenomena involving two heterogeneous system states. Such phenomena may arise in biology or communications, among other fields. Namely, we consider that a sequence of meaningful words is to be searched within a whole observation that also contains arbitrary one-by-one symbols. Moreover, a word may be interrupted at some site to be carried on later. Applying plain hidden Markov chains to such data, while ignoring their specificity, yields unsatisfactory results. The Phasic triplet Markov chain, proposed in this paper, overcomes this difficulty by means of an auxiliary underlying process in accordance with the triplet Markov chains theory. Related Bayesian restoration techniques and parameters estimation procedures according to the new model are then described. Finally, to assess the performance of the proposed model against the conventional hidden Markov chain model, experiments are conducted on synthetic and real data. PMID:26353069

  16. FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry.

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    La Fata, Giorgio; Gärtner, Annette; Domínguez-Iturza, Nuria; Dresselaers, Tom; Dawitz, Julia; Poorthuis, Rogier B; Averna, Michele; Himmelreich, Uwe; Meredith, Rhiannon M; Achsel, Tilmann; Dotti, Carlos G; Bagni, Claudia

    2014-12-01

    Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity. PMID:25402856

  17. Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain.

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    Salomons, Tim V; Nusslock, Robin; Detloff, Allison; Johnstone, Tom; Davidson, Richard J

    2015-02-01

    Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within-subject designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neural and affective responses when participants were exposed to either uncontrollable or controllable stress, two groups of participants received an identical series of stressors (thermal pain stimuli). One group ("controllable") was led to believe they had behavioral control over the pain stimuli, whereas another ("uncontrollable") believed they had no control. Controllable pain was associated with decreased state anxiety, decreased activation in amygdala, and increased activation in nucleus accumbens. In participants who perceived control over the pain, reduced state anxiety was associated with increased functional connectivity between each of these regions and ventral lateral/ventral medial pFC. The location of pFC findings is consistent with regions found to be critical for the anxiolytic effects of perceived control in rodents. Furthermore, interactions observed between pFC and both amygdala and nucleus accumbens are remarkably similar to neural mechanisms of emotion regulation through reappraisal in humans. These results suggest that perceived control reduces negative affect through a general mechanism involved in the cognitive regulation of emotion. PMID:25208742

  18. Large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection.

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    Li, Ze-Yuan; Xia, Jing; Chen, Zheng; Yu, Yang; Li, Quan-Feng; Zhang, Yu-Chan; Zhang, Jin-Ping; Wang, Cong-Ying; Zhu, Xiao-Yuan; Zhang, Weixiong; Chen, Yue-Qin

    2016-01-01

    Rice blast is a recurrent fungal disease, and resistance to fungal infection is a complex trait. Therefore, a comprehensive examination of rice transcriptome and its variation during fungal infection is necessary to understand the complex gene regulatory networks. In this study, adopting Next-Generation Sequencing we profiled the transcriptomes and microRNAomes of rice varieties, one susceptible and the other resistant to M. oryzae, at multiple time points during the fungal infection. Our results revealed a substantial variation in the plant transcriptome and microRNAome as well as change to rice innate immunity during fungal infection. A number of putative R gene candidates were identified from a perturbed rice transcriptome analysis. The expression of genes and non-coding RNA molecules changed in both fungal resistant and susceptible plants during M. oryzae invasion discovered distinct pathways triggered in the susceptible and resistant plants. In addition, a number of fungus genes in the susceptible and resistant plants were constantly expressed at different time points, suggesting that they were likely to be the potential AVR genes. Our results revealed large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection, which would help to develop more robust blast-resistant rice plants. PMID:27150822

  19. Investigating complex basal ganglia circuitry in the regulation of motor behaviour, with particular focus on orofacial movement.

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    Ikeda, Hiroko; Adachi, Kazunori; Fujita, Satoshi; Tomiyama, Katsunori; Saigusa, Tadashi; Kobayashi, Masayuki; Koshikawa, Noriaki; Waddington, John L

    2015-02-01

    Current concepts of basal ganglia function have evolved from the essentially motoric, to include a range of extramotoric functions that involve not only dopaminergic but also cholinergic, γ-aminobutyric acid (GABA)ergic and glutamatergic mechanisms. We consider these mechanisms and their efferent systems, including spiralling, feed-forward striato-nigro-striatal circuitry, involving the dorsal and ventral striatum and the nucleus accumbens (NAc) core and shell. These processes are illustrated using three behavioural models: turning-pivoting, orofacial movements in rats and orofacial movements in genetically modified mice. Turning-pivoting indicates that dopamine-dependent behaviour elicited from the NAc shell is funnelled through the NAc-nigro-striato-nigro-pedunculopontine pathway, whereas acetylcholine-dependent behaviour elicited from the NAc shell is funnelled through the NAc-ventral pallidum-mediodorsal thalamus pathway. Cooperative/synergistic interactions between striatal D1-like and D2-like dopamine receptors regulate individual topographies of orofacial movements that are funnelled through striatal projection pathways and involve interactions with GABAergic and glutamatergic receptor subtypes. This application of concerted behavioural, neurochemical and neurophysiological techniques implicates a network that is yet broader and interacts with other neurotransmitters and neuropeptides within subcortical, cortical and brainstem regions to 'sculpt' aspects of behaviour into its topographical collective. PMID:25485640

  20. Neural circuitry and immunity.

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    Pavlov, Valentin A; Tracey, Kevin J

    2015-12-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuro-immune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex, are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases define the emerging field of Bioelectronic Medicine. PMID:26512000

  1. NPR-9, a Galanin-Like G-Protein Coupled Receptor, and GLR-1 Regulate Interneuronal Circuitry Underlying Multisensory Integration of Environmental Cues in Caenorhabditis elegans.

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    Jason C Campbell

    2016-05-01

    Full Text Available C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson's, Alzheimer's, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration

  2. Phasic dopamine release in appetitive behaviors and drug abuse

    OpenAIRE

    Wanat, Matthew J.; Willuhn, Ingo; Clark, Jeremy J.; Phillips, Paul E.M.

    2009-01-01

    Short phasic bursts of neuronal activity in dopamine neurons produce rapid and transient increases in extracellular dopamine concentrations throughout the mesocorticolimbic system, which are associated with the initiation of goal-directed behaviors. It is well established that acute exposure to many addictive drugs produce increases in tonic dopamine levels that occur on the order of minutes. However, recent studies suggest that abused drugs similarly enhance phasic dopamine release events th...

  3. Science and Teachers: Cardboard Circuitry

    Science.gov (United States)

    Science and Children, 1977

    1977-01-01

    Diagrams a quick, improvised cardboard circuitry for battery holder, bulb socket, and switches. Materials include corrugated cardboard, paper clips, and rubber bands. Assembly useful in determining the electrical conductivity of substances. (CS)

  4. Phasic and Tonic Inhibition are Maintained Respectively by CaMKII and PKA in the Rat Visual Cortex

    OpenAIRE

    Joo, Kayoung; Yoon, Shin Hee; Rhie, Duck-Joo; Jang, Hyun-Jong

    2014-01-01

    Phasic and tonic γ-aminobutyric acidA (GABAA) receptor-mediated inhibition critically regulate neuronal information processing. As these two inhibitory modalities have distinctive features in their receptor composition, subcellular localization of receptors, and the timing of receptor activation, it has been thought that they might exert distinct roles, if not completely separable, in the regulation of neuronal function. Inhibition should be maintained and regulated depending on changes in ne...

  5. From laboratory to industry Phasics experience (Conference Presentation)

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    Wattellier, Benoit F.; Lebrun, Marie-Begoña.

    2016-03-01

    We describe several examples of technology transfer from academic laboratories to PHASICS. PHASICS was created in 2003 as a spin-off of LULI an academic laboratory working on plasma physics and developing high power lasers to create such objects which temperature and pressure conditions are close to those at the center of stars. In order to optimize the intensity at laser focus, several thesis treated the subject of adaptive optics for lasers. LULI decided to collaborate with ONERA who just invented a technique for wave front sensing called multiwave lateral shearing interferometry. Though developed at first for infrared metrology applications, this technique proved to be very efficient with lasers because it was able to analyze wave front of modulated beams with sharp edges. Before being industrialized the technique was further improved to a compact version called quadriwave lateral shearing interferometry. As soon as PHASICS was created, we felt the potential of making wave front images from transparent objects because of QWLSI high spatial resolution. PHASICS and Institut Fresnel started a collaboration to study applications in microscopy imaging. Research subjects include biological imaging, CARS microscopy, anisotropy imaging, or laser damage testing. The results of research were then included in PHASICS products but sometimes only a tool developed during the project became a product. We will present research works that led to transfers as well as the method we used to ensure fruitful collaboration and transfer.

  6. Phasic excitation of ventral tegmental dopamine neurons potentiates the initiation of conditioned approach behavior: Parametric and reinforcement-schedule analyses

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    Satoshi Ikemoto

    2014-05-01

    Full Text Available Midbrain dopamine neurons are implicated in motivation and learning. However, it is unclear how phasic excitation of dopamine neurons, which is implicated in learning, is involved in motivation. Here we used a self-stimulation procedure to examine how mice seek for optogenetically-induced phasic excitation of dopamine neurons, with an emphasis on the temporal dimension. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin-2 into the ventral tegmental area, resulting in selective expression of the opsin in dopamine neurons. These mice were trained to press on a lever for photo-pulse trains that phasically excited dopamine neurons. They learned to self-stimulate in a fast, constant manner, and rapidly reduced pressing during extinction. We first determined effective parameters of photo-pulse trains in self-stimulation. Lever-press rates changed as a function of the manipulation of pulse number, duration, intensity and frequency. We then examined effects of interval and ratio schedules of reinforcement on photo-pulse train reinforcement, which was contrasted with food reinforcement. Reinforcement with food inhibited lever pressing for a few seconds, after which pressing was robustly regulated in a goal-directed manner. In contrast, phasic excitation of dopamine neurons robustly potentiated the initiation of lever pressing; however, this effect did not last more than 1 s and quickly diminished. Indeed, response rates markedly decreased when lever pressing was reinforced with inter-reinforcement interval schedules of 3 or 10 s or ratio schedules requiring multiple responses per reinforcement. Thus, phasic excitation of dopamine neurons briefly potentiates the initiation of approach behavior with apparent lack of long-term motivational regulation.

  7. Asymmetry in prefrontal resting-state EEG spectral power underlies individual differences in phasic and sustained cognitive control.

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    Ambrosini, Ettore; Vallesi, Antonino

    2016-01-01

    In our daily life, we constantly exert sustained and phasic cognitive control processes to manage multiple competing task sets and rapidly switch between them. Increasing research efforts are attempting to unveil how the brain mediates these processes, highlighting the importance of the prefrontal cortex. An intriguing question concerns the influence of hemispheric asymmetries and whether it may be generalized to different cognitive domains depending on lateralized processing. Another currently open question concerns the underlying causes of the observed huge inter-individual variability in cognitive control abilities. Here we tackle these issues by investigating whether participants' hemispheric asymmetry in intrinsic (i.e., resting-state-related) brain dynamics can reflect differences in their phasic and/or sustained cognitive control abilities regardless of the cognitive domain. To this aim, we recorded human participants' resting-state electroencephalographic activity and performed a source-based spectral analysis to assess their lateralized brain dynamics at rest. Moreover, we used three task-switching paradigms involving different cognitive domains to assess participants' domain-general phasic and sustained cognitive control abilities. By performing a series of correlations and an intersection analysis, we showed that participants with stronger left- and right-lateralized intrinsic brain activity in the middle frontal gyrus were more able, respectively, to exert phasic and sustained cognitive control. We propose that the variability in participants' prefrontal hemispheric asymmetry in the intrinsic electrophysiological spectral profile reflects individual differences in preferentially engaging either the left-lateralized, phasic or the right-lateralized, sustained cognitive control processes to regulate their behavior in response to changing task demands, regardless of the specific cognitive domain involved. PMID:26416650

  8. Phasic temperature control appraised with the Ceres-Wheat model.

    Science.gov (United States)

    Volk, T; Bugbee, B; Tubiello, F

    1997-01-01

    Phasic control refers to the specification of a series of different environmental conditions during a crop's life cycle, with the goal of optimizing some aspect of productivity. Because of the enormous number of possible scenarios, phasic control is an ideal situation for modeling to provide guidance prior to experiments. Here we use the Ceres-Wheat model, modified for hydroponic growth chambers, to examine temperature effects. We first establish a baseline by running the model at constant temperatures from 10 degrees C to 30 degrees C. Grain yield per day peaks at 15 degrees C at a value that is 25% higher than the yield at the commonly used 23 degrees C. We then show results for phasic control limited to a single shift in temperature and, finally, we examine scenarios that allow each of the five phases of the life cycle to have a different temperature. Results indicate that grain yield might be increased by 15-20% over the best yield at constant temperature, primarily from a boosted harvest index, which has the additional advantage of less waste biomass. Such gains, if achievable, would help optimize food production for life support systems. Experimental work should first verify the relationship between yield and temperature, and then move to selected scenarios of phasic control, based on model predictions. PMID:11540452

  9. A slave interface circuitry facing to VMEbus

    International Nuclear Information System (INIS)

    A slave interface circuitry facing to VMEbus will be introduced briefly. This interface circuitry was developed for the multi-event selection electronics MUSE used for the medium energy nuclear action experiment system. This interface circuitry can support 32 bit single cycle data transfer and Chained Block Data Transfer (i.e. CB LT)

  10. Activity Dependent Regulation of Inhibitory Circuitry

    OpenAIRE

    Sharma, Nikhil

    2015-01-01

    Inhibition controls information flow through a neural circuit by modulating synaptic integration, restricting action potentials, and coordinating the activity of ensembles of neurons. These functions are mediated by a diverse array of inhibitory neuron subtypes that synapse on defined domains of a postsynaptic neuron. Activity-dependent transcription controls inhibitory synapse number and function, but how this transcription program affects the inhibitory inputs that form on di...

  11. Insect tricks: two-phasic foot pad secretion prevents slipping

    OpenAIRE

    Dirks, Jan-Henning; Clemente, Christofer J.; Federle, Walter

    2009-01-01

    Many insects cling to vertical and inverted surfaces with pads that adhere by nanometre-thin films of liquid secretion. This fluid is an emulsion, consisting of watery droplets in an oily continuous phase. The detailed function of its two-phasic nature has remained unclear. Here we show that the pad emulsion provides a mechanism that prevents insects from slipping on smooth substrates. We discovered that it is possible to manipulate the adhesive secretion in vivo using smooth polyimide substr...

  12. Influence of phasic and tonic dopamine release on receptor activation

    DEFF Research Database (Denmark)

    Dreyer, Jakob Kristoffer Kisbye; Herrik, Kjartan F; Berg, Rune W; Hounsgaard, Jørn D

    2010-01-01

    Tonic and phasic dopamine release is implicated in learning, motivation, and motor functions. However, the relationship between spike patterns in dopaminergic neurons, the extracellular concentration of dopamine, and activation of dopamine receptors remains unresolved. In the present study, we...... develop a computational model of dopamine signaling that give insight into the relationship between the dynamics of release and occupancy of D(1) and D(2) receptors. The model is derived from first principles using experimental data. It has no free parameters and offers unbiased estimation of the...

  13. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

    Directory of Open Access Journals (Sweden)

    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  14. Control of phasic firing by a background leak current in avian forebrain auditory neurons

    Directory of Open Access Journals (Sweden)

    Andre Andreotti Dagostin

    2015-12-01

    Full Text Available Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP phasic firing, produced by low-threshold voltage activated potassium currents (VAKCs, is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs than the other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons.

  15. Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons.

    Science.gov (United States)

    Dagostin, André A; Lovell, Peter V; Hilscher, Markus M; Mello, Claudio V; Leão, Ricardo M

    2015-01-01

    Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs to other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp, and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons. PMID:26696830

  16. Oscillatory Motion of a Bi-Phasic Slug in a Teflon Reactor

    Science.gov (United States)

    Abolhasani, Milad; Jensen, Klavs

    2015-11-01

    Bi-phasic physical/chemical processes require transfer of solute/reagent molecules across the interface. Continuous multi-phase flow approaches (using gas as the continuous phase), usually fail in providing sufficient interfacial area for transfer of molecules between the aqueous and organic phases. In continuous segmented flow platforms (with a fluorinated polymer-based reactor), the higher surface tension of the aqueous phase compared to the organic phase of a bi-phasic slug, in combination with the low surface energy of the reactor wall result in a more facile motion of the aqueous phase. Thus, upon applying a pressure gradient across the bi-phasic slug, the aqueous phase of the slug moves through the organic phase and leads the bi-phasic slug, thereby limiting the available interfacial area for the bi-phasic mass transfer only to the semi-spherical interface between the two phases. Disrupting the quasi-equilibrium state of the bi-phasic slug through reversing the pressure gradient across the bi-phasic slug causes the aqueous phase to move back through the organic phase. In this work, we experimentally investigate the dynamics of periodic alteration of the pressure gradient across a bi-phasic slug, and characterize the resulting enhanced interfacial area on the bi-phasic mass transfer rate. We demonstrate the enhanced mass transfer rate of the oscillatory flow strategy compared to the continuous multi-phase approach using bi-phasic Pd catalyzed carbon-carbon and carbon-nitrogen cross coupling reactions. NSERC Postdoctoral Fellowship, Novartis Center for Continuous Manufacturing.

  17. Oscillatory three-phase flow reactor for studies of bi-phasic catalytic reactions.

    Science.gov (United States)

    Abolhasani, Milad; Bruno, Nicholas C; Jensen, Klavs F

    2015-05-28

    A multi-phase flow strategy, based on oscillatory motion of a bi-phasic slug within a fluorinated ethylene propylene (FEP) tubular reactor, under inert atmosphere, is designed and developed to address mixing and mass transfer limitations associated with continuous slug flow chemistry platforms for studies of bi-phasic catalytic reactions. The technique is exemplified with C-C and C-N Pd catalyzed coupling reactions. PMID:25876959

  18. Oscillatory three-phase flow reactor for studies of bi-phasic catalytic reactions

    OpenAIRE

    Abolhasani, Milad; Bruno, Nicholas C.; Jensen, Klavs F.

    2015-01-01

    A multi-phase flow strategy, based on oscillatory motion of a bi-phasic slug within a fluorinated ethylene propylene (FEP) tubular reactor, under inert atmosphere, is designed and developed to address mixing and mass transfer limitations associated with continuous slug flow chemistry platforms for studies of bi-phasic catalytic reactions. The technique is exemplified with C–C and C–N Pd catalyzed coupling reactions.

  19. Insect tricks: two-phasic foot pad secretion prevents slipping.

    Science.gov (United States)

    Dirks, Jan-Henning; Clemente, Christofer J; Federle, Walter

    2010-04-01

    Many insects cling to vertical and inverted surfaces with pads that adhere by nanometre-thin films of liquid secretion. This fluid is an emulsion, consisting of watery droplets in an oily continuous phase. The detailed function of its two-phasic nature has remained unclear. Here we show that the pad emulsion provides a mechanism that prevents insects from slipping on smooth substrates. We discovered that it is possible to manipulate the adhesive secretion in vivo using smooth polyimide substrates that selectively absorb its watery component. While thick layers of polyimide spin-coated onto glass removed all visible hydrophilic droplets, thin coatings left the emulsion in its typical form. Force measurements of stick insect pads sliding on these substrates demonstrated that the reduction of the watery phase resulted in a significant decrease in friction forces. Artificial control pads made of polydimethylsiloxane showed no difference when tested on the same substrates, confirming that the effect is caused by the insects' fluid-based adhesive system. Our findings suggest that insect adhesive pads use emulsions with non-Newtonian properties, which may have been optimized by natural selection. Emulsions as adhesive secretions combine the benefits of 'wet' adhesion and resistance against shear forces. PMID:19755498

  20. Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Badgaiyan, Rajendra D.; Sinha, Sampada; Sajjad, Munawwar; Wack, David S.

    2015-01-01

    It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen’s flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand 11C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity. PMID:26422146

  1. A genetic time-delay circuitry in mammalian cells.

    Science.gov (United States)

    Weber, Wilfried; Kramer, Beat P; Fussenegger, Martin

    2007-11-01

    Gene expression circuitries with time-delayed expression profiles regulate key events, such as oscillating systems, noise elimination, and coordinated multi-step processes, in all organisms from bacteria to mammalian cells. We present the rational synthesis of a genetic circuit displaying time-delayed expression in silico and in mammalian cells. The network is based on a time-delay circuit, where the tetracycline-responsive transactivator (tTA) induces expression of the pristinamycin-responsive repressor PIP-KRAB, which silences expression of the terminal human placental secreted alkaline phosphatase (SEAP). While the addition of pristinamycin I inactivates PIP-KRAB and results in the immediate resumption of SEAP expression, addition of tetracycline abolishes PIP-KRAB synthesis. Consequently, SEAP production remains repressed until the PIP-KRAB buffer in the cell is eliminated. We characterized in silico and in vivo the time-delayed expression properties and analyzed the impact of the size and stability of the PIP-KRAB buffer on fine-tuning of the response kinetics. This tunable time-delay circuitry represents a biologic building block for emulating a fundamental circuit topology in integrated artificial synthetic gene networks for the design of tailor-made cell types and organisms. PMID:17461420

  2. The Development of Micromachined Gyroscope Structure and Circuitry Technology

    Directory of Open Access Journals (Sweden)

    Dunzhu Xia

    2014-01-01

    Full Text Available This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs, piezoelectric vibrating gyroscopes (PVGs, surface acoustic wave (SAW gyroscopes, bulk acoustic wave (BAW gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs, magnetically suspended gyroscopes (MSGs, micro fiber optic gyroscopes (MFOGs, micro fluid gyroscopes (MFGs, micro atom gyroscopes (MAGs, and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

  3. Bi-phasic Simulation of Metal Injection Moulding:Constitutive Determinations

    Institute of Scientific and Technical Information of China (English)

    Liu Baosheng(柳葆生); Barriere Thierry; Gelin Jean-Claude

    2003-01-01

    To predict the segregation effect in metal injection moulding (MIM) injection, a bi-phasic model based on mixture theory is adopted in simulation. An explicit algorithm is developed and realized by the authors, which conducts the simulation to be a cost-effective tool in MIM technology. In case of the bi-phasic simulation, the viscosity behaviours are necessary to be determined for the flows of each phase while only the viscosity of mixture is measurable by tests. It is a crucial problem for application of the bi-phasic simulation of MIM injection. A reasonable method is hence analysed and proposed to determine the viscosity behaviours of each phase. Even though this method may be furthermore modified in the future, it results in the practical simulation of segregation effects with reasonable parameters. The simulation results are compared with the measurements on injected specimens.

  4. Processing circuitry for single channel radiation detector

    Science.gov (United States)

    Holland, Samuel D. (Inventor); Delaune, Paul B. (Inventor); Turner, Kathryn M. (Inventor)

    2009-01-01

    Processing circuitry is provided for a high voltage operated radiation detector. An event detector utilizes a comparator configured to produce an event signal based on a leading edge threshold value. A preferred event detector does not produce another event signal until a trailing edge threshold value is satisfied. The event signal can be utilized for counting the number of particle hits and also for controlling data collection operation for a peak detect circuit and timer. The leading edge threshold value is programmable such that it can be reprogrammed by a remote computer. A digital high voltage control is preferably operable to monitor and adjust high voltage for the detector.

  5. Functional maps of neocortical local circuitry

    Directory of Open Access Journals (Sweden)

    Alex M Thomson

    2007-10-01

    Full Text Available This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided.This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized.

  6. Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

    OpenAIRE

    Doo-SupChoi; Jun HyunPark

    2014-01-01

    Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use...

  7. Static DC to DC Power Conditioning-Active Ripple Filter, 1 MHZ DC to DC Conversion, and Nonlinear Analysis. Ph.D. Thesis; [voltage regulation and conversion circuitry for spacecraft power supplies

    Science.gov (United States)

    Sander, W. A., III

    1973-01-01

    Dc to dc static power conditioning systems on unmanned spacecraft have as their inputs highly fluctuating dc voltages which they condition to regulated dc voltages. These input voltages may be less than or greater than the desired regulated voltages. The design of two circuits which address specific problems in the design of these power conditioning systems and a nonlinear analysis of one of the circuits are discussed. The first circuit design is for a nondissipative active ripple filter which uses an operational amplifier to amplify and cancel the sensed ripple voltage. A dc to dc converter operating at a switching frequency of 1 MHz is the second circuit discussed. A nonlinear analysis of the type of dc to dc converter utilized in designing the 1 MHz converter is included.

  8. Integrator Circuitry for Single Channel Radiation Detector

    Science.gov (United States)

    Holland, Samuel D. (Inventor); Delaune, Paul B. (Inventor); Turner, Kathryn M. (Inventor)

    2008-01-01

    Input circuitry is provided for a high voltage operated radiation detector to receive pulses from the detector having a rise time in the range of from about one nanosecond to about ten nanoseconds. An integrator circuit, which utilizes current feedback, receives the incoming charge from the radiation detector and creates voltage by integrating across a small capacitor. The integrator utilizes an amplifier which closely follows the voltage across the capacitor to produce an integrator output pulse with a peak value which may be used to determine the energy which produced the pulse. The pulse width of the output is stretched to approximately 50 to 300 nanoseconds for use by subsequent circuits which may then use amplifiers with lower slew rates.

  9. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    International Nuclear Information System (INIS)

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury

  10. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

    2013-11-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  11. Mapping the brain's metaphor circuitry: metaphorical thought in everyday reason

    OpenAIRE

    Lakoff, George

    2014-01-01

    An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry.

  12. Bi-phasic titanium dioxide nanoparticles doped with nitrogen and neodymium for enhanced photocatalysis

    Science.gov (United States)

    Gomez, Virginia; Bear, Joseph C.; McNaughter, Paul D.; McGettrick, James D.; Watson, Trystan; Charbonneau, Cecile; O'Brien, Paul; Barron, Andrew R.; Dunnill, Charles W.

    2015-10-01

    Bi-phasic or multi-phasic composite nanoparticles for use in photocatalysis have been produced by a new synthetic approach. Sol-gel methods are used to deposit multiple layers of active material onto soluble substrates. In this work, a layer of rutile (TiO2) was deposited onto sodium chloride pellets followed by an annealing step and a layer of anatase. After dissolving the substrate, bi-phasic nanoparticles containing half anatase and half rutile TiO2; with ``Janus-like'' characteristics are obtained. Nitrogen and neodymium doping of the materials were observed to enhance the photocatalytic properties both under UV and white light irradiation. The unique advantage of this synthetic method is the ability to systematically dope separate sides of the nanoparticles. Nitrogen doping was found to be most effective on the anatase side of the nanoparticle while neodymium was found to be most effective on the rutile side. Rhodamine B dye was effectively photodegraded by co-doped particles under white light.Bi-phasic or multi-phasic composite nanoparticles for use in photocatalysis have been produced by a new synthetic approach. Sol-gel methods are used to deposit multiple layers of active material onto soluble substrates. In this work, a layer of rutile (TiO2) was deposited onto sodium chloride pellets followed by an annealing step and a layer of anatase. After dissolving the substrate, bi-phasic nanoparticles containing half anatase and half rutile TiO2; with ``Janus-like'' characteristics are obtained. Nitrogen and neodymium doping of the materials were observed to enhance the photocatalytic properties both under UV and white light irradiation. The unique advantage of this synthetic method is the ability to systematically dope separate sides of the nanoparticles. Nitrogen doping was found to be most effective on the anatase side of the nanoparticle while neodymium was found to be most effective on the rutile side. Rhodamine B dye was effectively photodegraded by co

  13. Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Doo-SupChoi

    2014-09-01

    Full Text Available Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD. In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD.

  14. Impairment of GABA transporter GAT-1 terminates cortical recurrent network activity via enhanced phasic inhibition

    Directory of Open Access Journals (Sweden)

    David Johannes Hawellek

    2013-09-01

    Full Text Available In the central nervous system, GABA transporters (GATs very efficiently clear synaptically released GABA from the extracellular space, and thus exert a tight control on GABAergic inhibition. In neocortex, GABAergic inhibition is heavily recruited during recurrent phases of spontaneous action potential activity which alternate with neuronally quiet periods. Therefore, such activity should be quite sensitive to minute alterations of GAT function. Here, we explored the effects of a gradual impairment of GAT-1 and GAT-2/3 on spontaneous recurrent network activity – termed network bursts and silent periods – in organotypic slice cultures of rat neocortex. The GAT-1 specific antagonist NO-711 depressed activity already at nanomolar concentrations (IC50 for depression of spontaneous multiunit firing rate of 42 nM, reaching a level of 80% at 500-1000 nM. By contrast, the GAT-2/3 preferring antagonist SNAP-5114 had weaker and less consistent effects. Several lines of evidence pointed towards an enhancement of phasic GABAergic inhibition as the dominant activity-depressing mechanism: network bursts were drastically shortened, phasic GABAergic currents decayed slower, and neuronal excitability during ongoing activity was diminished. In silent periods, NO-711 had little effect on neuronal excitability or membrane resistance, quite in contrast to the effects of muscimol, a GABA mimetic which activates GABAA receptors tonically. Our results suggest that an enhancement of phasic GABAergic inhibition efficiently curtails cortical recurrent activity and may mediate antiepileptic effects of therapeutically relevant concentrations of GAT-1 antagonists.

  15. Oxytonergic circuitry sustains and enables creative cognition in humans.

    Science.gov (United States)

    De Dreu, Carsten K W; Baas, Matthijs; Roskes, Marieke; Sligte, Daniel J; Ebstein, Richard P; Chew, Soo Hong; Tong, Terry; Jiang, Yushi; Mayseless, Naama; Shamay-Tsoory, Simone G

    2014-08-01

    Creativity enables humans to adapt flexibly to changing circumstances, to manage complex social relations and to survive and prosper through social, technological and medical innovations. In humans, chronic, trait-based as well as temporary, state-based approach orientation has been linked to increased capacity for divergent rather than convergent thinking, to more global and holistic processing styles and to more original ideation and creative problem solving. Here, we link creative cognition to oxytocin, a hypothalamic neuropeptide known to up-regulate approach orientation in both animals and humans. Study 1 (N = 492) showed that plasma oxytocin predicts novelty-seeking temperament. Study 2 (N = 110) revealed that genotype differences in a polymorphism in the oxytocin receptor gene rs1042778 predicted creative ideation, with GG/GT-carriers being more original than TT-carriers. Using double-blind placebo-controlled between-subjects designs, Studies 3-6 (N = 191) finally showed that intranasal oxytocin (vs matching placebo) reduced analytical reasoning, and increased holistic processing, divergent thinking and creative performance. We conclude that the oxytonergic circuitry sustains and enables the day-to-day creativity humans need for survival and prosperity and discuss implications. PMID:23863476

  16. Circuitry for use with an ionizing-radiation detector

    International Nuclear Information System (INIS)

    An improved system of circuitry for use in combination with an ionizing-radiation detector over a wide range of radiation levels includes a current-to-frequency converter together with a digital data processor for respectively producing and measuring a pulse repetition frequency which is proportional to the output current of the ionizing-radiation detector, a dc-to-dc converter for providing closely regulated operating voltages from a rechargeable battery and a bias supply for providing high voltage to the ionization chamber. The ionizing-radiation detector operating as a part of this system produces a signal responsive to the level of ionizing radiation in the vicinity of the detector, and this signal is converted into a pulse frequency which will vary in direct proportion to such level of ionizing-radiation. The data processor, by counting the number of pulses from the converter over a selected integration interval, provides a digital indication of radiation dose rate, and by accumulating the total of all such pulses provides a digital indication of total integrated dose. Ordinary frequency-to-voltage conversion devices or digital display techniques can be used as a means for providing audible and visible indications of dose and dose-rate levels

  17. Nanocantilever based mass sensor integrated with cmos circuitry

    DEFF Research Database (Denmark)

    Davis, Zachary James; Abadal, G.; Campabadal, F.;

    2003-01-01

    We have demonstrated the successful integration of a cantilever based mass detector with standard CMOS circuitry. The purpose of the circuitry is to facilitate the readout of the cantilever's deflection in order to measure resonant frequency shifts of the cantilever. The principle and design of the...... mass detector are presented showing that miniaturization of such cantilever based resonant devices leads to highly sensitive mass sensors, which have the potential to detect single molecules. The design of the readout circuitry used for the first electrical characterization of an integrated cantilever...... integrated with CMOS circuitry is demonstrated. The electrical characterization of the device shows that the resonant behavior of the cantilever depends on the applied voltages, which corresponds to theory....

  18. Nanocantilever based mass sensor integrated with cmos circuitry

    OpenAIRE

    Davis, Zachary James; Abadal, G.; Campabadal, F; Figueras, E.; Esteve, J.; Verd, J.; Perez-Murano, F.; Borrise, X.; Nilsson, S. G.; Miximov, I.; Montelius, L.; Barniol, N.; Boisen, Anja

    2003-01-01

    We have demonstrated the successful integration of a cantilever based mass detector with standard CMOS circuitry. The purpose of the circuitry is to facilitate the readout of the cantilever's deflection in order to measure resonant frequency shifts of the cantilever. The principle and design of the mass detector are presented showing that miniaturization of such cantilever based resonant devices leads to highly sensitive mass sensors, which have the potential to detect single molecules. The d...

  19. Circuitry, systems and methods for detecting magnetic fields

    Science.gov (United States)

    Kotter, Dale K [Shelley, ID; Spencer, David F [Idaho Falls, ID; Roybal, Lyle G [Idaho Falls, ID; Rohrbaugh, David T [Idaho Falls, ID

    2010-09-14

    Circuitry for detecting magnetic fields includes a first magnetoresistive sensor and a second magnetoresistive sensor configured to form a gradiometer. The circuitry includes a digital signal processor and a first feedback loop coupled between the first magnetoresistive sensor and the digital signal processor. A second feedback loop which is discrete from the first feedback loop is coupled between the second magnetoresistive sensor and the digital signal processor.

  20. Phasic dopamine as a prediction error of intrinsic and extrinsic reinforcement driving both action acquisition and reward maximization: A simulated robotic study

    OpenAIRE

    Mirolli, Marco; Santucci, Vieri Giuliano; Baldassarre, Gianluca

    2013-01-01

    An important issue of recent neuroscientific research is to understand the functional role of the phasic release of dopamine in the striatum, and in particular its relation to reinforcement learning. The literature is split between two alternative hypotheses: one considers phasic dopamine as a reward prediction error similar to the computational TD-error, whose function is to guide an animal to maximize future rewards; the other holds that phasic dopamine is a sensory prediction error signal ...

  1. GABA regulates synaptic integration of newly generated neurons in the adult brain

    Science.gov (United States)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  2. Self-organizing circuitry and emergent computation in mouse embryonic stem cells.

    Science.gov (United States)

    Halley, J D; Smith-Miles, K; Winkler, D A; Kalkan, T; Huang, S; Smith, A

    2012-03-01

    Pluripotency is a cellular state of multiple options. Here, we highlight the potential for self-organization to contribute to stem cell fate computation. A new way of considering regulatory circuitry is presented that describes the expression of each transcription factor (TF) as a branching process that propagates through time, interacting and competing with others. In a single cell, the interactions between multiple branching processes generate a collective process called 'critical-like self-organization'. We explain how this phenomenon provides a valid description of whole genome regulatory circuit dynamics. The hypothesis of exploratory stem cell decision-making proposes that critical-like self-organization (also called rapid self-organized criticality) provides the backbone for cell fate computation in regulative embryos and pluripotent stem cells. Unspecific amplification of TF expression is predicted to initiate this self-organizing circuitry, where cascades of gene expression propagate and may interact either synergistically or antagonistically. The emergent and highly dynamic circuitry is affected by various sources of selection pressure, such as the expression of TFs with disproportionate influence over other genes, and extrinsic biological and physical stimuli that differentially modulate particular gene expression cascades. Extrinsic conditions continuously trigger waves of transcription that ripple throughout regulatory networks on multiple spatiotemporal scales, providing the context within which circuitry self-organizes. In this framework, a distinction between instructive and selective mechanisms of fate determination is misleading because it is the 'interference pattern', rather than any single instructing or selecting factor, that is ultimately responsible for computing and directing cell fate. Using this framework, we consider whether the idea of a naïve ground state of pluripotency and that of a fluctuating transcriptome are compatible, and

  3. GLP-1 and weight loss: unraveling the diverse neural circuitry.

    Science.gov (United States)

    Kanoski, Scott E; Hayes, Matthew R; Skibicka, Karolina P

    2016-05-15

    Glucagon-like peptide-1 (GLP-1) is currently one of the most promising biological systems for the development of effective obesity pharmacotherapies. Long-acting GLP-1 analogs potently reduce food intake and body weight, and recent discoveries reveal that peripheral administration of these drugs reduces food intake largely through humoral pathways involving direct action on brain GLP-1 receptors (GLP-1R). Thus, it is of critical importance to understand the neural systems through which GLP-1 and long-acting GLP-1 analogs reduce food intake and body weight. In this review, we discuss several neural, physiological, cellular and molecular, as well as behavioral mechanisms through which peripheral and central GLP-1R signaling reduces feeding. Particular attention is devoted to discussion regarding the numerous neural substrates through which GLP-1 and GLP-1 analogs act to reduce food intake and body weight, including various hypothalamic nuclei (arcuate nucleus of the hypothalamus, periventricular hypothalamus, lateral hypothalamic area), hindbrain nuclei (parabrachial nucleus, medial nucleus tractus solitarius), hippocampus (ventral subregion; vHP), and nuclei embedded within the mesolimbic reward circuitry [ventral tegmental area (VTA) and nucleus accumbens (NAc)]. In some of these nuclei [VTA, NAc, and vHP], GLP-1R activation reduces food intake and body weight without concomitant nausea responses, suggesting that targeting these specific pathways may be of particular interest for future obesity pharmacotherapy. The widely distributed neural systems through which GLP-1 and GLP-1 analogs act to reduce body weight highlight the complexity of the neural systems regulating energy balance, as well as the challenges for developing effective obesity pharmacotherapies that reduce feeding without producing parallel negative side effects. PMID:27030669

  4. Brain circuitry outside the synaptic cleft

    OpenAIRE

    Rusakov, Dmitri A.; Alexander E Dityatev

    2014-01-01

    A growing body of experimental evidence suggests that astroglia, and possibly microglia, play an important part in regulating synaptic networking of the brain. It has also emerged that extracellular matrix (ECM) structures that enwrap synaptic connections can generate molecular signals affecting both neuronal and glial activity. Thus it appears that the mechanism of information processing in the brain, which has hitherto been associated almost exclusively with neural circuits, could also invo...

  5. Automatic quadrature control and measuring system. [using optical coupling circuitry

    Science.gov (United States)

    Hamlet, J. F. (Inventor)

    1974-01-01

    A quadrature component cancellation and measuring system comprising a detection system for detecting the quadrature component from a primary signal, including reference circuitry to define the phase of the quadrature component for detection is described. A Raysistor optical coupling control device connects an output from the detection system to a circuit driven by a signal based upon the primary signal. Combining circuitry connects the primary signal and the circuit controlled by the Raysistor device to subtract quadrature components. A known current through the optically sensitive element produces a signal defining the magnitude of the quadrature component.

  6. The origin of behavioral bursts in decision-making circuitry.

    Directory of Open Access Journals (Sweden)

    Amanda Sorribes

    2011-06-01

    Full Text Available From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switches of wild-type Drosophila are very well described by the Weibull distribution, a common distribution of bursty dynamics in complex systems. The bursty dynamics of wild-type Drosophila walking activity are shown to be determined by this inter-event distribution alone and not by memory effects, thus resembling human dynamics. Further, using mutant flies that disrupt dopaminergic signaling or the mushroom body, circuitry implicated in decision-making, we show that the degree of behavioral burstiness can be modified. These results are thus consistent with the proposed link between decision-making circuitry and bursty dynamics, and highlight the importance of using simple experimental systems to test general theoretical models of behavior. The findings further suggest that analysis of bursts could prove useful for the study and evaluation of decision-making circuitry.

  7. Early GABAergic circuitry in the cerebral cortex.

    Science.gov (United States)

    Luhmann, Heiko J; Kirischuk, Sergei; Sinning, Anne; Kilb, Werner

    2014-06-01

    In the cerebral cortex GABAergic signaling plays an important role in regulating early developmental processes, for example, neurogenesis, migration and differentiation. Transient cell populations, namely Cajal-Retzius in the marginal zone and thalamic input receiving subplate neurons, are integrated as active elements in transitory GABAergic circuits. Although immature pyramidal neurons receive GABAergic synaptic inputs already at fetal stages, they are integrated into functional GABAergic circuits only several days later. In consequence, GABAergic synaptic transmission has only a minor influence on spontaneous network activity during early corticogenesis. Concurrent with the gradual developmental shift of GABA action from excitatory to inhibitory and the maturation of cortical synaptic connections, GABA becomes more important in synchronizing neuronal network activity. PMID:24434608

  8. Changes of phasic and tonic smooth muscle function of jejunum in type 2 diabetic Goto-Kakizaki rats

    DEFF Research Database (Denmark)

    Zhao, Jing-Bo; Chen, Peng-Min; Gregersen, Hans; Zhao, Jingbo

    2013-01-01

    AIM: To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions. METHODS: Seven diabetic Goto-Kakizaki (GK) male rats, 32-wk old (GK group), and 9 age-matched normal Wistar rats (Normal group...

  9. Adaptations and pathologies linked to dynamic stabilization of neural circuitry.

    Science.gov (United States)

    Kavanau, J L

    1999-05-01

    Brain circuits for infrequently employed memories are reinforced largely during sleep by self-induced, electrical slow-waves, a process referred to as "dynamic stabilization" (DS). The essence of waking brain function in the absence of volitional activity is sensory input processing, an enormous amount of which is visual. These two functions: circuit reinforcement by DS and sensory information processing come into conflict when both occur at a high level, a conflict that may have been the selective pressure for sleep's origin. As brain waves are absent at the low temperatures of deep torpor, essential circuitry of hibernating small mammals would lose its competence if the animals did not warm up periodically to temperatures allowing sleep and circuit reinforcement. Blind, cave-dwelling vertebrates require no sleep because their sensory processing does not interfere with DS. Nor does such interference arise in continuously-swimming fishes, whose need to process visual information is reduced greatly by life in visually relatively featureless, pelagic habitats, and by schooling. Dreams are believed to have their origin in DS of memory circuits. They are thought to have illusory content when the circuits are partially degraded (incompetent), with synaptic efficacies weakened through infrequent use. Partially degraded circuits arise normally in the course of synaptic efficacy decay, or pathologically through abnormal regimens of DS. Organic delirium may result from breakdown of normal regimens of DS of circuitry during sleep, leaving many circuits incompetent. Activation of incompetent circuits during wakefulness apparently produces delirium and hallucinations. Some epileptic seizures may be induced by abnormal regimens of DS of motor circuitry. Regimens of remedial DS during seizures induced by electroconvulsive therapy (ECT) apparently produce temporary remission of delirium by restoring functional or 'dedicated' synaptic efficacies in incompetent circuitry. Sparing

  10. Tamping Ramping: Algorithmic, Implementational, and Computational Explanations of Phasic Dopamine Signals in the Accumbens.

