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Sample records for prepulse inhibition ppi

  1. Prepulse inhibition (PPI) disrupting effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines.

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    Michel, Haidy E; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

    2013-06-07

    Liquorice extract was reported to have nootropic and/or antiamnestic effects. Prepulse inhibition (PPI) of startle response is a multimodal, cross-species phenomenon used as a measure of sensorimotor gating. Previous studies indicated that liquorice/its constituents augmented mouse brain monoamine levels. Increased brain monoamines' transmission was suggested to underlie PPI disruption. However, the effect of antiamnestic dose(s) of the extract on PPI has not been investigated despite the coexistence of impaired memory and PPI deficit in some neurological disorders. The effect of administration of the antiamnestic dose of the extract (150 mg/kg for 7 days) was tested on PPI of acoustic startle response in mice. It resulted in PPI disruption and therefore its effect on monoamines' levels was investigated in a number of mouse brain areas involved in PPI response mediation. Results demonstrated that the extract antiamnestic dose augmented cortical, hippocampal and striatal monoamine levels. It was therefore concluded that liquorice extract (150 mg/kg)-induced PPI deficit was mediated through augmenting monoaminergic transmission in the cortex, hippocampus and striatum. These findings can be further investigated in experimental models for autism, psychosis and Huntington's disease to decide the safety of using liquorice extract in ameliorating memory disturbance in disorders manifesting PPI deficit.

  2. Prepulse inhibition (PPI) of tactile startle response in recombinant congenic strains of mice:QTL mapping and comparison with acoustic PPI

    Institute of Scientific and Technical Information of China (English)

    Adam Torkamanzehi; Patricia Boksa; Ridha Joober

    2008-01-01

    Prepulse inhibition (PPI) of the startle response is a psychophysiological measure of sensorimotor gating believed to be cross-modal between different sensory systems.We analyzed the tactile startle response (TSR) and PPI of TSR (tPPD,using light as a prepulse stimulus,in the mouse strains A/J and C57BL/6J and 36 recombinant congenic strains derived from them.Parental strains were significantly different for TSR,but were comparable for tPPI.Among the congenic strains,variation for TSR was significant in both genetic backgrounds,but that of tPPI was significant only for the C57BL/6J background.Provisional mapping for loci modulating TSR and tPPI was carded out.Using mapping data from our previous study on acoustic startle responses (ASR) and PPI of ASR (aPPI),no common markers for aPPI and tPPI were identified.However,some markers were significantly associated with both ASR and TSIL at least in one genetic background.These results indicate cross-modal genetic regulation for the startle response but not for PPI,in these mouse strains.

  3. Reflex excitability regulates prepulse inhibition.

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    Schicatano, E J; Peshori, K R; Gopalaswamy, R; Sahay, E; Evinger, C

    2000-06-01

    Presentation of a weak stimulus, a prepulse, before a reflex-evoking stimulus decreases the amplitude of the reflex response relative to reflex amplitude evoked without a preceding prepulse. For example, presenting a brief tone before a trigeminal blink-eliciting stimulus significantly reduces reflex blink amplitude. A common explanation of such data are that sensory processing of the prepulse modifies reflex circuit behavior. The current study investigates the converse hypothesis that the intrinsic characteristics of the reflex circuit rather than prepulse processing determine prepulse modification of trigeminal and acoustic reflex blinks. Unilateral lesions of substantia nigra pars compacta neurons created rats with hyperexcitable trigeminal reflex blinks but normally excitable acoustic reflex blinks. In control rats, presentation of a prepulse reduced the amplitude of both trigeminal and acoustic reflex blinks. In 6-OHDA-lesioned rats, however, the same acoustic prepulse facilitated trigeminal reflex blinks but inhibited acoustic reflex blinks. The magnitude of prepulse modification correlated with reflex excitability. Humans exhibited the same pattern of prepulse modification. An acoustic prepulse facilitated the trigeminal reflex blinks of subjects with hyperexcitable trigeminal reflex blinks caused by Parkinson's disease. The same prepulse inhibited trigeminal reflex blinks of age-matched control subjects. Prepulse modification also correlated with trigeminal reflex blink excitability. These data show that reflex modification by a prepulse reflects the intrinsic characteristics of the reflex circuit rather than an external adjustment of the reflex circuit by the prepulse.

  4. Habituation and prepulse inhibition of acoustic startle in rodents.

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    Valsamis, Bridget; Schmid, Susanne

    2011-09-01

    The acoustic startle response is a protective response, elicited by a sudden and intense acoustic stimulus. Facial and skeletal muscles are activated within a few milliseconds, leading to a whole body flinch in rodents(1). Although startle responses are reflexive responses that can be reliably elicited, they are not stereotypic. They can be modulated by emotions such as fear (fear potentiated startle) and joy (joy attenuated startle), by non-associative learning processes such as habituation and sensitization, and by other sensory stimuli through sensory gating processes (prepulse inhibition), turning startle responses into an excellent tool for assessing emotions, learning, and sensory gating, for review see( 2, 3). The primary pathway mediating startle responses is very short and well described, qualifying startle also as an excellent model for studying the underlying mechanisms for behavioural plasticity on a cellular/molecular level(3). We here describe a method for assessing short-term habituation, long-term habituation and prepulse inhibition of acoustic startle responses in rodents. Habituation describes the decrease of the startle response magnitude upon repeated presentation of the same stimulus. Habituation within a testing session is called short-term habituation (STH) and is reversible upon a period of several minutes without stimulation. Habituation between testing sessions is called long-term habituation (LTH)(4). Habituation is stimulus specific(5). Prepulse inhibition is the attenuation of a startle response by a preceding non-startling sensory stimulus(6). The interval between prepulse and startle stimulus can vary from 6 to up to 2000 ms. The prepulse can be any modality, however, acoustic prepulses are the most commonly used. Habituation is a form of non-associative learning. It can also be viewed as a form of sensory filtering, since it reduces the organisms' response to a non-threatening stimulus. Prepulse inhibition (PPI) was originally

  5. Prepulse inhibition of auditory change-related cortical responses

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    Inui Koji

    2012-10-01

    Full Text Available Abstract Background Prepulse inhibition (PPI of the startle response is an important tool to investigate the biology of schizophrenia. PPI is usually observed by use of a startle reflex such as blinking following an intense sound. A similar phenomenon has not been reported for cortical responses. Results In 12 healthy subjects, change-related cortical activity in response to an abrupt increase of sound pressure by 5 dB above the background of 65 dB SPL (test stimulus was measured using magnetoencephalography. The test stimulus evoked a clear cortical response peaking at around 130 ms (Change-N1m. In Experiment 1, effects of the intensity of a prepulse (0.5 ~ 5 dB on the test response were examined using a paired stimulation paradigm. In Experiment 2, effects of the interval between the prepulse and test stimulus were examined using interstimulus intervals (ISIs of 50 ~ 350 ms. When the test stimulus was preceded by the prepulse, the Change-N1m was more strongly inhibited by a stronger prepulse (Experiment 1 and a shorter ISI prepulse (Experiment 2. In addition, the amplitude of the test Change-N1m correlated positively with both the amplitude of the prepulse-evoked response and the degree of inhibition, suggesting that subjects who are more sensitive to the auditory change are more strongly inhibited by the prepulse. Conclusions Since Change-N1m is easy to measure and control, it would be a valuable tool to investigate mechanisms of sensory gating or the biology of certain mental diseases such as schizophrenia.

  6. In silico whole genome association scan for murine prepulse inhibition.

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    Bradley Todd Webb

    Full Text Available BACKGROUND: The complex trait of prepulse inhibition (PPI is a sensory gating measure related to schizophrenia and can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups. METHODOLOGY/PRINCIPAL FINDINGS: We have implemented a method that addresses these issues by incorporating phylogenetic analyses, multilevel regression with mixed effects, and false discovery rate (FDR control. A genome-wide scan for PPI was conducted using over 17,000 single nucleotide polymorphisms (SNPs in 37 strains phenotyped. Eighty-nine SNPs were significant at a false discovery rate (FDR of 5%. After accounting for long-range linkage disequilibrium, we found 3 independent QTLs located on murine chromosomes 1 and 13. One of the PPI positives corresponds to a region of human chromosome 6p which includes DTNBP1, a gene implicated in schizophrenia. Another region includes the gene Tsn which alters PPI when knocked out. These genes also appear to have correlated expression with PPI. CONCLUSIONS/SIGNIFICANCE: These results support the usefulness of using an improved in silico mapping method to identify QTLs for complex traits such as PPI which can be then be used for to help identify loci influencing schizophrenia in humans.

  7. Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice

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    Moreno-Paublete, Rocio; Canlon, Barbara; Cederroth, Christopher R.

    2017-01-01

    Gap pre-pulse inhibition of the acoustic startle (GPIAS) is a behavioral paradigm used for inferring the presence of tinnitus in animal models as well as humans. In contrast to pre-pulse inhibition (PPI), the neural circuitry controlling GPIAS is poorly understood. To increase our knowledge on GPIAS, a comparative study with PPI was performed in mice combining these behavioral tests and c-Fos activity mapping in brain areas involved in the inhibition of the acoustic startle reflex (ASR). Both pre-pulses and gaps efficiently inhibited the ASR and abolished the induction of c-Fos in the pontine reticular nucleus. Differential c-Fos activation was found between PPI and GPIAS in the forebrain whereby PPI activated the lateral globus pallidus and GPIAS activated the primary auditory cortex. Thus, different neural maps are regulating the inhibition of the startle response by pre-pulses or gaps. To further investigate this differential response to PPI and GPIAS, we pharmacologically disrupted PPI and GPIAS with D-amphetamine or Dizocilpine (MK-801) to target dopamine efflux and to block NMDA receptors, respectively. Both D-amp and MK-801 efficiently decreased PPI and GPIAS. We administered Baclofen, an agonist GABAB receptor, but failed to detect any robust rescue of the effects of D-amp and MK-801 suggesting that PPI and GPIAS are GABAB-independent. These novel findings demonstrate that the inhibition of the ASR by pre-pulses or gaps is orchestrated by different neural pathways. PMID:28239338

  8. SSR504734 enhances basal expression of prepulse inhibition but exacerbates the disruption of prepulse inhibition by apomorphine

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    Singer, Philipp; Zhang, Weining; Yee, Benjamin K.

    2013-01-01

    Rationale Inhibition of glycine transporter 1 (GlyT1) elevates extracellular glycine and can thus increase N-methyl-D-aspartate receptor (NMDAR) excitability in the brain. The potent GlyT1 inhibitor, SSR504734, has also been shown to potentiate the behavioural effects of direct and indirect dopamine agonists. Thus, an acute systemic dose of SSR504734 was sufficient to exacerbate the motor-stimulant effect of the dopamine releaser amphetamine in C57BL/6 mice, even though SSR504734 alone exerted no significant effect on motor activity. Objectives Here, we explore if SSR504734 might modulate dopamine-dependent sensory gating in the paradigm of prepulse inhibition (PPI) of the acoustic startle reflex. Methods Experiment 1 characterized the effect of SSR504734 (10 and 30 mg/kg i.p.) on PPI expression when administered alone. Experiments 2 and 3 investigated the impact of SSR504734 when administered in conjunction with the dopamine receptor agonist, apomorphine (1 and 2 mg/kg s.c.), which is known to reliably disrupt PPI. Results When administered alone, acute SSR504734 enhanced PPI only at 30 mg/kg – a dose that has been shown to improve cognitive functions including working memory, which has been linked to enhanced NMDAR function resulting from the elevation of extracellular glycine. However, this effect did not allow SSR504734 to antagonise the PPI-disruptive effect of apomorphine. At the lower dose of 10 mg/kg – that was insufficient to enhance PPI when administered alone - SSR504734 even exacerbated the deleterious effect of apomorphine on PPI. Conclusions The therapeutic potential of GlyT1 inhibition against distinct behavioural/cognitive deficiency might require different magnitudes of GlyT1 inhibition. [246 words] PMID:23736281

  9. Dorsal striatum D1-expressing neurons are involved with sensorimotor gating on prepulse inhibition test.

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    Rodrigues, Samanta; Salum, Cristiane; Ferreira, Tatiana L

    2017-01-01

    Prepulse inhibition (PPI) is a behavioral test in which the startle reflex response to a high-intensity stimulus (pulse) is inhibited by the prior presentation of a weak stimulus (prepulse). The classic neural circuitry that mediates startle response is localized in the brainstem; however, recent studies point to the contribution of structures involved in higher cognitive functions in regulating the sensorimotor gating, particularly forebrain regions innervated by dopaminergic nuclei. The aim of the present study was to verify the role of dorsal striatum (DS) and dopaminergic transmitting mediated by D1 and D2 receptors on PPI test in rats. DS inactivation induced by muscimol injection did not affect PPI (%PPI and startle response), although it impaired the locomotor activity and caused catalepsy. Infusion of D1-like antagonist SCH23390 impaired %PPI but did not disturb the startle response and locomotor activity evaluated immediately after PPI test. D2 antagonist microinjection (sulpiride) did not affect %PPI and startle response, but impaired motor activity. These results point to an important role of DS, probably mediated by direct basal ganglia pathway, on modulation of sensorimotor gating, in accordance with clinical studies showing PPI deficits in schizophrenia, Tourette syndrome, and compulsive disorders - pathologies related to basal ganglia dysfunctions.

  10. Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced enhancement of prepulse inhibition in rats.

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    Zou, Dan; Huang, Juan; Wu, Xihong; Li, Liang

    2007-02-01

    Non-startling acoustic events presented shortly before an intense startling sound can inhibit the acoustic startle reflex. This phenomenon is called prepulse inhibition (PPI), and is widely used as a model of sensorimotor gating. The present study investigated whether PPI can be modulated by fear conditioning, whose acquisition can be blocked by the specific antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The results show that a gap embedded in otherwise continuous noise sounds, which were delivered by two spatially separated loudspeakers, could inhibit the startle reflex induced by an intense sound that was presented 50 ms after the gap. The inhibitory effect depended on the duration of the gap, and was enhanced by fear conditioning that was introduced by temporally pairing the gap with footshock. Intraperitoneal injection of MPEP (0.5 or 5mg/kg) 30 min before fear conditioning blocked the enhancing effect of fear conditioning on PPI, but did not affect either the baseline startle magnitude or PPI if no fear conditioning was introduced. These results indicate that PPI is enhanced when the prepulse signifies an aversive event after fear conditioning. Also, mGlu5Rs play a role in preserving the fear-conditioning-induced enhancement of PPI.

  11. Startle response and prepulse inhibition modulation by positive- and negative-induced affect.

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    De la Casa, Luis Gonzalo; Mena, Auxiliadora; Puentes, Andrea

    2014-02-01

    The startle response, a set of reflex behaviours intended to prepare the organism to face a potentially threatening stimulus, can be modulated by several factors as, for example, changes in affective state, or previous presentation of a weak stimulus (a phenomenon termed Pre-Pulse Inhibition [PPI]). In this paper we analyse whether the induction of positive or negative affective states in the participants modulates the startle response and the PPI phenomenon. The results revealed a decrease of the startle response and an increase of the PPI effect when registered while the participants were exposed to pleasant images (Experiment 1), and an increase of the startle response and of the PPI effect when they were exposed to a video-clip of unpleasant content (Experiment 2). These data are interpreted considering that changes in affective states correlate with changes in the startle reflex intensity, but changes in PPI might be the result of an attentional process.

  12. Prepulse inhibition of the startle reflex: a window on the brain in schizophrenia.

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    Braff, David L

    2010-01-01

    Prepulse inhibition (PPI) of the startle response is an important measure of information processing deficits and inhibitory failure in schizophrenia patients. PPI is especially useful because it occurs in the same lawful manner in all mammals, from humans to rodents, making it an ideal candidate for cross-species translational research. PPI deficits occur across the "schizophrenia spectrum" from schizophrenia patients to their clinically unaffected relatives. Parallel animal model and human brain imaging studies have demonstrated that PPI is modulated by cortico-striato-pallido-thalamic (and pontine) circuitry. This circuitry is also implicated in schizophrenia neuropathology and neurophysiology. The finding of PPI deficits in schizophrenia patients has been replicated by many groups, and these deficits correlate with measures of thought disorder and appear to be "normalized" by second generation antipsychotic (SGA) medications. Consistent pharmacological effects on PPI have been demonstrated; among these, dopamine agonists induce PPI deficits and (in animal models) these are reversed by first and SGA medications. PPI is also significantly heritable in humans and animals and can be used as a powerful endophenotype in studies of families of schizophrenia patients. Genomic regions, including the NRGL-ERBB4 complex with its glutamatergic influences, are strongly implicated in PPI deficits in schizophrenia. PPI continues to hold promise as an exciting translational cross-species measure that can be used to understand the pathophysiology and treatment of the schizophrenias via pharmacological, anatomic, and genetic studies.

  13. White matter hyperintensities and prepulse inhibition in a mixed elderly population

    DEFF Research Database (Denmark)

    Salem, Lise C; Hejl, Anne-Mette; Garde, Ellen;

    2011-01-01

    Prepulse inhibition (PPI) of the startle response, a measure for sensorimotor gating, exhibits a relatively high inter-individual variability in elderly subjects. The aim of this study was to investigate whether white matter hyperintensities (WMH), frequently identified on cranial magnetic...... resonance imaging (MRI) in elderly subjects with and without cognitive impairment, may contribute to variations in PPI. A passive acoustic PPI paradigm was applied in 92 human subjects (53 healthy and 39 patients with Alzheimer's disease or mild cognitive impairment) between 60 and 85years of age. WMH were...... rated visually on craniel MRI FLAIR images using the Fazekas scale. WMH were identified in 70% of all subjects. The latency to peak of the startle response increased significantly with increasing WMH load, whereas the inhibition of the startle response (PPI) was neither significantly related...

  14. Nitric oxide synthase inhibitors improve prepulse inhibition responses of Wistar rats.

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    Issy, A C; Lazzarini, M; Szawka, R E; Carolino, R O G; Anselmo-Franci, J A; Del Bel, E A

    2011-03-01

    Cognitive and attentional deficits in schizophrenia include impairment of the sensorimotor filter as measured by prepulse inhibition (PPI). In this way, the study of animals that naturally present low PPI responses could be a useful approach for screening new antipsychotic drugs. Several pieces of evidence suggest that dopamine and nitric oxide (NO) can modulate PPI but their role in those animals is unknown. The aim of this study was to investigate the role of dopamine and NO in Wistar rats with naturally low PPI response. Male Wistar rats with low PPI responses received an i.p. injection of the antipsychotics haloperidol (0.1, 0.3 or 1mg/kg) or clozapine (0.5, 1.5 or 5mg/kg), the anxiolytic diazepam (1 or 3mg/kg) or the NO synthase (NOS) inhibitors, N(G)- nitro-l-arginine (l-NOARG; 40mg/kg, acutely or sub-chronically) or 7-Nitroindazole (7-NI; 3, 10 or 30mg/kg). All animals were submitted to the PPI test 1h after injection. Striatal and cortical dopamine, DOPAC, and noradrenaline levels of rats with low PPI responses were compared to rats with normal PPI responses. We found increased levels of catecholamines on the striatum and prefrontal cortex of Wistar rats with low PPI. In these animals, both antipsychotics, typical and atypical, and NOS inhibitors significantly increased PPI. Taken together, our findings suggest that the low PPI phenotype may be driven by an overactive catecholamine system. Additionally, our results corroborate the hypothesis of dopamine and NO interaction on PPI modulation and suggest that Wistar rats with low PPI may represent an interesting non-pharmacological model to evaluate new potential antipsychotics. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Increased Prepulse Inhibition and Sensitization of the Startle Reflex in Autistic Children

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    Madsen, Gitte Falcher; Bilenberg, Niels; Cantio, Cathriona;

    2014-01-01

    The relation between autism spectrum disorders (ASD) and schizophrenia is a subject of intense debate and research due to evidence of common neurobiological pathways in the two disorders. The objective of this study was to explore whether deficits in prepulse inhibition (PPI) of the startle reflex...... and 40 matched NTD controls were tested in a psychophysiological test battery. The PPI of the acoustic startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials with less intense prestimuli (76 d....... The relation to PPI deficits observed in schizophrenia is not apparent. Future research should study the developmental course of PPI deficits in ASD patients in a longitudinal design. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc....

  16. The effects of imipramine on P50 suppression, prepulse inhibition and habituation of the startle response in humans

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    Hammer, Trine Bjørg; Oranje, Bob; Glenthoj, Birte Y

    2007-01-01

    Schizophrenic patients exhibit impairments in filtering of sensory information, as can be assessed by use of prepulse inhibition (PPI) of the acoustic startle response and P50 suppression paradigms. In the treatment of negative symptoms or depressive syndromes during the course of schizophrenia a...

  17. The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats.

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    Cathrin Rohleder

    2016-07-01

    Full Text Available Prepulse inhibition (PPI is a neuropsychological process during which a weak sensory stimulus (prepulse attenuates the motor response (startle reaction to a subsequent strong startling stimulus. It is measured as a surrogate marker of sensorimotor gating in patients suffering from neuropsychological diseases such as schizophrenia, as well as in corresponding animal models. A variety of studies has shown that PPI of the acoustical startle reaction comprises three brain circuitries for: i startle mediation, ii PPI mediation and iii modulation of PPI mediation. While anatomical connections and information flow in the startle and PPI mediation pathways are well known, spatial and temporal interactions of the numerous regions involved in PPI modulation are incompletely understood.We therefore combined [18F]fluoro-2-deoxyglucose positron-emission-tomography (FDG-PET with PPI and resting state control paradigms in awake rats. A battery of subtractive, correlative as well as seed-based functional connectivity analyses revealed a default mode-like network (DMN active during resting state only. Furthermore, two functional networks were observed during PPI: Metabolic activity in the lateral circuitry was positively correlated with PPI effectiveness and involved the auditory system and emotional regions. The medial network was negatively correlated with PPI effectiveness, i.e. associated with startle, and recruited a spatial/cognitive network. Our study provides evidence for two distinct neuronal networks, whose continuous interplay determines PPI effectiveness in rats, probably by either protecting the prepulse or facilitating startle processing.Discovering similar networks affected in neuropsychological disorders may help to better understand mechanisms of sensorimotor gating deficits and provide new perspectives for therapeutic strategies.

  18. Individual difference in prepulse inhibition does not predict spatial learning and memory performance in C57BL/6 mice.

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    Peleg-Raibstein, Daria; Philipp, Singer; Feldon, Joram; Yee, Benjamin K

    2015-12-01

    The startle reflex to an intense acoustic pulse stimulus is attenuated if the pulse stimulus is shortly preceded by a weak non-startling prepulse stimulus. This attenuation of the startle reflex represents a form of pre-attentional sensory gating known as prepulse inhibition (PPI). Although PPI does not require learning, its expression is regulated by higher cognitive processes. PPI deficits have been detected in several psychiatric conditions including schizophrenia where they co-exist with cognitive deficits. A potential link between PPI expression and cognitive performance has therefore been suggested such that poor PPI may predict, or may be mechanistically linked to, overt cognitive impairments. A positive relationship between PPI and strategy formation, planning efficiency, and execution speed has been observed in healthy humans. However, parallel studies in healthy animals are rare. It thus remains unclear what cognitive domains may be associated with, or orthogonal to, sensory gating in the form of PPI in healthy animals. The present study evaluated a potential link between the magnitude of PPI and spatial memory performance by comparing two subgroups of animals differing substantially in baseline PPI expression (low-PPI vs high-PPI) within a homogenous cohort of 100 male adult C57BL/6 mice. Assessment of spatial reference memory in the Morris water maze and spatial recognition memory in the Y-maze failed to reveal any difference between low-PPI and high-PPI subjects. These negative findings contrast with our previous reports that individual difference in PPI correlated with sustained attention and working memory performance in C57BL/6 mice.

  19. Characterizing cannabis-induced psychosis: a study with prepulse inhibition of the startle reflex.

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    Morales-Muñoz, Isabel; Jurado-Barba, Rosa; Ponce, Guillermo; Martínez-Gras, Isabel; Jiménez-Arriero, Miguel Ángel; Moratti, Stephan; Rubio, Gabriel

    2014-12-15

    Cannabis-induced psychotic disorder (CIPD) refers to psychotic symptoms that arise in the context of cannabis intoxication. Prepulse inhibition (PPI) deficits have been extensively identified in schizophrenia and in cannabis abusers. We aimed to characterize PPI in CIPD patients. We used a sample of 48 CIPD patients, 54 schizophrenia patients and cannabis abuse (SCHZ), 44 cannabis dependents (CD), and 44 controls. CIPD, SCHZ and CD were abstinent of cannabis consumption for 9 months. Participants were assessed with PPI at 30, 60, and 120 ms. At 30 ms, CIPD showed lower PPI levels than controls, and SCHZ obtained worse functioning than controls and CD. At 60 ms, only SCHZ exhibited worse PPI percentages (of object) than controls. Finally, at 120 ms, CIPD showed higher PPI levels than SCHZ, and SCHZ obtained lower percentages than controls. We found that CIPD and SCHZ patients showed deficits at the most pre-attentional levels, whereas CIPD patients performed better than SCHZ at higher attentional levels. These results suggest that CIPD constitutes a different group of patients than that of SCHZ. Deficits in PPI functioning at 30 ms could be a useful psychophysiological measure to detect CIPD patients, who are frequently confused with cannabis abusers whose symptoms may mimic that of schizophrenia.

  20. Dissociative identity disorder and prepulse inhibition of the acoustic startle reflex

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    Karl Yngvar Dale

    2008-06-01

    Full Text Available Karl Yngvar Dale1, Magne Arve Flaten1, Åke Elden1, Arne Holte21Department of Psychology, University of Tromsø, Norway; 2The Norwegian Institute of Public Health, Department of Mental Health, Oslo, Norway and University of Oslo, NorwayAbstract: A group of persons with dissociative identity disorder (DID was compared with a group of persons with other dissociative disorders, and a group of nondiagnosed controls with regard to prepulse inhibition (PPI of the acoustic startle reflex. The findings suggest maladaptive attentional processes at a controlled level, but not at a preattentive automatic level, in persons with DID. The prepulse occupied more controlled attentional resources in the DID group compared with the other two groups. Preattentive automatic processing, on the other hand, was normal in the DID group. Moreover, startle reflexes did not habituate in the DID group. In conclusion, increased PPI and delayed habituation is consistent with increased vigilance in individuals with DID. The present findings of reduced habituation of startle reflexes and increased PPI in persons with DID suggest the operation of a voluntary process that directs attention away from unpleasant or threatening stimuli. Aberrant voluntary attentional processes may thus be a defining characteristic in DID.Keywords: dissociation, DID, PPI, startle, habituation

  1. Effect of stress and attention on startle response and prepulse inhibition.

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    De la Casa, Luis Gonzalo; Mena, Auxiliadora; Ruiz-Salas, Juan Carlos

    2016-10-15

    The startle reflex magnitude can be modulated when a weak stimulus is presented before the onset of the startle stimulus, a phenomenon termed prepulse inhibition (PPI). Previous research has demonstrated that emotional processes can modulate PPI and startle intensity, but the available evidence is inconclusive. In order to obtain additional evidence in this domain, we conducted two experiments intended to analyze the effect of induced stress and attentional load on PPI and startle magnitude. Specifically, in Experiment 1 we used a between subject strategy to evaluate the effect on startle response and PPI magnitude of performing a difficult task intended to induce stress in the participants, as compared to a group exposed to a control task. In Experiment 2 we evaluated the effect of diverting attention from the acoustic stimulus on startle and PPI intensity. The results seem to indicate that induced stress can reduce PPI, and that startle reflex intensity is reduced when attention is directed away from the auditory stimulus that induces the reflex. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effects of Intravenous Nicotine on Prepulse Inhibition in Smokers and Nonsmokers: Relationship with Familial Smoking

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    Drobes, David J.; MacQueen, David A.; Blank, Melissa D.; Saladin, Michael E.; Malcolm, Robert J.

    2013-01-01

    Rationale The reinforcing properties of nicotine may be, in part, derived from its ability to enhance certain forms of cognitive processing. Several animal and human studies have shown that nicotine increases prepulse inhibition (PPI) of the startle reflex. However, it remains unclear whether these effects are related to smoking susceptibility. Objectives The current study examined the effects of intravenously delivered nicotine on PPI in smokers and nonsmokers, as well as its association with a quantitative index of familial smoking. Methods The sample consisted of 30 non-smokers and 16 smokers, who completed an initial assessment, followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions. Separate doses were used in smoker and non-smoker samples. Results Analyses indicated that both nicotine infusions acutely enhanced PPI among non-smokers, and this enhancement was positively related to the degree of smoking among first and second-degree relatives. Smokers also displayed PPI enhancement after receiving the first infusion, but this effect was unrelated to familial smoking. Conclusions These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk. PMID:23624809

  3. Acoustic startle and prepulse inhibition predict smoking lapse in posttraumatic stress disorder.

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    Vrana, Scott R; Calhoun, Patrick S; Dennis, Michelle F; Kirby, Angela C; Beckham, Jean C

    2015-10-01

    Most smokers who attempt to quit lapse within the first week and are ultimately unsuccessful in their quit attempt. Nicotine withdrawal exacerbates cognitive and attentional problems and may be one factor in smoking relapse. The startle reflex response and prepulse inhibition (PPI) of the response are sensitive to arousal and early attentional dysregulation. The current study examined whether startle response and PPI are related to early smoking lapse, and if this differs in people with and without posttraumatic stress disorder (PTSD). Participants with (N = 34) and without (N = 57) PTSD completed a startle reflex and PPI assessment during (1) ad lib smoking (2) on the first day of abstinence during a quit attempt. Most (88%) participants lapsed within the first week of the quit attempt. PTSD status predicted shorter time to lapse. Larger startle magnitude and greater PPI predicted a longer duration before smoking lapse. When diagnostic groups were examined separately, greater PPI predicted a longer successful quit attempt only in participants with a PTSD diagnosis. The startle reflex response and PPI may provide an objective, neurophysiological evaluation of regulation of arousal and early attentional processes by nicotine, which are important factors in smoking cessation success. © The Author(s) 2015.

  4. Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia.

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    Kumari, Veena; Das, Mrigen; Hodgins, Sheilagh; Zachariah, Elizabeth; Barkataki, Ian; Howlett, Michael; Sharma, Tonmoy

    2005-03-01

    Violent behaviour has a strong association with antisocial personality disorder (APD) and schizophrenia. Although developments in the understanding of socio-environmental factors associated with violence should not be ignored, advances in prevention and treatment of violent behaviour would benefit by improved understanding of its neurobiological and cognitive basis. The authors, therefore, investigated prepulse inhibition (PPI) of the startle response in APD and schizophrenia in relation to a history of serious violence. The neural substrates of PPI, especially the hippocampus, amygdala, thalamus and basal ganglia, are implicated in violence as well as in APD and schizophrenia. The study included four groups: (i) patients with APD and a history of violence, (ii) patients with schizophrenia and a history of violence, (iii) patients with schizophrenia without a history of violence, and (iv) healthy subjects with no history of violence or a mental disorder. All subjects were assessed identically on acoustic PPI. Compared to healthy subjects, significantly reduced PPI occurred in APD, violent schizophrenia and non-violent schizophrenia patients. Although PPI did not significantly differentiate the three clinical groups, high ratings of violence were modestly associated with reduced PPI across the entire study sample. Violent patients with impulsive and premeditated violence showed comparable PPI. The association between violent behaviour and impaired PPI suggests that neural structures and functions underlying PPI are implicated in (inhibition of) violence.

  5. Role of the NMDA-receptor in Prepulse Inhibition in the Rat

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    Klas Linderholm

    2010-02-01

    Full Text Available Kynurenic acid (KYNA is an endogenous metabolite of tryptophan. Studies have revealed increased brain KYNA levels in patients with schizophrenia. Prepulse inhibition (PPI is a behavioral model for sensorimotor gating and found to be reduced in schizophrenia. Previous studies have shown that pharmacologically elevated brain KYNA levels disrupt PPI in the rat. The aim of the present study was to investigate the receptor(s involved in this effect. Rats were treated with different drugs selectively blocking each of the sites that KYNA antagonizes, namely the glutamate recognition site of the N-methyl-D-aspartate receptor (NMDAR, the α7* nicotinic acetylcholine receptor (α7nAChR and the glycine site of the NMDAR. Kynurenine (200 mg/kg was given to replicate the effects of increased levels of KYNA on PPI. In order to block the glutamate recognition site of the NMDAR, CGS 19755 (10 mg/kg or SDZ 220–581 (2.5 mg/kg were administered and to antagonize the α7nAChR methyllycaconitine (MLA; 6 mg/kg was given. L-701,324 (1 and 4 mg/kg or 4-Chloro-kynurenine (4-Cl-KYN; 25, 50 and 100 mg/kg, a drug in situ converted to 7-Chloro-kynurenic acid, were used to block the glycine-site of the NMDAR. Administration of SDZ 220-581 or CGS 19755 was associated with a robust reduction in PPI, whereas L-701,324, 4-Cl-KYN or MLA failed to alter PPI. Kynurenine increased brain KYNA levels 5-fold and tended to decrease PPI. The present study suggests that neither antagonism of the glycine-site of the NMDA receptor nor antagonism of the α7nAChR disrupts PPI, rather with regard to the effects of KYNA, blockade of the glutamate recognition-site is necessary to reduce PPI.

  6. Hypnotizability, hypnosis and prepulse inhibition of the startle reflex in healthy women: an ERP analysis.

    Science.gov (United States)

    De Pascalis, Vilfredo; Russo, Emanuela

    2013-01-01

    A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs). Recent studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR), suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100 responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec) wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering) of irrelevant stimuli than LHs.

  7. Hypnotizability, hypnosis and prepulse inhibition of the startle reflex in healthy women: an ERP analysis.

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    Vilfredo De Pascalis

    Full Text Available A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs. Recent studies, using prepulse inhibition (PPI of the auditory startle reflex (ASR, suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a longer latency of the eyeblink startle reflex, (b reduced N100 responses to startle stimuli, and (c higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40 than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31. The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering of irrelevant stimuli than LHs.

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

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    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.

  9. Enhancement of acoustic prepulse inhibition by contextual fear conditioning in mice is maintained even after contextual fear extinction.

    Science.gov (United States)

    Ishii, Daisuke; Matsuzawa, Daisuke; Fujita, Yuko; Sutoh, Chihiro; Ohtsuka, Hiroyuki; Matsuda, Shingo; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi; Shimizu, Eiji

    2010-02-01

    Prepulse inhibition (PPI) of the acoustic startle response is one of the few and major paradigms for investigating sensorimotor gating systems in humans and rodents in a similar fashion. PPI deficits are observed not only in patients with schizophrenia, but also in patients with anxiety disorders. Previous studies have shown that PPI in rats can be enhanced by auditory fear conditioning. In this study, we evaluated the effects of contextual fear conditioning (FC) for six times a day and fear extinction (FE) for seven days on PPI in mice. C57BL/6J mice (male, 8-12 weeks) were divided into three groups; no-FC (control), FC and FC + FE. We measured PPI at the following three time points, (1) baseline before FC, (2) after FC, and (3) after FE. The results showed that PPI was increased after FC. Moreover, the enhanced PPI following FC was observed even after FE with decreased freezing behaviors. These results suggested contextual fear conditioning could enhance acoustic PPI, and that contextual fear extinction could decrease freezing behaviors, but not acoustic PPI.

  10. Cannabidiol, among Other Cannabinoid Drugs, Modulates Prepulse Inhibition of Startle in the SHR Animal Model: Implications for Schizophrenia Pharmacotherapy

    Science.gov (United States)

    Peres, Fernanda F.; Levin, Raquel; Almeida, Valéria; Zuardi, Antonio W.; Hallak, Jaime E.; Crippa, José A.; Abilio, Vanessa C.

    2016-01-01

    Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats) strain, and on the future prospects resulting from these findings. PMID:27667973

  11. Cannabidiol, among other cannabinoid drugs, modulates prepulse inhibition of startle in the SHR animal model: implications for schizophrenia pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Fernanda Fiel Peres

    2016-09-01

    Full Text Available Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats strain, and on the future prospects resulting from these findings.

  12. Effects of melatonin on prepulse inhibition, habituation and sensitization of the human startle reflex in healthy volunteers

    DEFF Research Database (Denmark)

    Lehtinen, Emilia K; Ucar, Ebru; Glenthøj, Birte Y

    2014-01-01

    Prepulse inhibition of the startle reflex (PPI) is an operational measure of sensorimotor gating, which is demonstrated to be impaired in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with blunted melatonin secretion is regularly found in patients...... with schizophrenia and it is theorized that these may contribute to their attentional deficits. The aim of this study was to assess the effects of acute melatonin on healthy human sensorimotor gating. Twenty-one healthy male volunteers were administered melatonin or placebo after which their levels of PPI were...... assessed. Melatonin significantly reduced startle magnitude and ratings of alertness, but did not influence PPI, nor sensitization and habituation. However, when taking baseline scores in consideration, melatonin significantly increased PPI in low scoring individuals while significantly decreasing...

  13. Whole-body prepulse inhibition protocol to test sensorymotor gating mechanisms in monkeys.

    Science.gov (United States)

    Saletti, Patricia G; Maior, Rafael S; Hori, Etsuro; Almeida, Ricardo Miyasaka de; Nishijo, Hisao; Tomaz, Carlos

    2014-01-01

    Prepulse inhibition (PPI) is the decrease of startle reflex amplitude when a slight stimulus is previously generated. This paradigm may provide valuable information about sensorimotor gating functionality. Here we aimed at determining the inhibited and uninhibited startle response of capuchin monkeys (Sapajus spp.), and to evaluate the role of the superior colliculus in PPI. Capuchin monkeys were tested in a whole-body protocol, to determine the best startle amplitude and interstimuli interval. Additionally we tested two subjects with bilateral superior colliculus damage in this protocol. Results show that 115 dB auditory pulse has induced the best startle response. In contrast to reports in other species, no habituation to the auditory stimuli was observed here in capuchins. Also, startle reflex inhibition was optimal after 120 msec interstimuli interval. Finally, there was a downward tendency of percentage inhibition in superior colliculus-lesioned monkeys. Our data provides the possibility of further studies with whole-body protocol in capuchin monkeys and reinforces the importance of the superior colliculus in PPI.

  14. Impaired prepulse inhibition of acoustic startle in Chinese patients with first-episode, medication-na(i)ve schizophrenia

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-ren; TAN Yun-long; YANG Fu-de; ZHANG Wu-fang; ZOU Yi-zhuang; TAN Shu-ping; SONG Chong-sheng

    2013-01-01

    Background Patients with schizophrenia have prominent abnormality in information processing that can be observed by measures of prepulse inhibition (PPI) of acoustic startle reflex and PPI deficits have been considered as a candidate endophenotypic marker of schizophrenia.However,there has been little information on PPI and related measures in Chinese patients with schizophrenia.The research was to explore the deficits of acoustic startle reflex that might exist in Chinese patients with schizophrenia.Methods Startle response to acoustic stimuli,habituation,and PPI were examined in 31 Chinese patients with first-episode,medication-naǐve schizophrenia and 30 age-and sex-matched healthy Chinese controls.At the same day of startle testing,psychopathological symptoms of the patients were assessed with the Positive and Negative Syndrome Scale (PANSS).Results Compared with healthy controls,patients exhibited the significant reduction in startle response and PPI deficits at 60 milliseconds (ms) intervals (PPI60,P <0.05) but not at 30 or 120 ms intervals.Furthermore,there was a relatively strong correlation between PPI60 (P <0.05) and scores of positive scale of PANSS in patients with schizophrenia.Conclusion Our findings confirmed impaired PPI in Chinese patients with schizophrenia and suggested that a relationship between sensorimotor gating deficits and clinical symptoms of patients with schizophrenia might exist.

  15. Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding.

    Science.gov (United States)

    Palmer, Abraham A; Printz, David J; Butler, Pamela D; Dulawa, Stephanie C; Printz, Morton P

    2004-01-23

    Epidemiological studies suggest that prenatal malnutrition increases the risk of developing schizophrenia. Animal models indicate that prenatal protein deprivation (PPD) affects many aspects of adult brain function. We tested the hypothesis that PPD in rats would alter prepulse inhibition (PPI), which is an operational measure of sensorimotor gating that is deficient in schizophrenia patients. Additionally, we examined dopaminergic and glutaminergic receptor binding in the striatum and hippocampus, which have been suggested to play a role in the etiology of schizophrenia. Rat dams were fed normal (25%) or low (6%) protein diets beginning 5 weeks prior to, and throughout pregnancy. The pups were tested at postnatal days (PND) 35 and 56 for PPI. Striatal and hippocampal NMDA receptor, and striatal dopamine receptor binding were quantified post-mortem in a subset of these rats. Female rats exposed to PPD had reduced levels of PPI at PND 56, but not PND 35, suggesting the emergence of a sensorimotor gating deficit in early adulthood. Striatal NMDA receptor binding was increased in PPD females. A decrease in initial startle response (SR) was also observed in all PPD rats relative to control rats. These results suggest that PPD causes age- and sex-dependent decreases in PPI and increases in NMDA receptor binding. This animal model may be useful for the investigation of neurodevelopmental changes that are associated with schizophrenia in humans.

  16. Effects of the hallucinogen psilocybin on habituation and prepulse inhibition of the startle reflex in humans.

    Science.gov (United States)

    Gouzoulis-Mayfrank, E; Heekeren, K; Thelen, B; Lindenblatt, H; Kovar, K A; Sass, H; Geyer, M A

    1998-11-01

    Schizophrenic patients exhibit deficits in indices of sensorimotor gating, such as habituation and prepulse inhibition (PPI) of the startle reflex. Hallucinogenic drug-induced states are putative models for the early and acute stages of schizophrenic and schizophrenia-spectrum disorders. Hallucinogenic drugs have been shown to disrupt PPI and/or retard habituation of the startle reflex in animal models of schizophrenia, consistent with the view of hallucinogen-induced states as 'model psychoses'. We evaluated the effects of the hallucinogen psilocybin on PPI and habituation of the startle reflex in a double-blind, placebo-controlled human study with 12 healthy subjects. In contrast to animal studies, in our small human sample, psilocybin increased PPI, while having no clear effect on habituation (n = 6). These findings must be considered preliminary because several factors, including dose regimens and experimental parameters, may influence the results of studies on startle plasticity. Further investigations both with psychotic patients in different stages of the disease and with human and animal models of schizophrenia are needed in order to explore the effects of hallucinogens on sensorimotor gating and the relationship between information processing in hallucinogenic drug-induced states and the naturally occurring psychoses.

  17. Pre-pulse inhibition of the acoustic startle eye-blink in the Göttingen minipig

    DEFF Research Database (Denmark)

    Arnfred, Sidse Marie; Lind, Nanna Marie; Hansen, Axel Kornerup;

    2004-01-01

    by a weak white noise pre-pulse (PP), the interval between the PP and the startle noise stimulus (SNS) determining the degree of inhibition. Aiming at developing a new animal model of schizophrenia, we have investigated the acoustic startle eye-blink and PPI in 10 Göttingen minipigs. The stimuli......Pre-pulse inhibition (PPI) of the startle response is a measure of sensorimotor gating which has been frequently shown to be deficient in schizophrenic patients. In humans it is typically measured as the attenuation of the startle eye-blink reflex EMG when a startle eliciting noise is preceded...... and the block design of the stimulation were similar to paradigms used in human research. Initially the startle habituation across trials and blocks, secondarily the PPI at PP to SNS intervals of 30, 60, 120, 220, 520, 1020 and 2020 ms was investigated. One pig out of ten did not have a startle response...

  18. Inhibition in Parkinson’s disease: A focus on prepulse inhibition and Rapid eye movement sleep Behavior Disorder (RBD)

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle

    2014-01-01

    ’s disease (PD), multiple system atrophy (MSA), and healthy subjects, 2) to study the relation between PPI, cognitive function, and the striatal dopamine transporter in PD, and 3) to investigate the relation between increased EMG-activity during sleep and dopamine function, as measured with 123I-FP-CIT SPECT...... in patients with iRBD, PD, and healthy subjects. Method: Objective 1) 10 patients with MSA, 12 patients with iRBD, 40 patients with PD, and 20 healthy subjects were assessed with prepulse inhibition of the acoustic blink reflex; Objective 2) 38 patients with PD were assessed with prepulse inhibition......-parametric analyses showed that MSA patients had significantly lower PPI, as measured with max-amplitude, than iRBD and PD patients on the 60 ms–85 dB and 120 ms–85 dB inter stimulus intervals (ISI). The same relation was found when using area under the curve. No differences were found between groups for the 30 ms-85...

  19. Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.

    Science.gov (United States)

    Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

    2016-02-01

    Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems.

  20. Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines.

    Science.gov (United States)

    Samocha, K E; Lim, J E; Cheng, R; Sokoloff, G; Palmer, A A

    2010-10-01

    Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating, a process that filters out extraneous sensory, motor and cognitive information. Humans with neurological and psychiatric disorders, including schizophrenia, obsessive-compulsive disorder and Huntington's disease, exhibit a reduction in PPI. Habituation of the startle response is also disrupted in schizophrenic patients. In order to elucidate the genes involved in sensorimotor gating, we phenotyped 472 mice from an F(2) cross between LG/J × SM/J for PPI and genotyped these mice genome-wide using 162 single nucleotide polymorphism (SNP) markers. We used prepulse intensity levels that were 3, 6 and 12 dB above background (PPI3, PPI6 and PPI12, respectively). We identified a significant quantitative trait locus (QTL) on chromosome 12 for all three prepulse intensities as well as a significant QTL for both PPI6 and PPI12 on chromosome 11. We identified QTLs on chromosomes 7 and 17 for the startle response when sex was included as an interactive covariate and found a QTL for habituation of the startle response on chromosome 4. We also phenotyped 135 mice from an F(34) advanced intercross line (AIL) between LG/J × SM/J for PPI and genotyped them at more than 3000 SNP markers. Inclusions of data from the AIL mice reduced the size of several of these QTLs to less than 5 cM. These results will be useful for identifying genes that influence sensorimotor gaiting and show the power of AIL for fine mapping of QTLs.

  1. Chronic morphine treatment decreases acoustic startle response and prepulse inhibition in rats

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The reward-related effects of addictive drugs primarily act via the dopamine system, which also plays an important role in sensorimotor gating. The mesolimbic dopamine system is the common pathway of drug addiction and sensorimotor gating. However, the way in which addictive drugs affect sensorimotor gating is currently unclear. In previous studies, we examined the effects of morphine treatment on sensory gating in the hippocampus. The present study investigated the effects of morphine on sensorimotor gating in rats during chronic morphine treatment and withdrawal. Rats were examined during treatment with morphine for 10 successive days, followed by a withdrawal period. Acoustic startle responses to a single startle stimulus (115 dB SPL) and prepulse inhibition responses were recorded. The results showed that acoustic startle responses were attenuated during morphine treatment, but not during withdrawal. PPI was impaired in the last 2 morphine treatment days, but returned to a normal level during withdrawal.

  2. Stability of prepulse inhibition and habituation of the startle reflex in schizophrenia: a 6-year follow-up study of initially antipsychotic-naive, first-episode schizophrenia patients

    DEFF Research Database (Denmark)

    Hammer, Trine Bjørg; Oranje, Bob; Fagerlund, Birgitte

    2011-01-01

    Deficits in information processing appear to be core features in the pathogenesis of schizophrenia. Prepulse inhibition (PPI) and habituation of the startle reflex are operational measures of early information processing. Impaired PPI in schizophrenia has been replicated in many studies and is re......Deficits in information processing appear to be core features in the pathogenesis of schizophrenia. Prepulse inhibition (PPI) and habituation of the startle reflex are operational measures of early information processing. Impaired PPI in schizophrenia has been replicated in many studies...... and is regarded as an endophenotype for schizophrenia. However, reports on the stability of PPI over a longer period of time are lacking, both for patients with schizophrenia and for healthy subjects. The current study examined 25 initially drug-naive, first-episode schizophrenia patients and 23 healthy matched...

  3. Effects of intravenous nicotine on prepulse inhibition in smokers and non-smokers: relationship with familial smoking.

    Science.gov (United States)

    Drobes, David J; MacQueen, David A; Blank, Melissa D; Saladin, Michael E; Malcolm, Robert J

    2013-09-01

    The reinforcing properties of nicotine may be, in part, derived from its ability to enhance certain forms of cognitive processing. Several animal and human studies have shown that nicotine increases prepulse inhibition (PPI) of the startle reflex. However, it remains unclear whether these effects are related to smoking susceptibility. The current study examined the effects of intravenously delivered nicotine on PPI in smokers and non-smokers, as well as its association with a quantitative index of familial smoking. The sample consisted of 30 non-smokers and 16 smokers, who completed an initial assessment, followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions. Separate doses were used in smoker and non-smoker samples. Analyses indicated that both nicotine infusions acutely enhanced PPI among non-smokers, and this enhancement was positively related to the degree of smoking among first and second-degree relatives. Smokers also displayed PPI enhancement after receiving the first infusion, but this effect was unrelated to familial smoking. These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk.

  4. Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy.

    Science.gov (United States)

    Howland, J G; Cazakoff, B N; Zhang, Y

    2012-01-10

    Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl-d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long-Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal

  5. LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor.

    Science.gov (United States)

    Halberstadt, Adam L; Geyer, Mark A

    2010-02-01

    Compounds that activate the 5-HT(2A) receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT(2A) agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT(2A) receptors in rats. We tested whether lisuride disrupts PPI in male Sprague-Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD. Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT(2A) antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT(1A) antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D(2)/D(3) receptor antagonist raclopride (0.1 mg/kg, s.c). The effect of LSD on PPI is mediated by the 5-HT(2A) receptor, whereas activation of the 5-HT(2A) receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT(2A) agonist.

  6. Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses.

    Directory of Open Access Journals (Sweden)

    Motoko Maekawa

    Full Text Available Prepulse inhibition (PPI is a compelling endophenotype (biological markers for mental disorders including schizophrenia. In a previous study, we identified Fabp7, a fatty acid binding protein 7 as one of the genes controlling PPI in mice and showed that this gene was associated with schizophrenia. We also demonstrated that disrupting Fabp7 dampened hippocampal neurogenesis. In this study, we examined a link between neurogenesis and PPI using different animal models and exploring the possibility of postnatal manipulation of neurogenesis affecting PPI, since gene-deficient mice show biological disturbances from prenatal stages. In parallel, we tested the potential for dietary polyunsaturated fatty acids (PUFAs, arachidonic acid (ARA and/or docosahexaenoic acid (DHA, to promote neurogenesis and improve PPI. PUFAs are ligands for Fabp members and are abundantly expressed in neural stem/progenitor cells in the hippocampus. Our results are: (1 an independent model animal, Pax6 (+/- rats, exhibited PPI deficits along with impaired postnatal neurogenesis; (2 methylazoxymethanol acetate (an anti-proliferative drug elicited decreased neurogenesis even in postnatal period, and PPI defects in young adult rats (10 weeks when the drug was given at the juvenile stage (4-5 weeks; (3 administering ARA for 4 weeks after birth promoted neurogenesis in wild type rats; (4 raising Pax6 (+/- pups on an ARA-containing diet enhanced neurogenesis and partially improved PPI in adult animals. These results suggest the potential benefit of ARA in ameliorating PPI deficits relevant to psychiatric disorders and suggest that the effect may be correlated with augmented postnatal neurogenesis.

  7. Gap prepulse inhibition and auditory brainstem evoked potentials as objective measures for tinnitus in guinea pigs.

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    Susanne eDehmel

    2012-05-01

    Full Text Available Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept.

  8. Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats.

    Science.gov (United States)

    Sánchez-González, Ana; Esnal, Aitor; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto

    2016-03-01

    This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms.

  9. BIS/BAS sensitivity and emotional modulation in a prepulse-inhibition paradigm: A brain potential study.

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    Sommer, Kathrin; van der Molen, Maurits W; De Pascalis, Vilfredo

    2016-02-01

    We investigated whether prepulse inhibition (PPI) is sensitive to emotion modulation vis-à-vis individual differences in the sensitivity of the behavioral inhibition system (BIS) and behavioral activation system (BAS). Participants (n=50) performed a PPI task while recording the eyeblink reflex and auditory evoked potentials (i.e., N100 and P200). The results showed an increase in PPI from positive to negative stimuli at parietal sites, for both the N100 and P200. The N100 wave of the auditory evoked potential was sensitive to emotional valence high in arousal, whereas the P200 wave was sensitive to emotional valence low in arousal. Importantly, individual differences in BAS sensitivity, but not BIS sensitivity, influenced the emotional modulation of the startle response and PPI. This influence was most evident for the N100. Our findings are consistent with previous reports showing that PPI is sensitive to emotion modulation. The current results extent previous findings by highlighting the importance of the combined influence of valence and arousal. The findings indicate that state and trait emotions bias selective encoding of affective stimuli thereby priming behavioral output.

  10. BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation

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    Elizabeth E Manning

    2013-06-01

    Full Text Available Brain-derived neurotrophic factor (BDNF has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous mutant mice (HET has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and WT littermates were treated during young-adulthood with METH and, following a two-week break, prepulse inhibition (PPI was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioural endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behaviour. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the

  11. M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition

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    Koshimizu Hisatsugu

    2012-04-01

    Full Text Available Abstract Background In the central nervous system (CNS, the muscarinic system plays key roles in learning and memory, as well as in the regulation of many sensory, motor, and autonomic processes, and is thought to be involved in the pathophysiology of several major diseases of the CNS, such as Alzheimer's disease, depression, and schizophrenia. Previous studies reveal that M4 muscarinic receptor knockout (M4R KO mice displayed an increase in basal locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI-disrupting effect of psychotomimetics, and normal basal PPI. However, other behaviorally significant roles of M4R remain unclear. Results In this study, to further investigate precise functional roles of M4R in the CNS, M4R KO mice were subjected to a battery of behavioral tests. M4R KO mice showed no significant impairments in nociception, neuromuscular strength, or motor coordination/learning. In open field, light/dark transition, and social interaction tests, consistent with previous studies, M4R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M4R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M4R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M4R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M4R KO mice demonstrated normal startle response. M4R KO mice also displayed normal performance in the Morris water maze test. Conclusions These findings indicate that M4R is involved in regulation of locomotor activity, social behavior, and sensorimotor gating in mice. Together with decreased PPI, abnormal social behavior, which was newly identified in the present study, may represent a behavioral abnormality related to psychiatric disorders including schizophrenia.

  12. Acoustic startle reflex and pre-pulse inhibition in tinnitus patients

    Institute of Scientific and Technical Information of China (English)

    Kelly Shadwick; Wei Sun

    2014-01-01

    Gap induced pre-pulse inhibition (Gap-PPI) of acoustic startle reflex has been used as a measurement of tinnitus in animal models. However, whether this test is sensitive to detect tinnitus in humans is still unclear. Based on the testing procedure used in animal studies, a human subject testing method was formulated and conducted to investigate if a similar result could be found in tinnitus patients. Audiologic and tinnitus assessments and acoustic startle reflex measurements were performed on seven tinnitus subjects and nine age matched subjects without tinnitus. There was no significant difference found between the control and tinnitus group on the Gap-PPI across the frequencies evaluated. The amplitude of the startle response in the tinnitus group with normal hearing thresholds was significantly higher than the control group and those with tinnitus and hearing loss. This preliminary result suggests that hyperexcitability in the central auditory system may be involved in tinnitus. There was no correlation between hearing thresholds and the increased amplitude of startle response.

  13. Simultaneous evaluation of prepulse inhibition with EMG and EEG using advanced artifact removal techniques.

    Science.gov (United States)

    Fraga, Francisco J; Noya, Claudemiro V; Zimiani, Maria I; Avila, Milton A; Shuhama, Rosana; Del-Ben, Cristina M; Menezes, Paulo R; Martin, Rodrigo S; Salum, Cristiane

    2016-08-01

    Prepulse inhibition (PPI) consists of a reduction of the acoustic startle reflex (SR) magnitude (measured with EMG) when a startling stimulus is preceded by a non-startling one. This behavior has been extensively investigated in studies related to schizophrenia, since sensory-motor deficit plays a central role in its pathophysiology. However, the same auditory stimuli that trigger the SR also provoke intense auditory evoked responses (AEP), which can be measured with EEG. Comparing these two types of responses, acquired simultaneously, is a great opportunity to investigate the dependence and interdependence of their neural pathways. Nonetheless, so far very few studies have dared to perform such simultaneous recordings, because SR produces strong eye blinks and muscle contraction artifacts that contaminate EEG electrodes placed on the scalp. In this study we investigated the possibility of simultaneously obtaining both the acoustic SR (using EMG) and the AEP (using EEG) measures, through the use of advanced artifact removal techniques, to better characterize PPI in healthy humans.

