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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

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    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. 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

  4. Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle.

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    Rattan, Satish; Ali, Mehboob

    2015-04-01

    Preliminary proteomics studies between tonic vs. phasic smooth muscles identified three distinct protein spots identified to be those of transgelin (SM22). The latter was found to be distinctly downregulated in the internal anal sphincter (IAS) vs. rectal smooth muscle (RSM) SMC. The major focus of the present studies was to examine the differential molecular control mechanisms by SM22 in the functionality of truly tonic smooth muscle of the IAS vs. the adjoining phasic smooth muscle of the RSM. We monitored SMC lengths before and after incubation with pFLAG-SM22 (for SM22 overexpression), and SM22 small-interfering RNA. pFLAG-SM22 caused concentration-dependent and significantly greater relaxation in the IAS vs. the RSM SMCs. Conversely, temporary silencing of SM22 caused contraction in both types of the SMCs. Further studies revealed a significant reverse relationship between the levels of SM22 phosphorylation and the amount of SM22-actin binding in the IAS and RSM SMC. Data showed higher phospho-SM22 levels and decreased SM22-actin binding in the IAS, and reverse to be the case in the RSM SMCs. Experiments determining the mechanism for SM22 phosphorylation in these smooth muscles revealed that Y-27632 (Rho kinase inhibitor) but not Gö-6850 (protein kinase C inhibitor) caused concentration-dependent decreased phosphorylation of SM22. We speculate that SM22 plays an important role in the regulation of basal tone via Rho kinase-induced phosphorylation of SM22.

  5. 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

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

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    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 ...

  7. Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity.

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    Gee, Dylan G

    2016-09-01

    Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental buffering regulates emotional behaviors and stress physiology as emotion regulation circuitry continues to mature. By contrast, disorganized or poor quality caregiving has profound and lasting consequences on the maturation of frontoamygdala circuitry essential for emotion regulation, even following termination of this early life stressor (e.g., adoption from orphanage). This article highlights how interactions between caregiving experiences and the biological state of the developing brain have broad implications for long-term health. PMID:27589500

  8. 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

  9. 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-

  10. 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...

  11. 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.

  12. 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.

  13. 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

  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. Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise.

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    Antoine Lutz

    Full Text Available Recent brain imaging studies using functional magnetic resonance imaging (fMRI have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices during meditation (versus rest. During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ, and right posterior superior temporal sulcus (pSTS in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in

  16. Neural circuitry underlying the regulation of conditioned fear and its relation to extinction.

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    Delgado, Mauricio R; Nearing, Katherine I; Ledoux, Joseph E; Phelps, Elizabeth A

    2008-09-11

    Recent efforts to translate basic research to the treatment of clinical disorders have led to a growing interest in exploring mechanisms for diminishing fear. This research has emphasized two approaches: extinction of conditioned fear, examined across species; and cognitive emotion regulation, unique to humans. Here, we sought to examine the similarities and differences in the neural mechanisms underlying these two paradigms for diminishing fear. Using an emotion regulation strategy, we examine the neural mechanisms of regulating conditioned fear using fMRI and compare the resulting activation pattern with that observed during classic extinction. Our results suggest that the lateral PFC regions engaged by cognitive emotion regulation strategies may influence the amygdala, diminishing fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction. These findings further suggest that humans may have developed complex cognition that can aid in regulating emotional responses while utilizing phylogenetically shared mechanisms of extinction.

  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. 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

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

    Science.gov (United States)

    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.

  20. 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

  1. 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

  2. Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence.

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    Mastwal, Surjeet; Ye, Yizhou; Ren, Ming; Jimenez, Dennisse V; Martinowich, Keri; Gerfen, Charles R; Wang, Kuan Hong

    2014-07-16

    The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in humans. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Using optogenetic stimulation and in vivo two-photon imaging in adolescent mice, we found that phasic, but not tonic, dopamine neuron activity induces the formation of mesofrontal axonal boutons. In contrast, in adult mice, the effect of phasic activity diminishes. Furthermore, our results showed that dopaminergic and glutamatergic transmission regulate this axonal plasticity in adolescence and inhibition of dopamine D2-type receptors restores this plasticity in adulthood. Finally, we found that phasic activation of dopamine neurons also induces greater changes in mesofrontal circuit activity and psychomotor response in adolescent mice than in adult mice. Together, our findings demonstrate that the structure and function of the mesofrontal circuit are modifiable by phasic activity in dopaminergic neurons during adolescence and suggest that the greater plasticity in adolescence may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control.

  3. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.

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    Shantelle L LaFayette

    Full Text Available Fungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC, which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which

  4. 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

  5. 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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    Campbell, Jason C.; Polan-Couillard, Lauren F.; Chin-Sang, Ian D.; Bendena, William G.

    2016-01-01

    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 and sensorimotor

  6. Tonic and phasic co-variation of peripheral arousal indices in infants

    Science.gov (United States)

    Wass, S.V.; de Barbaro, K.; Clackson, K.

    2015-01-01

    Tonic and phasic differences in peripheral autonomic nervous system (ANS) indicators strongly predict differences in attention and emotion regulation in developmental populations. However, virtually all previous research has been based on individual ANS measures, which poses a variety of conceptual and methodlogical challenges to comparing results across studies. Here we recorded heart rate, electrodermal activity (EDA), pupil size, head movement velocity and peripheral accelerometry concurrently while a cohort of 37 typical 12-month-old infants completed a mixed assessment battery lasting approximately 20 min per participant. We analysed covariation of these autonomic indices in three ways: first, tonic (baseline) arousal; second, co-variation in spontaneous (phasic) changes during testing; third, phasic co-variation relative to an external stimulus event. We found that heart rate, head velocity and peripheral accelerometry showed strong positive co-variation across all three analyses. EDA showed no co-variation in tonic activity levels but did show phasic positive co-variation with other measures, that appeared limited to sections of high but not low general arousal. Tonic pupil size showed significant positive covariation, but phasic pupil changes were inconsistent. We conclude that: (i) there is high covariation between autonomic indices in infants, but that EDA may only be sensitive at extreme arousal levels, (ii) that tonic pupil size covaries with other indices, but does not show predicted patterns of phasic change and (iii) that motor activity appears to be a good proxy measure of ANS activity. The strongest patterns of covariation were observed using epoch durations of 40 s per epoch, although significant covariation between indices was also observed using shorter epochs (1 and 5 s). PMID:26316360

  7. Extracorporeal membrane oxygenation circuitry.

    Science.gov (United States)

    Lequier, Laurance; Horton, Stephen B; McMullan, D Michael; Bartlett, Robert H

    2013-06-01

    The extracorporeal membrane oxygenation circuit is made of a number of components that have been customized to provide adequate tissue oxygen delivery in patients with severe cardiac and/or respiratory failure for a prolonged period of time (days to weeks). A standard extracorporeal membrane oxygenation circuit consists of a mechanical blood pump, gas-exchange device, and a heat exchanger all connected together with circuit tubing. Extracorporeal membrane oxygenation circuits can vary from simple to complex and may include a variety of blood flow and pressure monitors, continuous oxyhemoglobin saturation monitors, circuit access sites, and a bridge connecting the venous access and arterial infusion limbs of the circuit. Significant technical advancements have been made in the equipment available for short- and long-term extracorporeal membrane oxygenation applications. Contemporary extracorporeal membrane oxygenation circuits have greater biocompatibility and allow for more prolonged cardiopulmonary support time while minimizing the procedure-related complications of bleeding, thrombosis, and other physiologic derangements, which were so common with the early application of extracorporeal membrane oxygenation. Modern era extracorporeal membrane oxygenation circuitry and components are simpler, safer, more compact, and can be used across a wide variety of patient sizes from neonates to adults. PMID:23735989

  8. 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...

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    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...... of the boundaries of dopaminergic volume transmission. Bursts primarily increase occupancy of D(1) receptors, whereas pauses translate into low occupancy of D(1) and D(2) receptors. Phasic firing patterns, composed of bursts and pauses, reduce the average D(2) receptor occupancy and increase average D(1) receptor...... occupancy compared with equivalent tonic firing. Receptor occupancy is crucially dependent on synchrony and the balance between tonic and phasic firing modes. Our results provide quantitative insight in the dynamics of volume transmission and complement experimental data obtained with electrophysiology...

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

    Science.gov (United States)

    Ilango, Anton; Kesner, Andrew J; Broker, Carl J; Wang, Dong V; Ikemoto, Satoshi

    2014-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Anton eIlango

    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.

  13. 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...

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

    Science.gov (United States)

    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

  15. 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

  16. 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...

  17. Phasic phosphorylation of caldesmon and ERK 1/2 during contractions in human myometrium.

    Science.gov (United States)

    Paul, Jonathan; Maiti, Kaushik; Read, Mark; Hure, Alexis; Smith, Julia; Chan, Eng-Cheng; Smith, Roger

    2011-01-01

    Human myometrium develops phasic contractions during labor. Phosphorylation of caldesmon (h-CaD) and extracellular signal-regulated kinase 1/2 (ERK 1/2) has been implicated in development of these contractions, however the phospho-regulation of these proteins is yet to be examined during periods of both contraction and relaxation. We hypothesized that protein phosphorylation events are implicated in the phasic nature of myometrial contractions, and aimed to examine h-CaD and ERK 1/2 phosphorylation in myometrium snap frozen at specific stages, including; (1) prior to onset of contractions, (2) at peak contraction and (3) during relaxation. We aimed to compare h-CaD and ERK 1/2 phosphorylation in vitro against results from in vivo studies that compared not-in-labor (NIL) and laboring (L) myometrium. Comparison of NIL (n = 8) and L (n = 8) myometrium revealed a 2-fold increase in h-CaD phosphorylation (ser-789; P = 0.012) during onset of labor in vivo, and was associated with significantly up-regulated ERK2 expression (P = 0.022), however no change in ERK2 phosphorylation was observed (P = 0.475). During in vitro studies (n = 5), transition from non-contracting tissue to tissue at peak contraction was associated with increased phosphorylation of both h-CaD and ERK 1/2. Furthermore, tissue preserved at relaxation phase exhibited diminished levels of h-CaD and ERK 1/2 phosphorylation compared to tissue preserved at peak contraction, thereby producing a phasic phosphorylation profile for h-CaD and ERK 1/2. h-CaD and ERK 1/2 are phosphorylated during myometrial contractions, however their phospho-regulation is dynamic, in that h-CaD and ERK 1/2 are phosphorylated and dephosphorylated in phase with contraction and relaxation respectively. Comparisons of NIL and L tissue are at risk of failing to detect these changes, as L samples are not necessarily preserved in the midst of an active contraction.

  18. 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

  19. EEG spectral power in phasic and tonic REM sleep: different patterns in young adults and children.

    Science.gov (United States)

    Simor, Péter; Gombos, Ferenc; Szakadát, Sára; Sándor, Piroska; Bódizs, Róbert

    2016-06-01

    Rapid eye movement sleep is composed of phasic and tonic periods, two distinguishable microstates in terms of arousal thresholds and sensory processing. Background electroencephalogram oscillations are also different between periods with (phasic state) and periods without (tonic state) eye movements. In Study 1, previous findings analysing electroencephalogram spectral power in phasic and tonic rapid eye movement sleep were replicated, and analyses extended to the high gamma range (52-90 Hz). In Study 2, phasic and tonic spectral power differences within a group of 4-8-year-old children were examined. Based on the polysomnographic data of 20 young adults, the phasic state yielded increased delta and theta power in anterior sites, as well as generally decreased high alpha and beta power in comparison to the tonic state. Moreover, phasic periods exhibited greater spectral power in the lower and the higher gamma band. Interestingly, children (n = 18) exhibited a different pattern, showing increased activity in the low alpha range during phasic periods. Moreover, during phasic in contrast to tonic rapid eye movement sleep, increased low and high gamma and enhanced low gamma band power emerged in anterior and posterior regions, respectively. The current findings show that spectral activity within the high gamma range substantially contributes to the differences between phasic and tonic rapid eye movement sleep, especially in adults. Moreover, the current data underscore the heterogeneity of rapid eye movement sleep, and point to marked differences between young adults and children regarding phasic/tonic electroencephalogram spectral power. These results suggest that the differentiation between phasic and tonic rapid eye movement periods undergoes maturation.

  20. 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.

  1. Interface Electronic Circuitry for an Electronic Tongue

    Science.gov (United States)

    Keymeulen, Didier; Buehler, Martin

    2007-01-01

    Electronic circuitry has been developed to serve as an interface between an electronic tongue and digital input/output boards in a laptop computer that is used to control the tongue and process its readings. Electronic tongues can be used for a variety of purposes, including evaluating water quality, analyzing biochemicals, analyzing biofilms, and measuring electrical conductivities of soils.

  2. Optogenetic dissection of medial prefrontal cortex circuitry

    Directory of Open Access Journals (Sweden)

    Danai eRiga

    2014-12-01

    Full Text Available The medial prefrontal cortex (mPFC is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g. thalamus, striatum, amygdala and hippocampus, the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

  3. 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.

  4. 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

  5. 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.

  6. The Development of Micromachined Gyroscope Structure and Circuitry Technology

    Science.gov (United States)

    Xia, Dunzhu; Yu, Cheng; Kong, Lun

    2014-01-01

    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. PMID:24424468

  7. The development of micromachined gyroscope structure and circuitry technology.

    Science.gov (United States)

    Xia, Dunzhu; Yu, Cheng; Kong, Lun

    2014-01-01

    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.

  8. Pharyngeal pumping in Caenorhabditis elegans depends on tonic and phasic signaling from the nervous system

    Science.gov (United States)

    Trojanowski, Nicholas F.; Raizen, David M.; Fang-Yen, Christopher

    2016-01-01

    Rhythmic movements are ubiquitous in animal locomotion, feeding, and circulatory systems. In some systems, the muscle itself generates rhythmic contractions. In others, rhythms are generated by the nervous system or by interactions between the nervous system and muscles. In the nematode Caenorhabditis elegans, feeding occurs via rhythmic contractions (pumping) of the pharynx, a neuromuscular feeding organ. Here, we use pharmacology, optogenetics, genetics, and electrophysiology to investigate the roles of the nervous system and muscle in generating pharyngeal pumping. Hyperpolarization of the nervous system using a histamine-gated chloride channel abolishes pumping, and optogenetic stimulation of pharyngeal muscle in these animals causes abnormal contractions, demonstrating that normal pumping requires nervous system function. In mutants that pump slowly due to defective nervous system function, tonic muscle stimulation causes rapid pumping, suggesting tonic neurotransmitter release may regulate pumping. However, tonic cholinergic motor neuron stimulation, but not tonic muscle stimulation, triggers pumps that electrophysiologically resemble typical rapid pumps. This suggests that pharyngeal cholinergic motor neurons are normally rhythmically, and not tonically active. These results demonstrate that the pharynx generates a myogenic rhythm in the presence of tonically released acetylcholine, and suggest that the pharyngeal nervous system entrains contraction rate and timing through phasic neurotransmitter release. PMID:26976078

  9. 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.

  10. Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS).

    Science.gov (United States)

    McDougall, Stuart J; Bailey, Timothy W; Mendelowitz, David; Andresen, Michael C

    2008-03-01

    The anesthetic propofol is thought to induce rapid hypnotic sedation by facilitating a GABAergic tonic current in forebrain neurons. The depression of cardiovascular and respiratory regulation often observed during propofol suggests potential additional actions within the brainstem. Here we determined the impacts of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In horizontal brainstem slices, we recorded from NTS neurons directly activated by solitary tract (ST) axons. We identified these second-order NTS neurons by time-invariant ("jitter"NTS at lower concentrations than tonic current induction, opposite to the relative sensitivity observed in forebrain regions. These data suggest that therapeutic levels of propofol facilitate phasic (synaptic) inhibitory transmission in second-order NTS neurons which likely inhibits autonomic reflex pathways during anesthesia.

  11. 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.

  12. BaCl2- and 4-aminopyridine-evoked phasic contractions in the rat vas deferens.

    OpenAIRE

    Huang, Y.

    1995-01-01

    1. The actions of BaCl2 and 4-aminopyridine, blockers of K+ channels, on the mechanical activity of the epididymal half of the rat vas deferens were investigated. 2. Both BaCl2 and 4-aminopyridine dose-dependently evoked phasic contractions. High extracellular potassium (35-40 mM) caused a tonic contraction but abolished the BaCl2- and 4-aminopyridine-induced phasic activity and reduced the BaCl2-induced sustained component of contraction, but increased the 4-aminopyridine-induced tonic contr...

  13. 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.

  14. Semiconductors can be tested without removing them from circuitry

    Science.gov (United States)

    Allen, B. C.

    1966-01-01

    Oscilloscope, with specially developed test circuitry, quickly checks semiconductors without removing them from the circuitry. For transistors, approximate gain and linearity, as well as PNP or NPN determinations are made. When testing diodes, open or short circuits, and reverse polarity show up plainly.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Chelsea A Vadnie

    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.