    Science.gov (United States)

    Lloyd, Kevin; Dayan, Peter

    2015-12-01

    Substantial evidence suggests that the phasic activity of dopamine neurons represents reinforcement learning's temporal difference prediction error. However, recent reports of ramp-like increases in dopamine concentration in the striatum when animals are about to act, or are about to reach rewards, appear to pose a challenge to established thinking. This is because the implied activity is persistently predictable by preceding stimuli, and so cannot arise as this sort of prediction error. Here, we explore three possible accounts of such ramping signals: (a) the resolution of uncertainty about the timing of action; (b) the direct influence of dopamine over mechanisms associated with making choices; and (c) a new model of discounted vigour. Collectively, these suggest that dopamine ramps may be explained, with only minor disturbance, by standard theoretical ideas, though urgent questions remain regarding their proximal cause. We suggest experimental approaches to disentangling which of the proposed mechanisms are responsible for dopamine ramps. PMID:26699940

  11. A Process-Based Model for Simulating Phasic Development and Phenology in Rice

    Institute of Scientific and Technical Information of China (English)

    MENG Ya-li; CAO Wei-xing; ZHOU Zhi-guo; LIU Xin-wei

    2003-01-01

    A simulation model for phasic and phenological development of rice was developed using the scale of physiological development time, based on the ecophysiological development processes. The interaction of daily thermal effectiveness, photoperiod effectiveness and intrinsic earliness (before heading), and basic filling duration factor (after heading) determined the daily physiological effectiveness, which accumulated to get physiological development time. The Beta and quadratic functions were used to describe daily thermal and photoperiod effectiveness, respectively. Five specific genetic parameters were added to adjust the genotypic differences in rice development so that all different varieties could reach the same physiological development time at a given development stage. The stages of seedling emergence, panicle initiation, heading, and maturity were validated using sowing dates under different ecological environments, with the RMSE of 1.47, 5.10,4.58 and 3.37 days, respectively. The results showed that the model was not only explanatory and systematic but also accurate and applicable.

  12. Echocardiographic and hemodynamic determinants of right coronary artery flow reserve and phasic flow pattern in advanced non-ischemic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Mady Charles

    2007-09-01

    Full Text Available Abstract Background In patients with advanced non-ischemic cardiomyopathy (NIC, right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA flow pattern and flow reserve (CFR are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. Methods Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire data was obtained in RCA and left anterior descendent coronary artery (LAD before and after adenosine. Resting RCA phasic pattern (diastolic/systolic was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. Results LV fractional shortening and end diastolic diameter were 15.3 ± 3.5 % and 69.4 ± 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS; RCA vs. LAD was 1.35 vs. 2.85 (p Conclusion In patients with chronic advanced NIC, RCA phasic flow pattern has a mild diastolic predominance, less marked than in LAD, with no effects from pulmonary artery hypertension or RV dysfunction. There is no significant correlation between any cardiac mechanical-structural or

  13. Phasic alertness enhances processing of face and non-face stimuli in congenital prosopagnosia.

    Science.gov (United States)

    Tanzer, Michal; Weinbach, Noam; Mardo, Elite; Henik, Avishai; Avidan, Galia

    2016-08-01

    Congenital prosopagnosia (CP) is a severe face processing impairment that occurs in the absence of any obvious brain damage and has often been associated with a more general deficit in deriving holistic relations between facial features or even between non-face shape dimensions. Here we further characterized this deficit and examined a potential way to ameliorate it. To this end we manipulated phasic alertness using alerting cues previously shown to modulate attention and enhance global processing of visual stimuli in normal observers. Specifically, we first examined whether individuals with CP, similarly to controls, would show greater global processing when exposed to an alerting cue in the context of a non-facial task (Navon global/local task). We then explored the effect of an alerting cue on face processing (upright/inverted face discrimination). Confirming previous findings, in the absence of alerting cues, controls showed a typical global bias in the Navon task and an inversion effect indexing holistic processing in the upright/inverted task, while CP failed to show these effects. Critically, when alerting cues preceded the experimental trials, both groups showed enhanced global interference and a larger inversion effect. These results suggest that phasic alertness may modulate visual processing and consequently, affect global/holistic perception. Hence, these findings further reinforce the notion that global/holistic processing may serve as a possible mechanism underlying the face processing deficit in CP. Moreover, they imply a possible route for enhancing face processing in individuals with CP and thus shed new light on potential amelioration of this disorder. PMID:27364232

  14. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

    Directory of Open Access Journals (Sweden)

    Anne ePetzold

    2015-10-01

    Full Text Available Cholinergic neurons of the pedunculopontine nucleus (PPN are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state. During the transition, neurons were predominantly excited (phasically or tonically, but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation.

  15. Neural circuitry of stress-induced insomnia in rats

    OpenAIRE

    Cano, Georgina; Mochizuki, Takatoshi; Saper, Clifford B.

    2008-01-01

    Sleep architecture is often disturbed following a stressful event; nevertheless, little is known about the brain circuitry responsible for the sleep perturbations induced by stress. We exposed rats to a psychological stressor (cage exchange) that initially causes an acute stress response, but several hours later generates a pattern of sleep disturbances similar to that observed in stress-induced insomnia in humans: increased sleep latency, decreased nREM and REM sleep, increased fragmentation...

  16. The Origin of Behavioral Bursts in Decision-Making Circuitry

    OpenAIRE

    Amanda Sorribes; Armendariz, Beatriz G.; Diego Lopez-Pigozzi; Cristina Murga; de Polavieja, Gonzalo G.

    2011-01-01

    From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switche...

  17. Neural circuitry underlying affective response to peer feedback in adolescence

    OpenAIRE

    Guyer, Amanda E.; Choate, Victoria R.; Pine, Daniel S.; Nelson, Eric E.

    2011-01-01

    Peer feedback affects adolescents’ behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents’ emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9–17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents’ perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they fe...

  18. The neural circuitry of expertise: perceptual learning and social cognition

    OpenAIRE

    Michael Harre

    2013-01-01

    Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create ou...

  19. Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

    Directory of Open Access Journals (Sweden)

    Schaefer Ulf

    2009-12-01

    Full Text Available Abstract Background Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs. Current research suggests that microRNAs (miRNAs degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF→miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF→miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1 have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92, we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process.

  20. Phasic Burst Stimulation: A Closed-Loop Approach to Tuning Deep Brain Stimulation Parameters for Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Abbey B Holt

    2016-07-01

    Full Text Available We propose a novel, closed-loop approach to tuning deep brain stimulation (DBS for Parkinson's disease (PD. The approach, termed Phasic Burst Stimulation (PhaBS, applies a burst of stimulus pulses over a range of phases predicted to disrupt pathological oscillations seen in PD. Stimulation parameters are optimized based on phase response curves (PRCs, which would be measured from each patient. This approach is tested in a computational model of PD with an emergent population oscillation. We show that the stimulus phase can be optimized using the PRC, and that PhaBS is more effective at suppressing the pathological oscillation than a single phasic stimulus pulse. PhaBS provides a closed-loop approach to DBS that can be optimized for each patient.

  1. Phasic Burst Stimulation: A Closed-Loop Approach to Tuning Deep Brain Stimulation Parameters for Parkinson's Disease.

    Science.gov (United States)

    Holt, Abbey B; Wilson, Dan; Shinn, Max; Moehlis, Jeff; Netoff, Theoden I

    2016-07-01

    We propose a novel, closed-loop approach to tuning deep brain stimulation (DBS) for Parkinson's disease (PD). The approach, termed Phasic Burst Stimulation (PhaBS), applies a burst of stimulus pulses over a range of phases predicted to disrupt pathological oscillations seen in PD. Stimulation parameters are optimized based on phase response curves (PRCs), which would be measured from each patient. This approach is tested in a computational model of PD with an emergent population oscillation. We show that the stimulus phase can be optimized using the PRC, and that PhaBS is more effective at suppressing the pathological oscillation than a single phasic stimulus pulse. PhaBS provides a closed-loop approach to DBS that can be optimized for each patient. PMID:27415832

  2. Phasic alertness in a cued double-choice reaction time task: a Contingent Negative Variation (CNV) study.

    Science.gov (United States)

    Pauletti, Caterina; Mannarelli, Daniela; Grippo, Antonello; Currà, Antonio; Locuratolo, Nicoletta; De Lucia, Maria C; Fattapposta, Francesco

    2014-10-01

    A phasic change in alertness is produced every time that a warning stimulus precedes a target, and it enhances and maintains the response readiness to an impending stimulus. In the present study, we investigated the Contingent Negative Variation (CNV) phenomenon, as index of phasic alertness, during a S1-S2 paradigm in which the imperative stimulus was represented by a double-choice reaction time task, designed to increase the executive requests at S2. Subjects performed the task at three consecutive time points in order to explore the CNV activity over time. The repetition of a cued double-choice reaction time task reduced the reaction times (RTs), while CNV amplitude remained steady along the sessions. Our data suggest that the continuous recruitment of attentional resources does not undergo habituation when it is related to the brain activity required in the maintenance of working memory when the mental model of the stimulus environment is updated. PMID:25116758

  3. Phasic Burst Stimulation: A Closed-Loop Approach to Tuning Deep Brain Stimulation Parameters for Parkinson’s Disease

    Science.gov (United States)

    Holt, Abbey B.; Wilson, Dan; Moehlis, Jeff; Netoff, Theoden I.

    2016-01-01

    We propose a novel, closed-loop approach to tuning deep brain stimulation (DBS) for Parkinson’s disease (PD). The approach, termed Phasic Burst Stimulation (PhaBS), applies a burst of stimulus pulses over a range of phases predicted to disrupt pathological oscillations seen in PD. Stimulation parameters are optimized based on phase response curves (PRCs), which would be measured from each patient. This approach is tested in a computational model of PD with an emergent population oscillation. We show that the stimulus phase can be optimized using the PRC, and that PhaBS is more effective at suppressing the pathological oscillation than a single phasic stimulus pulse. PhaBS provides a closed-loop approach to DBS that can be optimized for each patient. PMID:27415832

  4. Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats

    OpenAIRE

    Saddoris, Michael P.; Wang, Xuefei; Sugam, Jonathan A; Carelli, Regina M.

    2016-01-01

    Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either ...

  5. Effects of muscle activity and number of resistance exercise repetitions on perceived exertion in tonic and phasic muscle of young Korean adults

    OpenAIRE

    An, Ho Jung; Choi, Wan Suk; Choi, Jung Hyun; Kim, Nyeon Jun; Min, Kyung Ok

    2015-01-01

    [Purpose] The aim of this study was to examine the effects of muscle activity and the number of resistance exercise repetitions on perceived exertion in tonic and phasic muscles in young Korean adults. [Subjects] Janda’s classification system was used to divide 40 Korean males and females in their 20s into a tonic muscle group (10 males, 10 females) and phasic muscle group (10 males, 10 females). [Methods] Each participant performed resistance exercise at 70% of maximum exertion for a single ...

  6. Evaluation of animal models of obsessive-compulsive disorder: correlation with phasic dopamine neuron activity.

    Science.gov (United States)

    Sesia, Thibaut; Bizup, Brandon; Grace, Anthony A

    2013-07-01

    Obsessive compulsive disorder (OCD) is a psychiatric condition defined by intrusive thoughts (obsessions) associated with compensatory and repetitive behaviour (compulsions). However, advancement in our understanding of this disorder has been hampered by the absence of effective animal models and correspondingly analysis of the physiological changes that may be present in these models. To address this, we have evaluated two current rodent models of OCD; repeated injection of dopamine D2 agonist quinpirole and repeated adolescent injection of the tricyclic agent clomipramine in combination with a behavioural paradigm designed to produce compulsive lever pressing. These results were then compared with their relative impact on the state of activity of the mesolimbic dopaminergic system using extracellular recoding of spontaneously active dopamine neurons in the ventral tegmental area (VTA). The clomipramine model failed to exacerbate compulsive lever pressing and VTA dopamine neurons in clomipramine-treated rats had mildly diminished bursting activity. In contrast, quinpirole-treated animals showed significant increases in compulsive lever pressing, which was concurrent with a substantial diminution of bursting activity of VTA dopamine neurons. Therefore, VTA dopamine activity correlated with the behavioural response in these models. Taken together, these data support the view that compulsive behaviours likely reflect, at least in part, a disruption of the dopaminergic system, more specifically by a decrease in baseline phasic dopamine signalling mediated by burst firing of dopamine neurons. PMID:23360787

  7. Phasic dopamine release in the medial prefrontal cortex enhances stimulus discrimination.

    Science.gov (United States)

    Popescu, Andrei T; Zhou, Michael R; Poo, Mu-Ming

    2016-05-31

    Phasic dopamine (DA) release is believed to guide associative learning. Most studies have focused on projections from the ventral tegmental area (VTA) to the striatum, and the action of DA in other VTA target regions remains unclear. Using optogenetic activation of VTA projections, we examined DA function in the medial prefrontal cortex (mPFC). We found that mice perceived optogenetically induced DA release in mPFC as neither rewarding nor aversive, and did not change their previously learned behavior in response to DA transients. However, repetitive temporal pairing of an auditory conditioned stimulus (CS) with mPFC DA release resulted in faster learning of a subsequent task involving discrimination of the same CS against unpaired stimuli. Similar results were obtained using both appetitive and aversive unconditioned stimuli, supporting the notion that DA transients in mPFC do not represent valence. Using extracellular recordings, we found that CS-DA pairings increased firing of mPFC neurons in response to CSs, and administration of D1 or D2 DA-receptor antagonists in mPFC during learning impaired stimulus discrimination. We conclude that DA transients tune mPFC neurons for the recognition of behaviorally relevant events during learning. PMID:27185946

  8. From Fibonacci to the mathematics of cows and quantum circuitry

    International Nuclear Information System (INIS)

    The Fibonacci sequence is a famously well-known integer sequence from the thirteenth century which has transcended its original motivation. It possesses many interested and varied applications within architecture, engineering and science. Less well known is the Narayana sequence which itself has interesting and wide-ranging Fibonacci-type connections. In this paper, we shall recall Narayana's original motivation that gives rise to the sequence bearing his name. We also provide an interesting application of this sequence to the construction to quantum gate circuitry used in quantum computation

  9. Implementing size-optimal discrete neural networks require analog circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-01

    This paper starts by overviewing results dealing with the approximation capabilities of neural networks, as well as bounds on the size of threshold gate circuits. Based on a constructive solution for Kolmogorov`s superpositions the authors show that implementing Boolean functions can be done using neurons having an identity transfer function. Because in this case the size of the network is minimized, it follows that size-optimal solutions for implementing Boolean functions can be obtained using analog circuitry. Conclusions and several comments on the required precision are ending the paper.

  10. Silent Synapse-Based Circuitry Remodeling in Drug Addiction.

    Science.gov (United States)

    Dong, Yan

    2016-05-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. PMID:26721952

  11. Low Power/Low Voltage Interface Circuitry for Capacitive Sensors

    DEFF Research Database (Denmark)

    Furst, Claus Efdmann

    This thesis focuses mainly on low power/low voltage interface circuits, implemented in CMOS, for capacitive sensors. A brief discussion of demands and possibilities for analog signal processing in the future is presented. Techniques for low power design is presented. This is done by analyzing power...... low power consumption. It is shown that the Sigma-Delta modulator is advantageous when embedded in a feedback loop with a mechanical sensor. Here a micro mechanical capacitive microphone. Feedback and detection circuitry for a capacitive microphone is presented. Practical implementations of low power...

  12. Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model

    Directory of Open Access Journals (Sweden)

    Hideo Hagihara

    2016-03-01

    Full Text Available Bipolar disorder, also known as manic-depressive illness, causes swings in mood and activity levels at irregular intervals. Such changes are difficult to predict, and their molecular basis remains unknown. Here, we use infradian (longer than a day cyclic activity levels in αCaMKII (Camk2a mutant mice as a proxy for such mood-associated changes. We report that gene-expression patterns in the hippocampal dentate gyrus could retrospectively predict whether the mice were in a state of high or low locomotor activity (LA. Expression of a subset of circadian genes, as well as levels of cAMP and pCREB, possible upstream regulators of circadian genes, were correlated with LA states, suggesting that the intrinsic molecular circuitry changes concomitant with infradian oscillatory LA. Taken together, these findings shed light onto the molecular basis of how irregular biological rhythms and behavior are controlled by the brain.

  13. Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model.

    Science.gov (United States)

    Hagihara, Hideo; Horikawa, Tomoyasu; Nakamura, Hironori K; Umemori, Juzoh; Shoji, Hirotaka; Kamitani, Yukiyasu; Miyakawa, Tsuyoshi

    2016-03-29

    Bipolar disorder, also known as manic-depressive illness, causes swings in mood and activity levels at irregular intervals. Such changes are difficult to predict, and their molecular basis remains unknown. Here, we use infradian (longer than a day) cyclic activity levels in αCaMKII (Camk2a) mutant mice as a proxy for such mood-associated changes. We report that gene-expression patterns in the hippocampal dentate gyrus could retrospectively predict whether the mice were in a state of high or low locomotor activity (LA). Expression of a subset of circadian genes, as well as levels of cAMP and pCREB, possible upstream regulators of circadian genes, were correlated with LA states, suggesting that the intrinsic molecular circuitry changes concomitant with infradian oscillatory LA. Taken together, these findings shed light onto the molecular basis of how irregular biological rhythms and behavior are controlled by the brain. PMID:27028761

  14. Advanced Data Acquisition Systems with Self-Healing Circuitry

    Science.gov (United States)

    Larson, William E.; Ihlefeld, Curtis M.; Medelius, Pedro J.; Delgado, H. (Technical Monitor)

    2001-01-01

    Kennedy Space Center's Spaceport Engineering & Technology Directorate has developed a data acquisition system that will help drive down the cost of ground launch operations. This system automates both the physical measurement set-up function as well as configuration management documentation. The key element of the system is a self-configuring, self-calibrating, signal-conditioning amplifier that automatically adapts to any sensor to which it is connected. This paper will describe the core technology behind this device and the automated data system in which it has been integrated. The paper will also describe the revolutionary enhancements that are planned for this innovative measurement technology. All measurement electronics devices contain circuitry that, if it fails or degrades, requires the unit to be replaced, adding to the cost of operations. Kennedy Space Center is now developing analog circuits that will be able to detect their own failure and dynamically reconfigure their circuitry to restore themselves to normal operation. This technology will have wide ranging application in all electronic devices used in space and ground systems.

  15. Microglia disrupt mesolimbic reward circuitry in chronic pain.

    Science.gov (United States)

    Taylor, Anna M W; Castonguay, Annie; Taylor, Alison J; Murphy, Niall P; Ghogha, Atefeh; Cook, Christopher; Xue, Lihua; Olmstead, Mary C; De Koninck, Yves; Evans, Christopher J; Cahill, Catherine M

    2015-06-01

    Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a decrease in opioid-evoked DA release in the ventral striatum, suggesting that the occurrence of chronic pain impairs reward-related behaviors. However, mechanisms by which pain modifies DA transmission remain elusive. Using in vivo microdialysis and microinjection of drugs into the mesolimbic DA system, we demonstrate in mice and rats that microglial activation in the VTA compromises not only opioid-evoked release of DA, but also other DA-stimulating drugs, such as cocaine. Our data show that loss of stimulated extracellular DA is due to impaired chloride homeostasis in midbrain GABAergic interneurons. Treatment with minocycline or interfering with BDNF signaling restored chloride transport within these neurons and recovered DA-dependent reward behavior. Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic signaling and reward behavior. These results have broad implications that are not restricted to the problem of pain, but are also relevant to affective disorders associated with disruption of reward circuitry. Because chronic pain causes glial activation in areas of the CNS important for mood and affect, our findings may translate to other disorders, including anxiety and depression, that demonstrate high comorbidity with chronic pain. PMID:26041913

  16. Phasic or terminal detrusor overactivity in women: age, urodynamic findings and sphincter behavior relationships

    Directory of Open Access Journals (Sweden)

    Françoise A. Valentini

    2011-12-01

    Full Text Available OBJECTIVES: To search for relationships between phasic (P and terminal (T DO with age, urodynamic findings and sphincter behavior during involuntary detrusor contraction in woman. MATERIALS AND METHODS: Urodynamic studies (triple lumen catheter 7F, seated position of 164 successive women referred for LUTS with diagnosis of DO were reviewed. Patients were stratified in 4 sub-groups: pre- (18-44y, peri- (45-54 y, post-menopause (55-74 y and oldest old (≥ 75 y. The urethral sensor was positioned at the level of the maximum urethral closure pressure for sphincter behavior analysis. A variation of at least 5 cmH2O in pressure (detrusor or urethra was chosen to assert DO or sphincter response. Sphincter response was classified as relaxation (re before or during DO, or steady (st. RESULTS: Occurrence of P and TDO was similar: 77 P and 87 T. The PDO group was significantly younger (p = 0.0003. TDO was more frequent in patients with a history of neurological disease. The percentage of PDO remained almost constant in age groups, while that of TDO increased with age from 6.7% to 23.2% (p = 0.0013. Uninhibited contraction occurred at a smaller bladder volume in the P group: 149 ± 95 vs. 221 ± 113 mL (p < 0.0001. Steady sphincter predominated in the TDO subgroup: 45.9% vs. 32.1% and increased significantly in each DO sub-group of ³ 75y. CONCLUSION: Steady sphincter during both P and TDO, and occurrence of TDO appear as specific of aging. The last result could be related to structural changes in the detrusor muscle with aging.

  17. Influence of norepinephrine on the tonic and phasic depression of Vmax by nifedipine and verapamil in guinea pig ventricle.

    Science.gov (United States)

    Woods, J P; West, T C

    1986-01-01

    Right ventricular strips from guinea pig hearts were used to study the interaction between norepinephrine (NE) and the Ca2+ channel blockers nifedipine and verapamil on maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. Barium ion (0.8 mM) was added to the bathing solution to restore excitability of the K+-depolarized tissue. Concentrations of verapamil (5 X 10(-7) M) and nifedipine (5 X 10(-8) M) were selected to produce optimal depression of Vmax under both tonic (rested) and phasic (pacing frequencies from 0.05 to 2.0 Hz) conditions. NE increased the tonic and phasic Vmax of control preparations in equal proportion at all stimulation frequencies. Thus, the physiological frequency dependence of Vmax was not altered by NE. NE (10(-6) M) produced an increase of 11.8 +/- 2.2% in the tonic Vmax of verapamil-treated preparations and an increase of 17.4 +/- 1.1% in the tonic Vmax of nifedipine-treated preparations. In each case the enhancement of Vmax by NE was proportional for both tonic and phasic conditions, thus showing no effect on the frequency-dependent action of either drug. In all cases, the NE-induced increase in Vmax was concentration dependent. Higher concentrations of NE thwarted the measurement of tonic Vmax due to the onset of spontaneous activity except in the presence of nifedipine (5 X 10(-8) M). The maximal concentration of NE that could be tolerated without the onset of spontaneous activity was directly related to the degree of tonic depression of Vmax induced by the Ca2+ channel blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2427818

  18. Usefulness of three-phasic bone scan in young male patients suspected of post-traumatic reflex sympathetic dystrophy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Woo; Kim, Tae Uk; Kim, Tae Hoon; Jung, Cheoul Yun; Moon, Jin Ho [Armed Forces Daejeon Hospital, Taejon (Korea, Republic of)

    2001-02-01

    In young male patients who suffered several kinds of trauma with subsequent suspicious reflex sympathetic dystrophy syndrome, we performed three-phasic bone scan in order to investigate its usefulness. Patients with narrow range of age (21-25. mean 22.8 {+-}1.3, all male) were included with suspicious reflex sympathetic dystrophy syndrome of 12 feet and 5 hands. Only one was bilateral feet case and 16 were ipsilateral (Rt:13, Lt:3). The etiologic traumas were 4 fractures, 4 sprains, 3 blunt trauma, 2 cellulitis, 1 tendon teat, 1 crush injury, 1 overexercise, and 1 unknown. Radiologically 3 showed osteoporotic changes. Three-phasic bone scans were performed 21.1 {+-}7.3 wks after trauma. According to symptom complex, confirmatory reflex sympathetic dystrophy syndrome 4 cases and suspicious 13 were analyzed. All confirmatory cases (100%) showed increased uptake at delay phase with periarticular accentuation. Of confirmatory 4 cases, 2 showed increased uptake in all three phases (perfusion: P, blood pool: B, and delay: D), and other 2 revealed decreased P but, both increased B and D. Of suspicious 13 cases, 9(69.2%) had increased D (4 periarticular and 5 focal), 2 decreased D, and 2 symmetric D. In 12 foot cases, so-called weight bearing patterns-increased contralateral sole at P and B- were revealed in 7(58.3%). Diffuse periarticular increased uptake at delay phase of three-phasic bone scan was a compatible finding to reflex sympathetic dystrophy syndrome in young male patients whose symptom complex strongly designated post traumatic reflex sympathetic dystrophy syndrome.

  19. Usefulness of three-phasic bone scan in young male patients suspected of post-traumatic reflex sympathetic dystrophy syndrome

    International Nuclear Information System (INIS)

    In young male patients who suffered several kinds of trauma with subsequent suspicious reflex sympathetic dystrophy syndrome, we performed three-phasic bone scan in order to investigate its usefulness. Patients with narrow range of age (21-25. mean 22.8 ±1.3, all male) were included with suspicious reflex sympathetic dystrophy syndrome of 12 feet and 5 hands. Only one was bilateral feet case and 16 were ipsilateral (Rt:13, Lt:3). The etiologic traumas were 4 fractures, 4 sprains, 3 blunt trauma, 2 cellulitis, 1 tendon teat, 1 crush injury, 1 overexercise, and 1 unknown. Radiologically 3 showed osteoporotic changes. Three-phasic bone scans were performed 21.1 ±7.3 wks after trauma. According to symptom complex, confirmatory reflex sympathetic dystrophy syndrome 4 cases and suspicious 13 were analyzed. All confirmatory cases (100%) showed increased uptake at delay phase with periarticular accentuation. Of confirmatory 4 cases, 2 showed increased uptake in all three phases (perfusion: P, blood pool: B, and delay: D), and other 2 revealed decreased P but, both increased B and D. Of suspicious 13 cases, 9(69.2%) had increased D (4 periarticular and 5 focal), 2 decreased D, and 2 symmetric D. In 12 foot cases, so-called weight bearing patterns-increased contralateral sole at P and B- were revealed in 7(58.3%). Diffuse periarticular increased uptake at delay phase of three-phasic bone scan was a compatible finding to reflex sympathetic dystrophy syndrome in young male patients whose symptom complex strongly designated post traumatic reflex sympathetic dystrophy syndrome

  20. Focusing on optic tectum circuitry through the lens of genetics

    Directory of Open Access Journals (Sweden)

    Nevin Linda M

    2010-09-01

    Full Text Available Abstract The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

  1. New materials strategies for creating hybrid electronic circuitry (Presentation Video)

    Science.gov (United States)

    Marks, Tobin J.

    2013-09-01

    This lecture focuses on the challenging design and realization of new materials for creating unconventional electronic circuitry. Fabrication methodologies to achieve these goals include high-throughput, large-area printing techniques. Materials design topics to be discussed include: 1. Rationally designed high-mobility p- and n-type organic semiconductors for printed organic CMOS, 2. Polycrystalline and amorphous oxide semiconductors for transparent and mechanically flexible electronics, 3) Self-assembled and printable high-k nanodielectrics enabling ultra-large capacitance, low leakage, high breakdown fields, minimal trapped interfacial charge, and device radiation hardness. 4) Combining these materials sets to fabricate a variety of high-performance thin-film transistor-based devices.

  2. Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

    KAUST Repository

    Schmeier, Sebastian

    2009-12-10

    Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

  3. Mapping the Brain’s Metaphor Circuitry:Is Abstract Thought Metaphorical Thought?

    OpenAIRE

    George eLakoff

    2014-01-01

    An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry.

  4. Functional microstates within human REM sleep: first evidence from fMRI of a thalamocortical network specific for phasic REM periods.

    Science.gov (United States)

    Wehrle, Renate; Kaufmann, Christian; Wetter, Thomas C; Holsboer, Florian; Auer, Dorothee P; Pollmächer, Thomas; Czisch, Michael

    2007-02-01

    High thalamocortical neuronal activity characterizes both, wakefulness and rapid eye movement (REM) sleep, but apparently this network fulfills other roles than processing external information during REM sleep. To investigate thalamic and cortical reactivity during human REM sleep, we used functional magnetic resonance imaging with simultaneous polysomnographic recordings while applying acoustic stimulation. Our observations indicate two distinct functional substates within general REM sleep. Acoustic stimulation elicited a residual activation of the auditory cortex during tonic REM sleep background without rapid eye movements. By contrast, periods containing bursts of phasic activity such as rapid eye movements appear characterized by a lack of reactivity to sensory stimuli. We report a thalamocortical network including limbic and parahippocampal areas specifically active during phasic REM periods. Thus, REM sleep has to be subdivided into tonic REM sleep with residual alertness, and phasic REM sleep with the brain acting as a functionally isolated and closed intrinsic loop. PMID:17328781

  5. A decentralized control scheme for an effective coordination of phasic and tonic control in a snake-like robot

    International Nuclear Information System (INIS)

    Autonomous decentralized control has attracted considerable attention because it enables us to understand the adaptive and versatile locomotion of animals and facilitates the construction of truly intelligent artificial agents. Thus far, we have developed a snake-like robot (HAUBOT I) that is driven by a decentralized control scheme based on a discrepancy function, which incorporates phasic control. In this paper, we investigate a decentralized control scheme in which phasic and tonic control are well coordinated, as an extension of our previous study. To verify the validity of the proposed control scheme, we apply it to a snake-like robot (HAUBOT II) that can adjust both the phase relationship between its body segments and the stiffness at each joint. The results indicate that the proposed control scheme enables the robot to exhibit remarkable real-time adaptability over various frictional and inclined terrains. These findings can potentially enable us to gain a deeper insight into the autonomous decentralized control mechanism underlying the adaptive and resilient locomotion of animals.

  6. A computational framework for ultrastructural mapping of neural circuitry.

    Directory of Open Access Journals (Sweden)

    James R Anderson

    2009-03-01

    Full Text Available Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM, mosaicking and registration (ir-tools, and large slice viewers (MosaicBuilder, Viking can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina, terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally

  7. Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

    OpenAIRE

    Grieder, Taryn E; George, Olivier; Tan, Huibing; George, Susan R.; Le Foll, Bernard; Laviolette, Steven R; van der Kooy, Derek

    2012-01-01

    Nicotine, the main psychoactive ingredient of tobacco smoke, induces negative motivational symptoms during withdrawal that contribute to relapse in dependent individuals. The neurobiological mechanisms underlying how the brain signals nicotine withdrawal remain poorly understood. Using electrophysiological, genetic, pharmacological, and behavioral methods, we demonstrate that tonic but not phasic activity is reduced during nicotine withdrawal in ventral tegmental area dopamine (DA) neurons, a...

  8. Smoking Increases Risk of Pain Chronification Through Shared Corticostriatal Circuitry

    Science.gov (United States)

    Petre, Bogdan; Torbey, Souraya; Griffith, James W.; De Oliveira, Gildasio; Herrmann, Kristine; Mansour, Ali; Baria, Alex T.; Baliki, Marwan N.; Schnitzer, Thomas J.; Apkarian, Apkar Vania

    2016-01-01

    Smoking is associated with increased incidence of chronic pain. However, the evidence is cross-sectional in nature, and underlying mechanisms remain unclear. In a longitudinal observational study, we examined the relationship between smoking, transition to chronic pain, and brain physiology. In 160 subjects with subacute back pain (SBP: back pain lasting 4–12 weeks, and no prior back pain [BP] for at least 1 year) pain characteristics, smoking status, and brain functional properties were measured repeatedly over 1 year. Sixty-eight completed the study, subdivided into recovering (SBPr, n = 31) and persisting (SBPp, n = 37), based on >20% decrease in BP over the year. Thirty-two chronic back pain (CBP: duration > 5 years) and 35 healthy controls were similarly monitored. Smoking prevalence was higher in SBP and CBP but not related to intensity of BP. In SBP, smoking status at baseline was predictive of persistence of BP 1 year from symptom onset (differentiating SBPp and SBPr with 0.62 accuracy). Smoking status combined with affective properties of pain and medication use improved prediction accuracy (0.82). Mediation analysis indicated the prediction of BP persistence by smoking was largely due to synchrony of fMRI activity between two brain areas (nucleus accumbens and medial prefrontal cortex, NAc-mPFC). In SBP or CBP who ceased smoking strength of NAc-mPFC decreased from precessation to postcessation of smoking. We conclude that smoking increases risk of transitioning to CBP, an effect mediated by corticostriatal circuitry involved in addictive behavior and motivated learning. PMID:25307796

  9. Altered reward circuitry in the norepinephrine transporter knockout mouse.

    Directory of Open Access Journals (Sweden)

    Joseph J Gallagher

    Full Text Available Synaptic levels of the monoamine neurotransmitters dopamine, serotonin, and norepinephrine are modulated by their respective plasma membrane transporters, albeit with a few exceptions. Monoamine transporters remove monoamines from the synaptic cleft and thus influence the degree and duration of signaling. Abnormal concentrations of these neuronal transmitters are implicated in a number of neurological and psychiatric disorders, including addiction, depression, and attention deficit/hyperactivity disorder. This work concentrates on the norepinephrine transporter (NET, using a battery of in vivo magnetic resonance imaging techniques and histological correlates to probe the effects of genetic deletion of the norepinephrine transporter on brain metabolism, anatomy and functional connectivity. MRS recorded in the striatum of NET knockout mice indicated a lower concentration of NAA that correlates with histological observations of subtle dysmorphisms in the striatum and internal capsule. As with DAT and SERT knockout mice, we detected minimal structural alterations in NET knockout mice by tensor-based morphometric analysis. In contrast, longitudinal imaging after stereotaxic prefrontal cortical injection of manganese, an established neuronal circuitry tracer, revealed that the reward circuit in the NET knockout mouse is biased toward anterior portions of the brain. This is similar to previous results observed for the dopamine transporter (DAT knockout mouse, but dissimilar from work with serotonin transporter (SERT knockout mice where Mn(2+ tracings extended to more posterior structures than in wildtype animals. These observations correlate with behavioral studies indicating that SERT knockout mice display anxiety-like phenotypes, while NET knockouts and to a lesser extent DAT knockout mice display antidepressant-like phenotypic features. Thus, the mainly anterior activity detected with manganese-enhanced MRI in the DAT and NET knockout mice is likely

  10. Epithelial-to-mesenchymal plasticity harnesses endocytic circuitries

    Directory of Open Access Journals (Sweden)

    Giorgio eScita

    2015-02-01

    Full Text Available The ability of cells to alter their phenotypic and morphological characteristics, known as cellular plasticity, is critical in embryonic development and adult tissue repair and contributes to the pathogenesis of diseases, such as organ fibrosis and cancer. The epithelial-to-mesenchymal transition (EMT is a type of cellular plasticity. This transition involves genetic and epigenetic changes as well as alterations in protein expression and posttranslational modifications. These changes result in reduced cell-cell adhesion, enhanced cell adhesion to the extracellular matrix, and altered organization of the cytoskeleton and of cell polarity. Among them, loss of cell polarity represents the nearly invariable feature of EMT that precedes the other traits or might even occur in their absence.Time-resolved proteomic and phosphoproteomic analyses of cells undergoing EMT recently identified thousands of changes in proteins involved in many cellular processes, including cell proliferation and motility, DNA repair, and – unexpectedly – membrane trafficking. These results have highlighted a picture of great complexity. First the EMT transition is not an all-or-none response but rather a gradual process. Second EMT events are dynamic and frequently reversible, involving cell-autonomous and non-autonomous mechanisms. Endocytic circuitries have emerged as complex connectivity infrastructures for cellular networks required for the execution of different biological processes, with a primary role in the control of polarized functions. Thus, they may be relevant for controlling certain aspects of EMT. Here, by discussing a few paradigmatic cases, we will outline how endocytosis may be harnessed by the EMT process to promote dynamic changes in cellular identity, and to increase cellular flexibility and adaptation to microenvironmental cues, ultimately impacting on physiological and pathological processes

  11. Spontaneously tonic smooth muscle has characteristically higher levels of RhoA/ROK compared with the phasic smooth muscle.

    Science.gov (United States)

    Patel, Chirag A; Rattan, Satish

    2006-11-01

    The internal anal sphincter (IAS) tone is important for the rectoanal continence. The RhoA/Rho kinase (ROK) pathway has been associated with the agonist-induced sustained contraction of the smooth muscle, but its role in the spontaneously tonic smooth muscle is not known. Present studies compared expression of different components of the RhoA/ROK pathway between the IAS (a truly tonic SM), the rectal smooth muscle (RSM) (a mixture of phasic and tonic), and anococcygeus smooth muscle (ASM) (a purely phasic SM) of rat. RT-PCR and Western blot analyses were performed to determine RhoA, ROCK-II, CPI-17, MYPT1, and myosin light-chain 20 (MLC20). Phosphorylated CPI-17 at threonine-38 residue (p(Thr38)-CPI-17), MYPT1 at threonine-696 residue (p(Thr696)-MYPT1), and MLC20 at threonine-18/serine-19 residues (p(Thr18/Ser19)-MLC20) were also determined in the basal state and after pretreatment with the ROK inhibitor Y 27632. In addition, we compared the effect of Y 27632 on the basal isometric tension and ROK activity in the IAS vs. the RSM. Our data show the highest levels of RhoA, ROCK-II, CPI-17, MLC20, and of phospho-MYPT1, -CPI-17, and -MLC20 in the IAS followed by in the RSM and ASM. Conversely, MYPT1 levels were lowest in the IAS and highest in the ASM. In the IAS, Y 27632 caused a concentration-dependent decrease in the basal tone, levels of phospho-MYPT1, -CPI-17, and -MLC20, and ROK activity. We conclude that RhoA/ROK plays a critical role in the basal tone in the IAS by the inhibition of MLC phosphatase via the phosphorylation of MYPT1 and CPI-17. PMID:16763289

  12. Assembly of the auditory circuitry by a Hox genetic network in the mouse brainstem.

    Directory of Open Access Journals (Sweden)

    Maria Di Bonito

    Full Text Available Rhombomeres (r contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN, and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem.

  13. Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Russ

    2013-09-01

    Full Text Available During perinatal development, corticospinal tract (CST projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65. In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of descending spinal pathways, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

  14. THE NEURAL CIRCUITRY UNDERLYING REINSTATEMENT OF HEROIN-SEEKING BEHAVIOR IN AN ANIMAL MODEL OF RELAPSE

    OpenAIRE

    Rogers, J. L.; GHEE, S.; SEE, R.E.

    2007-01-01

    Reinstatement of extinguished drug-seeking has been utilized in the study of the neural substrates of relapse to drugs of abuse, particularly cocaine. However, limited studies have examined the circuitry that drives the reinstatement of heroin-seeking behavior in the presence of conditioned cues, or by heroin itself. In order to test the hypothesis that the circuitry underlying reinstatement in heroin-experienced animals would show overlapping, yet distinct differences from cocaine-experience...

  15. Mapping the Hsp90 Genetic Network Reveals Ergosterol Biosynthesis and Phosphatidylinositol-4-Kinase Signaling as Core Circuitry Governing Cellular Stress

    Science.gov (United States)

    O’Meara, Teresa R.; Valaei, Seyedeh Fereshteh; Diezmann, Stephanie; Cowen, Leah E.

    2016-01-01

    Candida albicans is a leading human fungal pathogen that causes life-threatening systemic infections. A key regulator of C. albicans stress response, drug resistance, morphogenesis, and virulence is the molecular chaperone Hsp90. Targeting Hsp90 provides a powerful strategy to treat fungal infections, however, the therapeutic utility of current inhibitors is compromised by toxicity due to inhibition of host Hsp90. To identify components of the Hsp90-dependent circuitry governing virulence and drug resistance that are sufficiently divergent for selective targeting in the pathogen, we pioneered chemical genomic profiling of the Hsp90 genetic network in C. albicans. Here, we screen mutant collections covering ~10% of the genome for hypersensitivity to Hsp90 inhibition in multiple environmental conditions. We identify 158 HSP90 chemical genetic interactors, most of which are important for growth only in specific environments. We discovered that the sterol C-22 desaturase gene ERG5 and the phosphatidylinositol-4-kinase (PI4K) gene STT4 are HSP90 genetic interactors under multiple conditions, suggesting a function upstream of Hsp90. By systematic analysis of the ergosterol biosynthetic cascade, we demonstrate that defects in ergosterol biosynthesis induce cellular stress that overwhelms Hsp90’s functional capacity. By analysis of the phosphatidylinositol pathway, we demonstrate that there is a genetic interaction between the PI4K Stt4 and Hsp90. We also establish that Stt4 is required for normal actin polarization through regulation of Wal1, and suggest a model in which defects in actin remodeling induces stress that creates a cellular demand for Hsp90 that exceeds its functional capacity. Consistent with this model, actin inhibitors are synergistic with Hsp90 inhibitors. We highlight new connections between Hsp90 and virulence traits, demonstrating that Erg5 and Stt4 enable activation of macrophage pyroptosis. This work uncovers novel circuitry regulating Hsp90

  16. Type-dependent irreversible stochastic spin models for genetic regulatory networks at the level of promotion-inhibition circuitry

    Science.gov (United States)

    Mendonça, J. Ricardo G.; de Oliveira, Mário J.

    2015-12-01

    We describe an approach to model genetic regulatory networks at the level of promotion-inhibition circuitry through a class of stochastic spin models that includes spatial and temporal density fluctuations in a natural way. The formalism can be viewed as an agent-based model formalism with agent behaviour ruled by a classical spin-like pseudo-Hamiltonian playing the role of a local, individual objective function. A particular but otherwise generally applicable choice for the microscopic transition rates of the models also makes them of independent interest. To illustrate the formalism, we investigate (by Monte Carlo simulations) some stationary state properties of the repressilator, a synthetic three-gene network of transcriptional regulators that possesses oscillatory behaviour.

  17. Age differences in high frequency phasic heart rate variability and performance response to increased executive function load in three executive function tasks

    OpenAIRE

    Byrd, Dana L.; Reuther, Erin T.; McNamara, Joseph P. H.; DeLucca, Teri L.; Berg, William K.

    2015-01-01

    The current study examines similarity or disparity of a frontally mediated physiological response of mental effort among multiple executive functioning tasks between children and adults. Task performance and phasic heart rate variability (HRV) were recorded in children (6 to 10 years old) and adults in an examination of age differences in executive functioning skills during periods of increased demand. Executive load levels were varied by increasing the difficulty levels of three executive fu...