  14. Exploring the Role of 5-HT1A Receptors in the Regulation of Prepulse Inhibition in Mice: Implications for Cross-Species Comparisons

    Science.gov (United States)

    2012-01-01

    Prepulse inhibition (PPI) is a model of sensorimotor gating, a sensory filtering mechanism which is disrupted in schizophrenia. Here, investigation of the role of the serotonin-1A (5-HT1A) receptor in the regulation of PPI in two mouse strains, C57Bl/6 and Balb/c, was used to address findings in the PPI literature on species and mouse strain differences that question the usefulness of PPI as a cross-species preclinical test. Although the full 5-HT1A receptor agonist, 8-OH-DPAT, induced markedly different strain-specific responses in PPI, other selective 5-HT1A receptor ligands with partial agonist or antagonist activity elicited similar effects across strains. Pretreatment with the serotonin precursor, 5-HTP, to increase serotonergic activity in the brain, unmasked a decrease in PPI caused by 8-OH-DPAT in C57Bl/6 mice. Pretreatment with the serotonin synthesis inhibitor, PCPA, to decrease serotonergic activity in the brain, unmasked an 8-OH-DPAT-induced increase in PPI in this strain. These studies show that the strain-dependent involvement of 5-HT1A receptors in PPI can be modulated by the type of 5-HT1A ligand used, or increasing or decreasing serotonin levels in the brain. These results help to clarify some of the mouse strain and species differences in PPI regulation and strengthen its usefulness as a cross-species measure of sensorimotor gating. PMID:23336054

  15. Reversible disruption of pre-pulse inhibition in hypomorphic-inducible and reversible CB1-/- mice.

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    Maria Franca Marongiu

    Full Text Available Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes. Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout ((-/- mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1(-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1(-/- only in absence of doxycycline (Dox. In such mice, under Dox(+ or vehicle, as well as in wild-type (WT and CB1(-/-, two endophenotypes motor activity (increased in animal models of schizophrenia and pre-pulse inhibition (PPI of startle reflex (disrupted in schizophrenia were analyzed. Both CB1(-/- and IRh-CB1(-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1(-/- animals, was on the contrary highly and significantly disrupted only in Dox(+ IRh-CB1(-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1(-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1(-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in

  16. The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

    Science.gov (United States)

    Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

    2007-09-01

    Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

  17. Deletion of striatal adenosine A(2A) receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learning.

    Science.gov (United States)

    Singer, Philipp; Wei, Catherine J; Chen, Jiang-Fan; Boison, Detlev; Yee, Benjamin K

    2013-04-01

    Following early clinical leads, the adenosine A(2A)R receptor (A(2A)R) has continued to attract attention as a potential novel target for treating schizophrenia, especially against the negative and cognitive symptoms of the disease because of A(2A)R's unique modulatory action over glutamatergic in addition to dopaminergic signaling. Through (i) the antagonistic interaction with the dopamine D(2) receptor, and (ii) the regulation of glutamate release and N-methyl-d-aspartate receptor function, striatal A(2A)R is ideally positioned to fine-tune the dopamine-glutamate balance, the disturbance of which is implicated in the pathophysiology of schizophrenia. However, the precise function of striatal A(2A)Rs in the regulation of schizophrenia-relevant behavior is poorly understood. Here, we tested the impact of conditional striatum-specific A(2A)R knockout (st-A(2A)R-KO) on latent inhibition (LI) and prepulse inhibition (PPI) - behavior that is tightly regulated by striatal dopamine and glutamate. These are two common cross-species translational tests for the assessment of selective attention and sensorimotor gating deficits reported in schizophrenia patients; and enhanced performance in these tests is associated with antipsychotic drug action. We found that neither LI nor PPI was significantly affected in st-A(2A)R-KO mice, although a deficit in active avoidance learning was identified in these animals. The latter phenotype, however, was not replicated in another form of aversive conditioning - namely, conditioned taste aversion. Hence, the present study shows that neither learned inattention (as measured by LI) nor sensory gating (as indexed by PPI) requires the integrity of striatal A(2A)Rs - a finding that may undermine the hypothesized importance of A(2A)R in the genesis and/or treatment of schizophrenia.

  18. Preventive effect of α-lipoic acid on prepulse inhibition deficits in a juvenile two-hit model of schizophrenia.

    Science.gov (United States)

    Deslauriers, J; Racine, W; Sarret, P; Grignon, S

    2014-07-11

    Some pathophysiological models of schizophrenia posit that prenatal inflammation sensitizes the developing brain to second insults in early life and enhances brain vulnerability, thereby increasing the risk of developing the disorder during adulthood. We previously developed a two-hit animal model, based on the well-established prenatal immune challenge with poly-inosinic/cytidylic acid (polyI:C), followed by juvenile restraint stress (RS). We observed an additive disruption of prepulse inhibition (PPI) of acoustic startle in juvenile mice submitted to both insults. Previous studies have also reported that oxidative stress is associated with pathophysiological mechanisms of psychiatric disorders, including schizophrenia. We report here that PPI disruption in our two-hit animal model of schizophrenia is associated with an increase in oxidative stress. These findings led us to assess whether α-lipoic acid, an antioxidant, can prevent both increase in oxidative status and PPI deficits in our juvenile in vivo model of schizophrenia. In the offspring submitted to prenatal injection of polyI:C and to RS, treatment with α-lipoic acid prevented the development of PPI deficits 24h after the last period of RS. α-Lipoic acid also improved PPI performance in control mice. The reversal effect of α-lipoic acid pretreatment on these behavioral alterations was further accompanied by a normalization of the associated oxidative status and dopaminergic and GABAergic abnormalities in the prefrontal cortex. Based on our double insult paradigm, these results support the hypothesis that oxidative stress plays an important role in the development of PPI deficits, a well-known behavior associated with schizophrenia. These findings form the basis of future studies aiming to unravel mechanistic insights of the putative role of antioxidants in the treatment of schizophrenia, especially during the prodromal stage.

  19. Structural and functional abnormalities of the hippocampal formation in rats with environmentally induced reductions in prepulse inhibition of acoustic startle.

    Science.gov (United States)

    Greene, J R; Kerkhoff, J E; Guiver, L; Totterdell, S

    2001-01-01

    The effects of social isolation on prepulse inhibition of acoustic startle (PPI), electrophysiology and morphology of subicular pyramidal neurons and the densities of interneuronal sub-types in the hippocampal formation were examined. Wistar rats (male weanlings) were housed socially (socials, n=8) or individually (isolates, n=7). When tested eight weeks later, PPI was lower in isolates. Rats then received terminal anaesthesia before slices of hippocampal formation were made in which the electrophysiological properties of a total of 108 subicular neurons were characterized. There were no differences in neuronal sub-types recorded in socials compared with isolates. Intrinsically burst-firing and regular spiking pyramidal neurons were examined in detail. There were no differences in resting membrane potential or input resistance in isolates compared with socials but action potential height was reduced and action potential threshold raised in isolates. A limited morphological examination of Neurobiotin-filled intrinsically burst-firing neurons did not reveal differences in cell-body area or in number of primary dendrites. Sections from the contralateral hemispheres of the same rats were stained with antibodies to calretinin, parvalbumin and the neuronal isoform of nitric oxide synthase (nNOS). In isolates, the density of calretinin positive neurons was increased in the dentate gyrus but unchanged in areas CA3, CA1 and subiculum. Parvalbumin and nNOS positive neuronal densities were unchanged. Hence in rats with environmentally induced reductions in PPI there are structural and functional abnormalities in the hippocampal formation. If the reduction in PPI stems from these abnormalities, and reduced PPI in rats is relevant to schizophrenia, then drugs that correct the reported electrophysiological changes might have antipsychotic effects.

  20. Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis.

    Science.gov (United States)

    Heekeren, K; Neukirch, A; Daumann, J; Stoll, M; Obradovic, M; Kovar, K-A; Geyer, M A; Gouzoulis-Mayfrank, E

    2007-05-01

    Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

  1. Prepulse inhibition and latent inhibition deficits in Roman high-avoidance vs. Roman low-avoidance rats: Modeling schizophrenia-related features.

    Science.gov (United States)

    Esnal, Aitor; Sánchez-González, Ana; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto

    2016-09-01

    The aim of the present study was to obtain further evidence supporting the validity of a new genetically-based rat model for the study of schizophrenia-relevant symptoms. The Roman high- (RHA-I) and low-avoidance (RLA-I) inbred rats have been psychogenetically selected for their rapid versus extremely poor acquisition of the two-way avoidance task in the shuttle box and present two well-differentiated profiles regarding several traits related to anxiety, impulsivity and sensitivity to (dopaminergic) psychostimulants. In this study we have tested animals from both strains in two behavioral paradigms that are related to schizophrenia, i.e. prepulse inhibition (PPI) and latent inhibition (LI) of fear-potentiated startle (FPS). The results show that while RLA-I rats display good PPI and LI to the context, RHA-Is show an impairment of PPI and no sign of an LI effect, which goes in the direction of the results obtained in schizophrenic patients. Therefore, although further behavioral and psychopharmacological work needs to be done, the present findings and previous studies carried out in our laboratory and others allow us to propose the RHA-I rat strain as a putative genetic rat model of differential schizophrenia-related features.

  2. Adenosine AA Receptor Antagonists Do Not Disrupt Rodent Prepulse Inhibition: An Improved Side Effect Profile in the Treatment of Parkinson's Disease

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    Carina J. Bleickardt

    2012-01-01

    Full Text Available Parkinson's disease (PD is characterized by loss of dopaminergic neurons in the substantia nigra. Current treatments for PD focus on dopaminergic therapies, including L-dopa and dopamine receptor agonists. However, these treatments induce neuropsychiatric side effects. Psychosis, characterized by delusions and hallucinations, is one of the most serious such side effects. Adenosine A2A receptor antagonism is a nondopaminergic treatment for PD with clinical and preclinical efficacy. The present studies assessed A2A antagonists SCH 412348 and istradefylline in rodent prepulse inhibition (PPI, a model of psychosis. Dopamine receptor agonists pramipexole (0.3–3 mg/kg, pergolide (0.3–3 mg/kg, and apomorphine (0.3–3 mg/kg significantly disrupted PPI; ropinirole (1–30 mg/kg had no effect; L-dopa (100–300 mg/kg disrupted rat but not mouse PPI. SCH 412348 (0.3–3 mg/kg did not disrupt rodent PPI; istradefylline (0.1–1 mg/kg marginally disrupted mouse but not rat PPI. These results suggest that A2A antagonists, unlike dopamine agonists, have an improved neuropsychiatric side effect profile.

  3. Involvement of serotoninergic 5-HT1A/2A, alpha-adrenergic and dopaminergic D1 receptors in St. John's wort-induced prepulse inhibition deficit: a possible role of hyperforin.

    Science.gov (United States)

    Tadros, Mariane G; Mohamed, Mohamed R; Youssef, Amal M; Sabry, Gilane M; Sabry, Nagwa A; Khalifa, Amani E

    2009-05-16

    Prepulse inhibition (PPI) of acoustic startle response is a valuable paradigm for sensorimotor gating processes. Previous research showed that acute administration of St. John's wort extract (500 mg/kg, p.o.) to rats caused significant disruption of PPI while elevating monoamines levels in some brain areas. The cause-effect relationship between extract-induced PPI disruption and augmented monoaminergic transmission was studied using different serotoninergic, adrenergic and dopaminergic antagonists. The effects of hypericin and hyperforin, as the main active constituents of the extract, on PPI response were also tested. PPI disruption was prevented after blocking the serotoninergic 5-HT1A and 5-HT2A, alpha-adrenergic and dopaminergic D1 receptors. Results also demonstrated a significant PPI deficit after acute treatment of rats with hyperforin, and not hypericin. In some conditions manifesting disrupted PPI response, apoptosis coexists. Electrophoresis of DNA isolated from brains of hyperforin-treated animals revealed absence of any abnormal DNA fragmentation patterns. It is concluded that serotoninergic 5-HT1A and 5-HT2A, alpha-adrenergic and dopaminergic D1 receptors are involved in the disruptive effect of St. John's wort extract on PPI response in rats. We can also conclude that hyperforin, and not hypericin, is one of the active ingredients responsible for St. John's wort-induced PPI disruption with no relation to apoptotic processes.

  4. Infrared reflectance as an alternative to EMG for measuring prepulse inhibition of startle eyeblink.

    Science.gov (United States)

    Lovelace, Christopher T; Elmore, Wade R; Filion, Diane L

    2006-09-01

    The "gold standard" measure of the human startle eyeblink response is the ocular electromyogram (EMG). However, EMG measurement is not always feasible, as with special populations or during functional neuroimaging. We evaluated an alternative, nonelectrical, noncontact measure that uses infrared (IR) light reflected from the eye. By simultaneously recording IR and EMG during an acoustic prepulse inhibition of startle paradigm, we were able to directly compare the two measures and evaluate the relative reliability and validity of the IR measure as an index of startle response modulation. Although fewer responses were detected using IR than EMG, both measures were equally sensitive to prepulse modulation of response amplitude, latency, and probability. We conclude that when the goal is simply to assess the effects of a prepulse on the startle response, IR reflectance is an adequate alternative to EMG.

  5. The influence of DHEA pretreatment on prepulse inhibition and the HPA-axis stress response in rat offspring exposed prenatally to polyriboinosinic-polyribocytidylic-acid (PIC).

    Science.gov (United States)

    Maayan, Rachel; Ram, Edward; Biton, Doron; Cohen, Hagit; Baharav, Ehud; Strous, Rael D; Weizman, Abraham

    2012-07-11

    Prenatal exposure to maternal infection may be associated with the development of neurodevelopmental disorders as well as increased susceptibility to the development of schizophrenia. Prenatal administration of polyriboinosinic-polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce schizophrenia-like behavioral, neurochemical and neuorophysiological abnormalities in rodent offspring. In the present study PIC prenatal administration at gestation day 15 was associated with alterations in the acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress response in rat offspring on day 90. We show that pretreatment with dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female rats and normalizes HPA-axis stress response in a united group of male and female rats. Further research in both animal and human studies is recommended in order to confirm these preliminary findings and their application to the understanding and management of schizophrenia and related conditions.

  6. Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia-Gating of auditory-evoked potentials and prepulse inhibition

    DEFF Research Database (Denmark)

    Broberg, Brian Villumsen; Oranje, Bob; Yding, Birte;

    2010-01-01

    The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages...... of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist......, in the P1 suppression paradigm in the EEG. The results indicate that early postnatal PCP treatment to rats leads to a reduction in PPI of the acoustic startle response. Furthermore, treated animals were assessed in the P1 suppression paradigm and produced significant changes in auditory-evoked potentials...

  7. The role of stress and noradrenaline in prepulse inhibition, a rodent study : implications for schizophrenia

    NARCIS (Netherlands)

    Sontag, Thomas Alexander

    2003-01-01

    In this study we investigated the role of stress and noradrenaline in schizophrenia. Among others schizophrenic patients display reductions in prepulse inhibition. Since this behavioural response can be measured in both humans and animals it opens the possibility to use rats in schizophrenia researc

  8. Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively.

    Science.gov (United States)

    Riba, Jordi; Rodríguez-Fornells, Antoni; Barbanoj, Manel J

    2002-12-01

    Ayahuasca, a South American psychotropic plant tea, combines the psychedelic agent and 5-HT(2A/2C) agonist N, N-dimethyltryptamine (DMT) with beta-carboline alkaloids showing monoamine oxidase-inhibiting properties. Current human research with psychedelics and entactogens has explored the possibility that drugs displaying agonist activity at the 5-HT(2A/2C) sites temporally disrupt inhibitory neural mechanisms thought to intervene in the normal filtering of information. Suppression of the P50 auditory evoked potential (AEP) and prepulse inhibition of startle (PPI) are considered operational measures of sensory (P50 suppression) and sensorimotor (PPI) gating. Contrary to findings in lower animals, unexpected increases in sensorimotor gating have been found in humans following the administration of the serotonergic psychedelic psilocybin and the serotonin releaser 3,4-methylenedioxymethamphetamine (MDMA). In addition, to our knowledge P50 suppression has not been assessed previously in humans following the administration of a 5-HT(2A/2C) agonist. To assess the effects of the acute administration of ayahuasca on P50 suppression and PPI in humans, in order to evaluate the drug's modulatory actions on these measures of sensory and sensorimotor gating. Eighteen healthy volunteers with prior experience of psychedelic drug use participated in a clinical trial in which placebo or ayahuasca doses (0.6 mg and 0.85 mg DMT/kg body weight) were administered according to a double-blind, cross-over balanced design. P50 and startle reflex (pulse-alone and 60 ms, 120 ms, 240 ms and 2000 ms prepulse-to-pulse intervals) recordings were undertaken at 1.5 h and 2 h after drug intake, respectively. Ayahuasca produced diverging effects on each of the two gating measures evaluated. Whereas significant dose-dependent reductions of P50 suppression were observed after ayahuasca, no significant effects were found on the startle response, its habituation rate, or on PPI at any of the prepulse

  9. Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia

    Directory of Open Access Journals (Sweden)

    Ignasi eOliveras

    2015-08-01

    Full Text Available Animal models of schizophrenia-relevant symptoms are increasingly important for progress in our understanding of the neurobiological basis of the disorder and for discovering novel and more specific treatments. Prepulse inhibition (PPI and working memory, which are impaired in schizophrenic patients, are among the symptoms/processes modeled in those animal analogues. We have evaluated whether a genetically-selected rat model, the Roman high-avoidance inbred strain (RHA-I, displays PPI deficits as compared with its Roman low-avoidance (RLA-I counterpart and the genetically heterogeneous NIH-HS rat stock. We have investigated whether PPI deficits predict spatial working memory impairments (in the Morris water maze; MWM in these three rat types (Experiment 1, as well as in a separate sample of NIH-HS rats stratified according to their extreme (High, Medium, Low PPI scores (Experiment 2. The results from Exp. 1 show that RHA-I rats display PPI and spatial working memory deficits compared to both RLA-I and NIH-HS rats. Likewise, in Exp. 2, Low-PPI NIH-HS rats present significantly impaired working memory with respect to Medium-PPI and High-PPI NIH-HS subgroups. Further support to these results comes from correlational, factorial and multiple regression analyses, which reveal that PPI is positively associated with spatial working memory performance. Conversely, cued learning in the MWM was not associated with PPI. Thus, using genetically-selected and genetically heterogeneous rats, the present study shows, for the first time, that PPI is a positive predictor of performance in a spatial working memory task. These results may have translational value for schizophrenia symptom research in humans, as they suggest that either by psychogenetic selection or by focusing on extreme PPI scores from a genetically heterogeneous rat stock, it is possible to detect a useful (perhaps at risk phenotype to study cognitive anomalies linked to schizophrenia.

  10. Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia.

    Science.gov (United States)

    Oliveras, Ignasi; Río-Álamos, Cristóbal; Cañete, Toni; Blázquez, Gloria; Martínez-Membrives, Esther; Giorgi, Osvaldo; Corda, Maria G; Tobeña, Adolf; Fernández-Teruel, Alberto

    2015-01-01

    Animal models of schizophrenia-relevant symptoms are increasingly important for progress in our understanding of the neurobiological basis of the disorder and for discovering novel and more specific treatments. Prepulse inhibition (PPI) and working memory, which are impaired in schizophrenic patients, are among the symptoms/processes modeled in those animal analogs. We have evaluated whether a genetically-selected rat model, the Roman high-avoidance inbred strain (RHA-I), displays PPI deficits as compared with its Roman low-avoidance (RLA-I) counterpart and the genetically heterogeneous NIH-HS rat stock. We have investigated whether PPI deficits predict spatial working memory impairments (in the Morris water maze; MWM) in these three rat types (Experiment 1), as well as in a separate sample of NIH-HS rats stratified according to their extreme (High, Medium, Low) PPI scores (Experiment 2). The results from Experiment 1 show that RHA-I rats display PPI and spatial working memory deficits compared to both RLA-I and NIH-HS rats. Likewise, in Experiment 2, "Low-PPI" NIH-HS rats present significantly impaired working memory with respect to "Medium-PPI" and "High-PPI" NIH-HS subgroups. Further support to these results comes from correlational, factorial, and multiple regression analyses, which reveal that PPI is positively associated with spatial working memory performance. Conversely, cued learning in the MWM was not associated with PPI. Thus, using genetically-selected and genetically heterogeneous rats, the present study shows, for the first time, that PPI is a positive predictor of performance in a spatial working memory task. These results may have translational value for schizophrenia symptom research in humans, as they suggest that either by psychogenetic selection or by focusing on extreme PPI scores from a genetically heterogeneous rat stock, it is possible to detect a useful (perhaps "at risk") phenotype to study cognitive anomalies linked to schizophrenia.

  11. Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs.

    Science.gov (United States)

    Dehmel, Susanne; Eisinger, Daniel; Shore, Susan E

    2012-01-01

    Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not

  12. White matter hyperintensities and prepulse inhibition in a mixed elderly population

    DEFF Research Database (Denmark)

    Salem, Lise C; Hejl, Anne-Mette; Garde, Ellen;

    2011-01-01

    rated visually on craniel MRI FLAIR images using the Fazekas scale. WMH were identified in 70% of all subjects. The latency to peak of the startle response increased significantly with increasing WMH load, whereas the inhibition of the startle response (PPI) was neither significantly related...

  13. 前脉冲抑制在自闭症研究中的进展和展望%The progress and prospect of prepulse inhibition in autism

    Institute of Scientific and Technical Information of China (English)

    吴哲萌; 雷铭; 吴玺宏; 李量

    2014-01-01

    Prepulse inhibition (PPI) is suppression of the startle reflex when an intense startling stimulus is preceded by a weaker sensory stimulus (the prepulse).It is an operational measurement of sensorimotor gating mechanism to help human adapt to complex environment.This weak prepulse protect central cognitive processing by damping the effect of intense stimuli.Autistics cannot select out behaviorally important information from a lot of irrelevant resources and reflect abnormal gating mechanism and attentional abnormalities.Previous studies have not made agreement on whether autistic patients demonstrated deficits in PPI,because the results depend on age,sex,severity of the disease as well as the experimental parameters used.Moreover,these studies have not covered whether autistics have suffered deficits in higher-order processing.In this review,the "top-down" modulation of selective attention and subjective emotion are introduced into the PPI experiment.We also introduce fear conditioning and perceived spatial separation paradigm to further explore the interaction between autistic cognitive process and gating mechanism.%惊反射的前脉冲抑制(prepulse inhibition,PPI)是指当引发惊反射的强刺激之前出现了一个弱刺激(即前脉冲刺激)时,该弱刺激对惊反射有显著的抑制作用.PPI是一种大脑适应复杂环境的感觉运动门控过程,通过减弱惊反射使得由前脉冲刺激所引发的中枢加工活动得到保护.自闭症患者不仅存在感觉运动门控机制的缺失,还伴随注意加工的损害.但是对自闭症患者是否存在PPI的缺失还存在争议,这与患者的年龄、性别、疾病严重程度以及实验参数有关.前人的研究仅涉及对自闭症患者低水平门控机制的探讨,未探究自闭症患者高级认知加工过程是否存在缺损.本综述重点探讨注意和情绪等高级认知活动对PPI的调节作用,通过引入恐惧条件化和知觉空间分离去掩蔽范式,考

  14. Prepulse Inhibition is Associated with Attention, Processing Speed, and 123I-FP-CIT SPECT in Parkinson's Disease

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi B; Nikolic, Miki;

    2014-01-01

    cognitive information processing deficits such as slowed processing speed. Parkinson's disease is characterised by the degeneration of the midbrain dopaminergic system and is associated with cognitive dysfunction, including slowed information processing. Although sensorimotor processes in Parkinson......'s disease have been extensively studied in relation to motor function, less is known about the potential role of sensorimotor processes in cognitive function. Objective: We investigated the relationship between prepulse inhibition, cognition and nigrostriatal dysfunction, as measured with 123I...... performed better on cognitive measures tapping attention and processing speed than patients with a lower level of prepulse inhibition group. Furthermore, there were significant correlations between prepulse inhibition and 123I-FP-CIT uptake in the striatum. Conclusions: Our results suggest that the level...

  15. Effects of Cannabinoid Drugs on the Deficit of Prepulse Inhibition of Startle in an Animal Model of Schizophrenia: the SHR Strain

    Directory of Open Access Journals (Sweden)

    Raquel eLevin

    2014-02-01

    Full Text Available Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the Spontaneously Hypertensive Rats (SHR strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition of startle (PPI, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: 1 WIN55212,2 (cannabinoid agonist, 2 rimonabant (CB1 antagonist, 3 AM404 (anandamide uptake inhibitor, and 4 cannabidiol (indirect CB1/CB2 receptor antagonist, among other effects. Wistar rats (WR and SHRs were treated with vehicle or different doses of WIN55212 (0.3, 1 or 3 mg/kg, rimonabant (0.75, 1.5 or 3 mg/kg, AM404 (1, 5 or 10 mg/kg or cannabidiol (15, 30 or 60 mg/kg. Vehicle-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg cannabidiol. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.

  16. Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice.

    Science.gov (United States)

    André, Jessica M; Gulick, Danielle; Portugal, George S; Gould, Thomas J

    2008-07-19

    Nicotine withdrawal is associated with multiple symptoms such as anxiety, increased appetite, and disrupted cognition in humans. Although animal models have provided insights into the somatic and affective symptoms of nicotine withdrawal, less research has focused on the effects of nicotine withdrawal on cognition. Therefore, in this study, C57BL/6J mice were used to test the effects of withdrawal from chronic nicotine on foreground and background contextual fear conditioning, which present the context as a primary or secondary stimulus, respectively. Mice withdrawn from 12 days of chronic nicotine (6.3mg/kg/day) or saline were trained and tested in either foreground or background contextual fear conditioning; nicotine withdrawal-associated deficits in contextual fear conditioning were observed in both conditions. Mice were also tested for the effects of withdrawal on pre-pulse inhibition of the acoustic startle reflex (PPI), a measure of sensory gating, and on the acoustic startle reflex. Mice withdrawn from 12 days of chronic nicotine (6.3 or 12.6 mg/kg/day) or saline underwent one 30-min PPI and startle session; no effect of withdrawal from chronic nicotine on PPI or startle was observed for either dose at 24h after nicotine removal. Therefore, mice were tested at different time points following withdrawal from 12.6 mg/kg/day chronic nicotine (8, 24, and 48 h after nicotine removal). No effect of withdrawal from chronic nicotine was observed at any time point for PPI. Overall, these results demonstrate that nicotine withdrawal disrupts two methods of contextual learning but not sensory gating in C57BL/6J mice.

  17. The effects of prepulse inhibition timing on the startle reflex and reaction time.

    Science.gov (United States)

    Maslovat, Dana; Kennedy, Paul M; Forgaard, Christopher J; Chua, Romeo; Franks, Ian M

    2012-04-04

    A loud acoustic stimulus has been shown to provoke a reflexive startle response and accelerate simple reaction times. However, an auditory prepulse presented in advance of a startling stimulus can reduce the effect of the startling stimulus. The current study examined the effect of the timing of the prepulse on startle-induced reaction times and the startle reflex. The task was to perform a 30° arm extension movement in response to a visual "go" stimulus. On selected trials, an auditory prepulse (80dB) was presented either 100ms, 500ms or 1000ms prior to the "go" signal. In addition, an auditory startling stimulus (124dB) was presented in conjunction with the "go" signal on some trials. Our results indicated that an auditory prepulse presented 100ms, and to a lesser extent 500ms, significantly decreased the amplitude of the startle reflex; however, the reaction time acceleration associated with the startling acoustic stimulus (SAS) was unaffected. The differential effect of the prepulse on the startle reflex and reaction time acceleration confirm different neural pathways for these effects while the differential effect of the prepulse on the control and startle RTs suggest different mechanisms for movement initiation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine

    DEFF Research Database (Denmark)

    Lind, Nanna Marie; Arnfred, Sidse M; Hemmingsen, Ralf P;

    2004-01-01

    for validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg...... and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable...

  19. Modulation of prepulse inhibition and startle reflex by emotions: A comparison between young and older adults

    OpenAIRE

    2016-01-01

    This study examined whether or not the acoustic startle response and sensorimotor gating may be modulated by emotions differentially between young and older adults. Two groups of participants (mean age Young: 24 years old; Elderly: 63.6 years old) were presented with three types of auditory stimuli (Startle alone, High or Low frequency Prepulse) while viewing pleasant, neutral, or unpleasant images. Electromyographic activity of the eyeblink response was measured. Results show that older adul...

  20. Divergent effects of isolation rearing on prepulse inhibition, activity, anxiety and hippocampal-dependent memory in Roman high- and low-avoidance rats: A putative model of schizophrenia-relevant features.

    Science.gov (United States)

    Oliveras, Ignasi; Sánchez-González, Ana; Piludu, Maria Antonietta; Gerboles, Cristina; Río-Álamos, Cristóbal; Tobeña, Adolf; Fernández-Teruel, Alberto

    2016-11-01

    Social isolation of rats induces a constellation of behavioral alterations known as "isolation syndrome" that are consistent with some of the positive and cognitive symptoms observed in schizophrenic patients. In the present study we have assessed whether isolation rearing of inbred Roman high-avoidance (RHA-I) and Roman low-avoidance (RLA-I) strains can lead to the appearance of some of the key features of the "isolation syndrome", such as prepulse inhibition (PPI) deficits, increased anxious behavior, hyperactivity and memory/learning impairments. Compared to RLA-I rats, the results show that isolation rearing (IR) in RHA-I rats has a more profound impact, as they exhibit isolation-induced PPI deficits, increased anxiety, hyperactivity and long-term reference memory deficits, while isolated RLA-I rats only exhibit deficits in a spatial working memory task. These results give further support to the validity of RHA-I rats as a genetically-based model of schizophrenia relevant-symptoms.

  1. Microinfusion of the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of wistar rats does not affect latent inhibition and prepulse inhibition, but increases startle reaction and locomotor activity.

    Science.gov (United States)

    Zhang, W N; Bast, T; Feldon, J

    2000-01-01

    Latent inhibition (the retarded conditioning to a stimulus following its repeated non-reinforced pre-exposure) and prepulse inhibition (the reduction in the startle response to an intense acoustic stimulus when this stimulus is immediately preceded by a prepulse) reflect cognitive and sensorimotor gating processes, respectively, and are deficient in schizophrenic patients. The disruption of latent inhibition and prepulse inhibition in the rat is used as an animal model for the attentional deficits associated with schizophrenia. The present study tested the extent to which latent inhibition and prepulse inhibition, startle reaction and locomotor activity in the open field were affected by infusing the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats. We used the same dose of MK-801 (6.25microg/0.5microl per side) previously found to be effective in the disruption of prepulse inhibition when infused into the dorsal hippocampus of Sprague-Dawley rats [Bakshi V. P. and Geyer M. A. (1998) J. Neurosci. 18, 8394-8401; Bakshi V. P. and Geyer M. A. (1999) Neuroscience 92, 113-121]. Bilateral infusion of MK-801 into the dorsal hippocampus did not disrupt latent inhibition. Furthermore, in contrast to previous studies, we failed to find a significant disruption of prepulse inhibition after MK-801 infusion into the dorsal hippocampus, although MK-801 infusion was effective in increasing the startle amplitude as well as locomotor activity in an open field. From our results, we suggest that N-methyl-D-aspartate receptor-mediated processes within the dorsal hippocampus are not necessary for the normal maintenance of the attentional processes reflected by latent inhibition and prepulse inhibition.

  2. Modulation of prepulse inhibition and startle reflex by emotions: A comparison between young and older adults

    Directory of Open Access Journals (Sweden)

    Jolyanne eLe Duc

    2016-02-01

    Full Text Available This study examined whether or not the acoustic startle response and sensorimotor gating may be modulated by emotions differentially between young and older adults. Two groups of participants (mean age Young: 24 y.o.; Elderly: 63.6 y.o. were presented with three types of auditory stimuli (Startle alone, High or Low frequency Prepulse while viewing pleasant, neutral, or unpleasant images. Electromyographic activity of the eyeblink response was measured. Results show that older adults displayed diminished eyeblink responses whereas younger adults displayed enhanced eyeblink responses when viewing negative images. Sensorimotor gating also differed between young and older adults, with enhanced sensorimotor gating abilities while viewing positive pictures in older adults and diminished abilities while viewing negative pictures among younger adults. These results argue in favor of a differential emotional influence on the sensorimotor abilities of young and older adults, with a positivity bias among the latter.

  3. Modulation of Prepulse Inhibition and Startle Reflex by Emotions: A Comparison between Young and Older Adults.

    Science.gov (United States)

    Le Duc, Jolyanne; Fournier, Philippe; Hébert, Sylvie

    2016-01-01

    This study examined whether or not the acoustic startle response and sensorimotor gating may be modulated by emotions differentially between young and older adults. Two groups of participants (mean age Young: 24 years old; Elderly: 63.6 years old) were presented with three types of auditory stimuli (Startle alone, High or Low frequency Prepulse) while viewing pleasant, neutral, or unpleasant images. Electromyographic activity of the eyeblink response was measured. Results show that older adults displayed diminished eyeblink responses whereas younger adults displayed enhanced eyeblink responses when viewing negative images. Sensorimotor gating also differed between young and older adults, with enhanced sensorimotor gating abilities while viewing positive pictures in older adults and diminished abilities while viewing negative pictures among younger adults. These results argue in favor of a differential emotional influence on the sensorimotor abilities of young and older adults, with a positivity bias among the latter.

  4. Inhibition in the Human Auditory Cortex.

    Directory of Open Access Journals (Sweden)

    Koji Inui

    Full Text Available Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

  5. Effects of cigarette smoking on prepulse inhibition, its attentional modulation, and vigilance performance.

    Science.gov (United States)

    Rissling, Anthony J; Dawson, Michael E; Schell, Anne M; Nuechterlein, Keith H

    2007-07-01

    Startle eyeblink modification was measured during a degraded stimulus continuous performance test following both smoking and overnight abstinence among student smokers to measure the effects of smoking on both early and late attentional processes. A group of nonsmokers was tested twice without nicotine manipulation. A startling noise was presented either 240 or 1200 ms following target and nontarget stimuli presented during the task. Startle inhibition at 240 ms was greater following targets than nontargets following smoking and during both nonsmoker tests, but this attentional modulation was absent following abstinence. At the 1200-ms probe position, target and nontarget stimuli produced nondifferential inhibition during both tests for both groups. Abstinence among smokers produced reliably lower vigilance performance compared to ad lib smoking. The results indicate that smoking abstinence affects the early stages of stimulus processing.

  6. Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory.

    Directory of Open Access Journals (Sweden)

    Marei Typlt

    Full Text Available Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.

  7. The effects of imipramine on P50 suppression, prepulse inhibition and habituation of the startle response in humans

    DEFF Research Database (Denmark)

    Hammer, Trine Bjørg; Oranje, Bob; Glenthoj, Birte Y

    2007-01-01

    -controlled cross-over design, 20 healthy male volunteers received either placebo or a dose of 50 mg imipramine (a dual-acting antidepressant), after which they were tested in a P50 suppression paradigm, a PPI paradigm, and an habituation of the startle reflex paradigm. Imipramine significantly decreased PPI...

  8. Is prepulse modification altered by continuous theta burst stimulation? DAT1 genotype and motor threshold interact on prepulse modification following brain stimulation.

    Science.gov (United States)

    Notzon, S; Vennewald, N; Gajewska, A; Klahn, A L; Diemer, J; Winter, B; Fohrbeck, I; Arolt, V; Pauli, P; Domschke, K; Zwanzger, P

    2017-03-24

    Previous studies suggest an inhibitory top-down control of the amygdala by the prefrontal cortex (PFC). Both brain regions play a role in the modulation of prepulse modification (PPM) of the acoustic startle response by a pre-stimulus. Repetitive transcranial magnetic stimulation (rTMS) can modulate the activity of the PFC and might thus affect PPM. This study tested the effect of inhibitory rTMS on PPM accounting for a genetic variant of the dopamine transporter gene (DAT1). Healthy participants (N = 102) were stimulated with continuous theta burst stimulation (cTBS, an intense form of inhibitory rTMS) or sham treatment over the right PFC. Afterwards, during continuous presentation of a background white noise a louder noise burst was presented either alone (control startle) or preceded by a prepulse. Participants were genotyped for a DAT1 variable number tandem repeat (VNTR) polymorphism. Two succeeding sessions of cTBS over the right PFC (2 × 600 stimuli with a time lag of 15 min) attenuated averaged prepulse inhibition (PPI) in participants with a high resting motor threshold. An attenuation of PPI induced by prepulses with great distances to the pulse (480, 2000 ms) was observed following active cTBS in participants that were homozygous carriers of the 10-repeat-allele of the DAT1 genotype and had a high resting motor threshold. Our results confirm the importance of the prefrontal cortex for the modulation of PPM. The effects were observed in participants with a high resting motor threshold only, probably because they received a higher dose of cTBS. The effects in homozygous carriers of the DAT1 10-repeat allele confirm the relevance of dopamine for PPM. Conducting an exploratory study we decided against the use of a correction for multiple testing.

  9. The effects of increased central serotonergic activity on prepulse inhibition and habituation of the human startle response

    DEFF Research Database (Denmark)

    Jensen, Kristian S; Oranje, Bob; Wienberg, Malene

    2007-01-01

    modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences...... between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results...

  10. Neonatal intrahippocampal injection of lipopolysaccharide induces deficits in social behavior and prepulse inhibition and microglial activation in rats: Implication for a new schizophrenia animal model.

    Science.gov (United States)

    Zhu, Furong; Zhang, Lulu; Ding, Yu-qiang; Zhao, Jingping; Zheng, Yingjun

    2014-05-01

    Several lines of evidence have suggested that the dysregulation of immune system is involved in the pathogenesis of schizophrenia. Microglia are the resident macrophage of the brain and the major player in innate immunity in the brain. We hypothesized that microglia activation may be closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (PD7), and they were separately treated with saline or minocycline for consecutive 3days. Behavioral changes (locomotor activity, social interaction and prepulse inhibition) were examined in adulthood, and the number of microglia was assessed using immunohistochemistry at PD9, PD21 and PD67. The adult rats in LPS-injected group showed obvious behavioral alterations (deficits in social behavior and prepulse inhibition) and a persistently dramatic increase of number of activated microglial cells in the hippocampus, cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, pretreatment with minocycline could significantly rescue the behavioral deficits and prevent microglia activation. Our results suggest that neonatal intrahippocampal LPS injection may serve as a potential schizophrenia animal model, and inhibition of microglia activation may be a potential treatment strategy for schizophrenia.

  11. Prepulse inhibition of startle reflex in schizophrenics and healthy adults%首发未服药精神分裂症患者的惊跳反射弱刺激抑制和P50检测

    Institute of Scientific and Technical Information of China (English)

    吴荣琴; 宋立升; 吕坚; 黄军斌; 孙复林; 李桦; 陈兴时; 陈冲

    2015-01-01

    Objective To evaluate the characteristics of sensory gating inhibition and variation of schizophrenia with both prepulse inhibition (PPI) and P50.Methods The PPI of startle reflex and P50 were tested by an event-related potential (ERP) recorder in 82 first episode schizophrenics (FES) recruited from September 2007 to February 2014 at Shanghai Mental Health Hospital and 78 healthy controls (NC) from hospital staffs and local residents for the same period.All patients fulfilled the evaluation of PPI with strong stimulus alone and strong + weak stimulus paradigm,P50 with conditioning (S1)-testing (S2) paradigm.The psychotic symptoms were assessed with Positive and Negative Syndrome Scale (PANSS).Results (1) Compared with control group,schizophrenia group had increased PL (NC:(89 ± 14) ms,FES:(97 ± 17) ms,P < 0.05) and PPL,decreased amplitude (NC:(92 ± 21) ms,(24 ± 14) μV,FSZ:(96 ± 20) ms,(41 ± 29) μV,P < 0.05,0.01),lower PPI inhibition ratio (NC:(67 ± 32) %,FSZ:(41 ± 37) %,P < 0.05).(2) Compared with NC group,there were increased S2 amplitude [NC:(3 ± 2) μV vs FES:(5 ±3) μV,P <0.05] and ratio of S2/S1 amplitude [(43 ± 22) % vs (82 ±41)%,P <0.05] in schizophrenia group.And P50 inhibition decreased significantly.Conclusion Schizophrenics have both PPI and P50 impairments.And a combination of PPI inhibition ratio and S2/S1 (P50) may be a better electrocerebrophysiological index for schizophrenia.%目的 应用惊跳反射弱刺激抑制(PPI)和P50两项新技术共同评价精神分裂症感觉门抑制及其变异特点.方法 应用德国Brain Products公司的ERP记录与分析系统,PPI采用单独强刺激和弱刺激+强刺激范式,P50采用S1和S2范式,对82例首发精神分裂症患者(患者组,来源于2007年9月至2014年2月上海市精神卫生中心)和78名健康成人(健康对照组,来源于同时期医院工作人员及附近居民)作了PPI和P50检测.并用阳性和阴性症状量表(PANSS)

  12. The effects of increased central serotonergic activity on prepulse inhibition and habituation of the human startle response

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Oranje, Bob; Wienberg, Malene

    2007-01-01

    modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences...

  13. Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models.

    Science.gov (United States)

    Cheng, Jianjun; Giguere, Patrick M; Schmerberg, Claire M; Pogorelov, Vladimir M; Rodriguiz, Ramona M; Huang, Xi-Ping; Zhu, Hu; McCorvy, John D; Wetsel, William C; Roth, Bryan L; Kozikowski, Alan P

    2016-01-28

    A series of novel compounds with two halogen substituents have been designed and synthesized to further optimize the 2-phenylcyclopropylmethylamine scaffold in the quest for drug-like 5-HT2C agonists. Compound (+)-22a was identified as a potent 5-HT2C receptor agonist, with good selectivity against the 5-HT2B and the 5-HT2A receptors. ADMET assays showed that compound (+)-22a possessed desirable properties in terms of its microsomal stability, and CYP and hERG inhibition, along with an excellent brain penetration profile. Evaluation of (+)-22a in animal models of schizophrenia-related behaviors revealed that it had a desirable activity profile, as it reduced d-amphetamine-stimulated hyperlocomotion in the open field test, it restored d-amphetamine-disrupted prepulse inhibition, it induced cognitive improvements in the novel object recognition memory test in NR1-KD animals, and it produced very little catalepsy relative to haloperidol. These data support the further development of (+)-22a as a drug candidate for the treatment of schizophrenia.

  14. Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

    Science.gov (United States)

    Shibasaki, Y; Hayata-Takano, A; Hazama, K; Nakazawa, T; Shintani, N; Kasai, A; Nagayasu, K; Hashimoto, R; Tanida, M; Katayama, T; Matsuzaki, S; Yamada, K; Taniike, M; Onaka, Y; Ago, Y; Waschek, J A; Köves, K; Reglődi, D; Tamas, A; Matsuda, T; Baba, A; Hashimoto, H

    2015-06-25

    Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Dual channel selective fluorescence detection of Al(III) and PPi in aqueous media with an 'off-on-off' switch which mimics molecular logic gates (INHIBIT and EXOR gates).

    Science.gov (United States)

    Goswami, Shyamaprosad; Manna, Abhishek; Paul, Sima; Aich, Krishnendu; Das, Avijit K; Chakraborty, Shampa

    2013-06-14

    In this study, we have synthesized a simple Schiff base type isophthaloyl salicylaldehyde hydrazone (ISH) moiety which selectively detects Al(III) and PPi with a fluorescence enhancement at two different wavelengths in aqueous solution. The sensing phenomenon is also reversible and thus the sensor beautifully mimics logic gates (INHIBIT and EXOR gates).

  16. Prepulse minimization in KALI-5000

    Science.gov (United States)

    Kumar, D. Durga Praveen; Mitra, S.; Senthil, K.; Sharma, Vishnu K.; Singh, S. K.; Roy, A.; Sharma, Archana; Nagesh, K. V.; Chakravarthy, D. P.

    2009-07-01

    A pulse power system (1 MV, 50 kA, and 100 ns) based on Marx generator and Blumlein pulse forming line has been built for generating high power microwaves. The Blumlein configuration poses a prepulse problem and hence the diode gap had to be increased to match the diode impedance to the Blumlein impedance during the main pulse. A simple method to eliminate prepulse voltage using a vacuum sparkgap and a resistor is given. Another fundamental approach of increasing the inductance of Marx generator to minimize the prepulse voltage is also presented. Experimental results for both of these configurations are given.

  17. RADAR PPI Scope Overlay

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — RADAR PPI Scope Overlays are used to position a RADAR image over a station at the correct resolution. The archive maintains several different RADAR resolution types,...

  18. Simultaneous EMG-fMRI during startle inhibition in monosymptomatic enuresis--an exploratory study.

    Science.gov (United States)

    Schulz-Juergensen, Sebastian; Wunberg, David; Wolff, Stephan; Eggert, Paul; Siniatchkin, Michael

    2013-01-01

    Evidence is growing that monosymptomatic enuresis (ME) is a maturational disorder of the central nervous system with a lack of arousal and lacking inhibition of the micturition reflex. Previous studies have shown a significant reduction of prepulse inhibition (PPI) of startle in children with enuresis. However, it is still unclear whether the abnormal PPI in enuresis is based on an inhibitory deficit at brainstem or cortical level. Nine children with ME and ten healthy children were investigated using simultaneous recording of EMG from the M. orbicularis oculi and functional MRI. The experimental paradigm consisted of acoustic startle stimulation, with startle-alone stimuli and prepulse-startle combinations. Functional MRI data were processed using multiple regression and parametric modulation with startle amplitudes as a parameter. Neither patients with enuresis nor healthy children revealed measurable PPI in the MRI scanner. Startle stimuli caused equal hemodynamic changes in the acoustic cortex, medial prefrontal and orbitofrontal cortex in both groups. The amplitude of startle correlated with more prominent BOLD signal changes in the anterior cingulate cortex in healthy subjects than in patients with ME. This pronounced frontal activation in healthy controls was related to the PPI condition, indicating that the prefrontal cortex of healthy children was activated more strongly to inhibit startle than in patients with ME. In conclusion, apart from the possibility that recordings of PPI inside the MRI scanner may be compromised by methodological problems, the results of this study suggest that high cortical control mechanisms at the prefrontal level are relevant for the pathogenesis of ME.

  19. Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus.

    Science.gov (United States)

    Nakagawa, Kei; Inui, Koji; Yuge, Louis; Kakigi, Ryusuke

    2014-11-01

    We previously demonstrated that auditory-evoked cortical responses were suppressed by a weak leading stimulus in a manner similar to the prepulse inhibition (PPI) of startle reflexes. The purpose of the present study was to investigate whether a similar phenomenon was present in the somatosensory system, and also whether this suppression reflected an inhibitory process. We recorded somatosensory-evoked magnetic fields following stimulation of the median nerve and evaluated the extent by which they were suppressed by inserting leading stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold (ST) in healthy participants (Experiment 1). The results obtained demonstrated that activity in the secondary somatosensory cortex in the hemisphere contralateral to the stimulated side (cSII) was significantly suppressed by a weak leading stimulus with the intensity larger than 1.1-fold ST. This result implied that the somatosensory system had an inhibitory process similar to that of PPI. We then presented two successive leading stimuli before the test stimulus, and compared the extent of suppression between the test stimulus-evoked responses and those obtained with the second prepulse alone and with two prepulses (first and second) (Experiment 2). When two prepulses were preceded, cSII responses to the second prepulse were suppressed by the first prepulse, whereas the ability of the second prepulse to suppress the test stimulus remained unchanged. These results suggested the presence of at least two individual pathways; response-generating and inhibitory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

    Science.gov (United States)

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2012-08-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction).

  1. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors

    Directory of Open Access Journals (Sweden)

    Rushikesh Sable

    2015-06-01

    Full Text Available Blocking protein-protein interactions (PPI using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  2. Pulse compression and prepulse suppression apparatus

    Science.gov (United States)

    Dane, C.B.; Hackel, L.A.; George, E.V.; Miller, J.L.; Krupke, W.F.

    1993-11-09

    A pulse compression and prepulse suppression apparatus (10) for time compressing the output of a laser (14). A pump pulse (46) is separated from a seed pulse (48) by a first polarized beam splitter (20) according to the orientation of a half wave plate (18). The seed pulse (48) is directed into an SBS oscillator (44) by two plane mirrors (22, 26) and a corner mirror (24), the corner mirror (24) being movable to adjust timing. The pump pulse (46) is directed into an SBS amplifier 34 wherein SBS occurs. The seed pulse (48), having been propagated from the SBS oscillator (44), is then directed through the SBS amplifier (34) wherein it sweeps the energy of the pump pulse (46) out of the SBS amplifier (34) and is simultaneously compressed, and the time compressed pump pulse (46) is emitted as a pulse output (52). A second polarized beam splitter (38) directs any undepleted pump pulse 58 away from the SBS oscillator (44).

  3. Superhigh-resolution 200ppi series TFT-LCDs; Chokoseisai 200ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)

    Kawamata, K.; Hirai, H. [Toshiba Corp., Tokyo (Japan)

    2000-02-01

    We have developed a 202 pixels per inch (ppi) thin-film transistor liquid crystal display (TFT-LCD) using low-temperature polycrystalline silicon (LTPS) technology. The superhigh resolution of 202 ppi offers the same image quality as printed matter such as magazines. The 200 ppi series TFT-LCDs are expected to support further developments in such areas as electronic books (e-books) and personal digital-picture viewers. Our lineup of 200 ppi TFT-LCDs includes a 4-inch display with VGA resolution, which is suitable for palmtop-size applications, and a 6.3-inch display with XGA resolution, which is suitable for typical photograph or paperback book-size applications. Larger size LCDs with 200 ppi resolution will be developed. (author)

  4. HiPPI-based parallel computing

    Science.gov (United States)

    Jung, Charles C.

    1993-02-01

    The IBM Enhanced Clustered Fortran (ECF) advanced technology project combines parallel computing technology with a HiPPI-based LAN network. The ECF environment is a clustered, parallel computing environment which consists of IBM ES/90001 complexes and possibly other parallel machines connected by HiPPI. The ECF software, including the language processor, is independent of hardware architectures, operating systems, and the Fortran compiler and runtime library. The ECF software is highly portable because it is based on well-known, standard technology and transport protocols such as Remote Procedure Call (RPC), X/Open Transport Interface (XTI), and TCP/IP. The ECF software is transport-independent, and can accommodate other transport protocols concurrently. This paper describes the IBM ECF environment including the language extensions, the programming model, and the software layers and components. Also, this paper explains how to achieve portability and scalability. Lastly, this paper describes how effective task communication is accomplished in ECF through RPC, XTI, TCP/IP, and a customized enhancement over HiPPI. An analysis of network performance in terms of bottleneck conditions is presented, and empirical data indicating improved throughput is provided. Comparisons to alternative methodologies and technologies are also presented.

  5. Double pomeron exchange in the reactions pp --> pppi$^{+}$pi$^{-}$, K$^{+}$p --> K$^{+}$ppi$^{+}$pi$^{-}$, pi$^{+}$p --> pi$^{+}$ppi$^{+}$pi$^{-}$ and pi$^{-}$p --> pi$^{-}$ppi$^{+}$pi$^{-}$ at 147 GeV/c

    CERN Document Server

    Brick, D H; Shapiro, A M; Widgoff, M; Ansorge, Rainer E; Carter, J R; Neale, William W; Rushbrooke, John G; Ward, D R; Whyman, B M; Burnstein, R A; Rubin, H A; Cooper, J W; Snyder, A; Alyea, E D; Bachman, L; Chien, C Y; Lucas, P; Pevsner, A; Bober, J T; Elahi, M; Frank, T; Hafen, E S; Haridas, P; Hochman, D; Huang, D; Hulsizer, R I; Kistiakowsky, V; Levy, A; Lutz, P; Oh, S; Pless, I A; Stoughton, T B; Suchorebrow, V; Tether, S; Trepagnier, P C; Wu, Y; Yamamoto, R K; Grard, F; Hanton, J; Henri, V; Herquet, P; Lesceux, J M; Windmolders, R; Crijns, F; De Bock, H; Kittel, E W; Metzger, W J; Pols, C L A; Schouten, M M; Van de Walle, R T; Cohn, H O

    1980-01-01

    Double pomeron exchange in the reactions pp --> pppi$^{+}$pi$^{-}$, K$^{+}$p --> K$^{+}$ppi$^{+}$pi$^{-}$, pi$^{+}$p --> pi$^{+}$ppi$^{+}$pi$^{-}$ and pi$^{-}$p --> pi$^{-}$ppi$^{+}$pi$^{-}$ at 147 GeV/c

  6. Super high precision 200 ppi liquid crystal display series; Chokoseido 200 ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    In mobile equipment, in demand is a high precision liquid crystal display (LCD) having the power of expression equivalent to printed materials like magazines because of the necessity of displaying a large amount of information on a easily potable small screen. In addition, with the spread and high-quality image of digital still cameras, it is strongly desired to display photographed digital image data in high quality. Toshiba Corp., by low temperature polysilicone (p-Si) technology, commercialized the liquid crystal display series of 200 ppi (pixels per inch) precision dealing with the rise of the high-precision high-image quality LCD market. The super high precision of 200 ppi enables the display of smooth beautiful animation comparable to printed sheets of magazines and photographs. The display series are suitable for the display of various information services such as electronic books and electronic photo-viewers including internet. The screen sizes lined up are No. 4 type VGA (640x480 pixels) of a small pocket notebook size and No. 6.3 type XGA (1,024x768 pixels) of a paperback size, with a larger screen to be furthered. (translated by NEDO)

  7. Parvalbumin and GAD65 interneuron inhibition in the ventral hippocampus induces distinct behavioral deficits relevant to schizophrenia.

    Science.gov (United States)

    Nguyen, Robin; Morrissey, Mark D; Mahadevan, Vivek; Cajanding, Janine D; Woodin, Melanie A; Yeomans, John S; Takehara-Nishiuchi, Kaori; Kim, Jun Chul

    2014-11-05

    Hyperactivity within the ventral hippocampus (vHPC) has been linked to both psychosis in humans and behavioral deficits in animal models of schizophrenia. A local decrease in GABA-mediated inhibition, particularly involving parvalbumin (PV)-expressing GABA neurons, has been proposed as a key mechanism underlying this hyperactive state. However, direct evidence is lacking for a causal role of vHPC GABA neurons in behaviors associated with schizophrenia. Here, we probed the behavioral function of two different but overlapping populations of vHPC GABA neurons that express either PV or GAD65 by selectively inhibiting these neurons with the pharmacogenetic neuromodulator hM4D. We show that acute inhibition of vHPC GABA neurons in adult mice results in behavioral changes relevant to schizophrenia. Inhibiting either PV or GAD65 neurons produced distinct behavioral deficits. Inhibition of PV neurons, affecting ∼80% of the PV neuron population, robustly impaired prepulse inhibition of the acoustic startle reflex (PPI), startle reactivity, and spontaneous alternation, but did not affect locomotor activity. In contrast, inhibiting a heterogeneous population of GAD65 neurons, affecting ∼40% of PV neurons and 65% of cholecystokinin neurons, increased spontaneous and amphetamine-induced locomotor activity and reduced spontaneous alternation, but did not alter PPI. Inhibition of PV or GAD65 neurons also produced distinct changes in network oscillatory activity in the vHPC in vivo. Together, these findings establish a causal role for vHPC GABA neurons in controlling behaviors relevant to schizophrenia and suggest a functional dissociation between the GABAergic mechanisms involved in hippocampal modulation of sensorimotor processes.

  8. Ionic motion in PEDOT and PPy conducting polymer bilayers

    DEFF Research Database (Denmark)

    Zainudeen, Umer L.; Skaarup, Steen

    2006-01-01

    Conducting polymer bilayers with poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy), each containing dodecyl benzenesulfonate (DBS) as immobile dopant species, were synthesized galvanostatically. The electrochemical behaviour of the bilayers was investigated using cyclic voltammetry...

  9. Ionic motion in PEDOT and PPy conducting polymer bilayers

    DEFF Research Database (Denmark)

    Zainudeen, Umer L.; Skaarup, Steen

    2006-01-01

    Conducting polymer bilayers with poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy), each containing dodecyl benzenesulfonate (DBS) as immobile dopant species, were synthesized galvanostatically. The electrochemical behaviour of the bilayers was investigated using cyclic voltammetry...

  10. Robust Stability and Performance Comparison of PID and PPI Control

    Institute of Scientific and Technical Information of China (English)

    任正云; 张红; 邵惠鹤

    2004-01-01

    Predictive PI (PPI) control form, capable of time delay compensation, has been put forward recently. This control algorithm is essentially a PI controller with enhanced derivative action, which is not only suitable for long time delay process, but also of simple structure and excellent robust stability. The performance of PPI controller was demonstrated and compared with that of traditional PID controller by different tuning methods.