  17. A New Explicit Algorithm for Bi-Phasic Mixture Flow in MIM

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Metal injection moulding (MIM) is a new technology to manufacture small intricate parts in large quantity. Numerical simulation plays an important role in its development. To predict the specific segregation effect in MIM injection, mixture theory is adopted to model the injection flow by a bi-phasic model. This model conducts to the solution of two-coupled Stokes equations. It is an extremely computational consuming solution in the scope of the traditional algorithms, which induce a serious challenge to cost-effectivity of the MIM simulation. Referred to some methods proposed by Lewis in mono-phasic simulation and the implicit algorithms in MIM simulation, a new explicit algorithm is proposed and realized to perform efficiently this type of bi-phasic flow. Numerically this algorithm is devised to perform the simulation in a fully uncoupled manner except for a global solution of the pressure field in each time step. The physical coupling is taken into account in a sequential pattern by fractional steps. This special algorithm does not need any iteration, so it is straightforward and robust, suitable for MIM simulation and other sorts of simulations for multi-phasic flow.

  18. 76 FR 79215 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same...

    Science.gov (United States)

    2011-12-21

    ... COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same... importation of certain semiconductor chips with DRAM circuitry, and modules and products containing same by... after importation of certain semiconductor chips with DRAM circuitry, and modules and...

  19. Role of PKC and RhoA/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle.

    Science.gov (United States)

    Singh, Jagmohan; Rattan, Satish

    2013-04-15

    The role of PKC and RhoA/ROCK pathways in the phasic activities in the rectal smooth muscles (RSM) in the basal state is not known. We examined this issue by determining the effects of PKC inhibitors (calphostin C and Gö-6850) and a ROCK inhibitor (Y-27632) on the slow-rate (~3/min) and fast-rate (~25/min) phasic activities. We also examined the corresponding signal transduction cascades and the PKC and ROCK enzymatic activities in the RSM in the basal state. PKC inhibition with calphostin C and Gö-6850 (10(-5) M) caused a significant decrease (~25%) in slow-rate (but not fast-rate) phasic activity (monitored by frequency and amplitude of contractions) of the RSM. Conversely, ROCK inhibition with Y-27632 (10(-5) M) caused a significant decrease not only in slow-rate, but also fast-rate, phasic activity caused by ROCK inhibition in the RSM. Western blot analysis revealed that the PKC inhibition-induced decrease in RSM phasic activity was associated with decreases in PKCα translocation, phosphorylated (Thr(38)) PKC-potentiated inhibitor (CPI-17), and phosphorylated (Thr(18)/Ser(19)) 20-kDa myosin regulatory light chain. Conversely, decreases in the phasic activity in the RSM by ROCK inhibition were accompanied by the additional decrease in phosphorylated (Thr(696)) myosin phosphatase target subunit 1. Data show that while PKC and RhoA/ROCK pathways play a significant role in slow-rate high-amplitude spontaneous phasic activity, only the RhoA/ROCK pathway primarily mediates fast-rate low-amplitude phasic activity, in the RSM. Such knowledge is important in the understanding of the pathophysiology of large intestinal motility disorders. Relative contributions of the PKC vs. the RhoA/ROCK pathway in the phasic activity remain to be determined.

  20. 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...

  1. 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.

  2. 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

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

    OpenAIRE

    Ilango, Anton; Andrew J. Kesner; Broker, Carl J.; Wang, Dong V.; Ikemoto, Satoshi

    2014-01-01

    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, ...

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

    OpenAIRE

    Anton eIlango; Andrew J. Kesner; Broker, Carl J.; Wang, Dong V.; Satoshi eIkemoto

    2014-01-01

    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 are...

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

    Directory of Open Access Journals (Sweden)

    Daniel Simon Razik

    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.

  6. The Cortisol Paradox of Trauma-Related Disorders: Lower Phasic Responses but Higher Tonic Levels of Cortisol Are Associated with Sexual Abuse in Childhood

    Science.gov (United States)

    Schalinski, Inga; Elbert, Thomas; Steudte-Schmiedgen, Susann; Kirschbaum, Clemens

    2015-01-01

    Objectives Inconsistent findings exist for the activity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with stress related disorders. Recent studies point towards early life stress as a potential modulator. Methods We investigated the impact of childhood sexual abuse on phasic (saliva cortisol reactivity) and tonic (hair cortisol) regulation. Furthermore, we assessed predictors on cortisol accumulation in hair. Women (N = 43) with stress-related disorders underwent a standardized assessment of idiographic adverse and traumatic experiences and psychopathology, while measuring salivary cortisol and, heart rate and blood pressure. Results Comparing women with and without childhood sexual abuse revealed lower rates of responders and distinct levels of salivary cortisol to the interview in conjunction with a lower heart rate for the abused group. Childhood adversities, traumatic experiences, and depression contributed to higher hair cortisol levels. Conclusions Our finding of lower response rate and distinct salivary cortisol pattern in individuals with childhood sexual abuse compared to individuals without early sexual abuse supports the role of environmental programming for the HPA axis. Both, childhood adversities and traumatic stress emerge as crucial factors for long-term cortisol secretion. Lower or suppressed phasic cortisol responses to trauma-related stimuli may therefore be associated with higher tonic values. Thus, early exposure to adversities may result in a biological distinct phenotype in adult patients with stress-related disorders. PMID:26317554

  7. Functional characterization of obesogenic neural circuitries

    NARCIS (Netherlands)

    Boender, A.J.

    2015-01-01

    Obesity can be characterized as a disorder in which affected individuals fail to properly regulate the balance between energy intake and expenditure. Recently, genome-wide association studies have identified over 30 genetic variants that associate with increased body weight and thus provide clues on

  8. 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.

  9. 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...

  10. 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...... to solve the problem, namely freeze-drying and resist-assisted release. The fabrication results of cantilevers defined by laser and E-beam lithography are shown. Finally, an AFM based characterization setup is presented and the electrical characterization of a laser-defined cantilever fully integrated...

  11. 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 ...

  12. 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.

  13. 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.

  14. Activation of the motor cortex during phasic rapid eye movement sleep

    Science.gov (United States)

    De Carli, Fabrizio; Proserpio, Paola; Morrone, Elisa; Sartori, Ivana; Ferrara, Michele; Gibbs, Steve Alex; De Gennaro, Luigi; Lo Russo, Giorgio

    2016-01-01

    When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder. Ann Neurol 2016;79:326–330 PMID:26575212

  15. Temporal expectancy modulates phasic alerting in both detection and discrimination tasks.

    Science.gov (United States)

    Lu, Shena; Wang, Wei; Cai, Yongchun

    2015-02-01

    The aim of the present study was to investigate whether phasic alerting might be modulated by temporal expectancy and to determine the processing stages at which this modulation might occur. We manipulated participants' expectancy for the target appearance by systematically varying the cue-target stimulus onset asynchrony (SOA) distribution in both detection and discrimination tasks. There were three temporal expectancy conditions: the non-aging condition in which temporal expectancy was eliminated, the aging condition in which temporal expectancy increased as SOA increased, and the accelerated-aging condition in which temporal expectancy increased more dramatically as SOA increased than in the aging condition. We obtained the same pattern of results in both detection and discrimination tasks: the onset time of the alerting effect was postponed successively across the three temporal expectancy conditions. The present findings suggest that the time course of the alerting effect may be modulated by temporal expectancy, highlighting the importance of taking account into the influence of temporal expectancy in studies involving the time course of cognitive processes. Furthermore, since mechanisms underlying the detection and discrimination tasks may differ in early processing stages involving perceptual analysis and response selection, the same result pattern observed in both tasks is consistent with the hypothesis that the modulation of temporal expectancy on phasic alerting occurs at late processing stages involving motor preparation.

  16. Repeatability of phasic muscle activity: performance of surface and intramuscular wire electrodes in gait analysis.

    Science.gov (United States)

    Kadaba, M P; Wootten, M E; Gainey, J; Cochran, G V

    1985-01-01

    Repeatability is an important consideration for gait analysis data that are being used as an adjunct to clinical decision making. An index of repeatability may be based on a statistical criterion (variance ratio) that reflects similarity of wave forms over a number of identical cycles. The purpose of this study was to use the variance ratio to assess the repeatability of phasic muscle activity recorded with surface and bipolar intramuscular wire electrodes during gait on 10 normal subjects. Variance ratios were calculated using rectified and smoothed electromyographic data recorded simultaneously from the two types of electrodes. Three measures of repeatability (reproducibility, reliability, and constancy--defined as the cycle-to-cycle, run-to-run, and day-to-day repeatability of phasic muscle activity) were used to compare the performance of the two electrode techniques. Results show that the reproducibility and reliability were better for surface electrodes than for intramuscular wire electrodes, and constancy was good for surface electrodes and poor for intramuscular wire electrodes. Repeatability improved with increasing smoothing window lengths but was better for surface electrodes than wire electrodes, irrespective of the smoothing window. This study indicates that surface electrode data represent a more consistent measure of activity of superficial muscles, if comparisons are to be made between gait data from different test days.

  17. Phasic Mesolimbic Dopamine Signaling Encodes the Facilitation of Incentive Motivation Produced by Repeated Cocaine Exposure

    Science.gov (United States)

    Ostlund, Sean B; LeBlanc, Kimberly H; Kosheleff, Alisa R; Wassum, Kate M; Maidment, Nigel T

    2014-01-01

    Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the current study, we tested this hypothesis using fast-scan cyclic voltammetry to monitor phasic DA signaling in the nucleus accumbens core of cocaine-pretreated (6 once-daily injections of 15 mg/kg, i.p.) and drug-naive rats during a test of cue-evoked incentive motivation for food—the Pavlovian-to-instrumental transfer task. We found that prior cocaine exposure augmented both reward seeking and DA release triggered by the presentation of a reward-paired cue. Furthermore, cue-evoked DA signaling positively correlated with cue-evoked food seeking and was found to be a statistical mediator of this behavioral effect of cocaine. Taken together, these findings provide support for the hypothesis that repeated cocaine exposure enhances cue-evoked incentive motivation through augmented phasic mesolimbic DA signaling. This work sheds new light on a fundamental neurobiological mechanism underlying motivated behavior and its role in the expression of compulsive reward seeking. PMID:24804846

  18. 76 FR 72214 - Certain Semiconductor Chips with DRAM Circuitry, and Modules and Products Containing Same Receipt...

    Science.gov (United States)

    2011-11-22

    ... COMMISSION Certain Semiconductor Chips with DRAM Circuitry, and Modules and Products Containing Same Receipt... Commission has received a complaint entitled In Re Certain Semiconductor Chips with DRAM Circuitry, and... importation of certain semiconductor chips with dram circuitry, and modules and products containing same....

  19. Separate circuitries encode the hedonic and nutritional values of sugar.

    Science.gov (United States)

    Tellez, Luis A; Han, Wenfei; Zhang, Xiaobing; Ferreira, Tatiana L; Perez, Isaac O; Shammah-Lagnado, Sara J; van den Pol, Anthony N; de Araujo, Ivan E

    2016-03-01

    Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of sugar. During sugar intake, suppressing hedonic value inhibited dopamine release in ventral, but not dorsal, striatum, whereas suppressing nutritional value inhibited dopamine release in dorsal, but not ventral, striatum. Consistently, cell-specific ablation of dopamine-excitable cells in dorsal, but not ventral, striatum inhibited sugar's ability to drive the ingestion of unpalatable solutions. Conversely, optogenetic stimulation of dopamine-excitable cells in dorsal, but not ventral, striatum substituted for sugar in its ability to drive the ingestion of unpalatable solutions. Our data indicate that sugar recruits a distributed dopamine-excitable striatal circuitry that acts to prioritize energy-seeking over taste quality.

  20. 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...

  1. 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...

  2. NS19504: a novel BK channel activator with relaxing effect on bladder smooth muscle spontaneous phasic contractions.

    Science.gov (United States)

    Nausch, Bernhard; Rode, Frederik; Jørgensen, Susanne; Nardi, Antonio; Korsgaard, Mads P G; Hougaard, Charlotte; Bonev, Adrian D; Brown, William D; Dyhring, Tino; Strøbæk, Dorte; Olesen, Søren-Peter; Christophersen, Palle; Grunnet, Morten; Nelson, Mark T; Rønn, Lars C B

    2014-09-01

    Large-conductance Ca(2+)-activated K(+) channels (BK, KCa1.1, MaxiK) are important regulators of urinary bladder function and may be an attractive therapeutic target in bladder disorders. In this study, we established a high-throughput fluorometric imaging plate reader-based screening assay for BK channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization was achieved in manual whole-cell and inside-out patch-clamp studies in human embryonic kidney 293 cells expressing hBK channels: NS19504 caused distinct activation from a concentration of 0.3 and 10 µM NS19504 left-shifted the voltage activation curve by 60 mV. Furthermore, whole-cell recording showed that NS19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µM) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels in urinary bladder function. The pharmacologic profile of NS19504 indicates that this compound may have the potential to reduce nonvoiding contractions associated with spontaneous bladder overactivity while having a minimal effect on normal voiding.

  3. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration

    Directory of Open Access Journals (Sweden)

    Caroline E Bass

    2013-11-01

    Full Text Available There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2 on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  4. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.

    Science.gov (United States)

    Bass, Caroline E; Grinevich, Valentina P; Gioia, Dominic; Day-Brown, Jonathan D; Bonin, Keith D; Stuber, Garret D; Weiner, Jeff L; Budygin, Evgeny A

    2013-01-01

    There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  5. 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.

  6. Affect Intensity and Phasic REM Sleep in Depressed Men before and after Treatment with Cognitive-Behavioral Therapy.

    Science.gov (United States)

    Nofzinger, Eric A.; And Others

    1994-01-01

    Explored relationship between daytime affect and REM (rapid eye movement) sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in control group of 43 healthy subjects. For depressed subjects only, intensity of daytime affect correlated significantly and positively with phasic REM sleep measures at pre- and…

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Kevin Lloyd

    2015-12-01

    Full Text Available 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.

  9. 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

  10. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    Science.gov (United States)

    Willuhn, Ingo; Burgeno, Lauren M.; Groblewski, Peter A.; Phillips, Paul E. M.

    2014-01-01

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum (DLS) is thought to assume control over drug seeking. We measured striatal dopamine release during a cocaine self-administration regimen that produced escalation of drug taking in rats. Surprisingly, we found that phasic dopamine decreased in both regions as the rate of cocaine intake increased; with the decrement in dopamine in the VMS significantly correlated with the rate of escalation. Administration of the dopamine precursor L-DOPA at a dose that replenished dopamine signaling in the VMS reversed escalation, thereby demonstrating the causal relationship between diminished dopamine transmission and excessive drug use. Thus, together these data provide mechanistic and therapeutic insight into the excessive drug intake that emerges following protracted use. PMID:24705184

  11. 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

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

    Science.gov (United States)

    Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

    2015-01-01

    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 (AS). 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.

  13. 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.

  14. 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

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

    Science.gov (United States)

    Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

    2015-01-01

    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 (AS). 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. PMID:26582977

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  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. 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

  6. 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.

  7. 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.

  8. 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...... consumption of different amplifier topologies. Next, low power features of different amplifier types are analyzed on transistor level. A brief comparison of SI circuits for low power applications vs. SC circuits is presented. Methodologies for low voltage design is presented. This is followed by a collection...... 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...

  9. Arithmetic and local circuitry underlying dopamine prediction errors.

    Science.gov (United States)

    Eshel, Neir; Bukwich, Michael; Rao, Vinod; Hemmelder, Vivian; Tian, Ju; Uchida, Naoshige

    2015-09-10

    Dopamine neurons are thought to facilitate learning by comparing actual and expected reward. Despite two decades of investigation, little is known about how this comparison is made. To determine how dopamine neurons calculate prediction error, we combined optogenetic manipulations with extracellular recordings in the ventral tegmental area while mice engaged in classical conditioning. Here we demonstrate, by manipulating the temporal expectation of reward, that dopamine neurons perform subtraction, a computation that is ideal for reinforcement learning but rarely observed in the brain. Furthermore, selectively exciting and inhibiting neighbouring GABA (γ-aminobutyric acid) neurons in the ventral tegmental area reveals that these neurons are a source of subtraction: they inhibit dopamine neurons when reward is expected, causally contributing to prediction-error calculations. Finally, bilaterally stimulating ventral tegmental area GABA neurons dramatically reduces anticipatory licking to conditioned odours, consistent with an important role for these neurons in reinforcement learning. Together, our results uncover the arithmetic and local circuitry underlying dopamine prediction errors.

  10. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis

    Science.gov (United States)

    Averette, Anna F.; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E.

    2016-01-01

    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. A Computational Framework for Ultrastructural Mapping of Neural Circuitry

    Science.gov (United States)

    Anderson, James R; Jones, Bryan W; Yang, Jia-Hui; Shaw, Marguerite V; Watt, Carl B; Koshevoy, Pavel; Spaltenstein, Joel; Jurrus, Elizabeth; UV, Kannan; Whitaker, Ross T; Mastronarde, David; Tasdizen, Tolga; Marc, Robert E

    2009-01-01

    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, this framework

  16. Impaired Pavlovian predictive learning between temporally phasic but not static events in autism-model strain mice.

    Science.gov (United States)

    Kosaki, Yutaka; Watanabe, Shigeru

    2016-10-01

    Autism-spectrum disorder (ASD) is a multi-aspect developmental disorder characterised by various social and non-social behavioural abnormalities. Using BTBR T+ tf mouse strain (BTBR), a promising animal model displaying a number of behavioural and neural characteristics associated with ASD, we tested the hypothesis that at the core of various symptoms of ASD lies a fundamental deficit in predictive learning between events. In five experiments, we conducted a variety of Pavlovian conditioning tasks, some requiring the establishment of associations between temporally phasic events and others involving static events. BTBR mice were impaired in the acquisition of conditioned magazine approach responses with an appetitive unconditioned stimulus (US) (Experiment 1) and conditioned freezing with an electric shock US (Experiment 2). Both of these tasks had temporally phasic conditioned stimuli (CSs). Conversely, these mice showed normal acquisition of conditioned place preference (CPP), whether the US was a systemic injection of methamphetamine (Experiment 3A) or the presence of food (Experiment 3B). Experiment 4 showed normal acquisition of conditioned taste aversion (CTA) to a flavour-taste compound CS, although BTBR mice still exhibited an abnormal stimulus selection when learning for each element of the compound CS was assessed separately. Experiment 5 revealed a weaker latent inhibition of CTA in BTBR mice. The BTBR mouse's impaired predictive learning between phasic events and intact associations between static events are discussed in terms of dysfunctional contingency-based, but not contiguity-based learning, which may accompany abnormal selective attention to relevant cues. We propose that such dysfunctional contingency learning mechanisms may underlie the development of various social and non-social symptoms of ASD.