  18. Complete twelve month bone remodeling with a bi-phasic injectable bone substitute in benign bone tumors: a prospective pilot study

    OpenAIRE

    Kaczmarczyk, Jacek; Sowinski, Piotr; Goch, Maciej; Katulska, Katarzyna

    2015-01-01

    Background Benign primary bone tumors are commonly treated by surgery involving bone grafts or synthetic bone void fillers. Although synthetic bone grafts may provide early mechanical support while minimizing the risk of donor-site morbidity and disease transmission, difficult handling properties and less than optimal transformation to bone have limited their use. Methods In a prospective series, patients with benign bone tumors were treated by minimal invasive intervention with a bi-phasic a...

  19. The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study

    OpenAIRE

    Daniela Mannarelli; Caterina Pauletti; Antonello Grippo; Aldo Amantini; Vito Augugliaro; Antonio Currà; Paolo Missori; Nicoletta Locuratolo; Maria C. De Lucia; Steno Rinalduzzi; Francesco Fattapposta

    2015-01-01

    Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in...

  20. The contribution of delta subunit-containing GABAA receptors to phasic and tonic conductance changes in cerebellum, thalamus and neocortex.

    Directory of Open Access Journals (Sweden)

    Stephen G Brickley

    2013-12-01

    Full Text Available We have made use of the delta subunit-selective allosteric modulator DS2 (4-chloro-N-[2-(2-thienylimidazo[1,2-a]pyridine-3-yl benzamide to assay the contribution of delta-GABAARs to tonic and phasic conductance changes in the cerebellum, thalamus and neocortex. In cerebellar granule cells, an enhancement of the tonic conductance was observed for DS2 and the orthosteric agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. As expected, DS2 did not alter the properties of GABAA receptor-mediated inhibitory postsynaptic synaptic currents (IPSCs supporting a purely extrasynaptic role for delta-GABAARs in cerebellar granule cells. DS2 also enhanced the tonic conductance recorded from thalamic relay neurons of the visual thalamus with no alteration in IPSC properties. However, in addition to enhancing the tonic conductance DS2 also slowed the decay of IPSCs recorded from layer II/III neocortical neurons. A slowing of the IPSC decay also occurred in the presence of the voltage-gated sodium channel blocker TTX. Moreover, under conditions of reduced GABA release the ability of DS2 to enhance the tonic conductance was attenuated. These results indicate that delta-GABAARs can be activated following vesicular GABA release onto neocortical neurons and that the actions of DS2 on the tonic conductance may be influenced by the ambient GABA levels present in particular brain regions.

  1. Investigation of Phasic Process of Biogas Yield by Measuring pH, ORP and Electrical Power Changes

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Abdoli

    2016-04-01

    Full Text Available Background & Aims of the Study: Studying the phasic process of the biogas yieldis required to optimize the design and operations; it also helps to lower energy production costs by decreasing the capital investment and operational costs. Here we determine the biogas process by measuring pH, ORP, electrical power and make compatibility to the biogas production trend. Materials and Methods: In this research, one 1150 ml single chamber reactor is used. Biogas production trend was precisely followed by a probable compatibleness with pH, Oxidation Reduction Potential (ORP, electrical Power at a temperature of 37+ 0.5˚C with the substrate of cattle manure. The experiment was followed for 120 days approximately. Results: As a result, the phases of biogas yield could be determined by the measuring of pH, ORP and its compatibility to gas production. In the reactor, hydrolytic, acetogenic and methanogenic phases were occurred in the days 1-7, 8-16 and 17-104, respectively. Also the electrical power at first showed to be produced at high range but by increasing, the production of biogas decreased and then by decreasing the biogas production gradually, it increased slightly. Conclusion: Our results indicated that the phases of biogas production can be separated  completely and by diffracting the phases, the efficiency of biogas production could be increased.

  2. Superior perception of phasic physiological arousal and the detrimental consequences of the conviction to be aroused on worrying and metacognitions in GAD.

    Science.gov (United States)

    Andor, Tanja; Gerlach, Alexander L; Rist, Fred

    2008-02-01

    Although people suffering from generalized anxiety disorder (GAD) often report arousal symptoms, psychophysiological studies show no evidence of autonomic hyperarousal. Hypersensitivity toward and catastrophic interpretation of phasic arousal cues may explain this discrepancy. The authors tested (a) whether GAD sufferers perceive nonspecific skin conductance fluctuations (NSCFs), an indicator of phasic autonomic arousal, better than controls do and (b) whether the conviction to be aroused contributes to the maintenance of worrying and metacognitive beliefs about worrying. Thirty-three GAD sufferers and 34 healthy controls participated in 2 experiments. In Experiment 1, participants were asked to detect their own NSCFs during a signal detection task. GAD sufferers accurately detected more of their NSCFs than did controls, who tended to miss NSCFs. In Experiment 2, participants were instructed to relax following worry induction. While relaxing, they received nonveridical feedback indicating either arousal or relaxation. Arousal feedback conserved negative metacognitive beliefs regarding worrying and also maintained negative mood and worry exclusively in GAD participants. These findings suggest that superior perception of phasic arousal cues and their catastrophic misinterpretation increases worrying, negative metacognitive beliefs about worrying, and anxious mood in GAD. PMID:18266497

  3. DNA-decorated carbon-nanotube-based chemical sensors on complementary metal oxide semiconductor circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chia-Ling; Yang, Chih-Feng; Dokmeci, Mehmet R [Department of Electrical and Computer Engineering, NSF Nanoscale Science and Engineering Center for High-rate Nanomanufacturing, Northeastern University, 360 Huntington Avenue, Boston, MA 02115 (United States); Agarwal, Vinay; Sonkusale, Sameer [Department of Electrical and Computer Engineering, Tufts University, Medford, MA 02155 (United States); Kim, Taehoon; Busnaina, Ahmed [Department of Mechanical and Industrial Engineering, NSF Nanoscale Science and Engineering Center for High-rate Nanomanufacturing, Northeastern University, 360 Huntington Avenue, Boston, MA 02115 (United States); Chen, Michelle, E-mail: chen.ch@neu.edu, E-mail: yang.chi@neu.edu, E-mail: vinay.agarwal84@gmail.com, E-mail: thkim@coe.neu.edu, E-mail: sameer@ece.tufts.edu, E-mail: busnaina@coe.neu.edu, E-mail: michelle.chen@simmons.edu, E-mail: mehmetd@ece.neu.edu [Physics Department, Simmons College, 300 The Fenway, Boston, MA 02115 (United States)

    2010-03-05

    We present integration of single-stranded DNA (ss-DNA)-decorated single-walled carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS) circuitry as nanoscale chemical sensors. SWNTs were assembled onto CMOS circuitry via a low voltage dielectrophoretic (DEP) process. Besides, bare SWNTs are reported to be sensitive to various chemicals, and functionalization of SWNTs with biomolecular complexes further enhances the sensing specificity and sensitivity. After decorating ss-DNA on SWNTs, we have found that the sensing response of the gas sensor was enhanced (up to {approx} 300% and {approx} 250% for methanol vapor and isopropanol alcohol vapor, respectively) compared with bare SWNTs. The SWNTs coupled with ss-DNA and their integration on CMOS circuitry demonstrates a step towards realizing ultra-sensitive electronic nose applications.

  4. DNA-decorated carbon-nanotube-based chemical sensors on complementary metal oxide semiconductor circuitry

    International Nuclear Information System (INIS)

    We present integration of single-stranded DNA (ss-DNA)-decorated single-walled carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS) circuitry as nanoscale chemical sensors. SWNTs were assembled onto CMOS circuitry via a low voltage dielectrophoretic (DEP) process. Besides, bare SWNTs are reported to be sensitive to various chemicals, and functionalization of SWNTs with biomolecular complexes further enhances the sensing specificity and sensitivity. After decorating ss-DNA on SWNTs, we have found that the sensing response of the gas sensor was enhanced (up to ∼ 300% and ∼ 250% for methanol vapor and isopropanol alcohol vapor, respectively) compared with bare SWNTs. The SWNTs coupled with ss-DNA and their integration on CMOS circuitry demonstrates a step towards realizing ultra-sensitive electronic nose applications.

  5. DNA-decorated carbon-nanotube-based chemical sensors on complementary metal oxide semiconductor circuitry

    Science.gov (United States)

    Chen, Chia-Ling; Yang, Chih-Feng; Agarwal, Vinay; Kim, Taehoon; Sonkusale, Sameer; Busnaina, Ahmed; Chen, Michelle; Dokmeci, Mehmet R.

    2010-03-01

    We present integration of single-stranded DNA (ss-DNA)-decorated single-walled carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS) circuitry as nanoscale chemical sensors. SWNTs were assembled onto CMOS circuitry via a low voltage dielectrophoretic (DEP) process. Besides, bare SWNTs are reported to be sensitive to various chemicals, and functionalization of SWNTs with biomolecular complexes further enhances the sensing specificity and sensitivity. After decorating ss-DNA on SWNTs, we have found that the sensing response of the gas sensor was enhanced (up to ~ 300% and ~ 250% for methanol vapor and isopropanol alcohol vapor, respectively) compared with bare SWNTs. The SWNTs coupled with ss-DNA and their integration on CMOS circuitry demonstrates a step towards realizing ultra-sensitive electronic nose applications.

  6. A neuronal circuitry for relative movement discrimination by the visual system of the fly

    Science.gov (United States)

    Poggio, T.; Reichardt, W.; Hausen, K.

    1981-09-01

    We propose the basic structure of a neuronal circuitry possibly underlying the detection of discontinuities in the optical flow by the visual system of the housefly. The main features of the circuitry are: binocular cells summate elementary movement detectors over a large visual field and inhibit each one of them; inhibition is of the shunting type, with an inhibitory equilibrium potential very near the resting potential. A specific model implementing our proposal accounts for all the behavioral data on relative movement discrimination, including the characteristic dynamics of the response.

  7. Common stemness regulators of embryonic and cancer stem cells

    OpenAIRE

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we h...

  8. Morphogenetic circuitry regulating growth and development in the dimorphic pathogen Penicillium marneffei.

    Science.gov (United States)

    Boyce, Kylie J; Andrianopoulos, Alex

    2013-02-01

    Penicillium marneffei is an emerging human-pathogenic fungus endemic to Southeast Asia. Like a number of other fungal pathogens, P. marneffei exhibits temperature-dependent dimorphic growth and grows in two distinct cellular morphologies, hyphae at 25°C and yeast cells at 37°C. Hyphae can differentiate to produce the infectious agents, asexual spores (conidia), which are inhaled into the host lung, where they are phagocytosed by pulmonary alveolar macrophages. Within macrophages, conidia germinate into unicellular yeast cells, which divide by fission. This minireview focuses on the current understanding of the genes required for the morphogenetic control of conidial germination, hyphal growth, asexual development, and yeast morphogenesis in P. marneffei. PMID:23204189

  9. Neural Emotion Regulation Circuitry Underlying Anxiolytic Effects of Perceived Control Over Pain

    OpenAIRE

    Salomons, Tim V.; Nusslock, Robin; Detloff, Allison; Johnstone, Tom; Davidson, Richard J.

    2015-01-01

    Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within subjects-designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neu...

  10. Morphogenetic Circuitry Regulating Growth and Development in the Dimorphic Pathogen Penicillium marneffei

    OpenAIRE

    Kylie J Boyce; Andrianopoulos, Alex

    2013-01-01

    Penicillium marneffei is an emerging human-pathogenic fungus endemic to Southeast Asia. Like a number of other fungal pathogens, P. marneffei exhibits temperature-dependent dimorphic growth and grows in two distinct cellular morphologies, hyphae at 25°C and yeast cells at 37°C. Hyphae can differentiate to produce the infectious agents, asexual spores (conidia), which are inhaled into the host lung, where they are phagocytosed by pulmonary alveolar macrophages. Within macrophages, conidia germ...

  11. Phasic and tonic mGlu7 receptor activity modulates the thalamocortical network

    Directory of Open Access Journals (Sweden)

    Valériane eTassin

    2016-04-01

    Full Text Available Mutation of the metabotropic glutamate receptor type 7 (mGlu7 induces absence-like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics and pharmacology we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We found that mGlu7 is functionally expressed at both glutamatergic and GABAergic synapses, where it can inhibit neurotransmission and regulate short-term plasticity. These effects depend on the PDZ-ligand of the receptor, as they are lost in mutant mice. Interestingly, the very low affinity of mGlu7 receptors for glutamate raises the question of how it can be activated, namely at GABAergic synapses and in basal conditions. Inactivation of the receptor activity with the mGlu7 negative allosteric modulator (NAM, ADX71743, enhances thalamic synaptic transmission. In vivo administration of the NAM induces a lethargic state with spindle and/or spike-and-wave discharges accompanied by a behavioral arrest typical of absence epileptic seizures. This provides evidence for mGlu7 receptor-mediated tonic modulation of a physiological function in vivo preventing synchronous and potentially pathological oscillations.

  12. Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network.

    Science.gov (United States)

    Tassin, Valériane; Girard, Benoît; Chotte, Apolline; Fontanaud, Pierre; Rigault, Delphine; Kalinichev, Mikhail; Perroy, Julie; Acher, Francine; Fagni, Laurent; Bertaso, Federica

    2016-01-01

    Mutation of the metabotropic glutamate receptor type 7 (mGlu7) induces absence-like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics, and pharmacology, we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We found that mGlu7 is functionally expressed at both glutamatergic and GABAergic synapses, where it can inhibit neurotransmission and regulate short-term plasticity. These effects depend on the PDZ-ligand of the receptor, as they are lost in mutant mice. Interestingly, the very low affinity of mGlu7 receptors for glutamate raises the question of how it can be activated, namely at GABAergic synapses and in basal conditions. Inactivation of the receptor activity with the mGlu7 negative allosteric modulator (NAM), ADX71743, enhances thalamic synaptic transmission. In vivo administration of the NAM induces a lethargic state with spindle and/or spike-and-wave discharges accompanied by a behavioral arrest typical of absence epileptic seizures. This provides evidence for mGlu7 receptor-mediated tonic modulation of a physiological function in vivo preventing synchronous and potentially pathological oscillations. PMID:27199672

  13. Phasic release of newly synthesized secretory proteins in the unstimulated rat exocrine pancreas.

    Science.gov (United States)

    Arvan, P; Castle, J D

    1987-02-01

    Pancreatic lobules from fasted rats secrete pulse-labeled proteins in two phases comprising 15 and 85% of basal output, respectively. The first (0-6.5 h) is initially (less than or equal to 0.5 h) unstimulated by secretagogues, probably represents vesicular traffic of Golgi and post-Golgi origin (including condensing vaculoles/immature granules), and notably contains two groups of polypeptides with distinct release rates: zymogens (t1/2 approximately 2.4 h) and minor nonzymogens plus one unique zymogen (t1/2 approximately 1 h). The second phase (peak at 9-10 h) is stimulable, probably represents basal granule exocytosis (t1/2 approximately 5 h), and contains zymogens exclusively. Newly synthesized proteins released in both phases appear asynchronously, reiterating their asynchronous transport through intracellular compartments. Zymogens in both phases are secreted apically. The sorting of first from second phase zymogen release does not appear to be carrier-mediated, although the sorting of zymogens from other secretory proteins may use this process. Finally, data are presented that suggest that both secretory phases are subject to physiologic regulation. PMID:2433293

  14. Circuitry Linking the Csr and Stringent Response Global Regulatory Systems

    OpenAIRE

    Edwards, Adrianne N; Patterson-Fortin, Laura M.; Christopher A Vakulskas; Mercante, Jeffrey W.; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I.; Fields, Joshua A.; Thompson, Stuart A.; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-01-01

    CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined m...

  15. Balancing the Basal Ganglia Circuitry: A Possible New Role for Dopamine D2 Receptors in Health and Disease

    Science.gov (United States)

    Cazorla, Maxime; Kang, Un Jung; Kellendonk, Christoph

    2016-01-01

    Current therapies for treating movement disorders such as Parkinson’s disease are effective but limited by undesirable and intractable side effects. Developing more effective therapies will require better understanding of what causes basal ganglia dys-regulation and why medication-induced side effects develop. Although basal ganglia have been extensively studied in the last decades, its circuit anatomy is very complex, and significant controversy exists as to how the interplay of different basal ganglia nuclei process motor information and output. We have recently identified the importance of an underappreciated collateral projection that bridges the striatal output direct pathway with the indirect pathway. These bridging collaterals are extremely plastic in the adult brain and are involved in the regulation of motor balance. Our findings add a new angle to the classical model of basal ganglia circuitry that could be exploited for the development of new therapies against movement disorders. In this Scientific Perspective, we describe the function of bridging collaterals and other recent discoveries that challenge the simplicity of the classical basal ganglia circuit model. We then discuss the potential implication of bridging collaterals in the pathophysiology of Parkinson’s disease and schizophrenia. Because dopamine D2 receptors and striatal neuron excitability have been found to regulate the density of bridging collaterals, we propose that targeting these projections downstream of D2 receptors could be a possible strategy for the treatment of basal ganglia disorders. PMID:26018615

  16. Optogenetic deconstruction of sleep-wake circuitry in the brain

    Directory of Open Access Journals (Sweden)

    Antoine Adamantidis

    2010-01-01

    Full Text Available How does the brain regulate the sleep-wake cycle? What are the temporal codes of sleep- and wake-promoting neural circuits? How do these circuits interact with each other across the light/dark cycle? Over the past few decades, many studies from a variety of disciplines have made substantial progress in answering these fundamental questions. For example, neurobiologists have identified multiple, redundant wake-promoting circuits in the brainstem, hypothalamus, and basal forebrain. Sleep-promoting circuits have been found in the preoptic area and hypothalamus. One of the greatest challenges in recent years has been to selectively record and manipulate these sleep-wake centers in vivo with high spatial and temporal resolution. Recent developments in microbial opsin-based neuromodulation tools, collectively referred to as “optogenetics,” have provided a novel method to demonstrate causal links between neural activity and specific behaviors. Here, we propose to use optogenetics as a fundamental tool to probe the necessity, sufficiency, and connectivity of defined neural circuits in the regulation of sleep and wakefulness.

  17. Glycine and GABAA receptors mediate tonic and phasic inhibitory processes that contribute to prepulse inhibition in the goldfish startle network

    Directory of Open Access Journals (Sweden)

    Paul C.P. Curtin

    2015-03-01

    Full Text Available Prepulse inhibition (PPI is understood as an inhibitory process that attenuates sensory flow during early stages (20-1000ms of information processing. Here, we applied in vivo electrophysiology and pharmacology to determine if prepulse inhibition (PPI is mediated by glycine receptors (GlyRs and/or GABAA receptors (GABAARs in the goldfish auditory startle circuit. Specifically, we used selective antagonists to dissect the contributions of target receptors on sound-evoked postsynaptic potentials (PSPs recorded in the neurons that initiate startle, the Mauthner-cells (M-cell. We found that strychnine, a GlyR antagonist, disrupted a fast-activated (5 ms and rapidly (< 50ms decaying (feed-forward inhibitory process that disrupts PPI at 20 ms prepulse/pulse inter-stimulus intervals (ISI. Additionally we observed increases of the evoked postsynaptic potential (PSP peak amplitude (+87.43 ± 21.53%; N=9 and duration (+204 ± 48.91%, N=9. In contrast, treatment with bicuculline, a GABAAR antagonist, caused a general reduction in PPI across all tested ISIs (20-500 ms, essentially eliminating PPI at ISIs from 20-100 ms. Bicuculline also increased PSP peak amplitude (+133.8 ± 10.3%, N=5 and PSP duration (+284.95 ± 65.64%, N=5. Treatment with either antagonist also tonically increased post-synaptic excitability in the M-cells, reflected by an increase in the magnitude of antidromically-evoked action potentials (APs by 15.07 ± 3.21%, N=7 and 16.23 ± 7.08%, N=5 for strychnine and bicuculline, respectively. These results suggest that GABAARs and GlyRs are functionally segregated to short- and longer-lasting sound-evoked (phasic inhibitory processes that contribute to PPI, with the mediation of tonic inhibition by both receptor systems being critical for gain control within the M-cell startle circuit.

  18. Bi-phasic trends in mercury concentrations in blood of Wisconsin common loons during 1992–2010

    Science.gov (United States)

    Meyer, Michael W.; Rasmussen, Paul W.; Watras, Carl J.; Fevold, Brick M.; Kenow, Kevin P.

    2011-01-01

    Wisconsin Department of Natural Resources (WDNR) assessed the ecological risk of mercury (Hg) in aquatic systems by monitoring common loon (Gavia immer) population dynamics and blood Hg concentrations. We report temporal trends in blood Hg concentrations based on 334 samples collected from adults recaptured in subsequent years (resampled 2-9 times) and from 421 blood samples of chicks collected at lakes resampled 2-8 times 1992-2010.. Temporal trends were identified with generalized additive mixed effects models (GAMMs) and mixed effects models to account for the potential lack of independence among observations from the same loon or same lake. Trend analyses indicated that Hg concentrations in the blood of Wisconsin loons declined over the period 1992-2000, and increased during 2002-2010, but not to the level observed in the early 1990s. The best fitting linear mixed effects model included separate trends for the two time periods. The estimated trend in Hg concentration among the adult loon population during 1992-2000 was -2.6% per year and the estimated trend during 2002-2010 was +1.8% per year; chick blood Hg concentrations decreased by -6.5% per year during 1992-2000, but increased 1.8% per year during 2002-2010. This bi-phasic pattern is similar to trends observed for concentrations of methylmercury (meHg) and SO4 in lake water of a well studied seepage lake (Little Rock Lake, Vilas County) within our study area. A cause-effect relationship between these independent trends is hypothesized.

  19. CMOS instrumentation amplifier with offset cancellation circuitry and high PSRR for low power application

    International Nuclear Information System (INIS)

    This paper presents the design and development of a CMOS instrumentation amplifier for biomedical application. The instrumentation amplifier possesses a very high power-supply rejection ratio (PSRR) and is able to operate at single supply voltage for low power application with improved performance compared to existing work. It also has a full CMOS implementation of offset cancellation circuitry. (author)

  20. Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.

    Science.gov (United States)

    Hu, Wenqian; Yuan, Bingbing; Lodish, Harvey F

    2014-09-29

    While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation. PMID:25220394

  1. Epsilon-Near-Zero Photonics Wires for Mid-Infrared Optical Lumped Circuitry

    CERN Document Server

    Liu, Runyu; Zhong, Yujun; Podolskiy, Viktor; Wasserman, Daniel

    2016-01-01

    There has been recent interest in the development of optical analogues of lumped element circuitry, where optical elements act as effective optical inductors, capacitors, and resistors. Such optical circuitry requires the photonic equivalent of electrical wires, structures able carry optical frequency signals to and from the lumped circuit elements while simultaneously maintaining signal carrier wavelengths much larger than the size of the lumped elements. Here we demonstrate the design, fabrication, and characterization of hybrid metal/doped-semiconductor 'photonic wires' operating at optical frequencies with effective indices of propagation near-zero. Our samples are characterized by polarization and angle-dependent FTIR spectroscopy and modeled by finite element methods and rigorous coupled wave analysis. We demonstrate coupling to such photonic wires from free space, and show the effective wavelength of the excited mode to be approximately an order of magnitude larger than the free-space wavelength of our...

  2. Renewal of safety circuitry on a zero-energy research reactor using microprocessor units

    International Nuclear Information System (INIS)

    The conventional hard-wired safety-circuitry of the zero-energy research reactor at the Central Electricity Generating Board's Berkeley Nuclear Laboratories is being replaced by microprocessor-based units. The Paper describes how levels of reliability that are necessary for safety circuitry have been achieved by the use of two entirely different guard line systems based on a Motorola 6800 microprocessor and an Intel 8085A microprocessor. The two systems operate in parallel and either will trip the reactor. Each has been programmed by a different programmer using different philosophies. The two units and the test programme involving over 106 simulated guard line trips are described. An overall reliability of better than 10-6 per annum is claimed. (author)

  3. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive–like behaviors in mice

    OpenAIRE

    Shmelkov, Sergey V.; Hormigo, Adília; Jing, Deqiang; Proenca, Catia C.; Bath, Kevin G.; Milde, Till; Shmelkov, Evgeny; Kushner, Jared S; Baljevic, Muhamed; Dincheva, Iva; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Yancopoulos, George D.; Ninan, Ipe

    2010-01-01

    Obsessive-compulsive disorder (OCD) is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions, and it often encompasses anxiety and depressive symptoms1,2. Recently, the corticostriatal circuitry has been implicated in the pathogenesis of OCD3,4. However, the etiology, pathophysiology and molecular basis of OCD remain unknown. Several studies indicate that the pathogenesis of OCD has a genetic component5–8. Here we demonstrate that loss o...

  4. Basic development of one-chip control circuitry for commutatorless dc motors

    Science.gov (United States)

    Nutz, K. D.; Stromski, R.

    1984-12-01

    A monolithic one chip circuitry including the detection of rotor speed control and the direct load current drive of dc-motors with an electronic commutation was developed because of the increased efficiency of commutatorless dc-motors in which high-quality magnetic materials were used. The hardware demonstration of Hall-Sensor-elements in a power compatible technology was successful. A design based on the data is shown.

  5. NeuroArray: A Universal Interface for Patterning and Interrogating Neural Circuitry with Single Cell Resolution

    OpenAIRE

    Li, Wei; Xu, Zhen; Huang, Junzhe; Lin, Xudong; Luo, Rongcong; Chen, Chia-Hung; Shi, Peng

    2014-01-01

    Recreation of neural network in vitro with designed topology is a valuable tool to decipher how neurons behave when interacting in hierarchical networks. In this study, we developed a simple and effective platform to pattern primary neurons in array formats for interrogation of neural circuitry with single cell resolution. Unlike many surface-chemistry-based patterning methods, our NeuroArray technique is specially designed to accommodate neuron's polarized morphologies to make regular arrays...

  6. Online contributions of auditory feedback to neural activity in avian song control circuitry

    OpenAIRE

    Sakata, Jon T.; Michael S. Brainard

    2008-01-01

    Birdsong, like human speech, relies critically on auditory feedback to provide information about the quality of vocalizations. Although the importance of auditory feedback to vocal learning is well established, whether and how feedback signals influence vocal premotor circuitry has remained obscure. Previous studies in singing birds have not detected changes to vocal premotor activity following perturbations of auditory feedback, leading to the hypothesis that contributions of feedback to voc...

  7. Vasopressin Modulates Medial Prefrontal Cortex-Amygdala Circuitry During Emotion Processing in Humans

    OpenAIRE

    Zink, Caroline F.; Stein, Jason L; Kempf, Lucas; Hakimi, Shabnam; Meyer-Lindenberg, Andreas

    2010-01-01

    The neuropeptide, vasopressin, is a modulator of mammalian social behavior and emotion, particularly fear, aggression, and anxiety. In humans, the neural circuitry underlying behavioral effects of vasopressin is unknown. Using a double-blind crossover administration of 40 IU vasopressin or placebo and functional MRI during processing of facial emotions in healthy male volunteers, we show that vasopressin specifically reduces differential activation in the subgenual cingulate cortex. Structura...

  8. Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferents

    OpenAIRE

    Evans, Karleyton C.

    2010-01-01

    After nearly two decades of active research, functional neuroimaging has demonstrated utility in the identification of cortical, limbic, and paralimbic (cortico-limbic) brain regions involved in respiratory control and respiratory perception. Before the recent boon of human neuroimaging studies, the location of the principal components of respiratory-related cortico-limbic circuitry had been unknown and their function had been poorly understood. Emerging neuroimaging evidence in both healthy ...

  9. Longitudinal Monitoring of Motor Neuron Circuitry in FALS Rats Using in vivo phMRI

    OpenAIRE

    Choi, Ji-Kyung; Dedeoglu, Alpaslan; Jenkins, Bruce G.

    2010-01-01

    Amyotrophic lateral sclerosis (ALS) presents challenges for diagnosis and objective monitoring of disease progression. We demonstrate, using pharmacologic MRI, that alterations in motor circuitry can be characterized using a passive stimulus in a rat model of familial ALS (FALS) as a function of symptom progression. Pre-symptomatic FALS rats had a pattern of activation to amphetamine indistinguishable from wild-type controls. In contrast, symptomatic rats showed significantly decreased respon...

  10. Sex Differences and Chronic Stress Effects on the Neural Circuitry Underlying Fear Conditioning and Extinction

    OpenAIRE

    Farrell, Mollee R.; SENGELAUB, DALE R.; Wellman, Cara L.

    2013-01-01

    There are sex differences in the rates of many stress-sensitive psychological disorders such as post traumatic stress disorder (PTSD). As medial prefrontal cortex and amygdala are implicated in many of these disorders, understanding differential stress effects in these regions may shed light on the mechanisms underlying sex-dependent expression of disorders like depression and anxiety. Prefrontal cortex and amygdala are key regions in the neural circuitry underlying fear conditioning and exti...

  11. Stress, trauma and PTSD: translational insights into the core synaptic circuitry and its modulation.

    Science.gov (United States)

    Bennett, Maxwell R; Hatton, Sean N; Lagopoulos, Jim

    2016-06-01

    Evidence is considered as to whether behavioral criteria for diagnosis of post-traumatic stress disorder (PTSD) are applicable to that of traumatized animals and whether the phenomena of acquisition, extinction and reactivation of fear behavior in animals are also successfully applicable to humans. This evidence suggests an affirmative answer in both cases. Furthermore, the deficits in gray matter found in PTSD, determined with magnetic resonance imaging, are also observed in traumatized animals, lending neuropsychological support to the use of animals to probe what has gone awry in PTSD. Such animal experiments indicate that the core synaptic circuitry mediating behavior following trauma consists of the amygdala, ventral-medial prefrontal cortex and hippocampus, all of which are modulated by the basal ganglia. It is not clear if this is the case in PTSD as the observations using fMRI are equivocal and open to technical objections. Nevertheless, the effects of the basal ganglia in controlling glutamatergic synaptic transmission through dopaminergic and serotonergic synaptic mechanisms in the core synaptic circuitry provides a ready explanation for why modifying these mechanisms delays extinction in animal models and predisposes towards PTSD. In addition, changes of brain-derived neurotrophic factor (BDNF) in the core synaptic circuitry have significant effects on acquisition and extinction in animal experiments with single nucleotide polymorphisms in the BDNF gene predisposing to PTSD. PMID:25985955

  12. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S

    2012-07-01

    Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  13. Tricky Circuitry

    Science.gov (United States)

    Davies, Tony

    2014-01-01

    Teaching children about circuits and the way electricity works is a "tricky business" because it is invisible. Just imagine all eyes are on the teacher as he or she produces for the class what looks like a ping-pong ball and then, with a wave of their hand, the incredible happens! This wonderful white sphere begins to glow red and a…

  14. Corticostriatal circuitry.

    Science.gov (United States)

    Haber, Suzanne N

    2016-03-01

    Corticostriatal connections play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. The cortex projects to the striatum topographically. Thus, different regions of the striatum have been associated with these different functions: the ventral striatum with reward; the caudate nucleus with cognition; and the putamen with motor control. However, corticostriatal connections are more complex, and interactions between functional territories are extensive. These interactions occur in specific regions in which convergence of terminal fields from different functional cortical regions are found. This article provides an overview of the connections of the cortex to the striatum and their role in integrating information across reward, cognitive, and motor functions. Emphasis is placed on the interface between functional domains within the striatum. PMID:27069376

  15. Validation of a closed bi-phasic extraction system and of the pancake probe as instruments to radiopharmaceutical quality control procedures

    International Nuclear Information System (INIS)

    Aim: Quality control of radiopharmaceuticals is not a common practice in Nuclear Medicine Services in Brazil. One frequent limitation is that the well counter, used to radioactivity measurement of chromatographic strips, is not available in most services. On the other hand, it's mandatory that all services have a pancake probe to control contaminations. The purpose of this study was to evaluate the accuracy of the quality control (QC) of technetium-99m labeled radiopharmaceuticals using a pancake probe, including chromatography of 99mTc-MDP, 99mTc-DMSA, 99mTc-DMSA-V, 99mTc-Pyp, 99mTc-ECD, 99mTc-Dextran, 99mTc-colloid. Also, we had available a solvent extraction methods using a multi-use closed bi-phasic system to 99mTc-ECD and 99mTc-MIBI, to replace the classical single-use open bi-phasic system. Material and Methods: Classical chromatographic well counter reading and solvent extraction radiochemical controls were used as standards. To variant radiation reading method, pancake probe was covered with a lead disk 3 mm thick, with a 40x10 mm slit; the activity on chromatographic strips (80x10 mm) was read over the slit. The multi-use closed bi-phasic system was done closing the extremities of a 5 or 10 mL glass pipette using flame in the point side, and rubber septa in the other side. The pipette was filled with 2.5 or 3 mL, both organic solvent and aqueous NaCl 0.9 %; then two or three drops of the sample were applied and the tube shook during 30 seconds. Two minutes after, the activity was measured over each phase using the pancake detector. The same solvent mixture was used 3 times, with 48 h interval to allow radioactivity decay. Results: Radiochemical purity determined by the classical or the modified procedures showed Pearson's correlation of 0.973 (n=17) to chromatography; 0.993 to ECD (n=14) extraction and 0.919 to MIBI (n=21) extraction. Conclusion: Our findings suggest that the pancake can be used as a detection instrument in 99mTc-radiopharmaceuticals QC

  16. An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder.

    Science.gov (United States)

    Pavuluri, Mani N; O'Connor, Megan Marlow; Harral, Erin M; Sweeney, John A

    2008-04-15

    The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar

  17. The neural circuitry underlying reinstatement of heroin-seeking behavior in an animal model of relapse.

    Science.gov (United States)

    Rogers, J L; Ghee, S; See, R E

    2008-01-24

    Reinstatement of extinguished drug-seeking has been utilized in the study of the neural substrates of relapse to drugs of abuse, particularly cocaine. However, limited studies have examined the circuitry that drives the reinstatement of heroin-seeking behavior in the presence of conditioned cues, or by heroin itself. In order to test the hypothesis that the circuitry underlying reinstatement in heroin-experienced animals would show overlapping, yet distinct differences from cocaine-experienced animals, we used transient inhibition of several cortical, striatal, and limbic brain regions during reinstatement of heroin-seeking produced by heroin-paired cues, or by a single priming dose of heroin. Rats lever pressed for i.v. heroin discretely paired with a conditioned stimulus (CS) during daily 3-h sessions for a period of 2 weeks, followed by daily extinction of lever responding. Subsequent reinstatement of heroin-seeking was measured as lever responding in the absence of heroin reinforcement. The first set of reinstatement tests involved response-contingent CS presentations following bilateral intracranial infusion of either a combination of GABA receptor agonists (baclofen-muscimol, B/M) or vehicle (saline) into one of 13 different brain regions. The second set of reinstatement tests involved a single heroin injection (0.25 mg/kg, s.c.) following either B/M or vehicle infusions. Our results showed that vehicle-infused animals reinstated to both CS presentations and a priming injection of heroin, while B/M inactivation of several areas known to be important for the reinstatement of cocaine-seeking also attenuated heroin-seeking in response to CS presentations and/or a priming dose of heroin. However, as predicted, inactivation of areas previously shown to not affect cocaine-seeking significantly attenuated heroin-seeking, supporting the hypothesis that the circuitry underlying the reinstatement of heroin-seeking is more diffusely distributed than that for cocaine

  18. Microwave Technology for Waste Management Applications Including Disposition of Electronic Circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Wicks, G.G. [Westinghouse Savannah River Company, AIKEN, SC (United States); Clark, D.E. [University of Florida, Gainesville, FL (United States); Schulz, R.L. [University of Flordia, Gainesville, FL (United States)

    1998-06-01

    Advanced microwave technology is being developed nationally and internationally for a variety of waste management and environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of hazardous components into leach resistant forms. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from the undesirable consequences of hazardous materials. One application of special interest is the treatment of discarded electronic circuitry using a new hybrid microwave treatment process and subsequent reclamation of the precious metals within.

  19. Circuitry for monitoring a high direct current voltage supply for an ionization chamber

    International Nuclear Information System (INIS)

    An arrangement to measure the voltage of the supply and a switching means controlled by this is described. The voltage measurer consists of first and second signal coupling means, the input of the second (connected to the voltage supply) is connected in series with the output of the first. An ionization chamber with this circuitry may be used to monitor the radiation output of a particle accelerator more accurately. Faulty measurements of the dose output, caused by voltages in the earth circuit, are avoided. (U.K.)

  20. The unitary hypothesis: A common neural circuitry for novel manipulations, language, plan-ahead, and throwing?

    OpenAIRE

    Calvin, Prof William H

    1993-01-01

    Plan-ahead becomes necessary for those movements which are over-and-done in less time than it takes for the feedback loop to operate. Natural selection for one of the ballistic movements (hammering, clubbing, and throwing) could evolve a plan-ahead serial buffer for hand-arm commands that would benefit the other ballistic movements as well. This same circuitry may also sequence other muscles (children learning handwriting often screw up their faces and tongues) and so novel oral-facial sequen...

  1. Microwave technology for waste management applications including disposition of electronic circuitry

    International Nuclear Information System (INIS)

    Microwave technology is being developed nationally and internationally for a variety of environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of selected components. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from undesirable consequences of hazardous materials. Applications of microwave energy for environmental remediation will be discussed. Emphasized will be a newly developed microwave process designed to treat discarded electronic circuitry and reclaim the precious metals within for reuse

  2. Microwave Technology for Waste Management Applications Including Disposition of Electronic Circuitry

    International Nuclear Information System (INIS)

    Advanced microwave technology is being developed nationally and internationally for a variety of waste management and environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of hazardous components into leach resistant forms. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from the undesirable consequences of hazardous materials. One application of special interest is the treatment of discarded electronic circuitry using a new hybrid microwave treatment process and subsequent reclamation of the precious metals within

  3. Slow noise in the period of a biological oscillator underlies gradual trends and abrupt transitions in phasic relationships in hybrid neural networks.

    Science.gov (United States)

    Thounaojam, Umeshkanta S; Cui, Jianxia; Norman, Sharon E; Butera, Robert J; Canavier, Carmen C

    2014-05-01

    In order to study the ability of coupled neural oscillators to synchronize in the presence of intrinsic as opposed to synaptic noise, we constructed hybrid circuits consisting of one biological and one computational model neuron with reciprocal synaptic inhibition using the dynamic clamp. Uncoupled, both neurons fired periodic trains of action potentials. Most coupled circuits exhibited qualitative changes between one-to-one phase-locking with fairly constant phasic relationships and phase slipping with a constant progression in the phasic relationships across cycles. The phase resetting curve (PRC) and intrinsic periods were measured for both neurons, and used to construct a map of the firing intervals for both the coupled and externally forced (PRC measurement) conditions. For the coupled network, a stable fixed point of the map predicted phase locking, and its absence produced phase slipping. Repetitive application of the map was used to calibrate different noise models to simultaneously fit the noise level in the measurement of the PRC and the dynamics of the hybrid circuit experiments. Only a noise model that added history-dependent variability to the intrinsic period could fit both data sets with the same parameter values, as well as capture bifurcations in the fixed points of the map that cause switching between slipping and locking. We conclude that the biological neurons in our study have slowly-fluctuating stochastic dynamics that confer history dependence on the period. Theoretical results to date on the behavior of ensembles of noisy biological oscillators may require re-evaluation to account for transitions induced by slow noise dynamics. PMID:24830924

  4. In vivo imaging of functional disruption, recovery and alteration in rat olfactory circuitry after lesion.

    Science.gov (United States)

    Cross, Donna J; Flexman, Jennifer A; Anzai, Yoshimi; Morrow, Thomas J; Maravilla, Kenneth R; Minoshima, Satoshi

    2006-09-01

    Compensatory changes following disruption of neuronal circuitry have been indicated by previous imaging studies of stroke and other brain injury, but evidence of the pathways involved in such dynamic changes has not been shown in vivo. We imaged rats before and after lesion-induced disruption of the lateral olfactory tract to investigate the subsequent recovery and/or reorganization of functional neuronal circuitry. Serial magnetic resonance imaging was performed following intranasal administration of a paramagnetic track tracer Mn(2+). Images were analyzed using statistical mapping techniques in the stereotactic coordinate system. At 1 week post-lesion, Mn(2+) transport caudal to lesion was reduced as expected, and more importantly, increased transport through the anterior commissure was seen. At 4 weeks post-lesion, there was recovery of transport caudal to lesion, and increased transport through the anterior commissure extended to the contralateral olfactory cortex. Correlation analysis of regional Mn(2+) transport indicated that contralateral enhancement was not simply due to septal window spillover. This study demonstrates for the first time in vivo evidence of compensatory changes in functional neuronal activity to a contralateral pathway through the commissure following brain injury. PMID:16859928

  5. Electro-active sensor, method for constructing the same; apparatus and circuitry for detection of electro-active species

    Science.gov (United States)

    Buehler, Martin (Inventor)

    2009-01-01

    An electro-active sensor includes a nonconductive platform with a first electrode set attached with a first side of a nonconductive platform. The first electrode set serves as an electrochemical cell that may be utilized to detect electro-active species in solution. A plurality of electrode sets and a variety of additional electrochemical cells and sensors may be attached with the nonconductive platform. The present invention also includes a method for constructing the aforementioned electro-active sensor. Additionally, an apparatus for detection and observation is disclosed, where the apparatus includes a sealable chamber for insertion of a portion of an electro-active sensor. The apparatus allows for monitoring and detection activities. Allowing for control of attached cells and sensors, a dual-mode circuitry is also disclosed. The dual-mode circuitry includes a switch, allowing the circuitry to be switched from a potentiostat to a galvanostat mode.

  6. The role of BDNF in depression on the basis of its location in the neural circuitry

    Institute of Scientific and Technical Information of China (English)

    Hui YU; Zhe-yu CHEN

    2011-01-01

    Depression is one of the most prevalent and life-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Most attention in the field has focused on hippocampal and frontal cortical regions for their roles in depression and antidepressant action. While these regions no doubt play important roles in the mental illness, there is compelling evi-dence that other brain regions are also involved. Brain-derived neurotrophic factor (BDNF) is broadly expressed in the developing and adult mammalian brain and has been implicated in development, neural regeneration, synaptic transmission, synaptic plasticity and neurogenesis. Recently BDNF has been shown to play an important role in the pathophysiology of depression, however there are con-troversial reports about the effects of BDNF on depression. Here, we present an overview of the current knowledge concerning BDNF actions and associated intracellular signaling in hippocampus, prefrontal cortex, nucleus accumbens (NAc) and amygdala as their rela-tion to depression.