  11. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

    Science.gov (United States)

    Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

    2012-02-01

    The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

  12. Synthesis and microwave absorption properties of PPy/Co nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Juhua, E-mail: luojuhua@163.com [School of Materials Engineering, Yancheng Institute of Technology, Yancheng 224051 (China); Gao, Duoduo [School of Material Science and Engineering, Changzhou University, Changzhou 213164 (China)

    2014-11-15

    Polypyrrole (PPy)/cobalt (Co) nanocomposites were successfully prepared by an in-situ polymerization of pyrrole in the presence of synthesized Co nanoparticles. Characterization of the product was accomplished by XRD, TEM, FT-IR, VSM, and vector network analyzer techniques. XRD analysis revealed that characteristic diffraction peaks of polypyrrole and Co appeared at the same time in nanocomposites. FT-IR analysis indicated a successful conjugation of Co particles with polypyrrole. TEM confirmed the formation of a core-shell structure with a wide particle size distribution. Magnetization measurements showed that polypyrrole coating decreased the saturation magnetization of Co significantly. With the increase of the matching thickness, the absorption peak varied towards low frequency direction. When the matching thickness was 3.0 mm, the value of the maximum reflection loss (RL) was −20.0 dB at 13.8 GHz with the 7.2 GHz bandwidth. - Highlights: • The influence of PPy on the structure of Co is discussed. • The influence of PPy on the magnetic properties of Co is discussed. • The influence of PPy on the absorption property of Co is discussed. • PPy/Co possessed the excellent absorption property.

  13. Influence of Laser Prepulse in Ultra-short Laser-Driven Proton Acceleration

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Influence of laser prepulse in ultra-short laser-driven proton acceleration was investigated by the differences in spatial distribution and energy spectrum between different foil-targets. The laser system produced pulses having energies of up to

  14. The effects of insulating coatings and current prepulse on tungsten planar wire array Z-pinches

    Energy Technology Data Exchange (ETDEWEB)

    Li, M., E-mail: limo@nint.ac.cn; Li, Y. [State Key Laboratory of Electrical Insulation and Power Equipment, Xi' an Jiaotong University, Shaanxi 710049 (China); State Key Laboratory of Intense Pulsed Radiation Simulation and Effect, Northwest Institute of Nuclear Technology, Xi' an 710024 (China); Sheng, L.; Wang, L. P.; Zhao, C.; Yuan, Y.; Zhang, X. J.; Zhang, M.; Peng, B. D.; Zhang, J. H.; Zhang, S. G.; Qiu, M. T. [State Key Laboratory of Intense Pulsed Radiation Simulation and Effect, Northwest Institute of Nuclear Technology, Xi' an 710024 (China); Li, X. W. [State Key Laboratory of Electrical Insulation and Power Equipment, Xi' an Jiaotong University, Shaanxi 710049 (China)

    2015-12-15

    This paper presents experimental results on the effects of insulating coatings and current prepulse on tungsten planar wire array Z-pinches on ∼100 ns main current facility. Optical framing images indicated that without a current prepulse the wire ablation process was asymmetrical and the implosion was zippered. The x-ray peak power was ∼320 GW. By using insulating coatings on the wire surface the asymmetry remained, and the processes of ablation and implosion were delayed by ∼30 ns. The x-ray burst was narrow and decreased to ∼200 GW. When current prepulses were used on both standard and insulated wire arrays, implosion symmetry was improved and the x-ray burst was improved (to ∼520 GW peak power). In addition, there was a strong emitting precursor column for insulated loads with the current prepulse.

  15. OntoPIN: an ontology-annotated PPI database.

    Science.gov (United States)

    Guzzi, Pietro Hiram; Veltri, Pierangelo; Cannataro, Mario

    2013-09-01

    Protein-protein interaction (PPI) data stored in publicly available databases are queried by the use of simple query interfaces allowing only key-based queries. A typical query on such databases is based on the use of protein identifiers and enables the retrieval of one or more proteins. Nevertheless, a lot of biological information is available and is spread on different sources and encoded in different ontologies such as Gene Ontology. The integration of existing PPI databases and biological information may result in richer querying interfaces and successively could enable the development of novel algorithms that may use biological information. The OntoPIN project showed the effectiveness of the introduction of a framework for the ontology-based management and querying of Protein-Protein Interaction Data. The OntoPIN framework first merges PPI data with annotations extracted from existing ontologies (e.g. Gene Ontology) and stores annotated data into a database. Then, a semantic-based query interface enables users to query these data by using biological concepts. OntoPIN allows: (a) to extend existing PPI databases by using ontologies, (b) to enable a key-based querying of annotated data, and (c) to offer a novel query interface based on semantic similarity among annotations.

  16. Pedot and PPy Conducting Polymer Bilayer and Trilayer Actuators

    DEFF Research Database (Denmark)

    Zainudeen, Umer Lebbe; Careem, Mohamed Abdul; Skaarup, Steen

    2008-01-01

    Actuators based on conducting polymers are attracting increasing interest due to their desirable features such as large mechanical stress generated, sufficient maximum strain values, high reversibility, good safety properties and the possibility of precise control using small voltages. Many...... attempts have been made to improve the actuator performance. We report electromechanical measurements on actuators of bilayer and trilayer free standing films prepared with polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymers. Both types of conducting polymer are pre...

  17. Analisis Sedimentasi di Pelabuhan Pendaratan Ikan (PPI Logending

    Directory of Open Access Journals (Sweden)

    Sanidhya Nika Purnomo

    2015-04-01

    Full Text Available Pelabuhan Pendaratan Ikan (PPI Logending merupakan pelabuhan ikan yang dibangun di muara Sungai Ijo. Karena terletak di muara sungai, PPI tersebut sangat rawan terhadap sedimentasi yang dipengaruhi debit aliran sungai dari bagian hulu dan pasang surut air laut dari bagian hilir. Analisis sedimentasi di PPI Logending didahului dengan pengambilan data primer seperti data kecepatan aliran, sampel sedimen, dan potongan melintang sungai, serta data sekunder berupa data pasang surut di perairan Cilacap yang diperoleh dari BMKG Cilacap. Dengan menggunakan data tersebut, selanjutnya dilakukan analisis sedimentasi menggunakan software HEC-RAS berdasarkan pada Persamaan Ackers – White, Meyer – Peter Müller, dan Wilcock. Hasil dari simulasi menunjukkan bahwa Persamaan Meyer – Peter Müller dan Wilcock memberikan kesesuaian yang lebih baik dengan kondisi di lapangan daripada Persamaan Ackers - White, dimana pada tampang 3 (hulu terjadi erosi, sedangkan pada tampang 2 (tengah dan tampang 1 (hilir mengalami deposisi. Adanya proses deposisi yang signifikan di mulut sungai mengindikasikan perlunya pengerukan untuk pemeliharaan (maintenance dredging secara periodik yang seharusnya mendapat perhatian dari pihak pengelola pelabuhan.

  18. Effect of resistance to sintering on Pt/PPy-MWCNT catalysts for PEM fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. [Yonsei Univ., Seoul (Korea, Republic of). Specialized Graduate School of Hydrogen and Fuel Cell; Kim, H. [Yonsei Univ., Seoul (Korea, Republic of). Dept. of Chemical and Biomolecular Engineering

    2010-07-01

    Recent studies have suggested that platinum (Pt) growth contributes to the degradation of fuel cell performance, as the electrochemical surface area of Pt is decreased when the particles increase in size. This study investigated the effect of inhibition to the sintering effect and uniform dispersion of Pt in a polypyrrole(Pp) multiwalled carbon nanotube (MWCNT) composite supported Pt catalyst. The sintering effect was investigated under half-cell conditions using a 0.5M sulfuric acid (H{sub 2}SO{sub 4}) electrolyte with cyclic voltammetry ranging from 0 to 1.2 V with a 5 mV per second sweep rate. The hydrogen desorption peak was carried out from the charge under the electrochemically active surface area at 4000 cycle periods. The study showed that coating the MWCNT with Ppy showed higher Pt distribution and a lower Pt sintering effect. The results were attributed to the rough surface characteristics obtained using the Ppy. Results also indicated that the catalytic activity for the oxygen reduction reaction increased by improving the interaction and stability of the Pt. 1 ref.

  19. Role of pre-pulses in the interaction of intense, ultrashort lasers with structured surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Rajeev, P.P.; Kahaly, S.; Bagchi, S.; Bose, S.; Kiran, P.P.; Ayyub, P.; Ravindra Kumar, G. [Tata Institute of Fundamental Research, Mumbai (India)

    2006-06-15

    We examine enhanced hard X-ray emission (20 - 200 keV) from plasmas produced on nano-particles coated optically polished copper surface under different prepulse conditions. We observe that enhancement reduces with increasing prepulse intensity. The dynamics of the process is seen to be in the picosecond regime. We attribute this to pre-plasma formation on nano-particles and subsequent modification/destruction of the nano-structure layer before the arrival of the main pulse. It is suggested that high-contrast ultrashort pulses are essential for nano-particles to function as yield enhancer. (authors)

  20. Enhancement of Thermal Stability and Cycling Performance of Lithium-Ion Battery at High Temperature by Nano-ppy/OMMT-Coated Separator

    Directory of Open Access Journals (Sweden)

    Shuo Yang

    2017-01-01

    Full Text Available Nanopolypyrrole/organic montmorillonite- (nano-ppy/OMMT- coated separator is prepared by coating nano-ppy/OMMT on the surface of polyethylene (PE. Nano-ppy/OMMT-coated separator with three-dimensional and multilayered network structure is beneficial to absorb more organic electrolyte, enhancing the ionic conductivity (reach 4.31 mS·cm-1. Meanwhile, the composite separator exhibits excellent thermal stability and mechanical properties. The strong covalent bonds (Si-F are formed by the nucleophilic substitution reaction between F− from the thermal decomposition and hydrolysis of LiPF6 and the covalent bonds (Si-O of nano-ppy/OMMT. The Si-F can effectively prevent the formation of HF, POF3, and LiF, resulting in the inhibition of the disproportionation of Mn3+ in LiNi1/3Co1/3Mn1/3O2 material as well as reducing the internal resistance of the cell. Therefore, the nano-ppy/OMMT-coated separator exhibits outstanding capacity retention and cycling performance at 80°C.

  1. Naked-eye sensitive detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) based on a horseradish peroxidase catalytic colorimetric system with Cu(ii).

    Science.gov (United States)

    Shi, Dongmin; Sun, Yue; Lin, Lin; Shi, Chunjun; Wang, Guangfeng; Zhang, Xiaojun

    2016-10-07

    In this paper, a novel colorimetric method for the detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) was designed based on a Cu(2+)-horseradish peroxidase (HRP)-3,3',5,5'-tetra-methylbenzidine (TMB)-H2O2 system. In the presence of ALP, l-ascorbic acid-2-phosphate (AAP) could be hydrolyzed to ascorbic acid which could reduce Cu(2+) to Cu(+) to inhibit the enzymatic activity of HRP in the colorimetric system. The change in absorbance was found to be proportional to the ALP concentration with a linear detection range and a limit of detection of 5.4 mU mL(-1). In the presence of PPi, because Cu(2+) was chelated by PPi, the conversion of Cu(ii) by AA was effectively inhibited. The color of the HRP-TMB-H2O2 system with Cu(2+) showed blue. The HRP-TMB-H2O2 system with the Cu(2+) colorimetric system could also detect PPi with a satisfying result. In summary, this method possesses sensitivity, reproducibility, and cost-effectiveness without labelling and separation and the use of a colorimetric method is more in line with the requirements of on-site detection and green chemistry.

  2. APLIKASI PPI8255 DALAM SISTEM ANTRIAN ELEKTRONIK BERBASIS KOMPUTER

    Directory of Open Access Journals (Sweden)

    I Gst. Ag. Pt. Raka Agung

    2009-05-01

    Full Text Available Teknologi perangkat kontrol berkembang sangat pesat, mengikuti kebutuhan hidup manusia. Perangkat kontrol semakin banyak dibutuhkan untuk membantu manusia dalam kehidupan sehari-hari. Telah diketahui bersama, bahwa komputer dapat dimanfaatkan untuk berbagai keperluan, diantaranya sebagai pusat kontrol peralatan-peralatan tertentu yang diantarmukakan pada port masukkan dan keluaran (I/O port. Dengan perantaraan IC PPI 8255 dapat dibuat suatu sistem antrian berbasis komputer. Komponen pendukung lainnya adalah driver sevensegment, display seven segmen, printer, sound card dan saklar tekan, dengan memakai bahasa pemrograman Delphi. Dengan menggunakan sistem antrian ini diharapkan dapat membantu kenyamanan dan ketertiban suatu antrian pada pelayanan publik yang ramai. Aplikasi sistem ini adalah pada antrian layanan bank, rumah sakit, ataupun jasa layanan umum lainnya

  3. Simple and rapid synthesis of NiO/PPy thin films with improved electrochromic performance

    Energy Technology Data Exchange (ETDEWEB)

    Sonavane, A.C. [Thin Film Materials Laboratory, Department of Physics, Shivaji University, Kolhapur 416 004 (India); Inamdar, A.I. [Thin Film Materials Laboratory, Department of Physics, Shivaji University, Kolhapur 416 004 (India); Department of Semiconductor Science, Dongguk University, Seoul 100-715 (Korea, Republic of); Dalavi, D.S. [Thin Film Materials Laboratory, Department of Physics, Shivaji University, Kolhapur 416 004 (India); Deshmukh, H.P. [Department of Physics, Y.M. College, Bharati Vidyapeeth, Erandwane, Pune (India); Patil, P.S., E-mail: psp_phy@unishivaji.ac.i [Thin Film Materials Laboratory, Department of Physics, Shivaji University, Kolhapur 416 004 (India)

    2010-02-28

    Nickel oxide/polypyrrole (NiO/PPy) thin films were deposited by a two step process in which the NiO layer was electrodeposited potentiostatically from an aqueous solution of NiCl{sub 2}.6H{sub 2}O at pH 7.5 on fluorine doped tin oxide (FTO) coated conducting glass substrates, followed by the deposition of polypyrrole (PPy) thin films by chemical bath deposition (CBD) from pyrrole mixed with ammonium persulfate (APS). The NiO/PPy films were further characterized for their structural, optical, morphological and electrochromic properties. X-ray diffraction study indicates that the films composed of polycrystalline NiO and amorphous PPy. Infrared transmission spectrum reveals chemical bonding between NiO and PPy. Rectangular faceted grains were observed from scanning electron microscopy results. The electrochromic (EC) property of the film was studied using cyclic voltammogram (CV), chronoamperometry (CA) and optical modulation. The NiO/PPy presents superior EC properties than their individual counterparts. The coloration/bleaching kinetics (response time of few ms) and coloration efficiency (358 cm{sup 2}/C) were found to be improved appreciably. The dramatic improvement in electrochemical stability (from about 500 c/b cycles for PPy to 10,000 c/b cycles for NiO/PPy) was observed. This work therefore demonstrates a cost-effective and simple way of depositing highly efficient, faster and stable NiO/PPy electrodes for EC devices.

  4. Hohlraum glint and laser pre-pulse detector for NIF experiments using velocity interferometer system for any reflector.

    Science.gov (United States)

    Moody, J D; Clancy, T J; Frieders, G; Celliers, P M; Ralph, J; Turnbull, D P

    2014-11-01

    Laser pre-pulse and early-time laser reflection from the hohlraum wall onto the capsule (termed "glint") can cause capsule imprint and unwanted early-time shocks on indirect drive implosion experiments. In a minor modification to the existing velocity interferometer system for any reflector diagnostic on NIF a fast-response vacuum photodiode was added to detect this light. The measurements show evidence of laser pre-pulse and possible light reflection off the hohlraum wall and onto the capsule.

  5. Limitation on Pre-pulse Level for Cone-Guided Fast-Ignition ICF

    Energy Technology Data Exchange (ETDEWEB)

    MacPhee, A G; Akli, K U; Beg, F N; Chen, C D; Chen, H; Divol, L; Hey, D S; Freeman, R R; Henesian, M; Kemp, A J; Key, M H; Pape, S L; Link, A; Ma, T; Mackinnon, A J; Ovchinnikov, V M; Patel, P K; Phillips, T W; Stephens, R B; Tabak, M; Town, R; Van Woerkom, L D; Wei, M S; Wilks, S C

    2009-09-01

    The viability of fast-ignition (FI) inertial confinement fusion hinges on the efficient transfer of laser energy to the compressed fuel via multi-MeV electrons. Pre-formed plasma due to laser pre-pulse strongly influences ultra-intense laser plasma interactions and hot electron generation in the hollow cone of an FI target. We induced a prepulse and consequent preplasma in copper cone targets and measured the energy deposition zone of the main pulse by imaging the emitted K{sub {alpha}} radiation. An integrated simulation of radiation hydrodynamics for the pre-plasma and particle in cell for the main pulse interactions agree well with the measured deposition zones and provide an insight into the enrgy deposition mechanism and electron distribution. It was demonstrated that a under these conditions a 100mJ pre-pulse completely eliminates the forward going component of {approx}2-4MeV electrons. Consequences for cone-guided fast-ignition are discussed.

  6. Investigation of pre-pulse pumping laser for preserving temporal waveform of stimulated Raman scattering

    Science.gov (United States)

    Chen, Junchi; Su, Hongpeng; Peng, Yujie; Guo, Xiaoyang; Wang, Zhanshan; Leng, Yuxin

    2017-01-01

    A modified polarized beam combination technique is proposed for preserving the temporal waveforms of stimulated Raman scattering. 1064 nm pre-pulse pumping lasers prior to the main pumping laser with a delay time are generated and injected into a Ba(NO3)2 Raman medium to excite the crystal firstly. The influences of pre-pulse lasers with various energy levels on the temporal shapes of Raman lasers are investigated, and it is demonstrated that the temporal waveforms of the Raman laser are distorted once the energies of the pre-pulse are below and above the required energy for preserving the temporal shapes of Stokes radiation. It is also discovered that the temporal shape of the 1197 nm Raman laser cannot be perfectly preserved if the energy of the 1064 nm main laser is too low or the relative delay time is too large. Moreover, the optical conversion efficiency and Stokes laser energy obtained under pumping lasers with single and double intensity peaks are compared.

  7. SnO2/PPy Screen-Printed Multilayer CO2 Gas Sensor

    Directory of Open Access Journals (Sweden)

    S.A. WAGHULEY

    2007-05-01

    Full Text Available Tin dioxide (SnO2 plays a dominant role in solid state gas sensors and exhibit sensitivity towards oxidizing and reducing gases by a variation of its electrical properties. The electrical conducting polymer-polypyrrole (PPy has high anisotropy of electrical conduction and used as a gas sensor. SnO2/PPy multilayer, pure SnO2, pure PPy sensors were prepared by screen-printing method on Al2O3 layer followed by glass substrate. The sensors were used for different concentration (ppm of CO2 gas investigation at room temperature (303 K. The sensitivity of SnO2/PPy multilayer sensor was found to be higher, compared with pure SnO2 and pure PPy sensors. The multilayer sensor exhibited improved stability. The response and recovery time of multilayer sensor were found to be ~2 min and ~10 min respectively.

  8. Does the Sustainable PPI Investments Promote Financial Market’s Sustainable Development?

    Directory of Open Access Journals (Sweden)

    Tong Fu

    2016-01-01

    Full Text Available Since the late 1980s, most developing countries adopt a policy of attracting investments for Private Participation in Infrastructure (PPI projects. With a perspective of sustainability, this paper offers a first attempt to examine whether the sustainable PPI investments promote financial market development. First, we demonstrate how the PPI policy enlargers the size of financial markets and then fosters the liquidity of financial markets in the static and dynamic conditions. Using the data from 33 developing countries during 1997–2012, we discover the significant promotion effect of PPI investments on the development of financial markets in the dimensions of size and liquidity. Additionally, we confirm the significant mediator effect of financial market size for the positive relationship between PPI investments and financial market liquidity. Both the promotion effect and mediation effect are robust to different control variables and estimation techniques used.

  9. Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats

    DEFF Research Database (Denmark)

    Sandager-Nielsen, Karin; Andersen, Maibritt B; Sager, Thomas N;

    2004-01-01

    . Anoxia was experimentally induced by placing 9-day-old rat pups for 6 min in a chamber saturated with 100% nitrogen (N(2)). Exposure to anoxia on postnatal day (PND) 9 resulted in significantly reduced subcortical dopamine metabolism and turnover, as measured by striatal 3,4-dihydroxyphenylacetic acid...

  10. Assessing the Comprehensive Soldier Fitness Program: Measuring Startle Response and Prepulse Inhibition

    Science.gov (United States)

    2011-04-01

    illness. PTSD is associated with greater psychiatric co-morbidity and attempted suicide, increased frequency of bronchial asthma, hypertension , peptic...Changes in the Aftermath of Crisis ( pp. 215-238). Mahwah, N.J.: Lawrence Erlbaum Associates Publishers. This article suggests the reality and...greater psychiatric comorbidity and attempted suicide, increased frequency of bronchial asthma, hypertension , peptic ulcer and impaired social support

  11. Influence of disordered morphology on electrochromic stability of WO{sub 3}/PPy

    Energy Technology Data Exchange (ETDEWEB)

    Gaikwad, Digambar K. [D. Y. Patil College of Engineering & Technology, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India); Mali, Sawanta S.; Hong, Chang K. [Polymer Energy Materials Laboratory, Department of Advanced Chemical Engineering, Chonnam National University, Gwangju, 500-757 (Korea, Republic of); Kadam, Anamika V., E-mail: anamikasonavane@rediff.com [D. Y. Patil College of Engineering & Technology, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India); D.Y. Patil Medical University, Kasaba Bawada, Kolhapur, 416006, Maharashtra (India)

    2016-06-05

    Tungsten oxide (WO{sub 3}) films are critical for smart windows because of their capacity of varying the throughput of visible light and solar energy. This study highlights the evolution of structural and morphological changes of electrodeposited WO{sub 3} thin films coated with polypyrrole (PPy) by using chemical bath deposition. The structural and surface properties of WO{sub 3} thin films were studied using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrochemical stability was inspected using repetitive cyclic voltammetry (CV) cycles for each sample in LiClO{sub 4}-PC electrolyte for prolonged periods. The results showed an improvement in the electrochemical stability after the CV study. - Graphical abstract: Mechanism: A schematic of the mechanism is proposed in above fig. The mechanism is based on three step process: (i) WO{sub 3} coated on ITO by electrodeposition followed by thermal treatment. It produces ordered nanoarrayed morphology. (ii) A second step involving deposition of PPy by chemical bath deposition on ITO. It possesses globular morphology. (iii) When PPy coated on WO{sub 3}, PPy applies shearing force on WO{sub 3} and produces disordered nanoarrayed morphology. - Highlights: • Nanoarrayed WO{sub 3}/PPy composite was synthesized. • Interplanar spacing enhances due to PPy coating. • PPy applies shearing force on WO{sub 3} produces disordered morphology. • Nanocomposite showed high stability in LiClO{sub 4}-PC.

  12. Electrochemical Behaviour of a PPy(DBS)/Polyacrylonitrile (PAN):LITF:EC:PC/ Li Cell

    DEFF Research Database (Denmark)

    Vidanapathirana, K.; Skaarup, Steen; West, K.

    2006-01-01

    The electrochemical behaviour of Li rechargeable cells with Polypyrrole (PPy) as the cathode material was investigated using cyclic voltammetry. The PPy used was doped with the large surfactant anion dodecyl benzenesulphonate (DBS-). The cells were constructed with PAN:LiTF:EC:PC gel electrolyte...... with Li as anode. The results indicate that during the first reduction, cations are inserted into the PPy film forming LiDBS neutral salt. During the next oxidation/reduction cycles, the mechanism then switches to anion movement. Cyclic voltammetry studies also verified that complete electrochemical...

  13. Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

    Science.gov (United States)

    Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

    2016-01-01

    Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID:27282261

  14. Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy.

    Science.gov (United States)

    Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

    2016-11-15

    The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

  15. Small-Molecule Stabilization of the 14-3-3/Gab2 Protein-Protein Interaction (PPI) Interface.

    Science.gov (United States)

    Bier, David; Bartel, Maria; Sies, Katharina; Halbach, Sebastian; Higuchi, Yusuke; Haranosono, Yu; Brummer, Tilman; Kato, Nobuo; Ottmann, Christian

    2016-04-19

    Small-molecule modulation of protein-protein interactions (PPIs) is one of the most promising new areas in drug discovery. In the vast majority of cases only inhibition or disruption of PPIs is realized, whereas the complementary strategy of targeted stabilization of PPIs is clearly under-represented. Here, we report the example of a semi-synthetic natural product derivative--ISIR-005--that stabilizes the cancer-relevant interaction of the adaptor protein 14-3-3 and Gab2. The crystal structure of ISIR-005 in complex with 14-3-3 and the binding motif of Gab2 comprising two phosphorylation sites (Gab2pS210pT391) showed how the stabilizing molecule binds to the rim-of-the-interface of the protein complex. Only in the direct vicinity of 14-3-3/Gab2pT391 site is a pre-formed pocket occupied by ISIR-005; binding of the Gab2pS210 motif to 14-3-3 does not create an interface pocket suitable for the molecule. Accordingly, ISIR-005 only stabilizes the binding of the Gab2pT391 but not the Gab2pS210 site. This study represents structural and biochemical proof of the druggability of the 14-3-3/Gab2 PPI interface with important implications for the development of PPI stabilizers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. High-efficiency palladium catalysts supported on ppy-modified C60 for formic acid oxidation.

    Science.gov (United States)

    Bai, Zhengyu; Yang, Lin; Guo, Yuming; Zheng, Zhi; Hu, Chuangang; Xu, Pengle

    2011-02-14

    A facile preparation of polypyrrole-modified fullerene supported Pd nanoparticles catalyst is introduced; electrochemical measurements demonstrate that the obtained Pd/ppy-C(60) catalyst shows a good electrocatalytic activity and stability for the oxidation of formic acid.

  17. HomPPI: a class of sequence homology based protein-protein interface prediction methods

    Directory of Open Access Journals (Sweden)

    Dobbs Drena

    2011-06-01

    Full Text Available Abstract Background Although homology-based methods are among the most widely used methods for predicting the structure and function of proteins, the question as to whether interface sequence conservation can be effectively exploited in predicting protein-protein interfaces has been a subject of debate. Results We studied more than 300,000 pair-wise alignments of protein sequences from structurally characterized protein complexes, including both obligate and transient complexes. We identified sequence similarity criteria required for accurate homology-based inference of interface residues in a query protein sequence. Based on these analyses, we developed HomPPI, a class of sequence homology-based methods for predicting protein-protein interface residues. We present two variants of HomPPI: (i NPS-HomPPI (Non partner-specific HomPPI, which can be used to predict interface residues of a query protein in the absence of knowledge of the interaction partner; and (ii PS-HomPPI (Partner-specific HomPPI, which can be used to predict the interface residues of a query protein with a specific target protein. Our experiments on a benchmark dataset of obligate homodimeric complexes show that NPS-HomPPI can reliably predict protein-protein interface residues in a given protein, with an average correlation coefficient (CC of 0.76, sensitivity of 0.83, and specificity of 0.78, when sequence homologs of the query protein can be reliably identified. NPS-HomPPI also reliably predicts the interface residues of intrinsically disordered proteins. Our experiments suggest that NPS-HomPPI is competitive with several state-of-the-art interface prediction servers including those that exploit the structure of the query proteins. The partner-specific classifier, PS-HomPPI can, on a large dataset of transient complexes, predict the interface residues of a query protein with a specific target, with a CC of 0.65, sensitivity of 0.69, and specificity of 0.70, when homologs of

  18. Sonoelectrochemical Synthesis of PPy-MWCNTs-Chitosan Nanocomposite Coatings: Characterization and Corrosion Behavior

    Science.gov (United States)

    Ashassi-Sorkhabi, Habib; Bagheri, Robabeh; Rezaei-moghadam, Babak

    2015-01-01

    This study investigated the effect of co-incorporation of a kind of nanomaterials and organic additives in a polymer matrix coating on corrosion performance of St-12 steel. We synthesized sonoelectrochemically the polypyrrole (PPy), polypyrrole/chitosan (PPy-chitosan), polypyrrole/multiwalled carbon nanotubes (PPy/MWCNTs), and polypyrrole/MWCNTs/chitosan (PPy-MWCNTs-chitosan) films on the base alloy. In-situ polymerization carried out in a solution containing 0.1 mol/L oxalic acid, 100 mg/L dodecylbenzen sulfonic acid, and 0.1 mol/L pyrrole in the absence and presence of a certain amount of MWCNTs and chitosan. The corrosion protection behavior of the synthesized coatings in 3.5% NaCl aqueous solution was studied by the evolution of the open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy techniques. The results revealed that PPy-MWCNTs-chitosan nanocomposite coating exhibits significantly better corrosion protection than others. The PPy-MWCNTs-chitosan film acts as a physical barrier against the corrosive species, because it has a very dense and more compact structure. The surface morphology was investigated by scanning electron microscopy.

  19. iPPI-DB: an online database of modulators of protein-protein interactions.

    Science.gov (United States)

    Labbé, Céline M; Kuenemann, Mélaine A; Zarzycka, Barbara; Vriend, Gert; Nicolaes, Gerry A F; Lagorce, David; Miteva, Maria A; Villoutreix, Bruno O; Sperandio, Olivier

    2016-01-01

    In order to boost the identification of low-molecular-weight drugs on protein-protein interactions (PPI), it is essential to properly collect and annotate experimental data about successful examples. This provides the scientific community with the necessary information to derive trends about privileged physicochemical properties and chemotypes that maximize the likelihood of promoting a given chemical probe to the most advanced stages of development. To this end we have developed iPPI-DB (freely accessible at http://www.ippidb.cdithem.fr), a database that contains the structure, some physicochemical characteristics, the pharmacological data and the profile of the PPI targets of several hundreds modulators of protein-protein interactions. iPPI-DB is accessible through a web application and can be queried according to two general approaches: using physicochemical/pharmacological criteria; or by chemical similarity to a user-defined structure input. In both cases the results are displayed as a sortable and exportable datasheet with links to external databases such as Uniprot, PubMed. Furthermore each compound in the table has a link to an individual ID card that contains its physicochemical and pharmacological profile derived from iPPI-DB data. This includes information about its binding data, ligand and lipophilic efficiencies, location in the PPI chemical space, and importantly similarity with known drugs, and links to external databases like PubChem, and ChEMBL.

  20. PpiA, a surface PPIase of the cyclophilin family in Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Nicolas Trémillon

    Full Text Available BACKGROUND: Protein folding in the envelope is a crucial limiting step of protein export and secretion. In order to better understand this process in Lactococcus lactis, a lactic acid bacterium, genes encoding putative exported folding factors like Peptidyl Prolyl Isomerases (PPIases were searched for in lactococcal genomes. RESULTS: In L. lactis, a new putative membrane PPIase of the cyclophilin subfamily, PpiA, was identified and characterized. ppiA gene was found to be constitutively expressed under normal and stress (heat shock, H(2O(2 conditions. Under normal conditions, PpiA protein was synthesized and released from intact cells by an exogenously added protease, showing that it was exposed at the cell surface. No obvious phenotype could be associated to a ppiA mutant strain under several laboratory conditions including stress conditions, except a very low sensitivity to H(2O(2. Induction of a ppiA copy provided in trans had no effect i on the thermosensitivity of an mutant strain deficient for the lactococcal surface protease HtrA and ii on the secretion and stability on four exported proteins (a highly degraded hybrid protein and three heterologous secreted proteins in an otherwise wild-type strain background. However, a recombinant soluble form of PpiA that had been produced and secreted in L. lactis and purified from a culture supernatant displayed both PPIase and chaperone activities. CONCLUSIONS: Although L. lactis PpiA, a protein produced and exposed at the cell surface under normal conditions, displayed a very moderate role in vivo, it was found, as a recombinant soluble form, to be endowed with folding activities in vitro.

  1. Dramatic enhancement of organics degradation and electricity generation via strengthening superoxide radical by using a novel 3D AQS/PPy-GF cathode.

    Science.gov (United States)

    Zhang, Yan; Li, Jinhua; Bai, Jing; Li, Linsen; Xia, Ligang; Chen, Shuai; Zhou, Baoxue

    2017-08-24

    A dramatic enhancement of organics degradation and electricity generation has been achieved in a wastewater fuel cell (WFC) system via strengthening superoxide radical with radical chain reaction by using a novel 3D anthraquinone/polypyrrole modified graphite felt (AQS/PPy-GF) cathode. The AQS/PPy-GF was synthesized by one-pot electrochemical polymerization method and used to in-situ generate superoxide radical by reducing oxygen under self-imposed electric field. Results showed that methyl orange (MO) were effectively degraded in AQS/PPy-GF/Fe(2+) system with a high apparent rate constant (0.0677 min(-1)), which was 3.9 times that (0.0174 min(-1)) in the Pt/Fe(2+) system and even 9.4 times that (0.0072 min(-1)) in the traditional WFC system (without Fe(2+)). Meanwhile, it showed a superior performance for electricity generation and the maximum power density output (1.130 mW cm(-2)) was nearly 3.3 times and 5.0 times higher, respectively, when compared with the Pt/Fe(2+) system and traditional WFC. This dramatic advance was attributed to 3D AQS/PPy-GF cathode which produces more O2(-) via one-electron reduction process. The presence of O2(-) cannot only directly contribute to MO degradation, but also promotes the final complete mineralization by turning itself to OH. Additionally, O2(-) accelerates the Fe(2+)/Fe(3+) couple cycling, thus avoiding continuous addition of any external ferrous ions. Inhibition and probe studies were conducted to ascertain the role of several radicals (OH and O2(-)) on the MO degradation. Superoxide radicals were considered as the primary reactive oxidants, and the degradation mechanism of MO was proposed. The proposed WFC system provides a more economical and efficient way for energy recovery and wastewater treatment. Copyright © 2017. Published by Elsevier Ltd.

  2. PPI finder: a mining tool for human protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Min He

    Full Text Available BACKGROUND: The exponential increase of published biomedical literature prompts the use of text mining tools to manage the information overload automatically. One of the most common applications is to mine protein-protein interactions (PPIs from PubMed abstracts. Currently, most tools in mining PPIs from literature are using co-occurrence-based approaches or rule-based approaches. Hybrid methods (frame-based approaches by combining these two methods may have better performance in predicting PPIs. However, the predicted PPIs from these methods are rarely evaluated by known PPI databases and co-occurred terms in Gene Ontology (GO database. METHODOLOGY/PRINCIPAL FINDINGS: We here developed a web-based tool, PPI Finder, to mine human PPIs from PubMed abstracts based on their co-occurrences and interaction words, followed by evidences in human PPI databases and shared terms in GO database. Only 28% of the co-occurred pairs in PubMed abstracts appeared in any of the commonly used human PPI databases (HPRD, BioGRID and BIND. On the other hand, of the known PPIs in HPRD, 69% showed co-occurrences in the literature, and 65% shared GO terms. CONCLUSIONS: PPI Finder provides a useful tool for biologists to uncover potential novel PPIs. It is freely accessible at http://liweilab.genetics.ac.cn/tm/.

  3. Fabrication of ternary CNT/PPy/KxMnO2 composite nanowires for electrocatalytic applications.

    Science.gov (United States)

    Zheng, Tian; Lu, Xiaofeng; Bian, Xiujie; Zhang, Chengcheng; Xue, Yanpeng; Jia, Xiaoteng; Wang, Ce

    2012-02-15

    CNT/PPy/K(x)MnO(2), a novel ternary core-shell nanowires, was successfully prepared by a two-step self-assembly method and utilized as an electrocatalyst for the oxidation of hydrogen peroxide. The as-synthesized products were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX) spectroscopy and Fourier-transform infrared spectra (FTIR) measurements. The results exhibited that the K(x)MnO(2) nanosheets were grown on the surface of CNT/PPy core-shell nanotubes. The planes of the K(x)MnO(2) nanosheets were more or less perpendicular to the CNT/PPy nanotubes. Cyclic voltammetry (CV) results demonstrated that the CNT/PPy/K(x)MnO(2) composite nanowires, as a nonenzyme catalyst, performed well with regards to the oxidation of hydrogen peroxide in 0.1M phosphate buffer solution (pH 7.0). The composite had a fast response with a linear range of 5.0 μM to 9.7 mM and a relatively low detection limit of 2.4 μM (S/N=3). The sensitivity of the sensor for H(2)O(2) was 114.6 μA mM(-1)cm(-2). These excellent properties might be due to the large surface area of the composite nanowires and the quick electron transfer promoted by the combination of CNT and PPy.

  4. Oxadiazole-carbazole polymer (POC)-Ir(ppy)3 tunable emitting composites

    Science.gov (United States)

    Bruno, Annalisa; Borriello, Carmela; Di Luccio, Tiziana; Sessa, Lucia; Concilio, Simona; Haque, Saif A.; Minarini, Carla

    2017-04-01

    POC polymer is an oxadiazole-carbazole copolymer we have previously synthetized and established as light emitting material in Organic Light Emitting Devices (OLEDs), although POC quantum yield emission efficiency and color purity still need to be enhanced. On the other hand, tris[2-phenylpyridinato-C2,N]iridium(III) (Ir(ppy)3) complexes, namely Ir(ppy)3 are among the brightest luminophores employed in green light emitting devices. Our aim, in this work, is to take advantage of Ir(ppy)3 bright emission by combining the Ir complex with blue emitting POC to obtain tunable light emitting composites over a wide range of the visible spectrum. Here we have investigated the optical proprieties POC based nanocomposites with different concentrations of Ir(ppy)3, ranging from 1 to 10 wt%. Both spectral and time resolved fluorescence measurements show an efficient energy transfer from the polymer to the dopants, resulting in white-emitting composites. The most intense and stable emission has been found when POC was doped with about 5 wt% concentration of Ir(ppy)3.

  5. The Ampakine CX546 Restores the Prepulse Inhibition and Latent Inhibition Deficits in mGluR5-Deficient Mice

    National Research Council Canada - National Science Library

    Lipina, Tatiana; Weiss, Karin; Roder, John

    2007-01-01

    ...) as measured in a thirst-motivated conditioned emotional response procedure. Administration of the positive modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPAR...

  6. Maximum likelihood inference of the evolutionary history of a PPI network from the duplication history of its proteins.

    Science.gov (United States)

    Li, Si; Choi, Kwok Pui; Wu, Taoyang; Zhang, Louxin

    2013-01-01

    Evolutionary history of protein-protein interaction (PPI) networks provides valuable insight into molecular mechanisms of network growth. In this paper, we study how to infer the evolutionary history of a PPI network from its protein duplication relationship. We show that for a plausible evolutionary history of a PPI network, its relative quality, measured by the so-called loss number, is independent of the growth parameters of the network and can be computed efficiently. This finding leads us to propose two fast maximum likelihood algorithms to infer the evolutionary history of a PPI network given the duplication history of its proteins. Simulation studies demonstrated that our approach, which takes advantage of protein duplication information, outperforms NetArch, the first maximum likelihood algorithm for PPI network history reconstruction. Using the proposed method, we studied the topological change of the PPI networks of the yeast, fruitfly, and worm.

  7. Corrosion Protection Properties of PPy-ND Composite Coating: Sonoelectrochemical Synthesis and Design of Experiment

    Science.gov (United States)

    Ashassi-Sorkhabi, H.; Bagheri, R.; Rezaei-Moghadam, B.

    2016-02-01

    In this research, the nanocomposite coatings comprising the polypyrrole-nanodiamond, PPy-ND, on St-12 steel electrodes were electro-synthesized using in situ polymerization process under ultrasonic irradiation. The corrosion protection performance and morphology characterization of prepared coatings were investigated by electrochemical methods and scanning electron microscopy, SEM, respectively. Also, the experimental design was employed to determine the best values considering the effective parameters such as the concentration of nanoparticles, the applied current density and synthesis time to achieve the most protective films. A response surface methodology, RSM, involving a central composite design, CCD, was applied to the modeling and optimization of the PPy-ND nanocomposite deposition. Pareto graphic analysis of the parameters indicated that the applied current density and some of the interactions were effective on the response. The electrochemical results proved that the embedment of diamond nanoparticle, DNP, improves the corrosion resistance of PPy coatings significantly. Therefore, desirable correlation exists between predicted data and experimental results.

  8. Prepulse effects on the interaction of intense femtosecond laser pulses with high-Z solids

    Energy Technology Data Exchange (ETDEWEB)

    Zhidkov, Alexei; Sasaki, Akira; Utsumi, Takayuki; Fukumoto, Ichirou; Tajima, Toshiki; Saito, Fumikazu; Hironaka, Yoichiro; Nakamura, Kazutaka G.; Kondo, Ken-ichi; Yoshida, Masatake

    2000-11-01

    K{alpha} emission of high-Z solid targets irradiated by an intense, short (<100 fs) laser pulse in the 10 keV region is shown to be sensitive to the electron energy cutoff, which is strongly dependent on the density gradient of the plasma corona formed by a long prepulse. The absorption rate of short laser pulses, the hot electron distribution, and x-ray emission from a Cu slab target are studied via a hybrid model, which combines the hydrodynamics, collisional particle-in-cell, and Monte Carlo simulation techniques, and via a direct spectroscopic measurement. An absorption mechanism originating from the interaction of the laser pulse with plasma waves is found to increase the absorption rate by over 30% even for a very short, s-polarized laser pulse. Calculated and measured x-ray spectra are in good agreement, confirming the electron energy cutoff.

  9. The influence of plasma density decreasement by pre-pulse on the laser wakefield acceleration

    Directory of Open Access Journals (Sweden)

    Ke-Gong Dong

    2011-12-01

    Full Text Available In the laser wakefield acceleration, the generation of electron beam is very sensitive to the plasma density. Not only the laser-wakefield interaction, but also the electron trapping and acceleration would be effected by the plasma density. However, the plasma density could be changed in the experiment by different reasons, which will result in the mismatch of parameters arranged initially. Forward Raman scattering spectrum demonstrated that the interaction density was decreased obviously in the experiment, which was verified by the pre-pulse conditions and two-dimensional particle-in-cell simulations. It was demonstrated that the plasma density was very important on the self-evolutions and energy coupling of laser pulse and wakefield, and eventually the energy spectrum of electron beam.

  10. Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile X Syndrome

    Science.gov (United States)

    Yuhas, Jennifer; Cordeiro, Lisa; Tassone, Flora; Ballinger, Elizabeth; Schneider, Andrea; Long, James M.; Ornitz, Edward M.; Hessl, David

    2011-01-01

    Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS-A; n = 17), and idiopathic autism (IA; n = 15). Relative to…

  11. Viral proteins that bridge unconnected proteins and components in the human PPI network.

    Science.gov (United States)

    Rachita, H R; Nagarajaram, H A

    2014-07-29

    Viruses, despite having small genomes and few proteins, make an array of interactions with host proteins as they solely depend on host machinery for their replication and reproduction. Hence, analysis of the Human-Virus Protein-Protein Interaction Network (Hu-Vir PPI network) helps us to gain certain insights into the molecular mechanisms underlying the hijacking of host cell machinery by viruses for their perpetuation. Here we report an analysis of the Human-Virus Bridged PPI Networks that has led us to identify viral articulation points (VAPs) which connect unconnected components of the Human-PPI (Hu-PPI) network. VAPs cross-link peripheral nodes to the giant component of the Hu-PPI network. VAPs interact with a number of relatively lower topologically central human proteins and are conserved among related viruses. The linked nodes comprise of those that are mostly expressed during viral infection, as well as those that are found exclusively in some metabolic pathways, indicating that the novel viral mediation of certain human protein-protein interactions may form the basis for virus-specific tuning of the host machinery. The functional importance of VAPs and their interaction partners in virus replication make them potential drug targets against viral infection. Our investigations also led to the discovery of an example of a Human Endogenous Retrovirus (HERV) encoded protein, syncytin, as an Articulation Point (AP) in the Hu-PPI network, suggesting that VAPs may be retained in a genome if they result in any beneficial function in the host.

  12. Constructing Uniform Core-Shell PPy@PANI Composites with Tunable Shell Thickness toward Enhancement in Microwave Absorption.

    Science.gov (United States)

    Tian, Chunhua; Du, Yunchen; Xu, Ping; Qiang, Rong; Wang, Ying; Ding, Ding; Xue, Jianlei; Ma, Jun; Zhao, Hongtao; Han, Xijiang

    2015-09-16

    Highly uniform core-shell composites, polypyrrole@polyaniline (PPy@PANI), have been successfully constructed by directing the polymerization of aniline on the surface of PPy microspheres. The thickness of PANI shells, from 30 to 120 nm, can be well controlled by modulating the weight ratio of aniline and PPy microspheres. PPy microspheres with abundant carbonyl groups have very strong affinity to the conjugated chains of PANI, which is responsible for the spontaneous formation of uniform core-shell microstructures. However, the strong affinity between PPy microspheres and PANI shells does not promote the diffusion or reassembly of two kinds of conjugated chains. Coating PPy microspheres with PANI shells increases the complex permittivity and creates the mechanism of interfacial polarization, where the latter plays an important role in increasing the dielectric loss of PPy@PANI composites. With a proper thickness of PANI shells, the moderate dielectric loss will produce well matched characteristic impedance, so that the microwave absorption properties of these composites can be greatly enhanced. Although PPy@PANI composites herein consume the incident electromagnetic wave by absolute dielectric loss, their performances are still superior or comparable to most PANI-based composites ever reported, indicating that they can be taken as a new kind of promising lightweight microwave absorbers. More importantly, microwave absorption of PPy@PANI composites can be simply modulated not only by the thickness of the absorbers, but also the shell thickness to satisfy the applications in different frequency bands.

  13. Electrochemomechanical Behaviour of Bilayer and Trilayer Films with PEDOT and PPY Conducting Polymers

    DEFF Research Database (Denmark)

    Zainudeen, Umer L.; Careem, M.A.; Skaarup, Steen

    2008-01-01

    a constant load of 1.5 g. The cyclic voltammograms as well as the UV-visible spectra of PEDOT and PPy are very different, pointing towards the possibility of being able to separate the two layers experimentally – even when combined in a single film. Bilayer results show combined characteristics of each...

  14. Surprising volume change in PPy(DBS): An atomic force microscopy study

    DEFF Research Database (Denmark)

    Smela, E.; Gadegaard, N.

    1999-01-01

    Communication: Conjugated polymers such as polypyrrole (PPy) have potential use as artificial muscles or in microsystems such as valves for micro-fluid handling. One of the most important parameters in such uses is the magnitude of volume change during associated redox processes; however, until now...

  15. Electrochemomechanical Behaviour of Bilayer and Trilayer Films with PEDOT and PPY Conducting Polymers

    DEFF Research Database (Denmark)

    Zainudeen, Umer L.; Careem, M.A.; Skaarup, Steen

    2008-01-01

    a constant load of 1.5 g. The cyclic voltammograms as well as the UV-visible spectra of PEDOT and PPy are very different, pointing towards the possibility of being able to separate the two layers experimentally – even when combined in a single film. Bilayer results show combined characteristics of each...

  16. Preparation of conductive polypyrrole (PPy) composites under supercritical carbon dioxide conditions

    Institute of Scientific and Technical Information of China (English)

    LI Gang; LIAO Xia; SUN Xinghua; YU Jian; HE Jiasong

    2007-01-01

    Electrically conductive composites were prepared via the chemical oxidative polymerization of the pyrrole monomer in polystyrene (PS) and zinc neutralized sulfonated polystyrene (Zn-SPS) films under supercritical carbon dioxide (SC-CO2) conditions.The strong swelling effect of SCCO2 made polypyrrole (PPy) particles not only form on the surface,but also become incorporated into the film,resulting in a homogeneous structure with a relatively higher conductivity.By comparison,the composite prepared in aqueous solutions shows a skin-core structure and a conductivity of 3 to 4 orders of magnitude lower than that of the former due to the diffusion-controlled process of the pyrrole monomer.The percolation thresholds of PS/PPy and Zn-SPS/PPy composites were 6.2% and 2.7% of the volume fraction of PPy,respectively,much lower than the theoretically predicted value of 16%.Moreover,the conductive composites prepared under SC-CO2 conditions showed higher thermal stability,especially in the high-temperature region.

  17. Synthesis of Conductive PPy/SiO2 Aerogels Nanocomposites by In Situ Polymerization of Pyrrole

    Directory of Open Access Journals (Sweden)

    Daliana Muller

    2015-01-01

    Full Text Available Electrical conductive nanocomposite aerogels were synthesized through in situ oxidative polymerization of pyrrole (Py using ammonium persulfate (APS as an oxidizing agent in SiO2 gels. The effect of Py concentration on the electrical conductivity and physical and morphological properties of aerogels SiO2/PPy was evaluated. B.E.T. analysis indicated that the surface area of the composite SiO2/PPy decreases with increasing concentration of Py. CHN analysis showed an increase in the amount of PPy, from 13 wt.% to 23 wt.%, with increasing concentration of pyrrole synthesis. FTIR-ATR analysis of the composites revealed bands in the region of 1500–1400 cm−1, indicating the presence of the conductive polymer in the silica aerogel as well as the characteristic bands of Si-O-Si and Si-OH covalent bonds. TEM micrographs revealed the presence of particles of PPy with the increased size of the nanoparticles. The composites were successfully applied as passive components, in RC circuits, for low-pass frequency filters. The filters exhibited a cutoff frequency at approximately 435 Hz. The aerogels obtained in this work exhibited suitable electrical conductivity for use in various other applications in electronics.

  18. True-color 640 ppi OLED arrays patterned by CA i-line photolithography

    NARCIS (Netherlands)

    Malinowski, P.E.; Ke, T.; Nakamura, A.; Chang, T.-Y.; Gokhale, P.; Steudel, S.; Janssen, D.; Kamochi, Y.; Koyama, I.; Iwai,Y.; Heremans, P.

    2015-01-01

    In this paper, side-by-side patterning of red, green and blue OLEDs is demonstrated. To achieve 640 ppi arrays with 20 µm subpixel pitch, chemically amplified, i-line photoresist system with submicron resolution was used. These results show feasibility of obtaining full-color displays with ultra-hig

  19. PPI use in patients commenced on clopidogrel : a retrospective cross-sectional evaluation

    NARCIS (Netherlands)

    Luinstra, M.; Naunton, M.; Peterson, G. M.; Bereznicki, L.

    2010-01-01

    Background/Aims: Antiplatelet therapy with aspirin and clopidogrel is an important component of the management of acute coronary syndrome, but it also increases the risk of bleeding. There are no formal guidelines about the use of a proton pump inhibitor (PPI) for gastroprotection in patients on clo

  20. Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Charles C., E-mail: hsucc@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Hsu, Howard [Department of Radiation Oncology, New York University, New York, New York (United States); Pickett, Barby [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Crehange, Gilles [Department of Radiation Oncology, Dijon University, Dijon (France); Hsu, I-Chow Joe; Dea, Ryan [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Weinberg, Vivian [Biostatistics and Computational Biology Core, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Gottschalk, Alexander R. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Kurhanewicz, John [Department of Radiology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States)

    2013-02-01

    Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or {>=}7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

  1. Dynamic Interaction of the Sec Translocon with the Chaperone PpiD*

    Science.gov (United States)

    Sachelaru, Ilie; Petriman, Narcis-Adrian; Kudva, Renuka; Koch, Hans-Georg

    2014-01-01

    The Sec translocon constitutes a ubiquitous protein transport channel that consists in bacteria of the three core components: SecY, SecE, and SecG. Additional proteins interact with SecYEG during different stages of protein transport. During targeting, SecYEG interacts with SecA, the SRP receptor, or the ribosome. Protein transport into or across the membrane is then facilitated by the interaction of SecYEG with YidC and the SecDFYajC complex. During protein transport, SecYEG is likely to interact also with the protein quality control machinery, but details about this interaction are missing. By in vivo and in vitro site-directed cross-linking, we show here that the periplasmic chaperone PpiD is located in front of the lateral gate of SecY, through which transmembrane domains exit the SecY channel. The strongest contacts were found to helix 2b of SecY. Blue native PAGE analyses verify the presence of a SecYEG-PpiD complex in native Escherichia coli membranes. The PpiD-SecY interaction was not influenced by the addition of SecA and only weakly influenced by binding of nontranslating ribosomes to SecYEG. In contrast, PpiD lost contact to the lateral gate of SecY during membrane protein insertion. These data identify PpiD as an additional and transient subunit of the bacterial SecYEG translocon. The data furthermore demonstrate the highly modular and versatile composition of the Sec translocon, which is probably essential for its ability to transport a wide range of substrates across membranes in bacteria and eukaryotes. PMID:24951590

  2. Different Physiological Roles of ATP- and PPi-Dependent Phosphofructokinase Isoenzymes in the Methylotrophic Actinomycete Amycolatopsis methanolica

    NARCIS (Netherlands)

    Alves, A.M.C.R.; Euverink, G.J.W.; Santos, H.; Dijkhuizen, L.

    2001-01-01

    Cells of the actinomycete Amycolatopsis methanolica grown on glucose possess only a single, exclusively PPi-dependent phosphofructokinase (PPi-PFK) (A. M. C. R. Alves, G. J. W. Euverink, H. J. Hektor, J. van der Vlag, W. Vrijbloed, D.H.A. Hondmann, J. Visser, and L. Dijkhuizen, J. Bacteriol. 176:682

  3. Effect of a short weak prepulse on laser-triggered front-surface heavy-ion acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Bochkarev, S. G.; Bychenkov, V. Yu. [P. N. Lebedev Physical Institute, Russian Academy of Sciences, Moscow (Russian Federation); Golovin, G. V.; Uryupina, D. S.; Shulyapov, S. A.; Savel' ev, A. B. [M. V. Lomonosov Moscow State University, International Laser Centre and Faculty of Physics, Moscow (Russian Federation); Andriyash, A. V. [The All-Russia Research Institute of Automatics, Moscow (Russian Federation)

    2012-10-15

    A suppression of light-ion acceleration (from surface water contaminants) was observed when a moderate-intensity subpicosecond laser pulse was focused on a thick metal target. Simultaneously, an effective generation of high-energy multicharge ions of the target material (Fe) was experimentally observed. A numerical simulation based on the Boltzmann-Vlasov-Poisson model revealed that this is due to the very specific regime of cleaning contaminants from the target surface by the short weak prepulse preceding the main pulse by more than 10 ns and having an intensity below the surface breakdown threshold. Because this prepulse causes the contaminant layer to boil explosively, a low-density gap forms above the target surface. These conditions are consequently favorable for boosting the energy of heavy ions.

  4. Neural correlates of sensorimotor gating: A metabolic positron emission tomography study in awake rats

    Directory of Open Access Journals (Sweden)

    Cathrin eRohleder

    2014-05-01

    Full Text Available Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET. Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during passive PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating.

  5. Sensorimotor gating deficits in multiple system atrophy

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi Bryde; Nikolic, Miki

    2014-01-01

    Prepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently...... associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls....

  6. Acute effects of lysergic acid diethylamide in healthy subjects

    OpenAIRE

    2015-01-01

    After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.;...

  7. Prepulse controlled electron acceleration from solids by a femtosecond laser pulse in the slightly relativistic regime

    Science.gov (United States)

    Ivanov, K. A.; Tsymbalov, I. N.; Shulyapov, S. A.; Krestovskikh, D. A.; Brantov, A. V.; Bychenkov, V. Yu.; Volkov, R. V.; Savel'ev, A. B.

    2017-06-01

    We present results from the experimental and numerical study of electron heating and acceleration under the action of a 50 fs high contrast laser pulse [intensities ˜(1-4) × 1018 W/cm2] with a controlled preplasma that was created by a 6 ns laser "prepulse" with intensity ˜1012 W/cm2. A substantial increase both in the gamma yield and "temperature" was obtained by the proper adjustment of the time delay between the two pulses (0-5 ns), while the gamma yield dropped to almost zero values if the nanosecond pulse came 10-20 ns in advance of the femtosecond one. Comprehensive optical diagnostics (shadowgraphy, interferometry, and angular resolved self-emission measurements) data allowed us to estimate the electron density profile. The latter profile was used for making numerical Particle-in-cell simulations which describe the gamma yield enhancement well. We also illustrate how the observed drop in the gamma yield within a certain range of delays was due to ionization defocusing of the femtosecond beam in an expanding long-scale (L/λ > 1) preplasma.

  8. Selective Phosphonylation of 5'-Adenosine Monophosphate (5'-AMP) via Pyrophosphite [PPi(III)

    Science.gov (United States)

    Kaye, Karl; Bryant, David E.; Marriott, Katie E. R.; Ohara, Shohei; Fishwick, Colin W. G.; Kee, Terence P.