  17. 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.

  18. 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

  19. 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

  20. The Neural Circuitry of Expertise: Perceptual Learning and Social Cognition

    Directory of Open Access Journals (Sweden)

    Michael eHarre

    2013-12-01

    Full Text Available 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 our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is likely a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviourally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations. Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and

  1. 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

  2. Intensity of anxiety is modified via complex integrative stress circuitries.

    Science.gov (United States)

    Smith, Justin P; Prince, Melissa A; Achua, Justin K; Robertson, James M; Anderson, Raymond T; Ronan, Patrick J; Summers, Cliff H

    2016-01-01

    Escalation of anxious behavior while environmentally and socially relevant contextual events amplify the intensity of emotional response produces a testable gradient of anxiety shaped by integrative circuitries. Apprehension of the Stress-Alternatives Model apparatus (SAM) oval open field (OF) is measured by the active latency to escape, and is delayed by unfamiliarity with the passageway. Familiar OF escape is the least anxious behavior along the continuum, which can be reduced by anxiolytics such as icv neuropeptide S (NPS). Social aggression increases anxiousness in the SAM, reducing the number of mice willing to escape by 50%. The apprehension accompanying escape during social aggression is diminished by anxiolytics, such as exercise and corticotropin releasing-factor receptor 1 (CRF1) antagonism, but exacerbated by anxiogenic treatment, like antagonism of α2-adrenoreceptors. What is more, the anxiolytic CRF1 and anxiogenic α2-adrenoreceptor antagonists also modify behavioral phenotypes, with CRF1 antagonism allowing escape by previously submissive animals, and α2-adrenoreceptor antagonism hindering escape in mice that previously engaged in it. Gene expression of NPS and brain-derived neurotrophic factor (BDNF) in the central amygdala (CeA), as well as corticosterone secretion, increased concomitantly with the escalating anxious content of the mouse-specific anxiety continuum. The general trend of CeA NPS and BDNF expression suggested that NPS production was promoted by increasing anxiousness, and that BDNF synthesis was associated with learning about ever-more anxious conditions. The intensity gradient for anxious behavior resulting from varying contextual conditions may yield an improved conceptualization of the complexity of mechanisms producing the natural continuum of human anxious conditions, and potential therapies that arise therefrom. PMID:26555428

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

    Science.gov (United States)

    Harré, Michael

    2013-12-17

    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 our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific and interrelated types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviorally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations (SDEs). Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and social

  4. Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF.

    Science.gov (United States)

    Pun, San; Santos, Alexandre Ferrão; Saxena, Smita; Xu, Lan; Caroni, Pico

    2006-03-01

    Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally defined selective vulnerabilities of distinct synapses or axons. Here we derive a quantitative topographic map of muscle innervation in the hindlimb. We show that in two mouse models of motoneuron disease (G93A SOD1 and G85R SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Axonal vulnerability leads to synaptic vesicle stalling and accumulation of BC12a1-a, an anti-apoptotic protein. It is alleviated by ciliary neurotrophic factor and triggers proteasome-dependent pruning of peripheral axon branches. Thus, motoneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.

  5. 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.

  6. Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.

    Science.gov (United States)

    Gan, Zhenji; Rumsey, John; Hazen, Bethany C; Lai, Ling; Leone, Teresa C; Vega, Rick B; Xie, Hui; Conley, Kevin E; Auwerx, Johan; Smith, Steven R; Olson, Eric N; Kralli, Anastasia; Kelly, Daniel P

    2013-06-01

    The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

  7. Apparatus, system and method for providing cryptographic key information with physically unclonable function circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Areno, Matthew

    2015-12-08

    Techniques and mechanisms for providing a value from physically unclonable function (PUF) circuitry for a cryptographic operation of a security module. In an embodiment, a cryptographic engine receives a value from PUF circuitry and based on the value, outputs a result of a cryptographic operation to a bus of the security module. The bus couples the cryptographic engine to control logic or interface logic of the security module. In another embodiment, the value is provided to the cryptographic engine from the PUF circuitry via a signal line which is distinct from the bus, where any exchange of the value by either of the cryptographic engine and the PUF circuitry is for communication of the first value independent of the bus.

  8. 77 FR 33240 - Certain Semiconductor Chips With DRAM Circuitry, and Modules and Products Containing Same...

    Science.gov (United States)

    2012-06-05

    ... Memory (USA) Inc. of Sunnyvale, California (collectively, ``Elpida''). 76 FR 79215 (Dec. 21, 2011). The... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Certain Semiconductor Chips With DRAM Circuitry, and Modules and Products Containing...

  9. 78 FR 53159 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same: Notice...

    Science.gov (United States)

    2013-08-28

    ..., California (collectively, ``Elpida''). 76 FR 79215 (Dec. 21, 2011). The complaint alleged violations of... From the Federal Register Online via the Government Publishing Office ] INTERNATIONAL TRADE COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same:...

  10. 78 FR 24234 - Certain Semiconductor Chips With DRAM Circuitry, and Modules and Products Containing Same; Notice...

    Science.gov (United States)

    2013-04-24

    ... From the Federal Register Online via the Government Publishing Office ] INTERNATIONAL TRADE COMMISSION Certain Semiconductor Chips With DRAM Circuitry, and Modules and Products Containing Same; Notice..., which is a limited exclusion order barring the entry of unlicensed DRAM semiconductor chips...

  11. Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling.

    Science.gov (United States)

    Spoelder, Marcia; Tsutsui, Kimberly T; Lesscher, Heidi M B; Vanderschuren, Louk J M J; Clark, Jeremy J

    2015-12-01

    Adolescent alcohol use remains a major public health concern due in part to well-established findings implicating the age of onset in alcohol use in the development of alcohol use disorders and persistent decision-making deficits in adults. We have previously demonstrated that moderate adolescent alcohol consumption in rats promotes suboptimal decision making and an associated perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent incentive learning processes are an integral component of value-based decision making and a fundamental element to many theoretical accounts of addiction. Thus we tested the hypothesis that adolescent alcohol use selectively alters incentive learning processes through perturbation of mesolimbic dopamine systems. To assess incentive learning, behavioral and neurochemical measurements were made during the acquisition, maintenance, extinction, and reacquisition of a Pavlovian conditioned approach procedure in adult rats with a history of adolescent alcohol consumption. We show that moderate adolescent alcohol consumption potentiates stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan cyclic voltammetry, in adulthood and biases individuals toward a dopamine-dependent incentive learning strategy. Moreover, we demonstrate that animals exposed to alcohol in adolescence are more sensitive to an unexpected variation in reward outcomes. This pattern of phasic dopamine signaling and the associated bias in learning may provide a mechanism for the well-documented vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood.

  12. 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...

  13. Hybrid gate dielectric materials for unconventional electronic circuitry.

    Science.gov (United States)

    Ha, Young-Geun; Everaerts, Ken; Hersam, Mark C; Marks, Tobin J

    2014-04-15

    Recent advances in semiconductor performance made possible by organic π-electron molecules, carbon-based nanomaterials, and metal oxides have been a central scientific and technological research focus over the past decade in the quest for flexible and transparent electronic products. However, advances in semiconductor materials require corresponding advances in compatible gate dielectric materials, which must exhibit excellent electrical properties such as large capacitance, high breakdown strength, low leakage current density, and mechanical flexibility on arbitrary substrates. Historically, conventional silicon dioxide (SiO2) has dominated electronics as the preferred gate dielectric material in complementary metal oxide semiconductor (CMOS) integrated transistor circuitry. However, it does not satisfy many of the performance requirements for the aforementioned semiconductors due to its relatively low dielectric constant and intransigent processability. High-k inorganics such as hafnium dioxide (HfO2) or zirconium dioxide (ZrO2) offer some increases in performance, but scientists have great difficulty depositing these materials as smooth films at temperatures compatible with flexible plastic substrates. While various organic polymers are accessible via chemical synthesis and readily form films from solution, they typically exhibit low capacitances, and the corresponding transistors operate at unacceptably high voltages. More recently, researchers have combined the favorable properties of high-k metal oxides and π-electron organics to form processable, structurally well-defined, and robust self-assembled multilayer nanodielectrics, which enable high-performance transistors with a wide variety of unconventional semiconductors. In this Account, we review recent advances in organic-inorganic hybrid gate dielectrics, fabricated by multilayer self-assembly, and their remarkable synergy with unconventional semiconductors. We first discuss the principals and functional

  14. 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

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. 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.

  2. 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...

  3. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  4. 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)

  5. Non-contact structural damage detection using magnetic admittance approach with circuitry tuning

    Science.gov (United States)

    Wang, X.; Tang, J.

    2010-03-01

    One limitation of piezoelectric impedance/admittance approach is that the sensor is permanently fixed after it is bonded/embedded into the mechanical structure to be monitored. Recently, the magnetic transducer, which is essentially an electrical coil inserted with a permanent magnet, is explored for impedance/admittance-based damage detection. Since there is no direct contact between the magnetic sensor and the host structure, the magnetic impedance/admittance approach is capable of online health monitoring of structures with complicated geometries and boundaries. Also, the magnetic impedance/admittance sensor is moveable above the structure surface, which may reduce the number of sensors needed to cover a large structural area. In an earlier study a new magnetic impedance sensing scheme with circuitry integration is proposed, which can greatly enhance the signal-to-noise ratio and amplify the damage induced admittance change. In this research, we systematically study the sensor location on the performance of the magnetic impedance/admittance-based damage detection scheme with circuitry integration. By examining the resonant peaks in the circuitry impedance curves, the damage-induced change of circuitry admittance and the two-way magneto-mechanical coupling, the different amplification effects of the magnetic sensor on the dynamical responses around mechanical modes is investigated. The criteria of tuning the capacitance of the tunable capacitor to achieve significantly amplified admittance changes in a wide frequency range are also developed. Correlated numerical and experimental studies are carried out to validate our proposed tuning criteria.

  6. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

    NARCIS (Netherlands)

    Bos, Peter A.; Montoya, Estrella R.; Hermans, Erno J.; Keysers, Christian; van Honk, Jack

    2015-01-01

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have re

  7. 78 FR 41079 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same

    Science.gov (United States)

    2013-07-09

    ... Tokyo, Japan and Elpida Memory (USA) Inc. of Sunnyvale, California ] (collectively, ``Elpida''). 76 FR... Commission's action. See Presidential Memorandum of July 21, 2005, 70 FR 43251 (July 26, 2005). During this... COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same...

  8. 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...

  9. Distinguishing benign from malignant parotid gland tumours: low-dose multi-phasic CT protocol with 5-minute delay

    Energy Technology Data Exchange (ETDEWEB)

    Jin, G.Q.; Su, D.K.; Xie, D.; Liu, L.D.; Zhu, X.N. [Guangxi Medical University, Department of Radiology, Oncology Hospital, Nanning (China); Zhao, W. [Oncology Hospital Guangxi Medical University Nanning, Department of Radiation, Guangxi (China)

    2011-08-15

    To explore the percentage enhancement wash-out ratio (PEW) and relative PEW (RPEW) of low-dose multi-phasic computed tomography (CT) in distinguishing benign from malignant parotid gland tumours. This study was approved by the ethics committee, and informed patient consent was obtained. 51 patients with parotid tumours proven by histopathology received CT, including 18 with pleomorphic adenomas, 14 with Warthin's tumours and 19 with malignant tumours. Size and attenuation of parotid tumours were measured. Compared with 5-min attenuation, the 30-s and 90-s PEW (PEW{sub 30,} PEW{sub 90}) and RPEW (RPEW{sub 30}, RPEW{sub 90}) were calculated. There was a significant difference in PEW{sub 30}, RPEW{sub 30}, PEW{sub 90} and RPEW{sub 90} in the parotid neoplasms groups (P < 0.01), and statistical significance existed simultaneously in pleomorphic adenomas vs malignant tumours and Warthin's tumours vs malignant tumours according to SNK-q test. The optimal diagnosis results of malignancy with 100% specificity (32/32) was obtained by using a combination of the following criteria: -70% > PEW{sub 30} < 36%, -30% > PEW{sub 30} < 19%, PEW{sub 90} > 12%, and the sensitivity (74%) for diagnosis of malignancy was yield. Wash-out ratio may assist in differentiating the benign from malignant parotid gland tumours. Combining the percentage of enhanced wash-out ratios of CT protocols can yield diagnostic results for malignancy. (orig.)

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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...

  16. 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)

  17. Endocannabinoid-dependent modulation of phasic dopamine signaling encodes external and internal reward-predictive cues.

    Science.gov (United States)

    Wenzel, Jennifer M; Cheer, Joseph F

    2014-01-01

    The mesolimbic dopamine (DA) system plays an integral role in incentive motivation and reward seeking and a growing body of evidence identifies signal transduction at cannabinoid receptors as a critical modulator of this system. Indeed, administration of exogenous cannabinoids results in burst firing of DA neurons of the ventral tegmental area and increases extracellular DA in the nucleus accumbens (NAcc). Implementation of fast-scan cyclic voltammetry (FSCV) confirms the ability of cannabinoids to augment DA within the NAcc on a subsecond timescale. The use of FSCV along with newly developed highly selective pharmacological compounds advances our understanding of how cannabinoids influence DA transmission and highlights a role for endocannabinoid-modulated subsecond DAergic activation in the incentive motivational properties of not only external, but also internal reward-predictive cues. For example, our laboratory has recently demonstrated that in mice responding under a fixed-interval (FI) schedule for food reinforcement, fluctuations in NAcc DA signal the principal cue predictive of reinforcer availability - time. That is, as the interval progresses, NAcc DA levels decline leading to accelerated food seeking and the resulting characteristic FI scallop pattern of responding. Importantly, administration of WIN 55,212-2, a synthetic cannabinoid agonist, or JZL184, an indirect cannabinoid agonist, increases DA levels during the interval and disrupts this pattern of responding. Along with a wealth of other reports, these results illustrate the role of cannabinoid receptor activation in the regulation of DA transmission and the control of temporally guided reward seeking. The current review will explore the striatal beat frequency model of interval timing as it pertains to cannabinoid signaling and propose a neurocircuitry through which this system modulates interoceptive time cues. PMID:25225488

  18. Endocannabinoid-dependent modulation of phasic dopamine signaling encodes external and internal reward-predictive cues

    Directory of Open Access Journals (Sweden)

    Jennifer M. Wenzel

    2014-09-01

    Full Text Available The mesolimbic dopamine (DA system plays an integral role in incentive motivation and reward seeking and a growing body of evidence identifies signal transduction at cannabinoid receptors as a critical modulator of this system. Indeed, administration of exogenous cannabinoids results in burst firing of DA neurons of the ventral tegmental area and increases extracellular DA in the nucleus accumbens (NAcc. Implementation of fast-scan cyclic voltammetry (FSCV confirms the ability of cannabinoids to augment DA within the NAcc on a subsecond timescale. The use of FSCV along with newly developed highly selective pharmacological compounds advances our understanding of how cannabinoids influence DA transmission, and highlights a role for endocannabinoid-modulated subsecond DAergic activation in the incentive motivational properties of not only external, but also internal reward-predictive cues. For example, our laboratory has recently demonstrated that in mice responding under a fixed interval (FI schedule for food reinforcement, fluctuations in NAcc DA signal the principal cue predictive of reinforcer availability – time. That is, as the interval progresses, NAcc DA levels decline leading to accelerated food seeking and the resulting characteristic FI scallop pattern of responding. Importantly, administration of WIN 55,212-2, a synthetic cannabinoid agonist, or JZL184, an indirect cannabinoid agonist, increase DA levels during the interval and disrupt this pattern of responding. Along with a wealth of other reports, these results illustrate the role of cannabinoid receptor activation in the regulation of DA transmission and the control of temporally guided reward seeking. The current review will explore the striatal beat frequency model of interval timing as it pertains cannabinoid signaling and propose a neurocircuitry through which this system modulates interoceptive time cues.

  19. Endocannabinoid-dependent modulation of phasic dopamine signaling encodes external and internal reward-predictive cues.