  7. Broadband Energy Harvesting Using a Metamaterial Resonator Embedded With Non-Foster Impedance Circuitry

    CERN Document Server

    Fu, Guoqing

    2014-01-01

    Radio Frequency Identification (RFID) and implantable biomedical devices need efficient power and data transfer with very low profile antennas. We propose a low profile electrically small antenna for near-field wireless power and data telemetry employing a metamaterial Split Ring Resonator (SRR) antenna. SRRs can be designed for operation over wide frequencies from RF to visible. However, they are inherently narrowband making them sensitive to component mismatch with respect to external transmit antenna. Here we propose an embedding of a non-foster impedance circuitry into the metamaterial SRR structure that imparts conjugate negative complex impedance to this resonator antenna thereby increasing the effective bandwidth and thus overcoming the fundamental limit for efficient signal coupling. We demonstrate the concept through extensive numerical simulations and a prototype system at the board level using discrete off-the-shelf components and printed circuit SRR antenna at 500 MHz. We show that the power trans...

  8. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr., Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bobrek, Miljko [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-12-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios where human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments due the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is the final report of the activities involving the NEET 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays. We present a detailed functional block diagram of the proposed data acquisition system, the thought process leading to technical decisions, the implemented system, and the tested results from the systems. This system will be capable of monitoring at least three parameters of importance to nuclear reactor monitoring: temperature, radiation level, and pressure.

  9. Planar SQUID magnetometer integrated with bootstrap circuitry under different bias modes

    International Nuclear Information System (INIS)

    A planar superconducting quantum interference device (SQUID) magnetometer consisting of a parallel gradiometer SQUID with integrated input coils connected to an on-chip pickup loop was designed and fabricated in conventional niobium technology. SQUID bootstrap circuitry (SBC) incorporating suitable current and voltage feedbacks was also integrated into the design. For a SQUID inductance of Ls = 350 pH and a chip size of 5 × 5 mm2, the field resolution of the voltage-biased SQUID magnetometer reached −1/2 with the bootstrap circuit and an ordinary preamplifier. We also observed that the effective McCumber parameter βc of the junctions is influenced by the bias mode. Indeed, when the nominal junction βc was larger than unity, our SQUID magnetometer operated stably in the voltage bias mode. The device exhibited low noise even without SBC. (paper)

  10. Circuitry for the automatic tare balancing at radiometric weigh-feeder belts

    International Nuclear Information System (INIS)

    The invention has been aimed at a circuitry for the automatic tare balancing at radiometric weigh-feeder belts with digital data processing of the measurement pulse rate emitted by a radiation detector during a measuring cycle. To secure a non-perturbational and exact permanent pulse rate correction by the tare rate the measuring pulse rate is summed up under the operational mode 'taring' for a preselected rotation time of the empty belt and evaluated using a factor related to the length of measuring cycle. The resulting pulses are stored as an average value. Under the operational mode 'weighing' the difference between pulse rate and stored tare pulses will be formed and transmitted to a data processing unit

  11. Ubiquitin-SUMO circuitry controls activated fanconi anemia ID complex dosage in response to DNA damage.

    Science.gov (United States)

    Gibbs-Seymour, Ian; Oka, Yasuyoshi; Rajendra, Eeson; Weinert, Brian T; Passmore, Lori A; Patel, Ketan J; Olsen, Jesper V; Choudhary, Chunaram; Bekker-Jensen, Simon; Mailand, Niels

    2015-01-01

    We show that central components of the Fanconi anemia (FA) DNA repair pathway, the tumor suppressor proteins FANCI and FANCD2 (the ID complex), are SUMOylated in response to replication fork stalling. The ID complex is SUMOylated in a manner that depends on the ATR kinase, the FA ubiquitin ligase core complex, and the SUMO E3 ligases PIAS1/PIAS4 and is antagonized by the SUMO protease SENP6. SUMOylation of the ID complex drives substrate selectivity by triggering its polyubiquitylation by the SUMO-targeted ubiquitin ligase RNF4 to promote its removal from sites of DNA damage via the DVC1-p97 ubiquitin segregase complex. Deregulation of ID complex SUMOylation compromises cell survival following replication stress. Our results uncover a regulatory role for SUMOylation in the FA pathway, and we propose that ubiquitin-SUMO signaling circuitry is a mechanism that contributes to the balance of activated ID complex dosage at sites of DNA damage. PMID:25557546

  12. Bi-phasic effect of interferon (IFN)-alpha: IFN-alpha up- and down-regulates interleukin-4 signaling in human T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Sommer, Viveca Horst; Woetmann, Anders;

    2003-01-01

    Interferon (IFN)-alpha/beta is produced by virally infected cells and is believed to play an important role in early phases of the innate immune response. In addition, IFN-alpha/beta inhibits interleukin (IL)-4 signaling in B cells and monocytes, suggesting that IFN-alpha/beta (like IFN-gamma) is......Interferon (IFN)-alpha/beta is produced by virally infected cells and is believed to play an important role in early phases of the innate immune response. In addition, IFN-alpha/beta inhibits interleukin (IL)-4 signaling in B cells and monocytes, suggesting that IFN-alpha/beta (like IFN......-4-mediated STAT6 activation in both CD4+ and CD8+ human T cells. The effect is specific because (i) another interferon, IFN-gamma, does not enhance IL-4-mediated STAT6 activation, (ii) IFN-alpha-mediated STAT1 and STAT2 activation is not modulated by IL-4, and (iii) activation of Janus kinases...

  13. "Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

    Science.gov (United States)

    Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

    2012-01-01

    In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

  14. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

    Directory of Open Access Journals (Sweden)

    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  15. Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.

    Science.gov (United States)

    Youssef, Andrew M; Macefield, Vaughan G; Henderson, Luke A

    2016-07-01

    Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104478

  16. Neuroanatomical circuitry associated with exploratory eye movement in schizophrenia: a voxel-based morphometric study.

    Directory of Open Access Journals (Sweden)

    Linlin Qiu

    Full Text Available Schizophrenic patients present abnormalities in a variety of eye movement tasks. Exploratory eye movement (EEM dysfunction appears to be particularly specific to schizophrenia. However, the underlying mechanisms of EEM dysfunction in schizophrenia are not clearly understood. To assess the potential neuroanatomical substrates of EEM, we recorded EEM performance and conducted a voxel-based morphometric analysis of gray matter in 33 schizophrenic patients and 29 well matched healthy controls. In schizophrenic patients, decreased responsive search score (RSS and widespread gray matter density (GMD reductions were observed. Moreover, the RSS was positively correlated with GMD in distributed brain regions in schizophrenic patients. Furthermore, in schizophrenic patients, some brain regions with neuroanatomical deficits overlapped with some ones associated with RSS. These brain regions constituted an occipito-tempro-frontal circuitry involved in visual information processing and eye movement control, including the left calcarine cortex [Brodmann area (BA 17], the left cuneus (BA 18, the left superior occipital cortex (BA 18/19, the left superior frontal gyrus (BA 6, the left cerebellum, the right lingual cortex (BA 17/18, the right middle occipital cortex (BA19, the right inferior temporal cortex (BA 37, the right dorsolateral prefrontal cortex (BA 46 and bilateral precentral gyri (BA 6 extending to the frontal eye fields (FEF, BA 8. To our knowledge, we firstly reported empirical evidence that gray matter loss in the occipito-tempro-frontal neuroanatomical circuitry of visual processing system was associated with EEM performance in schizophrenia, which may be helpful for the future effort to reveal the underlying neural mechanisms for EEM disturbances in schizophrenia.

  17. Central autonomic control in spontaneously hypertensive rats: a study on phasic phenomena during rapid-eye-movement sleep

    OpenAIRE

    Berteotti, Chiara

    2007-01-01

    The cardiovascular regulation undergoes wide changes in the different states of sleepwake cycle. In particular, the relationship between spontaneous fluctuations in heart period and arterial pressure clearly shows differences between the two sleep states. In non rapid-eye-movement sleep, heart rhythm is under prevalent baroreflex control, whereas in rapid-eye-movement sleep central autonomic commands prevail (Zoccoli et al., 2001). Moreover, during rapid-eye-movement sleep the cardiovascul...

  18. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  19. The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study.

    Science.gov (United States)

    Mannarelli, Daniela; Pauletti, Caterina; Grippo, Antonello; Amantini, Aldo; Augugliaro, Vito; Currà, Antonio; Missori, Paolo; Locuratolo, Nicoletta; De Lucia, Maria C; Rinalduzzi, Steno; Fattapposta, Francesco

    2015-01-01

    Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in particular by using the Contingent Negative Variation (CNV), and repetitive 1-Hz Transcranial Magnetic Stimulation (rTMS). Transient virtual inhibition of the right DLPFC induced by real 1-Hz rTMS stimulation led to a significant decrease in total CNV and W1-CNV areas if compared with the basal and post-sham rTMS conditions. Reaction times (RTs) did not decrease after inhibitory rTMS, but they did improve after sham stimulation. These results suggest that the right DLPFC plays a crucial role in the genesis and maintenance of the alerting state and learning processes. PMID:26090234

  20. SDF-1/CXCL12 modulates mitochondrial respiration of immature blood cells in a bi-phasic manner.

    Science.gov (United States)

    Messina-Graham, Steven; Broxmeyer, Hal

    2016-05-01

    SDF-1/CXCL12 is a potent chemokine required for the homing and engraftment of hematopoietic stem and progenitor cells. Previous data from our group has shown that in an SDF-1/CXCL12 transgenic mouse model, lineage(-) Sca-1(+) c-Kit(+) (LSK) bone marrow cells have reduced mitochondrial membrane potential versus wild-type. These results suggested that SDF-1/CXCL12 may function to keep mitochondrial respiration low in immature blood cells in the bone marrow. Low mitochondrial metabolism helps to maintain low levels of reactive oxygen species (ROS), which can influence differentiation. To test whether SDF-1/CXCL12 regulates mitochondrial metabolism, we employed the human leukemia cell line HL-60, that expresses high levels of the SDF-1/CXCL12 receptor, CXCR4, as a model of hematopoietic progenitor cells in vitro. We treated HL-60 cells with SDF-1/CXCL12 for 2 and 24h. Oxygen consumption rates (OCR), mitochondrial-associated ATP production, mitochondrial mass, and mitochondrial membrane potential of HL-60 cells were significantly reduced at 2h and increased at 24h as compared to untreated control cells. These biphasic effects of SDF-1/CXCL12 were reproduced with lineage negative primary mouse bone marrow cells, suggesting a novel function of SDF-1/CXCL12 in modulating mitochondrial respiration by regulating mitochondrial oxidative phosphorylation, ATP production and mitochondrial content. PMID:27067482

  1. Transient analysis of electromagnets with emphasis on solid components, eddy currents, and driving circuitry

    Science.gov (United States)

    Batdorff, Mark A.

    Valves are commonly used in fluid power systems to control pressure and flow. The emerging field of digital hydraulics demands high-speed, low cost, on/off valves with improved performance. Electromagnets, or solenoids, are commonly used to actuate valves due to their low cost, high reliability, and moderate performance. This work develops a dynamic model for a solid steel electromagnet that can be used for design and optimization, and unveils design tradeoffs with geometry and driving circuitry that are often overlooked. This work develops an accurate, computationally efficient, nonlinear, coupled, dynamic, axisymmetric, high fidelity magnetic equivalent circuit (HFMEC) electromagnet model capable of predicting force, inductance, dynamic response, and energy consumption. The model is intended for applications where both accuracy and solution time are critical. Axisymmetric magnetic fringing and leakage permeances were derived in order to capture nonlinear magnetic field phenomena that affect force and inductance. The tradeoffs between solid-center and hollow-center electromagnets were investigated. It was shown with both simulation and measurement that a hollow-center electromagnet has a 37.7% shorter useful stroke due to increased magnetic fringing and leakage (from 4.0mm to 2.5mm). However, it was also shown that the hollow-center electromagnet has a 70% improved turn-off response (from 617ms to 362ms). A single objective optimization study was performed demonstrating that hollow-center electromagnets are advantageous and can up to 204% increased dynamic response for systems where dynamics are dominated by eddy current lag. Electromagnets experience dynamic lag when turning on and off due to inductance and eddy currents. Coil driving methods, such as peak-and-hold, are often used to minimize turn-on lag by using high initial voltages and currents. However, circuits often do not address turn-off lag, which can be significant. This work investigates the effects of

  2. Tapping into rhythm generation circuitry in humans during simulated weightlessness conditions

    Directory of Open Access Journals (Sweden)

    Irina Solopova

    2015-02-01

    Full Text Available An ability to produce rhythmic activity is ubiquitous for locomotor pattern generation and modulation. The role that the rhythmogenesis capacity of the spinal cord plays in injured populations has become an area of interest and systematic investigation among researchers in recent years, despite its importance being long recognized by neurophysiologists and clinicians. Given that each individual interneuron, as a rule, receives a broad convergence of various supraspinal and sensory inputs and may contribute to a vast repertoire of motor actions, the importance of assessing the functional state of the spinal locomotor circuits becomes increasingly evident. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by a reduction of external resistance. This article aims to provide a review on current issues related to the ‘locomotor’ state and interactions between spinal and supraspinal influences on the central pattern generator circuitry in humans, which may be important for developing gait rehabilitation strategies in individuals with spinal cord and brain injuries.

  3. Spectrotemporal sound preferences of neighboring inferior colliculus neurons: implications for local circuitry and processing

    Directory of Open Access Journals (Sweden)

    Chen eChen

    2012-09-01

    Full Text Available How do local circuits in the inferior colliculus (IC process and transform spectral and temporal sound information? Using a four-tetrode array we examined the functional properties of the IC and metrics of its micro circuitry by recording neural activity from neighboring single neurons in the cat. Spectral and temporal response preferences were compared for neurons found on the same and adjacent tetrodes, as well as across distant recording sites. We found that neighboring neurons had similar preferences while neurons recorded across distant sites were less similar. Best frequency was the most correlated parameter between neighboring neurons and best frequency differences exhibited unique clustering at ~0.3 octave intervals, indicative of the frequency band lamina. Other spectral and temporal parameters of the receptive fields were more similar for neighboring neurons than for those at distant sites and the receptive field similarity was larger for neurons with small differences in best frequency. Furthermore, correlated firing was stronger for neighboring neuron pairs and increased with proximity and decreasing best frequency difference. Thus although response selectivities are quite diverse in the IC, spectral and temporal preference within a local microcircuit are functionally quite similar. This suggests a scheme where local circuits are organized into zones that are specialized for processing distinct spectrotemporal cues.

  4. Integrated plasmonic circuitry on a vertical-cavity surface-emitting semiconductor laser platform

    Science.gov (United States)

    McPolin, Cillian P. T.; Bouillard, Jean-Sebastien; Vilain, Sebastien; Krasavin, Alexey V.; Dickson, Wayne; O'Connor, Daniel; Wurtz, Gregory A.; Justice, John; Corbett, Brian; Zayats, Anatoly V.

    2016-08-01

    Integrated plasmonic sources and detectors are imperative in the practical development of plasmonic circuitry for bio- and chemical sensing, nanoscale optical information processing, as well as transducers for high-density optical data storage. Here we show that vertical-cavity surface-emitting lasers (VCSELs) can be employed as an on-chip, electrically pumped source or detector of plasmonic signals, when operated in forward or reverse bias, respectively. To this end, we experimentally demonstrate surface plasmon polariton excitation, waveguiding, frequency conversion and detection on a VCSEL-based plasmonic platform. The coupling efficiency of the VCSEL emission to waveguided surface plasmon polariton modes has been optimized using asymmetric plasmonic nanostructures. The plasmonic VCSEL platform validated here is a viable solution for practical realizations of plasmonic functionalities for various applications, such as those requiring sub-wavelength field confinement, refractive index sensitivity or optical near-field transduction with electrically driven sources, thus enabling the realization of on-chip optical communication and lab-on-a-chip devices.

  5. Congenital prosopagnosia: multistage anatomical and functional deficits in face processing circuitry.

    Science.gov (United States)

    Dinkelacker, V; Grüter, M; Klaver, P; Grüter, T; Specht, K; Weis, S; Kennerknecht, I; Elger, C E; Fernandez, G

    2011-05-01

    Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition. PMID:21120515

  6. Dorsal MPFC circuitry in rodent models of cocaine use: Implications for drug-addiction therapies

    Science.gov (United States)

    Jasinska, Agnes J.; Chen, Billy T.; Bonci, Antonello; Stein, Elliot A.

    2014-01-01

    While the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking, and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms, and propose a framework to potentially reconcile the apparent discrepancy. We also draw parallels between these preclinical models of cocaine self-administration and human neuroimaging studies in cocaine users, and argue that both lines of evidence point to dynamic interactions between cue-reactivity processes and control processes within the dorsal MPFC circuitry. From a translational perspective, these findings underscore the importance of interventions and therapeutics targeting not just a brain region, but a specific computational process within that brain region, and may have implications for the design and implementation of more effective treatments for human cocaine addiction. PMID:24620898

  7. Integrated plasmonic circuitry on a vertical-cavity surface-emitting semiconductor laser platform

    Science.gov (United States)

    McPolin, Cillian P. T.; Bouillard, Jean-Sebastien; Vilain, Sebastien; Krasavin, Alexey V.; Dickson, Wayne; O'Connor, Daniel; Wurtz, Gregory A.; Justice, John; Corbett, Brian; Zayats, Anatoly V.

    2016-01-01

    Integrated plasmonic sources and detectors are imperative in the practical development of plasmonic circuitry for bio- and chemical sensing, nanoscale optical information processing, as well as transducers for high-density optical data storage. Here we show that vertical-cavity surface-emitting lasers (VCSELs) can be employed as an on-chip, electrically pumped source or detector of plasmonic signals, when operated in forward or reverse bias, respectively. To this end, we experimentally demonstrate surface plasmon polariton excitation, waveguiding, frequency conversion and detection on a VCSEL-based plasmonic platform. The coupling efficiency of the VCSEL emission to waveguided surface plasmon polariton modes has been optimized using asymmetric plasmonic nanostructures. The plasmonic VCSEL platform validated here is a viable solution for practical realizations of plasmonic functionalities for various applications, such as those requiring sub-wavelength field confinement, refractive index sensitivity or optical near-field transduction with electrically driven sources, thus enabling the realization of on-chip optical communication and lab-on-a-chip devices. PMID:27491686

  8. Decoding signal processing in thalamo-hippocampal circuitry: implications for theories of memory and spatial processing.

    Science.gov (United States)

    Tsanov, Marian; O'Mara, Shane M

    2015-09-24

    A major tool in understanding how information is processed in the brain is the analysis of neuronal output at each hierarchical level through which neurophysiological signals are propagated. Since the experimental brain operation performed on Henry Gustav Molaison (known as patient H.M.) in 1953, the hippocampal formation has gained special attention, resulting in a very large number of studies investigating signals processed by the hippocampal formation. One of the main information streams to the hippocampal formation, vital for episodic memory formation, arises from thalamo-hippocampal projections, as there is extensive connectivity between these structures. This connectivity is sometimes overlooked by theories of memory formation by the brain, in favour of theories with a strong cortico-hippocampal flavour. In this review, we attempt to address some of the complexity of the signals processed within the thalamo-hippocampal circuitry. To understand the signals encoded by the anterior thalamic nuclei in particular, we review key findings from electrophysiological, anatomical, behavioural and computational studies. We include recent findings elucidating the integration of different signal modalities by single thalamic neurons; we focus in particular on the propagation of two prominent signals: head directionality and theta rhythm. We conclude that thalamo-hippocampal processing provides a centrally important, substantive, and dynamic input modulating and moderating hippocampal spatial and mnemonic processing. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25498107

  9. A novel method for determining pulse counting circuitry dead time using the Nuclear Weapons Inspection System

    International Nuclear Information System (INIS)

    A novel method for measuring dead time in nuclear pulse processing circuitry has been developed using the autocorrelation measurement capability of the Nuclear Weapons Inspection System (NWIS). Initially developed for active neutron interrogation of nuclear weapons and other fissile assemblies, NWIS employs a custom gallium arsenide application specific integrated circuit and a new signature analysis software package to simultaneously acquire and display the autocorrelation and cross-correlation spectra of up to five detector/electronics systems. The system operates at clock frequencies up to 1 GHz, permitting the collection of timing pulses in bins as narrow as 1 ns. In normal operation NWIS uses well characterized detectors and constant fraction discriminators, but it may also be configured to accept pulses from any circuit and to use the autocorrelation spectrum to accurately determine dead-time. Unlike traditional dead-time assessment techniques that typically require multiple sources and an assumed dead-time model, NWIS provides single-measurement assessment of circuit dead time and does not require an assumed dead-time model or a calibrated high count-rate source

  10. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design

    Science.gov (United States)

    Kia, Kaveh Kazemi; Bonabi, Fahimeh

    2012-12-01

    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 μs. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  11. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design

    International Nuclear Information System (INIS)

    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 μs. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  12. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr., Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bobrek, Miljko [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-12-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios where human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments due the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is the final report of the activities involving the NEET 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays [1]. We present a detailed functional block diagram of the proposed data acquisition system, the thought process leading to technical decisions, the implemented system, and the tested results from the systems. This system will be capable of monitoring at least three parameters of importance to nuclear reactor monitoring: temperature, radiation level, and pressure.

  13. Regulation of body fat mass by the gut microbiota

    DEFF Research Database (Denmark)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik;

    2016-01-01

    New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries in the...

  14. Oxytocin Treatment, Circuitry, and Autism: A Critical Review of the Literature Placing Oxytocin Into the Autism Context.

    Science.gov (United States)

    Guastella, Adam J; Hickie, Ian B

    2016-02-01

    Observed impairment in reciprocal social interaction is a diagnostic hallmark of autism spectrum disorders. There is no effective medical treatment for these problems. Psychological treatments remain costly, time intensive, and developmentally sensitive for efficacy. In this review, we explore the potential of oxytocin-based therapies for social impairments in autism. Evidence shows that acute oxytocin administration improves numerous markers critical to the social circuitry underlying social deficits in autism. Oxytocin may optimize these circuits and enhance reward, motivation, and learning to improve therapeutic outcomes. Despite this, the current evidence of therapeutic benefit from extended oxytocin treatment remains very limited. We highlight complexity in crossing from the laboratory to the autism clinical setting in evaluation of this therapeutic. We discuss a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation. For the autism field, the therapeutic challenges will be resolved by a range of treatment strategies, including greater focus on specific interventions, such as oxytocin, that have a strong basis in the fundamental neurobiology of social behavior. More sophisticated and targeted clinical trials utilizing such approaches are now required, placing oxytocin into the autism context. PMID:26257243

  15. The banana code – Natural blend processing in the olfactory circuitry of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Marco eSchubert

    2014-02-01

    Full Text Available Odor information is predominantly perceived as complex odor blends. For Drosophila melanogaster one of the most attractive blends is emitted by an over-ripe banana. To analyze how the fly’s olfactory system processes natural blends we combined the experimental advantages of gas chromatography and functional imaging (GC-I. In this way, natural banana compounds were presented successively to the fly antenna in close to natural occurring concentrations. This technique allowed us to identify the active odor components, use these compounds as stimuli and measure odor-induced Ca2+ signals in input and output neurons of the Drosophila antennal lobe (AL, the first olfactory neuropil. We demonstrate that mixture interactions of a natural blend are very rare and occur only at the AL output level resulting in a surprisingly linear blend representation. However, the information regarding single components is strongly modulated by the olfactory circuitry within the AL leading to a higher similarity between the representation of individual components and the banana blend. This observed modulation might tune the olfactory system in a way to distinctively categorize odor components and improve the detection of suitable food sources. Functional GC-I thus enables analysis of virtually any unknown natural odorant blend and its components in their relative occurring concentrations and allows characterization of neuronal responses of complete neural assemblies. This technique can be seen as a valuable complementary method to classical GC/electrophysiology techniques, and will be a highly useful tool in future investigations of insect-insect and insect-plant chemical interactions.

  16. Effects of direct social experience on trust decisions and neural reward circuitry

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri

    2012-10-01

    Full Text Available The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball tossing game with three fictional partners manipulated to be perceived as good, bad or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction-error (PE learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning

  17. Intrinsic circuitry in the deep layers of the cat superior colliculus.

    Science.gov (United States)

    Behan, M; Kime, N M

    1996-01-01

    The mammalian superior colliculus is involved in the transformation of sensory signals into orienting behaviors. Sensory and motor signals are integrated in the colliculus to produce movements of the eyes, head, and neck. While there is a considerable amount of information available on the afferent and efferent connections of the colliculus, almost nothing is known about its intrinsic circuitry, particularly that of its deepest layers. It is likely that intrinsic connections in these deeper layers of the colliculus participate in the sensory-motor transformations leading to orienting movements. In this study, we used the neuroanatomical tracer biocytin to label small groups of neurons in the deeper layers of the cat superior colliculus and examine the distribution of their axons and terminals. We found a broadly distributed network of intrinsic projections throughout the deep layers of the superior colliculus. While the majority of terminals were found in a 1-2 mm radius around the injection site, labeled terminals were found throughout the deep layers of the colliculus up to 5 mm from the injection site. In addition, these injections sometimes labeled terminals in the superficial tectum. Extensive projections were demonstrated by the more superficial injections, but few terminals were found when injections were confined to the deepest layers of the colliculus. There was no evidence of anisotropy in the distribution of terminals from injections made at different rostrocaudal or mediolateral locations; neurons located in any one region in the colliculus could potentially influence any other region. This network of intrinsic connections in the cat superior colliculus could provide a means for deeper-layer efferent neurons to associate, and to modulate or coordinate their output. Interneurons could also provide a substrate for mutual inhibition between neurons at the rostral pole of the colliculus that are active during fixation, and more caudally located neurons

  18. Flexible thin film circuitry enabling ubiquitous electronics via post-fabrication customization (Presentation Recording)

    Science.gov (United States)

    Cobb, Brian

    2015-09-01

    For decades, the electronics industry has been accurately described by Moore's Law, where the march towards increasing density and smaller feature sizes has enabled continuous cost reductions and performance improvements. With flexible electronics, this perpetual scaling is not foreseen to occur. Instead, the industry will be dominated by Wright's Law, first proposed in 1936, where increasing demand for high volumes of product will drive costs down. We have demonstrated thin film based circuitry compatible with flexible substrates with high levels of functionality designed for such a high volume industry. This includes a generic 8-bit microprocessor totaling more than 3.5k TFTs operating at 2.1 kHz. We have also developed a post fabrication programming technique via inkjet printing of conductive spots to form a one-time programmable instruction generator, allowing customization of the processor for a specific task. The combination demonstrates the possibility to achieve the high volume production of identical products necessary to reap the benefits promised by Wright's Law, while still retaining the individualization necessary for application differentiation. This is of particular importance in the area of item level identification via RFID, where low cost and individualized identification are necessary. Remotely powered RFID tags have been fabricated using an oxide semiconductor based TFT process. This process is compatible with the post-fabrication printing process to detail individual identification codes, with the goal of producing low cost, high volume flexible tags. The goal is to produce tags compatible with existing NFC communication protocols in order to communicate with readers that are already ubiquitous in the market.

  19. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Report 3

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr, Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shelton, Jacob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-03-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios when human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments because of the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is a report of the activities involving Task 3 of the Nuclear Energy Enabling Technologies (NEET) 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays [1]. Evaluation of the performance of the system for both pre- and post-irradiation as well as operation at elevated temperature will be performed. Detailed performance of the system will be documented to ensure the design meets requirements prior to any extended evaluation. A suite of tests will be developed which will allow evaluation before and after irradiation and during temperature. Selection of the radiation exposure facilities will be determined in the early phase of the project. Radiation exposure will consist of total integrated dose (TID) up to 200 kRad or above with several intermediate doses during test. Dose rates will be in various ranges determined by the facility that will be used with a target of 30 kRad/hr. Many samples of the pre-commercial devices to be used will have been tested in previous projects to doses of at least 300 kRad and temperatures up to 125C. The complete systems will therefore be tested for performance at intermediate doses. Extended temperature testing will be performed up to the limit of the commercial sensors. The test suite performed at each test point will consist of operational testing of the three basic

  20. Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naive Adolescent Depression.

    Directory of Open Access Journals (Sweden)

    Haiyang Geng

    Full Text Available Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD. This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC. Fractional anisotropy (FA values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC region showing significant differences between the two groups was identified.Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

  1. Determining the Control Circuitry of Redox Metabolism at the Genome-Scale

    DEFF Research Database (Denmark)

    Federowicz, Stephen; Kim, Donghyuk; Ebrahim, Ali;

    2014-01-01

    regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs), ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic......, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome...

  2. Wired for behavior: from development to function of innate limbic system circuitry

    OpenAIRE

    Katie eSokolowski; Corbin, Joshua G.

    2012-01-01

    The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional or motivational salience, which includes innate behaviors such as mating, aggression and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents), and ...

  3. Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Goto

    Full Text Available Although left-right (L-R asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

  4. First realization of a tracking detector for high energy physics experiments based on Josephson digital readout circuitry

    CERN Document Server

    Pagano, S; Esposito, A P; Mukhanov, O; Rylov, S

    1999-01-01

    We have designed and realized a prototype of a high energy particle microstrip detector with Josephson readout circuits. The key features of this device are: minimum ionizing particle sensitivity, due to the use of semiconductive $9 sensors, fast speed and radiation hardness, due to the use of superconductive circuitry, and current discrimination, which allows the use of several types of semiconductors as detector (Si, GaAs, CVD-diamond) without loss in $9 performances. The Josephson circuitry, made by a combination of RSFQ and latching logic gates, realizes an 8-bit current discriminator and parallel to serial converter and can be directly interfaced to room temperature electronics. $9 This device, which is designed for application as vertex detector for the Compass and LHC-B accelerator experiments, has been tested with small radioactive sources acid will undergo to a test beam at the CERN SPS facility with 24 $9 GeV/c protons. Current results and future perspectives will be reported. (11 refs).

  5. Common stemness regulators of embryonic and cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Christiana; Hadjimichael; Konstantina; Chanoumidou; Natalia; Papadopoulou; Panagiota; Arampatzi; Joseph; Papamatheakis; Androniki; Kretsovali

    2015-01-01

    Pluripotency of embryonic stem cells(ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans-ducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors(cancer stem cells), provides a common conceptual and research frame-work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

  6. Wired for behavior: from development to function of innate limbic system circuitry

    Directory of Open Access Journals (Sweden)

    Katie eSokolowski

    2012-04-01

    Full Text Available The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional or motivational salience, which includes innate behaviors such as mating, aggression and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents, and is then processed in the brain by a set of delineated structures that primarily includes the amygdala and hypothalamus. While the basic neuroanatomy of these connections is well established, much remains unknown about how information is processed within innate circuits and how genetic hierarchies regulate development and function of these circuits. Utilizing innovative technologies including channel rhodopsin-based circuit manipulation and genetic manipulation in rodents, recent studies have begun to answer these central questions. In this article we review the current understanding of how limbic circuits regulate sexually dimorphism and how these circuits are established and shaped during pre- and post-natal development. We also discuss how understanding developmental processes of innate circuit formation may inform behavioral alterations observed in neurodevelopmental disorders, such as autism spectrum disorders, which are characterized by limbic system dysfunction.

  7. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

    Directory of Open Access Journals (Sweden)

    Salvatore Fusco

    2016-02-01

    Full Text Available Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.

  8. Regulatory interactions of stress and reward on rat forebrain opioidergic and GABAergic circuitry

    OpenAIRE

    Christiansen, A.M.; HERMAN, J. P.; Ulrich-Lai, Y.M.

    2011-01-01

    Palatable food intake reduces stress responses, suggesting that individuals may consume such “comfort” food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid (GABA)ergic signaling is critical for both reward and stress regulation suggesting that these systems are prime candidates for mediating s...

  9. A neurocomputational model of spinal circuitry for controlling the execution of arm voluntary movements

    OpenAIRE

    Parziale, Antonio; Festa, Jacopo; Marcelli, Angelo

    2015-01-01

    We present a model of the spinal cord in controlling one degree-of-freedom arm movements. The model includes both neural and musculoskeletal functions in an integrated framework. The model has been implemented by an artificial neural network coupled with a computational model of muscle publicly available. The experimental results show that the model is able to regulate the position of the arm and to mediate reflex actions by integrating commands from CNS and signals from proprioceptors.

  10. Determining the control circuitry of redox metabolism at the genome-scale.

    Directory of Open Access Journals (Sweden)

    Stephen Federowicz

    2014-04-01

    Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

  11. Function and evolution of the long noncoding RNA circuitry orchestrating X-chromosome inactivation in mammals.

    Science.gov (United States)

    Furlan, Giulia; Rougeulle, Claire

    2016-09-01

    X-chromosome inactivation (XCI) is a chromosome-wide regulatory process that ensures dosage compensation for X-linked genes in Theria. XCI is established during early embryogenesis and is developmentally regulated. Different XCI strategies exist in mammalian infraclasses and the regulation of this process varies also among closely related species. In Eutheria, initiation of XCI is orchestrated by a cis-acting locus, the X-inactivation center (Xic), which is particularly enriched in genes producing long noncoding RNAs (lncRNAs). Among these, Xist generates a master transcript that coats and propagates along the future inactive X-chromosome in cis, establishing X-chromosome wide transcriptional repression through interaction with several protein partners. Other lncRNAs also participate to the regulation of X-inactivation but the extent to which their function has been maintained in evolution is still poorly understood. In Metatheria, Xist is not conserved, but another, evolutionary independent lncRNA with similar properties, Rsx, has been identified, suggesting that lncRNA-mediated XCI represents an evolutionary advantage. Here, we review current knowledge on the interplay of X chromosome-encoded lncRNAs in ensuring proper establishment and maintenance of chromosome-wide silencing, and discuss the evolutionary implications of the emergence of species-specific lncRNAs in the control of XCI within Theria. WIREs RNA 2016, 7:702-722. doi: 10.1002/wrna.1359 For further resources related to this article, please visit the WIREs website. PMID:27173581

  12. Genome Wide Analysis of Chromatin Regulation by Cocaine Reveals a Novel Role for Sirtuins

    OpenAIRE

    Renthal, William; Kumar, Arvind; Xiao, Guanghua; Wilkinson, Matthew; Covington, Herbert E.; Maze, Ian; Sikder, Devanjan; Robison, Alfred J.; LaPlant, Quincey; Dietz, David M.; Russo, Scott J.; Vialou, Vincent; Chakravarty, Sumana; Kodadek, Thomas J.; Stack, Ashley

    2009-01-01

    Changes in gene expression contribute to the long-lasting regulation of the brain’s reward circuitry seen in drug addiction, however, the specific genes regulated and the transcriptional mechanisms underlying such regulation remain poorly understood. Here, we used chromatin immunoprecipitation coupled with promoter microarray analysis to characterize genome-wide chromatin changes in the mouse nucleus accumbens, a crucial brain reward region, after repeated cocaine administration. Our findings...

  13. Impaired Cholinergic Excitation of Prefrontal Attention Circuitry in the TgCRND8 Model of Alzheimer’s Disease

    Science.gov (United States)

    Proulx, Éliane; Fraser, Paul; McLaurin, JoAnne; Lambe, Evelyn K.

    2015-01-01

    Attention deficits in Alzheimer’s disease can exacerbate its other cognitive symptoms, yet relevant disruptions of key prefrontal circuitry are not well understood. Here, in the TgCRND8 mouse model of this neurological disorder, we demonstrate and characterize a disruption of cholinergic excitation in the major corticothalamic layer of the prefrontal cortex, in which modulation by acetylcholine is essential for optimal attentional function. Using electrophysiology with concurrent multiphoton imaging, we show that layer 6 pyramidal cells are unable to sustain cholinergic excitation to the same extent as their nontransgenic littermate controls, as a result of the excessive activation of calcium-activated hyperpolarizing conductances. We report that cholinergic excitation can be improved in TgCRND8 cortex by pharmacological blockade of SK channels, suggesting a novel target for the treatment of cognitive dysfunction in Alzheimer’s disease. PMID:26377466

  14. Programmable scan/read circuitry for charge coupled device imaging detectors. [spcecraft attitude control and star trackers

    Science.gov (United States)

    Salomon, P. M.; Smilowitz, K.

    1984-01-01

    A circuit for scanning and outputting the induced charges in a solid state charge coupled device (CCD) image detector is disclosed in an image detection system for use in a spacecraft attitude control system. The image detection system includes timing control circuitry for selectively controlling the output of the CCD detector so that video outputs are provided only with respect to induced charges corresponding to predetermined sensing element lines of the CCD detector. The timing control circuit and the analog to digital converter are controlled by a programmed microprocessor which defines the video outputs to be converted and further controls the timing control circuit so that no video outputs are provided during the delay associated with analog to digital conversion.

  15. “Liking” and “Wanting” Linked to Reward Deficiency Syndrome (RDS): Hypothesizing Differential Responsivity in Brain Reward Circuitry

    Science.gov (United States)

    Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

    2013-01-01

    In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: “liking,” “learning,” and “wanting” [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or “wanting” hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily self-administered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens, and they stimulate the functioning of brain reward circuitry (producing the “high” that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

  16. Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

    Science.gov (United States)

    Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

    2012-01-01

    Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

  17. Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry

    DEFF Research Database (Denmark)

    Haahr, M. E.; Rasmussen, Peter Mondrup; Madsen, K.;

    2012-01-01

    The neurobiology underlying obesity is not fully understood. The neurotransmitter serotonin (5-HT) is established as a satiety-generating signal, but its rewarding role in feeding is less well elucidated. From animal experiments there is now evidence that the 5-HT4 receptor (5-HT4R) is involved in...... food intake, and that pharmacological or genetic manipulation of the receptor in reward-related brain areas alters food intake.Here, we used positron emission tomography in humans to examine the association between cerebral 5-HT4Rs and common obesity.We found in humans a strong positive association...... between body mass index and the 5-HT4R density bilaterally in the two reward ‘hot spots’ nucleus accumbens and ventral pallidum, and additionally in the left hippocampal region and orbitofrontal cortex.These findings suggest that the 5-HT4R is critically involved in reward circuits that regulate people...

  18. Regulation of Bacterial Virulence by Csr (Rsm) Systems

    OpenAIRE

    Vakulskas, Christopher A.; Potts, Anastasia H.; Babitzke, Paul; Ahmer, Brian M. M.; Romeo, Tony

    2015-01-01

    Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional...

  19. Calcyon mRNA expression in the frontal-striatal circuitry and its relationship to vesicular processes and ADHD

    Directory of Open Access Journals (Sweden)

    Castellanos F Xavier

    2007-07-01

    Full Text Available Abstract Background Calcyon is a single transmembrane protein predominantly expressed in the brain. Very recently, calcyon has been implicated in clathrin mediated endocytosis, a critical component of synaptic plasticity. At the genetic level, preliminary evidence supports an association between attention-deficit/hyperactivity disorder (ADHD and polymorphisms in the calcyon gene. As little is known about the potential role of calcyon in ADHD, animal models may provide important insights into this issue. Methods We examined calcyon mRNA expression in the frontal-striatal circuitry of three-, five-, and ten-week-old Spontaneously Hypertensive Rats (SHR, the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived. As a complement, we performed a co-expression network analysis using a database of mRNA gene expression profiles of multiple brain regions in order to explore potential functional links of calcyon to other genes. Results In all age groups, SHR expressed significantly more calcyon mRNA in the medial prefrontal and orbital frontal cortices than WKY rats. In contrast, in the motor cortex, dorsal striatum and nucleus accumbens, calcyon mRNA expression was only significantly elevated in SHR in younger animals. In both strains, calcyon mRNA levels decreased significantly with age in all regions studied. In the co-expression network analysis, we found a cluster of genes (many of them poorly studied so far strongly connected to calcyon, which may help elucidate its role in the brain. The pair-wise relations of calcyon with other genes support its involvement in clathrin mediated endocytosis and, potentially, some other membrane/vesicular processes. Interestingly, no link was found between calcyon and the dopamine D1 receptor, which was previously shown to interact with the C-terminal of calcyon. Conclusion The results indicate an alteration in calcyon expression within the frontal-striatal circuitry

  20. Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Matsuo

    Full Text Available Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically

  1. A low-cost dielectric spectroscopic system using metamaterial open horn-ring resonator-inspired BSF and detection circuitry

    Science.gov (United States)

    Kumari, Ratnesh; Patel, Piyush N.

    2016-07-01

    The sensitivity in a lower microwave band dielectric spectroscopic system is relatively less compared to that of millimeter wave and terahertz system. This work reports modeling and development of an epsilon-negative metamaterial resonator-inspired microwave band-stop filter as a prototype device and its detection circuitry for the spectroscopic analysis of dielectric samples in S-band. The device structure consists of a diamond-shaped patch with a complementary open split horn-ring resonator, fabricated on a Neltech substrate of relative permittivity ( ɛ r = 3.2). The measured transmission coefficient at 2.2 GHz and simulated result at 2.24 GHz demonstrate an excellent accuracy in the device fabrication. A low-cost connector-type microwave signal detection system was assembled for the real-time transduction of device signal into an equivalent DC voltage. Further, a single channel cavity developed using polydimethylsiloxane was placed over the resonator gap for analyzing the perturbation effect of electric field intensity on the resonance and circuit output DC level for different dielectric samples under test. The performed calibrations show linearity up to 82.5 % in the device response.

  2. Dorsal medial prefrontal cortex (MPFC) circuitry in rodent models of cocaine use: implications for drug addiction therapies.

    Science.gov (United States)

    Jasinska, Agnes J; Chen, Billy T; Bonci, Antonello; Stein, Elliot A

    2015-03-01

    Although the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms and propose a framework to potentially reconcile the apparent discrepancy. We also draw parallels between these pre-clinical models of cocaine self-administration and human neuro-imaging studies in cocaine users, and argue that both lines of evidence point to dynamic interactions between cue-reactivity processes and control processes within the dorsal MPFC circuitry. From a translational perspective, these findings underscore the importance of interventions and therapeutics targeting not just a brain region, but a specific computational process within that brain region, and may have implications for the design and implementation of more effective treatments for human cocaine addiction. PMID:24620898

  3. Broadband wireless radio frequency power telemetry using a metamaterial resonator embedded with non-foster impedance circuitry

    Science.gov (United States)

    Fu, Guoqing; Sonkusale, Sameer

    2015-05-01

    Wireless powering of implantable biomedical devices and smart radio frequency identification (RFID) tags with very low profile antennas is desired. We propose a low profile electrically small antenna for near-field wireless power telemetry employing a metamaterial Split Ring Resonator (SRR) antenna. SRRs can be designed for operation over wide frequencies from RF to visible. However, they are inherently narrowband making them sensitive to component mismatch with respect to external transmit antenna. Here, we propose an embedding of a non-foster impedance circuitry into the metamaterial SRR structure that imparts conjugate negative complex impedance to this resonator antenna thereby increasing the effective bandwidth and thus overcoming the fundamental limit for efficient signal coupling. We demonstrate the concept through extensive numerical simulations and a prototype system at the board level using discrete off-the-shelf components and printed circuit SRR antenna at 500 MHz. We show that the power transfer between SRR receive antenna and the external transmit loop antenna is improved by more than 8 dB over a wide frequency band (from 525 MHz to 635 MHz), before and after non-foster circuit activation.