    2016-11-01

    We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H2P2O5 2-; PPi(III)], to the phosphate group of 5'-adenosine mono phosphate (5'-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M2+) and by organic co-factors such as acetate (AcO-). In this specific case of P-transfer from PPi(III) to 5'-AMP, we show a synergistic enhancement of transfer in the combined presence of M2+ & AcO-. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5'-AMP, [P(III)P(V)-5'-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.

  9. Preparation and Surface Analysis of PPY/SDBS Films on Aluminum Substrates

    Directory of Open Access Journals (Sweden)

    Lisete C. Scienza

    2001-09-01

    Full Text Available Polypyrrole films were generated on high purity aluminum substrates under anodic polarization from aqueous electrolytes comprised of pyrrole and sodium dodecylbenzene sulfonate. The methods employed to characterize the polymer films included scanning electron microscopy, Fourier-transform infrared and X-photoelectron spectroscopy and X-ray diffraction. PPY/SDBS films revealed nodular morphology with occasional appearing of "dendrites", high level of protonation, excess of counter-anions ([S]/[N] > [N+]/[N] and high degrees of disorder.

  10. PDI-, PPI- and chaperone-catalyzed refolding of recombinant human IL-2 and GM-CSF

    Institute of Scientific and Technical Information of China (English)

    徐明波; 孟文华; 马贤凯

    1995-01-01

    The studies on PDI-, PP1- and chaperone-catalyzed refolding of recombinant human IL-2 and GM-CSF show that PDI can prevent the mismatch of disalfide bonds and formation of aggregates by interchains linkage, furthermore, PDI can correct, the mismatching of disulflde bonds in IL-2 isomers. PPI can increase the rate of folding reaction while chaperone can prevent the aggregation during the folding process. In addition, there is a synergistic effect between them.

  11. Discovery of ravidasvir (PPI-668) as a potent pan-genotypic HCV NS5A inhibitor.

    Science.gov (United States)

    Zhong, Min; Peng, Eric; Huang, Ningwu; Huang, Qi; Huq, Anja; Lau, Meiyen; Colonno, Richard; Li, Leping

    2016-09-15

    This Letter describes the synthesis, representative structure activity relationship (SAR), activity and PK profiles of a series of functionalized benzimidazole-naphthylene-imidazole derivatives as HCV NS5A inhibitors. This effort successfully led to the discovery of ravidasvir (PPI-668), which has been well tolerated and shown high sustained viral response rates as a key component in all-oral combination regimens in multiple human clinical trials.

  12. Photoluminescence and magnetic circular dichroism of IrQ(ppy){sub 2}-5Cl

    Energy Technology Data Exchange (ETDEWEB)

    Polosan, S., E-mail: Spol68@yahoo.com [National Institute of Materials Physics, Bucharest-Magurele 077125 (Romania); Faculty of Engineering, Kyoto Sangyo University, Kamigamo, Kita-ku, Kyoto 603-8555 (Japan); Radu, I.C. [National Institute of Materials Physics, Bucharest-Magurele 077125 (Romania); Tsuboi, T. [Faculty of Engineering, Kyoto Sangyo University, Kamigamo, Kita-ku, Kyoto 603-8555 (Japan)

    2012-04-15

    Photoluminescence and magnetic circular dichroism of the IrQ(ppy){sub 2}-5Cl compound were investigated between 15 and 295 K. These results have been compared with the output files obtained from Density Functional Theory by using the Gaussian 03W software and some additional packages. The experimental results confirm the first triplet state absorption which arises from d to {pi}{sub Q} transition. The temperature dependence photoluminescence have shown a small interaction with the polystyrene, used for dispersion of IrQ(ppy){sub 2}-5Cl compound. The green and red phosphorescence have the same temperature dependence. The MCD spectra, especially at 15 K, reveals the main transitions involved in the Metal-to-Ligand Charge Transfer processes from the Ir towards the two ligands, phenylpyridine and quinoline, respectively. - Highlights: Black-Right-Pointing-Pointer Mixed-ligand of IrQ(ppy){sub 2}-5Cl synthesis with green and red phosphorescence. Black-Right-Pointing-Pointer Photoluminescence and magnetic circular dichroism measurements from 15 to 295 K. Black-Right-Pointing-Pointer Experimental results have been compared with DFT theoretical calculations. Black-Right-Pointing-Pointer Triplet state which arises from d to {pi}{sub Q} transition was experimentally confirmed. Black-Right-Pointing-Pointer Green and red phosphorescence have the same temperature dependence.

  13. A validity assessment of the Progress out of Poverty Index (PPI)™.

    Science.gov (United States)

    Desiere, Sam; Vellema, Wytse; D'Haese, Marijke

    2015-04-01

    Development organisations need easy-to-use and quick-to-implement indicators to quantify poverty when requested to measure program impact. In this paper we assess the validity of the Progress out of Poverty Index (PPI)™, a country-specific indicator based on ten closed questions on directly observable household characteristics, by its compliance to the SMART criteria. Each response receives a pre-determined score, such that the sum of these scores can be converted into the likelihood the household is living below the poverty line. We focus on the PPI scorecard for Rwanda, which was validated using two national household surveys conducted in 2005/06 and 2010/11. The PPI is Specific, Measurable, Available cost effectively, and Timely available. Yet, its Relevance depends on the way it is used. Although it accurately distinguishes poor from non-poor households, making it a useful reporting tool, its limited sensitivity to changes in poverty status restricts its usefulness for evaluating the impact of development projects.

  14. k-Partite cliques of protein interactions: A novel subgraph topology for functional coherence analysis on PPI networks.

    Science.gov (United States)

    Liu, Qian; Chen, Yi-Ping Phoebe; Li, Jinyan

    2014-01-07

    Many studies are aimed at identifying dense clusters/subgraphs from protein-protein interaction (PPI) networks for protein function prediction. However, the prediction performance based on the dense clusters is actually worse than a simple guilt-by-association method using neighbor counting ideas. This indicates that the local topological structures and properties of PPI networks are still open to new theoretical investigation and empirical exploration. We introduce a novel topological structure called k-partite cliques of protein interactions-a functionally coherent but not-necessarily dense subgraph topology in PPI networks-to study PPI networks. A k-partite protein clique is a maximal k-partite clique comprising two or more nonoverlapping protein subsets between any two of which full interactions are exhibited. In the detection of PPI's maximal k-partite cliques, we propose to transform PPI networks into induced K-partite graphs where edges exist only between the partites. Then, we present a maximal k-partite clique mining (MaCMik) algorithm to enumerate maximal k-partite cliques from K-partite graphs. Our MaCMik algorithm is then applied to a yeast PPI network. We observed interesting and unusually high functional coherence in k-partite protein cliques-the majority of the proteins in k-partite protein cliques, especially those in the same partites, share the same functions, although k-partite protein cliques are not restricted to be dense compared with dense subgraph patterns or (quasi-)cliques. The idea of k-partite protein cliques provides a novel approach of characterizing PPI networks, and so it will help function prediction for unknown proteins.

  15. Low temperature synthesis of lead germanate (PbGeO{sub 3})/polypyrrole (PPy) nanocomposites and their lithium storage performance

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Jinkui, E-mail: jinkui@sdu.edu.cn [Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan 250061 (China); Ci, Lijie; Qi, Yongxin; Lun, Ning [Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan 250061 (China); Xiong, Shenglin; Qian, Yitai [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China)

    2014-09-15

    Highlights: • PbGeO{sub 3}/PPy nanocomposites are successfully fabricated for the first time. • PbGeO{sub 3} nanowire and PbGeO{sub 3}/PPy nanocomposites were characterized as anode materials in lithium ion batteries for the first time. • PPy coating can improve the electrochemical performance of PbGeO{sub 3} by increasing the electronic conductivity and buffering the volume changes during cycling. • The PbGeO{sub 3}/PPy nanocomposites deliver a capacity of 662 mA h g{sup −1} after 50 cycles. - Abstract: PGO/PPy nanocomposites were prepared via a low temperature chemical coating method for the first time. Electrochemical measurements demonstrate that the PbGeO{sub 3} electrodes retain a capacity of 657 mA h g{sup −1} after 100 cycles and possess excellent rate capability indicating that the PGO/PPy nanocomposites could be used as a candidate as high-capacity anode for lithium batteries.

  16. Preparation of stable magnetic nanofluids containing Fe3O4@PPy nanoparticles by a novel one-pot route

    Directory of Open Access Journals (Sweden)

    Zhao Baobao

    2011-01-01

    Full Text Available Abstract Stable magnetic nanofluids containing Fe3O4@Polypyrrole (PPy nanoparticles (NPs were prepared by using a facile and novel method, in which one-pot route was used. FeCl3·6H2O was applied as the iron source, and the oxidizing agent to produce PPy. Trisodium citrate (Na3cit was used as the reducing reagent to form Fe3O4 NPs. The as-prepared nanofluid can keep long-term stability. The Fe3O4@PPy NPs can still keep dispersing well after the nanofluid has been standing for 1 month and no sedimentation is found. The polymerization reaction of the pyrrole monomers took place with Fe3+ ions as the initiator, in which these Fe3+ ions remained in the solution adsorbed on the surface of the Fe3O4 NPs. Thus, the core-shell NPs of Fe3O4@PPy were obtained. The particle size of the as-prepared Fe3O4@PPy can be easily controlled from 7 to 30 nm by the polymerization reaction of the pyrrole monomers. The steric stabilization and weight of the NPs affect the stability of the nanofluids. The as-prepared Fe3O4@PPy NPs exhibit superparamagnetic behavior.

  17. Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy

    DEFF Research Database (Denmark)

    Fiocca, R; Mastracci, L; Attwood, S E;

    2012-01-01

    Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals.......Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals....

  18. RedNemo: topology-based PPI network reconstruction via repeated diffusion with neighborhood modifications

    DEFF Research Database (Denmark)

    Alkan, Ferhat; Erten, Cesim

    2016-01-01

    tested on small-scale networks thus far and when applied on large-scale networks of popular PPI databases, the executions require unreasonable amounts of time, or may even crash without producing any output for some instances even after several months of execution. We provide an algorithm, Red...... material including source code, useful scripts, experimental data and the results are available at http://webprs.khas.edu.tr/∼cesim/Red Nemo. tar.gz CONTACT: cesim@khas.edu.trSupplementary information: Supplementary data are available at Bioinformatics online....

  19. Study of the reaction $\\gamma p\\to p\\pi^0\\eta$

    CERN Document Server

    Horn, I; Anton, G; Bantes, R; Bartholomy, O; Beck, R; Beloglazov, Y; Bogendorfer, R; Castelijns, R; Cred, V; Ehmanns, A; Ernst, J; Fabry, I; Flemming, H; Fsel, A; Fuchs, M; Funke, C; Gothe, R; Gridnev, A; Gutz, E; Hoffgen, S; Hol, J; Junkersfeld, J; Kalinowsky, H; Klein, F; Klempt, E; Koch, H; Konrad, M; Kopf, B; Krusche, B; Langheinrich, J; Löhner, H; Lopatin, I; Lotz, J; Matthy, H; Menze, D; Messchendorp, J; Metag, V; Nikonov, V A; Novinski, D; Ostrick, M; Van Pee, H; Radkov, A; Sarantsev, A V; Schmidt, C; Schmieden, H; Schoch, B; Suft, G; Sumachev, V; Szczepanek, T; Thoma, U; Walther, D; Weinheimer, C

    2008-01-01

    The reaction $\\gamma p\\to p\\pi^0\\eta$ has been studied with the CBELSA detector at the tagged photon beam of the Bonn electron stretcher facility. The reaction shows contributions from $\\Delta^+(1232)\\eta$, $N(1535)^+\\pi^0$ and $pa_0(980)$ as intermediate states. A partial wave analysis suggests that the reaction proceeds via formation of six $\\Delta$ resonances, $\\Delta(1600)P_{33}$, $\\Delta(1920)P_{33}$, $\\Delta(1700)D_{33}$, $\\Delta(1940)D_{33}$, $\\Delta(1905)F_{35}$, $\\Delta(2360)D_{33}$, and two nucleon resonances $N(1880)P_{11}$ and $N(2200)P_{13}$, for which pole positions and decay branching ratios are given.

  20. Synthesis of PPy-like Nanocrystallines by Oriented Plasma Polymerization at Atmospheric Pressure

    Institute of Scientific and Technical Information of China (English)

    FANG Xin-sheng; GUO Ying; XU Jin-zhou; ZHANG Jing

    2006-01-01

    Polymeric polypyrrole-like (PPy-like) nanocrystallines were fast synthesized through oriented plasma polymerization at atmospheric pressure and room temperature. The effects of discharge power on the nanocrystalline morphology were investigated. Larger power tends to produce longer nanocrystallines. 3 mm long nanowires were produced at the largest power in our experiment. TEM image and the sharp electronic diffraction spots in SAD suggest that the nanoparticles have a single crystal phase. The chemical structure of the nanocrystalline has been studied through FTIR, EDX etc. This novel polymerization method could have great applications in fabricating functional polymeric nanocrystallines.

  1. Alzheimer Europe's position on involving people with dementia in research through PPI (patient and public involvement)

    DEFF Research Database (Denmark)

    Gove, Dianne; Diaz-Ponce, Ana; Georges, Jean

    2017-01-01

    This paper reflects Alzheimer Europe's position on PPI (patient and public involvement) in the context of dementia research and highlights some of the challenges and potential risks and benefits associated with such meaningful involvement. The paper was drafted by Alzheimer Europe in collaboration...... with members of INTERDEM and the European Working Group of People with Dementia. It has been formally adopted by the Board of Alzheimer Europe and endorsed by the Board of INTERDEM and by the JPND working group 'Dementia Outcome Measures - Charting New Territory'. Alzheimer Europe is keen to promote...

  2. Prepulse-induced shock waves in the gas jet target of a laser plasma EUV radiation source

    Science.gov (United States)

    Garbaruk, A. V.; Gritskevich, M. S.; Kalmykov, S. G.; Mozharov, A. M.; Sasin, M. E.

    2017-01-01

    In experiments with a laser-plasma EUV-radiation source, the main IR Nd:YAG laser pulse was preceded by that of a UV KrF excimer laser. Dramatic modulations of EUV plasma emissivity have been observed at long interpulse times, from hundreds of nanoseconds up to microseconds. To discover the nature of these prepulse-produced long-living perturbations of the target, a fluid dynamics numerical simulation of the Xe gas jet has been carried out. The prepulse has been found to generate a quasi-spherical shock wave with a thin dense front layer and a vast rarefied inside area. In the course of time, the front expands and simultaneously drifts downstream along with the gas. Depending on the interpulse time, the IR laser beam either intersects the dense layer or propagates within the rarefied gas cavity whereby the above-mentioned variations in the plasma emission can be explained. The possibilities of making use of the discovered phenomena to enhance the observed EUV plasma brightness are discussed.

  3. Gap-prepulse inhibition of the startle reflex (GPIAS for tinnitus assessment: current status and future directions

    Directory of Open Access Journals (Sweden)

    Alexander eGalazyuk

    2015-04-01

    Full Text Available The progress in the field of tinnitus largely depends on the development of a reliable tinnitus animal model. Recently a new method based on the acoustic startle reflex modification was introduced for tinnitus screening in laboratory animals. This method was enthusiastically adopted and now widely used by many scientists in the field due to its seeming simplicity and a number of advantages over the other methods of tinnitus assessment. Furthermore, this method opened an opportunity for tinnitus assessment in humans as well. Unfortunately multiple modifications of data collection and interpretation implemented in different labs make comparisons across studies very difficult. In addition, recent animal and human studies have challenged the original filling-in interpretation of the paradigm. Here we review the current literature to emphasize on the commonalities and differences in data collection and interpretation across laboratories that are using this method for tinnitus assessment. We also propose future research directions that could be taken in order to establish whether or not this method is warranted as an indicator of the presence of tinnitus.

  4. Development of an amperometric sulfite biosensor based on SO(x)/PBNPs/PPY modified ITO electrode.

    Science.gov (United States)

    Rawal, Rachna; Pundir, C S

    2012-11-01

    A sulfite oxidase (SO(x)) (EC 1.8.3.1) purified from Syzygium cumini leaves was immobilized onto prussian blue nanoparticles/polypyrrole composite (PBNPs/PPY) electrodeposited onto the surface of indium tin oxide (ITO) electrode. An amperometric sulfite biosensor was fabricated using SO(x)/PBNPs/PPY/ITO electrode as working electrode, Ag/AgCl as standard and Pt wire as auxiliary electrode connected through a potentiostat. The working electrode was characterized by Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) before and after immobilization of SO(x). The biosensor showed optimum response within 2s, when operated at 20 mV s⁻¹ in 0.1M Tris-HCl buffer, pH 8.5 and at 35 °C. Linear range and minimum detection limit were 0.5-1000 μM and 0.12 μM (S/N=3) respectively. There was good correlation (r=0.99) between red wine samples sulfite value by standard DTNB method and the present method. The sensor was evaluated with 97% recovery of added sulfite in red wine samples and 2.2% and 4.3% within and between batch coefficients of variation respectively. The sensor was employed for determination of sulfite level in red and white wine samples. The enzyme electrode was used 200 times over a period of 3 months when stored at 4 °C.

  5. Search for $B_c^+$ decays to the $p\\overline p\\pi^+$ final state

    CERN Document Server

    Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baker, Sophie; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Fazzini, Davide; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hongming, Li; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusardi, Nicola; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Niess, Valentin; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavomira; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhong, Liang; Zhukov, Valery; Zucchelli, Stefano

    2016-01-01

    A search for the decays of the $B_c^+$ meson to $p\\overline p\\pi^+$ is performed for the first time using a data sample corresponding to an integrated luminosity of 3.0 $\\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. No signal is found and an upper limit, at 95$\\%$ confidence level, is set, $\\frac{f_c}{f_u}\\times\\mathcal{B}(B_c^+\\to p\\overline p\\pi^+)<3.6\\times10^{-8}$ in the kinematic region $m(p\\overline p)<2.85\\mathrm{\\,Ge\\kern -0.1em V\\!/}c^2$, $p_{\\rm T}(B)<20\\mathrm{\\,Ge\\kern -0.1em V\\!/}c$ and $2.0< {y}(B)<4.5$, where $\\mathcal{B}$ is the branching fraction and $f_c$ ($f_u$) is the fragmentation fraction of the $b$ quark into a $B_c^+$ ($B^+$) meson.

  6. A rapid method for determination of acid value in transformer oil by PPy modified electrode

    Institute of Scientific and Technical Information of China (English)

    熊英; 何德良; 冯勇; 周舟; 常新园; 刘芙蓉

    2014-01-01

    A polypyrrole-modified glassy carbon electrode (PPy/GC electrode) was prepared and its electrocatalytic behavior towards naphthoquinone in the presence of acid was characterized by linear sweep voltammetry (LSV). A well-defined new reduction peak appeared at a more positive potential than the original reduction peak. The new reduction peak current was linearly related to the acid value (AV) of oil. Based on it, a rapid electrochemical method for determining AV of transformer oil was developed using PPy/GC electrode. A working curve was obtained in the AV range of 0.01 to 0.40 mg(KOH)·g-1, with a sensitivity of 39.42μA0.5/(mg(KOH)·g-1) and the detection limit of 0.0014 mg(KOH)·g-1 (signal-to-noise ratio is 3, standard deviation is 2.247%). Moreover, the proposed method has been successfully applied to AV determination of several transformer oil samples with advantages of rapidness, high sensitivity and accuracy compared to the conventional method.

  7. Effect of TiO2 Rutile Additive on Electrical Properties of PPy/TiO2 Nanocomposite

    Directory of Open Access Journals (Sweden)

    Trong Tung Nguyen

    2016-01-01

    Full Text Available Polypyrrole/titanium dioxide nanocomposite (PPy/TiO2 was synthesized by in situ chemical polymerization of pyrrole (Py monomer in colloidal suspension of TiO2 rutile. TEM and SEM images show that the TiO2 is covered by PPy forming a core-shell structure. The PPy/TiO2 core-shell will create n-p junction and bring in an inversion layer on the PPy-shell surface. The feature is accounted for the modification in electrical properties of the PPy/TiO2 nanocomposite. On the exposure to oxygen the conductivity of the nanocomposite exhibits an increase in 16–18-folds that are accounted for the interaction between oxygen (an electron acceptor and the inversion layer. The cyclic voltammetry diagrams have shown that at around 15% TiO2 and scan rate 100 mV/s the nanocomposites can reach a specific capacitance about 176 F/g.

  8. Novel electrochemical immune sensor based on Hep-PGA-PPy nanoparticles for detection of α-Fetoprotein in whole blood.

    Science.gov (United States)

    Xu, Tingting; Chi, Bo; Gao, Jian; Chu, Meilin; Fan, Wenlu; Yi, Meihui; Xu, Hong; Mao, Chun

    2017-07-18

    A simple and accurate immune sensor for quantitative detection of α-Fetoprotein (AFP) was developed based on the immobilization of antigen on the surface of Hep-PGA-PPy nanoparticles modified glassy carbon electrodes (GCE). The obtained Hep-PGA-PPy nanoparticles were characterized by fourier transform infrared (FT-IR) spectra and transmission electron microscopy (TEM). And the blood compatibility of Hep-PGA-PPy nanoparticles was investigated by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Combining the conductive property of polypyrrole (PPy) and the biocompatibility of heparin (Hep), the Hep-PGA-PPy nanoparticles could improve not only the anti-biofouling effect the electrode, but also improved the electrochemical properties of the immune sensor. Under optimal conditions, the proposed immune sensor could detect AFP in a linear range from 0.1 to 100 ng mL(-1) with a detection limit of 0.099 ng mL(-1) at the signal-to-noise ratio of 3, and it also possessed good reproducibility and storage stability. Furthermore, the detection of AFP in five human blood samples also showed satisfactory accuracy with low relative errors. Thus, the developed immune sensor which showed acceptable reproducibility, selectivity, stability and accuracy could be potentially used for the detection of whole blood samples directly. Copyright © 2017. Published by Elsevier B.V.

  9. Performance of the Chemical and Electrochemical Composites of PPy/CNT as Electrodes in Type I Supercapacitors

    Directory of Open Access Journals (Sweden)

    S. C. Canobre

    2015-01-01

    Full Text Available Polypyrrole (PPy is one of the most studied conducting polymers and a very promising material for various applications such as lithium-ion secondary batteries, light-emitting devices, capacitors, and supercapacitors, owing to its many advantages, including good processability, easy handling, and high electronic conductivity. In this work, PPy films were chemically and electrochemically synthesized, both in and around carbon nanotubes (CNTs. The cyclic voltammograms of the device, composed of the electrochemically synthesized PPy/CNT composites as working and counter electrodes (Type I supercapacitor with p-type doping, showed a predominantly capacitive profile with low impedance values and good electrochemical stability, with the anodic charge remaining almost constant (11.38 mC, a specific capacitance value of 530 F g−1 after 50 charge and discharge cycles, and a coulombic efficiency of 99.2%. The electrochemically synthesized PPy/CNT composite exhibited better electrochemical properties compared to those obtained for the chemically synthesized composite. Thus, the electrochemically synthesized PPy/CNT composite is a promising material to be used as electrodes in Type I supercapacitors.

  10. Preparation and electrochemical characterization of PPy-LiFePO{sub 4}/C composites via vapor-phase polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Q.; Liao, X.Z.; He, Y.; Yang, Y.; Ma, Z.F. [Shanghai Jiao Tong Univ. (China). Dept. of Chemical Engineering

    2010-07-01

    Polypyrrole (PPy) is now being used as a means of improving the electrochemical performance of lithium-iron (LiFePO{sub 4}/C) composite electrode materials for Li-ion batteries. In this study, core-shell LiFePO{sub 4}/C-PPy composites were prepared using a chemical vapor-phase polymerization technique. Transmission electron microscopy (TEM) analyses demonstrated that the LiFePO{sub 4}/C particles were encapsulated with 7.5-nm thick PPy shells. Electrochemical analyses indicated that the high rate capacities and cycle stability of the composite materials was improved when compared with the performance of LiFePO{sub 4}/C composites. Tests on an MCMB/LiFePO{sub 4}-PPy fuel cell showed that the PPy coating reduced Fe dissolution from the LiFePO{sub 4} cathode, and alleviated subsequent Fe deposition on the MCMB anode, thereby enhancing the cell's life cycle. 7 refs., 2 figs.

  11. Sensory gating and sensorimotor gating in medication-free obsessive-compulsive disorder patients

    DEFF Research Database (Denmark)

    de Leeuw, Aart S; Oranje, Bob; van Megen, Harold J G M

    2010-01-01

    Obsessive-compulsive disorder (OCD) is associated with deficits in inhibition mechanisms. This is reflected in reports showing impaired sensorimotor and sensory gating in OCD patients, as measured with prepulse inhibition (PPI) of the startle reflex and P50 suppression paradigms. However, most...

  12. Sensory gating and sensorimotor gating in medication-free obsessive-compulsive disorder patients

    DEFF Research Database (Denmark)

    de Leeuw, Aart S; Oranje, Bob; van Megen, Harold J G M

    2010-01-01

    Obsessive-compulsive disorder (OCD) is associated with deficits in inhibition mechanisms. This is reflected in reports showing impaired sensorimotor and sensory gating in OCD patients, as measured with prepulse inhibition (PPI) of the startle reflex and P50 suppression paradigms. However, most...

  13. Dechlorination of pentachlorophenol (PCP) in aqueous solution on novel Pd-loaded electrode modified with PPy-SDBS composite film.

    Science.gov (United States)

    Sun, Zhirong; Wei, Xuefeng; Zhang, Huan; Hu, Xiang

    2015-03-01

    Pentachlorophenol (PCP) is a persistent pollutant and a suspected human carcinogen. It can be found in the air, water, and soil and enters the environment through evaporation from treated wood surfaces, industrial spills, and disposal at uncontrolled hazardous waste sites. Ecotoxicity of PCP necessitates the development of rapid and reliable remediation techniques. Electrocatalytic hydrogenolysis (ECH) has been proven as a promising method for detoxification of halogenated wastes, due to its rapid reaction rate, low apparatus cost, mild reaction conditions, and absence of secondary contaminants. Challenge for the application of ECH is to prepare a Pd-coated cathode with high stability, high catalytic activity, and low Pd loading level. In this work, Pd/polypyrrole-sodium dodecyl benzene sulfonate/meshed Ti (Pd/PPy-SDBS/Ti) electrode was prepared and was characterized by cyclic voltammetry, scanning electron microscopy, X-ray diffraction, and inductively coupled plasma-atomic emission spectrometry. Electrochemically reductive dechlorination of PCP on the Pd/PPy-SDBS/Ti electrode in aqueous solution was investigated. Pd microparticles were uniformly dispersed on PPy-SDBS film which was previously electrodeposited on the meshed Ti supporting electrode. The loading of Pd on the electrode was 0.72 mg cm(-2). Electrocatalytic dechlorination of PCP was performed in a two-compartment cell separated by cation-exchange membrane. The PCP removal on the Pd/PPy-SDBS/Ti electrode could reach 100 % within 70 min with dechlorination current 3 mA when PCP initial concentration was 10 mg L(-1) and initial pH was 2.4. Conversion of PCP on the Pd/PPy-SDBS/Ti electrode followed pseudo-first-order kinetics, and the apparent activation energy was 13.0 kJ mol(-1). The removal of PCP still kept 100 % after 70 min dechlorination when the Pd/PPy-SDBS/Ti cathode was reused ten times. The electrode exhibited promising dechlorination potential with high electrocatalytic activity, good stability

  14. GABA/progesterone-induced polyphosphoinositide (PPI) breakdown and its role in the acrosome reaction of guinea pig spermatozoa in vitro

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To investigate whether GABA/progesterone (P4) stimulates PPI breakdown and its role in the acrosome reaction (AR), spermatozoa of guinea pig were preincubated in MCM-LCa2+ for 5.5 h and then labeled with [32P]pi for 1 h. Samples were washed through a three-step gradient Percoll, adjusted to 5×107 cells/mL and exposed to 2 mmol/L Ca2+, 5 mmol/L GABA, 10 mmol/L P4 and other agents. Lipids were separated by t.l.c. and radioactivity in spots determined by scintillation counting. The AR was assessed by phase-contrast microscopy. The results showed that (i) when spermato-zoa were treated with GABA, 32P-label diminished rapidly in phosphatidylinositol 4, 5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), and increased in phosphatidic acid (PA). The loss of label from PPI was almost completed by 10 min. The time-course of the AR was much slower than PPI when spermatozoa reached a maximal response by 15 min; (ii) the pattern of PPI hydrolysis and stimulation of AR was similar for the three agonists tested;their potency followed the order A23187>progesterone≥GABA; (iii) GABA-induced PIP2 hydrolysis and rise in PA and the AR were prevented by inclusion of 10 mmol/L neomycin; (iv) the loss of PIP2 labeling and the increase in PA labeling abolished when spermatozoa were exposed to EGTA or Ca2+ channel blocker. These re-sults indicate that GABA or P4-induced PPI breakdown is an important and essential event in the series of changes to membrane fusion during the AR of guinea pig spermatozoa and this effect is mediated via calcium by activation of phosphatidylinositol-specific phospholipase C.

  15. Magnetic Fe2O3-polystyrene/PPy core/shell particles: bioreactivity and self-assembly.

    Science.gov (United States)

    Mangeney, Claire; Fertani, Meriem; Bousalem, Smain; Zhicai, Ma; Ammar, Souad; Herbst, Fréderic; Beaunier, Patricia; Elaissari, Abdelhamid; Chehimi, Mohamed M

    2007-10-23

    This paper describes the synthesis of new magnetic, reactive polystyrene/polypyrrole core/shell latex particles. The core consists of a polystyrene microsphere containing gamma-Fe2O3 superparamagnetic nanoparticles (PSmag), and the shell is made of reactive N-carboxylic acid-functionalized polypyrrole (PPyCOOH). These PSmag-PPyCOOH latex particles, average diameter 220 nm, were prepared by copolymerization of pyrrole (Py) and the active carboxyl-functionalized pyrrole (PyCOOH) in the presence of PSmag particles. PNVP was used as a steric stabilizer. The functionalized polypyrrole-coated PSmag particles were characterized in terms of their particle size, surface morphology, chemical composition, and electrochemical and magnetic properties using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry, and SQUID magnetometry. Activation of the particle surface carboxyl groups was achieved using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS), which helps transform the carboxyl groups into activated ester groups (NSE). The activated particles, PSmag-PPyNSE, were further evaluated as bioadsorbents of biotin used as a model biomolecule. It was shown that biotin was immobilized at the surface of the PSmag-PPyNSE particles by forming interfacial amide groups. The assemblies of PSmag-PPyCOOH particles on glass plates were further investigated. When no magnetic field is applied, the particles assemble into 3D colloidal crystals. In contrast, under a magnetic field, one-particle-thick chains gathered in hedgehog-like architectures are obtained. Furthermore, PSmag-PPyCOOH coated ITO electrodes were shown to be electroactive and electrochemically stable, thus offering potentialities for creating novel high-specific-area materials for biosensing devices where the conducting polymer component would act as the transducer through its conductive properties.

  16. Identification of functional modules in a PPI network by clique percolation clustering.

    Science.gov (United States)

    Zhang, Shihua; Ning, Xuemei; Zhang, Xiang-Sun

    2006-12-01

    Large-scale experiments and data integration have provided the opportunity to systematically analyze and comprehensively understand the topology of biological networks and biochemical processes in cells. Modular architecture which encompasses groups of genes/proteins involved in elementary biological functional units is a basic form of the organization of interacting proteins. Here we apply a graph clustering algorithm based on clique percolation clustering to detect overlapping network modules of a protein-protein interaction (PPI) network. Our analysis of the yeast Sacchromyces cerevisiae suggests that most of the detected modules correspond to one or more experimentally functional modules and half of these annotated modules match well with experimentally determined protein complexes. Our method of analysis can of course be applied to protein-protein interaction data for any species and even other biological networks.

  17. Quantifying Systemic Evolutionary Changes by Color Coding Confidence-Scored PPI Networks

    Science.gov (United States)

    Dao, Phuong; Schönhuth, Alexander; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Sahinalp, S. Cenk; Ester, Martin

    A current major challenge in systems biology is to compute statistics on biomolecular network motifs, since this can reveal significant systemic differences between organisms. We extend the “color coding” technique to weighted edge networks and apply it to PPI networks where edges are weighted by probabilistic confidence scores, as provided by the STRING database. This is a substantial improvement over the previously available studies on, still heavily noisy, binary-edge-weight data. Following up on such a study, we compute the expected number of occurrences of non-induced subtrees with k ≤ 9 vertices. Beyond the previously reported differences between unicellular and multicellular organisms, we reveal major differences between prokaryotes and unicellular eukaryotes. This establishes, for the first time on a statistically sound data basis, that evolutionary distance can be monitored in terms of elevated systemic arrangements.

  18. A Topology Potential-Based Method for Identifying Essential Proteins from PPI Networks.

    Science.gov (United States)

    Li, Min; Lu, Yu; Wang, Jianxin; Wu, Fang-Xiang; Pan, Yi

    2015-01-01

    Essential proteins are indispensable for cellular life. It is of great significance to identify essential proteins that can help us understand the minimal requirements for cellular life and is also very important for drug design. However, identification of essential proteins based on experimental approaches are typically time-consuming and expensive. With the development of high-throughput technology in the post-genomic era, more and more protein-protein interaction data can be obtained, which make it possible to study essential proteins from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. Most of these topology based essential protein discovery methods were to use network centralities. In this paper, we investigate the essential proteins' topological characters from a completely new perspective. To our knowledge it is the first time that topology potential is used to identify essential proteins from a protein-protein interaction (PPI) network. The basic idea is that each protein in the network can be viewed as a material particle which creates a potential field around itself and the interaction of all proteins forms a topological field over the network. By defining and computing the value of each protein's topology potential, we can obtain a more precise ranking which reflects the importance of proteins from the PPI network. The experimental results show that topology potential-based methods TP and TP-NC outperform traditional topology measures: degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), subgraph centrality (SC), eigenvector centrality (EC), information centrality (IC), and network centrality (NC) for predicting essential proteins. In addition, these centrality measures are improved on their performance for identifying essential proteins in biological network when controlled by topology potential.

  19. Orthogonal non-covalent binding forces in solid state supramolecular herringbone-shaped "interlocked dimers". Pseudopolymorphism in [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) complex.

    Science.gov (United States)

    Pérez, José; Espinosa, Arturo; Galiana, J Miguel; Pérez, Eduardo; Serrano, J Luis; Aranda, Miguel A G; Insausti, Maite

    2009-11-21

    The crystal structures of [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) (1) and two different solvatomorphs of it, [(ppy)Pd(mu-pz)](2) x 1/2 CH(2)Cl(2) (2) and [(ppy)Pd(mu-pz)](2) x 1/2 CHCl(3) (3) have been elucidated by powder (1 and 2) and single crystal (3) X-ray diffraction. In all of them two molecules fit together following a very similar pattern forming a "dimer". All neutral dinuclear square-planar complexes having mu-pz or related bridges and planar aromatic ligands completing the coordination spheres found in the CSD show a similar arrangement to those observed in compounds 1-3, consisting of "interlocked dimers" following a herringbone-like pattern. A DFT study reveals the simultaneous action of pi,pi- and T-stacking interactions occurring as two sets of orthogonally oriented binding forces, as well as anagostic bonds overlapped with the latter.

  20. Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Hammer, Trine B; Oranje, Bob; Skimminge, Arnold

    2013-01-01

    and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes. Results: We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain...... areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed...

  1. DrugScorePPI knowledge-based potentials used as scoring and objective function in protein-protein docking.

    Directory of Open Access Journals (Sweden)

    Dennis M Krüger

    Full Text Available The distance-dependent knowledge-based DrugScore(PPI potentials, previously developed for in silico alanine scanning and hot spot prediction on given structures of protein-protein complexes, are evaluated as a scoring and objective function for the structure prediction of protein-protein complexes. When applied for ranking "unbound perturbation" ("unbound docking" decoys generated by Baker and coworkers a 4-fold (1.5-fold enrichment of acceptable docking solutions in the top ranks compared to a random selection is found. When applied as an objective function in FRODOCK for bound protein-protein docking on 97 complexes of the ZDOCK benchmark 3.0, DrugScore(PPI/FRODOCK finds up to 10% (15% more high accuracy solutions in the top 1 (top 10 predictions than the original FRODOCK implementation. When used as an objective function for global unbound protein-protein docking, fair docking success rates are obtained, which improve by ∼ 2-fold to 18% (58% for an at least acceptable solution in the top 10 (top 100 predictions when performing knowledge-driven unbound docking. This suggests that DrugScore(PPI balances well several different types of interactions important for protein-protein recognition. The results are discussed in view of the influence of crystal packing and the type of protein-protein complex docked. Finally, a simple criterion is provided with which to estimate a priori if unbound docking with DrugScore(PPI/FRODOCK will be successful.

  2. PPI-IRO: A two-stage method for protein-protein interaction extraction based on interaction relation ontology

    KAUST Repository

    Li, Chuanxi

    2014-01-01

    Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical literature resources has been proven as an effective approach for the identifi cation of biological regulatory networks. This paper presents a novel method based on the idea of Interaction Relation Ontology (IRO), which specifi es and organises words of various proteins interaction relationships. Our method is a two-stage PPI extraction method. At fi rst, IRO is applied in a binary classifi er to determine whether sentences contain a relation or not. Then, IRO is taken to guide PPI extraction by building sentence dependency parse tree. Comprehensive and quantitative evaluations and detailed analyses are used to demonstrate the signifi cant performance of IRO on relation sentences classifi cation and PPI extraction. Our PPI extraction method yielded a recall of around 80% and 90% and an F1 of around 54% and 66% on corpora of AIMed and Bioinfer, respectively, which are superior to most existing extraction methods. Copyright © 2014 Inderscience Enterprises Ltd.

  3. Nanoclay-based hierarchical interconnected mesoporous CNT/PPy electrode with improved specific capacitance for high performance supercapacitors.

    Science.gov (United States)

    Oraon, Ramesh; De Adhikari, Amrita; Tiwari, Santosh Kumar; Nayak, Ganesh Chandra

    2016-05-31

    A natural layered clay known as montmorillonite, a lamellar aluminosilicate with ∼1 nm thickness, has attracted intense attention in ongoing research due to its large natural abundance and environmental friendliness. Endowed with highly active surface sites the nanoclay has been extensively used in various fields viz. catalysis, biosensors etc. even though the role played by nanoclay on energy storage performance has not been elucidated. In this present work, a series of nanoclay (Closite 30B) based hierarchical open interconnected mesoporous electrode materials for supercapacitors (SCs) has been synthesized in the presence of carbon nanotubes (CNTs) and polypyrrole (PPy) by a facile in situ and ex situ approach. The role of nanoclay was explored as a dopant and its substantial doping effect exerted on the electrochemical performance towards energy storage was investigated. A coating of PPy over CNTs and nanoclay was confirmed from FESEM analysis which revealed the genesis of a nanoclay-supported hierarchical interconnected mesoporous framework. Furthermore, a PPy-coated CNT array in the presence of nanoclay was found to be highly porous with a high specific surface area without obvious deterioration. These interconnected structures can contribute to better penetration of electrolyte ions by shortening the path length for rapid transport of ions and electrons even at high rates. Cyclic voltammetry measurements revealed that nanoclay based in situ composite (CNP) and ex situ composite (CPN) exhibited a maximum specific capacitance of 425 F g(-1) and 317 F g(-1), respectively at a scan rate of 10 mV s(-1), which is comparatively higher than that of CP (i.e. PPy-coated CNTs) (76.77 F g(-1)). Similarly, a 273% increase in the specific capacitance of PPy was achieved after nanoclay incorporation in the nanocomposite NP (i.e. PPy-coated nanoclay) as compared to virgin PPy. These results are in good agreement with the specific capacitance performance by galvanostatic

  4. An efficient strategy to assemble water soluble histidine-perylene diimide and graphene oxide for the detection of PPi in physiological conditions and in vitro.

    Science.gov (United States)

    Muthuraj, B; Mukherjee, Sudip; Chowdhury, Sayan Roy; Patra, Chitta Ranjan; Iyer, Parameswar K

    2017-03-15

    A strategy to develop water soluble, biocompatible nanocomposite probe for the detection of pyrophosphate (PPi) in physiological conditions and in in vitro live melanoma cancer cells (B16F10) is reported. The self-assembled nanocomposite probe comprised of amino acid (histidine) functionalized perylenediimide (PDI-HIS), copper ion and graphene oxide (GO) and that could be utilized as a highly effective sensing platform in biological conditions and cellular environment via fluorescence "turn-on" for PPi detection. This controlled fabrication of metal organic self-assembled spheres along with GO proved very valuable for the detection of PPi in unprecedented sensitivity over other competing ions. The PDI-HIS-Cu-GO (PCG) nanocomposite sensor provides a unique platform for the fluorogenic detection of PPi having a very low limit of detection (LOD) of 0.60×10(-7)M based on the strong affinity (1.0×10(6)M(-1)) between the copper complex of PDI-HIS receptor and PPi. The intracellular detection of PPi using PCG also carried out in B16F10 cells where >10 times observed as compared to the PDI-HIS+Cu(2+) complex. Thus early cancer detection via PPi recognition in physiological conditions and in live cells was possible using PCG. Furthermore, the fabrication of PDI-HIS and PCG with PVA hydrogel films and on thin layer chromatography plates demonstrated the practical utility for the detection of PPi anions by "off-on" response rapidly in a label free manner.

  5. Synthesis of an air-working trilayer artificial muscle using a conductive cassava starch biofilm (manihot esculenta, cranz) and polypyrrole (PPy)

    Science.gov (United States)

    Núñez D, Y. E.; Arrieta A, Á. A.; Segura B, J. A.; Bertel H, S. D.

    2016-02-01

    In this study, a methodology for obtaining a conductive cassava starch biofilm doped with lithium perchlorate (LiClO4) is shown, as well as the electrochemical technique for the synthesis of polypyrrole films, which are used for developing the trilayer artificial muscle PPy/Biopolymer/PPy designed to operate in air. Furthermore, results from the trilayer movement using chronoamperometric techniques are shown.

  6. Exploring the Relationship between PPI and CPI%PPI与CPI关系探析

    Institute of Scientific and Technical Information of China (English)

    刘敏; 张燕丽; 杨延斌

    2005-01-01

    This paper focuses on the demonstration study, through related analysis on various samples, on the relation between PPI and CPI, based on the resident consumption price index and the price index of industrial products in Shandong province since 1989. The paper also analyzes the relation among different price index' s, their transfer regulation and the degree of influence on one another. The study result shows that resident consumption price index relates the most to the factory price index of daily living products, the second to the factory price index of production materials, and the least to the purchase price index of raw materials, fuel and power. The price change of energy and raw materials at the upper level will naturally be reflected in the factory price of industrial products at the lower level and price of daily living products in the end. It is a long influence process from the price of raw materials for industrial production to the factory price of industrial products, including production materials and daily living products, and finally to the resident consumption price. The price influence process somehow lags behind the production and consumption process for a certain period. The rise and fall of industrial products price index is the earliest signal for economic development trend and to which the government and the industry must attach high importance.

  7. Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the rabbit: a new therapeutic strategy for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-12-01

    Full Text Available Abstract Introduction Docosahexaenoic acid (DHA and DHA-containing ethanolamine plasmalogens (PlsEtn are decreased in the brain, liver and the circulation in Alzheimer's disease. Decreased supply of plasmalogen precursors to the brain by the liver, as a result of peroxisomal deficits is a process that probably starts early in the AD disease process. To overcome this metabolic compromise, we have designed an orally bioavailable DHA-containing ether lipid precursor of plasmalogens. PPI-1011 is an alkyl-diacyl plasmalogen precursor with palmitic acid at sn-1, DHA at sn-2 and lipoic acid at sn-3. This study outlines the oral pharmacokinetics of this precursor and its conversion to PlsEtn and phosphatidylethanolamines (PtdEtn. Methods Rabbits were dosed orally with PPI-1011 in hard gelatin capsules for time-course and dose response studies. Incorporation into PlsEtn and PtdEtn was monitored by LC-MS/MS. Metabolism of released lipoic acid was monitored by GC-MS. To monitor the metabolic fate of different components of PPI-1011, we labeled the sn-1 palmitic acid, sn-2 DHA and glycerol backbone with13C and monitored their metabolic fates by LC-MS/MS. Results PPI-1011 was not detected in plasma suggesting rapid release of sn-3 lipoic acid via gut lipases. This conclusion was supported by peak levels of lipoic acid metabolites in the plasma 3 hours after dosing. While PPI-1011 did not gain access to the plasma, it increased circulating levels of DHA-containing PlsEtn and PtdEtn. Labeling experiments demonstrated that the PtdEtn increases resulted from increased availability of DHA released via remodeling at sn-2 of phospholipids derived from PPI-1011. This release of DHA peaked at 6 hrs while increases in phospholipids peaked at 12 hr. Increases in circulating PlsEtn were more complex. Labeling experiments demonstrated that increases in the target PlsEtn, 16:0/22:6, consisted of 2 pools. In one pool, the intact precursor received a sn-3

  8. Electrodos poliméricos de PPy/PVS y PPy/DBS cómo cátodos en baterías de Zinc y Magnesio

    OpenAIRE

    Granados García, Jorge Enrique

    2012-01-01

    En este proyecto se estudia la respuesta de los polímero PPy/PVS y PPy/DBS al ser usados como cátodos en baterías poliméricas con ánodos de Zinc y Magnesio. Se tratará de obtener las mejores películas poliméricas que incorporen estos cationes durante la descarga y los expulsen durante la recarga de la batería. Este esquema conjuga las buenas características del Zn y Mg metálico para ser usado como ánodo de baterías con las buenas propiedades de los polímeros conductores y la po...

  9. Clonidine Normalizes Sensorimotor Gating Deficits in Patients With Schizophrenia on Stable Medication

    DEFF Research Database (Denmark)

    Oranje, Bob; Glenthøj, Birte Y

    2013-01-01

    sensorimotor gating deficits in schizophrenia. Methods : In a double blind, placebo controlled, randomized, yet balanced, cross-over experiment, 20 male schizophrenia patients on stable medication were assessed in an auditory prepulse inhibition (PPI), sensitization, and habituation of the startle reflex...

  10. Evidence for a parity doublet Delta(1920)P33 and Delta(1940)D33 from gammap-->ppi;{0}eta.

    Science.gov (United States)

    Horn, I; Anisovich, A V; Anton, G; Bantes, R; Bartholomy, O; Beck, R; Beloglazov, Yu; Bogendörfer, R; Castelijns, R; Crede, V; Ehmanns, A; Ernst, J; Fabry, I; Flemming, H; Fösel, A; Fuchs, M; Funke, Chr; Gothe, R; Gridnev, A; Gutz, E; Höffgen, St; Hössl, J; Junkersfeld, J; Kalinowsky, H; Klein, F; Klempt, E; Koch, H; Konrad, M; Kopf, B; Krusche, B; Langheinrich, J; Löhner, H; Lopatin, I; Lotz, J; Matthäy, H; Menze, D; Messchendorp, J; Metag, V; Nikonov, V A; Novinski, D; Ostrick, M; van Pee, H; Sarantsev, A V; Schmidt, C; Schmieden, H; Schoch, B; Suft, G; Sumachev, V; Szczepanek, T; Thoma, U; Walther, D; Weinheimer, Chr

    2008-11-14

    Evidence is reported for the existence of a parity doublet of Delta resonances with total angular momentum J=3/2 from photoproduction of the ppi;{0}eta final state. The two parity partners Delta(1920)P33 and Delta(1940)D33 make significant contributions to the reaction. Cascades of resonances into Delta(1232)eta, N(1535)pi, and Na0(980) are clearly observed.

  11. A novel EIS field effect structures coated with TESUD-PPy-PVC-dibromoaza[7]helicene matrix for potassium ions detection

    OpenAIRE

    Tounsi, Moncef; Ben Braiek, Mourad; Barhoumi, Houcine; Baraket, Abdoullatif; Lee, Michael; Zine, Nadia; Maaref, Abderrazak; Errachid, Abdelhamid

    2016-01-01

    International audience; In this work, we describe the development of new Aza[7]helicene-containing PVC-based membranes for the K+ ions quantification. Here, silicon nitride-based structures (Si-p/SiO2/Si3N4) were developed and the surface was activated, functionalized with an aldehyde–silane (11-(Triethoxysilyl)undecanal (TESUD)), functionalized with polypyrrole (PPy), and coated with the polyvinylchloride (PVC)-membrane containing the Aza[7]helicene as ionophore. All stages of functionalizat...

  12. Fabrication of conductive and high-dispersed Ppy@Ag/g-C{sub 3}N{sub 4} composite photocatalysts for removing various pollutants in water

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhi; Tang, Xu [School of Chemistry and Chemical Engineering, Jiangsu University (China); Ma, Changchang [School of the Environment and Safety Engineering, Jiangsu University (China); Song, Minshan [School of Mathematics and Physics, Jiangsu University of Science and Technology (China); Gao, Nailing; Wang, Youshan; Huo, Pengwei [School of Chemistry and Chemical Engineering, Jiangsu University (China); Lu, Ziyang, E-mail: mrzhuzhi007@163.com [School of the Environment and Safety Engineering, Jiangsu University (China); Yan, Yongsheng, E-mail: gchxz206@126.com [School of Chemistry and Chemical Engineering, Jiangsu University (China)

    2016-11-30

    Highlights: • The high-dispersed Ag modified g-C{sub 3}N{sub 4} (Ag/g-C{sub 3}N{sub 4}) was successfully synthesized in situ deposited on the surface of g-C{sub 3}N{sub 4} during calcined melamine. • The as-prepared Ppy@Ag/g-C{sub 3}N{sub 4} could remove of various organic pollutants in water. • The enhanced photocatalytic activity of Ppy@Ag/g-C{sub 3}N{sub 4} comes from π conjugated electronic structures of Ppy and Ag species as the electron transfer mediator between Ppy and g-C{sub 3}N{sub 4}. • The Ppy@Ag/g-C{sub 3}N{sub 4} sample also showed a relatively good recycling stability. - Abstract: The ternary conductive Ppy@Ag/g-C{sub 3}N{sub 4} composite photocatalysts was successfully synthesized by polymerization process and surface polymerization technique. And the as-prepared Ppy@Ag/g-C{sub 3}N{sub 4} sample exhibited the higher photocatalytic activity for various pollutant (MO, DM, TC, CIP, GFLX and EH) remove than that of pure g-C{sub 3}N{sub 4} and Ag/g-C{sub 3}N{sub 4} under visible light irradiation. It mainly originated from the Ag nanoparticles anchored between g-C{sub 3}N{sub 4} and Ppy acted as electron transfer mediator that facilitated the charge carrier separation and then expending the lifetime of the carriers. Meanwhile, the obtained Ppy@Ag/g-C{sub 3}N{sub 4} sample also showed a relatively good recycling stability which was the crucial factor for photocatalyst practical application. This work provided a new facile strategy for improving photo-degradation activity of g-C{sub 3}N{sub 4} photocatalyst.

  13. PPI Network Analysis of mRNA Expression Profile of Ezrin Knockdown in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bingli Wu

    2014-01-01

    Full Text Available Ezrin, coding protein EZR which cross-links actin filaments, overexpresses and involves invasion, metastasis, and poor prognosis in various cancers including esophageal squamous cell carcinoma (ESCC. In our previous study, Ezrin was knock down and analyzed by mRNA expression profile which has not been fully mined. In this study, we applied protein-protein interactions (PPI network knowledge and methods to explore our understanding of these differentially expressed genes (DEGs. PPI subnetworks showed that hundreds of DEGs interact with thousands of other proteins. Subcellular localization analyses found that the DEGs and their directly or indirectly interacting proteins distribute in multiple layers, which was applied to analyze the shortest paths between EZR and other DEGs. Gene ontology annotation generated a functional annotation map and found hundreds of significant terms, especially those associated with cytoskeleton organization of Ezrin protein, such as “cytoskeleton organization,” “regulation of actin filament-based process,” and “regulation of actin cytoskeleton organization.” The algorithm of Random Walk with Restart was applied to prioritize the DEGs and identified several cancer related DEGs ranked closest to EZR. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile of Ezrin knockdown for future examination of the roles and mechanisms of Ezrin.

  14. Facile Synthesis of SrCO3-Sr(OH2/PPy Nanocomposite with Enhanced Photocatalytic Activity under Visible Light

    Directory of Open Access Journals (Sweden)

    Alfredo Márquez-Herrera

    2016-01-01

    Full Text Available Pyrrole monomer was chemically polymerized onto SrCO3-Sr(OH2 powders to obtain SrCO3-Sr(OH2/polypyrrole nanocomposite to be used as a candidate for photocatalytic degradation of methylene blue dye (MB. The material was characterized by Fourier transform infrared (FTIR spectroscopy, UV/Vis spectroscopy, and X-ray diffraction (XRD. It was observed from transmission electronic microscopy (TEM analysis that the reported synthesis route allows the production of SrCO3-Sr(OH2 nanoparticles with particle size below 100 nm which were embedded within a semiconducting polypyrrole matrix (PPy. The SrCO3-Sr(OH2 and SrCO3-Sr(OH2/PPy nanocomposites were tested in the photodegradation of MB dye under visible light irradiation. Also, the effects of MB dye initial concentration and the catalyst load on photodegradation efficiency were studied and discussed. Under the same conditions, the efficiency of photodegradation of MB employing the SrCO3-Sr(OH2/PPy nanocomposite increases as compared with that obtained employing the SrCO3-Sr(OH2 nanocomposite.

  15. Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD.

    Science.gov (United States)

    Mukaisho, Ken-ichi; Hagiwara, Tadashi; Nakayama, Takahisa; Hattori, Takanori; Sugihara, Hiroyuki

    2014-09-14

    The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

  16. OncoPPi-informed discovery of mitogen-activated protein kinase kinase 3 as a novel binding partner of c-Myc | Office of Cancer Genomics

    Science.gov (United States)

    Mitogen-activated protein kinase kinase 3 (MKK3) is a dual threonine/tyrosine protein kinase that regulates inflammation, proliferation and apoptosis through specific phosphorylation and activation of the p38 mitogen-activated protein kinase. However, the role of MKK3 beyond p38-signaling remains elusive. Recently, we reported a protein-protein interaction (PPI) network of cancer-associated genes, termed OncoPPi, as a resource for the scientific community to generate new biological models. Analysis of the OncoPPi connectivity identified MKK3 as one of the major hub proteins in the network.

  17. Darkness facilitates the acoustic startle reflex in humans.

    Science.gov (United States)

    Grillon, C; Pellowski, M; Merikangas, K R; Davis, M

    1997-09-15

    The effects of darkness on startle reactivity and prepulse inhibition were investigated in two studies with 25 subjects participating in each study. Acoustic startle stimuli that were or were not preceded by an acoustic prepulse were delivered in alternating periods of complete darkness or light. In both studies, darkness significantly increased the magnitude of startle but did not affect prepulse inhibition (PPI). The PPI results suggest that darkness did not increase attention to the auditory modality, so that the startle facilitation in the dark probably did not result from an attentional process. The increased startle in the dark was significantly correlated with the intensity of subjects' fear of the dark as children based on retrospective rating scales. It is hypothesized that the startle facilitation in the dark results from a change in affect rather than from a change in attention.

  18. Dynamic programming re-ranking for PPI interactor and pair extraction in full-text articles

    Directory of Open Access Journals (Sweden)

    Lai Po-Ting

    2011-02-01

    Full Text Available Abstract Background Experimentally verified protein-protein interactions (PPIs cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be facilitated by employing text-mining systems to identify genes which play the interactor role in PPIs and to map these genes to unique database identifiers (interactor normalization task or INT and then to return a list of interaction pairs for each article (interaction pair task or IPT. These two tasks are evaluated in terms of the area under curve of the interpolated precision/recall (AUC iP/R score because the order of identifiers in the output list is important for ease of curation. Results Our INT system developed for the BioCreAtIvE II.5 INT challenge achieved a promising AUC iP/R of 43.5% by using a support vector machine (SVM-based ranking procedure. Using our new re-ranking algorithm, we have been able to improve system performance (AUC iP/R by 1.84%. Our experimental results also show that with the re-ranked INT results, our unsupervised IPT system can achieve a competitive AUC iP/R of 23.86%, which outperforms the best BC II.5 INT system by 1.64%. Compared to using only SVM ranked INT results, using re-ranked INT results boosts AUC iP/R by 7.84%. Statistical significance t-test results show that our INT/IPT system with re-ranking outperforms that without re-ranking by a statistically significant difference. Conclusions In this paper, we present a new re-ranking algorithm that considers co-occurrence among identifiers in an article to improve INT and IPT ranking results. Combining the re-ranked INT results with an unsupervised approach to find associations among interactors, the proposed method can boost the IPT performance. We also implement score computation using dynamic programming, which is faster and more efficient than traditional approaches.