    Science.gov (United States)

    Wenzel, Jennifer M; Cheer, Joseph F

    2014-01-01

    The mesolimbic dopamine (DA) system plays an integral role in incentive motivation and reward seeking and a growing body of evidence identifies signal transduction at cannabinoid receptors as a critical modulator of this system. Indeed, administration of exogenous cannabinoids results in burst firing of DA neurons of the ventral tegmental area and increases extracellular DA in the nucleus accumbens (NAcc). Implementation of fast-scan cyclic voltammetry (FSCV) confirms the ability of cannabinoids to augment DA within the NAcc on a subsecond timescale. The use of FSCV along with newly developed highly selective pharmacological compounds advances our understanding of how cannabinoids influence DA transmission and highlights a role for endocannabinoid-modulated subsecond DAergic activation in the incentive motivational properties of not only external, but also internal reward-predictive cues. For example, our laboratory has recently demonstrated that in mice responding under a fixed-interval (FI) schedule for food reinforcement, fluctuations in NAcc DA signal the principal cue predictive of reinforcer availability - time. That is, as the interval progresses, NAcc DA levels decline leading to accelerated food seeking and the resulting characteristic FI scallop pattern of responding. Importantly, administration of WIN 55,212-2, a synthetic cannabinoid agonist, or JZL184, an indirect cannabinoid agonist, increases DA levels during the interval and disrupts this pattern of responding. Along with a wealth of other reports, these results illustrate the role of cannabinoid receptor activation in the regulation of DA transmission and the control of temporally guided reward seeking. The current review will explore the striatal beat frequency model of interval timing as it pertains to cannabinoid signaling and propose a neurocircuitry through which this system modulates interoceptive time cues.

  20. 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...

  1. Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human

    OpenAIRE

    Takashima, Yasuhiro; Guo, Ge; Loos, Remco; Nichols, Jennifer; Ficz, Gabriella; Krueger, Felix; Oxley, David; Santos, Fatima; Clarke, James; Mansfield, William; Reik, Wolf; Bertone, Paul; Smith, Austin

    2014-01-01

    Summary Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, a...

  2. 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...

  3. 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...

  4. 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 ...

  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. 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.

  7. 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.

  8. 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

  9. 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.

  10. The Neuro-Environmental Loop of Plasticity: A Cross-Species Analysis of Parental Effects on Emotion Circuitry Development Following Typical and Adverse Caregiving.

    Science.gov (United States)

    Callaghan, Bridget L; Tottenham, Nim

    2016-01-01

    Early experiences critically shape the structure and function of the brain. Perturbations in typical/species-expected early experiences are known to have profound neural effects, especially in regions important for emotional responding. Parental care is one species-expected stimulus that plays a fundamental role in the development of emotion neurocircuitry. Emerging evidence across species suggests that phasic variation in parental presence during the sensitive period of childhood affects the recruitment of emotional networks on a moment-to-moment basis. In addition, it appears that increasing independence from caregivers cues the termination of the sensitive period for environmental input into emotion network development. In this review, we examine how early parental care, the central nervous system, and behavior come together to form a 'neuro-environmental loop,' contributing to the formation of stable emotion regulation circuits. To achieve this end, we focus on the interaction of parental care and the developing amygdala-medial prefrontal cortex (mPFC) network-that is at the core of human emotional functioning. Using this model, we discuss how individual or group variations in parental independence, across chronic and brief timescales, might contribute to neural and emotional phenotypes that have implications for long-term mental health. PMID:26194419

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wicks, G.G. [Westinghouse Savannah River Co., Aiken, SC (United States); Clark, D.E.; Schulz, R.L.; Folz, D.C. [Univ. of Florida, Gainesville, FL (United States)

    1995-09-01

    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.

  13. Present state of power electronics circuitry and perspectives of its development

    OpenAIRE

    Sokol, Evgeny; Goncharov, Yuriy

    2011-01-01

    This paper is devoted mainly to the circuitry, because element base is a big independent issue. Let us say a few words about terminology. A modern converter can be rarely represented as a simple device like “rectifier”, “inverter” etc. It usually consists of the combination of several units, performing elementary functions. For such multistage units it makes sense to use a definition of converter “technology”, keeping in mind some actions with electric current for a certain purpose. It is si...

  14. 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

  15. Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry.

    Science.gov (United States)

    Navratilova, Edita; Xie, Jennifer Y; Okun, Alec; Qu, Chaoling; Eyde, Nathan; Ci, Shuang; Ossipov, Michael H; King, Tamara; Fields, Howard L; Porreca, Frank

    2012-12-11

    Relief of pain is rewarding. Using a model of experimental postsurgical pain we show that blockade of afferent input from the injury with local anesthetic elicits conditioned place preference, activates ventral tegmental dopaminergic cells, and increases dopamine release in the nucleus accumbens. Importantly, place preference is associated with increased activity in midbrain dopaminergic neurons and blocked by dopamine antagonists injected into the nucleus accumbens. The data directly support the hypothesis that relief of pain produces negative reinforcement through activation of the mesolimbic reward-valuation circuitry.

  16. 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

  17. Emotional Processing following Cortical and Subcortical Brain Damage: Contribution of the Fronto-Striatal Circuitry

    Directory of Open Access Journals (Sweden)

    Caterina Breitenstein

    1998-01-01

    Full Text Available The present study examined the differential contribution of cortical and subcortical brain structures in emotional processing by comparing patients with focal cortical lesions (n = 32 to those with primarily subcortical dysregulation of the basal ganglia (Parkinson’s disease n = 14. A standardized measure of emotional perception (Tübingen Affect Battery was used. Only patients in the more advanced stages of Parkinson’s disease and patients with focal damage to the (right frontal lobe differed significantly from controls in both facial expression and affective prosody recognition. The findings imply involvement of the fronto-striatal circuitry in emotional processing.

  18. Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography

    Directory of Open Access Journals (Sweden)

    Maria A. Bobes

    2016-01-01

    Full Text Available Although Capgras delusion (CD patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF and the inferior longitudinal (ILF. The superior longitudinal fasciculus (SLF and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

  19. Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography.

    Science.gov (United States)

    Bobes, Maria A; Góngora, Daylin; Valdes, Annette; Santos, Yusniel; Acosta, Yanely; Fernandez Garcia, Yuriem; Lage, Agustin; Valdés-Sosa, Mitchell

    2016-01-01

    Although Capgras delusion (CD) patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal (ILF). The superior longitudinal fasciculus (SLF) and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

  20. Resetting transcription factor control circuitry toward ground-state pluripotency in human.

    Science.gov (United States)

    Takashima, Yasuhiro; Guo, Ge; Loos, Remco; Nichols, Jennifer; Ficz, Gabriella; Krueger, Felix; Oxley, David; Santos, Fatima; Clarke, James; Mansfield, William; Reik, Wolf; Bertone, Paul; Smith, Austin

    2014-09-11

    Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, and are karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome state is globally realigned across multiple cell lines. Depletion of ground-state transcription factors, TFCP2L1 or KLF4, has marginal impact on conventional human pluripotent stem cells but collapses the reset state. These findings demonstrate feasibility of installing and propagating functional control circuitry for ground-state pluripotency in human cells. PMID:25215486

  1. Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Anne J Blood

    Full Text Available BACKGROUND: Previous studies of major depressive disorder (MDD have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN, and medial forebrain bundle (MFB. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity. CONCLUSIONS/SIGNIFICANCE: These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.

  2. Catecholaminergic innervation of central and peripheral auditory circuitry varies with reproductive state in female midshipman fish, Porichthys notatus.

    Directory of Open Access Journals (Sweden)

    Paul M Forlano

    Full Text Available In seasonal breeding vertebrates, hormone regulation of catecholamines, which include dopamine and noradrenaline, may function, in part, to modulate behavioral responses to conspecific vocalizations. However, natural seasonal changes in catecholamine innervation of auditory nuclei is largely unexplored, especially in the peripheral auditory system, where encoding of social acoustic stimuli is initiated. The plainfin midshipman fish, Porichthys notatus, has proven to be an excellent model to explore mechanisms underlying seasonal peripheral auditory plasticity related to reproductive social behavior. Recently, we demonstrated robust catecholaminergic (CA innervation throughout the auditory system in midshipman. Most notably, dopaminergic neurons in the diencephalon have widespread projections to auditory circuitry including direct innervation of the saccule, the main endorgan of hearing, and the cholinergic octavolateralis efferent nucleus (OE which also projects to the inner ear. Here, we tested the hypothesis that gravid, reproductive summer females show differential CA innervation of the auditory system compared to non-reproductive winter females. We utilized quantitative immunofluorescence to measure tyrosine hydroxylase immunoreactive (TH-ir fiber density throughout central auditory nuclei and the sensory epithelium of the saccule. Reproductive females exhibited greater density of TH-ir innervation in two forebrain areas including the auditory thalamus and greater density of TH-ir on somata and dendrites of the OE. In contrast, non-reproductive females had greater numbers of TH-ir terminals in the saccule and greater TH-ir fiber density in a region of the auditory hindbrain as well as greater numbers of TH-ir neurons in the preoptic area. These data provide evidence that catecholamines may function, in part, to seasonally modulate the sensitivity of the inner ear and, in turn, the appropriate behavioral response to reproductive acoustic

  3. Parametric study of dielectric loaded surface plasmon polariton add-drop filters for hybrid silicon/plasmonic optical circuitry

    Science.gov (United States)

    Dereux, A.; Hassan, K.; Weeber, J.-C.; Djellali, N.; Bozhevolnyi, S. I.; Tsilipakos, O.; Pitilakis, A.; Kriezis, E.; Papaioannou, S.; Vyrsokinos, K.; Pleros, N.; Tekin, T.; Baus, M.; Kalavrouziotis, D.; Giannoulis, G.; Avramopoulos, H.

    2011-01-01

    Surface plasmons polaritons are electromagnetic waves propagating along the surface of a conductor. Surface plasmons photonics is a promising candidate to satisfy the constraints of miniaturization of optical interconnects. This contribution reviews an experimental parametric study of dielectric loaded surface plasmon waveguides ring resonators and add-drop filters within the perspective of the recently suggested hybrid technology merging plasmonic and silicon photonics on a single board (European FP7 project PLATON "Merging Plasmonic and Silicon Photonics Technology towards Tb/s routing in optical interconnects"). Conclusions relevant for dielectric loaded surface plasmon switches to be integrated in silicon photonic circuitry will be drawn. They rely on the opportunity offered by plasmonic circuitry to carry optical signals and electric currents through the same thin metal circuitry. The heating of the dielectric loading by the electric current enables to design low foot-print thermo-optical switches driving the optical signal flow.

  4. 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...

  5. 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.

  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. "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

  8. 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.

  9. 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.

  10. The Impact of Emotional States on Cognitive Control Circuitry and Function.

    Science.gov (United States)

    Cohen, Alexandra O; Dellarco, Danielle V; Breiner, Kaitlyn; Helion, Chelsea; Heller, Aaron S; Rahdar, Ahrareh; Pedersen, Gloria; Chein, Jason; Dyke, Jonathan P; Galvan, Adriana; Casey, B J

    2016-03-01

    Typically in the laboratory, cognitive and emotional processes are studied separately or as a stream of fleeting emotional stimuli embedded within a cognitive task. Yet in life, thoughts and actions often occur in more lasting emotional states of arousal. The current study examines the impact of emotions on actions using a novel behavioral paradigm and functional neuroimaging to assess cognitive control under sustained states of threat (anticipation of an aversive noise) and excitement (anticipation of winning money). Thirty-eight healthy adult participants were scanned while performing an emotional go/no-go task with positive (happy faces), negative (fearful faces), and neutral (calm faces) emotional cues, under threat or excitement. Cognitive control performance was enhanced during the excited state relative to a nonarousing control condition. This enhanced performance was paralleled by heightened activity of frontoparietal and frontostriatal circuitry. In contrast, under persistent threat, cognitive control was diminished when the valence of the emotional cue conflicted with the emotional state. Successful task performance in this conflicting emotional condition was associated with increased activity in the posterior cingulate cortex, a default mode network region implicated in complex processes such as processing emotions in the context of self and monitoring performance. This region showed positive coupling with frontoparietal circuitry implicated in cognitive control, providing support for a role of the posterior cingulate cortex in mobilizing cognitive resources to improve performance. These findings suggest that emotional states of arousal differentially modulate cognitive control and point to the potential utility of this paradigm for understanding effects of situational and pathological states of arousal on behavior. PMID:26601909

  11. Trypanosoma cruzi disrupts thymic homeostasis by altering intrathymic and systemic stress-related endocrine circuitries.

    Directory of Open Access Journals (Sweden)

    Ailin Lepletier

    2013-11-01

    Full Text Available We have previously shown that experimental infection caused by Trypanosoma cruzi is associated with changes in the hypothalamus-pituitary-adrenal axis. Increased glucocorticoid (GC levels are believed to be protective against the effects of acute stress during infection but result in depletion of CD4(+CD8(+ thymocytes by apoptosis, driving to thymic atrophy. However, very few data are available concerning prolactin (PRL, another stress-related hormone, which seems to be decreased during T. cruzi infection. Considering the immunomodulatory role of PRL upon the effects caused by GC, we investigated if intrathymic cross-talk between GC and PRL receptors (GR and PRLR, respectively might influence T. cruzi-induced thymic atrophy. Using an acute experimental model, we observed changes in GR/PRLR cross-activation related with the survival of CD4(+CD8(+ thymocytes during infection. These alterations were closely related with systemic changes, characterized by a stress hormone imbalance, with progressive GC augmentation simultaneously to PRL reduction. The intrathymic hormone circuitry exhibited an inverse modulation that seemed to counteract the GC-related systemic deleterious effects. During infection, adrenalectomy protected the thymus from the increase in apoptosis ratio without changing PRL levels, whereas an additional inhibition of circulating PRL accelerated the thymic atrophy and led to an increase in corticosterone systemic levels. These results demonstrate that the PRL impairment during infection is not caused by the increase of corticosterone levels, but the opposite seems to occur. Accordingly, metoclopramide (MET-induced enhancement of PRL secretion protected thymic atrophy in acutely infected animals as well as the abnormal export of immature and potentially autoreactive CD4(+CD8(+ thymocytes to the periphery. In conclusion, our findings clearly show that Trypanosoma cruzi subverts mouse thymus homeostasis by altering intrathymic and

  12. Electrocatalytic Production of C3-C4 Compounds by Conversion of CO2 on a Chloride-Induced Bi-Phasic Cu2O-Cu Catalyst.

    Science.gov (United States)

    Lee, Seunghwa; Kim, Dahee; Lee, Jaeyoung

    2015-12-01

    Electrocatalytic conversion of carbon dioxide (CO2) has recently received considerable attention as one of the most feasible CO2 utilization techniques. In particular, copper and copper-derived catalysts have exhibited the ability to produce a number of organic molecules from CO2. Herein, we report a chloride (Cl)-induced bi-phasic cuprous oxide (Cu2O) and metallic copper (Cu) electrode (Cu2OCl) as an efficient catalyst for the formation of high-carbon organic molecules by CO2 conversion, and identify the origin of electroselectivity toward the formation of high-carbon organic compounds. The Cu2OCl electrocatalyst results in the preferential formation of multi-carbon fuels, including n-propanol and n-butane C3-C4 compounds. We propose that the remarkable electrocatalytic conversion behavior is due to the favorable affinity between the reaction intermediates and the catalytic surface.

  13. 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

  14. 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

  15. 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...

  16. 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.

  17. 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.

  18. 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.

  19. The neural circuitry of visual artistic production and appreciation: A proposition

    Directory of Open Access Journals (Sweden)

    Ambar Chakravarty

    2012-01-01

    Full Text Available The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF, relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

  20. 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.

  1. CONDITIONING AND PROTECTION CIRCUITRY FOR EXTERNAL MODULATION OF A PREPROGRAMMED GYROTRON CATHODE VOLTAGE COMMAND WAVEFORM

    Energy Technology Data Exchange (ETDEWEB)

    PONCE,D; FERRON,J.R; LEGG,R.A

    2003-10-01

    OAK-B135 The modulating voltages applied to the DIII-D gyrotrons are controlled by reference signals which are synthesized by arbitrary waveform generators.These generators allow ECH operators to pre-program reference waveforms consisting of ramps, flat tops, and various modulation shapes. This capability is independent of the DIII-D central timing and waveform facilities, which provides the ECH operators operational flexibility. The waveform generators include an amplitude modulation input, providing a means to control the pre-programmed waveform externally. This input is being used to allow the DIII-D plasma control system (PCS) to control gyrotron power in response top selected feedback signals. As the PCS control signal could potentially modulate the gyrotrons beyond operational limits or otherwise in a manner leading to recalcitrant rf generation, the control signal is conditioned so that its effect upon the ECH pre-programmed reference waveform is limited by conditions set by the ECH operators. The design of the circuitry which restricts the range over which the PCS control signal may modulate the reference waveform will be discussed. Test and DIII-D experimental results demonstrating the utility and effectiveness of gyrotron power modulated by the PCS will be presented.