  4. Regional specificity in the real-time development of phasic dopamine transmission patterns during acquisition of a cue-cocaine association

    OpenAIRE

    Aragona, Brandon J.; Day, Jeremy J.; Roitman, Mitchell F.; Cleaveland, Nathan A.; Wightman, R. Mark; Carelli, Regina M.

    2009-01-01

    Drug seeking is significantly regulated by drug-associated cues and associative learning between environmental cues and cocaine reward is mediated by dopamine transmission within the nucleus accumbens (NAc). However, dopamine transmission during early acquisition of a cue-cocaine association has never been assessed because of the technical difficulties associated with resolving cue-evoked and cocaine-evoked dopamine release within the same conditioning trial. Here, we used fast-scan cyclic vo...

  5. Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is due to a direct increase in phasic dopamine release events

    OpenAIRE

    Aragona, Brandon J.; Cleaveland, Nathan A.; Stuber, Garret D.; Day, Jeremy J.; Carelli, Regina M.; Wightman, R. Mark

    2008-01-01

    Preferential enhancement of dopamine transmission within the nucleus accumbens (NAc) shell is a fundamental aspect of the neural regulation of cocaine reward. Despite its importance, the nature of this effect is poorly understood. Here, we used fast-scan cyclic voltammetry to examine specific transmission processes underlying cocaine-evoked increases in dopamine transmission within the NAc core and shell. Initially, we examined altered terminal dopamine concentrations following global autorec...

  6. High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

    OpenAIRE

    Nieland, Thomas J. F.; Logan, David J.; Saulnier, Jessica; Lam, Daniel; Johnson, Caroline; Root, David E.; Carpenter, Anne E.; Sabatini, Bernardo L.

    2013-01-01

    The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experime...

  7. High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

    OpenAIRE

    Nieland, Thomas J. F.; Logan, David J.; Saulnier, Jessica; Lam, Daniel; Johnson, Caroline; Root, David E.; Carpenter, Anne E.; Sabatini, Bernardo L.

    2014-01-01

    The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experime...

  8. Regulating anxiety with extrasynaptic inhibition.

    Science.gov (United States)

    Botta, Paolo; Demmou, Lynda; Kasugai, Yu; Markovic, Milica; Xu, Chun; Fadok, Jonathan P; Lu, Tingjia; Poe, Michael M; Xu, Li; Cook, James M; Rudolph, Uwe; Sah, Pankaj; Ferraguti, Francesco; Lüthi, Andreas

    2015-10-01

    Aversive experiences can lead to complex behavioral adaptations including increased levels of anxiety and fear generalization. The neuronal mechanisms underlying such maladaptive behavioral changes, however, are poorly understood. Here, using a combination of behavioral, physiological and optogenetic approaches in mouse, we identify a specific subpopulation of central amygdala neurons expressing protein kinase C δ (PKCδ) as key elements of the neuronal circuitry controlling anxiety. Moreover, we show that aversive experiences induce anxiety and fear generalization by regulating the activity of PKCδ(+) neurons via extrasynaptic inhibition mediated by α5 subunit-containing GABAA receptors. Our findings reveal that the neuronal circuits that mediate fear and anxiety overlap at the level of defined subpopulations of central amygdala neurons and demonstrate that persistent changes in the excitability of a single cell type can orchestrate complex behavioral changes. PMID:26322928

  9. Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed.

    Science.gov (United States)

    Tomalin, Lewis Elwood; Day, Alison Michelle; Underwood, Zoe Elizabeth; Smith, Graham Robert; Dalle Pezze, Piero; Rallis, Charalampos; Patel, Waseema; Dickinson, Bryan Craig; Bähler, Jürg; Brewer, Thomas Francis; Chang, Christopher Joh-Leung; Shanley, Daryl Pierson; Veal, Elizabeth Ann

    2016-06-01

    Reactive oxygen species, such as H2O2, can damage cells but also promote fundamental processes, including growth, differentiation and migration. The mechanisms allowing cells to differentially respond to toxic or signaling H2O2 levels are poorly defined. Here we reveal that increasing external H2O2 produces a bi-phasic response in intracellular H2O2. Peroxiredoxins (Prx) are abundant peroxidases which protect against genome instability, ageing and cancer. We have developed a dynamic model simulating in vivo changes in Prx oxidation. Remarkably, we show that the thioredoxin peroxidase activity of Prx does not provide any significant protection against external rises in H2O2. Instead, our model and experimental data are consistent with low levels of extracellular H2O2 being efficiently buffered by other thioredoxin-dependent activities, including H2O2-reactive cysteines in the thiol-proteome. We show that when extracellular H2O2 levels overwhelm this buffering capacity, the consequent rise in intracellular H2O2 triggers hyperoxidation of Prx to thioredoxin-resistant, peroxidase-inactive form/s. Accordingly, Prx hyperoxidation signals that H2O2 defenses are breached, diverting thioredoxin to repair damage. PMID:26944189

  10. Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth.

    Science.gov (United States)

    Bertocci, M A; Bebko, G; Versace, A; Fournier, J C; Iyengar, S; Olino, T; Bonar, L; Almeida, J R C; Perlman, S B; Schirda, C; Travis, M J; Gill, M K; Diwadkar, V A; Forbes, E E; Sunshine, J L; Holland, S K; Kowatch, R A; Birmaher, B; Axelson, D; Horwitz, S M; Frazier, T W; Arnold, L E; Fristad, M A; Youngstrom, E A; Findling, R L; Phillips, M L

    2016-09-01

    Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions. PMID:26903272

  11. rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts.

    Science.gov (United States)

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S

    2015-03-01

    Recently, Willuhn et al. reported that cocaine use and even non-substance-related addictive behavior increases as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors and was also associated with lower activation of cues in occipital cortex and cerebellum, in a recent PET study by Volkow's et al. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of 10 heroin addicts undergoing protracted abstinence (average 16.9 months). In a randomized placebo-controlled crossover study of KB220Z, five subjects completed a triple-blinded experiment in which the subject, the person administering the treatment, and the person evaluating the response to treatment were blinded to the treatment that any particular subject was receiving. In addition, nine subjects were genotyped utilizing the GARSDX™ test. We preliminarily report that KB220Z induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following 1-hour acute administration. Furthermore, KB220Z also reduced resting-state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all 10 abstinent heroin-dependent subjects, we observed that three brain regions of interest were significantly activated from resting state by KB220Z compared to placebo (p addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results, and confirmation with additional research and ongoing rodent and human studies of KB220Z is required. PMID:25526228

  12. Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth

    Science.gov (United States)

    Bertocci, Michele A.; Bebko, Genna; Versace, Amelia; Fournier, Jay C.; Iyengar, Satish; Olino, Thomas; Bonar, Lisa; Almeida, Jorge R. C.; Perlman, Susan B.; Schirda, Claudiu; Travis, Michael J.; Gill, Mary Kay; Diwadkar, Vaibhav A.; Forbes, Erika E.; Sunshine, Jeffrey L.; Holland, Scott K; Kowatch, Robert A.; Birmaher, Boris; Axelson, David; Horwitz, Sarah M.; Frazier, Thomas W.; Arnold, L. Eugene; Fristad, Mary. A; Youngstrom, Eric A.; Findling, Robert L.; Phillips, Mary L.

    2015-01-01

    Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0(sd=2.0) from 3 clinical sites. Linear regression using the LASSO method for variable selection was used to predict severity of future behavioral and emotional dysregulation [measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)] at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors, and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained approximately one-third of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions. PMID:26903272

  13. Brain circuitry of compulsivity.

    Science.gov (United States)

    van den Heuvel, Odile A; van Wingen, Guido; Soriano-Mas, Carles; Alonso, Pino; Chamberlain, Samuel R; Nakamae, Takashi; Denys, Damiaan; Goudriaan, Anna E; Veltman, Dick J

    2016-05-01

    Compulsivity is associated with alterations in the structure and the function of parallel and interacting brain circuits involved in emotional processing (involving both the reward and the fear circuits), cognitive control, and motor functioning. These brain circuits develop during the pre-natal period and early childhood under strong genetic and environmental influences. In this review we bring together literature on cognitive, emotional, and behavioral processes in compulsivity, based mainly on studies in patients with obsessive-compulsive disorder and addiction. Disease symptoms normally change over time. Goal-directed behaviors, in response to reward or anxiety, often become more habitual over time. During the course of compulsive disorders the mental processes and repetitive behaviors themselves contribute to the neuroplastic changes in the involved circuits, mainly in case of chronicity. On the other hand, successful treatment is able to normalize altered circuit functioning or to induce compensatory mechanisms. We conclude that insight in the neurobiological characteristics of the individual symptom profile and disease course, including the potential targets for neuroplasticity is an unmet need to advance the field. PMID:26711687

  14. Translational Repression of NhaR, a Novel Pathway for Multi-Tier Regulation of Biofilm Circuitry by CsrA

    OpenAIRE

    Pannuri, Archana; Yakhnin, Helen; Vakulskas, Christopher A.; Edwards, Adrianne N.; Babitzke, Paul; Romeo, Tony

    2012-01-01

    The RNA binding protein CsrA (RsmA) represses biofilm formation in several proteobacterial species. In Escherichia coli, it represses the production of the polysaccharide adhesin poly-β-1,6-N-acetyl-d-glucosamine (PGA) by binding to the pgaABCD mRNA leader, inhibiting pgaA translation, and destabilizing this transcript. In addition, CsrA represses genes responsible for the synthesis of cyclic di-GMP, an activator of PGA production. Here we determined that CsrA also represses NhaR, a LysR-type...

  15. Melanocortin-4 receptor-regulated energy homeostasis.

    Science.gov (United States)

    Krashes, Michael J; Lowell, Bradford B; Garfield, Alastair S

    2016-02-01

    The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular components--two antagonistically acting ligands and two cognate receptors--this phylogenetically conserved system serves as a prototype for hierarchical energy balance regulation. Over the last decade the application of conditional genetic techniques has facilitated the neuroanatomical dissection of the melanocortinergic network and identified the specific neural substrates and circuits that underscore the regulation of feeding behavior, energy expenditure, glucose homeostasis and autonomic outflow. In this regard, the melanocortin-4 receptor is a critical coordinator of mammalian energy homeostasis and body weight. Drawing on recent advances in neuroscience and genetic technologies, we consider the structure and function of the melanocortin-4 receptor circuitry and its role in energy homeostasis. PMID:26814590

  16. Regulatory Circuitry of the CsrA/CsrB and BarA/UvrY Systems of Escherichia coli

    OpenAIRE

    Suzuki, Kazushi; Wang, Xin; Weilbacher, Thomas; Pernestig, Anna-Karin; Melefors, Öjar; Georgellis, Dimitris; Babitzke, Paul; Romeo, Tony

    2002-01-01

    The global regulator CsrA (carbon storage regulator) is an RNA binding protein that coordinates central carbon metabolism, activates flagellum biosynthesis and motility, and represses biofilm formation in Escherichia coli. CsrA activity is antagonized by the untranslated RNA CsrB, to which it binds and forms a globular ribonucleoprotein complex. CsrA indirectly activates csrB transcription, in an apparent autoregulatory mechanism. In the present study, we elucidate the intermediate regulatory...

  17. The RNA binding protein CPEB regulates dendrite morphogenesis and neuronal circuit assembly in vivo

    OpenAIRE

    Bestman, Jennifer E.; Cline, Hollis T.

    2008-01-01

    Visual system development requires experience-dependent mechanisms that regulate neuronal structure and function, including dendritic arbor growth, synapse formation, and stabilization. Although RNA binding proteins have been shown to affect some forms of synaptic plasticity in adult animals, their role in the development of neuronal structure and functional circuitry is not clear. Using two-photon time-lapse in vivo imaging and electrophysiology combined with morpholino-mediated knockdown an...

  18. Responses of motor units during the hind limb flexion withdrawal reflex evoked by noxious skin heating: phasic and prolonged suppression by midbrain stimulation and comparison with simultaneously recorded dorsal horn units.

    Science.gov (United States)

    Carstens, E; Campell, I G

    1992-02-01

    In rats anesthetized with sodium pentobarbital, we quantitatively analyzed descending modulation from the midbrain of a nociceptive flexion withdrawal reflex and responses of associated spinal neurons. We monitored the isometric force of hind limb withdrawal elicited by noxious heat stimuli (42-54 degrees C, 10 sec) on the hind paw. In one series of experiments, single-fiber EMG electrodes recorded responses of single muscle fibers (i.e., motor units) in biceps femoris during the hind limb withdrawal, without and during electrical stimulation in the midbrain periaqueductal gray (PAG) or lateral midbrain reticular formation (LRF). In a second series, responses of single lumbar dorsal horn neurons were also recorded simultaneously. Withdrawal force and associated motor unit responses were suppressed for prolonged periods (4 to greater than 60 min) following the initial episode of PAG or LRF stimulation in 40% of the rats, while they were suppressed phasically (i.e., only during brain stimulation) in the remainder. Motor unit responses increased in a graded fashion with increasing skin stimulus temperature from threshold (45 degrees C) to 54 degrees C. During PAG stimulation, the slope of the rate coding function was reduced with no change in threshold temperature. During LRF stimulation the rate coding function was shifted toward higher temperatures with increased threshold (47 degrees C). In 14 experiments 43 paired recordings were made from a dorsal horn and a motor unit during hind limb withdrawals. Mean latency to onset and peak of the heat-evoked response was shorter for dorsal horn compared to motor units. In 6/14 rats withdrawal force and motor unit responses were significantly suppressed for more than 8 min following mechanical placement of the stimulating electrodes and/or the initial episode of midbrain stimulation, while the simultaneously recorded dorsal horn unit responses remained constant. Following supplemental administration of pentobarbital (10

  19. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  20. Rapidly characterizing the fast dynamics of RNA genetic circuitry with cell-free transcription-translation (TX-TL) systems.

    Science.gov (United States)

    Takahashi, Melissa K; Chappell, James; Hayes, Clarmyra A; Sun, Zachary Z; Kim, Jongmin; Singhal, Vipul; Spring, Kevin J; Al-Khabouri, Shaima; Fall, Christopher P; Noireaux, Vincent; Murray, Richard M; Lucks, Julius B

    2015-05-15

    RNA regulators are emerging as powerful tools to engineer synthetic genetic networks or rewire existing ones. A potential strength of RNA networks is that they may be able to propagate signals on time scales that are set by the fast degradation rates of RNAs. However, a current bottleneck to verifying this potential is the slow design-build-test cycle of evaluating these networks in vivo. Here, we adapt an Escherichia coli-based cell-free transcription-translation (TX-TL) system for rapidly prototyping RNA networks. We used this system to measure the response time of an RNA transcription cascade to be approximately five minutes per step of the cascade. We also show that this response time can be adjusted with temperature and regulator threshold tuning. Finally, we use TX-TL to prototype a new RNA network, an RNA single input module, and show that this network temporally stages the expression of two genes in vivo. PMID:24621257

  1. What Happens in the Thymus Does Not Stay in the Thymus: How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function.

    Science.gov (United States)

    Vacchio, Melanie S; Bosselut, Rémy

    2016-06-15

    MHC-restricted CD4(+) and CD8(+) T cells are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. Although the transcriptional control of CD4(+)-CD8(+) lineage choice in the thymus is now better understood, less was known about what maintains the CD4(+) and CD8(+) lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in postthymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4(+)-CD8(+) lineage commitment in the thymus, is critical for CD4(+) T cell helper functions. PMID:27260768

  2. Die-level, post-CMOS processes for fabricating open-gate, field-effect biosensor arrays with on-chip circuitry

    International Nuclear Information System (INIS)

    Field-effect sensors have been applied extensively to numerous biomedical applications. To develop biosensor arrays in large scale, integration with signal-processing circuits on a single chip is crucial for avoiding wiring complexity and reducing noise interference. This paper proposes and compares two CMOS-compatible processes that allow open-gate, field-effect transistors (OGFETs) to be fabricated at the die level. The polygates of transistors are removed to maximize the transconductance. The CMOS compatibility further facilitates the monolithic integration with circuitry. Based on images and electrical measurements taken at different stages of the post-CMOS processes, a more feasible and reliable process is identified. The robustness of the fabricated OGFETs against the micromachining process and against moisture is further examined and discussed. Finally, the capability of the OGFETs in detecting ion concentrations, biomolecules, and electrophysiological signals is demonstrated

  3. Exposure to Glycolytic Carbon Sources Reveals a Novel Layer of Regulation for the MalT Regulon

    Directory of Open Access Journals (Sweden)

    Sylvia A. Reimann

    2011-01-01

    Full Text Available Bacteria adapt to changing environments by means of tightly coordinated regulatory circuits. The use of synthetic lethality, a genetic phenomenon in which the combination of two nonlethal mutations causes cell death, facilitates identification and study of such circuitry. In this study, we show that the E. coli ompR malTcon double mutant exhibits a synthetic lethal phenotype that is environmentally conditional. MalTcon, the constitutively active form of the maltose system regulator MalT, causes elevated expression of the outer membrane porin LamB, which leads to death in the absence of the osmoregulator OmpR. However, the presence and metabolism of glycolytic carbon sources, such as sorbitol, promotes viability and unveils a novel layer of regulation within the complex circuitry that controls maltose transport and metabolism.

  4. 下颌表面肌电提取和评价呼吸相关时相型成分%A method for extracting and evaluating inspiratory phasic component associated with respiration from mandibular surface electromyogram

    Institute of Scientific and Technical Information of China (English)

    张达; 曹征涛; 李彦如; 叶京英; 俞梦孙

    2014-01-01

    It is difficult to process the mandibularis surface myoelectric signal by means of conventional methods,not only because the sig-nal is weak but also susceptible to the activity of other physiological electrical signal and the electromagnetic interference of environment.In this manuscript,the mandibular surface electromyogram (SEMG)was analyzed by independent component analysis followed by empirical mode decomposition based on current electrodes and electromyographic instrument.We also introduced a method to evaluate the effect of signal processing combining with the respiratory signal.We processed the SEMG signal of normal and obstructive sleep apnea/hypopnea syndrome subjects in different sleep stages.The results demonstrated the signal-noise-rate of SEMG was increased from -0.85 ±6.11dB to 4.55 ±6.67dB.At the same time,the cross-correlation between respiration and the root-mean-square of SEMG was increased from 0.39 ± 0.13 to 0.52 ±0.19.These results indicated that the method could increase the signal-noise-rate of SEMG and extract phasic component from mandibular SEMG.%利用表面电极采集的下颌表面肌电信号比较微弱,又受周围其他生理电信号和外界电磁干扰的影响,信噪比很低,传统的信号处理方法已不能很好地解决。本文在现有电极数量、排布方式和肌电信号采集设备基础上,采用独立分量分析与经验模式分解相结合,对下颌表面肌电信号进行处理;并结合呼吸气流信号,提出针对下颌表面肌电信号处理的评价方法。我们同步采集了正常成年人和阻塞性睡眠呼吸暂停/低通气综合征患者在不同睡眠期的下颌表面肌电和呼吸气流信号。处理结果表明,下颌表面肌电信号的信噪比从处理前的-0.85±6.11 dB提高到4.55±6.67 dB;同时,呼吸与下颌表面肌电信号的均方根值之间的互相关也从0.39±0.13增加到0.52±0.19。说明,该方法能大幅提高信

  5. Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety.

    Science.gov (United States)

    Andolina, Diego; Di Segni, Matteo; Bisicchia, Elisa; D'Alessandro, Francesca; Cestari, Vincenzo; Ventura, Andrea; Concepcion, Carla; Puglisi-Allegra, Stefano; Ventura, Rossella

    2016-08-01

    Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34 family have been suggested to regulate synaptic plasticity and neurotransmission processes, which mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover, we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the BLA of stress-exposed TKO mice. We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction. Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential GRM7, 5-HT2C, and CRFR1 mRNA expression was noted in the mpFC and BLA between TKO and WT mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity. PMID:27026110

  6. From social behavior to neural circuitry: steroid hormones rapidly modulate advertisement calling via a vocal pattern generator.

    Science.gov (United States)

    Remage-Healey, Luke; Bass, Andrew H

    2006-09-01

    Across vertebrates, androgens are rapidly elevated within minutes in response to aggressive or reproductive stimuli, yet it is unclear what the causal relationship is between fast androgen elevation and the ongoing (minute-by-minute) expression of behavior. This study tested the hypothesis that rapid increases in plasma steroid levels induce similarly rapid increases in both vocal behavior and the neurophysiological output of a central pattern generator that governs vocal behavior. In Gulf toadfish (Opsanus beta), males call to attract females to their nesting sites, and both males and females vocalize in aggressive interactions. Previous field experiments with males showed that simulated territorial challenges produce rapid and concurrent elevations in ongoing calling behavior and circulating levels of the teleost-specific androgen 11-ketotestosterone (11kT), but not the glucocorticoid cortisol. The current field experiments showed that non-invasive (food) delivery of 11kT, but not cortisol, induced an elevation within 10 min in the ongoing calling behavior of males. Electrophysiological experiments revealed that intramuscular injections of either 11kT or cortisol, but neither testosterone nor 17-beta-estradiol, induced increases within 5 min in the output of the vocal pattern generator in males, whereas only cortisol had similarly fast effects in females. The field behavioral results support predictions generated by the challenge hypothesis and also parallel the 11kT-dependent modulation of the vocal pattern generator in males. The cortisol effect on the vocal pattern generator in both sexes predicts that glucocorticoids regulate vocalizations in non-advertisement contexts. Together, these experiments provide strong support for the hypothesis that surges in circulating steroid levels play a causal role in shaping rapid changes in social behavior (vocalizations) through non-genomic-like actions on neural (vocal motor) circuits that directly encode behavioral

  7. Sleep quality and neural circuit function supporting emotion regulation

    Directory of Open Access Journals (Sweden)

    Minkel Jared D

    2012-12-01

    Full Text Available Abstract Background Recent laboratory studies employing an extended sleep deprivation model have mapped sleep-related changes in behavior onto functional alterations in specific brain regions supporting emotion, suggesting possible biological mechanisms for an association between sleep difficulties and deficits in emotion regulation. However, it is not yet known if similar behavioral and neural changes are associated with the more modest variability in sleep observed in daily life. Methods We examined relationships between sleep and neural circuitry of emotion using the Pittsburgh Sleep Quality Index and fMRI data from a widely used emotion regulation task focusing on cognitive reappraisal of negative emotional stimuli in an unselected sample of 97 adult volunteers (48 women; mean age 42.78±7.37 years, range 30–54 years old. Results Emotion regulation was associated with greater activation in clusters located in the dorsomedial prefrontal cortex (dmPFC, left dorsolateral prefrontal cortex (dlPFC, and inferior parietal cortex. Only one subscale from the Pittsburgh Sleep Quality Index, use of sleep medications, was related to BOLD responses in the dmPFC and dlPFC during cognitive reappraisal. Use of sleep medications predicted lesser BOLD responses during reappraisal, but other aspects of sleep, including sleep duration and subjective sleep quality, were not related to neural activation in this paradigm. Conclusions The relatively modest variability in sleep that is common in the general community is unlikely to cause significant disruption in neural circuits supporting reactivity or regulation by cognitive reappraisal of negative emotion. Use of sleep medication however, may influence emotion regulation circuitry, but additional studies are necessary to determine if such use plays a causal role in altering emotional responses.

  8. Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area During Withdrawal from Chronic Morphine.

    Science.gov (United States)

    Taylor, Anna M W; Castonguay, Annie; Ghogha, Atefeh; Vayssiere, Pia; Pradhan, Amynah A A; Xue, Lihua; Mehrabani, Sadaf; Wu, Juli; Levitt, Pat; Olmstead, Mary C; De Koninck, Yves; Evans, Christopher J; Cahill, Catherine M

    2016-03-01

    Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing to addictive behaviors and risk of relapse. The current study presents a neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic circuitry that contributes to impaired reward behavior. Opioid dependence was induced in rodents by treatment with escalating doses of morphine. Microglial activation was observed in the VTA following spontaneous withdrawal from chronic morphine treatment. Opioid-induced microglial activation resulted in an increase in brain-derived neurotrophic factor (BDNF) expression and a reduction in the expression and function of the K(+)Cl(-) co-transporter KCC2 within VTA GABAergic neurons. Inhibition of microglial activation or interfering with BDNF signaling prevented the loss of Cl(-) extrusion capacity and restored the rewarding effects of cocaine in opioid-dependent animals. Consistent with a microglial-derived BDNF-induced disruption of reward, intra-VTA injection of BDNF or a KCC2 inhibitor resulted in a loss of cocaine-induced place preference in opioid-naïve animals. The loss of the extracellular Cl(-) gradient undermines GABAA-mediated inhibition, and represents a mechanism by which chronic opioid treatments can result in blunted reward circuitry. This study directly implicates microglial-derived BDNF as a negative regulator of reward in opioid-dependent states, identifying new therapeutic targets for opiate addictive behaviors. PMID:26202104

  9. Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area During Withdrawal from Chronic Morphine

    Science.gov (United States)

    Taylor, Anna M W; Castonguay, Annie; Ghogha, Atefeh; Vayssiere, Pia; Pradhan, Amynah A A; Xue, Lihua; Mehrabani, Sadaf; Wu, Juli; Levitt, Pat; Olmstead, Mary C; De Koninck, Yves; Evans, Christopher J; Cahill, Catherine M

    2016-01-01

    Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing to addictive behaviors and risk of relapse. The current study presents a neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic circuitry that contributes to impaired reward behavior. Opioid dependence was induced in rodents by treatment with escalating doses of morphine. Microglial activation was observed in the VTA following spontaneous withdrawal from chronic morphine treatment. Opioid-induced microglial activation resulted in an increase in brain-derived neurotrophic factor (BDNF) expression and a reduction in the expression and function of the K+Cl− co-transporter KCC2 within VTA GABAergic neurons. Inhibition of microglial activation or interfering with BDNF signaling prevented the loss of Cl− extrusion capacity and restored the rewarding effects of cocaine in opioid-dependent animals. Consistent with a microglial-derived BDNF-induced disruption of reward, intra-VTA injection of BDNF or a KCC2 inhibitor resulted in a loss of cocaine-induced place preference in opioid-naïve animals. The loss of the extracellular Cl− gradient undermines GABAA-mediated inhibition, and represents a mechanism by which chronic opioid treatments can result in blunted reward circuitry. This study directly implicates microglial-derived BDNF as a negative regulator of reward in opioid-dependent states, identifying new therapeutic targets for opiate addictive behaviors. PMID:26202104

  10. Using aeroelastic structures with nonlinear switching electronics to increase potential energy yield in airflow: investigating analog control circuitry for automated peak detection

    Science.gov (United States)

    Mihalca, Alexander G.; Drosinos, Jonathan G.; Grayson, Malika; Garcia, Ephrahim

    2015-03-01

    Bending piezoelectric transducers have the ability to harvest energy from aeroelastic vibrations induced by the ambient airflow. Such harvesters can have useful applications in the operation of low power devices, and their relatively small size makes them ideal for use in urban environments over civil infrastructure. One of the areas of focus regarding piezoelectric energy harvesting is the circuit topology used to store the harvested power. This study aims to further investigate the increase in potential energy yield from the piezoelectric harvester by optimizing the circuitry connecting the piezoelectric transducer and the power storage interface. When compared to an optimal resistive load case, it has been shown that certain circuit topologies, specifically synchronized switching and discharging to a storage capacitor through an inductor (SSDCI), can increase the charging power by as much as 400% if the circuit is completely lossless. This paper proposes a strategy for making a self-sufficient SSDCI circuit capable of peak detection for the synchronized switching using analog components. Using circuit simulation software, the performance of this proposed self-sufficient circuit is compared to an ideal case, and the effectiveness of the self-sufficient circuit strategy is discussed based on these simulation results. Further investigation of a physical working model of the new circuit proposal will be developed and experimental results of the circuit's performance obtained and compared to the estimated performance from the model.

  11. The neural circuitry supporting goal maintenance during cognitive control: a comparison of expectancy AX-CPT and dot probe expectancy paradigms.

    Science.gov (United States)

    Lopez-Garcia, Pilar; Lesh, Tyler A; Salo, Taylor; Barch, Deanna M; MacDonald, Angus W; Gold, James M; Ragland, J Daniel; Strauss, Milton; Silverstein, Steven M; Carter, Cameron S

    2016-02-01

    Goal maintenance is an aspect of cognitive control that has been identified as critical for understanding psychopathology according to criteria of the NIMH-sponsored CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) and Research Domain Criteria (RDoC) initiatives. CNTRICS proposed the expectancy AX-CPT, and its visual-spatial parallel the dot probe expectancy (DPX), as valid measures of the cognitive and neural processes thought to be relevant for goal maintenance. The goal of this study was to specifically examine the functional neural correlates and connectivity patterns of both goal maintenance tasks in the same subset of subjects to further validate their neural construct validity and clarify our understanding of the nature and function of the neural circuitry engaged by the tasks. Twenty-six healthy control subjects performed both the letter (AX) and dot pattern (DPX) variants of the CPT during fMRI. Behavioral performance was similar between tasks. The 2 tasks engaged the same brain networks including dorsolateral prefrontal cortex (DLPFC) and dorsal parietal regions, supporting their validity as complementary measures of the goal maintenance construct. Interestingly there was greater engagement of the frontal opercular insula region during the expectancy AX-CPT (letter) and greater functional connectivity between the PFC and medial temporal lobe in the DPX (dot pattern). These differences are consistent with differential recruitment of phonological and visual-spatial processes by the two tasks and suggest that additional long-term memory systems may be engaged by the dot probe version. PMID:26494483

  12. PREVALENCE OF IMPAIRED GLUCOSE REGULATION IN THE POPULATION OF TIANJIN

    Institute of Scientific and Technical Information of China (English)

    Xin-yue Zhi; Jian-hua Wang

    2008-01-01

    Objective To investigate the prevalence of impaired glucose regulation (IGR) in the population of Tianjin.Methods A cross-sectional study was conducted in Tianjin from June to September in 2005.The multi-phasic stratified cluster sampling method was adopted.Totally,21454 people were selected as survey sample.Information on risk factors was collected through face-to-face questionnaire interview.Fasting capillary whole blood glucose level and other clinical indexes were tested.Results The prevalence of impaired fasting glucose (IFG) in the population was 5.61% (5.32% in male,5.89% in female).The prevalence of impaired glucose tolerance (IGT) was 2.91% (2.59% in male,3.20% in female) in whole population,and the prevalence of female was significantly higher than that of male (P=0.04).The prevalences of IFG and IGT increased with the increasing of age.And the prevalences were also influenced by the profession,educational level,and income level.Conclusion The prevalences oflGT and IFG in Tianjin are similar to those in the other big cities of China.

  13. Telomerase Regulation

    OpenAIRE

    Cifuentes-Rojas, Catherine; Dorothy E Shippen

    2011-01-01

    The intimate connection between telomerase regulation and human disease is now well established. The molecular basis for telomerase regulation is highly complex and entails multiple layers of control. While the major target of enzyme regulation is the catalytic subunit TERT, the RNA subunit of telomerase is also implicated in telomerase control. In addition, alterations in gene dosage and alternative isoforms of core telomerase components have been described. Finally, telomerase localization,...

  14. Radiation regulation

    International Nuclear Information System (INIS)

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  15. Post-translational regulation of Oct4 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Jonathan P Saxe

    Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

  16. Neural stem cells and the regulation of adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Conover Joanne C

    2003-11-01

    Full Text Available Abstract Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ, which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis.

  17. Motor cortex-periaqueductal gray-spinal cord neuronal circuitry may involve in modulation of nociception: a virally mediated transsynaptic tracing study in spinally transected transgenic mouse model.

    Directory of Open Access Journals (Sweden)

    Da-Wei Ye

    Full Text Available Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R in the periaqueductal gray played an important role in neuropathic pain. This study was designed to assess whether MC4R signaling existed in motor cortex-periaqueductal gray-spinal cord neuronal circuitry modulated the activity of sympathetic pathway by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV-614 was injected into the left gastrocnemius muscle in adult male MC4R-green fluorescent protein (GFP transgenic mice (n = 15. After a survival time of 4-6 days, the mice (n = 5 were randomly assigned to humanely sacrifice, and spinal cords and brains were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the left gastrocnemius muscle were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML, periaqueductal gray and motor cortex. Our findings support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may participate in the modulation of the melanocortin-sympathetic signaling and contribute to the descending modulation of nociceptive transmission, suggesting that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may modulate the activity of sympathetic outflow sensitive to nociceptive signals.

  18. Reliability analysis and design guidelines for the 101SY VDTT vent header flow and dome/vent header pressure measurement trip circuitry. Final draft

    International Nuclear Information System (INIS)

    SEA has performed a reliability study and proposed design and operation guidelines in order to allow the VDTT flow circuit to be energized during 101SY mixing pump operation. The proposed/analyzed circuits are separate and independent from the DACS circuitry, with the possible exception of sharing common sensors, signal splatters, and power supplies. In addition, SEA has studied and modeled the probability of a wasteberg impact with the VDTT given random probability distributions of both the center of mass of the berg, as well as the location of the burp. Depending upon the method used to evaluate (numerical integration or Monte Carlo sampling), the numbers range from 0.04 to 0.07. As a result, the most conservative number, 0.07 was used. Details of the calculations are included as Appendix A in this report. The proposed circuit design in its analyzed configuration considered independent inputs from 2 separate vent header flow sensors, the single dome pressure sensor, and a single vent header pressure sensor. This results in a total of 4 independent inputs which utilize a differentiator to sense increases or decreases in pressure or flows. A simplified block diagram of the proposed circuit is included as part this report. In addition, the fault trees, significant event data quantification, failure to trip VDTT circuit event tree, and resulting dominant cutsets are included. Our results indicate that the conditional point estimate probability of failure to interrupt power to the VDTT flow circuit using the above defined circuit is 1.4 x 10-4. This quantification is based upon a single 4 hour operation of the pump in a 24 hour period

  19. Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry

    Directory of Open Access Journals (Sweden)

    Lebron-Milad Kelimer

    2012-04-01

    Full Text Available Abstract Background The amygdala, hippocampus, medial prefrontal cortex (mPFC and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI to investigate sex differences in brain activity in these regions during fear conditioning and extinction. Methods Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear conditioning and extinction learning occurred on day 1 and extinction recall occurred on day 2. The conditioned stimuli were visual cues and the unconditioned stimulus was a mild electric shock. Skin conductance responses (SCR were recorded throughout the experiment as an index of the conditioned response. fMRI data (blood-oxygen-level-dependent [BOLD] signal changes were analyzed using SPM8. Results Findings showed no significant sex differences in SCR during any experimental phases. However, during fear conditioning, there were significantly greater BOLD-signal changes in the right amygdala, right rostral anterior cingulate (rACC and dorsal anterior cingulate cortex (dACC in women compared with men. In contrast, men showed significantly greater signal changes in bilateral rACC during extinction recall. Conclusions These results indicate sex differences in brain activation within the fear circuitry of healthy subjects despite similar peripheral autonomic responses. Furthermore, we found that regions where sex differences were previously reported in response to stress, also exhibited sex differences during fear conditioning and extinction.

  20. The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation

    OpenAIRE

    Rosa, A.; Ballarino, M.; Sorrentino, A; Sthandier, O.; De Angelis, F. G.; Marchioni, M; Masella, B; Guarini, A.; Fatica, A.; Peschle, C; Bozzoni, I

    2007-01-01

    We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease i...

  1. Addiction: Beyond dopamine reward circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  2. Peripheral Neural Circuitry in Cough

    OpenAIRE

    Taylor-Clark, Thomas E

    2015-01-01

    Cough is a reflex that serves to protect the airways. Excessive or chronic coughing is a major health issue that is poorly controlled by current therapeutics. Significant effort has been made to understand the mechanisms underlying the cough reflex. The focus of this review is the evidence supporting the role of specific airway sensory nerve (afferent) populations in the initiation and modulation of the cough reflex in health and disease.

  3. Dopaminergic Circuitry Underlying Mating Drive.

    Science.gov (United States)

    Zhang, Stephen X; Rogulja, Dragana; Crickmore, Michael A

    2016-07-01

    We develop a new system for studying how innate drives are tuned to reflect current physiological needs and capacities, and how they affect sensory-motor processing. We demonstrate the existence of male mating drive in Drosophila, which is transiently and cumulatively reduced as reproductive capacity is depleted by copulations. Dopaminergic activity in the anterior of the superior medial protocerebrum (SMPa) is also transiently and cumulatively reduced in response to matings and serves as a functional neuronal correlate of mating drive. The dopamine signal is transmitted through the D1-like DopR2 receptor to P1 neurons, which also integrate sensory information relevant to the perception of females, and which project to courtship motor centers that initiate and maintain courtship behavior. Mating drive therefore converges with sensory information from the female at the point of transition to motor output, controlling the propensity of a sensory percept to trigger goal-directed behavior. PMID:27292538

  4. Addiction: Beyond dopamine reward circuitry

    International Nuclear Information System (INIS)

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  5. Transistor-based interface circuitry

    Science.gov (United States)

    Taubman, Matthew S.

    2007-02-13

    Among the embodiments of the present invention is an apparatus that includes a transistor, a servo device, and a current source. The servo device is operable to provide a common base mode of operation of the transistor by maintaining an approximately constant voltage level at the transistor base. The current source is operable to provide a bias current to the transistor. A first device provides an input signal to an electrical node positioned between the emitter of the transistor and the current source. A second device receives an output signal from the collector of the transistor.

  6. UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

    Science.gov (United States)

    Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

    2016-02-25

    The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. PMID:26919426

  7. Posttranscriptional regulation on a global scale: Form and function of Csr/Rsm systems

    OpenAIRE

    Romeo, Tony; Vakulskas, Christopher A.; Babitzke, Paul

    2012-01-01

    Originally described as a repressor of gene expression in the stationary phase of growth, CsrA (RsmA) regulates primary and secondary metabolic pathways, biofilm formation, motility, virulence circuitry of pathogens, quorum sensing, and stress response systems by binding to conserved sequences in its target mRNAs and altering their translation and/or turnover. While the binding of CsrA to RNA is understood at an atomic level, new mechanisms of gene activation and repression by this protein ar...

  8. NOISE REGULATION

    OpenAIRE

    Cristina Voican; Constantin Stanescu

    2012-01-01

    Noise regulation includes statutes or guidelines relating to sound transmission established by national, state or provincial and municipal levels of government. After the watershed passage of the United States Noise Control Act of 1972, other local and state governments passed further regulations. Although the UK and Japan enacted national laws in 1960 and 1967 respectively, these laws were not at all comprehensive or fully enforceable as to address generally rising ambient noise, enforceable...

  9. Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control.

    Science.gov (United States)

    Feil, Jodie; Sheppard, Dianne; Fitzgerald, Paul B; Yücel, Murat; Lubman, Dan I; Bradshaw, John L

    2010-11-01

    A principal feature of drug addiction is a reduced ability to regulate control over the desire to procure drugs regardless of the risks involved. Traditional models implicated the neural 'reward' system in providing a neurobiological model of addiction. Newer models however, have expanded on this circuitry to include two separate, but interconnecting systems, the limbic system in the incentive sensitization of drugs, and the prefrontal cortex (PFC) in regulating inhibitory control over drug use. Until the recent developments in neuroimaging and brain stimulation techniques, it has been extremely difficult to assess the involvement of the PFC in addiction. In the current review, we explore the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggest how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use. Following this, we investigate the recent neuropsychological, neuroimaging and brain stimulation studies that explore the presence of these inhibitory deficits, and frontostriatal dysfunctions, across various different substance groups. Further insight into these deficits could contribute to the development of treatment strategies which target these cognitive impairments, and frontostriatal dysfunction, in reducing drug-seeking behaviors. PMID:20223263

  10. Nicotine regulates cocaine-amphetamine-Regulated Transcript (Cart) in the mesocorticolimbic system.

    Science.gov (United States)

    Kaya, Egemen; Gozen, Oguz; Ugur, Muzeyyen; Koylu, Ersin O; Kanit, Lutfiye; Balkan, Burcu

    2016-07-01

    Cocaine-and-Amphetamine Regulated Transcript (CART) mRNA and peptides are intensely expressed in the brain regions comprising mesocorticolimbic system. Studies suggest that CART peptides may have a role in the regulation of reward circuitry. The present study aimed to examine the effect of nicotine on CART expression in the mesocorticolimbic system. Three different doses of nicotine (0.2, 0.4, 0.6 mg/kg free base) were injected subcutaneously for 5 days, and on day 6, rats were decapitated following a challenge dose. CART mRNA and peptide levels in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (DST), amygdala (AMG), lateral hypothalamic area (LHA), and ventral tegmental area (VTA) were measured by quantitative real-time PCR (qPCR) and Western Blot analysis, respectively. In the mPFC, 0.4 and 0.6 mg/kg nicotine, decreased CART peptide levels whereas there was no effect on CART mRNA levels. In the VTA, a down-regulation of CART peptide expression was observed with 0.2 and 0.6 mg/kg nicotine. Conversely, 0.4 and 0.6 mg/kg nicotine increased CART mRNA levels in the AMG without affecting the CART peptide expression. Nicotine did not regulate CART mRNA or CART peptide expression in the NAc, DST, and LHA. We conclude that nicotine regulates CART expression in the mesocorticolimbic system and this regulation may play an important role in nicotine reward. Synapse 70:283-292, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990424

  11. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  12. Wnt signaling in the regulation of adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Lorena eVarela-Nallar

    2013-06-01

    Full Text Available In the adult brain new neurons are continuously generated mainly in two regions, the subventricular zone of the lateral ventricles and the subgranular zone (SGZ in the hippocampal dentate gyrus. In the SGZ, radial neural stem cells give rise to granule cells that integrate into the hippocampal circuitry and are relevant for the plasticity of the hippocampus. Loss of neurogenesis impairs learning and memory, suggesting that this process is important for adult hippocampal function. Adult neurogenesis is tightly regulated by multiple signaling pathways, including the canonical Wnt/beta-catenin pathway. This pathway plays important roles during the development of neuronal circuits and in the adult brain it modulates synaptic transmission and plasticity. Here, we review current knowledge on the regulation of adult hippocampal neurogenesis by the Wnt/beta-catenin signaling cascade and the potential mechanisms involved in this regulation. Also we discuss the evidence supporting that the canonical Wnt pathway is part of the signaling mechanisms involved in the regulation of neurogenesis in different physiological conditions. Finally, some unsolved questions regarding the Wnt-mediated regulation of neurogenesis are discussed.