  19. Stabilizer-Guided Inhibition of Protein-Protein Interactions.

    Science.gov (United States)

    Milroy, Lech-Gustav; Bartel, Maria; Henen, Morkos A; Leysen, Seppe; Adriaans, Joris M C; Brunsveld, Luc; Landrieu, Isabelle; Ottmann, Christian

    2015-12-21

    The discovery of novel protein-protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein-stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X-ray crystallographic data from both stabilizer and inhibitor co-crystal complexes of the adapter protein 14-3-3 to characterize, down to the atomic scale, inhibitors of the 14-3-3/Tau PPI, a potential drug target to treat Alzheimer's disease. The most potent compound notably inhibited the binding of phosphorylated full-length Tau to 14-3-3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer-protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14-3-3 and other PPIs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Construction of a Hierarchical NiCo2S4@PPy Core-Shell Heterostructure Nanotube Array on Ni Foam for a High-Performance Asymmetric Supercapacitor.

    Science.gov (United States)

    Yan, Minglei; Yao, Yadong; Wen, Jiqiu; Long, Lu; Kong, Menglai; Zhang, Guanggao; Liao, Xiaoming; Yin, Guangfu; Huang, Zhongbing

    2016-09-21

    In this paper, a hierarchical NiCo2S4@polypyrrole core-shell heterostructure nanotube array on Ni foam (NiCo2S4@PPy/NF) was successfully developed as a bind-free electrode for supercapacitors. NiCo2S4@PPy-50/NF obtained under 50 s PPy electrodeposition shows a low charge-transfer resistance (0.31 Ω) and a high area specific capacitance of 9.781 F/cm(2) at a current density of 5 mA/cm(2), which is two times higher than that of pristine NiCo2S4/NF (4.255 F/cm(2)). Furthermore, an asymmetric supercapacitor was assembled using NiCo2S4@PPy-50/NF as positive electrode and activated carbon (AC) as negative electrode. The resulting NiCo2S4@PPy-50/NF//AC device exhibits a high energy density of 34.62 Wh/kg at a power density of 120.19 W/kg with good cycling performance (80.64% of the initial capacitance retention at 50 mA/cm(2) over 2500 cycles). The superior electrochemical performance can be attributed to the combined contribution of both component and unique core-shell heterostructure. The results demonstrate that the NiCo2S4@PPy-50 core-shell heterostructure nanotube array is promising as electrode material for supercapacitors in energy storage.

  1. A novel EIS field effect structures coated with TESUD-PPy-PVC-dibromoaza[7]helicene matrix for potassium ions detection

    Energy Technology Data Exchange (ETDEWEB)

    Tounsi, Moncef, E-mail: tounsi1981@live.fr [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France); Ben Braiek, Mourad [Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Faculté des Sciences, Université de Monastir, Avenue de l' environnement, 5019, Monastir (Tunisia); Barhoumi, Houcine [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Baraket, Abdoullatif; Lee, Michael; Zine, Nadia [Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France); Maaref, Abderrazak [Laboratoire des Interfaces et des Matériaux Avancés (LIMA), Faculté des Sciences de Monastir, Université de Monastir (Tunisia); Errachid, Abdelhamid, E-mail: abdelhamid.errachid-el-salhi@univ-lyon1.fr [Université de Lyon, Institut de Sciences Analytiques (ISA) – UMR 5280, 5 rue de la Doua, 69100 Villeurbanne (France)

    2016-04-01

    In this work, we describe the development of new Aza[7]helicene-containing PVC-based membranes for the K{sup +} ions quantification. Here, silicon nitride-based structures (Si-p/SiO{sub 2}/Si{sub 3}N{sub 4}) were developed and the surface was activated, functionalized with an aldehyde–silane (11-(Triethoxysilyl)undecanal (TESUD)), functionalized with polypyrrole (PPy), and coated with the polyvinylchloride (PVC)-membrane containing the Aza[7]helicene as ionophore. All stages of functionalization process have been thoroughly studied by contact angle measurements (CAMs) and atomic force microscopy (AFM). The developed ion-selective electrode (ISE) was then applied using electrochemical impedance spectroscopy (EIS) for the detection of potassium ions. A linear range was observed between 1.0 × 10{sup −8} M to 1.0 × 10{sup −3} M and a detection limit of 1.0 × 10{sup −8} M was observed. The EIS results have showed a good sensitivity to potassium ion using this novel technique. The target helicene exhibited good solubility and excellent thermal stability with a high decomposition temperature (Td > 300 °C) and it indicates that helicene may be a promising material as ionophore for ion-selective electrodes (ISEs) elaboration. - Highlights: • Synthesis and characterization of a new derivatives of Aza[7]helicenes • Manufacture of PPy structures on the SiO{sub 2}/Si{sub 3}N{sub 4} surface using the TESUD as cross linking agent. • The PPy fabricated microstructures can be used as support matrix in biosensing. • Impedimetric K{sup +}-ISEs was developed by using dibromoaza[7]helicene as ionophore for K{sup +} ions determination.

  2. The effect of polyethylene glycol spacer chain length on the tumor-targeting potential of folate-modified PPI dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Shrikant [Dr. Hari Singh Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India); Tekade, Rakesh K., E-mail: rakeshtekade@yahoo.com [University of Hawai' i at Hilo, College of Pharmacy (United States); Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. Hari Singh Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-05-15

    The objective of the present investigation was to assess the tumor-targeting potential of ligand-spacer-engineered poly (propylene imine) (PPI) dendrimers as nanoscale drug delivery units for site-specific delivery of a model anticancer agent, docetaxel (DTX). PPI dendrimers were engineered by direct and indirect conjugation of folic acid (FA) via different types of polyethylene glycols (PEGs) [Mw (molecular weight): 1,000, 4,000, 6,000, 7,500] as spacers. The synthesized nanoconjugates (PPIFA, PPIP1FA, PPIP4FA, PPIP6FA, and PPIP7.5FA) were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance ({sup 1}H-NMR) and transmission electron microscopic (TEM) studies. Nanoconjugates were evaluated for entrapment, in vitro drug release (under various pH conditions) and hemolytic studies. Cell uptake and cytotoxicity studies were performed on human malignant cell lines (MCF-7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay. This debut study explored the effect of PEG spacer length on the targeting potential of folate-conjugated 5.0 G PPI dendrimer. DTX entrapment and in vitro drug release from nanoconjugates augmented, and hemolytic toxicity of nanoconjugates slashed with the molecular weight of PEGs. Further, nanoconjugates with PEG 4000 displayed highest tumor-targeting potential as compared to other spacer conjugated nanoconjugates due to optimized steric hindrance and receptor mediated endocytosis among other PEGs. This work is expected to shed new light on the role of spacer chain length in targeting potential of folate-anchored dendrimer.Graphical Abstract.

  3. The polarization observables T, P, and H and their impact on $\\gamma p \\to p\\pi^0$ multipoles

    CERN Document Server

    Hartmann, J; Anisovich, A V; Bayadilov, D; Beck, R; Becker, M; Beloglazov, Y; Berlin, A; Bichow, M; Böse, S; Brinkmann, K -Th; Crede, V; Dieterle, M; Eberhardt, H; Elsner, D; Fornet-Ponse, K; Friedrich, St; Frommberger, F; Funke, Ch; Gottschall, M; Gridnev, A; Grüner, M; Görtz, St; Gutz, E; Hammann, Ch; Hannappel, J; Hannen, V; Herick, J; Hillert, W; Hoffmeister, Ph; Honisch, Ch; Jahn, O; Jude, T; Käser, A; Kaiser, D; Kalinowsky, H; Kalischewski, F; Klassen, P; Keshelashvili, I; Klein, F; Klempt, E; Koop, K; Krusche, B; Kube, M; Lang, M; Lopatin, I; Makonyi, K; Messi, F; Metag, V; Meyer, W; Müller, J; Nanova, M; Nikonov, V; Novinski, D; Novotny, R; Piontek, D; Reeve, S; Rosenbaum, Ch; Roth, B; Reicherz, G; Rostomyan, T; Runkel, St; Sarantsev, A; Schmidt, Ch; Schmieden, H; Schmitz, R; Seifen, T; Sokhoyan, V; Thämer, Ph; Thiel, A; Thoma, U; Urban, M; van Pee, H; Walther, D; Wendel, Ch; Wiedner, U; Wilson, A; Winnebeck, A; Witthauer, L

    2015-01-01

    Data on the polarization observables T, P, and H for the reaction $\\gamma p\\to p\\pi^0$ are reported. Compared to earlier data from other experiments, our data are more precise and extend the covered range in energy and angle substantially. The results were extracted from azimuthal asymmetries measured using a transversely polarized target and linearly polarized photons. The data were taken at the Bonn electron stretcher accelerator ELSA with the CBELSA/TAPS detector. Within the Bonn-Gatchina partial wave analysis, the new polarization data lead to a significant narrowing of the error band for the multipoles for neutral-pion photoproduction.

  4. The p/pi ratio pT-dependence in the RHIC range od baryo-chemical potential

    CERN Document Server

    Katrynska, N

    2008-01-01

    The BRAHMS measurement of proton-to-pion ratios in Au+Au and p+p collisions at 62.4 and 200 GeV is presented as a function of transverse momentum and collision centrality within the pseudorapidity range 0 = 1.5 GeV/c. For these energy and pseudorapidity interval no centrality dependency of p/pi ratio is observed. The baryon-to-meson ratio of nucleus-nucleus data are consistent with results obtained for p+p interactions.

  5. Microwave absorption of a TiO2@PPy hybrid and its nonlinear dielectric resonant attenuation mechanism

    Science.gov (United States)

    Jiang, Wanchun; Wang, Yu; Xie, Aming; Wu, Fan

    2016-09-01

    We report on a high-performance electromagnetic absorption material (TiO2@PPy) developed via a facile in situ polymerization process, where lower than  -60 dB maximum absorption and 6.56 dB effective absorption bandwidth (lower than  -10 dB) can be obtained under low thickness. The excellent electromagnetic wave absorption ability is attributed to the synthetic effect of improved impedance matching and the dual loss mechanism, which originates from the polarization relaxations of dipoles induced by vacancy defects and a conductive network constructed by aerogels. An equivalent circuit model is established to explicate the nonlinear dielectric resonant attenuation mechanism.

  6. A strategy for designing multi-taxa specific reference gene systems. example of application--ppi phosphofructokinase (ppi-PPF) used for the detection and quantification of three taxa: maize (Zea mays), cotton (Gossypium hirsutum) and rice (Oryza sativa).

    Science.gov (United States)

    Chaouachi, Maher; Giancola, Sandra; Romaniuk, Marcel; Laval, Valérie; Bertheau, Yves; Brunel, Dominique

    2007-10-03

    In the first part of the paper, we report the description of a new strategy for the development of a plant reference gene system that can be used for genetically modified organism (GMO) analysis. On the basis of in silico research for candidate genes, the design of degenerate primers allowed the obtention of genomic sequences of the selected gene ppi-phosphofructokinase ( ppi-PPF) for nine taxa in which GMOs have been developed. The comparison and the analysis of inter- and intraspecies sequence variability were performed using a large number of species and cultivars. As an example of application following the detection of single nucleotide polymorphism, we designed specific conventional and real-time polymerase chain reaction tests for the detection and quantification of three taxa, namely, maize, cotton, and rice. This system was highly specific and sensitive. The gene copy number conservation among different cultivars was analyzed and confirmed with a sequencing step. This reference gene system is adequate for use in routine assays for the quantification of GMOs. We then explain briefly the constraints faced and propose recommendations when designing a reference gene system depending on the species to be targeted.

  7. Application of silane coupling agent in the preparation of Ppy/SiO2 conducting nanocomposites%硅烷偶联剂在PPy/SiO2纳米导电复合材料制备中的应用

    Institute of Scientific and Technical Information of China (English)

    任丽; 成国祥; 王立新

    2005-01-01

    A new route for the preparation of polypyrrole-silica (PPy/SiO2) nanocomposites was described. Silica particles were first modified by silane coupling agent γ-aminopropyltriethoxysilane (APS), then PPy/APS-SiO2 nanocomposites were prepared by chemical polymerization. The influences of adding coupling agent and its action mechanism were described. The PPy content,conductivity and stability of composites were increased according to the pretreatment of silica. In them, the conductivity of PPy/10% APS-SiO2 is 38.46S/cm, which is the highest among PPy/APS-SiO2 nanocomposites. The influences of silane coupling agent to the morphology of PPy/SiO2 nanocomposites were also described.%描述了一种合成PPy/SiO2纳米复合材料的新方法.首先用不同百分含量的氨丙基三乙氧基硅烷(APS)处理SiO2,然后通过化学氧化聚合法合成PPy/APS-SiO2纳米复合材料.文中讨论了偶联剂的使用对复合材料的影响及其作用机理.结果表明,用APS处理过的SiO2合成的复合材料其PPy含量、电导率和稳定性都有很大提高,其中用1%APS-SiO2合成的复合材料电导率最高,为38.4S/cm.文中还阐述了偶联剂的预处理对PPy/SiO2纳米复合材料形貌的影响.

  8. Preparation of PPy-Coated MnO2 Hybrid Micromaterials and Their Improved Cyclic Performance as Anode for Lithium-Ion Batteries

    Science.gov (United States)

    Feng, Lili; Zhang, Yinyin; Wang, Rui; Zhang, Yanli; Bai, Wei; Ji, Siping; Xuan, Zhewen; Yang, Jianhua; Zheng, Ziguang; Guan, Hongjin

    2017-09-01

    MnO2@PPy core-shell micromaterials are prepared by chemical polymerization of pyrrole on the MnO2 surface. The polypyrrole (PPy) is formed as a homogeneous organic shell on the MnO2 surface. The thickness of PPy shell can be adjusted by the usage of pyrrole. The analysis of SEM, FT-IR, X-ray photoelectron spectroscopy (XPS), thermo-gravimetric analysis (TGA), and XRD are used to confirm the formation of PPy shell. Galvanostatic cell cycling and electrochemical impedance spectroscopy (EIS) are used to evaluate the electrochemical performance as anode for lithium-ion batteries. The results show that after formation of MnO2@PPy core-shell micromaterials, the cyclic performance as anode for lithium-ion batteries is improved. Fifty microliters of PPy-coated caddice-clew-like MnO2 has the best cyclic performances as has 620 mAh g-1 discharge specific capacities after 300 cycles. As a comparison, the discharge specific capacity of bare MnO2 materials falls to below 200 mAh g-1 after 10 cycles. The improved lithium-storage cyclic stability of the MnO2@PPy samples attributes to the core-shell hybrid structure which can buffer the structural expansion and contraction of MnO2 caused by the repeated embedding and disengagement of Li ions and can prevent the pulverization of MnO2. This experiment provides an effective way to mitigate the problem of capacity fading of the transition metal oxide materials as anode materials for (lithium-ion batteries) LIBs.

  9. Characterization of poly pyrrole/montmorillonite electro polymerised onto Pt; Caracterizacao de filmes PPy/montmorilonita eletropolimerizados sobre Pt

    Energy Technology Data Exchange (ETDEWEB)

    Castagno, K.R.L., E-mail: katiarlc@pelotas.ifsul.edu.b [Instituto Federal Sul-rio-grandense (IFSul), RS (Brazil). Dept. de Quimica; Azambuja, D.S.; Dalmoro, V.; Mauller, R.S. [Universidade Federal do Rio Grande do Sul (UFRGS), Pelotas, RS (Brazil). Inst. de Quimica

    2010-07-01

    In this study films of polypyrrole/montmorillonite (PPy/MT) were electropolymerized on platinum in order to evaluate the performance of this technique in the preparation of nanocomposite materials and to determine the thermal properties and conductivity of the composites. The films were synthesized from a solution containing pyrrole, dodecylbenzene sulfonate, acid and two types of clays: montmorillonite-Na + (MT-Na) and montmorillonite-30B (MT-M). The characterization of the films we have used FT-IR, TEM, XRD, TGA, DSC and resistivity measurement by the four-point van der Pauw method. The study showed that the adopted method of exfoliation and the electropolymerization method used, allows obtaining nanocomposite materials. Analyses of FT-IR, TEM and XRD show that the clays are exfoliated in the polymer matrix. Thermal analysis of the films indicates that the addition of clay reflects an enhancement in the thermal properties of the matrix of PPy, but decreases the conductivity of the same. (author)

  10. Review of neon-like and nickel-like ions lasing on the J = 0 {r_arrow} 1 line using the prepulse and multiple pulse techniques

    Energy Technology Data Exchange (ETDEWEB)

    Nilsen, J.; Moreno, J.C.; Da Silva, L.B.; Barbee, T.W. Jr. [Lawrence Livermore National Lab., CA (United States); Li, Y.; Lu, P.; Fill, E.E. [Max-Planck-Inst. fuer Quantenoptik, Garching (Germany); Fiedorowicz, H.; Bartnik, A. [Military Univ. of Technology, Warsaw (Poland). Inst. of Optoelectronics

    1995-11-01

    The authors discuss the use of a prepulse technique to achieve lasing in low-Z neon-like ions on the 3p {r_arrow} 3s(J = 0 {r_arrow} 1) transition. Lasing has now been observed on this transitions for neon-like ions from chlorine to selenium with wavelengths ranging from 528 {angstrom} to 182 {angstrom}. For the germanium targets they present two dimensional space resolves images of the laser output with magnification of ten. Using a gas puff target as an alternative to the prepulse technique, they observe lasing at 469 {angstrom} in neon-like argon. Using a series of 100 ps pulses 400 ps apart to illuminate germanium and selenium plasmas they present results which now show the 3p {r_arrow} 3s(J = 0 {r_arrow} 1) transition to dominate the other laser lines even for selenium. Applying the multiple pulse technique to nickel-like ions they observed lasing at 79 {angstrom} on the 4d {r_arrow} 4p(J = 0 {r_arrow} 1) transition in nickel-like neodymium (Z = 60) when a series of 100--150 ps pulses which are 400--500 ps apart are used to illuminate slab targets of neodymium. To maximize the laser output for neodymium they combine the advantages of coupling two slab targets, using the traveling wave geometry, and curving the target surface.

  11. Abarelix: abarelix-depot-F, abarelix-depot-M, abarelix-L, PPI 149, R 3827.

    Science.gov (United States)

    2003-01-01

    Abarelix [Abarelix-Depot-F, Abarelix-Depot-M, Abarelix-L, PPI 149, R 3827, Plenaxis] is a peptide consisting of natural and artificial amino acids. In females, abarelix is an estrogen production antagonist with potential for the treatment of breast cancer, endometriosis and other reproductive hormone diseases. In males it is a testosterone production antagonist and has potential as hormonal therapy of prostate cancer. Depot formulations of abarelix (abarelix-depot-M and abarelix-depot-F) are being developed for hormonally responsive prostate cancer and endometriosis, respectively. Clinical development of the depot formulations is currently being conducted by Praecis Pharmaceuticals, the originators of the agent. A non-depot formulation, abarelix-L, was also being conducted for prostate gland volume reduction. Praecis Pharmaceuticals has entered into a number of licensing agreements covering abarelix. However, all agreements have since been terminated leaving Praecis to develop and commercialise the agent on its own. The terminated agreements include an agreement between Praecis and Roche for the commercialisation of abarelix in the US. This agreement was terminated in November 1998. Praecis Pharmaceuticals also entered into a collaborative agreement with Amgen in March 1999, whereby the companies would develop abarelix and Amgen would commercialise the drug in the US, Canada, Australia, Asia and several secondary markets. However, in September 2001, Praecis and Amgen announced that they were terminating the agreement for all indications. Praecis stated at the time that it remained committed to developing abarelix for both prostate cancer and endometriosis. Amgen had submitted 'Lotestrol' to the US Patent and Trademarks Office as a possible tradename for abarelix-depot-M. Lotestrol may also have been under consideration as a tradename for abarelix-depot-F. Praecis had also sold European, African, Latin American and Middle Eastern rights to abarelix to Sanofi

  12. Magnetic Separation-Assistant Fluorescence Resonance Energy Transfer Inhibition for Highly Sensitive Probing of Nucleolin.

    Science.gov (United States)

    Li, Yan-Ran; Liu, Qian; Hong, Zhangyong; Wang, He-Fang

    2015-12-15

    For the widely used "off-on" fluorescence (or phosphorescence) resonance energy transfer (FRET or PRET) system, the separation of donors and acceptors species was vital for enhancing the sensitivity. To date, separation of free donors from FRET/PRET inhibition systems was somewhat not convenient, whereas separation of the target-induced far-between acceptors has hardly been reported yet. We presented here a novel magnetic separation-assistant fluorescence resonance energy transfer (MS-FRET) inhibition strategy for highly sensitive detection of nucleolin using Cy5.5-AS1411 as the donor and Fe3O4-polypyrrole core-shell (Fe3O4@PPY) nanoparticles as the NIR quenching acceptor. Due to hydrophobic interaction and π-π stacking of AS1411 and PPY, Cy5.5-AS1411 was bound onto the surface of Fe3O4@PPY, resulting in 90% of fluorescence quenching of Cy5.5-AS1411. Owing to the much stronger specific interaction of AS1411 and nucleolin, the presence of nucleolin could take Cy5.5-AS1411 apart from Fe3O4@PPY and restore the fluorescence of Cy5.5-AS1411. The superparamagnetism of Fe3O4@PPY enabled all separations and fluorescence measurements complete in the same quartz cell, and thus allowed the convenient but accurate comparison of the sensitivity and fluorescence recovery in the cases of separation or nonseparation. Compared to nonseparation FRET inhibition, the separation of free Cy5.5-AS1411 from Cy5.5-AS1411-Fe3O4@PPY solution (the first magnetic separation, MS-1) had as high as 25-fold enhancement of the sensitivity, whereas further separation of the nucleolin-inducing far-between Fe3O4@PPY from the FRET inhibition solution (the second magnetic separation, MS-2) could further enhance the sensitivity to 35-fold. Finally, the MS-FRET inhibition assay displayed the linear range of 0.625-27.5 μg L(-1) (8.1-359 pM) and detection limit of 0.04 μg L(-1) (0.05 pM) of nucleolin. The fluorescence intensity recovery (the percentage ratio of the final restoring fluorescence intensity

  13. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1

    Energy Technology Data Exchange (ETDEWEB)

    Hort, Y.; Shine, J.; Herzog, H. [Garvan Inst. of Medical Research, Sydney (Australia)

    1995-03-01

    Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related but functionally diverse peptides, encoded by separate genes and expressed in different tissues. Although the human NPY gene has been mapped to chromosome 7, the authors demonstrate here that the genes for human PYY and PP (PPY) are localized only 10 kb apart from each another on chromosome 17q21.1. The high degree of homology between the members of this gene family, both in primary sequence and exon/intron structure, suggests that the NYP and the PYY genes arose from an initial gene duplication event, with a subsequent tandem duplication of the PYY gene being responsible for the creation of the PPY gene. A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event. 27 refs., 5 figs.

  14. Vonoprazan-Based Regimen Is More Useful than PPI-Based One as a First-Line Helicobacter pylori Eradication: A Randomized Controlled Trial

    Science.gov (United States)

    Tanaka, Naoki; Kubota, Daisuke; Miyajima, Masayuki; Tokutake, Koujiro; Imai, Ryujiro; Fujisawa, Toru; Mori, Hiromitsu; Matsuda, Yoshiaki; Wada, Shuichi; Horiuchi, Akira; Kiyosawa, Kendo

    2017-01-01

    Background. A new agent, potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer advantages over conventional H. pylori eradication therapies. We aimed to compare the eradication rate between VPZ-based treatment and PPI-based one. Methods. This randomized controlled trial was designed to assign 141 patients with H. pylori-positive gastritis to VPZ group (VPZ 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days) or PPI group (rabeprazole 20 mg or lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days). Primary endpoints were eradication rates and adverse events. Results. Seventy of 72 patients in VPZ group and 63 of 69 patients in PPI group completed the treatment after 7 days. The eradication rate was significantly higher in VPZ group than PPI group by intention-to-treat analysis (95.8% versus 69.6%, P = 0.00003, 95% confidence interval [CI] 88.3-99.1% versus 57.3-80.1%) and per-protocol analysis (95.7% versus 71.4%, P = 0.0002, 95% CI 88.0-99.1% versus 58.7-82.1%). The incidence of adverse events was not different between the groups (26.3% in VPZ group versus 37.7% in PPI group, P = 0.15). Conclusion. VPZ-based regimen is more useful than that PPI-based regimen as a first-line H. pylori eradication therapy.

  15. Influence of Monomer Concentration on the Morphologies and Electrochemical Properties of PEDOT, PANI, and PPy Prepared from Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Shalini Kulandaivalu

    2016-01-01

    Full Text Available Poly(3,4-ethylenedioxyhiophene (PEDOT, polyaniline (PANI, and polypyrrole (PPy were prepared on indium tin oxide (ITO substrate via potentiostatic from aqueous solutions containing monomer and lithium perchlorate. The concentration of monomers was varied between 1 and 10 mM. The effects of monomer concentration on the polymers formation were investigated and compared by using Fourier transform infrared spectroscopy (FTIR, Raman spectroscopy, scanning electron microscopy (SEM, cyclic voltammetry (CV, and electrochemical impedance spectroscopy (EIS measurements. FTIR and Raman spectra showed no changes in the peaks upon the increment of the concentration. Based on the SEM images, the increment in monomer concentration gives significant effect on morphologies and eventually affects the electrochemical properties. PEDOT electrodeposited from 10 mM solution showed excellent electrochemical properties with the highest specific capacitance value of 12.8 mF/cm2.

  16. Electromagnetically Modified Filtration of Aluminum Melts—Part I: Electromagnetic Theory and 30 PPI Ceramic Foam Filter Experimental Results

    Science.gov (United States)

    Kennedy, Mark William; Akhtar, Shahid; Bakken, Jon Arne; Aune, Ragnhild E.

    2013-06-01

    In the present work, laboratory-scale continuous filtration tests of liquid A356 aluminum alloy have been performed. The tests were conducted using standard 30 PPI (pores per inch) ceramic foam filters combined with magnetic flux densities (~0.1 and 0.2 T), produced using two different induction coils operated at 50 Hz AC. A reference filtration test was also carried out under gravity conditions, i.e., without an applied magnetic field. The obtained results clearly prove that the magnetic field has a significant affect on the distribution of SiC particles. The influence of the electromagnetic Lorentz forces and induced bulk metal flow on the obtained filtration efficiencies and on the wetting behavior of the filter media by liquid aluminum is discussed. The magnitudes of the Lorentz forces produced by the induction coils are quantified based on analytical and COMSOL 4.2® finite element modeling.

  17. Disruption in a Neurodevelopmental Model of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Benjamin Rolland

    2012-01-01

    Full Text Available Oxidative stress has been implicated in neurodevelopmental theories of schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptors α (PPARα agonist fenofibrate has neuroprotective properties and could reverse early preclinical infringements that could trigger the illness. We have evaluated the neuroprotective interest of fenofibrate in a neurodevelopmental rat model of schizophrenia. The oxidative lesion induced by Kainic Acid (KA injection at postnatal day (PND 7 has previously been reported to disrupt Prepulse Inhibition (PPI at PND56 but not at PND35. In 4 groups of 15 male rats each, KN (KA-PND7 + normal postweaning food, KF (KA-PND7 + fenofibrate 0.2% food, ON (saline-PND7 + normal food, and OF (saline + fenofibrate food, PPI was recorded at PND35 and PND56. Three levels of prepulse were used: 73 dB, 76 dB, and 82 dB for a pulse at 120 dB. Four PPI scores were analyzed: PPI73, PPI76, PPI82, and mean PPI (PPIm. Two-way ANOVAs were used to evaluate the effects of both factors (KA + fenofibrate, and, in case of significant results, intergroup Student’s t-tests were performed. We notably found a significant difference (P<0.05 in PPIm between groups KN and KF at PND56, which supposes that fenofibrate could be worthy of interest for early neuroprotection in schizophrenia.

  18. The PPI3D web server for searching, analyzing and modeling protein-protein interactions in the context of 3D structures.

    Science.gov (United States)

    Dapkūnas, Justas; Timinskas, Albertas; Olechnovič, Kliment; Margelevičius, Mindaugas; Dičiūnas, Rytis; Venclovas, Česlovas

    2016-12-22

    The PPI3D web server is focused on searching and analyzing the structural data on protein-protein interactions. Reducing the data redundancy by clustering and analyzing the properties of interaction interfaces using Voronoi tessellation makes this software a highly effective tool for addressing different questions related to protein interactions.

  19. A Kappa Opioid Model of Atypical Altered Consciousness and Psychosis: U50488, DOI, AC90179 Effects on Prepulse Inhibition and Locomotion in Mice.

    Science.gov (United States)

    Ruderman, Michael A; Powell, Susan B; Geyer, Mark A

    2009-07-01

    Sensorimortor gating and locomotion are behaviors that reflect pre-attentive sensory filtering and higher order, top-down, sensory processing, respectively. These processes are thought to affect either the perception of novelty in an environment (filtering) or cognition (higher order processing), salient features of models of altered states of consciousness (ASC). Drugs with highly selective receptor affinities that produce ASC can help to establish neural correlates, pathways, and mechanisms underlying ASC. Furthermore, screening for substances that selectively reverse drug-induced sensory processing departures is valuable for development of experimental antipsychotics. This study investigated the anomalous opioid sub-type, the kappa opioid (KA) system, within the two ASC models. Significant interaction and reversal effects between KA and the serotonin/2A (5-HT2A) system - the serotonin sub-type associated with classical psychedelics - were observed in three BPM measures. These measures showed that KA activation-induced effects could be reversed by 5-HT2A deactivation. These results suggest that KA could function as an atypical antipsychotic medications and/or as a screening tool for new antipsychotic medicines. The experimental work for this study comprised dose-response and reversal experiments with drugs that activate and deactivate kappa opioid and serotonin systems in the two behavioral models for the first time in mice.

  20. Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia-Gating of auditory-evoked potentials and prepulse inhibition

    DEFF Research Database (Denmark)

    Broberg, Brian Villumsen; Oranje, Bob; Yding, Birte

    2010-01-01

    The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages of se...

  1. A precision measurement of the $p$($e,e^\\prime p\\,$)$\\pi^0$ reaction at threshold

    CERN Document Server

    Chirapatpimol, K; Lindgren, R A; Smith, L C; Annand, J R M; Higinbotham, D W; Moffit, B; Nelyubin, V; Norum, B E; Allada, K; Aniol, K; Ardashev, K; Armstrong, D S; Arndt, R A; Benmokhtar, F; Bernstein, A M; Bertozzi, W; Briscoe, W J; Bimbot, L; Camsonne, A; Chen, J -P; Choi, S; Chudakov, E; Cisbani, E; Cusanno, F; Dalton, M M; Dutta, C; Egiyan, K; Fernandez-Ramirez, C; Feuerbach, R; Fissum, K G; Frullani, S; Garibaldi, F; Gayou, O; Gilman, R; Gilad, S; Goity, J; Gomez, J; Hahn, B; Hamilton, D; Hansen, J -O; Huang, J; Igarashi, R; Ireland, D; de Jager, C W; Jin, X; Jiang, X; Jinasundera, T; Kellie, J; Keppel, C E; Kolb, N; LeRose, J; Liyanage, N; Livingston, K; McNulty, D; Mercado, L; Michaels, R; Mihovilovic, M; Qian, S; Qian, X; Mailyan, S; Mamyan, V; Marrone, S; Monaghan, P; Nanda, S; Perdrisat, C F; Piasetzky, E; Protopopescu, D; Punjabi, V; Qiang, Y; Rachek, I A; Rakhman, A; Ron, G; Rosner, G; Saha, A; Sawatzky, B; Shahinyan, A; Sirca, S; Sparveris, N; Subedi, R R; Suleiman, R; Strakovsky, I; Sulkosky, V; Moinelo, J; Voskanyan, H; Wang, K; Wang, Y; Watson, J; Watts, D; Wojtsekhowski, B; Workman, R L; Yao, H; Zhan, X; Zhang, Y

    2015-01-01

    New results are reported from an experiment to measure $\\pi^0$ electroproduction at and above threshold using the $p(e,e^{\\prime} p)\\pi^0$ reaction. The experiment was designed to precisely determine the energy dependence of $s-$ and $p-$wave electromagnetic multipoles as a stringent test of the predictions of Chiral Perturbation Theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the $\\phi^*_{\\pi}$ and $\\theta^*_{\\pi}$ angles in the $p \\pi^0$ center-of-mass was obtained for invariant energies above threshold from 0.5~MeV up to 15~MeV. The 4-momentum transfer $Q^2$ coverage ranges from 0.05 to 0.155 (GeV/c)$^2$ in fine steps. A simple phenomenological analysis of our data shows strong disagreement with $p-$wave predictions from ChPT for $Q^2>0.07$ (GeV/c)$^2$, while the $s-$wave predictions are in reasonable agreement.

  2. Ens-PPI: A Novel Ensemble Classifier for Predicting the Interactions of Proteins Using Autocovariance Transformation from PSSM

    Directory of Open Access Journals (Sweden)

    Zhen-Guo Gao

    2016-01-01

    Full Text Available Protein-Protein Interactions (PPIs play vital roles in most biological activities. Although the development of high-throughput biological technologies has generated considerable PPI data for various organisms, many problems are still far from being solved. A number of computational methods based on machine learning have been developed to facilitate the identification of novel PPIs. In this study, a novel predictor was designed using the Rotation Forest (RF algorithm combined with Autocovariance (AC features extracted from the Position-Specific Scoring Matrix (PSSM. More specifically, the PSSMs are generated using the information of protein amino acids sequence. Then, an effective sequence-based features representation, Autocovariance, is employed to extract features from PSSMs. Finally, the RF model is used as a classifier to distinguish between the interacting and noninteracting protein pairs. The proposed method achieves promising prediction performance when performed on the PPIs of Yeast, H. pylori, and independent datasets. The good results show that the proposed model is suitable for PPIs prediction and could also provide a useful supplementary tool for solving other bioinformatics problems.

  3. Synthesis and characterization of novel PPy/Bi{sub 2}O{sub 2}CO{sub 3} composite with improved photocatalytic activity for degradation of Rhodamine-B

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qizhao, E-mail: wangqizhao@163.com [College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Key Laboratory of Gansu Polymer Materials, Lanzhou 730070 (China); Zheng, Longhui; Chen, Yutao; Fan, Jiafeng [College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Key Laboratory of Gansu Polymer Materials, Lanzhou 730070 (China); Huang, Haohao, E-mail: scuthhh@hotmail.com [College of Materials Science and Engineering, South China University of Technology, Guangzhou 510640 (China); Su, Bitao [College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education of China, Key Laboratory of Gansu Polymer Materials, Lanzhou 730070 (China)

    2015-07-15

    Highlights: • A new photocatalyst PPy/Bi{sub 2}O{sub 2}CO{sub 3} was synthesized by a simple hydrothermal method. • The PPy/Bi{sub 2}O{sub 2}CO{sub 3} photocatalyst shows enhanced degradation activity of RhB under UV light irradiation. • A photocatalytic mechanism is proposed based on the synergistic effect of PPy and Bi{sub 2}O{sub 2}CO{sub 3}. - Abstract: Photocatalyst Bi{sub 2}O{sub 2}CO{sub 3} modified by polypyrrole (PPy) was synthesized via a facile hydrothermal method. As-prepared PPy/Bi{sub 2}O{sub 2}CO{sub 3} composites were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV–vis diffuse reflectance spectroscopy (DRS). Presence of PPy did not affect the crystal structure, but exerted great influence on the photocatalytic activity of Bi{sub 2}O{sub 2}CO{sub 3} and enhanced absorption band of pure Bi{sub 2}O{sub 2}CO{sub 3}. The photocatalytic activities of the PPy/Bi{sub 2}O{sub 2}CO{sub 3} samples were determined by photocatalytic degradation of Rhodamine-B (RhB) under ultra violet (UV) irradiation and 0.75 wt.% PPy/Bi{sub 2}O{sub 2}CO{sub 3} composite showed the highest photocatalytic activity. The enhanced photocatalytic performance could be attributed to the synergistic effect of PPy and Bi{sub 2}O{sub 2}CO{sub 3}. A possible photocatalytic mechanism of the PPy/Bi{sub 2}O{sub 2}CO{sub 3} photocatalysts was proposed in order to guide the further improvement of its photocatalytic performance.

  4. Facile fabrication of ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/PPy and application in water treatment

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Penghui; Zhao, Baobao; Nan, Zhaodong, E-mail: zdnan@yzu.edu.cn

    2013-12-01

    Graphical abstract: A core–shell structure of magnetic ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/PPy nanoparticles was facilely fabricated at room temperature. The ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/PPy shows higher adsorption rate and capacity in removal of anionic organic dye, methyl orange (MO), from water than that of ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}. -- Highlights: • A core–shell structure of ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/PPy nanoparticles was facilely fabricated at room temperature. • The saturation magnetization and electric conductivity of the sample are 26.0 ± 0.2 emu/g, 169 ± 2 S/cm, respectively. • The ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/PPy shows higher adsorption rate and capacity in removal of anionic organic dye, methyl orange (MO), from water than that of ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}. -- Abstract: A core–shell structure of magnetic ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/Polypyrrole (PPy) nanoparticles (NPs) was facilely fabricated at room temperature, in which FeCl{sub 3} was used as an initiator. Dodecyl sulfate anions (SDS) were adsorbed onto the outer surface of the ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4} through the charge compensation. The absorbed SDS induced the adhesion of the PPy to the surface of the ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4} along with polymerization. The as-prepared composite shows better performance in removal of pollutants like methyl orange (MO) from water by adsorption than that of the ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}. The adsorption experiments indicated that the adsorption was divided into two processes. The maximum adsorption capacity for MO was determined to be 76.34 mg/g. The experimental data fit the Langmuir model implying the single layer adsorption. The adsorption process was described by the pseudo-second-order kinetic model. The adsorption of MO onto the ZnLa{sub 0.02}Fe{sub 1.98}O{sub 4}/PPy was exothermic process, and the randomness decreased at the process. To decrease experimental temperature is

  5. Quasi-molecular electron promotion beyond the 1s$\\sigma$ and 2p$\\pi$ channels in slow collisions of He$^{2+}$ and He

    CERN Document Server

    Schmidt, L Ph H; Goihl, C; Jahnke, T; Schmidt-Böcking, H; Dörner, R

    2015-01-01

    The electron emission pattern of transfer-ionization in collisions of He$^{2+}$ with He was investigated for impact velocities between 0.53 a.u. and 0.77 a.u. (7 keV/u - 15 keV/u) employing recoil-ion momentum spectroscopy. This process is known to be dominated by the promotion of the 2p$\\pi$ molecular orbital into the continuum which results in "banana" shaped areas of high electron momentum densities extending from the target to the projectile in velocity space in the collision plain. Asymmetries are explained by a coherent superposition of the 2p$\\pi$ channel of the quasi molecular promotion with the 1s$\\sigma$ channel. Here we report on an additional contribution of higher angular momentum molecular states for close collisions which emerge at smaller impact velocities. They show up as highly structured electron emission patterns in the plane perpendicular to the direction of impact.

  6. Binder-free network-enabled MoS2-PPY-rGO ternary electrode for high capacity and excellent stability of lithium storage

    Science.gov (United States)

    Xie, D.; Wang, D. H.; Tang, W. J.; Xia, X. H.; Zhang, Y. J.; Wang, X. L.; Gu, C. D.; Tu, J. P.

    2016-03-01

    A unique MoS2-based composite composed of MoS2 nanosheets wrapped by a conductive polypyrrole (PPY) layer and closely incorporated within reduced graphene oxide (rGO) nanosheets is prepared by all-solution method. As a free-binder electrode for lithium-ion batteries, the ternary electrode delivers an initial discharge capacity of 1428 mAh g-1, maintains 1070 mAh g-1 after 400 cycles at a current density of 200 mA g-1, and also exhibits superior rate capacity of 600 mAh g-1 at a high current density of 2000 A g-1. The enhanced electrochemical performance is attributed to the advantageous combination of the 3D hierarchically rGO skeleton and in-situ formed conductive PPY coating. This design route represents a new direction for high-performance lithium ion batteries and related energy storage application with advanced nanostructured materials.

  7. Immobilization of actinide ions in thin layers of polypyrrole/polyacrylamidoglycolic acid (PPy/PAGA) composite. Application to the preparation of alpha spectrometry sources

    Energy Technology Data Exchange (ETDEWEB)

    Leroy, D.; Mignonsin, P.; Lambert, B. [Liege Univ. (Belgium). Coordination Chemistry and Radiochemistry; Martinot, L. [Liege Univ. (Belgium). Coordination Chemistry and Radiochemistry; Research Associate of the Inter-Univ., Brussels (Belgium). Inst. for Nuclear Sciences; Jerome, C.; Jerome, R. [Liege Univ. (BE). Center of Education and Research on Macromolecules (CERM)

    2002-07-01

    We propose a new fully aqueous electrochemical method for the preparation of high resolution alpha sources. Thin films of polypyrrole (PPy) are prepared by anodic electropolymerization, starting from aqueous solutions of the pyrrole monomer and an anionic polyelectrolyte which is able to complex actinide and play the role of PPy doping agent: polyacrylamidoglycolic acid (PAGA). These thin films can be prepared on various electrodes: stainless steel, platinum, glassy carbon and polyethylene doped by carbon-black. Peeling tests revealed their strong adhesion on stainless steel electrode. Alpha sources were prepared by simple immersion in actinide containing solutions. This easy process results in alpha sources with outstanding energy resolution (FWHM: around 9 keV for various isotopes). (orig.)

  8. Assessment on tracking error performance of Cascade P/PI, NPID and N-Cascade controller for precise positioning of xy table ballscrew drive system

    Science.gov (United States)

    Abdullah, L.; Jamaludin, Z.; Rafan, N. A.; Jamaludin, J.; Chiew, T. H.

    2013-12-01

    At present, positioning plants in machine tools are looking for high degree of accuracy and robustness attributes for the purpose of compensating various disturbance forces. The objective of this paper is to assess the tracking performance of Cascade P/PI, Nonlinear PID (NPID) and Nonlinear cascade (N-Cascade) controller with the existence of disturbance forces in the form of cutting forces. Cutting force characteristics at different cutting parameters; such as spindle speed rotations is analysed using Fast Fourier Transform. The tracking performance of a Nonlinear cascade controller in presence of these cutting forces is compared with NPID controller and Cascade P/PI controller. Robustness of these controllers in compensating different cutting characteristics is compared based on reduction in the amplitudes of cutting force harmonics using Fast Fourier Transform. It is found that the N-cascade controller performs better than both NPID controller and Cascade P/PI controller. The average percentage error reduction between N-cascade controller and Cascade P/PI controller is about 65% whereas the average percentage error reduction between cascade controller and NPID controller is about 82% at spindle speed of 3000 rpm spindle speed rotation. The finalized design of N-cascade controller could be utilized further for machining application such as milling process. The implementation of N-cascade in machine tools applications will increase the quality of the end product and the productivity in industry by saving the machining time. It is suggested that the range of the spindle speed could be made wider to accommodate the needs for high speed machining.

  9. Ultra-broad polypyrrole (PPy) nano-ribbons seeded by racemic surfactants aggregates and their high-performance electromagnetic radiation elimination

    Science.gov (United States)

    Jiao, Yingzhi; Wu, Fan; Zhang, Kun; Sun, Mengxiao; Xie, Aming; Dong, Wei

    2017-08-01

    Ribbon-like nano-structures possess high aspect ratios, and thus have great potential in the development of high-performance microwave absorption (MA) materials that can effectively eliminate adverse electromagnetic radiation. However, these nano-structures have been scarcely constructed in the field of MA, because of the lack of efficient synthetic routes. Herein, we developed an efficient method to successfully construct polypyrrole (PPy) nano-ribbons using the self-assembly aggregates of a racemic surfactant as the seeds. The frequency range with a reflection loss value of lower than -10 dB reached 7.68 GHz in the frequency range of 10.32-18.00 GHz, and surpassed all the currently reported PPy nano-structures, as well as most other MA nano-materials. Through changing the amount of surfactant, both the nano-structures and MA performance can be effectively regulated. Furthermore, the reason behind the high-performance MA of PPy nano-ribbons has been deeply explored. It opens up the opportunity for the application of conducting polymer nano-ribbons as a lightweight and tunable high-performance MA material, especially in applications of special aircraft and flexible electronics.

  10. Contribution of PPi-Hydrolyzing Function of Vacuolar H(+)-Pyrophosphatase in Vegetative Growth of Arabidopsis: Evidenced by Expression of Uncoupling Mutated Enzymes.

    Science.gov (United States)

    Asaoka, Mariko Mariko Asaoka; Segami, Shoji; Ferjani, Ali; Maeshima, Masayoshi

    2016-01-01

    The vacuolar-type H(+)-pyrophosphatase (H(+)-PPase) catalyzes a coupled reaction of pyrophosphate (PPi) hydrolysis and active proton translocation across the tonoplast. Overexpression of H(+)-PPase improves growth in various plant species, and loss-of-function mutants (fugu5s) of H(+)-PPase in Arabidopsis thaliana have post-germinative developmental defects. Here, to further clarify the physiological significance of this important enzyme, we newly generated three varieties of H(+)-PPase overexpressing lines with different levels of activity that we analyzed together with the loss-of-function mutant fugu5-3. The H(+)-PPase overexpressors exhibited enhanced activity of H(+)-PPase during vegetative growth, but no change in the activity of vacuolar H(+)-ATPase. Overexpressors with high enzymatic activity grew more vigorously with fresh weight increased by more than 24 and 44%, compared to the wild type and fugu5-3, respectively. Consistently, the overexpressors had larger rosette leaves and nearly 30% more cells in leaves than the wild type. When uncoupling mutated variants of H(+)-PPase, that could hydrolyze PPi but could not translocate protons, were introduced into the fugu5-3 mutant background, shoot growth defects recovered to the same levels as when a normal H(+)-PPase was introduced. Taken together, our findings clearly demonstrate that additional expression of H(+)-PPase improves plant growth by increasing cell number, predominantly as a consequence of the PPi-hydrolyzing activity of the enzyme.

  11. Habituation of the startle reflex depends on attention in cannabis users

    OpenAIRE

    Kedzior, Karina K.; Wehmann, Eileen; Martin-Iverson, Mathew

    2016-01-01

    Background Cannabis use is associated with an attention-dependent deficit in prepulse inhibition of the startle reflex (PPI). The aim of the current study was to investigate startle habituation in cannabis users and healthy controls during two attentional tasks. Methods Auditory startle reflex was recorded from orbicularis oculi muscle while participants (12 controls and 16 regular cannabis users) were either attending to or ignoring 100 dB startling pulses. Startle habituation was measured a...

  12. 介孔二氧化硅基导电聚合物复合材料热导率的实验研究%Thermal conductivity measurements on PANI/SBA-15 and PPy/SBA-15

    Institute of Scientific and Technical Information of China (English)

    黄丛亮; 冯妍卉; 张欣欣; 李威; 杨穆; 李静; 王戈

    2012-01-01

    Conductive polymers polyaniline(PANI) and polypyrrole(PPy) loaded mesoporous silica(SBA-15) composites are prepared and characterized.The one-dimensional reference bar method and the relevant devices to measure the thermal conductivity are introduced and established.The equivalent pore diameter is proposed to characterize the mesostructures of conductive polymers polyaniline(PANI) and polypyrrole(PPy) in PANI/SBA-15 and PPy/SBA-15 composites.The effects of the equivalent and the measurement pore diameters on thermal conductivities of PANI/SBA-15 and PPy/SBA-15 composites are analyzed.The result shows that thermal conductivities of PANI/SBA-15 and PPy/SBA-15 are higher than that of the substrate SBA-15;the thermal conductivity of PANI/SBA-15 is higher than that of PPy/SBA-15;loading of PANI and PPy in pores of PANI/SBA-15 and PPy/SBA-15 composites is more effective than loading outside of pores for improving the thermal conductivities of PANI/SBA-15 and PPy/SBA-15 composites.%本文首先制备并表征了介孔二氧化硅SBA-15、填充导电聚合物的复合材料PANI/SBA-15和复合材料PPy/SBA-15,并建立双流计实验台开展了材料压片情况下的热导率研究.在测量得到复合材料热导率的基础上,引入当量孔径,结合测量孔径对PANI/SBA-15和PPy/SBA-15复合材料热导率随填充量的变化进行了定性分析.分析表明:PANI/SBA-15和PPy/SBA-15复合材料的热导率比基材SBA-15的热导率大得多;在相同的测量孔径和当量孔径情况下,PANI/SBA-15复合材料的热导率比PPy/SBA-15复合材料的热导率大;导电聚合物填充到复合材料孔道内和孔道外都有助于热导率的提高,填充到孔道内比填充到孔道外对热导率提高的贡献更大.

  13. Postauricular reflexes elicited by soft acoustic clicks and loud noise probes: Reliability, prepulse facilitation, and sensitivity to picture contents.

    Science.gov (United States)

    Aaron, Rachel V; Benning, Stephen D

    2016-12-01

    The startle blink reflex is facilitated during early picture viewing, then inhibited by attention during pleasant and aversive pictures compared to neutral pictures, and finally potentiated during aversive pictures specifically. However, it is unclear whether the postauricular reflex, which is elicited by the same loud acoustic probe as the startle blink reflex but enhanced by appetitive instead of defensive emotion, has the same pattern and time course of emotional modulation. We examined this issue in a sample of 90 undergraduates using serially presented soft acoustic clicks that elicited postauricular (but not startle blink) reflexes in addition to standard startle probes. Postauricular reflexes elicited by both clicks and probes correlated during food and nurturant contents, during which they were potentiated compared to neutral pictures, suggesting clicks effectively elicit emotionally modulated postauricular reflexes. The postauricular reflex was initially facilitated during the first 500 ms of picture processing but was larger during pleasant than neutral pictures throughout picture processing, with larger effect sizes during the latter half of picture processing. Across reflexes and eliciting stimuli, measures of emotional modulation had higher coefficient alphas than magnitudes during specific picture contents within each valence, indicating that only emotional modulation measures assess higher-order appetitive or defensive processing. © 2016 Society for Psychophysiological Research.

  14. In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-10-01

    Full Text Available Abstract Background Childhood peroxisomal disorders and leukodystrophies are devastating diseases characterized by dysfunctional lipid metabolism. Plasmalogens (ether glycerophosphoethanolamine lipids are decreased in these genetic disorders. The biosynthesis of plasmalogens is initiated in peroxisomes but completed in the endoplasmic reticulum. We therefore undertook a study to evaluate the ability of a 3-substituted, 1-alkyl, 2-acyl glyceryl ether lipid (PPI-1011 to replace plasmalogens in rhizomelic chrondrodysplasia punctata type 1 (RCDP1 and rhizomelic chrondrodysplasia punctata type 2 (RCDP2 lymphocytes which possess peroxisomal mutations culminating in deficient plasmalogen synthesis. We also examined plasmalogen synthesis in Pelizaeus-Merzbacher disease (PMD lymphocytes which possess a proteolipid protein-1 (PLP1 missense mutation that results in abnormal PLP1 folding and it's accumulation in the endoplasmic reticulum (ER, the cellular site of the last steps in plasmalogen synthesis. In vivo incorporation of plasmalogen precursor into tissue plasmalogens was also evaluated in the Pex7 mouse model of plasmalogen deficiency. Results In both RCDP1 and RCDP2 lymphocytes, PPI-1011 repleted the target ethanolamine plasmalogen (PlsEtn16:0/22:6 in a concentration dependent manner. In addition, deacylation/reacylation reactions resulted in repletion of PlsEtn 16:0/20:4 in both RCDP1 and RCDP2 lymphocytes, repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP2 lymphocytes, and partial repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP1 lymphocytes. In the Pex7 mouse, oral dosing of labeled PPI-1011 demonstrated repletion of tissue levels of the target plasmalogen PlsEtn 16:0/22:6 with phospholipid remodeling also resulting in significant repletion of PlsEtn 16:0/20:4 and PlsEtn 16:0/18:1. Metabolic conversion of PPI-1011 to the target plasmalogen was most active in the liver. Conclusions Our data demonstrate that PPI-1011 is activated

  15. Penformance Study on Microspheres of PPy/Alginate Manganese%聚吡咯/海藻酸锰小球的性能研究

    Institute of Scientific and Technical Information of China (English)

    陈峰; 叶红; 彭湘红; 胡明

    2014-01-01

    Alginate mangane microspheres were prepared by dipping the alginate solution in the manganese chloride solution,and then used to adsorb the pyrrole monomer. Using acidic potassium permanganate solution as oxidation agent,the pyrrole monomer was polymerized to form the polypyr⁃role(PPy)on the surface of the alginate manganese spheres to form the composites microspheres of PPy/alginate manganese. The structure,morphology and electrochemical properties of the composite spheres were characterizated by the infrared spectroscopy,SEM and electrochemical workstation. The results showed that there was PPy microspheres with 200 to 500 nm diameter on the surface of the composites spheres of alginate manganese. As increasing the solidification time,PPy/alginate manganese alginate composite spheres had a tighter structure with a lower polypyrrole amount,its ca⁃pacitance decreased. Such spheres with the biocompatible and conduct properties will be widely ap⁃plied in the novel electrode field.%将海藻酸钠水溶液滴加到MnCl2水溶液中凝固成海藻酸锰小球。海藻酸锰小球吸附吡咯单体,在酸性KMnO4溶液中使吡咯单体氧化聚合成聚吡咯(PPy),得到聚吡咯/海藻酸锰复合小球(MPM)。用红外光谱仪、扫描电子显微镜和电化学工作站表征了复合小球的结构、形貌和电化学性能。结果表明:直径为200~500 nm的PPy微球聚集在海藻酸锰小球的表面。随着海藻酸钠在MnCl2水溶液的凝固时间增加,MPM的PPy含量偏低,复合小球的电容值减小。这种具有导电和生物相容性的MPM将在新型电极材料领域得到应用。

  16. Dynamics of the pi(-)p-->pi(0)pi(0)n reaction for p(pi(-))<750 MeV/c.

    Science.gov (United States)

    Craig, K; Comfort, J R; Allgower, C E; Bekrenev, V; Berger, E; Briscoe, W J; Clajus, M; Draper, B; Grosnick, D; Isenhower, D; Knecht, N; Koetke, D; Koulbardis, A; Kozlenko, N; Kruglov, S; Lolos, G J; Lopatin, I; Manley, D M; Manweiler, R; Marusić, A; McDonald, S; Nefkens, B M K; Olmsted, J; Papandreou, Z; Peaslee, D; Phaisangittisakul, N; Prakhov, S; Price, J W; Pulver, M; Ramirez, A F; Sadler, M E; Shafi, A; Spinka, H; Stanislaus, S; Starostin, A; Supek, I; Staudenmaier, H M; Tippens, W B

    2003-09-05

    Data are presented for the reaction pi(-)p-->pi(0)pi(0)n in the range from threshold to p(pi(-))=750 MeV/c. The systematics of the data and multipole analyses are examined for sensitivity to a f(0)(600) ("sigma") meson. A one-pion-exchange mechanism is found to be very weak, or absent. The reaction appears to become dominated by sequential pi(0) decays through the Delta(1232) resonance as the beam momentum increases, along with substantial interference effects from several competing mechanisms.