  2. 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

  3. Ultralow-Noise Atomic-Scale Structures for Quantum Circuitry in Silicon.

    Science.gov (United States)

    Shamim, Saquib; Weber, Bent; Thompson, Daniel W; Simmons, Michelle Y; Ghosh, Arindam

    2016-09-14

    The atomically precise doping of silicon with phosphorus (Si:P) using scanning tunneling microscopy (STM) promises ultimate miniaturization of field effect transistors. The one-dimensional (1D) Si:P nanowires are of particular interest, retaining exceptional conductivity down to the atomic scale, and are predicted as interconnects for a scalable silicon-based quantum computer. Here, we show that ultrathin Si:P nanowires form one of the most-stable electrical conductors, with the phenomenological Hooge parameter of low-frequency noise being as low as ≈10(-8) at 4.2 K, nearly 3 orders of magnitude lower than even carbon-nanotube-based 1D conductors. A in-built isolation from the surface charge fluctuations due to encapsulation of the wires within the epitaxial Si matrix is the dominant cause for the observed suppression of noise. Apart from quantum information technology, our results confirm the promising prospects for precision-doped Si:P structures in atomic-scale circuitry for the 11 nm technology node and beyond. PMID:27525390

  4. Super-Resolution Mapping of Neuronal Circuitry With an Index-Optimized Clearing Agent

    Directory of Open Access Journals (Sweden)

    Meng-Tsen Ke

    2016-03-01

    Full Text Available Super-resolution imaging deep inside tissues has been challenging, as it is extremely sensitive to light scattering and spherical aberrations. Here, we report an optimized optical clearing agent for high-resolution fluorescence imaging (SeeDB2. SeeDB2 matches the refractive indices of fixed tissues to that of immersion oil (1.518, thus minimizing both light scattering and spherical aberrations. During the clearing process, fine morphology and fluorescent proteins were highly preserved. SeeDB2 enabled super-resolution microscopy of various tissue samples up to a depth of >100 μm, an order of magnitude deeper than previously possible under standard mounting conditions. Using this approach, we demonstrate accumulation of inhibitory synapses on spine heads in NMDA-receptor-deficient neurons. In the fly medulla, we found unexpected heterogeneity in axon bouton orientations among Mi1 neurons, a part of the motion detection circuitry. Thus, volumetric super-resolution microscopy of cleared tissues is a powerful strategy in connectomic studies at synaptic levels.

  5. 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...

  6. Novel Circuitry Configuration with Paired-Cell Erase Operation for High-Density 90-nm Embedded Resistive Random Access Memory

    Science.gov (United States)

    Sato, Yoshihiro; Tsunoda, Koji; Aoki, Masaki; Sugiyama, Yoshihiro

    2009-04-01

    We propose a novel circuitry configuration for high-density 90-nm embedded resistive random access memory (ReRAM). The memory cells are operated at 2 V, and a small memory cell size of 6F2 consisting of a 1.2-V standard transistor and a resistive junction (1T-1R) is designed, where F is the feature size. The unique circuitry configuration is that each pair of source-lines connects to each source-line selective gate. Therefore, erasing is done by a pair of cells in turn in the whole sector, while the reading or programming is done by a random accessing operation. We simulated the ReRAM circuit for read and write operations with SPICE. As a result, we found that 5-ns high-speed read access was obtained in the 256-word lines (WLs) × 256-bit lines (BLs) and that the SET/RESET operation was stable.

  7. Apollo experience report: Detection and minimization of ignition hazards from water/glycol contamination of silver-clad electrical circuitry

    Science.gov (United States)

    Downs, W. R.

    1976-01-01

    The potential flammability hazard when a water/glycol solution contacts defectively insulated silver-clad copper circuitry or electrical components carrying a direct current is described. The chemical reactions and means for detecting them are explained. Methods for detecting and cleaning contaminated areas and the use of inhibitors to arrest chemical reactivity are also explained. Preventive measures to minimize hazards are given. Photomicrographs of the chemical reactions occurring on silver clad wires are also included.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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...

  13. 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

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    -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...... 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...

  16. 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 ...

  17. FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells

    Science.gov (United States)

    Fournier, Michèle; Bourriquen, Gaëlle; Lamaze, Fabien C.; Côté, Maxime C.; Fournier, Éric; Joly-Beauparlant, Charles; Caron, Vicky; Gobeil, Stéphane; Droit, Arnaud; Bilodeau, Steve

    2016-01-01

    Controlling the transcriptional program is essential to maintain the identity and the biological functions of a cell. The Mediator and Cohesin complexes have been established as central cofactors controlling the transcriptional program in normal cells. However, the distribution, recruitment and importance of these complexes in cancer cells have not been fully investigated. Here we show that FOXA and master transcription factors are part of the core transcriptional regulatory circuitry of cancer cells and are essential to recruit M ediator and Cohesin. Indeed, Mediator and Cohesin occupied the enhancer and promoter regions of actively transcribed genes and maintained the proliferation and colony forming potential. Through integration of publically available ChIP-Seq datasets, we predicted the core transcriptional regulatory circuitry of each cancer cell. Unexpectedly, for all cells investigated, the pioneer transcription factors FOXA1 and/or FOXA2 were identified in addition to cell-specific master transcription factors. Loss of both types of transcription factors phenocopied the loss of Mediator and Cohesin. Lastly, the master and pioneer transcription factors were essential to recruit Mediator and Cohesin to regulatory regions of actively transcribed genes. Our study proposes that maintenance of the cancer cell state is dependent on recruitment of Mediator and Cohesin through FOXA and master transcription factors. PMID:27739523

  18. 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.

  19. Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

    Directory of Open Access Journals (Sweden)

    Daniel Charles Castro

    2015-06-01

    Full Text Available The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc and ventral pallidum (VP, in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (‘liking’ and motivational incentive salience (‘wanting’ of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating versus intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including ‘liking’ and ‘wanting’ for food rewards.

  20. Phasic Sequential Preventive Maintenance Policy Based on Imperfect Maintenance for Deteriorating Systems%基于不完全维护的劣化系统分阶段顺序预防维护策略

    Institute of Scientific and Technical Information of China (English)

    曲玉祥; 吴甦

    2011-01-01

    The state of most systems after maintenance is somewhere between as good as new and as bad as old. Based on the imperfect maintenance theory, a new improvement factor considering the equipment working age and the maintenance cost is introduced. In order to make the policy more suitable in operation, the concept of phasic sequential preventive maintenance is put forward. By minimizing the cost rate of the maintenance in the life cycle of the system, two sequential preventive maintenance models are proposed, the general sequential one and the phasic sequential one. The optimal preventive maintenance intervals and the number of preventive maintenance activities are obtained from the model. The numerical results show that the phasic sequential preventive maintenance policy is more operable in the actual maintenance activities and more appropriate to the properties of the deteriorating systems. Compared with the general model, the phasic one achieves a better economical efficiency and operability at the same maintenance cost.%多数系统维护之后的状态介于"全新"和"如旧"之间.基于不完全维护理论,引入考虑设备工龄和维护成本的改善因子,结合维护活动的实际情况,提出分阶段顺序维护的概念.以设备整个维修周期内的成本率最低为优化目标,建立两种顺序预防维护模型,即一般顺序预防维护模型和分阶段顺序预防维护模型(模型Ⅰ和模型Ⅱ),得到系统最优维护时间间隔和在全寿命周期内执行预防维护的次数,通过数值验证对各自模型的特点和有效性进行讨论.结果表明,分阶段顺序预防维护模型在不明显增加系统维护成本的前提下,既可以很好地适应劣化系统失效率随工龄增加而增长的特点,又能够贴近维修生产实践,使其在寻求最优维护策略方面兼具更好的经济性和可行性.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Fusco, Salvatore; Leone, Lucia; Barbati, Saviana Antonella; Samengo, Daniela; Piacentini, Roberto; Maulucci, Giuseppe; Toietta, Gabriele; Spinelli, Matteo; McBurney, Michael; Pani, Giovambattista; Grassi, Claudio

    2016-02-01

    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. PMID:26804914

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

    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......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...

  9. 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…

  10. Multiple types of cerebellar target neurons and their circuitry in the vestibulo-ocular reflex.

    Science.gov (United States)

    Shin, Minyoung; Moghadam, Setareh H; Sekirnjak, Chris; Bagnall, Martha W; Kolkman, Kristine E; Jacobs, Richard; Faulstich, Michael; du Lac, Sascha

    2011-07-27

    The cerebellum influences behavior and cognition exclusively via Purkinje cell synapses onto neurons in the deep cerebellar and vestibular nuclei. In contrast with the rich information available about the organization of the cerebellar cortex and its synaptic inputs, relatively little is known about microcircuitry postsynaptic to Purkinje cells. Here we examined the cell types and microcircuits through which Purkinje cells influence an oculomotor behavior controlled by the cerebellum, the horizontal vestibulo-ocular reflex, which involves only two eye muscles. Using a combination of anatomical tracing and electrophysiological recordings in transgenic mouse lines, we identified several classes of neurons in the medial vestibular nucleus that receive Purkinje cell synapses from the cerebellar flocculus. Glycinergic and glutamatergic flocculus target neurons (FTNs) with somata densely surrounded by Purkinje cell terminals projected axons to the ipsilateral abducens and oculomotor nuclei, respectively. Of three additional types of FTNs that were sparsely innervated by Purkinje cells, glutamatergic and glycinergic neurons projected to the contralateral and ipsilateral abducens, respectively, and GABAergic neurons projected to contralateral vestibular nuclei. Densely innervated FTNs had high spontaneous firing rates and pronounced postinhibitory rebound firing, and were physiologically homogeneous, whereas the intrinsic excitability of sparsely innervated FTNs varied widely. Heterogeneity in the molecular expression, physiological properties, and postsynaptic targets of FTNs implies that Purkinje cell activity influences the neural control of eye movements in several distinct ways. These results indicate that the cerebellum regulates a simple reflex behavior via at least five different cell types that are postsynaptic to Purkinje cells.

  11. 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...

  12. When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation.

    Science.gov (United States)

    Krusemark, Elizabeth A; Novak, Lucas R; Gitelman, Darren R; Li, Wen

    2013-09-25

    Phylogenetically the most ancient sense, olfaction is characterized by a unique intimacy with the emotion system. However, mechanisms underlying olfaction-emotion interaction remain unclear, especially in an ever-changing environment and dynamic internal milieu. Perturbing the internal state with anxiety induction in human subjects, we interrogated emotion-state-dependent olfactory processing in a functional magnetic resonance imaging (fMRI) study. Following anxiety induction, initially neutral odors become unpleasant and take longer to detect, accompanied by augmented response to these odors in the olfactory (anterior piriform and orbitofrontal) cortices and emotion-relevant pregenual anterior cingulate cortex. In parallel, the olfactory sensory relay adapts with increased anxiety, incorporating amygdala as an integral step via strengthened (afferent or efferent) connections between amygdala and all levels of the olfactory cortical hierarchy. This anxiety-state-dependent neural circuitry thus enables cumulative infusion of limbic affective information throughout the olfactory sensory progression, thereby driving affectively charged olfactory perception. These findings could constitute an olfactory etiology model of emotional disorders, as exaggerated emotion-olfaction interaction in negative mood states turns innocuous odors aversive, fueling anxiety and depression with rising ambient sensory stress.

  13. 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.

  14. Emotional regulation: implications for the psychobiology of psychotherapy.

    Science.gov (United States)

    Stein, Dan J

    2008-03-01

    A range of studies have contributed to understanding the psychobiology of emotional regulation. Functional imaging studies have demonstrated that cortico-limbic circuitry plays an important role in mediating processes such as reappraisal and suppression. Dorsolateral prefrontal cortex may be important in conscious reframing, while ventromedial prefrontal cortex and orbitofrontal cortex may be particularly important in emotion evaluation. Gene variants and early environments impact underlying emotional regulation and its neurobiology. It may be hypothesized that during interventions such as psychotherapy there are improvements in emotional regulation, together with the normalization of related psychobiological mechanisms.

  15. 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

  16. 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

  17. Identification of CNS neural circuitry involved in the innervation of C7 spinal nerve: a viral transsynaptic tracing study

    Directory of Open Access Journals (Sweden)

    WEI Hai-feng

    2012-02-01

    Full Text Available 【Abstract】 Objective: Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS. This study tried to locate the CNS neuronal elements involved in the innervation of C7 spinal nerve. Method: Pseudorabies virus (PRV, TK/gG-, 2 祃, which expressed green fluorescent protein (GFP, was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats. After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7 segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV. Results: PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.. The number of PRV-labeled neurons in the CNS was increasing with rat抯 survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.. Conclusion: By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons, which modulates the activity of C7 spinal nerve, is located successfully in the CNS. Key words: Brachial plexus; Innervation; Spinal nerves; Central nervous system

  18. Identification of CNS neural circuitry involved in the innervation of C7 spinal nerve: a viral transsynaptic tracing study

    Institute of Scientific and Technical Information of China (English)

    WEI Hai-feng; CHEN Liang; GU Yu-dong

    2011-01-01

    Objective: Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS).This study tried to locate the CNS neuronal elements involved in the innervation ofC7 spinal nerve.Method: Pseudorabies virus (PRV, TK/gG-,2 μl), which expressed green fluorescent protein (GFP), was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats.After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV.Results: PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.). The number of PRV-labeled neurons in the CNS was increasing with rat's survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.).Conclusion: By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons,which modulates the activity of C7 spinal nerve, is located successfully in the CNS.

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

    Science.gov (United States)

    Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

    2015-01-01

    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 innervated sweat glands

  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. 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...

  2. 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...

  3. 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...

  4. 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

  5. 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...

  6. SUMO: regulating the regulator

    Directory of Open Access Journals (Sweden)

    Bossis Guillaume

    2006-06-01

    Full Text Available Abstract Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier family have emerged as key regulators of protein function and fate. While the past few years have seen an enormous increase in knowledge on SUMO enzymes, substrates, and consequences of modification, regulation of SUMO conjugation is far from being understood. This brief review will provide an overview on recent advances concerning (i the interplay between sumoylation and other post-translational modifications at the level of individual targets and (ii global regulation of SUMO conjugation and deconjugation.

  7. 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.

  8. Prolactin receptor in regulation of neuronal excitability and channels.

    Science.gov (United States)

    Patil, Mayur J; Henry, Michael A; Akopian, Armen N

    2014-01-01

    Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca(2+) influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca(2+) -dependent K(+) channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL.

  9. Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD). An fMRI study.

    Science.gov (United States)

    Jatzko, Alexander; Schmitt, Andrea; Demirakca, Traute; Weimer, Erik; Braus, Dieter F

    2006-03-01

    This study was designed to investigate the circuitry underlying movie-induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI-paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion-related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

  10. 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

  11. Aging-induced proteostatic changes in the rat hippocampus identify ARP3, NEB2 and BRAG2 as a molecular circuitry for cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Philipp Ottis

    Full Text Available Disturbed proteostasis as a particular phenotype of the aging organism has been advanced in C. elegans experiments and is also conceived to underlie neurodegenerative diseases in humans. Here, we investigated whether particular changes in non-disease related proteostasis can be identified in the aged mammalian brain, and whether a particular signature of aberrant proteostasis is related to behavioral performance of learning and memory. Young (adult, n = 30 and aged (2 years, n = 50 Wistar rats were tested in the Morris Water Maze (MWM to distinguish superior and inferior performers. For both young and old rats, the best and worst performers in the MWM were selected and the insoluble proteome, termed aggregome, was purified from the hippocampus as evidence for aberrant proteostasis. Quantitative proteomics (iTRAQ was performed. The aged inferior performers were considered as a model for spontaneous, age-associated cognitive impairment. Whereas variability of the insoluble proteome increased with age, absolute changes in the levels of insoluble proteins were small compared to the findings in the whole C. elegans insoluble proteome. However, we identified proteins with aberrant proteostasis in aging. For the cognitively impaired rats, we identified a changed molecular circuitry of proteins selectively involved in F-actin remodeling, synapse building and long-term depression: actin related protein 3 (ARP3, neurabin II (NEB2 and IQ motif and SEC7 domain-containing protein 1 (BRAG2. We demonstrate that aberrant proteostasis is a specific phenotype of brain aging in mammals. We identify a distinct molecular circuitry where changes in proteostasis are characteristic for poor learning and memory performance in the wild type, aged rat. Our findings 1. establish the search for aberrant proteostasis as a successful strategy to identify neuronal dysfunction in deficient cognitive behavior, 2. reveal a previously unknown functional network of proteins (ARP3

  12. 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

  13. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    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......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...... 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...

  14. 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

  15. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin.

    Science.gov (United States)

    Yosten, Gina L C; Samson, Willis K

    2014-05-15

    Nesfatin-1 is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central nesfatin-1 requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of nesfatin-1 as well. We hypothesized that the cardiovascular effect of nesfatin-1 also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated nesfatin-1-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of nesfatin-1 may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of α-melanocyte stimulating hormone (α-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while α-MSH-producing neurons are part of a core melanocortin-CRH-oxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by nesfatin-1 do mediate the hypertensive action of the peptide, α-MSH can signal independently from this circuit to increase MAP.

  16. 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.

  17. High voltage dc-dc converter with dynamic voltage regulation and decoupling during load-generated arcs

    Science.gov (United States)

    Shimer, Daniel W.; Lange, Arnold C.

    1995-01-01

    A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules.

  18. Adipostatic regulation of motivation and emotion.

    Science.gov (United States)

    Davis, Jon F

    2010-05-01

    The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. Research on intelligent circuitry board detection and diagnosis method based on functional model%基于功能模型的智能电路板检测诊断方法研究

    Institute of Scientific and Technical Information of China (English)

    董俊; 谭业双; 蒲秀英; 管海山

    2011-01-01

    为了克服智能电路板检测诊断难的问题,满足设备中板级检测维修的迫切需求,提出了一种基于功能模型和"嵌入+交互"式的智能电路板检测诊断方法.建立了智能电路板通用测试模型,研究了检测整体思想和具体的检测技术和方法.详细介绍了检软件件的设计思路和方法.采用支持向量机算法进行故障判定.最后进行了仿真实验.实验表明,该方法能对智能电路板进行有效的检测诊断,对智能电路板检测具有一定的指导作用.%In order to settle the issue of difficulty in intelligent circuitry board detection and meet the requirement of board-level detection and maintenance in the equipment, this paper propose a embedded and interactive detection and diagnosis method for intelligent circuitry board based on functional model.General test model is built, and collective test idea and concrete detection technology and method are researched. The design concept and method of the test software are presented in detail, and SVM algorithm is employed to carry through failure determination. Finally it conducts simulation. The experiment has shown that the method can conduct effective detection for intelligent circuitry board and gives guidance to inteUigent circuitry board detection.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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,...