  13. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog

  14. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-Zhong; Ai, Zhi-Ying [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Wang, Zhi-Wei [School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027 (China); Chen, Lin-Lin [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Guo, Ze-Kun, E-mail: gzknwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Zhang, Yong, E-mail: zylabnwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China)

    2015-09-25

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.

  15. Dynamic Transcriptional and Epigenetic Regulation of Human Epidermal Keratinocyte Differentiation.

    Science.gov (United States)

    Cavazza, Alessia; Miccio, Annarita; Romano, Oriana; Petiti, Luca; Malagoli Tagliazucchi, Guidantonio; Peano, Clelia; Severgnini, Marco; Rizzi, Ermanno; De Bellis, Gianluca; Bicciato, Silvio; Mavilio, Fulvio

    2016-04-12

    Human skin is maintained by the differentiation and maturation of interfollicular stem and progenitors cells. We used DeepCAGE, genome-wide profiling of histone modifications and retroviral integration analysis, to map transcripts, promoters, enhancers, and super-enhancers (SEs) in prospectively isolated keratinocytes and transit-amplifying progenitors, and retrospectively defined keratinocyte stem cells. We show that >95% of the active promoters are in common and differentially regulated in progenitors and differentiated keratinocytes, while approximately half of the enhancers and SEs are stage specific and account for most of the epigenetic changes occurring during differentiation. Transcription factor (TF) motif identification and correlation with TF binding site maps allowed the identification of TF circuitries acting on enhancers and SEs during differentiation. Overall, our study provides a broad, genome-wide description of chromatin dynamics and differential enhancer and promoter usage during epithelial differentiation, and describes a novel approach to identify active regulatory elements in rare stem cell populations. PMID:27050947

  16. Evidence for dynamic network regulation of Drosophila photoreceptor function from mutants lacking the neurotransmitter histamine

    Directory of Open Access Journals (Sweden)

    An eDau

    2016-03-01

    Full Text Available Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdcJK910 mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdcJK910 photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdcJK910 photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdcJK910 R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdcJK910 mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons.

  17. Evidence for Dynamic Network Regulation of Drosophila Photoreceptor Function from Mutants Lacking the Neurotransmitter Histamine.

    Science.gov (United States)

    Dau, An; Friederich, Uwe; Dongre, Sidhartha; Li, Xiaofeng; Bollepalli, Murali K; Hardie, Roger C; Juusola, Mikko

    2016-01-01

    Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdc (JK910) mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdc (JK910) photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdc (JK910) photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdc (JK910) R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdc (JK910) mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons. PMID:27047343

  18. Low stored energy 100 kV regulator for ion sources at LANSCE

    International Nuclear Information System (INIS)

    To minimize accelerating column damage caused by uncontrolled energy release during arc-downs, it is desirable to minimize the available stored electrical energy. For the Los Alamos Neutron Science Center (LANSCE) H- ion sources, the stored energy includes, in addition to the charge in the power supply output capacitance, the charge on the electronics racks. They are supported and insulated from ground by PVC pipe and have a capacitance to ground of approximately 900 pf. In 1988 (LANSCE) personnel designed a high-voltage current source using a low-stored-energy power supply and planar triode with the goal of eliminating uncontrolled release of charge stored in the power supply. Construction and testing were performed intermittently as resources permitted until 1993. When work on the Short Pulse Spallation Source (SPSS) started on the LANSCE Ion Source Test Stand (ISTS) it was recognized that a higher current power supply would be needed and work resumed on the regulator circuitry. A 120 kV power supply having low output capacitance, and a planar triode have been used to supply 40 mA, 120 Hz, 12% duty-factor current for the ISTS beam. The triode's cathode current is controlled by circuitry operating both at power-supply voltage level and at ground level via a fiber optic link. Voltage droop is approximately 600 V during the 1 ms beam pulse. The authors present the status of the regulator and its special challenges

  19. Easy to remember, difficult to forget: The development of fear regulation

    Directory of Open Access Journals (Sweden)

    D.C. Johnson

    2015-02-01

    Full Text Available Fear extinction learning is a highly adaptive process that involves the integrity of frontolimbic circuitry. Its disruption has been associated with emotional dysregulation in stress and anxiety disorders. In this article we consider how age, genetics and experiences shape our capacity to regulate fear in cross-species studies. Evidence for adolescent-specific diminished fear extinction learning is presented in the context of immature frontolimbic circuitry. We also present evidence for less neural plasticity in fear regulation as a function of early-life stress and by genotype, focusing on the common brain derived neurotrophin factor (BDNF Val66Met polymorphism. Finally, we discuss this work in the context of exposure-based behavioral therapies for the treatment of anxiety and stress disorders that are based on principles of fear extinction. We conclude by speculating on how such therapies may be optimized for the individual based on the patient's age, genetic profile and personal history to move from standard treatment of care to personalized and precision medicine.

  20. Action Regulation Introducing Stress Management Techniques and High Performance in Soccer

    Directory of Open Access Journals (Sweden)

    Saha Soumendra

    2015-01-01

    Full Text Available Fifty-two high performing soccer players of South-East Asian contingent were selected by three expert soccer instructors on the basis of their consistent high performance and on the basis of their performance on psychomotor and psychobiological parameters. All of these players were subjected to pre-intervention analyses of Sc orienting reflex indices (phasic components of electrodermal activity as well as sympathovagal activity based on HRV indices which were assessed simultaneously while the players were engaged in psychomotor reaction ability performances. Structural equations were done to identify the path regression related to performance excellence, which were suggestive of incoherence between the predictors. Short-term intensive self-regulation as well as action-regulation training modules was developed to foster ideomotor orientation in the players, which however was found effective in modification of the intrinsic psychobiological mechanism leading towards excellence in performance in the high-performer soccer players. Thus they were randomly categorised into four groups, comprising of one no-intervention control group (N = 13; experimental group I (N = 13 who received action-regulation training; experimental group II (N = 13, who received training of electromyography (EMG biofeedback, and experimental group III (N = 13, who received combined training of action - regulation and electromyography (EMG biofeedback (for 15 min.s/day, for 3 days per week, for 12 weeks. Repeated measure of ANOVA and multiple linear and polynomial regression analyses along with the predictive structural analyses were done to identify relationships between the psychobiological processes, in relation to the cognitive-affective and affective-motivational aspects of sports behaviour, revealed by the projective analyses of emotionality. These models were aptly able to explain the efficacy of the action-regulation intervention techniques, in inducing the cognitive

  1. RegulatING chromatin regulators

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Nabbi, Arash; Riabowol, Karl

    2013-01-01

    The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on...... the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine...... stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes...

  2. Cognitive Enhancement Therapy Improves Frontolimbic Regulation of Emotion in Alcohol and/or Cannabis Misusing Schizophrenia: A Preliminary Study.

    Science.gov (United States)

    Wojtalik, Jessica A; Hogarty, Susan S; Cornelius, Jack R; Phillips, Mary L; Keshavan, Matcheri S; Newhill, Christina E; Eack, Shaun M

    2015-01-01

    Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive enhancement therapy (CET) may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10) or usual care (n = 4) completed posttreatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic, and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in frontolimbic and striatal circuitries, which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems. PMID:26793128

  3. Cognitive Enhancement Therapy Improves Frontolimbic Regulation of Emotion in Alcohol and/or Cannabis Misusing Schizophrenia: A Preliminary Study

    Science.gov (United States)

    Wojtalik, Jessica A.; Hogarty, Susan S.; Cornelius, Jack R.; Phillips, Mary L.; Keshavan, Matcheri S.; Newhill, Christina E.; Eack, Shaun M.

    2016-01-01

    Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive enhancement therapy (CET) may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10) or usual care (n = 4) completed posttreatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic, and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in frontolimbic and striatal circuitries, which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems. PMID:26793128

  4. Nuclear regulation

    International Nuclear Information System (INIS)

    Today, 112 nuclear power plants, 22 facilities that support these plants, 54 reactors used in research, and approximately 23,000 organizations hold licenses from either the Nuclear Regulator Commission or various states to use radioactive material; other facilities are operated by various government agencies. Eventually most of these facilities will be decommissioned, which involves removing the radioactive material and terminating the license. NRC needs to ensure that licensees appropriately decontaminate their facilities because, under current regulations, NRC cannot specifically require additional cleanup once it terminates a license. This paper presents a GAO report on NRC's decommissioning procedures. In two of eight cases GAO reviewed, NRC fully or partially released sites for unrestricted use where radioactive contamination was higher than its guidelines allowed; in the other cases, NRC's information was inadequate or incomplete. Further, NRC lacks information on the types and amounts of radioactive waste buried on-site. At five sites reviewed by GAO, groundwater has been found to be contaminated by radioactive waste

  5. Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

    Science.gov (United States)

    Bracha, H Stefan

    2006-07-01

    The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing

  6. Regulation of bacterial virulence by Csr (Rsm) systems.

    Science.gov (United States)

    Vakulskas, Christopher A; Potts, Anastasia H; Babitzke, Paul; Ahmer, Brian M M; Romeo, Tony

    2015-06-01

    Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5' untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens. PMID:25833324

  7. Age-related changes in the structure and function of prefrontal cortex-amygdala circuitry in children and adolescents: a multi-modal imaging approach.

    Science.gov (United States)

    Swartz, Johnna R; Carrasco, Melisa; Wiggins, Jillian Lee; Thomason, Moriah E; Monk, Christopher S

    2014-02-01

    The uncinate fasciculus is a major white matter tract that provides a crucial link between areas of the human brain that underlie emotion processing and regulation. Specifically, the uncinate fasciculus is the major direct fiber tract that connects the prefrontal cortex and the amygdala. The aim of the present study was to use a multi-modal imaging approach in order to simultaneously examine the relation between structural connectivity of the uncinate fasciculus and functional activation of the amygdala in a youth sample (children and adolescents). Participants were 9 to 19years old and underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). Results indicate that greater structural connectivity of the uncinate fasciculus predicts reduced amygdala activation to sad and happy faces. This effect is moderated by age, with younger participants exhibiting a stronger relation. Further, decreased amygdala activation to sad faces predicts lower internalizing symptoms. These results provide important insights into brain structure-function relationships during adolescence, and suggest that greater structural connectivity of the uncinate fasciculus may facilitate regulation of the amygdala, particularly during early adolescence. These findings also have implications for understanding the relation between brain structure, function, and the development of emotion regulation difficulties, such as internalizing symptoms. PMID:23959199

  8. High content image analysis identifies novel regulators of synaptogenesis in a high-throughput RNAi screen of primary neurons.

    Directory of Open Access Journals (Sweden)

    Thomas J F Nieland

    Full Text Available The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.

  9. Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems.

    Science.gov (United States)

    Romeo, Tony; Vakulskas, Christopher A; Babitzke, Paul

    2013-02-01

    Originally described as a repressor of gene expression in the stationary phase of growth, CsrA (RsmA) regulates primary and secondary metabolic pathways, biofilm formation, motility, virulence circuitry of pathogens, quorum sensing and stress response systems by binding to conserved sequences in its target mRNAs and altering their translation and/or turnover. While the binding of CsrA to RNA is understood at an atomic level, new mechanisms of gene activation and repression by this protein are still emerging. In the γ-proteobacteria, small non-coding RNAs (sRNAs) use molecular mimicry to sequester multiple CsrA dimers away from mRNA. In contrast, the FliW protein of Bacillus subtilis inhibits CsrA activity by binding to this protein, thereby establishing a checkpoint in flagellum morphogenesis. Turnover of CsrB and CsrC sRNAs in Escherichia coli requires a specificity protein of the GGDEF-EAL domain superfamily, CsrD, in addition to the housekeeping nucleases RNase E and PNPase. The Csr system of E. coli contains extensive autoregulatory circuitry, which governs the expression and activity of CsrA. Interaction of the Csr system with transcriptional regulatory networks results in a variety of complex response patterns. This minireview will highlight basic principles and new insights into the workings of these complex eubacterial regulatory systems. PMID:22672726

  10. Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system.

    Science.gov (United States)

    Morale, M C; Gallo, F; Tirolo, C; Testa, N; Caniglia, S; Marletta, N; Spina-Purrello, V; Avola, R; Caucci, F; Tomasi, P; Delitala, G; Barden, N; Marchetti, B

    2001-08-01

    Bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life. Signals generated by the hypothalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the development of immune system function. Conversely, products generated by immune system activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to preperinatal experiences, including hormonal manipulations and immune challenges, which may influence the future predisposition to several disease entities. We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the central nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate major changes in response to hormonal manipulations and pro-inflammatory triggers. The interplay between LHRH, sex steroids, GC and pro-inflammatory mediators in some physiological and pathological states, together with the potential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmacological targeting with drugs acting at the neuroendocrine-immune interface. PMID:11488988

  11. Protein kinase C regulates tonic GABAA receptor-mediated inhibition in the hippocampus and thalamus

    Science.gov (United States)

    Bright, Damian P; Smart, Trevor G

    2013-01-01

    Tonic inhibition mediated by extrasynaptic GABAA receptors (GABAARs) is an important regulator of neuronal excitability. Phosphorylation by protein kinase C (PKC) provides a key mode of regulation for synaptic GABAARs underlying phasic inhibition; however, less attention has been focused on the plasticity of tonic inhibition and whether this can also be modulated by receptor phosphorylation. To address this issue, we used whole-cell patch clamp recording in acute murine brain slices at both room and physiological temperatures to examine the effects of PKC-mediated phosphorylation on tonic inhibition. Recordings from dentate gyrus granule cells in the hippocampus and dorsal lateral geniculate relay neurons in the thalamus demonstrated that PKC activation caused downregulation of tonic GABAAR-mediated inhibition. Conversely, inhibition of PKC resulted in an increase in tonic GABAAR activity. These findings were corroborated by experiments on human embryonic kidney 293 cells expressing recombinant α4β2δ GABAARs, which represent a key extrasynaptic GABAAR isoform in the hippocampus and thalamus. Using bath application of low GABA concentrations to mimic activation by ambient neurotransmitter, we demonstrated a similar inhibition of receptor function following PKC activation at physiological temperature. Live cell imaging revealed that this was correlated with a loss of cell surface GABAARs. The inhibitory effects of PKC activation on α4β2δ GABAAR activity appeared to be mediated by direct phosphorylation at a previously identified site on the β2 subunit, serine 410. These results indicate that PKC-mediated phosphorylation can be an important physiological regulator of tonic GABAAR-mediated inhibition. PMID:24102973

  12. Mutually repressing repressor functions and multi-layered cellular heterogeneity regulate the bistable Salmonella fliC census

    Science.gov (United States)

    Stewart, Mary K.; Cookson, Brad T.

    2014-01-01

    Summary Bistable flagellar and virulence gene expression generates specialized Salmonella subpopulations with distinct functions. Repressing flagellar genes allows Salmonella to evade caspase-1 mediated host defenses and enhances systemic colonization. By definition, bistability arises when intermediate states of gene expression are rendered unstable by the underlying genetic circuitry. We demonstrate sustained bistable fliC expression in virulent Salmonella 14028 and document dynamic control of the distribution, or single-cell census, of flagellar gene expression by the mutually repressing repressors YdiV and FliZ. YdiV partitions cells into the fliC-OFF subpopulation, while FliZ partitions cells into the fliC-HIGH subpopulation at late timepoints during growth. Bistability of ΔfliZ populations and ydiV-independent FliZ control of flagellar gene expression provide evidence that the YdiV-FliZ mutually repressing repressor circuit is not required for bistability. Repression and activation by YdiV and FliZ (respectively) can shape the census of fliC expression independently, and bistability collapses into a predominantly intermediate population in the absence of both regulators. Metered expression of YdiV and FliZ reveals variable sensitivity to these regulators and defines conditions where expression of FliZ enhances fliC expression and where FliZ does not alter the fliC census. Thus, this evolved genetic circuitry coordinates multiple layers of regulatory heterogeneity into a binary response. PMID:25315056

  13. Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jessica Ann Wojtalik

    2016-01-01

    Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

  14. Optical suppression of drug-evoked phasic dopamine release

    Directory of Open Access Journals (Sweden)

    James Edgar Mccutcheon

    2014-09-01

    Full Text Available Brief fluctuations in dopamine concentration (dopamine transients play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc of urethane-anesthetized rats. We targeted halorhodopsin (NpHR specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre+ rats. Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior.

  15. Covariation of phasic cortical and cardiovascular responses: Effects of alertness

    NARCIS (Netherlands)

    F.M. van der Veen; L.J.M. Mulder; G. Mulder

    1999-01-01

    Effects of maintaining an alert state on event-related brain potentials (ERPs) and evoked cardiovascular responses were examined in an auditory detection task. Subjects were instructed to detect a possible difference in frequency between two successively presented tones in 5 s periods. Two types of

  16. Adjustment of RVA-62 automatic field-current regulator

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, A.A.; Karkazov, E.I.

    1985-08-01

    While the RVA-62 automatic field-current regulator performs adequately with small and medium-size turbogenerators, its stability margin being often sufficiently large to compensate design inaccuracies, a refinement is nevertheless recommended to ensure reliability under no-load as well as during parallel operation of generators into a common busbar group. The procedure is based on necessary adjustments of over 40 units and applies to redesign, measurements, breadboard simulation, settings, reassembly, and testing. First it is necessary to determine the correct number of primary and secondary turns in the universal controlled phase-compounding transformer, taking into account the parameters of associated equipment (autotransformer, filter choke, power rectifier, current transformer) as well as various modes of generator instability and the use of automatic field suppression. Revisions in testing circuitry and procedure are proposed, including more precise and some extra measurements, also replacement of selenium rectifiers with silicon diodes. Adjustments according to this scheme have been made in the RVA-62 regulators for 6-60 kW generators with VT exciters and 3000-12,000 kW generators, including Skoda, Siemens-Schuckert GmbH, Parsons Ltd units.

  17. 基于 P-Type 多晶硅TFT技术的集成型有源 OLED 驱动电路%An Integrated Driving Circuitry by Employing P-Type Poly-Si TFTs for AMOIED

    Institute of Scientific and Technical Information of China (English)

    丁媛媛; 司玉娟; 郎六琪

    2008-01-01

    Low-temperature poly-Si (LTPS) is becoming an attracted technology for the fabrication of thin film transistors (TFTs) used in active matrix organic light emissive displays (AMOLED). Because the TFT fabrication process can be simplified by p-type technology, an integrated driving circuitry employing only p-type poly-Si TFTs for AMOLED is proposed, including gate driver, data sampling driver and pixel array. The output pads of the panel are largely decreased by using a block sequential method. An improved p-type shift register is proposed to realize line-by-line selection. And a buffer which is made up of four p-type inverters is used to enhance the driving capability of the circuitry. In order to verify the validity of the proposed scheme, circuit simulation using HSPICE has been done. The simulation result indicated that the circuitry worked welL Utilizing the advantage of Korea Seoul National University and Neo Poly Inc on making poly-Si TFT,we have already fabricated 96×3×128 AMOLED using the design above.%低温多晶硅(LTPS:Low-temperature poly-Si)技术已经成为薄膜晶体管(TFT:thin film transistor)制作中最具吸引力的技术,并应用在AMOLED显示器中.P-type 技术能够简化 TFT 的制作过程.本文提出了一种应用 p-type 多晶硅 TFT的 AMOLED 驱动电路结构,包括栅极驱动器、数据驱动器以及像素阵列.数据驱动器采用分块方法,使得显示屏的输出线数大大减少.作者采用一种改进的 p-type 移位寄存器实现逐行选通的功能,并采用由 4 个 p-type 反相器级联构成的缓冲器来提高电路的驱动能力.为了验证上述电路结构的正确性,作者采用 HSPICE 软件进行仿真分析.结果表明,电路工作正常.利用韩国汉城国立大学及 Neo Poly 公司在多晶硅制作方面的优势,我们已经合作完成了应用上述电路结构的分辨率为96×3×128的有源 OLED 的制作.

  18. Neuroimaging brainstem circuitry supporting cardiovagal response to pain: a combined heart rate variability/ultrahigh-field (7 T) functional magnetic resonance imaging study.

    Science.gov (United States)

    Sclocco, Roberta; Beissner, Florian; Desbordes, Gaelle; Polimeni, Jonathan R; Wald, Lawrence L; Kettner, Norman W; Kim, Jieun; Garcia, Ronald G; Renvall, Ville; Bianchi, Anna M; Cerutti, Sergio; Napadow, Vitaly; Barbieri, Riccardo

    2016-05-13

    Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2 min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain. PMID:27044996

  19. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS: a commentary

    Directory of Open Access Journals (Sweden)

    Waite Roger L

    2008-11-01

    Full Text Available Abstract Background and hypothesis Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc dopamine receptors (D1-D5, whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing

  20. Regulations and instructions

    International Nuclear Information System (INIS)

    Regulations and instructions for operating the RA reactor consist of the following chapters: general regulations with the fundamental RA reactor characteristics, operating regulations and instructions for the personnel on duty, regulations for accidental conditions, training program for the staff of the Laboratory for reactor operation

  1. Regulating Rho GTPases and their regulators.

    Science.gov (United States)

    Hodge, Richard G; Ridley, Anne J

    2016-08-01

    Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases. PMID:27301673

  2. Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions

    Directory of Open Access Journals (Sweden)

    Alexis M. Stranahan

    2012-01-01

    Full Text Available The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db and nondiabetic wild-type (C57/Bl/6 animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds.

  3. Sensory integration regulating male courtship behavior in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dimitrije Krstic

    Full Text Available The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i between initiation and maintenance of courtship, (ii between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior.

  4. The ERβ ligand 5α-androstane, 3β,17β-diol (3β-diol) regulates hypothalamic oxytocin (Oxt) gene expression.

    Science.gov (United States)

    Sharma, Dharmendra; Handa, Robert J; Uht, Rosalie M

    2012-05-01

    The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression. PMID:22434086

  5. Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder

    Science.gov (United States)

    Goodman, Marianne; Carpenter, David; Tang, Cheuk Y.; Goldstein, Kim E.; Avedon, Jennifer; Fernandez, Nicolas; Mascitelli, Kathryn A.; Blair, Nicholas J.; New, Antonia S.; Triebwasser, Joseph; Siever, Larry J.; Hazlett, Erin A.

    2014-01-01

    circuitry underlying emotional dysregulation in BPD. Future work includes examining how DBT-induced amygdala changes interact with frontal-lobe regions implicated in emotion regulation. PMID:25038629

  6. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  7. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  8. Regulation of Genetic Tests

    Science.gov (United States)

    ... advertised. The Commission has the authority to regulate advertising that delivers health-related information to consumers to ensure that it is not false or misleading. Top of page FDA Regulation and ...

  9. Activists versus Captured Regulators

    OpenAIRE

    Daubanes, Julien; Rochet, Jean-Charles

    2013-01-01

    We analyze the consequences of activism in a regulated industry where the regulator has been captured by the industry. Unlike ordinary economic agents, activists are insensitive to monetary incentives. Moreover, they are less well informed than regulators and their actions generate dead-weight costs. Yet we find that activism may increase social welfare because it disciplines captured regulators and reduces the social cost of imperfect regulatory systems.

  10. Hepcidin: regulation of the master iron regulator

    OpenAIRE

    2015-01-01

    Iron, an essential nutrient, is required for many diverse biological processes. The absence of a defined pathway to excrete excess iron makes it essential for the body to regulate the amount of iron absorbed; a deficiency could lead to iron deficiency and an excess to iron overload and associated disorders such as anaemia and haemochromatosis respectively. This regulation is mediated by the iron-regulatory hormone hepcidin. Hepcidin binds to the only known iron export protein, ferroportin (FP...

  11. Flexible Skins Containing Integrated Sensors and Circuitry

    Science.gov (United States)

    Liu, Chang

    2007-01-01

    Artificial sensor skins modeled partly in imitation of biological sensor skins are undergoing development. These sensor skins comprise flexible polymer substrates that contain and/or support dense one- and two-dimensional arrays of microscopic sensors and associated microelectronic circuits. They afford multiple tactile sensing modalities for measuring physical phenomena that can include contact forces; hardnesses, temperatures, and thermal conductivities of objects with which they are in contact; and pressures, shear stresses, and flow velocities in fluids. The sensor skins are mechanically robust, and, because of their flexibility, they can be readily attached to curved and possibly moving and flexing surfaces of robots, wind-tunnel models, and other objects that one might seek to equip for tactile sensing. Because of the diversity of actual and potential sensor-skin design criteria and designs and the complexity of the fabrication processes needed to realize the designs, it is not possible to describe the sensor-skin concept in detail within this article.

  12. Addiction circuitry in the human brain (*).

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  13. Addiction Circuitry in the Human Brain*

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo

    2011-01-01

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person’s risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circ...

  14. Neural circuitry for rat recognition memory

    Science.gov (United States)

    Warburton, E.C.; Brown, M.W.

    2015-01-01

    Information concerning the roles of different brain regions in recognition memory processes is reviewed. The review concentrates on findings from spontaneous recognition memory tasks performed by rats, including memory for single objects, locations, object–location associations and temporal order. Particular emphasis is given to the potential roles of different regions in the circuit of interacting structures involving the perirhinal cortex, hippocampus, medial prefrontal cortex and medial dorsal thalamus in recognition memory for the association of objects and places. It is concluded that while all structures in this circuit play roles critical to such memory, these roles can potentially be differentiated and differences in the underlying synaptic and biochemical processes involved in each region are beginning to be uncovered. PMID:25315129

  15. Adaptive Pulvinar Circuitry Supports Visual Cognition.

    Science.gov (United States)

    Bridge, Holly; Leopold, David A; Bourne, James A

    2016-02-01

    The pulvinar is the largest thalamic nucleus in primates and one of the most mysterious. Endeavors to understand its role in vision have focused on its abundant connections with the visual cortex. While its connectivity mapping in the cortex displays a broad topographic organization, its projections are also marked by considerable convergence and divergence. As a result, the pulvinar is often regarded as a central forebrain hub. Moreover, new evidence suggests that its comparatively modest input from structures such as the retina and superior colliculus may critically shape the functional organization of the visual cortex, particularly during early development. Here we review recent studies that cast fresh light on how the many convergent pathways through the pulvinar contribute to visual cognition. PMID:26553222

  16. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  17. Views of the regulators

    International Nuclear Information System (INIS)

    In dealing with a challenging problem in occupational exposure the nuclear regulator in South Africa concluded that the involvement of stake holders was critical. Valuable lessons were learnt in the process. These related to co-operation amongst regulators, the involvement of regulators in addressing occupational exposure problems, the training of workers by the regulator and the need for technical training of the workers. In general, it was also learnt that regulators should establish mechanisms to measure and continuously improve the satisfaction of their stake holders. (author)

  18. Neuropeptide Regulation of Appetite and Reproduction

    Directory of Open Access Journals (Sweden)

    Small CJ

    2004-01-01

    Full Text Available It is now recognised that appropriate regulation of reproduction, energy intake and energy expenditure, and thus maintenance of body weight and fertility, relies on complex hypothalamic neuro-circuitry. Feeding and reproductive function are closely linked. During times of under nourishment and falling body fat the reproductive axis is down regulated. Circulating factors and hypothalamic circuits co-ordinate these responses. Leptin has been described to be an important peripheral signal that indicates body fat stores to the hypothalamus and thus links nutrition and reproduction. Leptin acts by altering neuropeptide circuits in the hypothalamus, which alter gonadotrophin releasing hormone (GnRH release and food intake. The importance of key neuropeptide systems identified in rodents is now being established in man. Notably mutations in the melanocortin MC4 receptor are found in up to 4 % of the morbidly obese whilst in a proportion of patients with anorexia nervosa mutations have been identified in the agoutirelated peptide (AgRP gene, which codes for an endogenous antagonist of this receptor. Intranasal administration of a melanocortin fragment known to activate the MC4 receptor decreases adiposity in humans. The melanocortin system has been shown to influence the reproductive axis in rodents. However, the role of the melanocortin system in the control of reproduction in humans remains to be established. Since the discovery of leptin, attention has also been focused on peripheral signals that regulate reproduction, food intake and energy expenditure, either directly or via feedback on hypothalamic circuits. Notable new discoveries in this area include the gastric hormone ghrelin. Circulating ghrelin stimulates food intake in rodents and humans although an influence on the reproductive axis is yet to be reported. Neuropeptidregulation von Appetit und Reproduktion. Mittlerweile gilt es als anerkannt, daß eine entsprechende Regulation der

  19. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The Nuclear Safety Regulations for Nuclear Installations and Nuclear Safety Codes for Nuclear Pressure Retaining Components were issued by the NNSA in 1995. The Atomic Act and Regulations on the Safety Regulation for Transportation of Radioactive Materials have been finished and submitted to the State Council in 1995. At the same time the NNSA organized a revised collection of regulations on nuclear safety in both Chinese and English, titled 'The Collection of Regulations on Nuclear Safety of the People's Republic of China'. To enhance the implementation of newly issued nuclear safety regulations, the NNSA conducted seven times of propagating activities in relation to the regulations for nuclear pressure retaining components and research reactors design and operating in 1995

  20. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  1. The development of regulations

    International Nuclear Information System (INIS)

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

  2. Differential effects of a selective dopamine D1-like receptor agonist on motor activity and c-fos expression in the frontal-striatal circuitry of SHR and Wistar-Kyoto rats

    Directory of Open Access Journals (Sweden)

    Diaz Heijtz Rochellys

    2006-05-01

    . Conclusion The present results suggest a potential alteration in D1R neurotransmission within the frontal-striatal circuitry of SHR involved in motor control. These findings extend our understanding of the molecular alterations in SHR, a heuristically useful model of ADHD.

  3. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The enactment of nuclear safety regulations in 1996 is mainly focused on the preparation of related regulations, and safety guides for nuclear materials control, the reprocessing installations of spent fuels, the treatment and disposal for radioactive waste. The NNSA also assists the departments concerned of the State Council for modification on the 'Atomic Energy Act' (draft) and the' Regulations on the Safety Supervision and Control of Radioactive Materials Transportation' (draft)

  4. Attention in emotion regulation

    OpenAIRE

    Gelow, Stefan

    2013-01-01

    The concept of emotion and how to regulate it is a central aspect of modern psychology. Within the process model of emotion regulation (Gross, 1998), one issue is how attentional deployment affects emotion regulation and how this can be measured. In task 1, pictures of positive or negative valence were showed in two conditions, either attend or decrease emotional reaction, while participants’ eye movements were followed with an eye tracker. Ratings of arousal and valence were significantly af...

  5. Accounting Regulation in Ukraine

    OpenAIRE

    Hora, Michal; Chyzevska, Ludmila

    2013-01-01

    The aim of the paper is to evaluate the regulation and organization of accounting in Ukraine under the changes in the national economic system development and impact of IFRS implementation. The system of legal regulation of accounting in Ukraine is presented by five levels, each comprised of a number of corresponding subjects of regulation and documents. Typical Chart of Accounts is evidence of the continental accounting model in Ukraine. The accounting standards provide freedom of choice as ...

  6. Emotional regulation and friendship

    OpenAIRE

    Zaccagnini, J.L.; Ruiz-Aranda, D.

    2013-01-01

    Previous literature has been shown that emotional regulation facilitates the establishment and maintenance of social relations (Dodge Garber, 1991; Saarni, 1999). The objective of the present study was to analyze the influence of emotional regulation (Gross y John, 2003) in positive friendship (Berscheid, 2003), specifically at the level of intimacy with friends. In addition, we examined the mediating role of positive emotions in the relationship between the emotional regulation and the leve...

  7. Benchmarking and regulation

    OpenAIRE

    Agrell, Per Joakim; Bogetoft, Peter

    2013-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publication...

  8. Better Regulation in Europe

    OpenAIRE

    Wiener, Jonathan B.

    2006-01-01

    "Better Regulation" is afoot in Europe. After several transatlantic conflicts over regulatory topics such as the precautionary principle, genetically modified foods, and climate change, Europe and America now appear to be converging on the analytic basis for regulation. In a process of hybridization, European institutions are borrowing "Better Regulation" reforms from both the US approach to regulatory review using benefit-cost analysis and from European member states' initiatives on administ...

  9. MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis

    International Nuclear Information System (INIS)

    Post-transcriptional regulation of gene expression by microRNA (miRNA) has recently attracted major interest in relation to its involvement in cancer development. miRNA is a member of small non-coding RNA, consists of 22-24 nucleotides and regulates expression of target mRNA species in a post-transcriptional manner by being incorporated with RNA-induced silencing complex (RISC). Staphylococcal nuclease homology domain containing 1 (SND1), a component of RISC, is frequently up-regulated in human colon cancers and also chemically induced colon cancers in animals. We here showed that SDN1 is involved in miRNA-mediated gene suppression and overexpression of SND1 in colon cancer cells causes down-regulation of APC without altering APC mRNA levels. As for the miRNA expression profile in human colon cancer, miR-34a was among the list of down-regulated miRNA. Expression of miR-34a is tightly regulated by p53, and ectopic expression of miR-34a in colon cancer cells causes remarkable reduction of cell proliferation and induces senescence-like phenotypes. MiR-34a also participates in the positive feedback loop of the p53 tumor suppressor network. This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.

  10. Emotion-regulation choice

    NARCIS (Netherlands)

    Sheppes, Gal; Scheibe, Susanne; Suri, Gaurav; Gross, James J.

    2011-01-01

    Despite centuries of speculation about how to manage negative emotions, little is actually known about which emotion-regulation strategies people choose to use when confronted with negative situations of varying intensity. On the basis of a new process conception of emotion regulation, we hypothesiz

  11. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    nchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The applica...

  12. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... literature. First, contrary to what is commonly argued, we claim that strong states in Asia promote civil regulation in what we call the “paradox of the weak state”. Second, we not only argue that civil regulation is mainly enforced by multinational enterprises willing to promote international social and...... environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

  13. Attention regulation and monitoring in meditation

    OpenAIRE

    Lutz, Antoine; Slagter, Heleen A.; Dunne, John D.; Davidson, Richard J.

    2008-01-01

    This article explores initial findings and the implications of neuroscientific research on meditation. Meditation is conceptualized here as a family of complex emotional and attentional regulatory training regimes developed for various ends, including the cultivation of well-being and emotional balance. The review focuses on the mental processes and the underlying neural circuitry that are critically involved in two styles of meditation. One style, Focused Attention (FA) meditation, entails t...

  14. Regulation of megakaryocytopoiesis.

    Science.gov (United States)

    Caen, J P; Han, Z C; Bellucci, S; Alemany, M

    1999-09-01

    After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use in a wide variety of clinical megakaryocytic and platelet disorders has been expected and clinical trials have been undertaken. To date, the reported encouraging pre-clinical studies indicate that, as with erythropoietin or G-CSF, minimal toxicity can be expected. A potential limiting side-effect of TPO could be the induction of thrombosis. Nevertheless, it is too early to know whether this cytokine will be of major therapeutic importance for patients with life-threatening thrombocytopenia, such as patients undergoing bone marrow transplantation or subjected to a high dose of chemotherapy. Several experimental and clinical studies are still needed to determine the efficacy of TPO in the prevention or the amelioration of bleeding, which is the ultimate goal for the appropriate use of cytokines with haemostatic benefit. Basic and clinical studies on regulators of megakaryocytopoiesis have rapidly progressed. Now, there is no doubt that some of these regulators are effective in correcting haematopoietic disorders of various aetiologies. Studies on negative regulators not only are important to understand the regulation of megakaryocytopoiesis in normal and pathological states but also have a potential clinical application. Some of these regulators have been shown to be effective in the treatment of essential thrombocythaemia and other myeloproliferative disorders. Platelet factor 4 (PF4) and some other chemokines are also capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs. However, detailed investigations are still required to determine the precise mechanism(s) of action of these regulators and to establish the optimal clinical protocols of negative regulators alone or in association with positive regulators for the treatment of various

  15. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F

    1966-01-01

    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  16. The power of regulation

    International Nuclear Information System (INIS)

    Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

  17. Sport Fishing Regulations

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The regulations for sport fishing on St. Vincent National Wildlife Refuge are outlined in this document. Fishing is only permitted from sunrise to sunset, and only...

  18. Legislation and regulation

    International Nuclear Information System (INIS)

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation

  19. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  20. Optimal Regulation of Auditing

    OpenAIRE

    Pagano, Marco; Immordino, Giovanni

    2007-01-01

    We study regulation of the auditing profession in a model where audit quality is unobservable and enforcing regulation is costly. The optimal audit standard falls short of the first-best audit quality, and is increasing in the riskiness of firms and in the amount of funding they seek. The model can encompass collusion between clients and auditors, arising from the joint provision of auditing and consulting services: deflecting collusion requires less ambitious standards. Finally, banning the ...

  1. Restructuring nuclear regulations.

    OpenAIRE

    Mossman, Kenneth L.

    2003-01-01

    Nuclear regulations are a subset of social regulations (laws to control activities that may negatively impact the environment, health, and safety) that concern control of ionizing radiation from radiation-producing equipment and from radioactive materials. The impressive safety record among nuclear technologies is due, in no small part, to the work of radiation safety professionals and to a protection system that has kept pace with the rapid technologic advancements in electric power generati...

  2. Rethinking financial regulation

    OpenAIRE

    Thomas M. Hoenig

    1996-01-01

    In recent years, revolutionary changes in financial markets, combined with incidents such as Barings and Daiwa, have revived concerns about the adequacy of financial regulation. Historically, financial regulatory policy has been driven by the view that to maintain the health of the financial system you must maintain the health of individual institutions.> In light of ongoing changes in financial markets, however, extending the traditional approach to financial market regulation may not work. ...

  3. Supermarkets and Planning Regulation

    OpenAIRE

    Griffith, Rachel; Harmgart, Heike

    2008-01-01

    We are interested in evaluating the impact of restrictive planning regulation on entry into the UK grocery retail industry. We estimate a model similar to Bresnahan and Reiss (1991) where we allow for multiple store formats. We find that more restrictive planning regulation reduces the number of large format supermarkets in equilibrium. However, the impact is overstated if variation in demographic characteristics across markets is not also controlled for. Our estimates suggest that restrictiv...

  4. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  5. Summary of the regulations

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency (IAEA) prescribes regulations for the international movement of all radioactive materials among member nations. The U.S. governmental agencies regulating the transportation of radioactive materals include the Department of Transportation (DOT), which is responsible for safety in packaging, shipping, carriage, stowage, storage, and handling of all radioactive materials; the Nuclear Regulatory Commission (NRC), which is responsible for (1) safety and safeguards in receipt, possession, use, transfer of by-product, source, and special nuclear materials and (2) safety in packaging of fissile and radioactive materials in quantities exceeding Type A limits, defined in the Code of Federal Regulations; the Energy Research and Development Administration, which is responsible for safety in all aspects of radioactive material transport by its license-exempt contractors; and the Postal Service, which is responsible for safety in shipment by mail. Current regulatory actions involving NRC that may influence the transportation of radioactive materials include the examination of the regulations, legal contests, and the adoption of new regulations. The NRC published a draft of an environmental impact statement on transportation in March 1976 and will conduct a rulemaking proceeding after the final version of the statement is published in the fall. Of the new regulations, the most recent innovations in the IAEA regulations and a quality assurance program of increased rigor are foremost. The two most prominent ideas of the reguations IAEA regulations are the assignment of radiotoxicity values to each radionuclide rather than to grups of radionuclides, providing for increased flexibility in package limits for most radionuclides, and the allowance of small releases from Type B packages under hypothetical accident conditions. The DOT and NRC are in the process of adopting these IAEA revisions

  6. Financial Regulation Going Forward

    OpenAIRE

    Franklin Allen; Elena Carletti

    2010-01-01

    The financial sector is heavily regulated in order to prevent financial crises. The recent crisis showed how ineffective this regulation and other types of government intervention were in achieving this aim. We argue that the crisis was primarily caused by housing price bubbles. These occurred because of too loose monetary policies and the easy availability of credit resulting from the build up of large foreign exchange reserves by Asian central banks. A number of regulatory reforms are sugge...

  7. On Globalisation of Regulation

    Directory of Open Access Journals (Sweden)

    Bob Wessels

    2009-04-01

    Full Text Available In this article the opinion that financial regulation should be dealt with on a national, and not on a global scale is criticised. The objections against global regulation are discussed and dismissed. The greater good of a solid global system is inconsistent with maintaining the full force of national social or economic policies. Bob Wessels submits that the best way forward is to look for (a combination of the best methods of regulation on the basis of geography, the nature of regulation itself (hard law, best practices, guidelines, the function of certain rules in relation to the goals or the expectations they aim to address and the character of these rules. A parallel is drawn with the way in which cross-border insolvencies are regulated, including solutions from practitioners in the global insolvency of Lehman Brothers Group of Companies. Given the essential role courts play the presence of new rules of the international insolvency should be supported by more robust rules for the cross-border judicial coordination of cross-border cases, such as a convention. The body of financial regulation should be guided by international accepted principles and guidelines and international regulation and national implementation should reflect a balance between what is necessary in the light of the past events, while still leaving room for fair national demands and policies. The allocation of clear responsibility and authority to regulating bodies should warrant an efficient and effective answer for what, at the core, is a global problem, related to international financial markets.

  8. Corruption, Institutions and Regulation

    OpenAIRE

    Breen, Michael; Gillanders, Robert

    2011-01-01

    We analyze the effects of corruption and institutional quality on the quality of business regulation. Our key findings indicate that corruption negatively affects the quality of regulation and that general institutional quality is insignificant once corruption is con- trolled for. These findings hold over a number of specifications which include additional exogenous historical and geographic controls. The findings imply that policy-makers should focus on curbing corruption to improve regulati...