  17. NaYF4:Yb/Er@PPy core-shell nanoplates: an imaging-guided multimodal platform for photothermal therapy of cancers

    Science.gov (United States)

    Huang, Xiaojuan; Li, Bo; Peng, Chen; Song, Guosheng; Peng, Yuxuan; Xiao, Zhiyin; Liu, Xijian; Yang, Jianmao; Yu, Li; Hu, Junqing

    2015-12-01

    Imaging guided photothermal agents have attracted great attention for accurate diagnosis and treatment of tumors. Herein, multifunctional NaYF4:Yb/Er@polypyrrole (PPy) core-shell nanoplates are developed by combining a thermal decomposition reaction and a chemical oxidative polymerization reaction. Within such a composite nanomaterial, the core of the NaYF4:Yb/Er nanoplate can serve as an efficient nanoprobe for upconversion luminescence (UCL)/X-ray computed tomography (CT) dual-modal imaging, the shell of the PPy shows strong near infrared (NIR) region absorption and makes it effective in photothermal ablation of cancer cells and infrared thermal imaging in vivo. Thus, this platform can be simultaneously used for cancer diagnosis and photothermal therapy, and compensates for the deficiencies of individual imaging modalities and satisfies the higher requirements on the efficiency and accuracy for diagnosis and therapy of cancer. The results further provide some insight into the exploration of multifunctional nanocomposites in the photothermal theragnosis therapy of cancers.Imaging guided photothermal agents have attracted great attention for accurate diagnosis and treatment of tumors. Herein, multifunctional NaYF4:Yb/Er@polypyrrole (PPy) core-shell nanoplates are developed by combining a thermal decomposition reaction and a chemical oxidative polymerization reaction. Within such a composite nanomaterial, the core of the NaYF4:Yb/Er nanoplate can serve as an efficient nanoprobe for upconversion luminescence (UCL)/X-ray computed tomography (CT) dual-modal imaging, the shell of the PPy shows strong near infrared (NIR) region absorption and makes it effective in photothermal ablation of cancer cells and infrared thermal imaging in vivo. Thus, this platform can be simultaneously used for cancer diagnosis and photothermal therapy, and compensates for the deficiencies of individual imaging modalities and satisfies the higher requirements on the efficiency and accuracy for

  18. Search for $^6_\\Lambda$H hypernucleus by the $^6$Li$(\\pi^-,K^+)$ reaction at $p_{\\pi^-}$ = 1.2 GeV/$c$

    CERN Document Server

    Sugimura, H; Ahn, J K; Ajimura, S; Akazawa, Y; Amano, N; Aoki, K; Bhang, H C; Chiga, N; Endo, M; Evtoukhovitch, P; Feliciello, A; Fujioka, H; Fukuda, T; Hasegawa, S; Hayakawa, S; Honda, R; Hosomi, K; Hwang, S H; Ichikawa, Y; Igarashi, Y; Imai, K; Ishibashi, N; Iwasaki, R; Joo, C W; Kiuchi, R; Lee, J K; Lee, J Y; Matsuda, K; Matsumoto, Y; Matsuoka, K; Miwa, K; Mizoi, Y; Moritsu, M; Nagae, T; Nagamiya, S; Nakagawa, M; Naruki, M; Noumi, H; Ota, R; Roy, B J; Saha, P K; Sakaguchi, A; Sako, H; Samanta, C; Samoilov, V; Sasaki, Y; Sato, S; Sekimoto, M; Shimizu, Y; Shiozaki, T; Shirotori, K; Soyama, T; Takahashi, T; Takahashi, T N; Tamura, H; Tanabe, K; Tanaka, T; Tanida, K; Tokiyasu, A O; Tsamalaidze, Z; Ukai, M; Yamamoto, T O; Yamamoto, Y; Yang, S B; Yoshida, K

    2014-01-01

    We have carried out an experiment to search for a neutron-rich hypernucleus, $^6_{\\Lambda}$H, by the $^6$Li($\\pi^-,K^+$) reaction at $p_{\\pi^-}$ =1.2 GeV/$c$. The obtained missing mass spectrum with an estimated energy resolution of 3.2 MeV (FWHM) showed no peak structure corresponding to the $^6_{\\Lambda}$H hypernucleus neither below nor above the $^4_{\\Lambda}$H$+2n$ particle decay threshold. An upper limit of the production cross section for the bound $^6_{\\Lambda}$H hypernucleus was estimated to be 1.2 nb/sr at 90% confidence level.

  19. Comparison study of the effect of alkyl-modified and unmodified PAMAM and PPI dendrimers on solubility and antitumor activity of crocetin.

    Science.gov (United States)

    Soltani, Fatemeh; Ramezani, Mohammad; Amel Farzad, Sara; Mokhtarzadeh, Ahad; Hashemi, Maryam

    2016-10-31

    Poor water solubility of hydrophobic drugs is one of the major problems in pharmaceutical sciences. Herein, in order to address the poor solubility of crocetin, the 30% of primary amines of PAMAM G4 and PPI G4 were alkylated and evaluated as drug delivery vectors. According to the results, this modification could improve the drug delivery efficiency in term of drug solubility, release pattern and cytotoxicity; however, the encapsulation yield was decreased. Accordingly, it can be concluded that the designed alkylated dendrimers are able to improve the drug delivery efficiency, may be through improving the solubility and cellular uptake of crocetin.

  20. Targeting Hsp90-Cdc37: a promising therapeutic strategy by inhibiting Hsp90 chaperone function.

    Science.gov (United States)

    Wang, Lei; Li, Li; Gu, Kai; Xu, Xiao-Li; You, Qi-Dong; Sun, Hao-Peng

    2016-05-27

    The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein-protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function.

  1. Effects of REM sleep deprivation on sensorimotor gating and startle habituation in rats: role of social isolation in early development.

    Science.gov (United States)

    Chang, Hsin-An; Liu, Yia-Ping; Tung, Che-Se; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Huang, San-Yuan

    2014-07-11

    The present study examined the role of rapid eye movement (REM) sleep on sensorimotor gating function in a developmentally rodent model of schizophrenic-spectrum disorders. Startle magnitude, prepulse inhibition (PPI) and startle habituation in an acoustic startle test were measured after 72-h of REM sleep deprivation (REMSD) in 14-week-old rats that were reared in one of the following conditions: control social interaction, 2-week isolation, and continuous isolation, since weaning. The results showed that REMSD significantly inhibited rats' PPI in socially controlled rats, and rats in two isolation groups appeared less sensitive to REMSD. After REMSD, startle habituation was significantly reduced in continuous-isolated rats but not in 2-week-isolated rats. These data indicate that REM sleep is essential for PPI; REMSD inhibits startle habituation in rats with continuous social isolation. In addition, social interaction, in early life or for the whole life, functions differently to the sensorimotor gating.

  2. Desalting of phosphopeptides by tandem polypyrrole-c18 reverse phase micropipette tip (TMTip{sub PPY-C18}) based on hybrid electrostatic, {Pi}-{Pi} stacking and hydrophobic interactions for mass spectrometric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Shi; Wang Xiaoli; Fu Jieying; Hu Xuejiao; Xiao Xiao; Huang Lulu; Zhou Youe [Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079 (China); Zhong Hongying, E-mail: hyzhong@mail.ccnu.edu.cn [Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079 (China)

    2012-04-29

    Highlights: Black-Right-Pointing-Pointer A new micropipette tip TMTip{sub PPY-C18} was developed for desalting of phosphopeptides. Black-Right-Pointing-Pointer TMTip{sub PPY-C18} is based on polypyrrole in tandem with C18 chromatographic material. Black-Right-Pointing-Pointer TMTip{sub PPY-C18} combines electrostatic, {Pi}-{Pi} stacking and hydrophobic interactions. Black-Right-Pointing-Pointer TMTip{sub PPY-C18} can be used in both acidic and basic experimental conditions. - Abstract: Desalting and concentration of peptides using reverse phase (RP) C18 chromatographic material based on hydrophobic interaction is a routine approach used in mass spectrometry (MS)-based proteomics. However, MS detection of small hydrophilic peptides, in particular, phosphopeptides that bear multiple negative charges, is challenging due to the insufficient binding to C18 stationary phase. We described here the development of a new desalting method that takes the unique properties of polypyrrole (PPY). The presence of positively charged nitrogen atoms under acidic conditions and polyunsaturated bonds in polypyrrole provide a prospect for enhanced adsorption of phosphopeptides or hydrophilic peptides through extra electrostatic and {Pi}-{Pi} stacking interactions in addition to hydrophobic interactions. In tandem with reversed phase C18 chromatographic material, the new type of desalting method termed as TMTip{sub PPY-C18} can significantly improve the MS detection of phosphopeptides with multiple phosphate groups and other small hydrophilic peptides. It has been applied to not only tryptic digest of model proteins but also the analysis of complex lysates of zebrafish eggs. The number of detected phosphate groups on a peptide ranged from 1 to 6. Particularly, polypyrrole based method can also be used in basic condition. Thus it provides a useful means to handle peptides that may not be detectable in acidic condition. It can be envisioned that the TMTip{sub PPY-C18} should be able to

  3. Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.

    Directory of Open Access Journals (Sweden)

    Akiko Watanabe

    2007-11-01

    Full Text Available Deficits in prepulse inhibition (PPI are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6 animals that show high PPI with C3H/He (C3 animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain, a gene with functional links to the N-methyl-D-aspartic acid (NMDA receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming.

  4. Preparation and characterization of PPy/LiFePO4 composite material as cathode%聚吡咯/磷酸铁锂复合正极材料的制备与表征

    Institute of Scientific and Technical Information of China (English)

    任丽; 韩杨

    2012-01-01

    采用化学氧化法, 以吡咯为单体、 三氯化铁为氧化剂、 苯磺酸钠为掺杂剂在磷酸铁锂颗粒表面进行原位聚合, 制备了聚吡咯/磷酸铁锂(PPy/LiFePO4)复合材料。用FTIR、 XRD和SEM对PPy/LiFePO4复合材料进行了结构与形貌表征。用电化学工作站和充放电测试系统对复合材料的电化学性能进行了表征。结果表明: PPy/LiFePO4复合材料作锂二次电池正极具有良好的充放电循环性能。当PPy质量分数为17%, 充放电电流为0.1 mA时, PPy/LiFePO4复合材料最高放电比容量达163 mAh·g^-1, 50次循环之后放电比容量仍为初始时的94.9%; 与LiFePO4相比, 当PPy的含量适当时, PPy/LiFePO4复合正极材料的放电比容量会有明显提高。PPy的加入提高了LiFePO4的电子电导率, 从而提高了活性物质有效利用率, 因此PPy/LiFePO4复合材料的比容量和循环性能均得到了提升。%Polypyrrole was coated onto pure LiFePO4 particles to form polypyrrole/lithium iron phosphate(PPy/ LiFePO4) composite material by chemical oxidative polymerization, with ferric trichloride (FeC13) as oxidant, benzene sulfonic acid sodium salt as dopant. The molecular structure and morphology of PPy/LiFePO4 were characterized by FTIR, XRD and SEM. The electrochemical performances of composite were measured by electrochemical workstation and charge - discharge test system. It is found that the battery with PPy/LiFePO4 composite as cathode shows better charge - discharge performance. The discharge capacity of PPy/LiFePO4 composite is 163 mAh·g-1, which is higher than that of LiFePO4, when the mass fraction of PPy is 17.0% and the current is 0.1 mA. The discharge specific capacity of composite is still 94. 9% of initial capacity after 50 cycles. Compared with pure LiFePO4, the coating of proper amount of PPy can improve the electronic conductivity of LiFePO4. As the effective utilization of LiFePO4 increases, both the specific capacity and cycle

  5. Study of DBS-PPy as cathode material for lithium-ion batteries%DBS-PPy作为锂离子电池正极材料的性能研究

    Institute of Scientific and Technical Information of China (English)

    田方华; 刘黎; 杨振华; 王先友; 陈权启

    2011-01-01

    通过化学氧化法合成了掺杂十二烷基苯磺酸阴离子(DBS-)的聚吡咯( PPy).采用FTIR、SEM对其结构及形貌进行了表征,并采用恒流充放电、循环伏安、交流阻抗等电化学测试手段对其用作锂离子电池正极材料时的电化学性能进行了系统研究.探讨了氧化剂三氯化铁的量对其电化学性能的影响.结果表明,当FeCl3/Py摩尔比为0.75时,材料具有最佳的电化学性能.%DBS-Ppy (dodecylbenzene sulfonate-polypyrrole) was chemically synthesized by an oxidative polymerization of pyrrole monomer using ferric chloride as oxidizing agent. The structure and morphology of DBS-Ppy were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The electrochemical performance of DBS-Ppy was studied by galvanostatic cycling tests, cyclic voltammetry (CV) and electrochemical impedance spectra. The effect of the mass of ferric chloride on electrochemical properties was researched. The results show that DBS-Ppy has the best electrochemical performances when n (FeCI3)/n (Py) is 0.75.

  6. ZnO/PPy异质纳米复合材料的制备、表征及其气敏特性%Synthesis and Characterization of ZnO/PPy Hetero-Nanocomposites and Their Gas Sensing Properties

    Institute of Scientific and Technical Information of China (English)

    杜海英; 王兢; 乔俏; 孙炎辉; 邵强; 李晓干

    2015-01-01

    Pyrrole (Py) was oxidized by ferric(III) chloride solution in water for the synthesis of polypyrrole (PPy) nanoparticles on the substrate slide by in-situ polymerization at room temperature. Zinc oxide nanorods grew on the PPy nanoparticles when in a water bath at 90 °C. ZnO/PPy hetero-nanocomposites were obtained by a hydrothermal method and characterized using X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). Gas sensors were fabricated based on the ZnO/PPy hetero-nanocomposites to detect ammonia at room temperature. The gas sensing properties of these hetero-nanocomposites were measured in the concentration range of 10×10-6-150×10-6 (volume fraction). The relationship of the sensitivity of the sensors to the ammonia concentration showed linearity. The gas sensor based on ZnO/PPy hetero-nanocomposites showed good selectivity to ammonia when in the presence of interfering gases such as methanol, acetone, and toluene. The formation mechanism of the ZnO/PPy hetero-nanocomposites was briefly analyzed.%室温下,采用原位聚合法,以吡咯(PY)为单体,氯化铁(FeCl3∙6H2O)为氧化剂,在塑料基片上聚合生长了聚吡咯(PPy)纳米微球。然后在聚吡咯基片上生长ZnO种子,将表面种有ZnO种子的PPy元件置于六次甲基四胺与硝酸锌的混合溶液中,90°C水浴中,在PPy微球上生长了ZnO纳米棒,合成了PPy/ZnO异质纳米复合材料。分别通过X射线衍射仪(XRD)和场发射扫描电镜(FESEM)对PPy/ZnO异质纳米复合材料的结构和形貌进行了表征。制备了塑料基的PPy/ZnO异质纳米复合材料气体传感器,在室温下,对10×10-6-150×10-6(体积分数)浓度范围的氨气进行了气敏测试, PPy/ZnO气敏元件对氨气响应的灵敏度基本呈线性关系,且对甲醇、丙酮、甲苯等有机气体表现出很好的选择性。最后,对PPy/ZnO异质纳米复合材料的形成机理进行了简要分析。

  7. Rapid amperometric detection of trace metals by inhibition of an ultrathin polypyrrole-based glucose biosensor.

    Science.gov (United States)

    Ayenimo, Joseph G; Adeloju, Samuel B

    2016-02-01

    A sensitive and reliable inhibitive amperometric glucose biosensor is described for rapid trace metal determination. The biosensor utilises a conductive ultrathin (55 nm thick) polypyrrole (PPy) film for entrapment of glucose oxidase (GOx) to permit rapid inhibition of GOx activity in the ultrathin film upon exposure to trace metals, resulting in reduced glucose amperometric response. The biosensor demonstrates a relatively fast response time of 20s and does not require incubation. Furthermore, a complete recovery of GOx activity in the ultrathin PPy-GOx biosensor is quickly achieved by washing in 2mM EDTA for only 10s. The minimum detectable concentrations achieved with the biosensor for Hg(2+), Cu(2+), Pb(2+) and Cd(2+) by inhibitive amperometric detection are 0.48, 1.5, 1.6 and 4.0 µM, respectively. Also, suitable linear concentration ranges were achieved from 0.48-3.3 µM for Hg(2+), 1.5-10 µM for Cu(2+), 1.6-7.7 µM for Pb(2+) and 4-26 µM for Cd(2+). The use of Dixon and Cornish-Bowden plots revealed that the suppressive effects observed with Hg(2+) and Cu(2+) were via non-competitive inhibition, while those of Pb(2+) and Cd(2+) were due to mixed and competitive inhibition. The stronger inhibition exhibited by the trace metals on GOx activity in the ultrathin PPy-GOx film was also confirmed by the low inhibition constant obtained from this analysis. The biosensor was successfully applied to the determination of trace metals in tap water samples.

  8. Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy@Au spheres: Fabrication, characterization and application in SERS

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Guohong; Shang, Mengying; Zou, Hanzhi; Wang, Wenqin, E-mail: wangwenqin@nbu.edu.cn

    2016-04-15

    In this work, the sulfonic acid (–SO{sub 3}H) group terminated Fe{sub 3}O{sub 4}@SiO{sub 2} magnetic spheres were prepared. Polypyrrole (PPy) was in-situ polymerized on Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H spheres due to the dual roles of the –SO{sub 3}H groups: acting as both “anchoring sites” for adsorbing of pyrrole monomer and dopant agent in PPy. By adsorbing gold nanoseeds on the as-prepared Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy spheres followed the seed-mediated growth method, the multifunctional Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy@Au spheres were obtained. The application of Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy@Au spheres in surface-enhanced Raman scattering (SERS) was investigated, and the results exhibited the enhancement in the order of 10{sup 4} using 4-aminothiophenol as the probe molecule. - Highlights: • The sulfonic acid-terminated Fe{sub 3}O{sub 4}@SiO{sub 2} (Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H) spheres were prepared. • The –SO{sub 3}H groups of Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H spheres played dual roles in adsorbing pyrrole and protonating polypyrrole. • Fe{sub 3}O{sub 4}@SiO{sub 2}–SO{sub 3}H@PPy core/gold shell composites can act as SERS substrate for detecting 4-ATP molecule.

  9. Development of a novel biosensor based on a polypyrrole-dodecylbenzene sulphonate (PPy-DBS) film for the determination of amperometric cholesterol.

    Science.gov (United States)

    Özer, Bayram Oğuz; Çete, Servet

    2017-06-01

    Herein a novel amperometric biosensor based on a conducting polymer with anionic dopant modified electrode was successfully developed for detection of cholesterol. Polypyrrole is deposited on a platinum surface and the sodium dodecylbenzene sulphonate (DBS) ion-doped polypyrrole film was electrochemically prepared by scanning the electrode potential between -0.8 and +0.8 V at a scan rate of 20 mV/s. The present electrochemical biosensor was optimized in terms of working potential, number of cycles, concentrations of monomer, and anionic dopant. Cholesterol oxidase (ChOx) was physically entrapped in PPy-DBS to construct an amperometric cholesterol biosensor. Amperometric determination is based on the electrochemical detection of H2O2 generated in the enzymatic reaction of cholesterol. Kinetic parameters, operational and storage stabilities, pH, and temperature dependencies were determined. Km and Imax were calculated as 0.11 μM and 0.967 nM/min, respectively. The operational stability results showed that 90.0% of the response current was retained after 30 activity assays. Morphology of electrodes was characterized by SEM and AFM. Additionally, contact angle measurements were made with 1 μL water of polymer film and enzyme electrode. As a result, the cholesterol biosensor suggested in this study is easy to prepare and is highly cost-effective. This composite (PPy-DBS) can supply a biocompatible and electrochemical microenvironment for immobilization of the enzyme, making this material a good candidate for the fabrication of highly sensitive and selective cholesterol biosensors.

  10. 软件化雷达P显实时坐标变换与实现%Real-Time Coordinate Transform of PPI Raster Display for Software Radar

    Institute of Scientific and Technical Information of China (English)

    管行; 李方圆; 许稼; 聂明新

    2013-01-01

    软件化雷达PPI光栅显示需完成极坐标测量数据向直角坐标的实时转换,而传统的利用简单数学公式直接转换的方式存在映射非均匀和运算量大等难题.基于整体映射和一一映射等不同逆映射方法,研究并提出了一种改进的一一映射新方案.新方法可有效解决量化漏点和区域重叠的问题,显著提高了映射查找表的形成效率,保证了PPI显示效果和实时性.最后,给出了新方法的具体实现流程,比较了与现有方法的效果,证明了新方法的有效性.%It is necessary for PPI raster display of software radar to real-time transfer the real measuring data from polar coordination into Cartesian coordination. However, the direct transform via mathematical formula may cause the problems like non-uniformly mapping and large computational burden. Based on existing inverse mapping methods like unitary mapping and one-to-one mapping, a novel mapping solution is proposed in this paper based on the modification of one-to-one mapping. The proposed method can effectively solve the missing points and regions overlapping. Also, the forming efficiency of mapping table is improved remarkably to ensure the real-time PPI raster display, and the detailed implementation is further presented for this method. Finally, the effectiveness of the proposed method is demonstrated by the performance comparisons among different solutions.

  11. Effects of nicotine on quinpirole- and dizocilpine (MK-801)-induced sensorimotor gating impairments in rats.

    Science.gov (United States)

    Nespor, Amy A; Tizabi, Yousef

    2008-10-01

    Prepulse inhibition (PPI) of the acoustic startle response (ASR) is used as an index of sensorimotor gating to assess preattentive processes. Impairments in PPI have been observed in many neuropsychiatric disorders, especially schizophrenia. Administration of the glutamate N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) or dopamine receptor (D2/D3) agonist quinpirole (QNP) results in impairment (reduction) of PPI in rats. Nicotine, on the other hand, may have beneficial effects on attentional/cognitive functions. The purpose of the current set of experiments was to investigate the effects of acute and chronic nicotine on MK-801- and QNP-induced PPI impairments. Adult female Sprague-Dawley rats were treated acutely or chronically by various doses of nicotine alone or followed by an acute dose of MK-801 (0.15 mg/kg) or QNP (0.5 mg/kg). All drugs were administered intraperitoneally. Controls received saline in lieu of any drug, and ASR and PPI in each animal was evaluated 10 min after the last injection. Both MK-801 and QNP consistently impaired PPI. Administration of nicotine acutely (0.05-0.4 mg/kg) or chronically (0.2 or 0.4 mg/kg daily for 1 week) did not have any effect of its own on ASR or PPI or on MK-801-induced PPI impairment. Acute administration of 0.2 mg/kg nicotine did not have any effect on QNP-induced reduction in PPI, whereas the higher dose of 0.4 mg/kg significantly attenuated this impairment. Chronic daily administration of either 0.2 or 0.4 mg/kg nicotine for 1 week nearly normalized the QNP-induced impairments in PPI. The effect of nicotine on sensorimotor gating is dependent on the procedure as well as the dose of nicotine and appears to be efficacious against dopaminergic rather than glutamatergic disruption of PPI in rats.

  12. Inhibition of adenylyl and guanylyl cyclase isoforms by the antiviral drug foscarnet.

    Science.gov (United States)

    Kudlacek, O; Mitterauer, T; Nanoff, C; Hohenegger, M; Tang, W J; Freissmuth, M; Kleuss, C

    2001-02-02

    The pyrophosphate (PP(i)) analog foscarnet inhibits viral DNA-polymerases and is used to treat cytomegalovirus and human immunodeficiency vius infections. Nucleotide cyclases and DNA-polymerases catalyze analogous reactions, i.e. a phosphodiester bond formation, and have similar topologies in their active sites. Inhibition by foscarnet of adenylyl cyclase isoforms was therefore tested with (i) purified catalytic domains C1 and C2 of types I and VII (IC1 and VIIC1) and of type II (IIC2) and (ii) membrane-bound holoenzymes (from mammalian tissues and types I, II, and V heterologously expressed in Sf9 cell membranes). Foscarnet was more potent than PP(i) in suppressing forskolin-stimulated catalysis by both, IC1/IIC2 and VIIC1/IIC2. Stimulation of VIIC1/IIC2 by Galpha(s) relieved the inhibition by foscarnet but not that by PP(i). The IC(50) of foscarnet on membrane-bound adenylyl cyclases also depended on their mode of regulation. These findings predict that receptor-dependent cAMP formation is sensitive to inhibition by foscarnet in some, but not all, cells. This was verified with two cell lines; foscarnet blocked cAMP accumulation after A(2A)-adenosine receptor stimulation in PC12 but not in HEK-A(2A) cells. Foscarnet also inhibited soluble and, to a lesser extent, particulate guanylyl cylase. Thus, foscarnet interferes with the generation of cyclic nucleotides, an effect which may give rise to clinical side effects. The extent of inhibition varies with the enzyme isoform and with the regulatory input.

  13. Tail-pinch stress and REM sleep deprivation differentially affect sensorimotor gating function in modafinil-treated rats.

    Science.gov (United States)

    Liu, Yia-Ping; Tung, Che-Se; Chuang, Chia-Hsin; Lo, Shih-Mao; Ku, Yu-Chi

    2011-05-16

    Prepulse inhibition (PPI) is a phenomenon in which a mild stimulus attenuates a cross-modality startle response to later intense stimulation. PPI is thought to index the central inhibitory mechanism through which behavioural responses are filtered. The present study compared the effects of two stress paradigms on the acoustic startle response (ASR) and on PPI in a rat model. The tail-pinch (TP) method produces an acute and immediate stressful condition, whereas rapid eye movement (REM) sleep deprivation (REMSD) leads to a more persistent and long-term stress. Our results demonstrated that in rats, TP stress reduced the size of the ASR, and REMSD impaired PPI. The wake-promoting agent modafinil (MOD) had no effect on PPI if given alone. However, MOD reduced the ASR and PPI under TP stress, whereas only PPI was reduced by MOD after 96 h of REMSD. These results suggest that distinct stress paradigms differentially mediated sensorimotor gating abilities in terms of either responsiveness to the stimulus or information-filtering capabilities.

  14. Intersystem-crossing and phosphorescence rates in fac-Ir{sup III}(ppy){sub 3}: A theoretical study involving multi-reference configuration interaction wavefunctions

    Energy Technology Data Exchange (ETDEWEB)

    Kleinschmidt, Martin; Marian, Christel M., E-mail: Christel.Marian@hhu.de [Institute of Theoretical and Computational Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf (Germany); Wüllen, Christoph van [Fachbereich Chemie and Forschungszentrum OPTIMAS, Technical University of Kaiserslautern, Erwin-Schrödinger-Straße 52, 67663 Kaiserslautern (Germany)

    2015-03-07

    We have employed combined density functional theory and multi-reference configuration interaction methods including spin–orbit coupling (SOC) effects to investigate the photophysics of the green phosphorescent emitter fac-tris-(2-phenylpyridine)iridium (fac-Ir(ppy){sub 3}). A critical evaluation of our quantum chemical approaches shows that a perturbational treatment of SOC is the method of choice for computing the UV/Vis spectrum of this heavy transition metal complex while multi-reference spin–orbit configuration interaction is preferable for calculating the phosphorescence rates. The particular choice of the spin–orbit interaction operator is found to be of minor importance. Intersystem crossing (ISC) rates have been determined by Fourier transformation of the time correlation function of the transition including Dushinsky rotations. In the electronic ground state, fac-Ir(ppy){sub 3} is C{sub 3} symmetric. The calculated UV/Vis spectrum is in excellent agreement with experiment. The effect of SOC is particularly pronounced for the metal-to-ligand charge transfer (MLCT) band in the visible region of the absorption spectrum which does not only extend its spectral onset towards longer wavelengths but also experiences a blue shift of its maximum. Pseudo-Jahn-Teller interaction leads to asymmetric coordinate displacements in the lowest MLCT states. Substantial electronic SOC and a small energy gap make ISC an ultrafast process in fac-Ir(ppy){sub 3}. For the S{sub 1}↝T{sub 1} non-radiative transition, we compute a rate constant of k{sub ISC} = 6.9 × 10{sup 12} s{sup −1} which exceeds the rate constant of radiative decay to the electronic ground state by more than six orders of magnitude, in agreement with the experimental observation of a subpicosecond ISC process and a triplet quantum yield close to unity. As a consequence of the geometric distortion in the T{sub 1} state, the T{sub 1} → S{sub 0} transition densities are localized on one of the

  15. A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network.

    Science.gov (United States)

    Ignatieva, Elena V; Afonnikov, Dmitry A; Saik, Olga V; Rogaev, Evgeny I; Kolchanov, Nikolay A

    2016-12-22

    Obesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation. The compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein-coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most

  16. Preparation and electrochemical performance of PPy/MWNTs/GO composites%PPy/MWNTs/GO复合材料的制备与电化学性能研究

    Institute of Scientific and Technical Information of China (English)

    王攀; 刘羽熙; 王永贵

    2016-01-01

    Polypyrrole/multi⁃walled carbon nanotubes/graphene oxide ( PPy/MWNTs/GO ) composites are prepared by in situ chemical polymerization using pyrrole (Py) as monomer, MWNTs and GO as templates, and ammonium persulfate as an oxidant. The structure, morphology and electrochemical performance of the resulting composites are investigated by Fourier transform infrared ( FTIR ) spectroscopy, X⁃ray diffraction ( XRD ) , scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy ( EIS) techniques, respectively. Furthermore, the relationship between capacitance properties of the composites and effect of the ratio of MWNTs and GO, and the dosage of pyrrole are also discussed in detail. The results indicate that the PPy/MWNTs/GO composites have higher specific capacitance and good cycle stability, while have low charge transfer resistance, which are close to the ideal electrode materials for supercapacitors.%以吡咯为单体,多壁碳纳米管和氧化石墨烯为模板,过硫酸铵为氧化剂,采用原位化学聚合法制备了聚吡咯/多壁碳纳米管/氧化石墨烯( PPy/MWNTs/GO)复合材料。利用傅里叶变换红外光谱( FTIR)、X射线衍射谱( XRD)、扫描电镜( SEM)、循环伏安法( CV)和电化学交流阻抗谱( EIS)对制备复合材料的结构、微观形貌和电化学性能进行了研究,探讨了多壁碳纳米管/氧化石墨烯比例、吡咯用量对复合材料电容性能的影响。研究结果显示,PPy/MWNTs/GO复合材料具有较大的比电容和良好的循环稳定性,且具有较小的电荷转移电阻,接近于理想的超级电容器用电极材料。

  17. The Periplasmic Chaperone Network of Campylobacter jejuni: Evidence that SalC (Cj1289) and PpiD (Cj0694) Are Involved in Maintaining Outer Membrane Integrity

    Science.gov (United States)

    Taylor, Aidan J.; Zakai, Shadi A. I.; Kelly, David J.

    2017-01-01

    holdase-type chaperone activity. Cj0694 is most similar to the PpiD class of chaperones but is unusual in possessing PPIase activity. Taken together, our data show that in addition to PEB4, Cj1289 (SalC; SurA-like chaperone) and Cj0694 (PpiD) are also key proteins involved in OM biogenesis and integrity in C. jejuni.

  18. Inhibitive potentiometric detection of trace metals with ultrathin polypyrrole glucose oxidase biosensor.

    Science.gov (United States)

    Ayenimo, Joseph G; Adeloju, Samuel B

    2015-05-01

    A method, based on the inhibition of an ultrathin polypyrrole-glucose oxidase (PPy-GOx) potentiometric biosensor response, is described for the detection of Cu(2+), Hg(2+), Cd(2+) and Pb(2+) ions. Based on experimental conditions (0.2 M pyrrole, 500 U mL(-1) GOx, and an applied current density of 0.05 mA cm(-2) and a polymerization period of 500s) previously published by us, PPy-GOx films of approximately 55 nm thick were used to demonstrate the inhibitive potentiometric detection of selected trace metals down to 0.079 μM Cu(2+), 0.025 μM Hg(2+), 0.024 μM Pb(2+) and 0.044 μM Cd(2+). Furthermore, good linear concentration ranges were achieved for Cu(2+) (0.079-16 μM), Hg(2+) (0.025-5 μM), Pb(2+) (0.10-15 μM) and Cd(2+) (0.04-62 μM). The analysis of the nature of the inhibition of glucose oxidase in the PPy-GOx biosensor by these metals was achieved by Dixon and Cornish-Bowden plots. The shapes of the curves (exponential decay, parabolic and linear) obtained for the inhibitors suggest that the inhibition by the metal ions may not be exclusively directed at the essential -SH group, but involve additional binding sites of the enzyme. Dixon and Cornish-Bowden plots suggest that the inhibition is competitive for Cd(2+), while non-competitive inhibition was observed for other metal ions. The ultra-thin PPy-GOx film enabled improved permeability to the metal inhibitors than possible with conventional biosensors with thicker films and, hence, better reflects the actual inhibition effect of the trace metals on the enzyme activity. The use of the ultra-thin film also eliminated the usual need for incubation of the enzyme electrode for a long period in the presence of the inhibitors. Furthermore, a rapid recovery of the enzyme activity was achieved by simply washing the electrode with water and storing in phosphate buffer for 10-15 min. The proposed biosensing approach was successfully used for the detection of individual trace metals in tap water, achieving a 98

  19. Testing a decades' old assumption

    DEFF Research Database (Denmark)

    Bak, N; Mann, J John; Fagerlund, B

    2017-01-01

    and attention. Parameters from the PPI and P50 suppression paradigms were significantly associated with the distractor effects on strategy formation, cognitive inhibition and flexibility, visual short-term memory, and the level of subjective distraction. Subjectively reported distraction was significantly...... to the effect of distraction on strategy formation, cognitive inhibition and flexibility, as well as visual short term memory. Future studies should investigate if gating deficits affect the distractibility of the same specific cognitive functions in patients with schizophrenia....... with the P50 suppression and pre-pulse inhibition of the startle reflex (PPI) paradigms. Additionally, a neurocognitive test battery was administered in a cross-over design: with/without auditory distraction. Significant effects of distraction were found in response inhibition, and verbal working memory...

  20. ppi, Momo, Eloíse e Grimble: apoios para se pensar a infância com ou sem tutela

    Directory of Open Access Journals (Sweden)

    Renata Sieiro Fernandes

    Full Text Available A partir dos personagens infantis: Píppi Meialonga, Momo, Eloíse e Grimble, pretende-se discutir aspectos presentes na apresentação de tais personagens e suas infâncias narradas de forma literária. Uma característica comum a essas personagens é a ausência da convivência com seus pais, embora em seus grupos de socialização e convivência existam adultos. Isso leva à ideia de que sejam personagens-crianças vivendo seu mundo infantil sem a tutela adulta, talvez um sonho ou um desejo de muitas crianças reais. Será mostrado como os seus autores os inserem em paisagens e cenários e lhes atribuem pensamentos e ações baseados em seus próprios projetos ou concepções de infância, muitas vezes nostálgica, romantizada ou sentimental. Algumas proposições serão feitas para ajudar a pensar se é possível tratar da infância com ausência de tutela adulta.

  1. The Clopidogrel-PPI Interaction

    DEFF Research Database (Denmark)

    Juel, Jacob; Pareek, Manan; Jensen, Svend Eggert

    2014-01-01

    the potential for PPIs, especially omeprazole, to decrease the efficacy of clopidogrel, and both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have issued warnings regarding the concomitant use of these medications. A review of the literature revealed that the pharmacodynamic...

  2. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy.

    Science.gov (United States)

    Casado Arroyo, Rubén; Polo-Tomas, Mónica; Roncalés, Maria P; Scheiman, James; Lanas, Angel

    2012-05-01

    Patients undergoing percutaneous coronary intervention require dual antiplatelet therapy. Proton-pump inhibitor (PPI) therapy is recommended for the prevention of upper GI complications. No study has determined the rate and type of GI bleeding events in such patients in routine clinical practice. Observational study with a prospective follow-up to confirm medication use and occurrence of events, which were validated. We have followed up a cohort of 1219 consecutive patients admitted for percutaneous coronary intervention in Zaragoza (Spain). Major GI bleeding and cardiovascular events. At discharge, 96.7% of patients were on dual antiplatelet therapy and 76.6% on PPI therapy, which increased up to 87.9% during follow-up of 2107.6 patient (pt) s-years (1.72±1.07 years/patient). There were eight patients who developed GI bleeding during hospitalisation and 27 patients during follow-up, (1.52 bleeds per 100 pt-years). Most GI bleeding events (81.4%) occurred during the first year (mean time to bleeding event: 7.03±7.65 months) and 84.6% of patients were on long-term PPI at the time of the bleed. Lower GI bleeding occurred more frequently than upper GI bleeding (74% lower vs. 26% upper). Peptic ulcer history and concomitant warfarin therapy were the only risk factors identified for upper or lower GI bleeding respectively. Among patients on dual antiplatelet therapy and PPI co-therapy, gastrointestinal bleeding episodes are more frequent in the lower GI tract. This changing pattern of bleeding may reflect the success of gastroprotection and focuses attention on research to address lower GI bleeding in this population.

  3. Study on Forest Products PPI Index Fluctuation in China Based on ARCH Family-HP Filter Model%中国林产品PPI指数波动的ARCH族-HP滤波分析

    Institute of Scientific and Technical Information of China (English)

    张宇青; 周应恒

    2013-01-01

    了解林产品生产者价格指数波动的特征对稳定林产品PPI和价格水平有重要意义。采用ARCH-LM和残差平方和相关图方法检验后认为:木材、竹材PPI序列不存在不存在ARCH效应;HP滤波分析显示木材和竹材行业的P P I指数长期趋势比较平稳,相比于木材市场,近期竹材的市场供求状态相对合理;采用GARCH-M、 TARCH和EARCH模型分析认为胶脂和果实类林产品市场不存在“高风险-高收益”特征,但胶脂和果实类林产品PPI指数波动存在非对称性。%It’s important to Learn characteristics of forest products producer price index volatility for stable PPI and the price level. After Using ARCH-LM and the residual sum of squares correlation di-agram method. We considerst that: wood, bamboo PPI does not exist ARCH effect, HP filter analy-sis shows wood and bamboo industry PPI index slong-term trend is relatively stable, compared to the timber market, supply and demand status of bamboo market relatively reasonable;using GARCH-M, TARCH and EARCH model analysis that plastic resin and fruit category forest products does not exist“high risk - high return” feature, but it’s PPI index fluctuations exist asymmetry.

  4. Association study of polymorphisms in the alpha 7 nicotinic acetylcholine receptor subunit and catechol-o-methyl transferase genes with sensory gating in first-episode schizophrenia.

    Science.gov (United States)

    Liu, Xia; Hong, Xiaohong; Chan, Raymond C K; Kong, Fanzhi; Peng, Zhizhen; Wan, Xiaona; Wang, Changqing; Cheng, Lu

    2013-10-30

    The purpose of the current study was to explore the association of auditory P50 sensory gating (P50) and prepulse inhibition (PPI) of schizophrenia with polymorphisms in the CHRNA7 and COMT genes. One hundred and fourty patients with schizophrenia participated in this study. They were administered the tests P50 and PPI. Moreover, three single nucleotide polymorphisms (SNPs) (rs2337980, rs1909884 and rs883473) in CHRNA7 and three SNPs (rs4680, rs737865 and rs165599) in COMT were selected to be genotyped by polyacrylamide gel microarray techniques. P50 index showed significant reduction in S2 amplitude between wild-type and mutation groups in the COMT rs4680. S1 amplitude of mutation group in the COMT rs737865 was also lower compared to wild-type group. PPI index revealed a shorter pulse latency of mutation group in the rs4680. The suppression ratio of mutation group was lower in COMT rs165599. Negative findings were shown between comparisons in all the CHRNA7 SNPs. We find that P50 and PPI may be influenced by COMT rs4680 polymorphisms in schizophrenia; more excitingly, we find that P50 might be influenced by COMT rs737865 polymorphisms and PPI may be influenced by COMT rs165599 polymorphisms in schizophrenia, and their mutations are associated with the reduction of the risk of P50 or PPI defects in schizophrenia. Futher studies with a larger number of subjects are needed to verify the present findings.

  5. The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism.

    Science.gov (United States)

    Petrovsky, Nadine; Ettinger, Ulrich; Kessler, Henrik; Mössner, Rainald; Wolfsgruber, Steffen; Dahmen, Norbert; Maier, Wolfgang; Wagner, Michael; Quednow, Boris B

    2013-09-01

    Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence. We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI. We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured. Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation. The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.

  6. Gastric acid inhibition in the treatment of peptic ulcer hemorrhage.

    Science.gov (United States)

    Ghassemi, Kevin A; Kovacs, Thomas O G; Jensen, Dennis M

    2009-12-01

    Upper gastrointestinal bleeding from peptic ulcer disease is a common clinical event, resulting in considerable patient morbidity and significant health care costs. Inhibiting gastric acid secretion is a key component in improving clinical outcomes, including reducing rebleeding, transfusion requirements, and surgery. Raising intragastric pH promotes clot stability and reduces the influences of gastric acid and pepsin. Patients with high-risk stigmata for ulcer bleeding (arterial bleeding, nonbleeding visible vessels, and adherent clots) benefit significantly from and should receive high-dose intravenous proton pump inhibitors (PPIs) after successful endoscopic hemostasis. For patients with low-risk stigmata (flat spots or clean ulcer base), oral PPI therapy alone is sufficient. For oozing bleeding (an intermediate risk finding), successful endoscopic hemostasis and oral PPI are recommended. Using intravenous PPIs before endoscopy appears to reduce the frequency of finding high-risk stigmata on later endoscopy, but has not been shown to improve clinical outcomes. High-dose oral PPIs may be as effective as intravenous infusion in achieving positive clinical outcomes, but this has not been documented by randomized studies and its cost-effectiveness is unclear.

  7. Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

    Science.gov (United States)

    Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

    2014-10-01

    It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction.

  8. Relations between sensorimotor integration and speech disorders in Parkinson's disease.

    Science.gov (United States)

    Millian-Morell, Lymarie; López-Alburquerque, Tomás; Rodríguez-Rodríguez, Andrea; Gómez-Nieto, Ricardo; Carro, Juan; Meilán, Juan José G; Martínez-Sánchez, Francisco; Sancho, Consuelo; López, Dolores E

    2017-08-28

    Sensorimotor integration mechanisms can be affected by many factors, among which are those involving neuromuscular disorders. Parkinson's disease (PD) is characterized by well-known motor symptoms, among which lately have been included motor speech deficits. Measurement of the acoustic startle reflex (ASR) and its modulations (prepulse inhibition and prepulse facilitation, PPI and PPF respectively) represent a simple and quantifiable tool to assess sensorimotor function. However, it remains unknown whether measures of the PPI and PPF are associated with motor speech deficits in PD. A total of 88 subjects participated in this study, 52 diagnosed with PD and 36 control subjects. After obtaining written informed consent, participants were assessed with PPI at several interstimulus intervals, and PPF at 1000 ms using the SRH-Lab system (San Diego, CA). Percentage of change in the amplitude and latency of the ASR was analyzed between groups. Voice recordings were register of a specific text given to the subjects with a professional recorder and temporal patterns of speech were analyzed. Statistical analyses conducted in this study showed differences in PPI and PPF in subjects with PD compared to controls. In addition, discriminative parameters of voice abnormalities were observed in PD subjects related to control subjects showing a reduction in phonation time, vowel pulses, breaks, breakage and voice speech periods. PD presents a disruption in sensorimotor filter mechanisms and speech disorders, and there is a relationship between these alterations. The correlation between the PPI and PPF with an alteration of the voice in PD subjects contributes toward understanding mechanism underlying the neurophysiological alterations in both processes. Overall, easy and non-invasive tests such as PPI, PPF together with voice analysis may be useful to identify early stages of PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Startle response during smoking and 24 h after withdrawal predicts successful smoking cessation.

    Science.gov (United States)

    Postma, P; Kumari, V; Sharma, T; Hines, M; Gray, J A

    2001-07-01

    The startle response is thought to reflect changes in attentional processes in humans. The startle response shows a number of forms of plasticity, of which prepulse inhibition (PPI) refers to the attenuation of the startle response to a strong sensory stimulus (pulse), when such a pulse is preceded by a stimulus of lower intensity (prepulse). Recent studies have shown that nicotine modulates startle and PPI of the startle reflex in humans and animals. The present study examined individual differences in cognitive benefits obtained from smoking as indexed by startle response and PPI. We investigated, using a within-subjects design, the effects of cigarette smoking via a comparison of baseline and withdrawal measures of startle and PPI in 18 subjects wishing to quit cigarette smoking. The relapse of five of these subjects enabled a between-group comparison of these measures with the successful quitters. Startle and PPI were measured on three separate occasions: before quitting, 24 h after quitting and 1 month after quitting. The presence of a high startle response amplitude while subjects were still engaged in their normal smoking patterns (baseline) and the occurrence of a significant drop of startle amplitude in withdrawal relative to baseline factors were found to be predictive of an individual's ability to quit smoking. Changes in PPI were found to reflect these changes in startle amplitude. The observed response patterns are discussed in terms of individual differences in commitment to quitting and self-dosing to manipulate attentional mechanisms as measured by the acoustic startle response. Furthermore, it is suggested that these specific response profiles may be predictive of the ability to quit smoking.

  10. Lamotrigine effects sensorimotor gating in WAG/Rij rats

    Directory of Open Access Journals (Sweden)

    Ipek Komsuoglu Celikyurt

    2012-01-01

    Full Text Available Introduction: Prepulse inhibition (PPI is a measurable form of sensorimotor gating. Disruption of PPI reflects the impairment in the neural filtering process of mental functions that are related to the transformation of an external stimuli to a response. Impairment of PPI is reported in neuropsychiatric illnesses such as schizophrenia, Huntington′s disease, Parkinson′s diseases, Tourette syndrome, obsessive compulsive disorder, and temporal lobe epilepsy with psychosis. Absence epilepsy is the most common type of primary generalized epilepsy. Lamotrigine is an antiepileptic drug that is preferred in absence epilepsy and acts by stabilizing the voltage-gated sodium channels. Aim: In this study, we have compared WAG-Rij rats (genetically absence epileptic rats with Wistar rats, in order to clarify if there is a deficient sensorimotor gating in absence epilepsy, and have examined the effects of lamotrigine (15, 30 mg/kg, i.p. on this phenomenon. Materials and Methods: Depletion in PPI percent value is accepted as a disruption in sensory-motor filtration function. The difference between the Wistar and WAG/Rij rats has been evaluated with the student t test and the effects of lamotrigine on the PPI percent have been evaluated by the analysis of variance (ANOVA post-hoc Dunnett′s test. Results: The PPI percent was low in the WAG/Rij rats compared to the controls (P<0.0001, t:9,612. Although the PPI percent value of the control rats was not influenced by lamotrigine, the PPI percent value of the WAG/Rij rats was raised by lamotrigine treatment (P<0.0001, F:861,24. Conclusions: As a result of our study, PPI was disrupted in the WAG/Rij rats and this disruption could be reversed by an antiepileptic lamotrigine.

  11. Psychophysiological markers of vulnerability to psychopathology in men with an extra X chromosome (XXY.

    Directory of Open Access Journals (Sweden)

    Sophie van Rijn

    Full Text Available Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome (47,XXY is one of the most common sex chromosomal aneuploidies (1 in 650 male births and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three "classic" psychophysiological markers of psychosis in Klinefelter syndrome (KS: smooth pursuit eye movements (SPEM, prepulse inhibition (PPI and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM (reflecting visuo-motor control as well as PPI and P50 suppression (reflecting sensory gating were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response (PPI (effect size 1.6. No abnormalities were found in suppression of the P50 (effect size 0.6. We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to

  12. Immobilization of Tyrosinase from Avocado Crude Extract in Polypyrrole Films for Inhibitive Detection of Benzoic Acid

    Directory of Open Access Journals (Sweden)

    André Brisolari

    2014-07-01

    Full Text Available Inhibition-based biosensors were developed by immobilizing tyrosinase (Tyr, polyphenol oxidase from the crude extract of avocado fruit on electrochemically prepared polypyrrole (PPy films. The biosensors were prepared during the electropolymerization of pyrrole in a solution containing a fixed volume of the crude extract of avocado. The dependence of the biosensor responses on the volume used from the crude extract, values of pH and temperature was studied, and a substrate, catechol, at different concentrations, was amperometrically detected by these biosensors. Benzoic acid, a competitive inhibitor of Try, was added to the catechol solutions at specific concentrations aimed at obtaining the inhibition constant, K’m, which ranged from 1.7 to 4.6 mmol∙L−1 for 0.0 and 60 µmol∙L−1 of benzoic acid, respectively. Studies on the inhibition caused by benzoic acid by using PPy/Try films, and catechol as a substrate, allowed us propose how to develop, under optimized conditions, simple and low-cost biosensors based on the use of avocado fruit.

  13. Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Oranje, Bob; Melchior, Linea;

    2015-01-01

    Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (α7n......AChR), is suggested as a susceptibility factor for schizophrenia. CHRNA7 has also been genetically linked to the P50 auditory evoked potential deficit, a candidate endophenotype of schizophrenia, but not to prepulse inhibition of the startle reflex (PPI). In this study, 95 antipsychotic-naïve schizophrenic patients...

  14. Sensorimotor gating characteristics of violent men with comorbid psychosis and dissocial personality disorder: Relationship with antisocial traits and psychosocial deprivation.

    Science.gov (United States)

    Sedgwick, Ottilie; Young, Susan; Greer, Ben; Arnold, Jack; Parsons, Aisling; Puzzo, Ignazio; Terracciano, Mariafatima; Das, Mrigendra; Kumari, Veena

    2017-07-06

    Evidence suggests violence amongst those with psychosis is not aetiologically homogeneous, and that a large proportion of those who engage in violent behaviour have a comorbid antisocial personality disorder. Initial investigations indicate that this subgroup has distinct historical and neuropsychological characteristics, which may indicate diverse treatment needs. This study investigated sensorimotor gating characteristics of violent men with diagnoses of both psychosis and dissocial personality disorder (DPD) (n=21) relative to violent men with psychosis alone (n=12), DPD alone (n=14) and healthy, non-violent male controls (n=27), using the prepulse inhibition (PPI) paradigm. The results indicated that, relative to the psychosis alone and healthy control groups, the comorbid group had lower PPI, especially at 60-ms prepulse-to-pulse interval. The DPD group took an intermediary position and did not differ from any group. Antisocial personality traits (factor two scores of the Psychopathy Checklist - Revised), and greater severity of childhood psychosocial deprivation (including physical and sexual abuse), were significantly correlated with poor PPI across the clinical sample. The findings suggest diverse sensorimotor gating profiles amongst subgroups of violent offenders, with comorbid psychosis and DPD showing most impairment. This is consistent with a 'double dose' of deficit explanation amongst those with both diagnoses, explained at least in part by presence of antisocial personality traits and childhood psychosocial deprivation. Copyright © 2017. Published by Elsevier B.V.

  15. Preparation of Fe3O4@PPy magnetic nanoparticles as solid-phase extraction sorbents for preconcentration and separation of phthalic acid esters in water by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Zhao, Hongyan; Huang, Manyan; Wu, Jianrong; Wang, Li; He, Hua

    2016-02-01

    The purpose of this paper is to introduce a solid-phase extraction method of separating and determining of phthalic acid esters (PAEs) by PPy-coated Fe3O4 magnetic nanoparticles (Fe3O4@PPy MNPs). In the process, nanoparticles were served as sorbents and the optimal conditions of the extraction have been explored. The composite was synthesized through the chemical oxidation method, combining pyrrole monomer with Fe3O4 magnetic ball in the form of aggregation state and the coated nanoparticles possessed core-shell construction. The PPy-coated Fe3O4 magnetic microspheres have been extensively characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and vibrating sample magnetometry. The optimum conditions were investigated by orthogonal experimental design, which was used to testing the influence of main factors and the interactions among them. The orthoplan is famous for the merit that it can study the whole experiments comprehensively through minimal tests. Under the optimal extraction conditions: 20mg of modified magnetite nanoparticles, eluting with acetic ester of 2mL, 40min of MSPE, eluting in 1h and 20mL of sample volume, good linearity (r(2)>0.9912) of all calibration curves was obtained in validation experiments. And the limits of detection (LODs) were from 0.006 to 0.021ng/mL. The recoveries in different sample matrices were in the range from 80.4% to 108.2% with relative standard deviations less than 12.8%. The present work demonstrates the applicability of the developed method for the determination of PAEs in water sample and the results justified that it can be applied successfully to the selective isolation and enrichment of PAEs in real water samples.

  16. Theoretical Studies on the Fe-M Interactions and 31p NMR in Fe(CO)3(EtPhPpy)2MX2 (X=NCS, SCN, CI; M=Zn, Cd, Hg)

    Institute of Scientific and Technical Information of China (English)

    Xiao-xuan Huang; Xuan Xu; Mei-xiang Xie

    2008-01-01

    To study the Fe-M interactions and their effects on 31p NMR, the structures of Fe(CO)3(EtPhPpy)21,Fe(CO)3(EtPhPpy)2M(NCS)2 (2: M=Zn, 3: M=Cd, 4: M=Hg) and Fe(CO)3(EtPhPpy)2CdX2 (5: X=CI,6: X=SCN) were investigated by density functional theory (DFT) PBE0 method. The stabilities S of complexes follow S(2)>S(3)>S(4) and S(3)~S(6)>S(5), indicating that 6 is stable and may be synthesized.The complexes with thiocyanate are more stable than that with chloride in Fe(CO)3(EtPhPpy)2CdX2.The strength I of Fe-M interactions follows I(2)≈I(3)

  17. The Effects of Nicotine on the Attentional Modification of the Acoustic Startle Response in Non-Smokers

    Science.gov (United States)

    Baschnagel, Joseph S.; Hawk, Larry W.

    2008-01-01

    Rationale & Objective Research on nicotine and attention has mainly utilized samples of deprived smokers and tasks requiring volitional responses, raising the question of whether nicotine improves attention or simply alleviates withdrawal or improves motor speed. This study used the startle eyeblink reflex to assess nicotine effects on auditory attention in non-smokers. Method Sixty-seven healthy young adult non-smokers completed a tone discrimination task. Acoustic startle probes were presented 60, 120, 240, or 4500 ms after onset of 2/3 of the tones and during intertrial intervals. Attention was assessed via 1) short-lead prepulse inhibition (PPI) of startle, a measure of early filtering; 2) long-lead prepulse facilitation (PPF) of startle, a measure of sustained processing, and 3) the modification of PPI and PPF by focused attention. Participants completed two lab sessions, once while wearing a 7 mg transdermal nicotine patch, and once while wearing a placebo patch. Patches were administered in a double-blind procedure. Results Nicotine increased overall PPI, ηp2 = .09. Attention increased long-lead PPF ηp2 = .25, but not short-lead PPI. Nicotine did not reliably enhance early or late controlled attentional processing in the sample overall. However, correlational analyses demonstrated that nicotine most improved attentional modification of short-lead PPI among participants with the weakest early attentional processing under placebo conditions. Conclusions Nicotine enhanced early attentional filtering in general, and the effects of nicotine on early, focused attention were dependent upon individual differences in placebo levels of attentional processing. The present data suggest the effects of nicotine on attention extend beyond the alleviation of withdrawal and simple motor speeding. PMID:18338158

  18. Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women.

    Science.gov (United States)

    Comasco, Erika; Hellgren, Charlotte; Olivier, Jocelien; Skalkidou, Alkistis; Sundström Poromaa, Inger

    2015-10-01

    Pregnancy is a period characterized by a supraphysiological hormonal status, and greater anxiety proneness, which can lead to peripartum affective symptoms with dramatic consequences not only for the woman but also for the child. Clinical psychiatry is heavily hampered by the paucity of objective and biology-based intermediate phenotypes. Prepulse inhibition (PPI) of the startle response, a neurophysiological measure of sensorimotor gating, has been poorly investigated in relation to anxiety and in pregnant women. In the present study, the PPI of healthy non-pregnant women (n = 82) and late pregnant women (n = 217) was investigated. Age, BMI, depression and anxiety symptoms, tobacco use, and antidepressant medication were considered. We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMT Val158Met Val/Val genotype compared to Met carriers. Altogether, a reduced sensorimotor gating as an effect of supraphysiological hormonal status, anxiety disorders, SSRIs, and catecholaminergic genotype, implicate the putative relevance of lower PPI as an objective biological correlate of anxiety proneness in pregnant women. These findings call for prospective studies to dissect the multifactorial influences on PPI in relation to mental health of pregnant women.

  19. Effect of cannabidiol in a MK-801-rodent model of aspects of schizophrenia.

    Science.gov (United States)

    Gururajan, Anand; Taylor, David Alan; Malone, Daniel Thomas

    2011-09-23

    Cannabidiol is a non-psychoactive phytocannabinoid which, based on several previous preclinical and clinical reports, is purported to have antipsychotic potential. The purpose of this investigation was to further investigate if these effects would be seen using an MK-801-induced rat model of aspects of schizophrenia. MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviours which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. Following a 4-day acclimatisation to the holding room, rats were acclimatised to startle chambers on day 5 and their prepulse inhibition (PPI) determined on day 6 following treatment with cannabidiol or vehicle and MK-801 or vehicle. On day 9, rats were acclimatised to the social interaction testing arena and on day 10, were tested for social interaction and locomotor activity following the same treatments. Cannabidiol treatment alone disrupted PPI and produced hyperactivity but had no effect on social behaviour. Cannabidiol had no effect on MK-801-induced disruption of PPI or hyperactivity but showed potential towards inhibiting MK-801-induced social withdrawal. As a comparator, we also tested the effect of the atypical antipsychotic clozapine which only partially reversed MK-801-induced disruption of PPI but was able to reverse MK-801-induced hyperactivity and social withdrawal. In conclusion, cannabidiol showed both propsychotic activity and partial antipsychotic activity in an MK-801-induced model of aspects of schizophrenia. Further behavioural studies would be required using a range of species, strains, animal models and testing paradigms to conclusively establish the antipsychotic potential of cannabidiol.

  20. Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats

    DEFF Research Database (Denmark)

    Hougaard, K.S.; Mandrup, Karen; Kjaer, S.L.