  13. 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.

  14. 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.

  15. 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.

  16. GABAergic regulation of the HPA and HPG axes and the impact of stress on reproductive function.

    Science.gov (United States)

    Camille Melón, Laverne; Maguire, Jamie

    2016-06-01

    The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes are regulated by GABAergic signaling at the level of corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH) neurons, respectively. Under basal conditions, activity of CRH and GnRH neurons are controlled in part by both phasic and tonic GABAergic inhibition, mediated by synaptic and extrasynaptic GABAA receptors (GABAARs), respectively. For CRH neurons, this tonic GABAergic inhibition is mediated by extrasynaptic, δ subunit-containing GABAARs. Similarly, a THIP-sensitive tonic GABAergic current has been shown to regulate GnRH neurons, suggesting a role for δ subunit-containing GABAARs; however, this remains to be explicitly demonstrated. GABAARs incorporating the δ subunit confer neurosteroid sensitivity, suggesting a potential role for neurosteroid modulation in the regulation of the HPA and HPG axes. Thus, stress-derived neurosteroids may contribute to the impact of stress on reproductive function. Interestingly, excitatory actions of GABA have been demonstrated in both CRH neurons at the apex of control of the HPA axis and in GnRH neurons which mediate the HPG axis, adding to the complexity for the role of GABAergic signaling in the regulation of these systems. Here we review the effects that stress has on GnRH neurons and HPG axis function alongside evidence supporting GABAARs as a major interface between the stress and reproductive axes.

  17. Sixth Warren K. Sinclair keynote address: The role of a strong regulator in safe and secure nuclear energy.

    Science.gov (United States)

    Lyons, Peter B

    2011-01-01

    The history of nuclear regulation is briefly reviewed to underscore the early recognition that independence of the regulator was essential in achieving and maintaining public credibility. The current licensing process is reviewed along with the status of applications. Challenges faced by both the NRC and the industry are reviewed, such as new construction techniques involving modular construction, digital controls replacing analog circuitry, globalization of the entire supply chain, and increased security requirements. The vital area of safety culture is discussed in some detail, and its importance is emphasized.

  18. 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...

  19. Regulating Transplants

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Legislation to determine brain death is viewed as essential in controlling the organ transplant industry Organ transplant represents a very sensitive and complicated issue. Experts say the temporary administrative regulations recently promulgated by the Central Government are an important step, but relevant laws and regulations must follow. Among these, the

  20. 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

  1. 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...

  2. 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...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation.

    Science.gov (United States)

    Haldar, Saptarsi M; Jeyaraj, Darwin; Anand, Priti; Zhu, Han; Lu, Yuan; Prosdocimo, Domenick A; Eapen, Betty; Kawanami, Daiji; Okutsu, Mitsuharu; Brotto, Leticia; Fujioka, Hisashi; Kerner, Janos; Rosca, Mariana G; McGuinness, Owen P; Snow, Rod J; Russell, Aaron P; Gerber, Anthony N; Bai, Xiaodong; Yan, Zhen; Nosek, Thomas M; Brotto, Marco; Hoppel, Charles L; Jain, Mukesh K

    2012-04-24

    The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids. PMID:22493257

  18. 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.

  19. 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

  20. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor.

    Science.gov (United States)

    Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Seunghee; Lee, Soo-Kyung; Lee, Jae W

    2013-10-01

    Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance.

  1. 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

  2. Disruption of dopamine neuron activity pattern regulation through selective expression of a human KCNN3 mutation.

    Science.gov (United States)

    Soden, Marta E; Jones, Graham L; Sanford, Christina A; Chung, Amanda S; Güler, Ali D; Chavkin, Charles; Luján, Rafael; Zweifel, Larry S

    2013-11-20

    The calcium-activated small conductance potassium channel SK3 plays an essential role in the regulation of dopamine neuron activity patterns. Here we demonstrate that expression of a human disease-related SK3 mutation (hSK3Δ) in dopamine neurons of mice disrupts the balance between tonic and phasic dopamine neuron activity. Expression of hSK3Δ suppressed endogenous SK currents, reducing coupling between SK channels and NMDA receptors (NMDARs) and increasing permissiveness for burst firing. Consistent with enhanced excitability of dopamine neurons, hSK3Δ increased evoked calcium signals in dopamine neurons in vivo and potentiated evoked dopamine release. Specific expression of hSK3Δ led to deficits in attention and sensory gating and heightened sensitivity to a psychomimetic drug. Sensory-motor alterations and psychomimetic sensitivity were recapitulated in a mouse model of transient, reversible dopamine neuron activation. These results demonstrate the cell-autonomous effects of a human ion channel mutation on dopamine neuron physiology and the impact of activity pattern disruption on behavior.

  3. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons.

    Science.gov (United States)

    Chaudhury, Dipesh; Walsh, Jessica J; Friedman, Allyson K; Juarez, Barbara; Ku, Stacy M; Koo, Ja Wook; Ferguson, Deveroux; Tsai, Hsing-Chen; Pomeranz, Lisa; Christoffel, Daniel J; Nectow, Alexander R; Ekstrand, Mats; Domingos, Ana; Mazei-Robison, Michelle S; Mouzon, Ezekiell; Lobo, Mary Kay; Neve, Rachael L; Friedman, Jeffrey M; Russo, Scott J; Deisseroth, Karl; Nestler, Eric J; Han, Ming-Hu

    2013-01-24

    Ventral tegmental area (VTA) dopamine neurons in the brain's reward circuit have a crucial role in mediating stress responses, including determining susceptibility versus resilience to social-stress-induced behavioural abnormalities. VTA dopamine neurons show two in vivo patterns of firing: low frequency tonic firing and high frequency phasic firing. Phasic firing of the neurons, which is well known to encode reward signals, is upregulated by repeated social-defeat stress, a highly validated mouse model of depression. Surprisingly, this pathophysiological effect is seen in susceptible mice only, with no apparent change in firing rate in resilient individuals. However, direct evidence--in real time--linking dopamine neuron phasic firing in promoting the susceptible (depression-like) phenotype is lacking. Here we took advantage of the temporal precision and cell-type and projection-pathway specificity of optogenetics to show that enhanced phasic firing of these neurons mediates susceptibility to social-defeat stress in freely behaving mice. We show that optogenetic induction of phasic, but not tonic, firing in VTA dopamine neurons of mice undergoing a subthreshold social-defeat paradigm rapidly induced a susceptible phenotype as measured by social avoidance and decreased sucrose preference. Optogenetic phasic stimulation of these neurons also quickly induced a susceptible phenotype in previously resilient mice that had been subjected to repeated social-defeat stress. Furthermore, we show differences in projection-pathway specificity in promoting stress susceptibility: phasic activation of VTA neurons projecting to the nucleus accumbens (NAc), but not to the medial prefrontal cortex (mPFC), induced susceptibility to social-defeat stress. Conversely, optogenetic inhibition of the VTA-NAc projection induced resilience, whereas inhibition of the VTA-mPFC projection promoted susceptibility. Overall, these studies reveal novel firing-pattern- and neural

  4. 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.

  5. Volume changes of cortical and subcortical reward circuitry in the brain of patients with type 2 diabetes mellitus%2型糖尿病患者脑部皮层及皮层下奖赏环路研究

    Institute of Scientific and Technical Information of China (English)

    陈志晔; 李金锋; 刘梦雨; 马林

    2013-01-01

    Objective To elucidate the volume changes of cortical and subcortical reward circuitry in patients with type 2 diabetes mellitus. Methods High-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI images were obtained from 16 patients with type 2 diabetes mellitus and 16 normal controls, and 11 type 2 diabetic patients also received the same MRI scans after insulin therapy for 1 year. Volumetric analysis was performed and analysis of covariance and paired t test were applied. Results A decreased volume was found in the left insular lobe, left nucleus accumbens area, right hippocampus, putamen and amygdala in type 2 diabetic patients compared with normal controls (P0.05), and bilateral ventral diencephalon area showed an increased volume after the treatment (left, 3.26±0.68 ml;right, 3.20±0.78 ml) compared with the baseline (left, 2.96 ± 0.76 ml;right, 2.82 ± 0.90 ml) (P<0.05). Conclusion Type 2 diabetic patients have a decreased volume of the cortical and subcortical reward circuitry, and insulin therapy can reverse such changes and improve the damage of reward circuitry.%目的探索2型糖尿病患者皮层及皮层下奖赏环路体积变化,以及胰岛素治疗对奖赏环路的影响。方法对16名2型糖尿病患者及16名健康志愿者进行脑形态学分析,其中11名2型糖尿病患者进行基线(胰岛素治疗前)及随访水平(胰岛素治疗1年)的体积测量。统计学方法采用协方差分析及配对t检验。结果2型糖尿病患者左侧岛叶及伏隔核区、右侧海马、壳核及杏仁核体积显著小于对照组。接受胰岛素治疗1年后双侧皮层奖赏系统体积(左侧:33.65±3.66 ml;右侧:33.35±4.25 ml)显著高于基线水平(左侧:31.45±2.90 ml;右侧:31.12±2.97 ml);双侧基底节食物奖赏系统结构体积无显著差异;双侧腹侧间脑体积随访水平(左侧:3.26±0.68 ml;右侧:3.20±0.78 ml)较基线水平(左侧:2

  6. 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.

  7. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality☆

    Science.gov (United States)

    van Tol, Marie-José; Veer, Ilya M.; van der Wee, Nic J.A.; Aleman, André; van Buchem, Mark A.; Rombouts, Serge A.R.B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication-free MDD patients without current or past comorbidity and matched controls (n = 25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject's connectivity with each standard network were used to evaluate between-group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic–cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior. PMID:24179829

  8. 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

  9. 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.

  10. 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

  11. Siah regulation of Pard3A controls neuronal cell adhesion during germinal zone exit.

    Science.gov (United States)

    Famulski, Jakub K; Trivedi, Niraj; Howell, Danielle; Yang, Yuan; Tong, Yiai; Gilbertson, Richard; Solecki, David J

    2010-12-24

    The brain's circuitry is established by directed migration and synaptogenesis of neurons during development. Although neurons mature and migrate in specific patterns, little is known about how neurons exit their germinal zone niche. We found that cerebellar granule neuron germinal zone exit is regulated by proteasomal degradation of Pard3A by the Seven in Absentia homolog (Siah) E3 ubiquitin ligase. Pard3A gain of function and Siah loss of function induce precocious radial migration. Time-lapse imaging using a probe to measure neuronal cell contact reveals that Pard3A promotes adhesive interactions needed for germinal zone exit by recruiting the epithelial tight junction adhesion molecule C to the neuronal cell surface. Our findings define a Siah-Pard3A signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche.

  12. Input- and Output-Specific Regulation of Serial Order Performance by Corticostriatal Circuits.

    Science.gov (United States)

    Rothwell, Patrick E; Hayton, Scott J; Sun, Gordon L; Fuccillo, Marc V; Lim, Byung Kook; Malenka, Robert C

    2015-10-21

    The serial ordering of individual movements into sequential patterns is thought to require synaptic plasticity within corticostriatal circuits that route information through the basal ganglia. We used genetically and anatomically targeted manipulations of specific circuit elements in mice to isolate the source and target of a corticostriatal synapse that regulates the performance of a serial order task. This excitatory synapse originates in secondary motor cortex, terminates on direct pathway medium spiny neurons in the dorsolateral striatum, and is strengthened by serial order learning. This experience-dependent and synapse-specific form of plasticity may sculpt the balance of activity in basal ganglia circuits during sequential movements, driving a disparity in striatal output that favors the direct pathway. This disparity is necessary for execution of responses in serial order, even though both direct and indirect pathways are active during movement initiation, suggesting dynamic modulation of corticostriatal circuitry contributes to the choreography of behavioral routines.

  13. [Methods for quantifying phasic skin conductance amplitudes: threats to validity?].

    Science.gov (United States)

    Zimmer, H; Vossel, G

    1993-01-01

    Two methods of determining the event-related skin conductance response (SCR) amplitude are in common use. In one of these, the difference in conductance between the point of onset and the peak level of a single wave is measured (method 1). The second approach is to determine the difference between two measures, one characterizing the prestimulus level, the other the highest conductance point of the SCR reached within a fixed period following the stimulus (method 2). A problem with quantifying the SCR amplitude occurs when a SCR is elicited before an immediately preceding response has had time to recover, because in this case the two methods lead to quite different values. If the amplitude of each response is measured from its own individual deflection point, the measurable amplitude of the second response will be smaller when it occurs immediately after or in the ascending limb of the first response. The problem is most evident in situations with a high probability of response superimposition, such as when a large number of nonspecific responses occur at the same time as the SCRs. This is found in individuals with a high degree of electrodermal lability. Electrodermal lability refers to a psychophysiological construct that is operationally defined by the frequency of spontaneous electrodermal fluctuations. In the present study, we therefore systematically investigated the effects of the two score methods on SCR amplitude in relation to lability by analyzing electrodermal data from two habituation studies. As expected, several method-specific effects which were related to lability emerged. Results and questions concerning the relevance of the findings are discussed, with special emphasis on the validity of psychophysiological investigations.

  14. 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

  15. Optical suppression of drug-evoked phasic dopamine release.

    Science.gov (United States)

    McCutcheon, James E; Cone, Jackson J; Sinon, Christopher G; Fortin, Samantha M; Kantak, Pranish A; Witten, Ilana B; Deisseroth, Karl; Stuber, Garret D; Roitman, Mitchell F

    2014-01-01

    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.

  16. 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.

  17. Role of the human high-affinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy.

    Science.gov (United States)

    Kuo, Macus Tien; Fu, Siqing; Savaraj, Niramol; Chen, Helen H W

    2012-09-15

    The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation.

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. Method and circuitry for CMOS transconductor linearization

    NARCIS (Netherlands)

    Kundur Subramaniyan, Harish; Klumperink, Eric; Srinivasan, Venkatesh; Kiaei, Ali; Nauta, Bram

    2016-01-01

    Third order distortion is reduced in a CMOS transconductor circuit that includes a first N-channel transistor and a first P-channel transistor, gates of the first N-channel transistor and the first P-channel transistor being coupled to receive an input signal. Drains of the first N-channel transisto

  5. 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

  6. 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...

  7. 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 ...

  8. 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

  9. General Theories of Regulation

    NARCIS (Netherlands)

    Hertog, J.A. den

    1999-01-01

    This chapter makes a distinction between three types of theories of regulation: public interest theories, the Chicago theory of regulation and the public choice theories. The Chicago theory is mainly directed at the explanation of economic regulation; public interest theories and public choice theor

  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. 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

  12. 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)

  13. 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

  14. Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction

    Science.gov (United States)

    Yeger-Lotem, Esti; Sattath, Shmuel; Kashtan, Nadav; Itzkovitz, Shalev; Milo, Ron; Pinter, Ron Y.; Alon, Uri; Margalit, Hanah

    2004-04-01

    Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription-regulation or protein-protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription-regulation and protein-protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein-protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.

  15. Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation.

    Science.gov (United States)

    Van Roey, Kim; Davey, Norman E

    2015-01-01

    A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules. PMID:26626130

  16. Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle.

    Science.gov (United States)

    Hristov, Kiril L; Smith, Amy C; Parajuli, Shankar P; Malysz, John; Petkov, Georgi V

    2014-03-01

    Large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca(2+) imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca(2+) sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca(2+) levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca(2+)-dependent mechanism, thus increasing DSM contractility.

  17. 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)

  18. 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.

  19. 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)

  20. 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...

  1. 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 ...

  2. A role for histamine in cardiovascular regulation in late stage embryos of the red-footed tortoise, Chelonoidis carbonaria Spix, 1824.

    Science.gov (United States)

    Crossley, Dane A; Sartori, Marina R; Abe, Augusto S; Taylor, Edwin W

    2013-08-01

    A chorioallantoic membrane artery in embryos of the red-footed tortoise, Chelonoidis carbonaria was occlusively cannulated for measurement of blood pressure and injection of drugs. Two age groups of embryos in the final 10 % of incubation were categorized by the ratio of embryonic body to yolk mass. All embryos first received cholinergic and β-adrenergic blockade. This revealed that β-adrenergic control was established in both groups whereas cholinergic control was only established in the older group immediately prior to hatching. The study then progressed as two series. Series one was conducted in a subset of embryos treated with histamine before or after injection of ranitidine, the antagonist of H2 receptors. Injection of histamine caused an initial phasic hypertension which recovered, followed by a longer lasting hypertensive response accompanied by a tachycardia. Injection of the H2 receptor antagonist ranitidine itself caused a hypotensive tachycardia with subsequent recovery of heart rate. Ranitidine also abolished the cardiac effects of histamine injection while leaving the initial hypertensive response intact. In series, two embryos were injected with histamine after injection of diphenhydramine, the antagonist to H1 receptors. This abolished the whole of the pressor response to histamine injection but left the tachycardic response intact. These data indicate that histamine acts as a non-adrenergic, non-cholinergic factor, regulating the cardiovascular system of developing reptilian embryos and that its overall effects are mediated via both H1 and H2 receptor types.