  9. The regulator's viewpoint

    International Nuclear Information System (INIS)

    The speaker recalls the task of regulators in establishing criteria and standards and assessing and controlling their fulfillment, as well as the fact that there are many types of radiological regulators, depending on their targets, structures, level of independence, and others. She also stresses that regulators take the environment presently into account to protect people as far as ionising radiation is concerned, that is, environmental protection is provided by present regulations, although implicitly based on an anthropocentric focus. In this sense, there is a clear need to develop a framework for the protection of environment, on the basis of the evolution of the present system. There is a preference for a unique, coherent, timely, integrated and manageable radiological human and environment protection system, which has to be developed internationally. Such an enhanced environmental protection framework needs of clearly defined specific 'bricks' (principles/criteria/tools). Regulators will face important challenges in adapting to an integrated man/environment protection framework, and need to act nationally in the meantime to fulfill obligations, as well as actively encourage international initiatives. A proposal on a radiological environmental framework is laid down, and finally she states the overall regulators viewpoint on this process: 'The path towards pragmatism and credibility'. (author)

  10. Regulating energy industries

    International Nuclear Information System (INIS)

    The concept of sector-based regulation takes on significant importance in the context of market liberalization. The overall aim is to conciliate, in the considered sector, fair competition with the achievement of public service missions. However, the nature of the authority in charge of this regulation is not prone to harmonized clauses, even in Europe. For electricity for example, the 96/92/CE directive of 19 December 1996 concerning common rules for the inner electricity market, does not state this and Germany, which has not designed any sector-based regulator, applies the general procedure of litigation settlement by the equivalent of the competition Council. In France, the law Nr 2000-108 of 10 February 2000 defines the CRE (Electricity Regulation Commission) is article 28 as including six members, three of which are appointed by Government and the three others respectively by each of the presidents of the parliamentary assemblies. Many other countries have made the same choice. However, the scope of the missions given to these specialized authorities varies considerably according to the country. At European level, what are the different models of organisation of sector-based regulation in the energy field? How are the new regulators organised in relation with the competition authorities? Will the new models converge on the medium term or on the long term? Must we anticipate the creation of European regulation authorities to rule the problems concerning several national markets? What can we learn from the recent electricity crisis in California? To try and answer these questions, Mr Michel Matheu presented a European comparative study and before the debate started, Mr Pierre Couveinhes suggested a reflection on the practical implications of the analyses carried out. (authors)

  11. Nuclear regulation in transition

    International Nuclear Information System (INIS)

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

  12. Radiation emitting devices regulations

    International Nuclear Information System (INIS)

    The Radiation Emitting Devices Regulations are the regulations referred to in the Radiation Emitting Devices Act and relate to the operation of devices. They include standards of design and construction, standards of functioning, warning symbol specifications in addition to information relating to the seizure and detention of machines failing to comply with the regulations. The radiation emitting devices consist of the following: television receivers, extra-oral dental x-ray equipment, microwave ovens, baggage inspection x-ray devices, demonstration--type gas discharge devices, photofluorographic x-ray equipment, laser scanners, demonstration lasers, low energy electron microscopes, high intensity mercury vapour discharge lamps, sunlamps, diagnostic x-ray equipment, ultrasound therapy devices, x-ray diffraction equipment, cabinet x-ray equipment and therapeutic x-ray equipment

  13. Probiotics and Appetite Regulation

    DEFF Research Database (Denmark)

    Bjerg, Anne Toksvig

    resistance and blood lipid profile among others. Probiotics which are health promoting bacteria can potentially be used to affect the GM and thereby change metabolic outcomes of the host. Animal studies have shown associations between intake of probiotics and appetite regulation, but currently no human...... intestine, in an animal study and in two human studies the effect of the probiotic bacteria Lactobacillus paracasei subsp. paracasei L. casei W8 (W8) on appetite regulation, blood lipids and blood fatty acids. In addition, it was investigated if W8 had an effect on the fecal microbiota of the human...... (GCG) gene encoding GLP-1 and GLP-2 and expression of the gene SCD1 encoding stearoyl-CoA desaturase-1 (SCD1); which is involved in the formation of triacylglycerol (TAG); was studied in piglets supplemented with W8 for two weeks. To study the acute effect of W8 on appetite regulation, glycemic...

  14. Staff rules and regulations

    CERN Multimedia

    HR Department

    2007-01-01

    The 11th edition of the Staff Rules and Regulations, dated 1 January 2007, adopted by the Council and the Finance Committee in December 2006, is currently being distributed to departmental secretariats. The Staff Rules and Regulations, together with a summary of the main modifications made, will be available, as from next week, on the Human Resources Department's intranet site: http://cern.ch/hr-web/internal/admin_services/rules/default.asp The main changes made to the Staff Rules and Regulations stem from the five-yearly review of employment conditions of members of the personnel. The changes notably relate to: the categories of members of the personnel (e.g. removal of the local staff category); the careers structure and the merit recognition system; the non-residence, installation and re-installation allowances; the definition of family, family allowances and family-related leave; recognition of partnerships; education fees. The administrative circulars, some of which are being revised following the ...

  15. ANTICIPATING AND REGULATING BIOSYSTEM

    Directory of Open Access Journals (Sweden)

    Ion Iorga Siman

    2010-06-01

    Full Text Available Regulating biosystems closely related to human beings are structures still difficult to understand.Numerous intimate processes taking place in these systems, even their actual constitution, are insufficiently decoded, and that they have populated the world long before man invented the first regulator, appears not to have contributed much to their knowledge. This work is intended to highlight what regulating biosystems are.There is no secret that somatic muscles perform control operations which no act of moving would be possible without. All actions are the result of dynamic controlled processes adjusted to strict control laws. By treating them very seriously may lead to knowledge of processes occurring in complex systems

  16. Environmentally regulated aerospace coatings

    Science.gov (United States)

    Morris, Virginia L.

    1995-01-01

    Aerospace coatings represent a complex technology which must meet stringent performance requirements in the protection of aerospace vehicles. Topcoats and primers are used, primarily, to protect the structural elements of the air vehicle from exposure to and subsequent degradation by environmental elements. There are also many coatings which perform special functions, i.e., chafing resistance, rain erosion resistance, radiation and electric effects, fuel tank coatings, maskants, wire and fastener coatings. The scheduled promulgation of federal environmental regulations for aerospace manufacture and rework materials and processes will regulate the emissions of photochemically reactive precursors to smog and air toxics. Aerospace organizations will be required to identify, qualify and implement less polluting materials. The elimination of ozone depleting chemicals (ODC's) and implementation of pollution prevention requirements are added constraints which must be addressed concurrently. The broad categories of operations affected are the manufacture, operation, maintenance, and repair of military, commercial, general aviation, and space vehicles. The federal aerospace regulations were developed around the precept that technology had to be available to support the reduction of organic and air toxic emissions, i.e., the regulations cannot be technology forcing. In many cases, the regulations which are currently in effect in the South Coast Air Quality Management District (SCAQMD), located in Southern California, were used as the baseline for the federal regulations. This paper addresses strategies used by Southern California aerospace organizations to cope with these regulatory impacts on aerospace productions programs. All of these regulatory changes are scheduled for implementation in 1993 and 1994, with varying compliance dates established.

  17. Regulation as Rhetoric

    DEFF Research Database (Denmark)

    Boll, Karen; Györy, Csaba

    This paper analyses the way regulatory agencies strategically use public ‘rhetoric’ and ‘management of appearance’ to strengthen their regulation. It reports a comparative study of the Securities and Exchange Commission (SEC) which is the US federal securities regulator and the Danish Tax and...... environment, these two agencies apply strategies that appear to be strikingly similar, and these similarities are worth investigating not despite, but exactly because of the differing political and social environment. We track recent shifts in organizational practice at these two agencies and argue that both...

  18. Nuclear regulation and safety

    International Nuclear Information System (INIS)

    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed

  19. Nuclear regulations and environment

    International Nuclear Information System (INIS)

    After an historical overview of the nuclear regulation system in Argentina a description is made of the country's Nuclear Regulatory Authority (ARN) and of its regulation and control functions. Its organic structure is also outlined. A detailed report is given of the environmental monitoring activities in the sites of the operating Argentine nuclear power plants as well as those of the nuclear research centres. A special reference is made of the monitoring of the relevant uranium mining districts in Argentina. The radon determination in houses of several regions of the country is also mentioned

  20. Regulated underground storage tanks

    International Nuclear Information System (INIS)

    This guidance package is designed to assist DOE Field operations by providing thorough guidance on the underground storage tank (UST) regulations. [40 CFR 280]. The guidance uses tables, flowcharts, and checklists to provide a ''roadmap'' for DOE staff who are responsible for supervising UST operations. This package is tailored to address the issues facing DOE facilities. DOE staff should use this guidance as: An overview of the regulations for UST installation and operation; a comprehensive step-by-step guidance for the process of owning and operating an UST, from installation to closure; and a quick, ready-reference guide for any specific topic concerning UST ownership or operation

  1. Regulation, Competition, and Information

    OpenAIRE

    Mian Muhammad Javed

    2002-01-01

    You know it is very hard after the Governor, State Bank, to make a presentation but I will try to do it in a very mundane way. You know the Regulatory Bodies specially in the Economic Sector in recent times. There has been a sort of resurgence, leaving aside the regulation of the financial sector, which has been doing very well. Our old memory of regulation is not so pleasant. Long ago, there used to be a transport Authority which used to dole out “Route Permits” as political favours, and the...

  2. Cyberplagiarism in University Regulations

    Directory of Open Access Journals (Sweden)

    Santiago Cavanillas

    2008-12-01

    Full Text Available The article examines the legal framework for plagiarism, and its twofold nature of illicit appropriation (from the author of the plagiarized work and fraud (with regard to the target audience of the plagiarism. Based on these premises, academic cyberplagiarism is analysed as a form of plagiarism carried out using electronic tools in the university setting. The question of responsibility (who can regulate the legal consequences of plagiarism? before and after the Ley Orgánica de Universidades (organic law on universities, LOU is studied, as is the disciplinary handling of cyberplagiarism with the limited regulations currently in place at universities.

  3. The Impact of Regulating Social Science Research with Biomedical Regulations

    Science.gov (United States)

    Durosinmi, Brenda Braxton

    2011-01-01

    The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

  4. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The Departmental Rules and The Safety Guides were issued by the NNSA in 1998. The NNSA performed the activities of propagation and implementation of nuclear safety regulations at QTNPP in order to improve the nuclear safety culture of operating organization and construct and contract organizations

  5. Emotion regulation during isolation

    Czech Academy of Sciences Publication Activity Database

    Poláčková Šolcová, Iva; Šolcová, Iva

    2012-01-01

    Roč. 47, Suppl. 1 (2012). ISSN 0020-7594. [International Congress of Psychology /30./. 22.07.2012-27.07.2012, Cape Town] R&D Projects: GA ČR(CZ) GAP407/11/2226 Institutional support: RVO:68081740 Keywords : emotion regulation * isolation * Mars500 Subject RIV: AN - Psychology

  6. International telecommunications market regulation

    OpenAIRE

    Productivity Commission

    2001-01-01

    On 23 February 1999 the Assistant Treasurer referred international telecommunic-ations market regulation for inquiry and report within six months. The report focused on the reform of international telecommunications markets, in particular on the payment arrangements between providers of international telecommunications services.

  7. Regulation after Bush

    OpenAIRE

    Hahn Robert; Passell Peter

    2008-01-01

    Barack Obama and John McCain have staked out very different positions on serious questions involving economic regulation everything from housing finance to alternative energy mandates but practical considerations will dissolve many of these differences, according to Robert Hahn and Peter Passell.

  8. Vehicle recycling regulations

    DEFF Research Database (Denmark)

    Smink, Carla

    2007-01-01

    The number of end-of-life vehicles (ELVs) in the EU is increasing continously. Around 75 percent of an ELV are recyclable metals. The forecast growth in the number of ELVs calls for regulation that aims to minimise the environmental impact of a car. Using Denmark as an example, this article...

  9. Jordan Corporate Governance Regulations

    OpenAIRE

    Jordan Institute of Directors

    2013-01-01

    As the importance of Corporate Governance increases, an awareness and understanding of the different relevant regulations becomes of paramount value. The importance and value of Corporate Governance is not the core of this publication. The publication is built around the premise that Corporate Governance is important and increasingly becoming of significant importance for growth, continued...

  10. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.

    2013-01-01

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  11. Legislation and regulation

    International Nuclear Information System (INIS)

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the legislative and regulatory framework, regulatory body and responsibility of the license holder

  12. Regulating the Internet

    Science.gov (United States)

    Anderson, Byron

    2007-01-01

    The Internet's breakthrough to primetime usage beginning in the mid-1990s evolved in an era of openness. Unfettered access seemed key to Internet development. An important foundation for the 1996 Telecommunications Act was the theory that the telecom industry would work best if it were free of government regulation, a guiding principle that has…

  13. Metabolic regulation of yeast

    Science.gov (United States)

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  14. Regulating emerging technologies

    International Nuclear Information System (INIS)

    Full text: The presentation is designed for individuals who are involved in therapeutic administration of radioactive material and the implementation of the radiation safety programme. The United States Nuclear Regulatory Commission (NRC) has regulatory authority over the medical use of by-product material and the radiation from by-product material. The presentation will address how the NRC regulates new medical uses (i.e. emerging technologies) used in radiation oncology that are too new to be covered in the current regulations. NRC's process that allows licensees to get approved for these emerging technologies until regulations are promulgated for the new modalities will be described. The presentation will also cover NRC's reporting requirements for medical events and other radiation safety-related incidents. Some examples of errors that have occurred for these new NRC-regulated activities will be provided. The root causes in these events will be identified to prevent similar additional incidents from occurring in other facilities performing the same type of therapy. (author)

  15. Regulation of Energy Balance.

    Science.gov (United States)

    Bray, George A.

    1985-01-01

    Explains relationships between energy intake and expenditure focusing on the cellular, chemical and neural mechanisms involved in regulation of energy balance. Information is referenced specifically to conditions of obesity. (Physicians may earn continuing education credit by completing an appended test). (ML)

  16. Regulating nuclear fuel waste

    International Nuclear Information System (INIS)

    When Parliament passed the Atomic Energy Control Act in 1946, it erected the framework for nuclear safety in Canada. Under the Act, the government created the Atomic Energy Control Board and gave it the authority to make and enforce regulations governing every aspect of nuclear power production and use in this country. The Act gives the Control Board the flexibility to amend its regulations to adapt to changes in technology, health and safety standards, co-operative agreements with provincial agencies and policy regarding trade in nuclear materials. This flexibility has allowed the Control Board to successfully regulate the nuclear industry for more than 40 years. Its mission statement 'to ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment' concisely states the Control Board's primary objective. The Atomic Energy Control Board regulates all aspects of nuclear energy in Canada to ensure there is no undue risk to health, safety, security or the environment. It does this through a multi-stage licensing process

  17. Lysosomal Trafficking Regulator (LYST).

    Science.gov (United States)

    Ji, Xiaojie; Chang, Bo; Naggert, Jürgen K; Nishina, Patsy M

    2016-01-01

    Regulation of vesicle trafficking to lysosomes and lysosome-related organelles (LROs) as well as regulation of the size of these organelles are critical to maintain their functions. Disruption of the lysosomal trafficking regulator (LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, prolonged bleeding, severe immunodeficiency, recurrent bacterial infection, neurologic dysfunction and hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes, cytolytic granules and platelet dense bodies. The most striking CHS ocular pathology observed is an enlargement of melanosomes in the retinal pigment epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and results in photophobia and decreased visual acuity. Understanding the molecular function of LYST and identification of its interacting partners may provide therapeutic targets for CHS and other diseases associated with the regulation of LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania amazonensis infections. PMID:26427484

  18. Inconsistent Regulators: Evidence From Banking

    OpenAIRE

    Sumit Agarwal; David Lucca; Amit Seru; Francesco Trebbi

    2012-01-01

    US state chartered commercial banks are supervised alternately by state and federal regulators. Each regulator supervises a given bank for a fixed time period according to a predetermined rotation schedule. We use unique data to examine differences between federal and state regulators for these banks. Federal regulators are significantly less lenient, downgrading supervisory ratings about twice as frequently as state supervisors. Under federal regulators, banks report higher nonperforming loa...

  19. Regulating the private security industry

    CERN Document Server

    Percy, Sarah

    2002-01-01

    The under-regulation of the private security industry has increasingly become a topic of media and academic interest. This Adelphi Paper enters the debate by explaining why the industry requires further regulation, and what is wrong with the current system. It begins by briefly defining the industry and explaining the need for more effective regulation, before analysing three types of regulation: domestic, international and informal (including self-regulation).

  20. Leadership and the Independent Regulator

    OpenAIRE

    Jamison, Mark A.

    2005-01-01

    Being a utility regulator has perils because the independence of the regulator necessarily removes power from politicians, operators, and others. Furthermore, regulators are sometimes scapegoats for unpopular policies and unavoidably become involved in shaping the policies that they are supposed to implement. As a result of such frictions, regulators are sometimes removed from office or marginalized in some way. How can regulators not only survive in such an environment, but also thrive? Jami...

  1. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    Science.gov (United States)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  2. Regulation of motor patterns by the central spike initiation zone of a sensory neuron

    OpenAIRE

    Daur, Nelly; Nadim, Farzan; Stein, Wolfgang

    2009-01-01

    Sensory feedback from muscles and peripheral sensors acts to initiate, tune or reshape motor activity according to the state of the body. Yet, sensory neurons often show low levels of activity even in the absence of sensory input. Here we examine the functional role of spontaneous low-frequency activity of such a sensory neuron. The anterior gastric receptor (AGR) is a muscle tendon organ in the crab stomatogastric nervous system whose phasic activity shapes the well-characterized gastric mil...

  3. Markets, religion, regulation

    DEFF Research Database (Denmark)

    Fischer, Johan

    2016-01-01

    of regulation, certification and standardization on a global scale. Building on research on global kosher (a Hebrew term meaning “fit” or “proper”), halal (an Arabic word that literally means “permissible” or “lawful”) and Hindu vegetarianism this paper argues that these economies or markets to a...... large extent are conditioned by and themselves condition forms of transnational governmentality, that is, new and often overlapping practices of government and grassroots politics. I explore religious economies and markets at three interrelated levels of the social scale: state and non-state regulation......Most recent scholarship on moral economies or religious markets argues for the compatibility of economies/markets and religious practices in particular national or regional contexts. However, over the last couple of decades or so religious markets have entered a new phase characterized by new forms...

  4. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  5. Volume Regulation in Epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    We review studies on regulatory volume decrease (RVD) and regulatory volume increase (RVI) of major ion and water transporting vertebrate epithelia. The rate of RVD and RVI is faster in cells of high osmotic permeability like amphibian gallbladder and mammalian proximal tubule as compared to...... amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... function of iso-osmotic fluid transport that depends on Na+ recirculation. The causative relationship is discussed for a fluid-absorbing and a fluid-secreting epithelium of which the Na+ recirculation mechanisms have been identified. A large number of transporters and ion channels involved in cell volume...

  6. Auditing and Regulations

    OpenAIRE

    Pettinicchio, A.K.

    2011-01-01

    Effective financial reporting has become of critical importance in our economic markets and the international accounting scandals of the last decades have accentuated the role of auditing in protecting stakeholders' interests and contributing to an efficient functioning of financial markets. Auditing regulation has been at the centre of recent international debates (e.g. EU Green paper; 2010) and different regulatory interventions have been put in place in different countries and in different...

  7. POTENT REGULATORS OF METABOLISM

    OpenAIRE

    Brun, Pierre-Jacques; Yang, Kryscilla Jian Zhang; Lee, Seung-Ah; Yuen, Jason J.; Blaner, William S.

    2012-01-01

    Retinoids (vitamin A and its analogs) are highly potent regulators of cell differentiation, cell proliferation, and apoptosis. Because of these activities, retinoids have been most extensively studied in the contexts of embryonic development and of proliferative diseases, especially cancer and skin disease. Recently, there has been considerable new research interest focused on gaining understanding of the roles that retinoids and/or retinoid-related proteins may have in the development of met...

  8. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  9. Regulating hate speech online

    OpenAIRE

    Banks, James

    2010-01-01

    The exponential growth in the Internet as a means of communication has been emulated by an increase in far-right and extremist web sites and hate based activity in cyberspace. The anonymity and mobility afforded by the Internet has made harassment and expressions of hate effortless in a landscape that is abstract and beyond the realms of traditional law enforcement. This paper examines the complexities of regulating hate speech on the Internet through legal and technological frameworks. It ex...

  10. Iron regulation by hepcidin

    OpenAIRE

    Zhao, Ningning; Zhang, An-Sheng; Enns, Caroline A

    2013-01-01

    Hepcidin is a key hormone that is involved in the control of iron homeostasis in the body. Physiologically, hepcidin is controlled by iron stores, inflammation, hypoxia, and erythropoiesis. The regulation of hepcidin expression by iron is a complex process that requires the coordination of multiple proteins, including hemojuvelin, bone morphogenetic protein 6 (BMP6), hereditary hemochromatosis protein, transferrin receptor 2, matriptase-2, neogenin, BMP receptors, and transferrin. Misregulati...

  11. Gastrointestinal hormones regulating appetite

    OpenAIRE

    Chaudhri, Owais; Small, Caroline; Bloom, Steve

    2006-01-01

    The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably cons...

  12. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    2014-01-01

    This paper examines a tax/subsidy on hunters based on game population. The tax/subsidy is the difference between actual and optimal population multiplied by an individual, variable tax rate. The tax rate is, among other things, based on the difference between the marginal value of the game...... population to the hunter and the regulator and differences in user costs of the population. The paper shows that the population tax/subsidy secures a first-best optimum....

  13. Cyberplagiarism in University Regulations

    OpenAIRE

    Santiago Cavanillas

    2008-01-01

    The article examines the legal framework for plagiarism, and its twofold nature of illicit appropriation (from the author of the plagiarized work) and fraud (with regard to the target audience of the plagiarism). Based on these premises, academic cyberplagiarism is analysed as a form of plagiarism carried out using electronic tools in the university setting. The question of responsibility (who can regulate the legal consequences of plagiarism?) before and after the Ley Orgánica de Universidad...

  14. Fibronectin Mechanobiology Regulates Tumorigenesis

    OpenAIRE

    Wang, Karin; Seo, Bo Ri; Fischbach, Claudia; Gourdon, Delphine

    2015-01-01

    Fibronectin (Fn) is an essential extracellular matrix (ECM) glycoprotein involved in both physiological and pathological processes. The structure–function relationship of Fn has been and is still being studied, as changes in its molecular structure are integral in regulating (or dysregulating) its biological activities via its cell, matrix component, and growth factor binding sites. Fn comprises three types of repeating modules; among them, FnIII modules are mechanically unstable domains that...

  15. Beyond State Regulation

    OpenAIRE

    Madanat, Philip; Pies, Judith

    2011-01-01

    Holding the news media accountable has traditionally been a task of the state in Jordan. Media laws and regulations are numerous and do not leave too much space for self-regulatory practices on a national basis. The Jordan Press Association (JPA) is the core of so-called established media accountability institutions. It conducted a law-like code of ethics in 2003 and runs ombuds committees (currently three) dealing with mishaps of the media to prevent journalists from legal liability. Thou...

  16. Improving CS regulations.

    Energy Technology Data Exchange (ETDEWEB)

    Nesse, R.J.; Scheer, R.M.; Marasco, A.L.; Furey, R.

    1980-10-01

    President Carter issued Executive Order 12044 (3/28/78) that required all Federal agencies to distinguish between significant and insignificant regulations, and to determine whether a regulation will result in major impacts. This study gathered information on the impact of the order and the guidelines on the Office of Conservation and Solar Energy (CS) regulatory practices, investigated problems encountered by the CS staff when implementing the order and guidelines, and recommended solutions to resolve these problems. Major tasks accomplished and discussed are: (1) legislation, Executive Orders, and DOE Memoranda concerning Federal administrative procedures relevant to the development and analysis of regulations within CS reviewed; (2) relevant DOE Orders and Memoranda analyzed and key DOE and CS staff interviewed in order to accurately describe the current CS regulatory process; (3) DOE staff from the Office of the General Counsel, the Office of Policy and Evaluation, the Office of the Environment, and the Office of the Secretary interviewed to explore issues and problems encountered with current CS regulatory practices; (4) the regulatory processes at five other Federal agencies reviewed in order to see how other agencies have approached the regulatory process, dealt with specific regulatory problems, and responded to the Executive Order; and (5) based on the results of the preceding four tasks, recommendations for potential solutions to the CS regulatory problems developed. (MCW)

  17. Staff rules and regulations

    CERN Multimedia

    HR Department

    2007-01-01

    The 11th edition of the Staff Rules and Regulations, dated 1 January 2007, adopted by the Council and the Finance Committee in December 2006, is currently being distributed to departmental secretariats. The Staff Rules and Regulations, together with a summary of the main modifications made, will be available, as from next week, on the Human Resources Department's intranet site: http://cern.ch/hr-web/internal/admin_services/rules/default.asp The main changes made to the Staff Rules and Regulations stem from the five-yearly review of employment conditions of members of the personnel. The changes notably relate to: the categories of members of the personnel (e.g. removal of the local staff category); the careers structure and the merit recognition system; the non-residence, installation and re-installation allowances; the definition of family, family allowances and family-related leave; recognition of partnerships; education fees. The administrative circulars, some of which are being revised following the m...

  18. Taiwan Regulation of Biobanks.

    Science.gov (United States)

    Fan, Chien-Te; Hung, Tzu-Hsun; Yeh, Chan-Kun

    2015-01-01

    This paper introduces legal framework and governance structure in relation to the management and development of biobanks in Taiwan. At first, we briefly describe Taiwan's population, political system and health care system. Secondly, this research introduces biobanking framework of Taiwan including 25 biobanks established with the approval of the Ministry of Health and Welfare. In those biobanks, "Taiwan Biobank" is the first and the largest government-supported biobank which comprises population-based cohort study and disease- oriented study. Since the collection of information, data, and biological specimen of biobanks often involve highly sensitive personal information, in the legal framework of Taiwan, there is a specific regulation, "Human Biobank Management Act" (HBMA), which plays an important role in regulating biobanks in Taiwan. HBMA, the Personal Information Act and other regulations constitute a comprehensive legal and regulatory privacy framework of biobanks. Through the introduction and analysis of the current legal framework applicable to biobanks, we found that there are several challenges that need to be solved appropriately that involve duplicate review systems, the obstacles in the international collaboration, and data sharing between biobanks in Taiwan. PMID:26711420

  19. Whither tobacco product regulation?

    Science.gov (United States)

    McNeill, Ann; Hammond, David; Gartner, Coral

    2012-03-01

    Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets. PMID:22345253

  20. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit. PMID:25782435

  1. Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating.

    Science.gov (United States)

    Hurley, Matthew M; Maunze, Brian; Block, Megan E; Frenkel, Mogen M; Reilly, Michael J; Kim, Eugene; Chen, Yao; Li, Yan; Baker, David A; Liu, Qing-Song; Choi, SuJean

    2016-01-01

    While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding). In contrast, inhibition of the nucleus accumbens (NAc), through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive. PMID:27597817

  2. Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear.

    Science.gov (United States)

    Yang, Hongbin; Yang, Junhua; Xi, Wang; Hao, Sijia; Luo, Benyan; He, Xiaobin; Zhu, Liya; Lou, Huifang; Yu, Yan-Qin; Xu, Fuqiang; Duan, Shumin; Wang, Hao

    2016-02-01

    Innate fear has a critical role in survival of animals. Unlike conditioned fear, the neuronal circuitry underlying innate fear is largely unknown. We found that the laterodorsal tegmentum (LDT) and lateral habenula (LHb) are specifically activated by the mouse predator odorant trimethylthiazoline (TMT). Using optogenetics to selectively stimulate GABAergic neurons in the LDT immediately produced fear-like responses (freezing, accelerated heart rate and increased serum corticosterone), whereas prolonged stimulation caused anxiety-like behaviors. Notably, although selective stimulation of parvalbumin (PV)-positive interneurons similarly induced fear-like responses, stimulation of somatostatin-positive interneurons or inhibition of PV neurons in the LDT suppressed TMT-induced fear-like responses without affecting conditioned fear. Finally, activation of LHb glutamatergic inputs to LDT interneurons was sufficient to generate fear-like responses. Thus, the LHb-LDT pathway is important for regulating olfactory cue-induced innate fear. Our results provide a potential target for therapeutic intervention for anxiety disorder. PMID:26727549

  3. The international radioactive transportation regulations: A model for national regulations

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

  4. Nuclear regulation in 2000

    International Nuclear Information System (INIS)

    A key prerequisite to the development of a nuclear program to provide a country's electricity is that governments and the public are confident that a nuclear accident 'will not occur' over the whole life of the program. This can only be achieved by three elements being equally strong: an excellent design, a highly competent and safety conscious operator, and a strong competent regulator with appropriate legal powers. This paper will outline what is necessary to achieve the third of these prerequisites. It will outline the principles by which a Regulatory Agency ensures that licensees meet their responsibility for the safety of their nuclear plant, based on both internationally accepted ideas, the Nuclear Safety Convention, and Canadian practice. The paper will cover legislative principles -- what to include in legislation, what to include in regulations, and what to include in standards and guides. The problem of 'prescriptive requirements' versus 'general performance statements' in regulations will be addressed, and the implications of this problem on ensuring licensees retain responsibility for safety, and on licensees' desire for a high degree of certainty in what is expected of them, both to get a licence and to keep it, in today's economic climate. The paper will also address compliance and the differences between the lawyers' definition of compliance (meeting specific requirements defined by law) and the nuclear safety engineers' view of compliance, (meeting commitments made at the time a licence was given), and how these views can be reconciled. The paper will discuss how Canada's new Nuclear Safety and Control Act has addressed some of these issues, and how the Canadian Nuclear Safety Commission is implementing the new Act. The issue of transfer of regulatory programs and technology to the regulatory agencies of countries buying a nuclear plant from Canadian companies will be discussed, and examples given of how this has been accomplished to the benefit of

  5. Situated bio-regulation

    DEFF Research Database (Denmark)

    Prainsack, Barbara; Wahlberg, Ayo

    2013-01-01

    Several years ago, both authors engaged in research into bioscience and biomedical regulation in Asian countries. One of us (BP) explored why the regulatory and discursive embedding of human embryonic stem cell in Israel was much more permissive than elsewhere. The other author (AW) sought to und...... case studies meant bringing what we call ‘ethnographic sensibility’ to our research. This paper discusses the implications of this approach, which often entails rendering visible the contradictions and ‘disorders’ in what seems coherent and orderly....

  6. Regulering og simulering

    DEFF Research Database (Denmark)

    Steen-Thøde, Mogens

    Dette notat er primært udarbejdet til brug i undervisningen i kurset Energisystemer og Regulering pa civilingeniørlinien lndeklima og Energiøkonomi på Aalborg Universitet, hvilket naturligvis sætter sit spor bade i omfang og udvælgelse af emner. Hensigten er at give en introduktion til det teoret...... teoretiske grundlag for reguleringsteknikken samtidig med en indføring i simulering af dynamiske systemer, således at læseren får en rimelig forståelse af dynamiske systemers virkemåde og karakteristika....

  7. Ionising radiations regulations 1985

    International Nuclear Information System (INIS)

    The (UK) Ionising Radiations Regulations 1985 come into force on 1.1.86 with supporting Approved Code of Practice. They are discussed under the headings: introduction; notifications to start work with ionising radiations; dose limitation (ALARP -as low as reasonably practicable); designation of controlled and supervised areas; Radiation Protection Advisers to be appointed by employers; Local Rules; Radiation Protection Supervisors to be appointed by employers from among employees; instruction and training; dosimetry and medical surveillance; control of radioactive substances; radiation monitoring; assessment of hazards; articles and equipment. (U.K.)

  8. FACTORS REGULATING LIBERAL TRANSLATION

    Institute of Scientific and Technical Information of China (English)

    龚海红

    2012-01-01

    Literal translation and liberal translation are two important methods and both play key roles in translation.However,some textbooks say that most translations are literal translations while others maintain most are liberal ones,besides,some others suggest a combination of the two.This paper focuses on the facts that regulate liberal translation.Because of the differences in culture,society,history,geography,and so on,there exists a great difference between Chinese language and English language,which does naturally lead to the liberal translation.

  9. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    multiplied by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good...... of the individual harvest. However, information about the individual harvest may be costly to obtain. Thus, we may have to look for alternatives to the existing system. This paper proposes a population tax/subsidy as an alternative which is the difference between the actual and optimal population...

  10. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1992-01-01

    This report describes accomplishments over the past year on understanding of terpene synthesis in mint plants and sage. Specifically reported are the fractionation of 4-S-limonene synthetase, the enzyme responsible for the first committed step to monoterpene synthesis, along with isolation of the corresponding RNA and DNA cloning of its gene; the localization of the enzyme within the oil glands, regulation of transcription and translation of the synthetase, the pathway to camphor biosynthesis,a nd studies on the early stages and branch points of the isoprenoid pathway.

  11. Wiring regulations in brief

    CERN Document Server

    Tricker, Ray

    2012-01-01

    Tired of trawling through the Wiring Regs?Perplexed by Part P?Confused by cables, conductors and circuits?Then look no further! This handy guide provides an on-the-job reference source for Electricians, Designers, Service Engineers, Inspectors, Builders, Students, DIY enthusiastsTopic-based chapters link areas of working practice - such as cables, installations, testing and inspection, special locations - with the specifics of the Regulations themselves. This allows quick and easy identification of the official requirements relating to the situati

  12. REGULATION OF VASCULOGENESIS AND ANGIOGENESIS

    Science.gov (United States)

    Regulation of vasculogenesis and angiogenesis.B.D. AbbottReproductive Toxicology Division, Environmental Protection Agency, Research Triangle Park, North Carolina, USA Vasculogenesis and angiogenesis are regulated by a complex, interactive family of receptors and lig...

  13. The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation.

    Science.gov (United States)

    Rosa, A; Ballarino, M; Sorrentino, A; Sthandier, O; De Angelis, F G; Marchioni, M; Masella, B; Guarini, A; Fatica, A; Peschle, C; Bozzoni, I

    2007-12-11

    We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease in NFI-A levels is important for the activation of differentiation-specific genes such as M-CSFr. In line with these data, both RNAi against NFI-A and ectopic expression of miR-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of NFI-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human CD34+ differentiation. These data point to the important role of miR-424 and NFI-A in controlling the monocyte/macrophage differentiation program. PMID:18056638

  14. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Science.gov (United States)

    Guzman, Monica S; De Jaeger, Xavier; Raulic, Sanda; Souza, Ivana A; Li, Alex X; Schmid, Susanne; Menon, Ravi S; Gainetdinov, Raul R; Caron, Marc G; Bartha, Robert; Prado, Vania F; Prado, Marco A M

    2011-11-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease. PMID:22087075

  15. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  16. Regulation of CsrB/C sRNA decay by EIIA(Glc) of the phosphoenolpyruvate: carbohydrate phosphotransferase system.

    Science.gov (United States)

    Leng, Yuanyuan; Vakulskas, Christopher A; Zere, Tesfalem R; Pickering, Bradley S; Watnick, Paula I; Babitzke, Paul; Romeo, Tony

    2016-02-01

    Csr is a conserved global regulatory system, which uses the sequence-specific RNA-binding protein CsrA to activate or repress gene expression by binding to mRNA and altering translation, stability and/or transcript elongation. In Escherichia coli, CsrA activity is regulated by two sRNAs, CsrB and CsrC, which bind to multiple CsrA dimers, thereby sequestering this protein away from its mRNA targets. Turnover of CsrB/C sRNAs is tightly regulated by a GGDEF-EAL domain protein, CsrD, which targets them for cleavage by RNase E. Here, we show that EIIA(Glc) of the glucose-specific PTS system is also required for the normal decay of these sRNAs and that it acts by binding to the EAL domain of CsrD. Only the unphosphorylated form of EIIA(Glc) bound to CsrD in vitro and was capable of activating CsrB/C turnover in vivo. Genetic studies confirmed that this mechanism couples CsrB/C sRNA decay to the availability of a preferred carbon source. These findings reveal a new physiological influence on the workings of the Csr system, a novel function for the EAL domain, and an important new way in which EIIA(Glc) shapes global regulatory circuitry in response to nutritional status. PMID:26507976

  17. The Involvement of Neuron-Specific Factors in Dendritic Spinogenesis: Molecular Regulation and Association with Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Hsiao-Tang Hu

    2016-01-01

    Full Text Available Dendritic spines are the location of excitatory synapses in the mammalian nervous system and are neuron-specific subcellular structures essential for neural circuitry and function. Dendritic spine morphology is determined by the F-actin cytoskeleton. F-actin remodeling must coordinate with different stages of dendritic spinogenesis, starting from dendritic filopodia formation to the filopodia-spines transition and dendritic spine maturation and maintenance. Hundreds of genes, including F-actin cytoskeleton regulators, membrane proteins, adaptor proteins, and signaling molecules, are known to be involved in regulating synapse formation. Many of these genes are not neuron-specific, but how they specifically control dendritic spine formation in neurons is an intriguing question. Here, we summarize how ubiquitously expressed genes, including syndecan-2, NF1 (encoding neurofibromin protein, VCP, and CASK, and the neuron-specific gene CTTNBP2 coordinate with neurotransmission, transsynaptic signaling, and cytoskeleton rearrangement to control dendritic filopodia formation, filopodia-spines transition, and dendritic spine maturation and maintenance. The aforementioned genes have been associated with neurological disorders, such as autism spectrum disorders (ASDs, mental retardation, learning difficulty, and frontotemporal dementia. We also summarize the corresponding disorders in this report.

  18. The Involvement of Neuron-Specific Factors in Dendritic Spinogenesis: Molecular Regulation and Association with Neurological Disorders.

    Science.gov (United States)

    Hu, Hsiao-Tang; Shih, Pu-Yun; Shih, Yu-Tzu; Hsueh, Yi-Ping

    2016-01-01

    Dendritic spines are the location of excitatory synapses in the mammalian nervous system and are neuron-specific subcellular structures essential for neural circuitry and function. Dendritic spine morphology is determined by the F-actin cytoskeleton. F-actin remodeling must coordinate with different stages of dendritic spinogenesis, starting from dendritic filopodia formation to the filopodia-spines transition and dendritic spine maturation and maintenance. Hundreds of genes, including F-actin cytoskeleton regulators, membrane proteins, adaptor proteins, and signaling molecules, are known to be involved in regulating synapse formation. Many of these genes are not neuron-specific, but how they specifically control dendritic spine formation in neurons is an intriguing question. Here, we summarize how ubiquitously expressed genes, including syndecan-2, NF1 (encoding neurofibromin protein), VCP, and CASK, and the neuron-specific gene CTTNBP2 coordinate with neurotransmission, transsynaptic signaling, and cytoskeleton rearrangement to control dendritic filopodia formation, filopodia-spines transition, and dendritic spine maturation and maintenance. The aforementioned genes have been associated with neurological disorders, such as autism spectrum disorders (ASDs), mental retardation, learning difficulty, and frontotemporal dementia. We also summarize the corresponding disorders in this report. PMID:26819769

  19. Self-Regulation in School

    OpenAIRE

    Nett, Ulrike Elisabeth

    2010-01-01

    Successful self-regulation depends on the ability to regulate the self both motivationally and emotionally in order to protect the self and the learning process against competing personal needs as well as situational distractions. Successful self-regulation further requires students to adequately use metacognitive and cognitive learning strategies to organize the learning process efficiently. The studies presented in this dissertation focus on students' strategies for regulating themselves in...

  20. Mergers in Regulated Industries: Electricity

    OpenAIRE

    Dennis W. Carlton

    2007-01-01

    Mergers in any industry can raise complicated questions about the elimination of competition and the achievement of efficiencies. Mergers in regulated industries such as electricity raise even more complicated issues as the analyst needs to grapple with the constraining effects of regulation, multiple levels of regulation, the ability to evade regulation, and the desire for efficiency. This paper discusses the electricity industry in general and one particular electricity merger that the U.S....

  1. Strategic Behaviour under Regulation Benchmarking

    OpenAIRE

    Jamasb, Tooraj; Nillesen, Paul; Michael G. Pollitt

    2003-01-01

    Liberalisation of generation and supply activities in the electricity sectors is often followed by regulatory reform of distribution networks. In order to improve the efficiency of distribution utilities, some regulators have adopted incentive regulation schemes that rely on performance benchmarking. Although regulation benchmarking can influence the ?regulation game?, the subject has received limited attention. This paper discusses how strategic behaviour can result in inefficient behav...

  2. Nuclear regulation - the Canadian approach

    International Nuclear Information System (INIS)

    Although the Atomic Energy Control Board was established 35 years ago the basic philosophy of nuclear regulation in Canada and the underlying principles of the regulatory process remain essentially unchanged. This paper outlines the Canadian approach to nuclear regulation and explains in practical terms how the principles of regulation are applied. (author)

  3. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  4. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  5. Regulation as delegation

    Directory of Open Access Journals (Sweden)

    Oren Bar-Gill

    2016-03-01

    Full Text Available Objective to consider the conception of reverse delegation when the government acts a principal and an individual ndash an agent from the point of view of behavioral PrincipalAgent Theory. Methods statistical method sociological polling. Results In diverse areas ndash from retirement savings to consumer credit to prescription drug use to fuel economy and energy efficiency rules to tobacco consumption to food and beverage consumption ndash government makes decisions for us or endeavors to help us make better decisions thus serving as our agent. From the point of view of PrincipalAgent Theory and behavioral PrincipalAgent Theory a great deal of modern regulation can be helpfully evaluated as a hypothetical delegation. Shifting from personal decisions to public goods problems the authors view the idea of reverse delegation with the government as principal and the individuals as agents. They show that the essence of delegation changes depending on the context. The article describes conditions under which various approaches will make sense. Scientific novelty the paper is devoted to the foreign experience of regulation through delegation by the example of a country with developed market economy the USA. It shows the prospects of such approach in solving both the public and the private tasks. Application of PrincipalAgent Theory and behavioral PrincipalAgent Theory is viewed to distinguish between such types of hypothetical delegation as information default rules incentives precommitments mandates and prohibitions. The article considers the benefits and costs of delegation and circumstances in which one or another approach makes sense. Practical significance PrincipalAgent Theory is widely used in economics and political science and can serve as a convenient tool to consider the optimal scale and essence of the assistance rendered to us by the government as our agent. The paper is of interest for the Russian legal science as the institution of

  6. A pressure regulator

    International Nuclear Information System (INIS)

    A device for regulating the pressure of a gas in a glove box comprises a resiliently biassed pressure sensitive diaphragm and a spool valve operable by deflection of the diaphragm. The diaphragm is arranged to be exposed on one side to atmospheric pressure and on the other side to the pressure of the gas in the glove box, and the spool valve is used to control simultaneously the rates at which gas is pumped in and out of the glove box. The valve spool has two axially spaced circumferential grooves A, B which provide communication between conduits C, D and E, F respectively, the flow control along each path being effected by means of apertures in a sleeve within which the spool slides. (author)

  7. NCAM regulates cell motility

    DEFF Research Database (Denmark)

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna;

    2002-01-01

    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells...... independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a...... fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine...

  8. Views of the regulators

    International Nuclear Information System (INIS)

    It is important to remember what the concept and objective of optimization are and the role of dose constraints. In relation to exposures from any particular source within a practice, radiation protection shall be optimized so that the magnitude of individual doses, except for therapeutic medical exposures, the number of exposed people and the likelihood of incurring exposures will all be kept 'as low as reasonably achievable' (ALARA), economic and social factors being taken into account, within the restriction that the dose to individuals delivered by the source be subject to dose constraints. Dose constraints and dose limits to occupational exposures are necessary since the workers are not the direct beneficiaries of the exposures and the optimization procedures based on collective doses could result in inequities. The dose constraint has the secondary function of ensuring that the sum of the doses that an individual received from different practices to which the individual can be exposed does not exceed the dose limit. Before discussing co-operation, it is fundamental to provide a description of the role and responsibilities of the regulatory authority, employers and workers. The role and responsibilities of the regulatory authority in establishing regulations, granting authorizations, undertaking inspections, ensuring enforcement, and dealing with accidents and emergencies are set by the national legislation. To achieve this objective, the licensee is required to use, to the extent practicable, procedures and engineering controls that are based upon sound radiation protection and safety principles. The regulations establish that the licensees and employers of workers who are engaged in activities that involve or could involve occupational exposure shall be responsible for the protection of these workers against any occupational exposure that is not excluded from regulatory control

  9. TFEB regulates lysosomal proteostasis.

    Science.gov (United States)

    Song, Wensi; Wang, Fan; Savini, Marzia; Ake, Ashley; di Ronza, Alberto; Sardiello, Marco; Segatori, Laura

    2013-05-15

    Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a β-hexosaminidase mutant associated with the development of another LSD, Tay-Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs. PMID:23393155

  10. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  11. Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala.