    2011-01-01

    An increasing number of scientific studies indicate that maternal stress during pregnancy influences fetal development of the nervous system and thereby the behavioural phenotype. We have previously reported attenuated prepulse inhibition (PPI) of the startle reaction in adult female rats derived...... from dams exposed to chronic mild stress (CMS) during gestation. In humans, decreased PPI has been reported to be associated with anxiety. Because of its potential translational value across species, the modulation of startle reactivity may be a useful tool in examining altered emotional reactivity...... following prenatal insults. The present study aimed at investigating whether prenatally stressed male offspring would display altered startle phenotype. Stress was induced by maternal gestational exposure to alternating procedures, i.e. CMS. At the age of 3 months, half of the offspring were blood sampled...

  1. Response inhibition in the parametric go/no-go task and its relation to impulsivity and subclinical psychopathy.

    Science.gov (United States)

    Weidacker, Kathrin; Whiteford, Seb; Boy, Frederic; Johnston, Stephen J

    2017-03-01

    The current study utilizes the parametric go/no-go task (PGNG), a task that examines changes in inhibitory performance as executive function load increases, to examine the link between psychopathic traits, impulsivity, and response inhibition in a cohort of healthy participants. The results show that as executive function load increased, inhibitory ability decreased. High scores on the Cognitive Complexity subscale of the Barratt Impulsivity Scale (BIS-11) predict poor inhibitory ability in the PGNG. Similarly, high scores on the Psychopathy Personality Inventory-Revised (PPI-R) Blame Externalization subscale predict response inhibition deficits in the PGNG, which loads more on the executive functions than the standard go/no-go task. The remaining BIS-11 as well as PPI-R subscales did not interact with inhibitory performance in the PGNG highlighting the specificity of associations between aspects of personality and impulsivity with inhibitory performance as cognitive load is increased. These data point towards the sensitivity of the PGNG in studying response inhibition in the context of highly impulsive populations and its utility as a measure of impulsivity.

  2. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion.

    Science.gov (United States)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie

    2014-06-13

    The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-l-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

  3. 融合人工鱼群机理的PPI网络聚类模型与算法%PPI Networks Clustering Model and Algorithm Combining with the Principle of Artificial Fish School

    Institute of Scientific and Technical Information of China (English)

    吴爽; 雷秀娟

    2012-01-01

    Predicting function of unknown proteins in the protein-protein interaction networks is a hot topic in the bioin-formatics. Recently functional flow method has effectively solved the problem of clustering PPI networks. However, the accuracy is relatively low and the time complexity is high. So the PPI networks clustering algorithm combining with the principle of artificial fish school was proposed, which considered an artificial fish as a set of cluster centers. The foraging behavior was regarded as searching the neighbor nodes of initial cluster centers and adding the nodes into cluster module. Afterwards the set of cluster modules having the highest fitness value was selected as the initial cluster result, which was corresponding to the following behavior of artificial fish school. Then other artificial fish began to execute swarming behavior and judged the similarities between the corresponding cluster modules and initial cluster result If the similarity was lower than given threshold, the cluster module was added into the initial cluster result The simulation experiment on PPI datasets shows that this algorithm can automatically determine cluster number. In addition, both the accuracy of cluster result and efficiency of algorithm are superior to functional flow algorithm.%预测蛋白质交互作用(Protein-Protein Interaction,PPI)网络中未知蛋白质的功能,是生物信息学的一个研究热点.目前基于功能流的方法能有效地解决PPI网络的聚类问题,但是其正确率偏低、时间复杂度较高.为此提出了一种融合人工鱼群机理的PPI网络聚类模型与算法:将人工鱼看作一组聚类中心,觅食行为是指从每个聚类中心开始向它的邻接结点搜索并添加结点到该聚类模块中;接下来将目标函数值最大的人工鱼对应的一组聚类模块看作初始的聚类结果,对应鱼群的追尾行为;剩下的人工鱼开始执行聚群行为,判断对应的聚类模块与初始的聚类结

  4. Energy Dependence of $K/\\pi$, $p/\\pi$, and $K/p$ Fluctuations in Au+Au Collisions from $\\rm \\sqrt{s_{NN}}$ = 7.7 to 200 GeV

    CERN Document Server

    Abdelwahab, N M; Adkins, J K; Agakishiev, G; Aggarwal, M M; Ahammed, Z; Alekseev, I; Alford, J; Anson, C D; Aparin, A; Arkhipkin, D; Aschenauer, E C; Averichev, G S; Banerjee, A; Beavis, D R; Bellwied, R; Bhasin, A; Bhati, A K; Bhattarai, P; Bielcik, J; Bielcikova, J; Bland, L C; Bordyuzhin, I G; Borowski, W; Bouchet, J; Brandin, A V; Brovko, S G; Bültmann, S; Bunzarov, I; Burton, T P; Butterworth, J; Caines, H; Sánchez, M Calderón de la Barca; Campbell, J M; Cebra, D; Cendejas, R; Cervantes, M C; Chaloupka, P; Chang, Z; Chattopadhyay, S; Chen, H F; Chen, J H; Chen, L; Cheng, J; Cherney, M; Chikanian, A; Christie, W; Chwastowski, J; Codrington, M J M; Contin, G; Cramer, J G; Crawford, H J; Cui, X; Das, S; Leyva, A Davila; De Silva, L C; Debbe, R R; Dedovich, T G; Deng, J; Derevschikov, A A; de Souza, R Derradi; di Ruzza, B; Didenko, L; Dilks, C; Ding, F; Djawotho, P; Dong, X; Drachenberg, J L; Draper, J E; Du, C M; Dunkelberger, L E; Dunlop, J C; Efimov, L G; Engelage, J; Engle, K S; Eppley, G; Esha, R; Eun, L; Evdokimov, O; Eyser, O; Fatemi, R; Fazio, S; Fedorisin, J; Filip, P; Fisyak, Y; Flores, C E; Gagliardi, C A; Gangadharan, D R; Garand, D; Geurts, F; Gibson, A; Girard, M; Gliske, S; Greiner, L; Grosnick, D; Gunarathne, D S; Guo, Y; Gupta, A; Gupta, S; Guryn, W; Haag, B; Hamad, A; Hamed, A; Han, L-X; Haque, R; Harris, J W; Heppelmann, S; Hirsch, A; Hoffmann, G W; Hofman, D J; Horvat, S; Huang, B; Huang, H Z; Huang, X; Huck, P; Humanic, T J; Igo, G; Jacobs, W W; Jang, H; Judd, E G; Kabana, S; Kalinkin, D; Kang, K; Kauder, K; Ke, H W; Keane, D; Kechechyan, A; Kesich, A; Khan, Z H; Kikola, D P; Kisel, I; Kisiel, A; Koetke, D D; Kollegger, T; Konzer, J; Koralt, I; Kosarzewski, L K; Kotchenda, L; Kraishan, A F; Kravtsov, P; Krueger, K; Kulakov, I; Kumar, L; Kycia, R A; Lamont, M A C; Landgraf, J M; Landry, K D; Lauret, J; Lebedev, A; Lednicky, R; Lee, J H; Li, C; Li, W; Li, X; Li, Y; Li, Z M; Lisa, M A; Liu, F; Ljubicic, T; Llope, W J; Lomnitz, M; Longacre, R S; Luo, X; Ma, G L; Ma, Y G; Mahapatra, D P; Majka, R; Margetis, S; Markert, C; Masui, H; Matis, H S; McDonald, D; McShane, T S; Minaev, N G; Mioduszewski, S; Mohanty, B; Mondal, M M; Morozov, D A; Mustafa, M K; Nandi, B K; Nasim, Md; Nayak, T K; Nelson, J M; Nigmatkulov, G; Nogach, L V; Noh, S Y; Novak, J; Nurushev, S B; Odyniec, G; Ogawa, A; Oh, K; Ohlson, A; Okorokov, V; Oldag, E W; Olvitt, D L; Page, B S; Pan, Y X; Pandit, Y; Panebratsev, Y; Pawlak, T; Pawlik, B; Pei, H; Perkins, C; Pile, P; Planinic, M; Pluta, J; Poljak, N; Poniatowska, K; Porter, J; Poskanzer, A M; Pruthi, N K; Przybycien, M; Putschke, J; Qiu, H; Quintero, A; Ramachandran, S; Raniwala, R; Raniwala, S; Ray, R L; Riley, C K; Ritter, H G; Roberts, J B; Rogachevskiy, O V; Romero, J L; Ross, J F; Roy, A; Ruan, L; Rusnak, J; Rusnakova, O; Sahoo, N R; Sahu, P K; Sakrejda, I; Salur, S; Sandacz, A; Sandweiss, J; Sangaline, E; Sarkar, A; Schambach, J; Scharenberg, R P; Schmah, A M; Schmidke, W B; Schmitz, N; Seger, J; Seyboth, P; Shah, N; Shahaliev, E; Shanmuganathan, P V; Shao, M; Sharma, B; Shen, W Q; Shi, S S; Shou, Q Y; Sichtermann, E P; Simko, M; Skoby, M J; Smirnov, D; Smirnov, N; Solanki, D; Sorensen, P; Spinka, H M; Srivastava, B; Stanislaus, T D S; Stevens, J R; Stock, R; Strikhanov, M; Stringfellow, B; Sumbera, M; Sun, X; Sun, X M; Sun, Y; Sun, Z; Surrow, B; Svirida, D N; Symons, T J M; Szelezniak, M A; Takahashi, J; Tang, A H; Tang, Z; Tarnowsky, T; Thomas, J H; Timmins, A R; Tlusty, D; Tokarev, M; Trentalange, S; Tribble, R E; Tribedy, P; Trzeciak, B A; Tsai, O D; Turnau, J; Ullrich, T; Underwood, D G; Van Buren, G; van Nieuwenhuizen, G; Vandenbroucke, M; Vanfossen,, J A; Varma, R; Vasconcelos, G M S; Vasiliev, A N; Vertesi, R; Videbæk, F; Viyogi, Y P; Vokal, S; Voloshin, S A; Vossen, A; Wada, M; Wang, F; Wang, G; Wang, H; Wang, J S; Wang, X L; Wang, Y; Webb, G; Webb, J C; Wen, L; Westfall, G D; Wieman, H; Wissink, S W; Wu, Y F; Xiao, Z; Xie, W; Xin, K; Xu, H; Xu, J; Xu, N; Xu, Q H; Xu, Y; Xu, Z; Yan, W; Yang, C; Yang, Y; Ye, Z; Yepes, P; Yi, L; Yip, K; Yoo, I-K; Yu, N; Zbroszczyk, H; Zha, W; Zhang, J B; Zhang, J L; Zhang, S; Zhang, X P; Zhang, Y; Zhang, Z P; Zhao, F; Zhao, J; Zhong, C; Zhu, X; Zhu, Y H; Zoulkarneeva, Y; Zyzak, M

    2014-01-01

    A search for the quantum chromodynamics (QCD) critical point was performed by the STAR experiment at the Relativistic Heavy Ion Collider, using dynamical fluctuations of unlike particle pairs. Heavy-ion collisions were studied over a large range of collision energies with homogeneous acceptance and excellent particle identification, covering a significant range in the QCD phase diagram where a critical point may be located. Dynamical $K/\\pi$, $p/\\pi$, and $K/p$ fluctuations as measured by the STAR experiment in central 0-5% Au+Au collisions from center-of-mass collision energies $\\rm \\sqrt{s_{NN}}$ = 7.7 to 200 GeV are presented. The observable $\\rm \

  5. Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study.

    Science.gov (United States)

    Milroy, Lech-Gustav; Brunsveld, Luc; Ottmann, Christian

    2013-01-18

    Small-molecule modulation of protein-protein interactions (PPIs) is one of the most exciting but also difficult fields in chemical biology and drug development. As one of the most important "hub" proteins with at least 200-300 interaction partners, the 14-3-3 proteins are an especially fruitful case for PPI intervention. Here, we summarize recent success stories in small-molecule modulation, both inhibition and stabilization, of 14-3-3 PPIs. The chemical breath of modulators includes natural products such as fusicoccin A and derivatives but also compounds identified via high-throughput and in silico screening, which has yielded a toolbox of useful inhibitors and stabilizers for this interesting class of adapter proteins. Protein-protein interactions (PPIs) are involved in almost all biological processes, with any given protein typically engaged in complexes with other proteins for the majority of its lifetime. Hence, proteins function not simply as single, isolated entities but display their roles by interacting with other cellular components. These different interaction patterns are presumably as important as the intrinsic biochemical activity status of the protein itself. The biological role of a protein is therefore decisively dependent on the underlying PPI network that furthermore can show great spatial and temporal variations. A thorough appreciation and understanding of this concept and its regulation mechanisms could help to develop new therapeutic agents and concepts.

  6. Structural basis for the potent inhibition of the HIV integrase-LEDGF/p75 protein-protein interaction.

    Science.gov (United States)

    Ribone, Sergio R; Quevedo, Mario A

    2017-08-01

    Integrase (IN) constitutes one of the key enzymes involved in the lifecycle of the Human Immunodeficiency Virus (HIV), the etiological agent of AIDS. The biological role of IN strongly depends on the recognition and binding of cellular cofactors belonging to the infected host cell. Thus, the inhibition of the protein-protein interaction (PPI) between IN and cellular cofactors has been envisioned as a promising therapeutic target. In the present work we explore a structure-activity relationship for a set of 14 compounds reported as inhibitors of the PPI between IN and the lens epithelium-derived growth factor (LEDGF/p75). Our results demonstrate that the possibility to adopt the bioactive conformation capable of interacting with the hotspots IN-LEDGF/p75 hotspots residues constitutes a critical feature to obtain a potent inhibition. A ligand efficiency (|Lig-Eff|) quantitative descriptor combining both interaction energetics and conformational requirements was developed and correlated with the reported biological activity. Our results contribute to the rational development of IN-LEDGF/p75 interaction inhibitors providing a solid quantitative structure-activity relationship aimed for the screening of new IN-LEDGF/p75 interaction inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Electrophysiology meets fMRI: neural correlates of the startle reflex assessed by simultaneous EMG-fMRI data acquisition.

    Science.gov (United States)

    Neuner, Irene; Stöcker, Tony; Kellermann, Thilo; Ermer, Veronika; Wegener, Hans Peter; Eickhoff, Simon B; Schneider, Frank; Shah, N Jon

    2010-11-01

    The startle reflex provides a unique tool for the investigation of sensorimotor gating and information processing. Simultaneous EMG-fMRI acquisition (i.e., online stimulation and recording in the MR environment) allows for the quantitative assessment of the neuronal correlates of the startle reflex and its modulations on a single trial level. This serves as the backbone for a startle response informed fMRI analysis, which is fed by data acquired in the same brain at the same time. We here present the first MR study using a single trial approach with simultaneous acquired EMG and fMRI data on the human startle response in 15 healthy young men. It investigates the neural correlates for isolated air puff startle pulses (PA), prepulse-pulse inhibition (PPI), and prepulse facilitation (PPF). We identified a common core network engaged by all three conditions (PA, PPI, and PPF), consisting of bilateral primary and secondary somatosensory cortices, right insula, right thalamus, right temporal pole, middle cingulate cortex, and cerebellum. The cerebellar vermis exhibits distinct activation patterns between the startle modifications. It is differentially activated with the highest amplitude for PPF, a lower activation for PA, and lowest for PPI. The orbital frontal cortex exhibits a differential activation pattern, not for the type of startle response but for the amplitude modification. For pulse alone it is close to zero; for PPI it is activated. This is in contrast to PPF where it shows deactivation. In addition, the thalamus, the cerebellum, and the anterior cingulate cortex add to the modulation of the startle reflex.

  8. The CPI and the PPI Relation Research About our CountryBased on the Seasonally Adjusted Data Analysis%对罪国CPI与PPI关系研莽——基于季节调整后的数据分析

    Institute of Scientific and Technical Information of China (English)

    张立

    2012-01-01

    选取1997年1月-2011年12月间我国月度CPI和PPI数据进行了定基处理和季节调整,然后在其基础上建立了VAR模型。该模型分析的结果表明CPI和PPI之间存在协整关系。格兰杰因果检验分析结果表明,在5%的显著性水平下,CPI与PPI互为格兰杰因果。方差分解的结果表明,CPI和PPI自己对自己的变化的贡献率比较大。%This article based China' s monthly CPI and PPI data from January 1997 to December 2011 which was processed and seasonal adjusted, then adjusts the data to establish VAR model. The analysis of the model results show that the CPI and the PPI is cointegration relationship. Granger causality analysis results show that, at the 5% significance level, CPI and PPI are Grainger causality. Variance decomposition results show that, CPI and PPI to own change contribution rate is relatively large.

  9. Analysis of the chronic intake of and withdrawal from diazepam on emotional reactivity and sensory information processing in rats.

    Science.gov (United States)

    De Ross, J; Castilho, V M; Brandão, M L; Nobre, M J

    2008-04-01

    It has been demonstrated that, on abrupt withdrawal, patients with chronic exposure can experience a number of symptoms indicative of a dependent state. In clinical patients, the earliest to arise and most persistent signal of withdrawal from chronic benzodiazepine (Bzp) treatment is anxiety. In laboratory animals, anxiety-like effects following abrupt interruption of chronic Bzp treatment can also be reproduced. In fact, signs that oscillate from irritability to extreme fear behaviours and seizures have been described already. As anxiety remains one of the most important symptoms of Bzp withdrawal, in this study we evaluated the anxiety levels of rats withdrawn from diazepam. Also studied were the effects on the motor performance and preattentive sensory gating process of rats under diazepam chronic treatment and upon 48-h withdrawal on three animal models of anxiety, the elevated plus-maze (EPM), ultrasonic vocalizations (USV) and startle+prepulse inhibition tests. Data obtained showed an anxiolytic- and anxiogenic-like profile of the chronic intake of and withdrawal from diazepam regimen in the EPM test, 22-KHz USV and startle reflex. Diazepam chronic effects or its withdrawal were ineffective in promoting any alteration in the prepulse inhibition (PPI). However, an increase of PPI was achieved in both sucrose and diazepam pretreated rats on 48-h withdrawal, suggesting a procedural rather than a specific effect of withdrawal on sensory gating processes. It is also possible that the prepulse can function as a conditioned stimulus to informing the delivery of an aversive event, as the auditory startling-eliciting stimulus. All these findings are indicative of a sensitization of the neural substrates of aversion in diazepam-withdrawn animals without concomitant changes on the processing of sensory information.

  10. Histamine H3 Receptor Regulates Sensorimotor Gating and Dopaminergic Signaling in the Striatum.

    Science.gov (United States)

    Kononoff Vanhanen, Jenni; Nuutinen, Saara; Tuominen, Mervi; Panula, Pertti

    2016-05-01

    The brain histamine system has been implicated in regulation of sensorimotor gating deficits and in Gilles de la Tourette syndrome. Histamine also regulates alcohol reward and consumption via H3 receptor (H3R), possibly through an interaction with the brain dopaminergic system. Here, we identified the histaminergic mechanism of sensorimotor gating and the role of histamine H3R in the regulation of dopaminergic signaling. We found that H3R knockout mice displayed impaired prepulse inhibition (PPI), indicating deficiency in sensorimotor gating. Histamine H1 receptor knockout and histidine decarboxylase knockout mice had similar PPI as their controls. Dopaminergic drugs increased PPI of H3R knockout mice to the same level as in control mice, suggesting that changes in dopamine receptors might underlie deficient PPI response when H3R is lacking. Striatal dopamine D1 receptor mRNA level was lower, and D1 and D2 receptor-mediated activation of extracellular signal-regulated kinase 1/2 was absent in the striatum of H3R knockout mice, suggesting that H3R is essential for the dopamine receptor-mediated signaling. In conclusion, these findings demonstrate that H3R is an important regulator of sensorimotor gating, and the lack of H3R significantly modifies striatal dopaminergic signaling. These data support the usefulness of H3R ligands in neuropsychiatric disorders with preattentional deficits and disturbances in dopaminergic signaling.

  11. Synthesis and Photoelectrical Properties of Room-Temperature Phosphorescent (ppy)2lr(pybi) Complex%室温磷光材料二(2-苯基吡啶)(2-(2-吡啶)苯并咪唑)合铱(Ⅲ)的合成及光电特性

    Institute of Scientific and Technical Information of China (English)

    岳岩; 许慧侠; 郝玉英; 解晓东; 屈丽桃; 王华; 许并社

    2012-01-01

    以2-苯基毗啶(PPY)为主配体,2-(2-毗啶)苯并咪唑(pybiH)为辅助配体合成了一种室温蓝绿色磷光发射材料二(2-苯基吡啶)(2-(2-吡啶)苯并咪唑)合铱(Ⅲ)((ppy)2lr(pybi)),通过傅里叶变换红外(FTIR)光谱、核磁共振氢谱(1H NMR)、质谱(MS)、元素分析对其结构进行了表征.利用紫外-可见吸收光谱、荧光激发和发射光谱、循环伏安曲线,结合含时密度泛函理论(TD-DFT)模拟计算研究了(ppy)2(l)r(pybi)的光物理特性及能级结构,并研究了其电致发光性能.(ppy)2(l)r(pybi)的紫外吸收峰分别位于250,295,346和442 nm,与理论模拟计算吻合得很好;(PPY)2(l)r(pybi)为蓝绿光发射,发光峰分别位于495和518 nm; (ppy)2(l)r(pybi)的最高占据轨道(HOMO)和最低空轨道(LUMO)能级分别为-6.11和-3.43 eV,光学带隙为2.68 eV;以(ppy)zlr(pybi)为掺杂剂,4,4'-N,N'-二咔唑基联苯(CBP)为主体材料,制备电致磷光器件,电致发射峰位于508 nm,最大亮度为8451 cd·m-2,最大电流效率为17.6 cd·A-1.这些研究为(PPY)2lr(pybi)在有机电致发光领域的应用提供实验依据.%A blue-green emitter of iridium(Ⅲ) complex (ppy)2lr(pybi), has been synthesized (ppy= 2-phenyridine and pybi=2-(2-pyridyl)benzimdazole) and its structure was characterized by Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR), mass spectroscopy (MS), and elemental analysis. Its photophysical properties and energy-level structure were studied by UV-Vis absorption, excitation and emission spectroscopy, and cyclic voltammetry combining time-dependent density functional theory (TD-DFT). The electrophosphorescent performance of (ppy)2lr(pybi) was characterized by using 4,4-bis(9-carbazolyl)-1,1'-biphenyl (CBP) as host. The results indicated that the UV-Vis absorption bands were located at 250, 295, 346, and 442 nm, which were in good agreement with the TD-DFT simulation results. The blue-green phosphorescent emission was

  12. 血红素在聚吡咯-十二烷基苯磺酸修饰电极上的直接电化学%Direct Electrochemistry Bchavior of Heme on Ppy - DDSB Modified Electrode

    Institute of Scientific and Technical Information of China (English)

    程发良; 宁满霞; 莫金垣; 戴晓云

    2002-01-01

    用循环伏安法研究了血红素(Heme)在聚吡咯(Ppy)-十二烷基苯磺酸(DDSB)修饰电极上的直接电化学行为.探讨了影响血红素电化学反应速率的诸因素.并提出了用聚吡咯-十二烷基苯磺酸修饰电极测定的方法.结果表明:聚吡咯是血红素电子转移反应的稳定媒价体,血红素在聚吡咯-十二烷基苯磺酸修饰电极表面起准可逆氧化还原反应,-206.1mv处还原峰电流的1.5次微分与血红素浓度在5.0×10-6~1.0 ×10-8mol/L范围成线性关系.

  13. Design of PPI protocol by using single chip microcomputer as the slave station of $7-200 PLC%以单片机作为S7—200PLC从站的PPI协议的设计

    Institute of Scientific and Technical Information of China (English)

    孟强; 梅大成; 秦勃; 叶强

    2012-01-01

    为了将单片机加入到SIEMENSS7—200系列PLC的PPI(点对点协议)通信网络中,就需要分析PPI通信协议格式。本文利用CommMonitor6.0(串口监视精灵)工具,监控PLC与PLC之间的通信,通过总结分析出其数据格式,然后编写相应的单片机C51程序,使PLC能够使用NetR/NetW(网络读写命令)与单片机进行数据交换。%In order to add single chip to the SIEMENS $7-200 series PLC PPI(point to point protocol) communication network, if needs to analyse the PPI communication protocol format. The paper uses CommMontior6.0 to monitor the communication between PLCs, analyzes the data formats, then writes the corresponding C51 program. It achieves the communication between single chip and PLC using NetR/NetW.

  14. ACOUSTIC STARTLE RESPONSE AFFECTED BY AGING AND CHOLINERGIC NEUROTRANSMITTERS

    Institute of Scientific and Technical Information of China (English)

    Anna Hansen; SUN Wei

    2014-01-01

    The acoustic startle response has been used to evaluate tinnitus and hyperacusis in animal models. Gap induced prepulse in-hibition of the acoustic startle reflex (gap-PPI) is affected by tinnitus and loudness changes. Since tinnitus and reduced sound tolerance are commonly seen in elderly, we measured gap-PPI in Fischer 344 rats, an aging related hearing loss model, at dif-ferent ages: 3-5 months, 9-12 months, and 15-17 months. The startle response was induced by three different intensity of sound:105, 95 and 85 dB SPL. Gap-PPI was induced by different duration of silent gaps from 1 to 100 ms. When the startle was induced by 105 dB SPL sound intensity, the gap-PPI induced by 50 ms silent gap was significantly lower than those in-duced by 25 or 100 ms duration, showing a“notch”in the gap-PPI function. The“notch”disappeared with the reduction of startle sound, suggesting the“notch”may be related with hyper-sensitivity to loud sound. As the intensity of the stimulus de-creased, the appearance of the hyperacusis-like effect decreased more quickly for the youngest group of rats. We also tested scopolamine, a muscarinic acetylcholine receptor antagonist, and mecamylamine, a nicotinic acetylcholine receptor antago-nist, on the effect of gap-PPI. When scopolamine was administered, the results indicated no addition effect on the hyperacu-sis-like phenomenon in the two older groups. Mecamylamine, the nicotinic antagonist also showed effects on the appearance of hyperacusis on rats in different ages. The information derived from the study will be fundamental for the further research in determining the cause and treatment for hyperacusis.

  15. Safety of long-term PPI therapy

    DEFF Research Database (Denmark)

    Reimer, Christina

    2013-01-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published...... is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead...

  16. Clinical efficacy of endoscopic high-frequency electrocoagulation combined with PPI in treatment of short-segment Barrett's esophagus%内镜下高频电凝加PPI治疗短段Barrett食管的临床研究

    Institute of Scientific and Technical Information of China (English)

    何远琴; 侯俊; 李静娴; 赖敏莉

    2014-01-01

    目的:探讨内镜下高频电凝加PPI治疗短段Barrett食管(SSBE)疗效及安全性。方法经内镜及病理检查确诊的60例舌型及岛型SSBE患者分为两组,治疗组30例行内镜下高频电凝加口服雷贝拉唑20 mg,2次/日,维持抑酸治疗4周;对照组30例单纯给予口服雷贝拉唑20 mg,2次/日,治疗4周,后减量至20 mg,1次/日,维持治疗1年;分别于治疗后3、6、12、18及24个月复查胃镜并取活组织送病理检查。治疗组中复查胃镜未达显效的患者,再次行内镜下高频电凝治疗并予口服PPI治疗4周。结果治疗组平均显效率为87.0%,总有效率为100%,与对照组(8.1%,27.8%)相比,差异有统计学意义(P<均0.01);治疗组未出现出血、穿孔及食管狭窄等并发症。结论内镜下高频电凝加PPI治疗SSBE疗效明显,安全,并发症少。%Objective To study the clinical efficacy of endoscopic high-frequency electrocoagulation combined with proton pump inhibitor (PPI)in the treatment of tongue-and island-type SSBE. Methods Sixty patients pathologically diagnosed with tongue-and island-type SSBE were divided into the treatment (n=30 ) and control groups (n =30 ). In the treatment group,patients were treated with endoscopic high-frequency electrocoagulation combined with 20 mg of rabeprazole twice daily for 4 consecutive weeks,while the counter-parts in the control group were treated with 20 mg of rabeprazole twice daily for 4 consecutive weeks,and the dose was reduced to 20 mg of rabeprazole once daily and the maintenance therapy was delivered for 1 year. All patients underwent gastroscopy and biopsy samples were collected for pathological examination at 3,6,12,18 and 24 months after treatment beginning. The patients in the treatment group achieved no significant efficacy repeatedly received endoscopic high-frequency electrocoagulation and rabeprazole administration for another 4 weeks

  17. 改进的果蝇算法及其在 PPI网络中的应用%A MODIFIED FRUIT FLY ALGORITHM AND ITS APPLICATION IN PPI NETWORK

    Institute of Scientific and Technical Information of China (English)

    杨书佺; 舒勤; 何川

    2014-01-01

    针对基本功能流聚类算法计算复杂度高、聚类正确率较低的缺点,提出一种基于改进的果蝇算法与功能流算法相融合的聚类分析算法Flow-IFOA。通过引入果蝇因子,根据离最优解果蝇的距离自适应地调整每个果蝇个体的搜索步长,保证了算法的搜索精度和速度。将改进后的果蝇算法与功能流算法融合,在PPI网络数据库上的仿真结果表明,改进算法相比其他聚类算法得到了较好的聚类正确率和较快的收敛速度,是一种行之有效的方法。%The paper proposes a new clustering analysis algorithm FLOW-IFOA, which is based on the combination of improved fruit fly algorithm and function flow clustering algorithm and aims at the drawbacks of basic function flow clustering algorithm such as high time com-plexity and low clustering accuracy.The searching accuracy and speed of the proposed algorithm are guaranteed by introducing the fruit fly factor and adaptively adjusting the searching step size of individual fruit fly according to the distance to optimal solution fruit fly.Simulations on the PPI network database indicate that the proposed algorithm has better clustering accuracy and faster converging rate compared with other clustering algorithms, so it is an effective method.

  18. Voltage-Gated R-Type Calcium Channel Inhibition via Human μ-, δ-, and κ-opioid Receptors Is Voltage-Independently Mediated by Gβγ Protein Subunits.

    Science.gov (United States)

    Berecki, Géza; Motin, Leonid; Adams, David J

    2016-01-01

    Elucidating the mechanisms that modulate calcium channels via opioid receptor activation is fundamental to our understanding of both pain perception and how opioids modulate pain. Neuronal voltage-gated N-type calcium channels (Cav2.2) are inhibited by activation of G protein-coupled opioid receptors (ORs). However, inhibition of R-type (Cav2.3) channels by μ- or κ-ORs is poorly defined and has not been reported for δ-ORs. To investigate such interactions, we coexpressed human μ-, δ-, or κ-ORs with human Cav2.3 or Cav2.2 in human embryonic kidney 293 cells and measured depolarization-activated Ba(2+) currents (IBa). Selective agonists of μ-, δ-, and κ-ORs inhibited IBa through Cav2.3 channels by 35%. Cav2.2 channels were inhibited to a similar extent by κ-ORs, but more potently (60%) via μ- and δ-ORs. Antagonists of δ- and κ-ORs potentiated IBa amplitude mediated by Cav2.3 and Cav2.2 channels. Consistent with G protein βγ (Gβγ) interaction, modulation of Cav2.2 was primarily voltage-dependent and transiently relieved by depolarizing prepulses. In contrast, Cav2.3 modulation was voltage-independent and unaffected by depolarizing prepulses. However, Cav2.3 inhibition was sensitive to pertussis toxin and to intracellular application of guanosine 5'-[β-thio]diphosphate trilithium salt and guanosine 5'-[γ-thio]triphosphate tetralithium salt. Coexpression of Gβγ-specific scavengers-namely, the carboxyl terminus of the G protein-coupled receptor kinase 2 or membrane-targeted myristoylated-phosducin-attenuated or abolished Cav2.3 modulation. Our study reveals the diversity of OR-mediated signaling at Cav2 channels and identifies neuronal Cav2.3 channels as potential targets for opioid analgesics. Their novel modulation is dependent on pre-existing OR activity and mediated by membrane-delimited Gβγ subunits in a voltage-independent manner.

  19. Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats

    Directory of Open Access Journals (Sweden)

    Uta Waterhouse

    2016-10-01

    Full Text Available Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg at one of three neurodevelopmental time periods [gestation days (GD 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND 60] and included: prepulse inhibition (PPI, latent inhibition (LI and delayed non-matching to sample (DNMTS. Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously were administered, and animals were re-tested in the same tasks (PND 110. Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11 resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI and selective (LI improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI and induced a global enhancement of sensorimotor gating (PPI.

  20. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.

    Science.gov (United States)

    Jo, Sooyeon; Bean, Bruce P

    2017-04-01

    Lacosamide is an antiseizure agent that targets voltage-dependent sodium channels. Previous experiments have suggested that lacosamide is unusual in binding selectively to the slow-inactivated state of sodium channels, in contrast to drugs like carbamazepine and phenytoin, which bind tightly to fast-inactivated states. Using heterologously expressed human Nav1.7 sodium channels, we examined the state-dependent effects of lacosamide. Lacosamide induced a reversible shift in the voltage dependence of fast inactivation studied with 100-millisecond prepulses, suggesting binding to fast-inactivated states. Using steady holding potentials, lacosamide block was very weak at -120 mV (3% inhibition by 100 µM lacosamide) but greatly enhanced at -80 mV (43% inhibition by 100 µM lacosamide), where there is partial fast inactivation but little or no slow inactivation. During long depolarizations, lacosamide slowly (over seconds) put channels into states that recovered availability slowly (hundreds of milliseconds) at -120 mV. This resembles enhancement of slow inactivation, but the effect was much more pronounced at -40 mV, where fast inactivation is complete, but slow inactivation is not, than at 0 mV, where slow inactivation is maximal, more consistent with slow binding to fast-inactivated states than selective binding to slow-inactivated states. Furthermore, inhibition by lacosamide was greatly reduced by pretreatment with 300 µM lidocaine or 300 µM carbamazepine, suggesting that lacosamide, lidocaine, and carbamazepine all bind to the same site. The results suggest that lacosamide binds to fast-inactivated states in a manner similar to other antiseizure agents but with slower kinetics of binding and unbinding.

  1. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2014-06-13

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

  2. Study the Nonlinear Granger Causality between CPI and PPI---Based on Shenzhen's Monthly Data%CPI与PPI的非线性Granger因果关系研究--基于深圳市月度数据的实证分析

    Institute of Scientific and Technical Information of China (English)

    黄智淋

    2014-01-01

    Based on Shenzhen's CPI and PPI from January 2005 to December 2013, this paper investigates the nonlinear relationship between CPI and PPI by using nonlinear Granger causality test , then dynamic analyzes the nonlinear relationship between CPI and PPI at different period by using step-test procedure. The results of nonlinear Granger causality test indicate that there exists a unidirectional nonlinear Granger causality from PPI to CPI during the sample period. What's more , step-test shows that PPI is the nonlinear Granger causality of CPI. This suggests that the supply side factors have played a more important role than demand side factors in CPI inflation, and implies that price rise of upstream factors of production will lead to increase in downstream consumer prices, then result in enlarge the pressures of cost-push inflation. Therefore, we'd better consider the supply side for inflation control and adopt macro-control policies according to the dynamic relationship between CPI and PPI.%文章基于深圳市2005年1月至2013年12月的居民消费价格指数(CPI)和工业生产者出厂价格指数(PPI),运用非线性Granger因果关系检验,从非线性的角度考察深圳市的CPI与PPI之间的作用关系,并采用逐步检验方法对CPI与PPI之间在不同时期的作用关系进行动态分析。非线性Granger因果关系检验的结果表明,在所考察的样本时期内,存在着由PPI到CPI的单向非线性Granger因果关系。逐步检验则进一步显示, PPI是引起CPI变化的非线性Granger因果原因。这说明供给因素在以CPI衡量的通货膨胀中占优于需求因素,也意味着上游生产要素的价格上涨将传导至下游消费品的价格,以致加大了成本推动通货膨胀的压力。因此,治理通货膨胀应采取以供给调控为主的政策,并适时适度地根据CPI与PPI之间的动态关系进行宏观调控。

  3. CPI、PPI、PMI对经济发展影响的实证研究--基于SVAR模型的分析%An Applied Study on the Economic Development by CPI, PPI, PMI---Based on SVAR Model

    Institute of Scientific and Technical Information of China (English)

    赵怡

    2016-01-01

    随着社会主义市场经济和经济全球化进程的深入发展,市场竞争日益激烈,影响经济发展的因素也日渐繁多。这一变化固然给国家经济发展带来了更多的机遇,但也增加了经济增长预测的难度。由此,及时准确地把握市场经济走向,了解经济运行态势显得尤为重要。将价格指数CPI、PPI与采购经理指数PMI相结合,且用月度的工业增加值来代替季度的GDP指标,运用结构向量自回归(SVAR)模型来建立一个新的经济增长预测模型。实证结果表明,综合考虑了CPI、PPI、PMI三个指标的新模型,具有更好的拟合效果和预测效果。%With the deep development of the socialist market economy and economic globalization, market competition becomes fiercer than ever before and the factors that affect economic development are also increasing. This change brings more opportunities to the national economic development, but it also increases the difficulty of economic growth forecast. Therefore, timely and accurately to grasp the trend of market economy and to learn the economic situation is particularly important. This thesis combines the price index CPI, PPI and Purchase Managers Index (PMI) to discuss the above problem, and the quarterly GDP index is replaced by the monthly industrial added value in addition. In this paper, a new model of economic growth forecast is established by using the Structural Vector Auto-regression and the result suggest that the new model has the better fitting effect and prediction effect.

  4. Reciprocal inhibition in man.

    Science.gov (United States)

    Crone, C

    1993-11-01

    Reciprocal inhibition is the automatic antagonist alpha motor neurone inhibition which is evoked by contraction of the agonist muscle. This so-called natural reciprocal inhibition is a ubiquitous and pronounced phenomenon in man and must be suspected of playing a major role in the control of voluntary movements. The spinal pathways underlying this inhibitory phenomenon were studied. The disynaptic reciprocal Ia inhibitory pathway between the tibial anterior muscle and the soleus alpha motor neurones was identified and described in man. It was shown that the inhibition can be evoked in most healthy subjects at rest, but the degree of inhibition varies considerably from one subject to another. It was concluded that it corresponds to the disynaptic reciprocal Ia inhibitory pathway which has been extensively described in animal experiments. The disynaptic reciprocal inhibition was shown to increase during the dynamic phase of a dorsiflexion movement of the foot, but not during the tonic phase. However, when the peripheral afferent feedback from the contracting muscle was blocked by ischaemia, an increase of the inhibition was revealed also during the tonic phase of the dorsiflexion. The concealment of this increase during unrestrained peripheral feedback from the muscle was thought to be due to the post-activation depression mechanism; a mechanism which was described further and which probably involves reduced transmitter release at Ia afferent terminals as a result of previous activation of these afferent fibers. Hence the hypothesis was supported that alpha motor neurones and the corresponding inhibitory interneurones, which project reciprocal inhibition to the antagonist motor neurones, are activated in parallel during voluntary contraction of agonist muscles. An additional reciprocal inhibitory mechanism, the long latency reciprocal inhibition, was described between the tibial anterior muscle and the soleus alpha motor neurones. It was shown to be evoked by group I

  5. Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats.

    Science.gov (United States)

    Harte, M K; Powell, S B; Swerdlow, N R; Geyer, M A; Reynolds, G P

    2007-07-01

    Post-mortem studies have provided evidence for abnormalities of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia. The calcium-binding proteins (CBPs), parvalbumin (PV), calbindin (CB) and calretinin (CR) can be used as markers for specific subpopulations of GABAergic neurons in the brain. Isolation rearing of rats is a non-pharmacological, non-lesion manipulation that leads to deficits in prepulse inhibition of the startle reflex (PPI) and other behavioural and neurochemical alterations reminiscent of schizophrenia. Female rats were reared in social housing (groups of three) or singly for 11 weeks post weaning and PPI was measured. Brains were removed and hippocampal CBP- containing neurons determined following immunocytochemical staining. Compared to socially housed rats, isolated rats exhibited PPI deficits and reductions in PV and CB-immunoreactive cells in the hippocampus, with no significant change in CR. These findings demonstrate selective abnormalities of sub-populations of GABAergic interneurons in the hippocampus of isolation reared rats, which resemble the neuronal deficits seen in this region in schizophrenia.

  6. P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating.

    Directory of Open Access Journals (Sweden)

    Hiroki Takeuchi

    Full Text Available Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI, a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD, in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions.

  7. Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History.

    Science.gov (United States)

    Greenwood, Tiffany A; Light, Gregory A; Swerdlow, Neal R; Calkins, Monica E; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Freedman, Robert; Braff, David L

    2016-04-01

    The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.

  8. Polyphosphates inhibit extracellular matrix mineralization in MC3T3-E1 osteoblast cultures.

    Science.gov (United States)

    Hoac, Betty; Kiffer-Moreira, Tina; Millán, José Luis; McKee, Marc D

    2013-04-01

    measured by Pi release. Importantly, at the concentrations of polyphosphates used in this study which inhibited bone cell culture mineralization, the polyphosphates competitively saturated TNAP, thus potentially interfering with its ability to hydrolyze mineralization-inhibiting pyrophosphate (PPi) and mineralizing-promoting β-glycerophosphate (in cell culture). In the biological setting, polyphosphates may regulate mineralization by shielding the essential inhibitory substrate pyrophosphate from TNAP degradation, and in the same process, delay the release of phosphate from this source. In conclusion, the inhibition of mineralization by polyphosphates is shown to occur via direct binding to apatitic mineral and by mixed inhibition of TNAP.

  9. Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine.

    Science.gov (United States)

    Halberstadt, Adam L

    2016-04-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100,635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by

  10. Behavioral and Pharmacokinetic Interactions Between Monoamine Oxidase Inhibitors and the Hallucinogen 5-Methoxy-N,N-dimethyltryptamine

    Science.gov (United States)

    Halberstadt, Adam L.

    2016-01-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography–electrospray ionization–selective reaction monitoring–tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1 mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI

  11. Potentiation of latent inhibition.

    Science.gov (United States)

    Rodriguez, Gabriel; Hall, Geoffrey

    2008-07-01

    Rats were given exposure either to an odor (almond) or a compound of odor plus taste (almond plus saline), prior to training in which the odor served as the conditioned stimulus. It was found, for both appetitive and aversive procedures, that conditioning was retarded by preexposure (a latent inhibition effect), and the extent of the retardation was greater in rats preexposed to the compound (i.e., latent inhibition to the odor was potentiated by the presence of the taste). In contrast, the presence of the taste during conditioning itself overshadowed learning about the odor. We argue that the presence of the salient taste in compound with the odor enhances the rate of associative learning, producing a rapid loss in the associability of the odor. This loss of associability will generate both overshadowing and the potentiation of latent inhibition that is observed after preexposure to the compound.

  12. Differential expression of brain immune genes and schizophrenia-related behavior in C57BL/6N and DBA/2J female mice.

    Science.gov (United States)

    Ma, Li; Kulesskaya, Natalia; Võikar, Vootele; Tian, Li

    2015-03-30

    Mounting evidence suggests the association of immune genes with complex neuropsychiatric diseases, such as schizophrenia. However, immune gene expression in the brain and their involvement in schizophrenia-related behavior in animal models have not been well studied so far. We analyzed the social (resident-intruder) and sensorimotor gating (pre-pulse inhibition (PPI) of acoustic startle) behaviors, and expression profiles of several brain immune genes in adult C57BL/6N and DBA/2J female mice. Compared to C57BL/6N mice, DBA/2J mice exhibited less social interaction in the resident-intruder test and reduced pre-pulse inhibition. The mRNA levels of Il1b and Il6 genes were significantly higher in the cortex and hypothalamus, while the mRNA level of C1qb was lower in the cortex, hippocampus and hypothalamus of DBA/2J mice compared to C57BL/6N mice. Furthermore, Tnfsf13b was up-regulated in the cortex and hippocampus, and so did Cd47 in the hippocampus, while Cx3cl1 was down-regulated in the cortex of DBA/2J mice. Our study demonstrates the differential expression of several immune genes in C57BL/6N and DBA/2J strains and more importantly provides clues on their potential importance in regulating schizophrenia-related endophenotypes in animal models.

  13. Influence of emotional states on inhibitory gating: animals models to clinical neurophysiology.

    Science.gov (United States)

    Cromwell, Howard C; Atchley, Rachel M

    2015-01-01

    Integrating research efforts using a cross-domain approach could redefine traditional constructs used in behavioral and clinical neuroscience by demonstrating that behavior and mental processes arise not from functional isolation but from integration. Our research group has been examining the interface between cognitive and emotional processes by studying inhibitory gating. Inhibitory gating can be measured via changes in behavior or neural signal processing. Sensorimotor gating of the startle response is a well-used measure. To study how emotion and cognition interact during startle modulation in the animal model, we examined ultrasonic vocalization (USV) emissions during acoustic startle and prepulse inhibition. We found high rates of USV emission during the sensorimotor gating paradigm and revealed links between prepulse inhibition (PPI) and USV emission that could reflect emotional and cognitive influences. Measuring inhibitory gating as P50 event-related potential suppression has also revealed possible connections between emotional states and cognitive processes. We have examined the single unit responses during the traditional gating paradigm and found that acute and chronic stress can alter gating of neural signals in regions such as amygdala, striatum and medial prefrontal cortex. Our findings point to the need for more cross-domain research on how shifting states of emotion can impact basic mechanisms of information processing. Results could inform clinical work with the development of tools that depend upon cross-domain communication, and enable a better understanding and evaluation of psychological impairment.

  14. Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction

    Science.gov (United States)

    Manigrasso, Michaele B.; Pan, Jinhong; Rai, Vivek; Zhang, Jinghua; Reverdatto, Sergey; Quadri, Nosirudeen; DeVita, Robert J.; Ramasamy, Ravichandran; Shekhtman, Alexander; Schmidt, Ann Marie

    2016-01-01

    The receptor for advanced glycation endproducts (RAGE) binds diverse ligands linked to chronic inflammation and disease. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. The cytoplasmic tail (ct) of RAGE is essential for RAGE ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE signaling requires interaction of ctRAGE with the intracellular effector, mammalian diaphanous 1 or DIAPH1. We screened a library of 58,000 small molecules and identified 13 small molecule competitive inhibitors of ctRAGE interaction with DIAPH1. These compounds, which exhibit in vitro and in vivo inhibition of RAGE-dependent molecular processes, present attractive molecular scaffolds for the development of therapeutics against RAGE-mediated diseases, such as those linked to diabetic complications, Alzheimer’s disease, and chronic inflammation, and provide support for the feasibility of inhibition of protein-protein interaction (PPI). PMID:26936329

  15. Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction.

    Science.gov (United States)

    Manigrasso, Michaele B; Pan, Jinhong; Rai, Vivek; Zhang, Jinghua; Reverdatto, Sergey; Quadri, Nosirudeen; DeVita, Robert J; Ramasamy, Ravichandran; Shekhtman, Alexander; Schmidt, Ann Marie

    2016-03-03

    The receptor for advanced glycation endproducts (RAGE) binds diverse ligands linked to chronic inflammation and disease. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. The cytoplasmic tail (ct) of RAGE is essential for RAGE ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE signaling requires interaction of ctRAGE with the intracellular effector, mammalian diaphanous 1 or DIAPH1. We screened a library of 58,000 small molecules and identified 13 small molecule competitive inhibitors of ctRAGE interaction with DIAPH1. These compounds, which exhibit in vitro and in vivo inhibition of RAGE-dependent molecular processes, present attractive molecular scaffolds for the development of therapeutics against RAGE-mediated diseases, such as those linked to diabetic complications, Alzheimer's disease, and chronic inflammation, and provide support for the feasibility of inhibition of protein-protein interaction (PPI).

  16. Phenytoin inhibits the persistent sodium current in neocortical neurons by modifying its inactivation properties.

    Directory of Open Access Journals (Sweden)

    Elisa Colombo

    Full Text Available The persistent Na⁺ current (I(NaP is important for neuronal functions and can play a role in several pathologies, although it is small compared to the transient Na⁺ current (I(NaT. Notably, I(NaP is not a real persistent current because it undergoes inactivation with kinetics in the order of tens of seconds, but this property has often been overlooked. Na⁺ channel blockers, drugs used for treating epilepsy and other diseases, can inhibit I(NaP, but the mechanism of this action and the conditions in which I(NaP can be actually inhibited have not been completely clarified yet. We evaluated the action of phenytoin (PHT, a prototype anti-epileptic Na⁺ channel blocker, on I(NaP inactivation in pyramidal neurons of rat sensorimotor cortical slices at different concentrations, from 5 to 100 µM. PHT did not modify I(NaP evoked with depolarizing voltage ramps of 50 or 100 mVs⁻¹, but decreased I(NaP evoked by slower voltage ramps (10 mVs⁻¹. However, at all of the tested concentrations, PHT decreased I(NaP evoked by faster ramps when they were preceded by inactivating pre-pulses. Moreover, PHT shifted towards negative potentials the voltage-dependence of I(NaP inactivation and accelerated its kinetics of development also at depolarized potentials (+40 mV, not consistently with a simple inactivated state stabilizer. Therefore, our study shows a prominent PHT effect on I(NaP inactivation rather than an open channel block, which is instead often implied. I(NaP is inhibited by PHT only in conditions that induce major I(NaP inactivation. These results highlight the importance of I(NaP inactivation not only for physiological functions but also as drug target, which could be shared by other therapeutic drugs. Through this action PHT can reduce I(NaP-induced long-lasting pathological depolarisations and intracellular sodium overload, whereas shorter I(NaP actions should not be modified. These properties set the conditions of efficacy and the limits

  17. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  18. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  19. Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: clinical rescue by d-serine.

    Directory of Open Access Journals (Sweden)

    Hiroko Hagiwara

    Full Text Available BACKGROUND: D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA receptor, is synthesized from L-serine by serine racemase (SRR. Given the role of D-serine in both neurodevelopment and the pathophysiology of schizophrenia, we examined whether neonatal disruption of D-serine synthesis by SRR inhibition could induce behavioral abnormalities relevant to schizophrenia, in later life. METHODOLOGY/PRINCIPAL FINDINGS: Neonatal mice (7-9 days were injected with vehicle or phenazine methosulfate (Met-Phen: 3 mg/kg/day, an SRR inhibitor. Behavioral evaluations, such as spontaneous locomotion, novel object recognition test (NORT, and prepulse inhibition (PPI were performed at juvenile (5-6 weeks old and adult (10-12 weeks old stages. In addition, we tested the effects of D-serine on PPI deficits in adult mice after neonatal Met-Phen exposure. Finally, we assessed whether D-serine could prevent the onset of schizophrenia-like behavior in these mice. Neonatal Met-Phen treatment reduced D-serine levels in the brain, 24 hours after the final dose. Additionally, this treatment caused behavioral abnormalities relevant to prodromal symptoms in juveniles and to schizophrenia in adults. A single dose of D-serine improved PPI deficits in adult mice. Interestingly, chronic administration of D-serine (900 mg/kg/day from P35 to P70 significantly prevented the onset of PPI deficits after neonatal Met-Phen exposure. CONCLUSIONS/SIGNIFICANCE: This study shows that disruption of D-serine synthesis during developmental stages leads to behavioral abnormalities relevant to prodromal symptoms and schizophrenia, in later life. Furthermore, early pharmacological intervention with D-serine may prevent the onset of psychosis in adult.

  20. Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.

    Directory of Open Access Journals (Sweden)

    Peiyan Wong

    Full Text Available Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS, which has been suggested to enhance cognitive functions through GABA(A receptor signaling by its metabolites. It has been shown that the level of pregnenolone is altered in certain brain areas of schizophrenic patients, and clozapine enhances pregnenolone in the CNS in rats, suggesting that pregnenolone could be used to treat certain symptoms of schizophrenia. In addition, early phase proof-of-concept clinical trials have indicated that pregnenolone is effective in reducing the negative symptoms and cognitive deficits of schizophrenia patients. Here, we evaluate the actions of pregnenolone on a mouse model for schizophrenia, the dopamine transporter knockout mouse (DAT KO. DAT KO mice mirror certain symptoms evident in patients with schizophrenia, such as the psychomotor agitation, stereotypy, deficits of prepulse inhibition and cognitive impairments. Following acute treatment, pregnenolone was found to reduce the hyperlocomotion, stereotypic bouts and pre-pulse inhibition (PPI deficits in DAT KO mice in a dose-dependent manner. At 60 mg/kg of pregnenolone, there were no significant differences in locomotor activities and stereotypy between wild-type and DAT KO mice. Similarly, acute treatment of 60 mg/kg of pregnenolone fully rescued PPI deficits of DAT KO mice. Following chronic treatment with pregnenolone at 60 mg/kg, the cognitive deficits of DAT KO mice were rescued in the paradigms of novel object recognition test and social transmission of food preference test. Pregnenolone thus holds promise as a therapeutic candidate in schizophrenia.

  1. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  2. Inhibition and Brain Work

    OpenAIRE

    Buzsáki, György; Kaila, Kai; Raichle, Marcus

    2007-01-01

    The major part of the brain’s energy budget (~60%–80%) is devoted to its communication activities. While inhibition is critical to brain function, relatively little attention has been paid to its metabolic costs. Understanding how inhibitory interneurons contribute to brain energy consumption (brain work) is not only of interest in understanding a fundamental aspect of brain function but also in understanding functional brain imaging techniques which rely on measurements related to blood flow...

  3. Latent inhibition in schizophrenia.

    Science.gov (United States)

    Swerdlow, N R; Braff, D L; Hartston, H; Perry, W; Geyer, M A

    1996-05-01

    Latent inhibition (LI) refers to the retarded acquisition of a conditioned response that occurs if the subject being tested is first preexposed to the to-be-conditioned stimulus (CS) without the paired unconditioned stimulus (UCS). Because the 'irrelevance' of the to-be-conditioned stimulus is established during non-contingent preexposure, the slowed acquisition of the CS-UCS association is thought to reflect the process of overcoming this learned irrelevance. Latent inhibition has been reported to be diminished in acutely hospitalized schizophrenia patients. If acutely hospitalized schizophrenia patients are preexposed to the CS, they learn the association as fast as, and perhaps faster than, patients who are not preexposed to the CS. This finding has been interpreted as reflecting the inability of acute schizophrenia patients to ignore irrelevant stimuli. In this study, the LI paradigm was identical to the one used in previous reports of LI deficits in schizophrenia patients (Baruch et al., 1988). Latent inhibition was observed in normal control subjects (n = 73), including individuals identified as 'psychosis-prone' based on established screening criteria, and in anxiety (n = 19) and mood disorder (n = 13) patients. Learning scores (trials to criterion) in "acutely' hospitalized as well as "chronic' hospitalized schizophrenia patients (n = 45) were significantly elevated in both preexposed and non-preexposed subjects, compared to controls. Acute schizophrenia patients exhibited intact LI. Separate cohorts of acute and chronic schizophrenia patients (n = 23) and normal controls (n = 34) exhibited intact LI when tested in a new, easier-to-acquire computerized LI paradigm. These results fail to identify specific LI deficits in schizophrenia patients, and raise the possibility that previously observed LI deficits in schizophrenia patients may reflect, at least in part, performance deficits related to learning acquisition.

  4. Beneficial bacteria inhibit cachexia.

    Science.gov (United States)

    Varian, Bernard J; Goureshetti, Sravya; Poutahidis, Theofilos; Lakritz, Jessica R; Levkovich, Tatiana; Kwok, Caitlin; Teliousis, Konstantinos; Ibrahim, Yassin M; Mirabal, Sheyla; Erdman, Susan E

    2016-03-15

    Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny.

  5. Conducting polymer PPy nanowire-based triboelectric nanogenerator and its application for self-powered electrochemical cathodic protection† †Electronic supplementary information (ESI) available: Microscope images, OCP variation and Tafel curves of Q235 carbon steel which is connected to the cathodic protection system driven by W-TENG are reported here. See DOI: 10.1039/c6sc02562e Click here for additional data file.