  3. Plant Growth Regulators.

    Science.gov (United States)

    Nickell, Louis G.

    1978-01-01

    Describes the effect of "plant growth regulators" on plants, such as controlling the flowering, fruit development, plant size, and increasing crop yields. Provides a list of plant growth regulators which includes their chemical, common, and trade names, as well as their different use(s). (GA)

  4. Mortgage market regulation: Europe

    NARCIS (Netherlands)

    M.B. Aalbers

    2012-01-01

    Despite several European Union (EU) initiatives, there is only limited pan-European mortgage market regulation. The EU strategy can be characterised as one of parallel liberalisation and consolidation. This article highlights the key differences in regulation among European mortgage markets. Mortgag

  5. 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

  6. 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...

  7. 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......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 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 publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  8. The diversity and evolution of cell cycle regulation in alpha-proteobacteria: a comparative genomic analysis

    Directory of Open Access Journals (Sweden)

    Mengoni Alessio

    2010-04-01

    Full Text Available Abstract Background In the bacterium Caulobacter crescentus, CtrA coordinates DNA replication, cell division, and polar morphogenesis and is considered the cell cycle master regulator. CtrA activity varies during cell cycle progression and is modulated by phosphorylation, proteolysis and transcriptional control. In a phosphorylated state, CtrA binds specific DNA sequences, regulates the expression of genes involved in cell cycle progression and silences the origin of replication. Although the circuitry regulating CtrA is known in molecular detail in Caulobacter, its conservation and functionality in the other alpha-proteobacteria are still poorly understood. Results Orthologs of Caulobacter factors involved in the regulation of CtrA were systematically scanned in genomes of alpha-proteobacteria. In particular, orthologous genes of the divL-cckA-chpT-ctrA phosphorelay, the divJ-pleC-divK two-component system, the cpdR-rcdA-clpPX proteolysis system, the methyltransferase ccrM and transcriptional regulators dnaA and gcrA were identified in representative genomes of alpha-proteobacteria. CtrA, DnaA and GcrA binding sites and CcrM putative methylation sites were predicted in promoter regions of all these factors and functions controlled by CtrA in all alphas were predicted. Conclusions The regulatory cell cycle architecture was identified in all representative alpha-proteobacteria, revealing a high diversification of circuits but also a conservation of logical features. An evolutionary model was proposed where ancient alphas already possessed all modules found in Caulobacter arranged in a variety of connections. Two schemes appeared to evolve: a complex circuit in Caulobacterales and Rhizobiales and a simpler one found in Rhodobacterales.

  9. 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

  10. 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

  11. 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

  12. On-chip boost regulator with projected off- and on-time control*

    Institute of Scientific and Technical Information of China (English)

    Xiao-ru XU; Meng-lian ZHAO; Xiao-bo WU

    2009-01-01

    The boost type power supplies are widely used in portable consumer electronics to step up the input voltage to adapt for the high voltage applications like light-emitting diode (LED) driving and liquid crystal display (LCD) biasing. In these applications, a regulator with small volume, fewer external components and high efficiency is highly desired. This paper proposes a projected off- and on-time boost control scheme, based on which a monolithic IC with an on-chip VDMOS with 0.2 Ω on-stateresistance RDS-ON was implemented in 1.5 μm bipolar-CMOS-DMOS (BCD) process. A 12V, 0.3A boost regulator prototype ispresented as well. With projected off-time and modulated on-time in continuous conduction mode (CCM), a quasi fixed frequency,which is preferred for ripple control, is realized. With projected on-time and modulated off-time in discontinuous conduction mode (DCM), pulse frequency modulation (PFM) operation, which is beneficial to light load efficiency improvement, is achieved without extra control circuitry. Measurement results show that an efficiency of 3% higher than that of a conventional method under 0.5 W output is achieved while a step load transient response comparable to that of current mode control is maintained as well.

  13. Oxytocin: an emerging regulator of prolactin secretion in the female rat.

    Science.gov (United States)

    Kennett, J E; McKee, D T

    2012-03-01

    In the female rat, a complex interplay of both stimulatory and inhibitory hypothalamic factors controls the secretion of prolactin. Prolactin regulates a large number of physiological processes from immunity to stress. Here, we have chosen to focus on the control of prolactin secretion in the female rat in response to suckling, mating and ovarian steroids. In all three of these states, dopamine, released from neurones in the mediobasal hypothalamus, is a potent inhibitory signal regulating prolactin secretion. Early research has determined that the relief of dopaminergic tone is not sufficent to account for the full surge of prolactin secretion observed in response to the suckling stimulus, launching a search for possible prolactin-releasing factors. This research has subsequently broadened to include searching for prolactin-releasing factors controlling prolactin secretion after mating or ovarian steroids. A great deal of literature has suggested that this prolactin-releasing factor may include oxytocin. Oxytocin receptors are present on lactotrophs. These oxytocin receptors respond to exogenous oxytocin and antagonism of endogenous oxytocin inhibits lactotroph activity. In addition, the pattern of oxytocin neuronal activity and oxytocin release correlate with the release of prolactin. Here, we suggest not only that oxytocin is stimulating prolactin secretion, but also that prolactin secretion is controlled by a complex network of positive (oxytocin) and negative (dopamine) feedback loops. We discuss the available literature and attempt to describe the circuitry we believe may be responsible for controlling prolactin secretion.

  14. Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation.

    Science.gov (United States)

    Alvarez-Dominguez, Juan R; Hu, Wenqian; Yuan, Bingbing; Shi, Jiahai; Park, Staphany S; Gromatzky, Austin A; van Oudenaarden, Alexander; Lodish, Harvey F

    2014-01-23

    Erythropoiesis is regulated at multiple levels to ensure the proper generation of mature red cells under multiple physiological conditions. To probe the contribution of long noncoding RNAs (lncRNAs) to this process, we examined >1 billion RNA-seq reads of polyadenylated and nonpolyadenylated RNA from differentiating mouse fetal liver red blood cells and identified 655 lncRNA genes including not only intergenic, antisense, and intronic but also pseudogene and enhancer loci. More than 100 of these genes are previously unrecognized and highly erythroid specific. By integrating genome-wide surveys of chromatin states, transcription factor occupancy, and tissue expression patterns, we identify multiple lncRNAs that are dynamically expressed during erythropoiesis, show epigenetic regulation, and are targeted by key erythroid transcription factors GATA1, TAL1, or KLF1. We focus on 12 such candidates and find that they are nuclear-localized and exhibit complex developmental expression patterns. Depleting them severely impaired erythrocyte maturation, inhibiting cell size reduction and subsequent enucleation. One of them, alncRNA-EC7, is transcribed from an enhancer and is specifically needed for activation of the neighboring gene encoding BAND 3. Our study provides an annotated catalog of erythroid lncRNAs, readily available through an online resource, and shows that diverse types of lncRNAs participate in the regulatory circuitry underlying erythropoiesis.

  15. 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...

  16. 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

  17. 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 ...

  18. 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...

  19. Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.

    Science.gov (United States)

    Isogai, Ayu; Lee, Ken; Mitsui, Retsu; Hashitani, Hikaru

    2016-09-01

    We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 μM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 μM), large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 μM), a blocker of L-type voltage-dependent Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the tonic contraction. PMID:27497848

  20. 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)

  1. 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)

  2. Photoperiodic regulation of satiety mediating neuropeptides in the brainstem of the seasonal Siberian hamster (Phodopus sungorus).

    Science.gov (United States)

    Helwig, Michael; Archer, Zoë A; Heldmaier, Gerhard; Tups, Alexander; Mercer, Julian G; Klingenspor, Martin

    2009-07-01

    Central regulation of energy balance in seasonal mammals such as the Siberian hamster is dependent on the precise integration of short-term satiety information arising from the gastrointestinal tract with long-term signals on the status of available energy reserves (e.g. leptin) and prevailing photoperiod. Within the central nervous system, the brainstem nucleus of the solitary tract (NTS) and the parabrachial nucleus (PBN) are major relay nuclei that transmit information from the gastrointestinal tract to higher forebrain centres. We extended studies on the seasonal programming of the hypothalamus to examine the effect of the photoperiod on neuropeptidergic circuitries of this gut-brain axis. In the NTS and PBN we performed gene expression and immunoreactivity (-ir) studies on selected satiety-related neuropeptides and receptors: alpha-melanocyte stimulating hormone, melanocortin-3 receptor, melanocortin-4 receptor (MC4-R), growth hormone secretagogue-receptor, cocaine- and amphetamine-regulated transcript, preproglucagon (PPG), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY, galanin, neurotensin, and corticotrophin releasing hormone (CRH). Gene expression of PPG and MC4-R, and -ir of CCK and GLP-1, in the NTS were up-regulated after 14 weeks in long-day photoperiod (16 h light:8 h dark) compared to short-days (8 h light:16 h dark), whereas CRH-ir and NT-ir were increased in short-days within the PBN. We suggest that brainstem neuroendocrine mechanisms contribute to the long-term regulation of body mass in the Siberian hamster by a photoperiod-related modulation of satiety signalling.

  3. Worldwide regulations for mycotoxins.

    Science.gov (United States)

    van Egmond, Hans P

    2002-01-01

    Since the discovery of the aflatoxins in the 1960s, regulations have been established in many countries to protect the consumer from the harmful effects of mycotoxins that may contaminate foodstuffs. Various factors play a role in the decision-making process of setting limits for mycotoxins. These include scientific factors such as the availability of toxicological data, survey data, knowledge about the distribution of mycotoxins in commodities, and analytical methodology. Economical and political factors such as commercial interests and sufficiency of food supply have their impact as well. International enquiry's on existing mycotoxin legislation in foodstuffs and animal feedstuffs have been carried out several times in the 1980s and 1990s and details about tolerances, legal basis, responsible authorities, official protocols of analysis and sampling have been published. Recently a comprehensive update on worldwide regulations was published as FAO Food and Nutrition Paper 64. It appeared that at least 77 countries now have specific regulations for mycotoxins, 13 countries are known to have no specific regulations, whereas no data are available for about 50 countries, many of them in Africa. Over the years, a large diversity in tolerance levels for mycotoxins has remained. Some free trade zones (EU, MERCOSUR) are in the process of harmonizing the limits and regulations for mycotoxins in their respective member states, but it is not likely that worldwide harmonized limits for mycotoxins will soon be within reach.

  4. Ly6h regulates trafficking of alpha7 nicotinic acetylcholine receptors and nicotine-induced potentiation of glutamatergic signaling.

    Science.gov (United States)

    Puddifoot, Clare A; Wu, Meilin; Sung, Rou-Jia; Joiner, William J

    2015-02-25

    α7 nAChRs are expressed widely throughout the brain, where they are important for synaptic signaling, gene transcription, and plastic changes that regulate sensory processing, cognition, and neural responses to chronic nicotine exposure. However, the mechanisms by which α7 nAChRs are regulated are poorly understood. Here we show that trafficking of α7-subunits is controlled by endogenous membrane-associated prototoxins in the Ly6 family. In particular, we find that Ly6h reduces cell-surface expression and calcium signaling by α7 nAChRs. We detect Ly6h in several rat brain regions, including the hippocampus, where we find it is both necessary and sufficient to limit the magnitude of α7-mediated currents. Consistent with such a regulatory function, knockdown of Ly6h in rat hippocampal pyramidal neurons enhances nicotine-induced potentiation of glutamatergic mEPSC amplitude, which is known to be mediated by α7 signaling. Collectively our data suggest a novel cellular role for Ly6 proteins in regulating nAChRs, which may be relevant to plastic changes in the nervous system including rewiring of glutamatergic circuitry during nicotine addiction. PMID:25716842

  5. 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

  6. 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

  7. Staff rules and regulations

    CERN Document Server

    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 ...

  8. 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.

  9. 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...

  10. 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

  11. 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

  12. 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...

  13. 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.

  14. 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...

  15. 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…

  16. 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

  17. 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...

  18. 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…

  19. Regulating multiple externalities

    DEFF Research Database (Denmark)

    Waldo, Staffan; Jensen, Frank; Nielsen, Max;

    2016-01-01

    instruments. However, solving the open-access externality problem also affects CO2 emissions. By using a bio-economic model covering Iceland, Norway, Denmark, Sweden, and the Faroe Islands, it is shown that regulations of the open-access externality problem have a large effect on both economic performance...

  20. 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...

  1. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    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...

  2. Legislation and regulation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-09-01

    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.

  3. 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...

  4. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    expressed ICl, swell will decrease proliferation in several cell types, including Ehrlich cells. A differentiated expression of ICl, swell in the cell cycle has been described in different cell types indicating a regulating role. In Ehrlich Lettré ascites (ELA) cells we suggest the differentiated expression...

  5. 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

  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 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)

  8. 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

  9. 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).

  10. 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

  11. Phenotypic variation in bacteria : The role of feedback regulation

    NARCIS (Netherlands)

    Smits, Wiep; Kuipers, O.P.; Veening, J.W.

    2006-01-01

    To survive in rapidly changing environmental conditions, bacteria have evolved a diverse set of regulatory pathways that govern various adaptive responses. Recent research has reinforced the notion that bacteria use feedback-based circuitry to generate population heterogeneity in natural situations.

  12. 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, the marketplace......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...

  13. 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

  14. 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...

  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. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Rab GTPases Regulate Vesicle Traffic%Rab蛋白调控胞内囊泡运输

    Institute of Scientific and Technical Information of China (English)

    冯婉娟; 徐子静; 孟令锋; 张蓉颖

    2012-01-01

    细胞内各个细胞器之间通过囊泡的膜转运是真核细胞存在的基本.Rab蛋白确保了转运蛋白被运输至正确的目的地.Rab蛋白是小GTP酶中的一大家族,它通过募集其效应物蛋白,其中包括接头蛋白,栓系因子,激酶,磷酸酶以及动力蛋白等,调控了细胞膜的选取,囊泡出芽,去包被,转运以及膜融合等过程.本文主要从Rab蛋白循环着手,依次论述了Rab蛋白在囊泡出芽,去包被,转运和膜融合等过程中起到的作用,从而使读者对Rab蛋白能有一个更加系统的了解.%Rab GTPases is a targe family of small GTPases. Rab GTPases regulate vesicle traffic which is fundamental to the existence of eukaryotic cells. Rab GTPases recruit their effect proteins including sorting adaptors, tethering factors, kinases, phosphatases and motors, control membrane identity and vesicle budding, uncoating, motility and fusion. This paper introduced the circuitry of Rab GTPases and their function in vesicle budding, uncoating, motility and fusion.

  3. 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)

  4. 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.

  5. Ensembl regulation resources.

    Science.gov (United States)

    Zerbino, Daniel R; Johnson, Nathan; Juetteman, Thomas; Sheppard, Dan; Wilder, Steven P; Lavidas, Ilias; Nuhn, Michael; Perry, Emily; Raffaillac-Desfosses, Quentin; Sobral, Daniel; Keefe, Damian; Gräf, Stefan; Ahmed, Ikhlak; Kinsella, Rhoda; Pritchard, Bethan; Brent, Simon; Amode, Ridwan; Parker, Anne; Trevanion, Steven; Birney, Ewan; Dunham, Ian; Flicek, Paul

    2016-01-01

    New experimental techniques in epigenomics allow researchers to assay a diversity of highly dynamic features such as histone marks, DNA modifications or chromatin structure. The study of their fluctuations should provide insights into gene expression regulation, cell differentiation and disease. The Ensembl project collects and maintains the Ensembl regulation data resources on epigenetic marks, transcription factor binding and DNA methylation for human and mouse, as well as microarray probe mappings and annotations for a variety of chordate genomes. From this data, we produce a functional annotation of the regulatory elements along the human and mouse genomes with plans to expand to other species as data becomes available. Starting from well-studied cell lines, we will progressively expand our library of measurements to a greater variety of samples. Ensembl's regulation resources provide a central and easy-to-query repository for reference epigenomes. As with all Ensembl data, it is freely available at http://www.ensembl.org, from the Perl and REST APIs and from the public Ensembl MySQL database server at ensembldb.ensembl.org. Database URL: http://www.ensembl.org. PMID:26888907

  6. Staff rules and regulations

    CERN Document Server

    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...

  7. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    Science.gov (United States)

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto

    2016-01-01

    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large

  8. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    Science.gov (United States)

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C.; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C.; Salgado, Humberto

    2016-01-01

    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented—in order of decreasing affinity for the catecholamine—by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing—in turn—a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a

  9. 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

  10. Reactive oxygen species regulate the levels of dual oxidase (Duox1-2 in human neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Simona Damiano

    Full Text Available Dual Oxidases (DUOX 1 and 2 are efficiently expressed in thyroid, gut, lung and immune system. The function and the regulation of these enzymes in mammals are still largely unknown. We report here that DUOX 1 and 2 are expressed in human neuroblastoma SK-N-BE cells as well as in a human oligodendrocyte cell line (MO3-13 and in rat brain and they are induced by platelet derived growth factor (PDGF. The levels of DUOX 1 and 2 proteins and mRNAs are induced by reactive oxygen species (ROS produced by the membrane NADPH oxidase. As to the mechanism, we find that PDGF stimulates membrane NADPH oxidase to produce ROS, which stabilize DUOX1 and 2 mRNAs and increases the levels of the proteins. Silencing of gp91(phox (NOX2, or of the other membrane subunit of NADPH oxidase, p22(phox, blocks PDGF induction of DUOX1 and 2. These data unravel a novel mechanism of regulation of DUOX enzymes by ROS and identify a circuitry linking NADPH oxidase activity to DUOX1 and 2 levels in neuroblastoma cells.