    Science.gov (United States)

    Zhang, Wei; Rosenkranz, J Amiel

    2016-08-01

    The adolescent age is associated with lability of mood and emotion. The onset of depression and anxiety disorders peaks during adolescence and there are differences in symptomology during adolescence. This points to differences in the adolescent neural circuitry that underlies mood and emotion, such as the amygdala. The human adolescent amygdala is more responsive to evocative stimuli, hinting to less local inhibitory regulation of the amygdala, but this has not been explored in adolescents. The amygdala, including the lateral nucleus (LAT) of the basolateral amygdala complex, is sensitive to stress. The amygdala undergoes maturational processes during adolescence, and therefore may be more vulnerable to harmful effects of stress during this time period. However, little is known about the effects of stress on the LAT during adolescence. GABAergic inhibition is a key regulator of LAT activity. Therefore, the purpose of this study was to test whether there are differences in the local GABAergic regulation of the rat adolescent LAT, and differences in its sensitivity to repeated stress. We found that LAT projection neurons are subjected to weaker GABAergic inhibition during adolescence. Repeated stress reduced in vivo endogenous and exogenous GABAergic inhibition of LAT projection neurons in adolescent rats. Furthermore, repeated stress decreased measures of presynaptic GABA function and interneuron activity in adolescent rats. In contrast, repeated stress enhanced glutamatergic drive of LAT projection neurons in adult rats. These results demonstrate age differences in GABAergic regulation of the LAT, and age differences in the mechanism for the effects of repeated stress on LAT neuron activity. These findings provide a substrate for increased mood lability in adolescents, and provide a substrate by which adolescent repeated stress can induce distinct behavioral outcomes and psychiatric symptoms. PMID:26924679

  12. CBP regulates the differentiation of interneurons from ventral forebrain neural precursors during murine development.

    Science.gov (United States)

    Tsui, David; Voronova, Anastassia; Gallagher, Denis; Kaplan, David R; Miller, Freda D; Wang, Jing

    2014-01-15

    The mechanisms that regulate appropriate genesis and differentiation of interneurons in the developing mammalian brain are of significant interest not only because interneurons play key roles in the establishment of neural circuitry, but also because when they are deficient, this can cause epilepsy. In this regard, one genetic syndrome that is associated with deficits in neural development and epilepsy is Rubinstein-Taybi Syndrome (RTS), where the transcriptional activator and histone acetyltransferase CBP is mutated and haploinsufficient. Here, we have asked whether CBP is necessary for the appropriate genesis and differentiation of interneurons in the murine forebrain, since this could provide an explanation for the epilepsy that is associated with RTS. We show that CBP is expressed in neural precursors within the embryonic medial ganglionic eminence (MGE), an area that generates the vast majority of interneurons for the cortex. Using primary cultures of MGE precursors, we show that knockdown of CBP causes deficits in differentiation of these precursors into interneurons and oligodendrocytes, and that overexpression of CBP is by itself sufficient to enhance interneuron genesis. Moreover, we show that levels of the neurotransmitter synthesis enzyme GAD67, which is expressed in inhibitory interneurons, are decreased in the dorsal and ventral forebrain of neonatal CBP(+/-) mice, indicating that CBP plays a role in regulating interneuron development in vivo. Thus, CBP normally acts to ensure the differentiation of appropriate numbers of forebrain interneurons, and when its levels are decreased, this causes deficits in interneuron development, providing a potential explanation for the epilepsy seen in individuals with RTS. PMID:24247009

  13. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    Full Text Available We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR, however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25 and sphingolipid biosynthesis (AUR1 and SCS7 genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron

  14. A circadian oscillator in the fungus Botrytis cinerea regulates virulence when infecting Arabidopsis thaliana.

    Science.gov (United States)

    Hevia, Montserrat A; Canessa, Paulo; Müller-Esparza, Hanna; Larrondo, Luis F

    2015-07-14

    The circadian clock of the plant model Arabidopsis thaliana modulates defense mechanisms impacting plant-pathogen interactions. Nevertheless, the effect of clock regulation on pathogenic traits has not been explored in detail. Moreover, molecular description of clocks in pathogenic fungi--or fungi in general other than the model ascomycete Neurospora crassa--has been neglected, leaving this type of question largely unaddressed. We sought to characterize, therefore, the circadian system of the plant pathogen Botrytis cinerea to assess if such oscillatory machinery can modulate its virulence potential. Herein, we show the existence of a functional clock in B. cinerea, which shares similar components and circuitry with the Neurospora circadian system, although we found that its core negative clock element FREQUENCY (BcFRQ1) serves additional roles, suggesting extracircadian functions for this protein. We observe that the lesions produced by this necrotrophic fungus on Arabidopsis leaves are smaller when the interaction between these two organisms occurs at dawn. Remarkably, this effect does not depend solely on the plant clock, but instead largely relies on the pathogen circadian system. Genetic disruption of the B. cinerea oscillator by mutation, overexpression of BcFRQ1, or by suppression of its rhythmicity by constant light, abrogates circadian regulation of fungal virulence. By conducting experiments with out-of-phase light:dark cycles, we confirm that indeed, it is the fungal clock that plays the main role in defining the outcome of the Arabidopsis-Botrytis interaction, providing to our knowledge the first evidence of a microbial clock modulating pathogenic traits at specific times of the day. PMID:26124115

  15. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    Science.gov (United States)

    Hameed, Saif; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Goswami, Shyamal K; Prasad, Rajendra

    2011-01-01

    We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR), however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS) based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25) and sphingolipid biosynthesis (AUR1 and SCS7) genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron deprived Candida

  16. Regulation of the power sector

    CERN Document Server

    2013-01-01

    Regulation of the Power Sector is a unified, consistent and comprehensive treatment of the theories and practicalities of regulation in modern power-supply systems. The need for generation to occur at the time of use occasioned by the impracticality of large-scale electricity storage coupled with constant and often unpredictable changes in demand make electricity-supply systems large, dynamic and complex and their regulation a daunting task. Conceptually arranged in four parts, this book addresses both traditional regulatory frameworks and also liberalized and re-regulated environments. First, an introduction gives a full characterization of power supply including engineering, economic and regulatory viewpoints. The second part presents the fundamentals of regulation and the third looks at the regulation of particular components of the power sector in detail. Advanced topics and subjects still open or subject to dispute form the content of the fourth part. In a sector where regulatory design is the key driver...

  17. Nanomaterials: Regulation and Risk Assessment

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Grieger, Khara Deanne; Baun, Anders

    2013-01-01

    The topics of regulation and risk assessment of nanomaterials have never been more relevant and controversial in Europe than they are at this point in time. In this entry, we present and discuss a number of major pieces of legislation relevant for the regulation of nanomaterials, including REACH...... Foods Regulation. Chemical risk assessment provides a fundamental element in support of existing legislation. Risk assessment is normally said to consist of four elements, i.e., hazard identification, dose–response assessment, exposure assessment, and risk characterization. Each of these four elements......, the Water Framework Directive, pharmaceuticals regulation, and the Novel Foods Regulation. Current regulation of nanomaterials entail three overall challenges: 1) limitations in regard to terminology and definitions of key terms such as a “substance,” “novel food,” etc.; 2) safety assessment...

  18. Regulation of sphingomyelin metabolism.

    Science.gov (United States)

    Bienias, Kamil; Fiedorowicz, Anna; Sadowska, Anna; Prokopiuk, Sławomir; Car, Halina

    2016-06-01

    Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD). PMID:26940196

  19. Self-Regulated Reionization

    CERN Document Server

    Iliev, I T; Shapiro, P R; Pen, U L; Iliev, Ilian T.; Mellema, Garrelt; Shapiro, Paul R.; Pen, Ue-Li

    2006-01-01

    Recently, we have presented the first large-scale radiative transfer simulations of reionization. Here we present new simulations which extend the source halo mass range downward to 10^8M_solar, to capture the full range of halo masses thought to be primarily responsible for reionization by their star formation following atomic hydrogen radiative cooling and gravitational collapse. Haloes below about 10^9M_solar, however, are subject to Jeans-mass filtering in the ionized regions, which suppresses their baryonic content and their ability to release ionizing radiation. By including these smaller-mass haloes but accounting for their suppression, too, we find that reionization is ``self-regulating,'' as follows. As the mean ionized fraction rises, so does the fraction of the volume within which suppression occurs. Hence, the degree of suppression is related to the mean ionized fraction. Since low-mass haloes with high emissivity achieve a given mean ionized fraction earlier than do those with low efficiency, Jea...

  20. Between regulation and independence

    International Nuclear Information System (INIS)

    This article stresses, first, on the differences between electricity and gas in terms of storability and place of production before introducing the gas sector and its reorganization and re-structuration in the framework of energy markets deregulation. Then, it presents the actions carried out by the commission of energy regulation (CRE) intended to improve the operation of the gas market: improvement of transparency, incitation to invest in transportation infrastructures, organisation of the downstream market and development of regional gas markets. Since July 1, 2007, the opening of gas market is juridically and technically complete. The role of CRE is also to inform the consumers and to warrant a non-discriminatory access to infrastructures in a context of sound competition. On this point, the new situation is satisfactory but improvements are needed to increase the offer. The future objectives of CRE is to maintain a climate favorable to investments, to implement stable and efficient conditions of access to infrastructures and, finally, to regularly work at the European scale for the building up of a domestic gas market synonymous of security of supplies, sustainable development and competitiveness. (J.S.)

  1. Auditing and bank capital regulation

    OpenAIRE

    Edward Simpson Prescott

    2004-01-01

    Auditing is introduced into a model of bank capital regulation. Deterministic and stochastic auditing strategies are studied. Contrary to intuition, auditing of bank risk should be focused on the safest banks because they hold the least amount of capital. Risky banks, which hold more capital, need to be audited less. The importance of auditing by regulators and penalties for non-compliance are discussed in light of the Basel II capital regulation proposals. Emphasis is placed on the importanc...

  2. Regulations for RA reactor operation

    International Nuclear Information System (INIS)

    Regulations for RA reactor operation are written in accordance with the legal regulations defined by the Law about radiation protection and related legal acts, as well as technical standards according to the IAEA recommendations. The contents of this book include: fundamental data about the reactor; legal regulations for reactor operation; organizational scheme for reactor operation; general and detailed instructions for operation, behaviour in the reactor building, performing experiments; operating rules for operation under steady state and accidental conditions

  3. Regulations on Open Government Information

    Institute of Scientific and Technical Information of China (English)

    YOU XUEYUN

    2007-01-01

    @@ On April 24, 2007 the State Council promulgated Regulations of the People's Republic of China on Open Government Information (referred to as Regulations below), which will become effective on May 1, 2008. As the first administrative rule of the central government of China that aims to safeguard the public's right to know, the Regulations are of great significance in China's democratization and its establishment of the rule of law.

  4. Financial Private Regulation and Enforcement

    OpenAIRE

    Miller, Geoffrey

    2011-01-01

    This paper has been delivered within the context of the research project "Transnational Private Regulatory Regimes: Constitutional foundations and governance design". This paper considers the topic of private regulation and enforcement for internationally active financial services firms. The paper documents the following types of regulation and enforcement that involve significant private input: house rules, contracts, internal compliance, management-based regulation, private standard-sett...

  5. Strategic automation of emotion regulation

    OpenAIRE

    Schweiger-Gallo, Inge; Keil, Andreas; McCulloch, Kathleen C.; Rockstroh, Brigitte; Gollwitzer, Peter M.

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i...

  6. Uniform Practical Nonlinear Output Regulation

    OpenAIRE

    Marconi, Lorenzo; Praly, Laurent

    2008-01-01

    International audience In this paper, we present a solution to the problem of asymptotic and practical semiglobal regulation by output feedback for nonlinear systems. A key feature of the proposed approach is that practical regulation is achieved uniformly with respect to the dimension of the internal model and to the gain of the stabilizer near the zero error manifold. This property renders the approach interesting for a number of real cases by bridging the gap between output regulation t...

  7. Platelets actively sequester angiogenesis regulators

    OpenAIRE

    Lakka Klement, Giannoula; Yip, Tai-Tung; Cassiola, Flavia; Kikuchi, Lena; Cervi, David; Podust, Vladimir; Italiano, Joseph E.; Wheatley, Erin; Abou-Slaybi, Abdo; Bender, Elise; Almog, Nava; Kieran, Mark W.; Folkman, Judah

    2009-01-01

    Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor...

  8. The next restructuring: Environmental regulation

    International Nuclear Information System (INIS)

    From oil, to natural gas, and now electricity, the regulation of energy markets has been successively restructured to allow greater scope to market forces. The likely next domain for restructuring, environmental regulation, may seem far-fetched now, but it is no more so than the restructuring of electric utility regulation would have seemed to be twenty years ago. The grand experiment with emissions trading under the US acid rain program has set a propitious example by showing that markets in environmental goods can be constructed and that the explicit recognition of property rights in the use of the environment is compatible with effective and non-intrusive environmental regulation

  9. Utility regulation and competition policy

    International Nuclear Information System (INIS)

    Contents: 1. The New Electricity Trading Arrangements in England and Wales: A Review - David Currie, 2. A Critique of Rail Regulation - Dieter Helm, 3. Moving to a Competitive Market in Water - Colin Robinson, 4. The New Gas Trading Arrangements - George Yarrow, 5. A Review of Privatization and Regulation Experience in Britain - Irwin M. Stelzer, 6. Converging Communications: Implications for Regulation - Mark Armstrong, 7. Opening European Electricity and Gas Markets - Graham Shuttleworth, 8. Concurrency or Convergence? Competition and Regulation Under the Competition Act 1998 - Tom Sharpe QC, 9. Ten Years of European Merger Control - Paul Seabright. (Author)

  10. Power-MOSFET Voltage Regulator

    Science.gov (United States)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  11. Regulation of electricity prices?

    International Nuclear Information System (INIS)

    In this paper author deals with the regulation of electricity prices in the Slovak Republic. Author contests the social policy of the government through doped prices of electricity. Two thirds of electricity is generated in nuclear power plants in Slovakia. Hence, it is necessary to focus on the solution of problem of nuclear waste. In 2004 Ministry of Economy stated, that the deficit in nuclear fund, from which the country have to fully cover the costs of liquidation and final disposal of nuclear waste, is estimated in the amount of around 89 billion Slovak crowns (≅ 3.7 billion $). From it, so called historical deficit, which originated because of late foundation of fund, represents officially 15 billion Slovak crowns (≅ 0.62 billion $). In Slovakia exists the real risk, that by maintenance of present state by creation and draw of the fund, it will be possible to ensure only 39 per cent of financial sources necessary for full financial handling of the back part of nuclear energetic. Even though the Ministry of Economy in connection with privatisation of Slovenske elektrarne designed to decrease the transfers of operators of nuclear power plants into nuclear fund. In 2006 the Parliament decreased by the law the level of gains of the fund from sale of nuclear electricity (the second from two components of the gains of the fund) from 6.8 to 5.95 per cent from annual revenues. So the tax of forced reduction of the price of nuclear electricity will be represented by loading of the further generations

  12. Views of the regulators

    International Nuclear Information System (INIS)

    The International Commission on Radiological Protection (ICRP) offers its recommendations to regulatory and advisory bodies and provides advice to help management and professional staff with responsibility for radiation protection. The ICRP has no formal power to impose its proposals. However, legislation and regulations in most countries adhere closely to ICRP recommendations. The recommendations of the ICRP are based upon the fundamental principles and quantitative bases upon which appropriate radiation protection measures can be established. The radiation protection system recommended by the ICRP in its Publication 60 is based upon: (a) Justification principle: A practice or an activity that involves ionizing radiation exposure is justified if the anticipated benefit is greater than the risk incurred. (b) Optimization principle: All exposures from justified practices shall be kept as low as reasonably achievable (ALARA), economic and social factors being taken into account. (c) Individual dose and risk limits: Individual doses resulting from all relevant practices shall be subject to dose limits and risk limits in cases where potential exposures are likely. To manage risks, three levels are usually distinguished: unacceptable risk, tolerable risk and acceptable risk. The aim of radiation protection is to reduce the radiation exposure level to below that designated as having unacceptable risk. When radiation protection is optimized, the residual risk level becomes acceptable. Any additional measure is ineffective both from economic and social points of view. Regulatory limits adopted from ICRP recommendations are set such that continued exposure at a dose just above the limit would be unacceptable on any reasonable ground. Continued exposure at a level just below the dose limit might be tolerated but would not be welcome. Acceptable doses are those that are below the limit. Individual doses are only acceptable if they are optimized

  13. Regulating Pornography: A Public Dilemma.

    Science.gov (United States)

    Thompson, Margaret E.; And Others

    1990-01-01

    Examines attitudes toward sex and pornography by means of a telephone survey of Dane County, Wisconsin, adults. Describes survey questions about sexual attitudes, perceived effects of pornography, and pornography regulation. Concludes that adults who feel more strongly that pornography has negative effects are more opposed to its regulation. (SG)

  14. The economics of bank regulation

    OpenAIRE

    Bhattacharya, Sudipto; Arnoud W.A. Boot; Anjan V. Thakor

    1995-01-01

    The object of this paper is to survey and synthesize the literature on the regulation of financial intermediaries, including the theoretical framework and also the applied literature on specific regulations such as deposit insurance, capital controls, line of business restrictions, etc.

  15. Environmental awareness, legislations and regulations

    International Nuclear Information System (INIS)

    This paper presents a brief review of environmental awareness, legislation and regulation policies adopted in Indian nuclear power programme. Brief account of environmental legislations in India, water act, air act, environmental protection act, regulations pertaining to accidents, constitutional procedures, regulatory frame work for the protection of the environment from ionizing radiation are also discussed. (author)

  16. Deceptive Business Practices: Federal Regulations.

    Science.gov (United States)

    Rohrer, Daniel Morgan

    Federal regulations to prevent deceptive advertising seek to balance the advertiser's freedom of speech with protection of the consumer. This paper discusses what the Federal Trade Commission (FTC) has done to regulate advertising and evaluates the adequacy of its controls. The commission uses cease-and-desist orders, affirmative disclosure,…

  17. Assessing self-regulation strategies

    DEFF Research Database (Denmark)

    de Vet, Emely; de Ridder, Denise T. D.; Stok, Marijn;

    2014-01-01

    Background: Applying self-regulation strategies have proven important in eating behaviors, but it remains subject to investigation what strategies adolescents report to use to ensure healthy eating, and adequate measures are lacking. Therefore, we developed and validated a self-regulation questio...

  18. Splicing regulators: targets and drugs

    OpenAIRE

    Yeo, Gene Wei-Ming

    2005-01-01

    Silencing of splicing regulators by RNA interference, combined with splicing-specific microarrays, has revealed a complex network of distinct alternative splicing events in Drosophila, while a high-throughput screen of more than 6,000 compounds has identified drugs that interfere specifically and directly with one class of splicing regulators in human cells.

  19. RNA-guided transcriptional regulation

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  20. Regulation of gas infrastructure expansion

    International Nuclear Information System (INIS)

    The topic of this dissertation is the regulation of gas infrastructure expansion in the European Union (EU). While the gas market has been liberalised, the gas infrastructure has largely remained in the regulated domain. However, not necessarily all gas infrastructure facilities - such as gas storage facilities, LNG import terminals and certain gas transmission pipelines - need to be regulated, as there may be scope for competition. In practice, the choice of regulation of gas infrastructure expansion varies among different types of gas infrastructure facilities and across EU Member States. Based on a review of economic literature and on a series of in-depth case studies, this study explains these differences in choices of regulation from differences in policy objectives, differences in local circumstances and differences in the intrinsic characteristics of the infrastructure projects. An important conclusion is that there is potential for a larger role for competition in gas infrastructure expansion.

  1. Strategic automation of emotion regulation.

    Science.gov (United States)

    Gallo, Inge Schweiger; Keil, Andreas; McCulloch, Kathleen C; Rockstroh, Brigitte; Gollwitzer, Peter M

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i.e., an if-then plan), and a no-self-regulation control group. Only implementation-intention participants succeeded in reducing their disgust and fear reactions as compared to goal-intention and control participants. In Study 3, electrocortical correlates (using dense-array electroencephalography) revealed differential early visual activity in response to spider slides in ignore implementation-intention participants, as reflected in a smaller P1. Theoretical and applied implications of the present findings for emotion regulation via implementation intentions are discussed. PMID:19210061

  2. Designing Next Generation Telecom Regulation

    DEFF Research Database (Denmark)

    Henten, Anders; Samarajiva, Rohan

    – ICT convergence regulation and multisector utility regulation. Whatever structure of next generation telecom regulation is adopted, all countries will need to pay much greater attention to the need for increased coordination of policy directions and regulatory activities both across the industries......Continuously expanding applications of information and communication technologies (ICT) are transforming local, national, regional and international economies into network economies, the foundation for information societies. They are being built upon expanded and upgraded national telecom networks...... to creating an environment to foster a massive expansion in the coverage and capabilities of the information infrastructure networks, with national telecom regulators as the key implementers of the policies of reform. The first phase of reform has focused on industry specific telecom policy and regulation...

  3. The regulator's view

    International Nuclear Information System (INIS)

    Spanish experience holds a relatively important position in the field of the decommissioning of nuclear and radioactive facilities. Nuclear facilities are subject to a system of prior authorization by the competent authorities before they come into service and to subsequent regulation and control during their operating life. Nuclear and radioactive facilities that stop operating, for technical or financial reasons or because they are compelled to, remain subject to this regulatory control system as long as the competent authorities consider that their residual radioactivity represents a potential source of radiological hazard to the individuals affected or entails an unacceptable environmental risk. The decommissioning of nuclear facilities is contemplated in Spain a further or an additional step of their life cycle in which, in principle, the whole regulatory framework in force during the previous stages - sitting, construction, commissioning, operation, etc. - remains applicable. The term decommissioning is used to delineate the final stage of the life of a definitely non-operational facility and also to introduce a new licensing regime and a new regulatory control scheme. In the regulatory context, the decommissioning of a facility is understood as a set of administrative and technical actions and processes whose purpose, once a facility has been withdrawn from service, is to release it from regulatory control and so to relieve the former licensee of its previous responsibilities relating to the facility's safety. With the increasing age of nuclear and radioactive facilities in service, and as the number of facilities reaching the end of their operating life rises, the administrative process required in order to decommissioning them safely has become a real challenge in all countries, especially in those like Spain with an old nuclear power programme. Let me first give you a quick overview of the Spanish regulatory decommissioning framework. Then I will try to

  4. Regulation of synaptic plasticity in a schizophrenia model

    OpenAIRE

    Gisabella, Barbara; Bolshakov, Vadim Y.; Benes, Francine M.

    2005-01-01

    The pathology of schizophrenia is characterized by increased hippocampal activity at baseline and during auditory hallucinations. Animal-model studies in which the flow of activity to the hippocampus is increased through decreased amygdalar GABAergic inhibition have shown alterations of hippocampal circuitry similar to schizophrenia, but the functional importance of this phenomenon remains unclear. We provide evidence of decreased hippocampal feed-forward and tonic GABA-mediated inhibition in...

  5. Cerebello-Thalamo-Cortical Connectivity Regulates Penetrance in Dystonia

    OpenAIRE

    Argyelan, Miklos; Carbon, Maren; Niethammer, Martin; Uluğ, Aziz M.; Voss, Henning U.; Bressman, Susan B.; Dhawan, Vijay; Eidelberg, David

    2009-01-01

    Dystonia is a brain disorder characterized by sustained involuntary muscle contractions. It is typically inherited as an autosomal dominant trait with incomplete penetrance. While lacking clear degenerative neuropathology, primary dystonia is thought to involve microstructural and functional changes in neuronal circuitry. In the current study, we used magnetic resonance (MR) diffusion tensor imaging (DTI) and probabilistic tractography to identify the specific circuit abnormalities that under...

  6. Group III metabotropic glutamate receptors and drug addiction.

    Science.gov (United States)

    Mao, Limin; Guo, Minglei; Jin, Daozhong; Xue, Bing; Wang, John Q

    2013-12-01

    Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates). PMID:24078068

  7. The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation.

    Science.gov (United States)

    Wang, Xiaowei; Shaw, Dana K; Hammond, Holly L; Sutterwala, Fayyaz S; Rayamajhi, Manira; Shirey, Kari Ann; Perkins, Darren J; Bonventre, Joseph V; Velayutham, Thangam S; Evans, Sean M; Rodino, Kyle G; VieBrock, Lauren; Scanlon, Karen M; Carbonetti, Nicholas H; Carlyon, Jason A; Miao, Edward A; McBride, Jere W; Kotsyfakis, Michail; Pedra, Joao H F

    2016-08-01

    Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL)-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum. PMID:27482714

  8. Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period.

    Science.gov (United States)

    Sabihi, Sara; Dong, Shirley M; Durosko, Nicole E; Leuner, Benedetta

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors. PMID:25147513

  9. The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation

    Science.gov (United States)

    Wang, Xiaowei; Shaw, Dana K.; Hammond, Holly L.; Sutterwala, Fayyaz S.; Rayamajhi, Manira; Shirey, Kari Ann; Perkins, Darren J.; Bonventre, Joseph V.; Velayutham, Thangam S.; Evans, Sean M.; Rodino, Kyle G.; VieBrock, Lauren; Scanlon, Karen M.; Carbonetti, Nicholas H.; Carlyon, Jason A.; Miao, Edward A.; McBride, Jere W.; Kotsyfakis, Michail

    2016-01-01

    Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL)-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum. PMID:27482714

  10. Regulation of Local Ambient GABA Levels via Transporter-Mediated GABA Import and Export for Subliminal Learning.

    Science.gov (United States)

    Hoshino, Osamu

    2015-06-01

    Perception of supraliminal stimuli might in general be reflected in bursts of action potentials (spikes), and their memory traces could be formed through spike-timing-dependent plasticity (STDP). Memory traces for subliminal stimuli might be formed in a different manner, because subliminal stimulation evokes a fraction (but not a burst) of spikes. Simulations of a cortical neural network model showed that a subliminal stimulus that was too brief (10 msec) to perceive transiently (more than about 500 msec) depolarized stimulus-relevant principal cells and hyperpolarized stimulus-irrelevant principal cells in a subthreshold manner. This led to a small increase or decrease in ongoing-spontaneous spiking activity frequency (less than 1 Hz). Synaptic modification based on STDP during this period effectively enhanced relevant synaptic weights, by which subliminal learning was improved. GABA transporters on GABAergic interneurons modulated local levels of ambient GABA. Ambient GABA molecules acted on extrasynaptic receptors, provided principal cells with tonic inhibitory currents, and contributed to achieving the subthreshold neuronal state. We suggest that ongoing-spontaneous synaptic alteration through STDP following subliminal stimulation may be a possible neuronal mechanism for leaving its memory trace in cortical circuitry. Regulation of local ambient GABA levels by transporter-mediated GABA import and export may be crucial for subliminal learning. PMID:25774546

  11. Regulated electricity retailing in Chile

    Energy Technology Data Exchange (ETDEWEB)

    Galetovic, Alexander, E-mail: alexander@galetovic.cl [Facultad de Ciencias Economicas y Empresariales, Universidad de los Andes, Santiago, Chile. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago (Chile); Munoz, Cristian M., E-mail: cmunozm@aes.com [AES Gener and Departamento de Ingenieria Electrica, Universidad Catolica de Chile (Chile)

    2011-10-15

    While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: > We review Chile's experience with regulated electricity retailing. > Distortions emerge when energy wholesale prices are volatile and prices stabilized. > Regulated retailers gain little by mitigating or correcting distortions. > Sometimes price distortions increase retailers' profits. > We estimate the cost of three distortions, which retailers have not corrected.

  12. Regulated electricity retailing in Chile

    International Nuclear Information System (INIS)

    While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: → We review Chile's experience with regulated electricity retailing. → Distortions emerge when energy wholesale prices are volatile and prices stabilized. → Regulated retailers gain little by mitigating or correcting distortions. → Sometimes price distortions increase retailers' profits. → We estimate the cost of three distortions, which retailers have not corrected.

  13. Grandfather regulations, new source bias, and state air toxics regulations

    International Nuclear Information System (INIS)

    This paper uses plant-level data from the Census of Manufactures and the variation in toxic air pollution regulations across states to measure the effects of laws that are more stringent for new sources of pollution than for existing sources (so-called 'grandfather' regulations). Of particular interest is the resulting 'new source bias' and its effects on capital vintage and investment. Two industries are examined: commercial printing, which has a local product market; and paint manufacturing, which has a more national market. In general, there seem to be no statistically significant differences in capital vintage or investment between plants in states that grandfather new sources of pollution, plants in states that have no air toxics regulations, and plants in states that regulate both new and existing sources

  14. Nanometrology - challenges for health regulation

    Directory of Open Access Journals (Sweden)

    Jailton Carreteiro Damasceno

    2013-11-01

    Full Text Available The relationship between metrology, nanotechnology and nanoscience and sanitary regulation is discussed from the point of view of its importance and the interrelationship between the themes for the development of products and services involving nanotech-nology. The discussion involves the main techniques for measuring dimensional, chemical and biological properties of materials, and presents some of the challenges for the future. Issues such as processes of standardization and regulation in Europe, U.S. and Brazil are also addressed, providing an overview of how these processes are related to sanitary regulation.

  15. Introduction to international radio regulations

    International Nuclear Information System (INIS)

    These lecture notes contain an overview of basic problems of the International Radio Regulations. Access to the existing information infrastructure, and to that of the future Information Society, depends critically on radio, especially in poor, remote and sparsely populated regions with under-developed telecommunication infrastructure. How the spectrum of radio frequencies is regulated has profound impact on the society, its security, prosperity, and culture. The radio regulations represent a very important framework for an adequate use of radio and should be known by all of those working in the field

  16. Designing Next Generation Telecom Regulation

    DEFF Research Database (Denmark)

    Henten, Anders; Samarajiva, Rohan; Melody, William H.

    2003-01-01

    This article critically examines the multiple rationales for telecom, IT, media convergence regulation, on the one hand, and multisector utility regulation, on the other, and the practical questions of implementation they pose, with a view to contributing to informed policy and regulatory decisions...... to the regulatory process such as scarcity of regulatory resources and safeguards for regulatory independence, are examined. It is concluded that ICT and media convergence issues are primarily about improving the efficiency of market economies, and how changes in regulation can facilitate this process. Multi...

  17. FDA 101: Regulating Biological Products

    Science.gov (United States)

    ... and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to Z ... public health needs enforces regulations to prevent the introduction or spread of communicable diseases within the country ...

  18. Comparison of some European regulations

    Energy Technology Data Exchange (ETDEWEB)

    Argyriadis, K. [Germanisher Lloyd, Hamburg (Germany)

    1996-09-01

    Fatigue calculations are an essential part in certification of a wind turbine. Manufacturers have to fulfill recommendations of several different regulations throughout Europe with the result that the design has often to be altered to satisfy them. In general three national (D/GL, NL, DK), and two international (GL, IEC) regulations are in use, with the IEC standard getting more importance with wind energy deploying to more in regions with no yet clearly defined national standards (India, Spain). The Germanischer Lloyd made calculations for wind turbines they are certifying and in one case we compared the resulting damages for different regulations and classes on a 600 kW, three bladed, stall regulated wind turbine. (EG) 18 refs.

  19. PDH regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian

    state is determined by the overall content / activity of the regulatory proteins PDH kinase (PDK), of which there are 4 isoforms, and PDH phosphatase (PDP), of which there are 2 isoforms. The overall aim of the PhD project was to elucidate 4 issues. 1: Role of muscle type in resting and exercise......-induced PDH regulation in human skeletal muscle. 2: Effect of muscle glycogen on PDH regulation in human skeletal muscle at rest and during exercise. 3: The impact of physical inactivity on PDH regulation in human skeletal muscle at rest and during exercise. 4: Elucidating the importance of PGC-1? in PDH...... regulation in mouse skeletal muscle at rest and in response to fasting and during recovery from exercise. The studies indicate that the content of PDH-E1? in human muscle follows the metabolic profile of the muscle, rather than the myosin heavy chain fiber distribution of the muscle. The larger lactate...

  20. EPA's Environmental Laws and Regulations

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web page provides access to search and read the environmental laws and regulations related to EPA's mission. Regulatory guidance documents and rulemaking...

  1. Hydrography - Boating Special Regulation Streams

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This layer contains those streams/rivers within Pennsylvania that have specifc special regulations related to boating as defined by the Pennsylvania Fish and Boat...

  2. Network Regulation and Support Schemes

    DEFF Research Database (Denmark)

    Ropenus, Stephanie; Schröder, Sascha Thorsten; Jacobsen, Henrik

    2009-01-01

    -in tariffs to market-based quota systems, and network regulation approaches, comprising rate-of-return and incentive regulation. National regulation and the vertical structure of the electricity sector shape the incentives of market agents, notably of distributed generators and network operators....... This article seeks to investigate the interactions between the policy dimensions of support schemes and network regulation and how they affect the deployment of distributed generation. Firstly, a conceptual analysis examines how the incentives of the different market agents are affected. In particular......, it will be shown that there frequently exists a trade-off between the creation of incentives for distributed generators and for distribution system operators to facilitate the integration of distributed generation. Secondly, the interaction of these policy dimensions is analyzed, including case studies based...

  3. Electronic Code of Federal Regulations

    Data.gov (United States)

    National Archives and Records Administration — The Electronic Code of Federal Regulations (e-CFR) is the codification of the general and permanent rules published in the Federal Register by the executive...

  4. Regulations concerning nuclear facilities decommissioning

    International Nuclear Information System (INIS)

    After a short presentation of the French nuclear regulations, a short overview of their application is given. Finally, are presented the points related to the fiscality specific of nuclear basis facilities

  5. Automated Negotiation for Traffic Regulation

    OpenAIRE

    Gaciarz, Matthis; Aknine, Samir; BHOURI, Neila

    2015-01-01

    Urban congestion is a major problem in our society for quality of life and for productivity. The increasing communication abilities of vehicles and recent advances in artificial intelligence allow new solutions to be considered for traffic regulation, based on real-time information and distributed cooperative decision-making models. The paper presents a mechanism allowing a distributed regulation of the right-of-way of the vehicles at an intersection. The decision-making relies on an automati...

  6. How should Bitcoin be regulated ?

    OpenAIRE

    SHCHERBAK, Sergii

    2014-01-01

    The lack of clarity about Bitcoin’s legal framework has meant that none of the regulators across the EU have yet achieved sufficient clarity in the legal treatment of Bitcoin and its stakeholders. This uncertainty poses a number of substantial risks to Bitcoin stakeholders and creates challenges for regulatory authorities. Therefore, there is a need for a clear strategy for Bitcoin’s regulation aiming to ensure the maximum possible balance between the interests of Bitcoin stakeholders longing...

  7. Money laundering and its regulations

    OpenAIRE

    Chong, Alberto; López-de-Silanes, Florencio

    2007-01-01

    The recent wave of terrorist attacks has increased the attention paid to money laundering activities. Using several methodologies, this paper investigates empirically the determinants of money laundering and its regulation in over 80 countries by assembling a cross-country dataset on proxies for money laundering and the prevalence of feeding activities. The paper additionally constructs specific money laundering regulation indices based on available information on laws and their mechanisms of...

  8. Money Laundering and its Regulation

    OpenAIRE

    Chong, Alberto E.; Florencio López-de-Silanes

    2007-01-01

    The recent wave of terrorist attacks has increased the attention paid to money laundering activities. Using several methodologies, this paper investigates empirically the determinants of money laundering and its regulation in over 80 countries by assembling a cross-country dataset on proxies for money laundering and the prevalence of feeding activities. The paper additionally constructs specific money laundering regulation indices based on available information on laws and their mechanisms of...

  9. BIOTECHNOLOGY REGULATIONS AND THE WTO

    OpenAIRE

    Sheldon, Ian M.; Josling, Timothy E.

    2002-01-01

    This paper examines the regulation of trade in genetically modified organisms (GMOs) by the World Trade Organization (WTO). Despite rapid adoption of GMOs by a few exporters, many importers have developed relatively restrictive procedures for pre-market approval of GMOs, and are introducing mandatory labeling. While exporters have yet to seek a ruling from the WTO on these regulations, a trade dispute over GMOs is likely to occur before too long. Exporting countries will likely argue that imp...

  10. Emotion regulation and sport performance

    OpenAIRE

    Wagstaff, Chris

    2014-01-01

    This study used a single-blind, within-participant, counterbalanced, repeated-measures design to examine the relationship between emotional self-regulation and sport performance. Twenty competitive athletes completed four laboratory-based conditions; familiarization, control, emotion suppression, and nonsuppression. In each condition participants completed a 10-km cycling time trial requiring self-regulation. In the experimental conditions participants watched an upsetting video before perfor...

  11. Regulation and Corporate Board Composition

    OpenAIRE

    Staubo, Siv

    2014-01-01

    This thesis is in the field of corporate governance. The corporate governance structure involves laws, rules, and regulations on the distribution of rights and responsibilities among the different stakeholders in the firm. Due to several financial crises in the late 1990s and early 2000s, there has been an increased interest in the regulation of corporate governance. In particular, the composition of the corporate board has achieved extensive attention. The first essay in the thesis inve...

  12. Civilsamfundets ABC: R for Regulering

    DEFF Research Database (Denmark)

    Meyer, Gitte; Lund, Anker Brink

    2016-01-01

    Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering.......Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering....

  13. Corporate governance and banking regulation

    OpenAIRE

    Alexander, Kern

    2004-01-01

    The globalisation of banking markets has raised important issues regarding corporate governance regulation for banking institutions. This research paper addresses some of the major issues of corporate governance as it relates to banking regulation. The traditional principal-agent framework will be used to analyse some of the major issues involving corporate governance and banking institutions. It begins by analysing the emerging international regime of bank corporate governance. This has been...

  14. Quality of government regulated goods

    OpenAIRE

    Moszoro, Marian

    2010-01-01

    Regulators face the difficult task of determining the sets of price and quality of government-regulated goods. While the profit-maximizing monopoly always produces less in quantity than under free competition, the level of quality produced by the monopoly is not unequivocal: it depends on its cost and demand functions. The social effect of quality change is not unequivocal either, because it depends, apart from the cost function change, on the shift and tilt change of the demand curve. The pr...

  15. Regulating Power from Supermarket Refrigeration

    DEFF Research Database (Denmark)

    O'Connell, Niamh; Madsen, Henrik; Pinson, Pierre;

    2014-01-01

    This paper presents an analysis of the demand response capabilities of a supermarket refrigeration system, with a particular focus on the suitability for participation in the regulating power market. An ARMAX model of a supermarket refrigeration system is identified using experimental data from t...... represented in a manner that is sufficiently simple to communicate to a market operator in the form of a bid for the provision of regulating power....

  16. Dividend Policy in Regulated Firms

    OpenAIRE

    rondi, laura; Cambini, Carlo; bremberger, francisca; GUGLER, Klaus

    2013-01-01

    We study the impact of different regulatory and ownership regimes on the dividend policy of regulated firms. Using a panel of 106 publicly traded European electric utilities in the period 1986-2010, we link payout and smoothing decisions to the implementation of different regulatory mechanisms (cost plus vs. incentive regulation) and to firm ownership (state vs. private). After controlling for the potential endogeneity of the regulatory mechanism, our results show that utilities subject to i...

  17. International Competitiveness and Environmental Regulations

    OpenAIRE

    Babool, Md. Ashfaqul Islam; Michael R. Reed

    2005-01-01

    This study follows the standard factor endowment approach to explain the effects of environmental regulations on net exports in different product-based industries. It constructs an econometric model which includes factor endowments and environmental regulations to examine how strict environmental policy impact export competitiveness. Cross-sectional and time series (panel) data for 6 countries and 17 years were used in this model. In this study, capital services increase net exports in labor-...

  18. Environmental regulation and technology transfers

    OpenAIRE

    Asano, Takao; Matsushima, Noriaki

    2012-01-01

    This paper analyzes the situation in which a national government introduces environmental regulations. Within the framework of an international duopoly with environmental regulations, this paper shows that an environmental tax imposed by the government in the home country can induce a foreign firm with advanced abatement technology to license it to a domestic firm without this technology. Furthermore, when the domestic firm's production technology is less efficient than that of the foreign fi...

  19. Social defeat during adolescence and adulthood differentially induce BDNF-regulated immediate early genes

    Directory of Open Access Journals (Sweden)

    Caroline M. Coppens

    2011-11-01

    Full Text Available Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP and brain-derived neurotrophic factor (BDNF signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats.

  20. Functionally Similar WRKY Proteins Regulate Vacuolar Acidification in Petunia and Hair Development in Arabidopsis.

    Science.gov (United States)

    Verweij, Walter; Spelt, Cornelis E; Bliek, Mattijs; de Vries, Michel; Wit, Niek; Faraco, Marianna; Koes, Ronald; Quattrocchio, Francesca M

    2016-03-01

    The WD40 proteins ANTHOCYANIN11 (AN11) from petunia (Petunia hybrida) and TRANSPARENT TESTA GLABRA1 (TTG1) fromArabidopsis thalianaand associated basic helix-loop-helix (bHLH) and MYB transcription factors activate a variety of differentiation processes. In petunia petals, AN11 and the bHLH protein AN1 activate, together with the MYB protein AN2, anthocyanin biosynthesis and, together with the MYB protein PH4, distinct genes, such asPH1andPH5, that acidify the vacuole. To understand how AN1 and AN11 activate anthocyanin biosynthetic andPHgenes independently, we isolatedPH3 We found thatPH3is a target gene of the AN11-AN1-PH4 complex and encodes a WRKY protein that can bind to AN11 and is required, in a feed-forward loop, together with AN11-AN1-PH4 for transcription ofPH5 PH3 is highly similar to TTG2, which regulates hair development, tannin accumulation, and mucilage production in Arabidopsis. Like PH3, TTG2 can bind to petunia AN11 and the Arabidopsis homolog TTG1, complementph3in petunia, and reactivate the PH3 target genePH5 Our findings show that the specificity of WD40-bHLH-MYB complexes is in part determined by interacting proteins, such as PH3 and TTG2, and reveal an unanticipated similarity in the regulatory circuitry that controls petunia vacuolar acidification and Arabidopsis hair development. PMID:26977085