  11. 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

  12. 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

  13. MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development.

    Science.gov (United States)

    Lu, Cecilia S; Zhai, Bo; Mauss, Alex; Landgraf, Matthias; Gygi, Stephen; Van Vactor, David

    2014-09-26

    Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins.

  14. 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.

  15. 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

  16. 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

  17. [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.

  18. 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....

  19. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    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 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 alternative...

  20. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor...... of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings...... of a regulatory effect of the PFC on the emotional control of our actions....

  1. 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.

  2. 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

  3. Public Regulators and CSR

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2016-01-01

    The social licence to operate (SLO) concept is little developed in the academic literature so far. Deployment of the term was made by the United National (UN) Guiding Principles on Business and Human Rights and the UN ‘Protect, Respect and Remedy’ Framework, which apply SLO as an argument...... analysis of an expansion of law into the normative framing of what constitutes responsible business conduct, we demonstrate a process of juridification entailing a legal framing of social expectations of companies, a proliferation of law into the field of business ethics, and an increased regulation by law...

  4. 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...

  5. 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....

  6. 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)

  7. The Quality of Regulation

    Directory of Open Access Journals (Sweden)

    Emil BĂLAN

    2011-11-01

    Full Text Available Good governance also involves the affirmation and practice of some principles that allow the structures of the public space to administrate the general interest in the respect of the democracy and of the state of law pre-requisites, as well as the ones of a good administration: trust and predictability, openness and transparency, responsibility, efficiency and efficacy. The assurance of such desideratum imposes that the rules invested with the force of law, applicable to the juridical rapports to be clear, not equivoques, predictable, to allow both the protection of public interest and the respect of the citizens’ dignity and interests. The evaluation of the quality of regulation represents a necessary process of the appreciation of the impact that juridical norms are intended to produce and measures in which the outcomes of the implementation correspond to the ones established during the stage of formulating the public policy. The study tries to identify ways of evaluating the quality of regulation, valid in a social and political space governed by democratic rules and principles.

  8. [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.

  9. 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

  10. 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

  11. 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)

  12. 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...

  13. Probiotics and Appetite Regulation

    DEFF Research Database (Denmark)

    Bjerg, Anne Toksvig

    Summary There is emerging focus on the gut microbiota’s (GM) effects on health. GM is suggested to be a contributing factor to the rapid development of obesity and its related diseases like type 2 diabetes and cardiovascular disease. The omposition of the GM has been associated with weight, insulin...... 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......-armed parallel four weeks intervention study with W8 (1010 CFU) or placebo capsules was performed on young, normal to overweight participants. In the four weeks intervention study the effects of W8 on appetite, blood lipids, SCD1 activity and fecal microbiota were also investigated. Finally, associations between...

  14. 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

  15. Regulation of melanopsin expression.

    Science.gov (United States)

    Hannibal, Jens

    2006-01-01

    Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light-detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non-imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of melanopsin, an opsin-like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking melanopsin. Furthermore, heterologous expression of melanopsin in non-neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of melanopsin exists, little is known about the regulation of melanopsin gene expression. Studies in albino Wistar rats showed that the expression of melanopsin is diurnal at both the mRNA and protein levels. The diurnal changes in melanopsin expression seem, however, to be overridden by prolonged exposure to light or darkness. Significant increase in melanopsin expression was observed from the first day in constant darkness and the expression continued to increase during prolonged exposure in constant darkness. Prolonged exposure to constant light, on the other hand, decreased melanopsin expression to an almost undetectable level after 5 days of constant light. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 days. These observations show that dual mechanisms regulate melanopsin gene expression and that the intrinsic light-responsive RGCs in the albino Wistar rat adapt their expression of melanopsin to environmental light and darkness.

  16. 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

  17. [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.

  18. A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate

    Directory of Open Access Journals (Sweden)

    Antonis Giakountis

    2016-06-01

    Full Text Available The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal cancer and correlates with increased metastatic potential and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1.

  19. Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations.

    Science.gov (United States)

    2014-07-28

    This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register.

  20. 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...

  1. 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...

  2. 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...

  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. 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...

  6. 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...

  7. 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...

  8. 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

  9. 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

  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. 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,…

  12. 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.

  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. 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.

  15. 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...

  16. 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...

  17. Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats

    Science.gov (United States)

    Rodd, Zachary A.; Bell, Richard L.; Oster, Scott M.; Toalston, Jamie E.; Pommer, Tylene J.; McBride, William J.; Murphy, James M.

    2015-01-01

    Several studies indicated the involvement of serotonin-3 (5-HT3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self-administration. P rats readily acquired ethanol self-administration by the 4th session. The three highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self-administration. During the acquisition post-injection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS significantly increased responding on the ethanol lever; following the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125% w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration, and/or repeated treatments with a 5-HT3 receptor antagonist may alter neuronal circuitry within the posterior VTA. PMID:20682192

  18. 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...

  19. 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......, 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 requirements...... a number of limitations specific to nanomaterials, i.e., the fact that mass might not be the proper metric to describe the dose in dose–response assessment. These limitations are not easily overcome despite the fact that a lot of effort is being put into investigating the applicability of each...

  20. REGULATION OF NATIONAL QUALIFICATIONS SYSTEMS

    Directory of Open Access Journals (Sweden)

    Anna A. Muravyeva

    2014-01-01

    Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

  1. 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.

  2. 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

  3. 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

  4. Complement Receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function.

    Science.gov (United States)

    Lindblom, Rickard P F; Aeinehband, Shahin; Ström, Mikael; Al Nimer, Faiez; Sandholm, Kerstin; Khademi, Mohsen; Nilsson, Bo; Piehl, Fredrik; Ekdahl, Kristina N

    2016-05-01

    Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on C3 activation. Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing-remitting MS (n=33; 6.2ng/mL) and secondary-progressive MS (n=9; 7.0ng/mL) as compared to controls (n=18; 4.1ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of C3b to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3. These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions. PMID:27085202

  5. 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

  6. 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

  7. Dynamic membrane depolarization is an early regulator of ependymoglial cell response to spinal cord injury in axolotl.

    Science.gov (United States)

    Sabin, Keith; Santos-Ferreira, Tiago; Essig, Jaclyn; Rudasill, Sarah; Echeverri, Karen

    2015-12-01

    Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional spinal cord after injury. However, the molecular circuitry required to initiate a pro-regenerative response after spinal cord injury is not well understood. To address this question we developed a spinal cord injury model in axolotls and used in vivo imaging of labeled ependymoglial cells to characterize the response of these cells to injury. Using in vivo imaging of ion sensitive dyes we identified that spinal cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits ependymoglial cell proliferation and subsequent axon regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful spinal cord regeneration in axolotl.

  8. 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

  9. 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.

  10. Precipitated silica as flow regulator.

    Science.gov (United States)

    Müller, Anne-Kathrin; Ruppel, Joanna; Drexel, Claus-Peter; Zimmermann, Ingfried

    2008-08-01

    Flow regulators are added to solid pharmaceutical formulations to improve the flow properties of the powder mixtures. The primary particles of the flow regulators exist in the form of huge agglomerates which are broken down into smaller aggregates during the blending process. These smaller aggregates adsorb at the surface of the solid's grains and thus diminish attractive Van-der-Waals-forces by increasing the roughness of the host's surface. In most cases amorphous silica is used as flow additive but material properties like particle size or bond strength influence the desagglomeration tendency of the agglomerates and thus the flow regulating potency of each silica. For some silica types we will show that the differences in their flow regulating potency are due to the rate and extent by which they are able to cover the surface of the host particles. Binary powder mixtures consisting of a pharmaceutical excipient and an added flow regulator were blended in a Turbula mixer for a defined period of time. As pharmaceutical excipient corn starch was used. The flow regulators were represented by a selection of amorphous silicon dioxide types like a commercial fumed silica and various types of SIPERNAT precipitated silica provided by Evonik-Degussa GmbH, Hanau, Germany. Flowability parameters of the mixtures were characterized by means of a tensile strength tester. The reduction of tensile strength with the blending time can be correlated with an increase in fragmentation of the flow regulator. PMID:18595668

  11. 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.

  12. 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

  13. 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

  14. Voltage Regulators for Photovoltaic Systems

    Science.gov (United States)

    Delombard, R.

    1986-01-01

    Two simple circuits developed to provide voltage regulation for highvoltage (i.e., is greater than 75 volts) and low-voltage (i.e., is less than 36 volts) photovoltaic/battery power systems. Use of these circuits results in voltage regulator small, low-cost, and reliable, with very low power dissipation. Simple oscillator circuit controls photovoltaic-array current to regulate system voltage and control battery charging. Circuit senses battery (and system) voltage and adjusts array current to keep battery voltage from exceeding maximum voltage.

  15. 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...

  16. 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.

  17. 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

  18. Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease.

    Science.gov (United States)

    Verwey, Michael; Dhir, Sabine; Amir, Shimon

    2016-01-01

    Circadian clock proteins form an autoregulatory feedback loop that is central to the endogenous generation and transmission of daily rhythms in behavior and physiology. Increasingly, circadian rhythms in clock gene expression are being reported in diverse tissues and brain regions that lie outside of the suprachiasmatic nucleus (SCN), the master circadian clock in mammals. For many of these extra-SCN rhythms, however, the region-specific implications are still emerging. In order to gain important insights into the potential behavioral, physiological, and psychological relevance of these daily oscillations, researchers have begun to focus on describing the neurochemical, hormonal, metabolic, and epigenetic contributions to the regulation of these rhythms. This review will highlight important sites and sources of circadian control within dopaminergic and striatal circuitries of the brain and will discuss potential implications for psychopathology and disease . For example, rhythms in clock gene expression in the dorsal striatum are sensitive to changes in dopamine release, which has potential implications for Parkinson's disease and drug addiction. Rhythms in the ventral striatum and limbic forebrain are sensitive to psychological and physical stressors, which may have implications for major depressive disorder. Collectively, a rich circadian tapestry has emerged that forces us to expand traditional views and to reconsider the psychopathological, behavioral, and physiological importance of these region-specific rhythms in brain areas that are not immediately linked with the regulation of circadian rhythms. PMID:27635233

  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. The Fuzzy Logic of MicroRNA Regulation: A Key to Control Cell Complexity.

    Science.gov (United States)

    Ripoli, Andrea; Rainaldi, Giuseppe; Rizzo, Milena; Mercatanti, Alberto; Pitto, Letizia

    2010-08-01

    Genomic and clinical evidence suggest a major role of microRNAs (miRNAs) in the regulatory mechanisms of gene expression, with a clear impact on development and physiology; miRNAs are a class of endogenous 22-25 nt single-stranded RNA molecules, that negatively regulate gene expression post-transcriptionally, by imperfect base pairing with the 3' UTR of the corresponding mRNA target. Because of this imperfection, each miRNA can bind multiple targets, and multiple miRNAs can bind the same mRNA target; although digital, the miRNAs control mechanism is characterized by an imprecise action, naturally understandable in the theoretical framework of fuzzy logic.A major practical application of fuzzy logic is represented by the design and the realization of efficient and robust control systems, even when the processes to be controlled show chaotic, deterministic as well unpredictable, behaviours. The vagueness of miRNA action, when considered together with the controlled and chaotic gene expression, is a hint of a cellular fuzzy control system. As a demonstration of the possibility and the effectiveness of miRNA based fuzzy mechanism, a fuzzy cognitive map -a mathematical formalism combining neural network and fuzzy logic- has been developed to study the apoptosis/proliferation control performed by the miRNA-17-92 cluster/E2F1/cMYC circuitry.When experimentally demonstrated, the concept of fuzzy control could modify the way we analyse and model gene expression, with a possible impact on the way we imagine and design therapeutic intervention based on miRNA silencing.

  1. Assessing self-regulation strategies

    DEFF Research Database (Denmark)

    de Vet, Emely; de Ridder, Denise T. D.; Stok, Marijn;

    2014-01-01

    participants were aged between 10 and 17 years. Results: Study 1 resulted in a 24-item questionnaire assessing adolescent-reported use of six specific strategies for healthy eating that represent three general self-regulation approaches. Study 2 showed that the easy-to-administer theory-based TESQ-E has...... general self-regulation and motivation measures. Conclusions: The TESQ-E provides a reliable and valid measure to assess six theory-based self-regulation strategies that adolescents may use to ensure their healthy eating.......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...

  2. 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 ...

  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. 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.

  5. Lipid Regulation of Sodium Channels.

    Science.gov (United States)

    D'Avanzo, N

    2016-01-01

    The lipid landscapes of cellular membranes are complex and dynamic, are tissue dependent, and can change with the age and the development of a variety of diseases. Researchers are now gaining new appreciation for the regulation of ion channel proteins by the membrane lipids in which they are embedded. Thus, as membrane lipids change, for example, during the development of disease, it is likely that the ionic currents that conduct through the ion channels embedded in these membranes will also be altered. This chapter provides an overview of the complex regulation of prokaryotic and eukaryotic voltage-dependent sodium (Nav) channels by fatty acids, sterols, glycerophospholipids, sphingolipids, and cannabinoids. The impact of lipid regulation on channel gating kinetics, voltage-dependence, trafficking, toxin binding, and structure are explored for Nav channels that have been examined in heterologous expression systems, native tissue, and reconstituted into artificial membranes. Putative mechanisms for Nav regulation by lipids are also discussed. PMID:27586290

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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....

  15. 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...

  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. Guidelines on Building Regulations 2008

    DEFF Research Database (Denmark)

    Thse guidelines clarify and intepret the provisions of the Building Regulations of 2008 (BR08). The Guidelines, which match BR08 in terms of organisation into Parts, are accompanied by the full text of the regulations and the explanatory notes issued by the Danish Enterprise and Construction...... climate, energy consumotion and services. The Guidelines are aimed at all professionals involved in building projects, particularly building design consultants, contractors and municipal application officers....

  19. Compact pulse width modulation circuitry for silicon photomultiplier readout.

    Science.gov (United States)

    Bieniosek, M F; Olcott, P D; Levin, C S

    2013-08-01

    The adoption of solid-state photodetectors for positron emission tomography (PET) system design and the interest in 3D interaction information from PET detectors has lead to an increasing number of readout channels in PET systems. To handle these additional readout channels, PET readout electronics should be simplified to reduce the power consumption, cost, and size of the electronics for a single channel. Pulse-width modulation (PWM), where detector pulses are converted to digital pulses with width proportional to the detected photon energy, promises to simplify PET readout by converting the signals to digital form at the beginning of the processing chain, and allowing a single time-to-digital converter to perform the data acquisition for many channels rather than routing many analogue channels and digitizing in the back end. Integrator based PWM systems, also known as charge-to-time converters (QTCs), are especially compact, reducing the front-end electronics to an op-amp integrator with a resistor discharge, and a comparator. QTCs, however, have a long dead-time during which dark count noise is integrated, reducing the output signal-to-noise ratio. This work presents a QTC based PWM circuit with a gated integrator that shows performance improvements over existing QTC based PWM. By opening and closing an analogue switch on the input of the integrator, the circuit can be controlled to integrate only the portions of the signal with a high signal-to-noise ratio. It also allows for multiplexing different detectors into the same PWM circuit while avoiding uncorrelated noise propagation between photodetector channels. Four gated integrator PWM circuits were built to readout the spatial channels of two position sensitive solid-state photomultiplier (PS-SSPM). Results show a 4 × 4 array 0.9 mm × 0.9 mm × 15 mm of LYSO crystals being identified on the 5 mm × 5 mm PS-SSPM at room temperature with no degradation for twofold multiplexing. In principle, much larger multiplexing ratios are possible, limited only by count rate issues. PMID:23831601

  20. Evolutionary Optimization of Electronic Circuitry Cooling Using Nanofluid

    Directory of Open Access Journals (Sweden)

    Manu Mital

    2012-01-01

    Full Text Available Liquid cooling electronics using microchannels integrated in the chips is an attractive alternative to bulky aluminum heat sinks. Cooling can be further enhanced using nanofluids. The goals of this study are to evaluate heat transfer in a nanofluid heat sink with developing laminar flow forced convection, taking into account the pumping power penalty. The proposed model uses semi-empirical correlations to calculate effective nanofluid thermophysical properties, which are then incorporated into heat transfer and friction factor correlations in literature for single-phase flows. The model predicts the thermal resistance and pumping power as a function of four design variables that include the channel diameter, velocity, number of channels, and nanoparticle fraction. The parameters are optimized with minimum thermal resistance as the objective function and fixed specified value of pumping power as the constraint. For a given value of pumping power, the benefit of nanoparticle addition is evaluated by independently optimizing the heat sink, first with nanofluid and then with water. Comparing the minimized thermal resistances revealed only a small benefit since nanoparticle addition increases the pumping power that can alternately be diverted towards an increased velocity in a pure water heat sink. The benefit further diminishes with increase in available pumping power.