    Science.gov (United States)

    Cui, Siwen; Zheng, Youbin; Liang, Jun

    2016-01-01

    As a new type of energy harvesting device, the triboelectric nanogenerator (TENG) can convert almost all kinds of mechanical energy into electricity based on the coupling of triboelectrification and electrostatic induction. Here, a novel TENG is constructed with a conducting polymer polypyrrole nanowire (PPy NW) electrode, which is prepared by an electrochemical polymerization method with anodic aluminum oxide (AAO) as the template. The PPy NW-based TENG shows high output performance with a maximum short circuit current density of 23.4 mA m–2 and output voltage of 351 V, which can light 372 commercial red LEDs. Moreover, a self-powered anticorrosion system powered by the PPy NW-based TENG is designed, which can provide extra electrons to inject into the surface of the protected metals, forming effective impressed current cathodic protection by harvesting mechanical energy or wind energy. This smart device has potential applications for protecting metals from corrosion in daily life, industrial production and ocean exploration by harvesting the energies in the ambient environment. PMID:28451105

  6. Pharmacological characterization of social isolation-induced hyperactivity.

    Science.gov (United States)

    Fabricius, Katrine; Helboe, Lone; Fink-Jensen, Anders; Wörtwein, Gitta; Steiniger-Brach, Björn

    2011-05-01

    Social isolation (SI) of rats directly after weaning is a non-pharmacological, non-lesion animal model based on the neurodevelopmental hypothesis of schizophrenia. The model causes several neurobiological and behavioral alterations consistent with observations in schizophrenia. In the present study, we evaluated if isolated rats display both a pre-pulse inhibition (PPI) deficit and hyperactivity. Furthermore, the sensitivity of SI hyperactivity to antipsychotic was evaluated. Rats were socially isolated or group-housed for 12 weeks starting on postnatal day 25. In one batch of animals, the PPI and hyperactivity response were repeatedly compared. Furthermore, we investigated the robustness of the SI-induced hyperactivity by testing close to 50 batches of socially isolated or group-housed rats and tested the sensitivity of the assay to first- and second-generation antipsychotics, haloperidol, olanzapine, and risperidone, as well as the group II selective metabotrobic glutamate receptor agonist (LY404039). Socially isolated rats showed a minor PPI deficit and a robust increase in hyperactivity compared with controls. Furthermore, SI-induced hyperactivity was selectively reversed by all antipsychotics, as well as the potential new antipsychotic, LY404039. SI-induced hyperactivity was more pronounced and robust, as compared with SI-induced PPI deficits. Furthermore, SI-induced hyperactivity might be predictive for antipsychotic efficacy, as current treatment was effective in the model. Finally, using LY404039, a compound in development against schizophrenia, we have shown that the hyperactivity assay is sensitive to potential novel mechanisms of action. Thus, SI-induced hyperactivity might be a robust and novel in vivo screening assay of antipsychotic efficacy.

  7. Individual differences in responses to nicotine: tracking changes from adolescence to adulthood

    Institute of Scientific and Technical Information of China (English)

    Ming LI; Alexa MEAD; Rick A BEVINS

    2009-01-01

    Aim: The present study determined the extent to which individual differences in responses to the psychostimulating effect of nicotine during adolescence predict similar individual differences during adulthood in rats. We also examined the possible long-term effects of adolescent nicotine exposure on adult prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating ability.Methods: During the adolescent phase, rats were administered saline, 0.10, 0.40, or 0.60 mg/kg nicotine via subcutaneous injections for 8 days, and motor activity was measured daily. During the adult phase, these rats were treated with the same nicotine dose as in adolescence for 8 additional days. The adolescent saline rats (now adults) were subdivided into four groups and administered saline, 0.10, 0.40, or 0.60 mg/kg nicotine, respectively. PPI was assessed 12 days after the last nicotine treatment.Results: During both phases, nicotine increased motor activity across test days in a dose-dependent manner. Motor activity of rats treated with nicotine during adolescence was positively correlated with the activity recorded from the same rats during adulthood. In both phases, there were profound individual differences in the responses to the nicotine treatments. In addition, adolescent rats treated with nicotine did not show decreased motor response to the initial exposure to nicotine. Finally, adolescent exposure to nicotine at 0.4 mg/kg, but not adulthood exposure to the same dose of nicotine, produced a robust disruption of PPI, with individual rats showing different degrees of PPI disruption.Conclusion: These findings suggest that adolescent rats have increased sensitivity to the psychostimulating effect and decreased sensitivity to the aversive effect of nicotine. Also, nicotine exposure during adolescence may have long-term detrimental effects on sensorimotor gating ability.

  8. Effects of SPAK knockout on sensorimotor gating, novelty exploration, and brain area-dependent expressions of NKCC1 and KCC2 in a mouse model of schizophrenia.

    Science.gov (United States)

    Yang, Sung-Sen; Huang, Chuen-Lin; Chen, Huei-E; Tung, Che-Se; Shih, Han-Peng; Liu, Yia-Ping

    2015-08-01

    SPAK (Sterile 20/SPS1-related proline/alanine-rich kinase) is a protein kinase belonging to the mitogen-activated protein kinase (MAPK) superfamily that has been found to be extensively distributed across the body. The SPAK downstream substrates NKCC1 and KCC2 in the central nervous system are important in the interpretation of developmental mental disorders. The present study aimed to clarify the role of SPAK-NKCC1/KCC2 using a rodent schizophrenia-like model. The mouse paradigm of isolation rearing (IR) was employed, as it simulates the sensorimotor gating abnormalities of schizophrenia. SPAK transgenic mice were used and were divided into four groups: social-wild type, social-SPAK(-/-), isolation-wild type, and isolation-SPAK(-/-). The prepulse inhibition (PPI) test and the novel object recognition test (NORT) were used to measure schizophrenia-associated dysfunctions in gating ability and the novelty recognition, respectively. Finally, the protein expressions of NKCC1/KCC2 in the prefrontal cortex and hippocampus were detected to determine correlations with the behavioral data. Our results demonstrated that SPAK-null mice had superior PPI and novelty recognition relative to wild type controls, with a concomitant increase in KCC2 in the prefrontal cortex. IR disrupted PPI and NORT performances with an associated increase in KCC2. Furthermore, rearing environment and gene manipulation had mutually interactive effects, as the IR-induced effects on PPI and NORT were reversed by SPAK knockout, and the increase in KCC2 and the decreased in the NKCC1/KCC2 ratio in the prefrontal cortex induced by SPAK knockout were reversed by IR. Our data supported the gene-environment hypothesis and demonstrated the potential value of SPAK manipulation in future schizophrenia studies.

  9. Behavioral characterization of a mutant mouse strain lacking D-amino acid oxidase activity.

    Science.gov (United States)

    Zhang, Min; Ballard, Michael E; Basso, Ana M; Bratcher, Natalie; Browman, Kaitlin E; Curzon, Pete; Konno, Ryuichi; Meyer, Axel H; Rueter, Lynne E

    2011-02-02

    D-amino acid oxidase (DAO), an enzyme that degrades d-serine, has been suggested as a susceptibility factor for schizophrenia. Here we sought to understand more about the behavioral consequence of lacking DAO and the potential therapeutic implication of DAO inhibition by characterizing a mouse strain (ddY/DAO(-)) lacking DAO activity. We found that the mutant mice showed enhanced prepulse inhibition responses (PPI). Intriguingly, DAO-/- mice had increased sensitivity to the PPI-disruptive effect induced by the competitive NMDA antagonist, SDZ 220-581. In the 24-h inhibitory avoidance test, DAO-/- mice were not different from DAO+/+ mice during the recall. In Barnes Maze, we found that DAO-/- mice had a shortened latency to enter the escape tunnel. Interestingly, although these mice were hypoactive when tested in a protected open field, they showed a profound increase of activity on the edge of the unprotected open field of the Barnes Maze even with the escape tunnel removed. This increased edge activity does not appear to be related to a reduced level of anxiety given that there were no significant genotype effects on the measures of anxiety-like behaviors in two standard animal models of anxiety, elevated plus maze and novelty suppressed feeding. Our data suggest that DAO-/- mice might have altered functioning of NMDARs. However, these results provide only modest support for manipulations of DAO activity as a potential therapeutic approach to treat schizophrenia.

  10. Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells via IL-6/STAT3 Pathway Inhibition.

    Science.gov (United States)

    Lou, Wei; Chen, Yan; Zhu, Ke-Ying; Deng, Huizi; Wu, Tianhao; Wang, Jun

    2017-08-01

    Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties. In the current work, we aimed to testify whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired resistance with strong features of EMT. PPI effectively restored drug sensitivity of cells that obtained acquired resistance. PPI reversed EMT and decreased interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway activation in erlotinib-resistant cells. Moreover, addition of IL-6 partially abolished the sensitization response of PPI. Furthermore, co-treatment of erlotinib and PPI completed abrogation of tumor growth in xenografts, which was associated with EMT reversal. In conclusion, PPI serves as a novel solution to conquer the EGFR-TKI resistance of NSCLC via reversing EMT by modulating IL-6/STAT3 signaling pathway. Combined PPI and erlotinib treatment provides a promising future for lung cancer patients to strengthen drug response and prolong survival.

  11. Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages.

    Science.gov (United States)

    Hyam, Supriya R; Lee, In-Ah; Gu, Wan; Kim, Kyung-Ah; Jeong, Jin-Ju; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

    2013-05-15

    Seeds of Arctium lappa, containing arctigenin and its glycoside arctiin as main constituents, have been used as a diuretic, anti-inflammatory and detoxifying agent in Chinese traditional medicine. In our preliminary study, arctigenin inhibited IKKβ and NF-κB activation in peptidoglycan (PGN)- or lipopolysaccharide (LPS)-induced peritoneal macrophages. To understand the anti-inflammatory effect of arctigenin, we investigated its anti-inflammatory effect in LPS-stimulated peritoneal macrophages and on LPS-induced systemic inflammation as well as 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Arctigenin inhibited LPS-increased IL-1β, IL-6 and TNF-α expression in LPS-stimulated peritoneal macrophages, but increased LPS-reduced IL-10 and CD204 expression. Arctigenin inhibited LPS-induced PI3K, AKT and IKKβ phosphorylation, but did not suppress LPS-induced IRAK-1 phosphorylation. However, arctigenin did not inhibit NF-κB activation in LPS-stimulated PI3K siRNA-treated peritoneal macrophages. Arctigenin suppressed the binding of p-PI3K antibody and the nucleus translocation of NF-κB p65 in LPS-stimulated peritoneal macrophages. Arctigenin suppressed blood IL-1β and TNF-α level in mice systemically inflamed by intraperitoneal injection of LPS. Arctigenin also inhibited colon shortening, macroscopic scores and myeloperoxidase activity in TNBS-induced colitic mice. Arctigenin inhibited TNBS-induced IL-1β, TNF-α and IL-6 expression, as well as PI3K, AKT and IKKβ phosphorylation and NF-κB activation in mice, but increased IL-10 and CD204 expression. However, it did not affect IRAK-1 phosphorylation. Based on these findings, arctigenin may ameliorate inflammatory diseases, such as colitis, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages.

  12. A low cost setup for behavioral audiometry in rodents.

    Science.gov (United States)

    Tziridis, Konstantin; Ahlf, Sönke; Schulze, Holger

    2012-10-16

    In auditory animal research it is crucial to have precise information about basic hearing parameters of the animal subjects that are involved in the experiments. Such parameters may be physiological response characteristics of the auditory pathway, e.g. via brainstem audiometry (BERA). But these methods allow only indirect and uncertain extrapolations about the auditory percept that corresponds to these physiological parameters. To assess the perceptual level of hearing, behavioral methods have to be used. A potential problem with the use of behavioral methods for the description of perception in animal models is the fact that most of these methods involve some kind of learning paradigm before the subjects can be behaviorally tested, e.g. animals may have to learn to press a lever in response to a sound. As these learning paradigms change perception itself (1,2) they consequently will influence any result about perception obtained with these methods and therefore have to be interpreted with caution. Exceptions are paradigms that make use of reflex responses, because here no learning paradigms have to be carried out prior to perceptual testing. One such reflex response is the acoustic startle response (ASR) that can highly reproducibly be elicited with unexpected loud sounds in naïve animals. This ASR in turn can be influenced by preceding sounds depending on the perceptibility of this preceding stimulus: Sounds well above hearing threshold will completely inhibit the amplitude of the ASR; sounds close to threshold will only slightly inhibit the ASR. This phenomenon is called pre-pulse inhibition (PPI) (3,4), and the amount of PPI on the ASR gradually depends on the perceptibility of the pre-pulse. PPI of the ASR is therefore well suited to determine behavioral audiograms in naïve, non-trained animals, to determine hearing impairments or even to detect possible subjective tinnitus percepts in these animals. In this paper we demonstrate the use of this method in a

  13. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  14. Lateral inhibition during nociceptive processing

    DEFF Research Database (Denmark)

    Quevedo, Alexandre S.; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2017-01-01

    of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits spatial summation of pain and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition......Spatial summation of pain is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is sub-additive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation...... for sub-additive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit spatial summation of pain, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer...

  15. A single high dose of escitalopram disrupts sensory gating and habituation, but not sensorimotor gating in healthy volunteers

    DEFF Research Database (Denmark)

    Oranje, Bob; Wienberg, Malene; Glenthøj, Birte Yding

    2011-01-01

    Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers. In the ......Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers....... In the current study a higher dose of 15mg was used. The hypothesis was that this higher dose of escitalopram would not only disrupt habituation, but also sensory and sensorimotor gating. Twenty healthy male volunteers received either placebo or 15mg escitalopram, after which they were tested in a P50...... suppression, and a habituation and prepulse inhibition (PPI) of the startle reflex paradigm. Escitalopram significantly decreased P50 suppression and habituation, but had no effect on PPI. The results indicate that habituation and sensory gating are disrupted by increased serotonergic activity, while...

  16. Acoustic trauma-induced auditory cortex enhancement and tinnitus

    Institute of Scientific and Technical Information of China (English)

    Erin Laundrie; Wei Sun

    2014-01-01

    There is growing evidence suggests that noise-induced cochlear damage may lead to hyperexcitability in the central auditory system (CAS) which may give rise to tinnitus. However, the correlation between the onset of the neurophysiological changes in the CAS and the onset of tinnitus has not been well studied. To investigate this relationship, chronic electrodes were implanted into the auditory cortex (AC) and sound evoked activities were measured from awake rats before and after noise exposure. The auditory brainstem response (ABR) was used to assess the degree of noise-induced hearing loss. Tinnitus was evaluated by measuring gap-induced prepulse inhibition (gap-PPI). Rats were exposed monaurally to a high-intensity narrowband noise centered at 12 kHz at a level of 120 dB SPL for 1 h. After the noise exposure, all the rats developed either permanent (>2 weeks) or temporary (<3 days) hearing loss in the exposed ear(s). The AC amplitudes increased significantly 4 h after the noise exposure. Most of the exposed rats also showed decreased gap-PPI. The post-exposure AC enhancement showed a positive correlation with the amount of hearing loss. The onset of tinnitus-like behavior was happened after the onset of AC enhancement.

  17. Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.

    Science.gov (United States)

    Shortall, Sinead E; Green, A Richard; Fone, Kevin Cf; King, Madeleine V

    2016-07-01

    Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs.

  18. Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.

    Science.gov (United States)

    Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

    2015-08-25

    Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.

  19. Disruptions of sensorimotor gating, cytokines, glycemia, monoamines, and genes in both sexes of rats reared in social isolation can be ameliorated by oral chronic quetiapine administration.

    Science.gov (United States)

    Ko, Chih-Yuan; Liu, Yia-Ping

    2016-01-01

    The pathogenesis of schizophrenia in patients with metabolic abnormalities remains unclear. Our previous study demonstrated that isolation rearing (IR) induced longitudinal concomitant changes of pro-inflammatory cytokine (pro-CK) levels and metabolic abnormalities with a developmental origin. However, the general consensus, believes that these abnormalities are caused by antipsychotic treatment in schizophrenic patients. The IR paradigm presents with face, construct, and predictive validity for schizophrenia. Therefore, we employed IR rats of both sexes to examine whether chronic quetiapine (QTP, a second-generation antipsychotic medication) treatment induces disruptions of metabolism (body weight, blood pressure, and the glycemic and lipid profiles) or cytokines [interleukin (IL)-1 beta, IL-6, IL-10, interferon-gamma, and tumor necrosis factor (TNF)-alpha], and further, whether it reverses deficits of behaviors [locomotor activity and prepulse inhibition (PPI)] and the expression of monoamines (dopamine and serotonin) and related genes (Htr1a, Htr2a, Htr3a, Drd1a, and Gabbr2). IR induced higher levels of pro-CK, dysglycemia, blood pressure, locomotor activity, and impaired PPI, simultaneously destabilizing cortico-striatal monoamines and relevant genes in both sexes, while QTP demonstrated dose-dependent reversal of these changes, suggesting that QTP might reduce the pro-CKs to regulate these abnormalities. Our data implied that antipsychotics may not be the solitary factor causing metabolic problems in schizophrenia and suggested that inflammatory changes may play a vital role in the developmental pathophysiology of schizophrenia and related metabolic abnormalities.

  20. Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments.

    Science.gov (United States)

    Borsoi, Milene; Antonio, Camila Boque; Viana, Alice Fialho; Nardin, Patrícia; Gonçalves, Carlos-Alberto; Rates, Stela Maris Kuze

    2015-03-01

    The forced swim test (FST) is widely used to evaluate the antidepressant-like activity of compounds and is sensitive to stimuli that cause depression-like behaviors in rodents. The immobility behavior observed during the test has been considered to represent behavioral despair. In addition, some studies suggest that the FST impairs rats' performance on cognitive tests, but these findings have rarely been explored. Thus, we investigated the effects of the FST on behavioral tests related to neuropsychiatric diseases that involve different cognitive components: novel object recognition (NOR), the object location test (OLT) and prepulse inhibition (PPI). Brain-derived neurotrophic factor (BDNF) levels in the frontal cortex and hippocampus were evaluated. The rats were forced to swim twice (15-min session followed by a 5-min session 24h later) and underwent cognitive tests 24h after the last swimming exposure. The FST impaired the rats' performance on the OLT and reduced the PPI and acoustic startle responses, whereas the NOR was not affected. The cognitive impairments were not correlated with an immobility behavior profile, but a significant negative correlation between the frontal BDNF levels and immobility behavior was identified. These findings suggest a protective role of BDNF against behavioral despair and demonstrate a deleterious effect of the FST on spatial memory and pre-attentive processes, which point to the FST as a tool to induce cognitive impairments analogous to those observed in depression and in other neuropsychiatric disorders.

  1. Safety Evaluation of Self-assembling Peptide Gel after Intracranial Administration to Rats Using the Open Field Test.

    Science.gov (United States)

    Tsunoda, Masashi; Sugaya, Chiemi; Sugiura, Yumiko; Nagai, Yusuke; Sakanishi, Kotaro

    2016-01-01

    Self-assembling peptides have been developed as clinical materials, which could scaffold to regenerate nerve cells and hemostatic materials in vivo. However, there has not been enough information for their in vivo application. The safety of self-assembling peptides for the application on the brain was examined using behavioral tests for each rat in this study. Self-assembling peptide gel was administered to the surface of the brain at a volume of 20 µL at 1.5%. After 2 months, the open field test and the prepulse inhibition (PPI) test were performed. There were no significant differences between the peptide gel and the control groups in locomotor distances and in %PPIs in the PPI test. The mean values of the percentage of time the rats stayed in the central area of the open field during the first 5 min and instances of center rearing or face washing in the peptide gel group were significantly higher than those in the control. There were amorphous substance in the subarachnoid region, and infiltrations of mononuclear cells were also observed in the self-assembling peptide gel group. Although the meaning of the effects observed in this study was not fully elucidated, the self-assembling gel produced marginal but significant behavioral and histological effects.

  2. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

    2015-01-01

    +/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

  3. Lateral inhibition during nociceptive processing.

    Science.gov (United States)

    Quevedo, Alexandre S; Mørch, Carsten Dahl; Andersen, Ole K; Coghill, Robert C

    2017-06-01

    Spatial summation of pain (SSP) is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is subadditive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation for subadditive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit SSP, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer-controlled CO2 laser. Lines (5 mm wide) of variable lengths (4, 8 cm) were compared with 2-point stimuli delivered at the same position/separation as the length of lines. When compared with one-point control stimuli, 2-point stimulus patterns produced statistically significant SSP, while no such summation was detected during line stimulus patterns. Direct comparison of pain intensity evoked by 2-point pattern stimuli with line pattern stimuli revealed that 2-point patterns were perceived as significantly more painful, despite the fact that the 2-point pattern stimulated far smaller areas of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits SSP and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition may contribute substantially to the radiation of some types of chronic pain.

  4. Activated sludge inhibition capacity index

    Directory of Open Access Journals (Sweden)

    V. Surerus

    2014-06-01

    Full Text Available Toxic compounds in sewage or industrial wastewater may inhibit the biological activity of activated sludge impairing the treatment process. This paper evaluates the Inhibition Capacity Index (ICI for the assessment of activated sludge in the presence of toxicants. In this study, activated sludge was obtained from industrial treatment plants and was also synthetically produced. Continuous respirometric measurements were carried out in a reactor, and the oxygen uptake rate profile obtained was used to evaluate the impact of inhibiting toxicants, such as dissolved copper, phenol, sodium alkylbenzene sulfonate and amoxicillin, on activated sludge. The results indicate that ICI is an efficient tool to quantify the intoxication capacity. The activated sludge from the pharmaceutical industry showed higher resistance than the sludge from other sources, since toxicants are widely discharged in the biological treatment system. The ICI range was from 58 to 81% when compared to the synthetic effluent with no toxic substances.

  5. Homo economicus belief inhibits trust.

    Directory of Open Access Journals (Sweden)

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  6. Homo economicus belief inhibits trust.

    Science.gov (United States)

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  7. Relationships among parvalbumin-immunoreactive neuron density, phase-locked gamma oscillations, and autistic/schizophrenic symptoms in PDGFR-β knock-out and control mice.

    Directory of Open Access Journals (Sweden)

    Tomoya Nakamura

    Full Text Available Cognitive deficits and negative symptoms are important therapeutic targets for schizophrenia and autism disorders. Although reduction of phase-locked gamma oscillation has been suggested to be a result of reduced parvalbumin-immunoreactive (putatively, GABAergic neurons, no direct correlations between these have been established in these disorders. In the present study, we investigated such relationships during pharmacological treatment with a newly synthesized drug, T-817MA, which displays neuroprotective and neurotrophic effects. In this study, we used platelet-derived growth factor receptor-β gene knockout (PDGFR-β KO mice as an animal model of schizophrenia and autism. These mutant mice display a reduction in social behaviors; deficits in prepulse inhibition (PPI; reduced levels of parvalbumin-immunoreactive neurons in the medical prefrontal cortex, hippocampus, amygdala, and superior colliculus; and a deficit in of auditory phase-locked gamma oscillations. We found that oral administration of T-817MA ameliorated all these symptoms in the PDGFR-β KO mice. Furthermore, phase-locked gamma oscillations were significantly correlated with the density of parvalbumin-immunoreactive neurons, which was, in turn, correlated with PPI and behavioral parameters. These findings suggest that recovery of parvalbumin-immunoreactive neurons by pharmacological intervention relieved the reduction of phase-locked gamma oscillations and, consequently, ameliorated PPI and social behavioral deficits. Thus, our findings suggest that phase-locked gamma oscillations could be a useful physiological biomarker for abnormality of parvalbumin-immunoreactive neurons that may induce cognitive deficits and negative symptoms of schizophrenia and autism, as well as of effective pharmacological interventions in both humans and experimental animals.

  8. Schizophrenia risk gene CAV1 is both pro-psychotic and required for atypical antipsychotic drug actions in vivo.

    Science.gov (United States)

    Allen, J A; Yadav, P N; Setola, V; Farrell, M; Roth, B L

    2011-08-16

    Caveolin-1 (Cav-1) is a scaffolding protein important for regulating receptor signaling cascades by partitioning signaling molecules into membrane microdomains. Disruption of the CAV1 gene has recently been identified as a rare structural variant associated with schizophrenia. Although Cav-1 knockout (KO) mice displayed no baseline behavioral disruptions, Cav-1 KO mice, similar to schizophrenic individuals, exhibited increased sensitivity to the psychotomimetic N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). Thus, PCP disruption of prepulse inhibition (PPI) and PCP-induced mouse locomotor activity were both enhanced by genetic deletion of Cav-1. Interestingly, genetic deletion of Cav-1 rendered the atypical antipsychotics clozapine and olanzapine and the 5-HT(2A)-selective antagonist M100907 ineffective at normalizing PCP-induced disruption of PPI. We also discovered that genetic deletion of Cav-1 attenuated 5-HT(2A)-induced c-Fos and egr-1 expression in mouse frontal cortex and also reduced 5-HT(2A)-mediated Ca(2+) mobilization in primary cortical neuronal cultures. The behavioral effects of the 5-HT(2A) agonist (2,5-dimethoxy-4-iodoamphetamine) including head twitch responses and disruption of PPI were also attenuated by genetic deletion of Cav-1, indicating that Cav-1 is required for both inverse agonist (that is, atypical antipsychotic drug) and agonist actions at 5-HT(2A) receptors. This study demonstrates that disruption of the CAV1 gene--a rare structural variant associated with schizophrenia--is not only pro-psychotic but also attenuates atypical antipsychotic drug actions.

  9. Dual effects of limbic seizures on psychosis-relevant behaviors shown by nucleus accumbens kindling in rats

    Science.gov (United States)

    Ma, Jingyi; Leung, L. Stan

    2016-01-01

    Background A paradox in epilepsy and psychiatry is that temporal lobe epilepsy is often predisposed to schizophrenic-like psychosis, whereas convulsive therapy can relieve schizophrenic symptoms. We have previously demonstrated that the nucleus accumbens is a key structure in mediating postictal psychosis induced by a hippocampal electrographic seizure. Objective/Hypothesis The purpose of this study is to test a hypothesis that accumbens kindling cumulating in a single (1-time) or repeated (5-times) convulsive seizures have different effects on animal models of psychosis. Methods Electrical stimulation at 60 Hz was applied to nucleus accumbens to evoke afterdischarges until one, or five, convulsive seizures that involved the hind limbs (stage 5 seizures) were attained. Behavioral tests, performed at 3 days after the last seizure, included gating of hippocampal auditory evoked potentials (AEP) and prepulse inhibition to an acoustic startle response (PPI), tested without drug injection or after ketamine (3 mg/kg s.c.) injection, as well as locomotion induced by ketamine or methamphetamine (1 mg/kg i.p.). Results Compared to non-kindled control rats, 1-time, but not 5-times, convulsive seizures induced PPI deficit and decreased gating of hippocampal AEP, without drug injection. Compared to non-kindled rats, 5-times, but not 1-time, convulsive seizures antagonized ketamine-induced hyperlocomotion, ketamine-induced PPI deficit and AEP gating decrease. However, both 1- and 5-times convulsive seizures, significantly enhanced methamphetamine-induced locomotion as compared to non-kindled rats. Conclusions Accumbens kindling ending with 1 convulsive seizure may induce schizophrenic-like behaviors, while repeated (≥ 5) convulsive seizures induced by accumbens kindling may have therapeutic effects on dopamine independent psychosis. PMID:27267861

  10. Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour.

    Science.gov (United States)

    Llorente-Berzal, Alvaro; Fuentes, Sílvia; Gagliano, Humberto; López-Gallardo, Meritxell; Armario, Antonio; Viveros, María-Paz; Nadal, Roser

    2011-10-01

    Early life experiences such as maternal deprivation (MD) exert long-lasting changes in adult behaviour and reactivity to stressors. Adolescent exposure to cannabinoids is a predisposing factor in developing certain psychiatric disorders. Therefore, the combination of the two factors could exacerbate the negative consequences of each factor when evaluated at adulthood. The objective of this study was to investigate the long-term effects of early MD [24 hours at postnatal day (PND) 9] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (0.4 mg/kg, PND 28-42) on diverse behavioural and physiological responses of adult male and female Wistar rats. We tested them in the prepulse inhibition (PPI) of the startle response and analysed their exploratory activity (holeboard) and anxiety (elevated plus maze, EPM). In addition, we evaluated their adrenocortical reactivity in response to stress and plasma leptin levels. Maternal behaviour was measured before and after deprivation. MD induced a transient increase of maternal behaviour on reuniting. In adulthood, maternally deprived males showed anxiolytic-like behaviour (or increased risk-taking behaviour) in the EPM. Adolescent exposure to the cannabinoid agonist induced an impairment of the PPI in females and increased adrenocortical responsiveness to the PPI test in males. Both, MD and adolescent cannabinoid exposure also induced sex-dependent changes in plasma leptin levels and body weights. The present results indicate that early MD and adolescent cannabinoid exposure exerted distinct sex-dependent long-term behavioural and physiological modifications that could predispose to the development of certain neuropsychiatric disorders, though no synergistic effects were found.

  11. Effects of SB-269970, a 5-HT7 receptor antagonist, in mouse models predictive of antipsychotic-like activity.

    Science.gov (United States)

    Galici, Ruggero; Boggs, Jamin D; Miller, Kirsten L; Bonaventure, Pascal; Atack, John R

    2008-03-01

    5-HT7 receptors have been linked to a number of psychiatric disorders including anxiety and depression. The localization of 5-HT7 receptors in the thalamus, a key sensory processing center, and the high affinity of many atypical antipsychotic compounds for these receptors have led to the speculation of the utility of 5-HT7 antagonists in schizophrenia. The goal of these studies was to examine the effects of pharmacologic blockade and genetic ablation of 5-HT7 receptors in animal models predictive of antipsychotic-like activity. We evaluated the effects of SB-269970, a selective 5-HT7 receptor antagonist, on amphetamine and ketamine-induced hyperactivity and prepulse inhibition (PPI) deficits. In addition, sensorimotor gating function and locomotor activity were evaluated in 5-HT7 knockout mice. Locomotor activity was measured for up to 180 min using an automated infrared photobeam system, and PPI was evaluated in startle chambers. SB-269970 (3, 10 and 30 mg/kg, intraperitoneally) significantly blocked amphetamine [3 mg/kg, subcutaneously (s.c.)] and ketamine (30 mg/kg, s.c.)-induced hyperactivity and reversed amphetamine (10 mg/kg, s.c.)-induced but not ketamine (30 mg/kg, s.c.)-induced PPI deficits, without changing spontaneous locomotor activity and startle amplitude. The largest dose of SB-269970 did not block the effects of amphetamine in 5-HT7 knockout mice. Collectively, these results indicate that blockade of 5-HT7 receptors partially modulates glutamatergic and dopaminergic function and could be clinically useful for the treatment of positive symptoms of schizophrenia.

  12. Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus.

    Directory of Open Access Journals (Sweden)

    Andrea S Lowe

    Full Text Available Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN paradigm to assess tinnitus in mice using the auditory brainstem response (ABR. We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS, which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2 to peak 1 (P1 and peak 4 (P4 to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.

  13. Strigolactone inhibition of shoot branching

    NARCIS (Netherlands)

    Gomez-Roldan, M.V.; Fermas, S.; Brewer, P.B.; Puech-Pages, V.; Dun, E.A.; Pillot, J.P.; Letisse, F.; Matusova, R.; Danoun, S.; Portais, J.C.; Bouwmeester, H.J.; Becard, G.; Beveridge, C.A.; Rameau, C.; Rochange, S.F.

    2008-01-01

    A carotenoid-derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence

  14. Strigolactone inhibition of shoot branching

    NARCIS (Netherlands)

    Gomez-Roldan, M.V.; Fermas, S.; Brewer, P.B.; Puech-Pages, V.; Dun, E.A.; Pillot, J.P.; Letisse, F.; Matusova, R.; Danoun, S.; Portais, J.C.; Bouwmeester, H.J.; Becard, G.; Beveridge, C.A.; Rameau, C.; Rochange, S.F.

    2008-01-01

    A carotenoid-derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence

  15. Methanogenic inhibition by arsenic compounds.

    Science.gov (United States)

    Sierra-Alvarez, Reyes; Cortinas, Irail; Yenal, Umur; Field, Jim A

    2004-09-01

    The acute acetoclastic methanogenic inhibition of several inorganic and organic arsenicals was assayed. Trivalent species, i.e., methylarsonous acid and arsenite, were highly inhibitory, with 50% inhibitory concentrations of 9.1 and 15.0 microM, respectively, whereas pentavalent species were generally nontoxic. The nitrophenylarsonate derivate, roxarsone, displayed moderate toxicity.

  16. Inhibition of carcinogenesis by tea.

    Science.gov (United States)

    Yang, Chung S; Maliakal, Pius; Meng, Xiaofeng

    2002-01-01

    Tea has received a great deal of attention because tea polyphenols are strong antioxidants, and tea preparations have inhibitory activity against tumorigenesis. The bioavailability and biotransformation of tea polyphenols, however, are key factors limiting these activities in vivo. The inhibition of tumorigenesis by green or black tea preparations has been demonstrated in animal models on different organ sites such as skin, lung, oral cavity, esophagus, forestomach, stomach, small intestine, colon, pancreas, and mammary gland. Epidemiological studies, however, have not yielded clear conclusions concerning the protective effects of tea consumption against cancer formation in humans. The discrepancy between the results from humans and animal models could be due to 1) the much higher doses of tea used in animals in comparison to human consumption, 2) the differences in causative factors between the cancers in humans and animals, and 3) confounding factors limiting the power of epidemiological studies to detect an effect. It is possible that tea may be only effective against specific types of cancer caused by certain etiological factors. Many mechanisms have been proposed for the inhibition of carcinogenesis by tea, including the modulation of signal transduction pathways that leads to the inhibition of cell proliferation and transformation, induction of apoptosis of preneoplastic and neoplastic cells, as well as inhibition of tumor invasion and angiogenesis. These mechanisms need to be evaluated and verified in animal models or humans in order to gain more understanding on the effect of tea consumption on human cancer.

  17. Testing of Biologically Inhibiting Surface

    DEFF Research Database (Denmark)

    Bill Madsen, Thomas; Larsen, Erup

    2003-01-01

    The main purpose of this course is to examine a newly developed biologically inhibiting material with regards to galvanic corrosion and electrochemical properties. More in detail, the concern was how the material would react when exposed to cleaning agents, here under CIP cleaning (Cleaning...

  18. Islam Does Not Inhibit Science.

    Science.gov (United States)

    Shanavas, T. O.

    1999-01-01

    Compares the science/religion relationship in both Christian and Islamic countries. Presents Muslim scholars' ideas about the presence of humans on earth. Presents ideas on active nature, Noah's curse, and the age of the universe. Refutes the notion that Islam inhibited science and advocates the belief that Islam promoted science. (YDS)

  19. Epigallocatechin gallate inhibits endothelial exocytosis.

    Science.gov (United States)

    Yamakuchi, Munekazu; Bao, Clare; Ferlito, Marcella; Lowenstein, Charles J

    2008-07-01

    Consumption of green tea is associated with a decrease in cardiovascular mortality. The beneficial health effects of green tea are attributed in part to polyphenols, organic compounds found in tea that lower blood pressure, reduce body fat, decrease LDL cholesterol, and inhibit inflammation. We hypothesized that epigallocatechin gallate (EGCG), the most abundant polyphenol in tea, inhibits endothelial exocytosis, the initial step in leukocyte trafficking and vascular inflammation. To test this hypothesis, we treated human umbilical-vein endothelial cells with EGCG and other polyphenols, and then measured endothelial exocytosis. We found that EGCG decreases endothelial exocytosis in a concentration-dependent manner, with the effects most prominent after 4 h of treatment. Other catechin polyphenols had no effect on endothelial cells. By inhibiting endothelial exocytosis, EGCG decreases leukocyte adherence to endothelial cells. In searching for the mechanism by which EGCG affects endothelial cells, we found that EGCG increases Akt phosphorylation, eNOS phosphorylation, and nitric oxide (NO) production. NOS inhibition revealed that NO mediates the anti-inflammatory effects of EGCG. Our data suggest that polyphenols can decrease vascular inflammation by increasing the synthesis of NO, which blocks endothelial exocytosis.

  20. Infant Predictors of Behavioural Inhibition

    Science.gov (United States)

    Moehler, Eva; Kagan, Jerome; Oelkers-Ax, Rieke; Brunner, Romuald; Poustka, Luise; Haffner, Johann; Resch, Franz

    2008-01-01

    Behavioural inhibition in the second year of life is a hypothesized predictor for shyness, social anxiety and depression in later childhood, adolescence and even adulthood. To search for the earliest indicators of this fundamental temperamental trait, this study examined whether behavioural characteristics in early infancy can predict behavioural…

  1. Protein-Protein Interactions (PPI) reagents: | Office of Cancer Genomics

    Science.gov (United States)

    The CTD2 Center at Emory University has a library of genes used to study protein-protein interactions in mammalian cells. These genes are cloned in different mammalian expression vectors. A list of available cancer-associated genes can be accessed below.

  2. Protein-Protein Interactions (PPI) reagents: | Office of Cancer Genomics

    Science.gov (United States)

    The CTD2 Center at Emory University has a library of genes used to study protein-protein interactions in mammalian cells. These genes are cloned in different mammalian expression vectors. A list of available cancer-associated genes can be accessed below.

  3. 32 CFR 701.115 - Protected personal information (PPI).

    Science.gov (United States)

    2010-07-01

    ..., should be e-mailed to CNO (DNS-36) with “Identity Theft Notification” in the subject line. (3) If the DON... section, the activity shall immediately inform CNO (DNS-36) as to the reasons why. CNO (DNS-36) will,...

  4. Effects of smoking abstinence on impulsive behavior among smokers high and low in ADHD-like symptoms.

    Science.gov (United States)

    Ashare, Rebecca L; Hawk, Larry W

    2012-01-01

    Impulsivity, a multifaceted construct that includes inhibitory control and heightened preference for immediate reward, is central to models of drug use and abuse. Within a self-medication framework, abstinence from smoking may lead to an increase in impulsive behavior and the likelihood of relapse, particularly among persons with disorders (e.g., attention-deficit/hyperactivity disorder, ADHD) and personality traits (e.g., impulsivity) linked to impulsive behavior. This study aimed to examine the effects of smoking abstinence on multiple measures of impulsivity among a non-clinical sample of adult smokers selected for high and low levels of ADHD symptoms. In a within-subjects design, participants selected for high or low levels of self-reported ADHD symptoms (N = 56) completed sessions following overnight abstinence and when smoking as usual (order counterbalanced). Measures of impulsive behavior included response inhibition (i.e., stop signal task), interference control (i.e., attentional modification of prepulse inhibition (PPI) of startle), and impulsive choice (i.e., hypothetical delay discounting). As hypothesized, abstinence decreased response inhibition and PPI. Although ADHD symptoms moderated abstinence effects on impulsive choice and response inhibition, the pattern was opposite to our predictions: the low-ADHD group responded more impulsively when abstinent, whereas the high-ADHD group was relatively unaffected by abstinence. These findings highlight the importance of utilizing multiple laboratory measures to examine a multifactorial construct such as impulsive behavior and raise questions about how best to assess symptoms of ADHD and impulsivity among non-abstinent smokers.

  5. Variable effects of acoustic trauma on behavioral and neural correlates of tinnitus in individual animals

    Directory of Open Access Journals (Sweden)

    Ryan James Longenecker

    2016-10-01

    Full Text Available The etiology of tinnitus is known to be diverse in the human population. An appropriate animal model of tinnitus should incorporate this pathological diversity. Previous studies evaluating the effect of acoustic over exposure (AOE have found that animals typically display increased spontaneous firing rates and bursting activity of auditory neurons, which often has been linked to behavioral evidence of tinnitus. However, only a subset of studies directly associated these neural correlates to individual animals. Furthermore the vast majority of tinnitus studies were conducted on anesthetized animals. The goal of this study was to test for a possible relationship between tinnitus, hearing loss, hyperactivity, and bursting activity in the auditory system of individual unanesthetized animals following AOE. Sixteen mice were unilaterally exposed to 116dB SPL narrowband noise (centered at 12.5 kHz for 1 hour under ketamine/xylazine anesthesia. Gap-induced prepulse inhibition of the acoustic startle reflex (GPIAS was used to assess behavioral evidence of tinnitus whereas hearing performance was evaluated by measurements of auditory brainstem response (ABR thresholds and prepulse inhibition (PPI audiometry. Following behavioral assessments, single neuron firing activity was recorded from the inferior colliculus (IC of four awake animals and compared to recordings from four unexposed controls. We found that AOE increased spontaneous activity in all mice tested, independently of tinnitus behavior or severity of threshold shifts. Bursting activity did not increase in two animals identified as tinnitus positive (T+, but did so in a tinnitus negative (T- animal with severe hearing loss (SHL. Hyperactivity does not appear to be a reliable biomarker of tinnitus. Our data suggest that multidisciplinary assessments on individual animals following AOE could offer a powerful experimental tool to investigate mechanisms of tinnitus.

  6. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

    Directory of Open Access Journals (Sweden)

    Song Xueqin

    2011-12-01

    Full Text Available Abstract Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α and interleukin-10 (IL-10 levels was determined by enzyme-linked immunosorbent assays (ELISA. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI, passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.

  7. Gum Chewing Inhibits the Sensory Processing and the Propagation of Stress-Related Information in a Brain Network

    Science.gov (United States)

    Yu, Hongbo; Chen, Xi; Liu, Jinting; Zhou, Xiaolin

    2013-01-01

    Stress is prevalent in human life and threatens both physical and mental health; stress coping is thus of adaptive value for individual's survival and well-being. Although there has been extensive research on how the neural and physiological systems respond to stressful stimulation, relatively little is known about how the brain dynamically copes with stress evoked by this stimulation. Here we investigated how stress is relieved by a popular coping behavior, namely, gum chewing. In an fMRI study, we used loud noise as an acute stressor and asked participants to rate their feeling of stress in gum-chewing and no-chewing conditions. The participants generally felt more stressful when hearing noise, but less so when they were simultaneously chewing gum. The bilateral superior temporal sulcus (STS) and the left anterior insula (AI) were activated by noise, and their activations showed a positive correlation with the self-reported feeling of stress. Critically, gum chewing significantly reduced the noise-induced activation in these areas. Psychophysiological interaction (PPI) analysis showed that the functional connectivity between the left AI and the dorsal anterior cingulate cortex (dACC) was increased by noise to a lesser extent when the participants were chewing gum than when not chewing gum. Dynamic causality modeling (DCM) demonstrated that gum chewing inhibited the connectivity from the STS to the left AI. These findings demonstrate that gum chewing relieves stress by attenuating the sensory processing of external stressor and by inhibiting the propagation of stress-related information in the brain stress network. PMID:23573184

  8. Rapid efflux of Ca2+ from heart mitochondria in the presence of inorganic pyrophosphate.

    Science.gov (United States)

    Vercesi, A; Lehninger, A L

    1984-01-13

    Inorganic pyrophosphate (PPi) in the intracellular concentration range causes rapid efflux of Ca2+ from rat heart mitochondria oxidizing pyruvate + malate in a low Na+ medium. Half-maximal rates of Ca2+ efflux were given by 20 microM PPi. During and after PPi-stimulated Ca2+ efflux the mitochondria retain their structural integrity and complete respiratory control. Carboxyatractyloside inhibits PPi-stimulated Ca2+ efflux, indicating PPi must enter the matrix in order to promote Ca2+ efflux. Heart mitochondria have a much higher affinity for PPi uptake and PPi-induced Ca2+ efflux than liver mitochondria.

  9. Corrosion Chemistry in Inhibited HDA.

    Science.gov (United States)

    1980-11-30

    Titanium and chromium have sufficiently low Flade potentials to pass- ivate in non-oxidising acids, but Iron will only exhibit self-passivity if the...inhibition e.g. involving organic and pickling inhibitors* the rest potential can actually 4.5,4.6become more negative " This is due to cathodic rather...media. 321 stainless steel, titanium stabilised, was the particular steel studied, being very similar in composition to the 347also stainless steel

  10. Notch Signaling Inhibits Axon Regeneration

    OpenAIRE

    Bejjani, Rachid El; Hammarlund, Marc

    2012-01-01

    Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian CNS do not regenerate, and even neurons in the PNS often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neuron...

  11. Th2 cytokines inhibit lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Ira L Savetsky

    Full Text Available Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2 cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4 and interleukin-13 (IL-13 have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.

  12. Conditioned inhibition and reinforcement rate.

    Science.gov (United States)

    Harris, Justin A; Kwok, Dorothy W S; Andrew, Benjamin J

    2014-07-01

    We investigated conditioned inhibition in a magazine approach paradigm. Rats were trained on a feature negative discrimination between an auditory conditioned stimulus (CS) reinforced at one rate versus a compound of that CS and a visual stimulus (L) reinforced at a lower rate. This training established L as a conditioned inhibitor. We then tested the inhibitory strength of L by presenting it in compound with other auditory CSs. L reduced responding when tested with a CS that had been reinforced at a high rate, but had less or even no inhibitory effect when tested with a CS that had been reinforced at a low rate. The inhibitory strength of L was greater if it signaled a decrease in reinforcement from an already low rate than if it signaled an equivalent decrease in reinforcement from a high rate. We conclude that the strength of inhibition is not a linear function of the change in reinforcement that it signals. We discuss the implications of this finding for models of learning (e.g., Rescorla & Wagner, 1972) that identify inhibition with a difference (subtraction) rule.

  13. Pharmacological Investigations of the Dissociative ‘Legal Highs’ Diphenidine, Methoxphenidine and Analogues

    Science.gov (United States)

    Colestock, Tristan; Morris, Hamilton; Bortolotto, Zuner A.; Lodge, David; Halberstadt, Adam L.; Brandt, Simon D.

    2016-01-01

    1,2-Diarylethylamines including lanicemine, lefetamine, and remacemide have clinical relevance in a range of therapeutic areas including pain management, epilepsy, neurodegenerative disease and depression. More recently 1,2-diarylethylamines have been sold as ‘legal highs’ in a number of different forms including powders and tablets. These compounds are sold to circumvent governmental legislation regulating psychoactive drugs. Examples include the opioid MT-45 and the dissociative agents diphenidine (DPH) and 2-methoxy-diphenidine (2-MXP). A number of fatal and non-fatal overdoses have been linked to abuse of these compounds. As with many ‘legal highs’, little is known about their pharmacology. To obtain a better understanding, the effects of DPH, 2-MXP and its 3- and 4-MeO- isomers, and 2-Cl-diphenidine (2-Cl-DPH) were investigated using binding studies at 46 central nervous system receptors including the N-methyl-D-aspartate receptor (NMDAR), serotonin, dopamine, norepinephrine, histamine, and sigma receptors as well as the reuptake transporters for serotonin, dopamine and norepinephrine. Reuptake inhibition potencies were measured at serotonin, norepinephrine and dopamine transporters. NMDAR antagonism was established in vitro using NMDAR-induced field excitatory postsynaptic potential (fEPSP) experiments. Finally, DPH and 2-MXP were investigated using tests of pre-pulse inhibition of startle (PPI) in rats to determine whether they reduce sensorimotor gating, an effect observed with known dissociative drugs such as phencyclidine (PCP) and ketamine. The results suggest that these 1,2-diarylethylamines are relatively selective NMDAR antagonists with weak off-target inhibitory effects on dopamine and norepinephrine reuptake. DPH and 2-MXP significantly inhibited PPI. DPH showed greater potency than 2-MXP, acting with a median effective dose (ED50) of 9.5 mg/kg, which is less potent than values reported for other commonly abused dissociative drugs such as

  14. Does prenatal valproate interact with a genetic reduction in the serotonin transporter?A rat study on anxiety and cognition

    Directory of Open Access Journals (Sweden)

    Bart A Ellenbroek

    2016-09-01

    Full Text Available There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA enhances the risk of developing Autism Spectrum Disorders (ASD. In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors. Given that VPA significantly impacts on the serotonergic system, and serotonin has strong biochemical and genetic links to ASD, we aimed to investigate the interaction between genetic reduction in the serotonin transporter and prenatal valproate administration. More specifically, we exposed both wildtype (SERT+/+ rats and rats heterozygous for the serotonin transporter deletion (SERT+/- to a single injection of 400 mg/kg VPA at gestational day (GD 12. The offspring, in adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI and latent inhibition as measures for cognition and information processing. The results show that prenatal VPA significantly increased anxiety in both paradigm, reduced PPI and reduced conditioning in the latent inhibition paradigm. However, we failed to find a significant gene – environment interaction. We propose that this may be related to the timing of the VPA injection and suggest that whereas GD12 might be optimal for affecting normal rat, rats with a genetically compromised serotonergic system may be more sensitive to VPA at earlier time points during gestation. Overall our data are the first to investigate gene * environmental interactions in a genetic rat model for ASD suggest that timing may be of crucial importance to the long-term outcome.

  15. Dual inhibitor of PDE7 and GSK-3-VP1.15 acts as antipsychotic and cognitive enhancer in C57BL/6J mice.

    Science.gov (United States)

    Lipina, Tatiana V; Palomo, Valle; Gil, Carmen; Martinez, Ana; Roder, John C

    2013-01-01

    Cognitive deficit is a core of schizophrenia and it is not effectively treated by the available antipsychotic drugs, hence new and more effective therapy is needed. Schizophrenia is considered as a pathway disorder where Disrupted-In-Schizophrenia-1 (DISC1) is important molecular player that regulates multiple cellular cascades. We recently reported synergistic action between phosphodiesterase-4 (PDE4) and glycogen synthase kinase-3 (GSK-3) as DISC1 interacting proteins. In the current study we characterized behavioural effects of a newly developed compound, VP1.15 that inhibits both PDE7 and GSK-3 with main focus on its antipsychotic and cognitive capacities. VP1.15 reduced ambulation in C57BL/6J mice in a dose-dependent manner (7.5 mg/kg and 3 mg/kg, respectively) and, hence, lower dose was chosen for the further analysis. VP1.1.5 facilitated pre-pulse inhibition (PPI), reversed amphetamine- but not MK-801-induced PPI deficit. The drug was able to ameliorate the disrupted latent inhibition (LI) induced by the increased number of conditioning trials and reversed amphetamine-induced LI deficit, supporting further its antipsychotic effects. The drug also significantly improved episodic memory in the spatial object recognition test, facilitated working memory in Y-maze and enhanced cued fear memory, but had no effect on executive function in the Puzzle box and contextual fear conditioning. Taken together, VP1.15 elicited antipsychotic effects and also facilitated cognitive domains in mice, suggesting that multitarget drugs, affecting molecular substrates from the same pathway, perhaps could be antipsychotics of new-generation that open a new possibilities in drug discoveries. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  16. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  17. Graphene: corrosion-inhibiting coating.

    Science.gov (United States)

    Prasai, Dhiraj; Tuberquia, Juan Carlos; Harl, Robert R; Jennings, G Kane; Rogers, Bridget R; Bolotin, Kirill I

    2012-02-28

    We report the use of atomically thin layers of graphene as a protective coating that inhibits corrosion of underlying metals. Here, we employ electrochemical methods to study the corrosion inhibition of copper and nickel by either growing graphene on these metals, or by mechanically transferring multilayer graphene onto them. Cyclic voltammetry measurements reveal that the graphene coating effectively suppresses metal oxidation and oxygen reduction. Electrochemical impedance spectroscopy measurements suggest that while graphene itself is not damaged, the metal under it is corroded at cracks in the graphene film. Finally, we use Tafel analysis to quantify the corrosion rates of samples with and without graphene coatings. These results indicate that copper films coated with graphene grown via chemical vapor deposition are corroded 7 times slower in an aerated Na(2)SO(4) solution as compared to the corrosion rate of bare copper. Tafel analysis reveals that nickel with a multilayer graphene film grown on it corrodes 20 times slower while nickel surfaces coated with four layers of mechanically transferred graphene corrode 4 times slower than bare nickel. These findings establish graphene as the thinnest known corrosion-protecting coating.

  18. Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.

    Science.gov (United States)

    Zhang, Feng-Ying; Hu, Yi; Que, Zhong-You; Wang, Ping; Liu, Yun-Hui; Wang, Zhen-Hua; Xue, Yi-Xue

    2015-10-09

    Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated β-catenin (p-β-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1).

  19. Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine

    Directory of Open Access Journals (Sweden)

    Feng-Ying Zhang

    2015-10-01

    Full Text Available Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2 and matrix metalloproteinase-9 (MMP-9 and the expression of phosphorylated β-catenin (p-β-catenin and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1.

  20. Greener Approach towards Corrosion Inhibition

    Directory of Open Access Journals (Sweden)

    Neha Patni

    2013-01-01

    Full Text Available Corrosion control of metals is technically, economically, environmentally, and aesthetically important. The best option is to use inhibitors for protecting metals and alloys against corrosion. As organic corrosion inhibitors are toxic in nature, so green inhibitors which are biodegradable, without any heavy metals and other toxic compounds, are promoted. Also plant products are inexpensive, renewable, and readily available. Tannins, organic amino acids, alkaloids, and organic dyes of plant origin have good corrosion-inhibiting abilities. Plant extracts contain many organic compounds, having polar atoms such as O, P, S, and N. These are adsorbed on the metal surface by these polar atoms, and protective films are formed, and various adsorption isotherms are obeyed. Various types of green inhibitors and their effect on different metals are mentioned in the paper.

  1. Inhibiting scale in oil wells

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, M.J.; Adler, S.F.

    1972-09-27

    An oil well treatment is described to inhibit the formation of hard scale by precipitation from the oil well brine of scale-forming water insoluble sulfate, carbonate, and other salts. The process consists of incorporating into the oil well during a fracturing treatment, a fluid containing a solid polymeric material characterized by molecular weight in the range of 1,000 to 15,000 and a substantially linear structure, derived by the linear polymerization of at least one monoolefinically unsaturated compound through the olefinically unsaturated group. The linear structure has pendent groups, 50% of which are carboxy groups, the carboxy groups being neutralized with a sufficient proportion of at least one compound having a cation of a metal selected from alkaline earth metals, chromium, aluminum, iron, cobalt, zinc, nickel or copper to render the polymer soluble in water at 25$C to a concentration of not more than 50 ppm. (8 claims)

  2. Latent inhibition in human adults without masking.

    Science.gov (United States)

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  3. Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats.

    Science.gov (United States)

    Páleníček, Tomáš; Fujáková, Michaela; Brunovský, Martin; Horáček, Jiří; Gorman, Ingmar; Balíková, Marie; Rambousek, Lukáš; Syslová, Kamila; Kačer, Petr; Zach, Petr; Bubeníková-Valešová, Věra; Tylš, Filip; Kubešová, Anna; Puskarčíková, Jana; Höschl, Cyril

    2013-01-01

    Behavioral, neurochemical and pharmaco-EEG profiles of a new synthetic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats were examined. Locomotor effects, prepulse inhibition (PPI) of acoustic startle reaction (ASR), dopamine and its metabolite levels in nucleus accumbens (NAc), EEG power spectra and coherence in freely moving rats were analysed. Amphetamine was used as a reference compound. 2C-B had a biphasic effect on locomotion with initial inhibitory followed by excitatory effect; amphetamine induced only hyperlocomotion. Both drugs induced deficits in the PPI; however they had opposite effects on ASR. 2C-B increased dopamine but decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the NAc. Low doses of 2C-B induced a decrease in EEG power spectra and coherence. On the contrary, high dose of 2C-B 50 mg/kg had a temporally biphasic effect with an initial decrease followed by an increase in EEG power; decrease as well as increase in EEG coherence was observed. Amphetamine mainly induced an increase in EEG power and coherence in theta and alpha bands. Increases in the theta and alpha power and coherence in 2C-B and amphetamine were temporally linked to an increase in locomotor activity and DA levels in NAc. 2C-B is a centrally active compound similar to other hallucinogens, entactogens and stimulants. Increased dopamine and decreased DOPAC in the NAc may reflect its psychotomimetic and addictive potential and monoaminoxidase inhibition. Alterations in brain functional connectivity reflected the behavioral and neurochemical changes produced by the drug; a correlation between EEG changes and locomotor behavior was observed.

  4. Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes.

    Science.gov (United States)

    O'Tuathaigh, Colm M P; Clarke, Gerard; Walsh, Jeremy; Desbonnet, Lieve; Petit, Emilie; O'Leary, Claire; Tighe, Orna; Clarke, Niamh; Karayiorgou, Maria; Gogos, Joseph A; Dinan, Ted G; Cryan, John F; Waddington, John L

    2012-10-01

    Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of dopamine and disturbance in dopamine function is proposed to be central to the pathogenesis of schizophrenia. Clinical epidemiological studies have indicated cannabis use to confer a 2-fold increase in risk for subsequent onset of psychosis, with adolescent-onset use conveying even higher risk. There is evidence that a high activity COMT polymorphism moderates the effects of adolescent exposure to cannabis on risk for adult psychosis. In this paper we compared the effect of chronic adolescent exposure to the cannabinoid WIN 55212 on sensorimotor gating, behaviours related to the negative symptoms of schizophrenia, anxiety- and stress-related behaviours, as well as ex-vivo brain dopamine and serotonin levels, in COMT KO vs. wild-type (WT) mice. Additionally, we examined the effect of pretreatment with the COMT inhibitor tolcapone on acute effects of this cannabinoid on sensorimotor gating in C57BL/6 mice. COMT KO mice were shown to be more vulnerable than WT to the disruptive effects of adolescent cannabinoid treatment on prepulse inhibition (PPI). Acute pharmacological inhibition of COMT in C57BL/6 mice also modified acute cannabinoid effects on startle reactivity, as well as PPI, indicating that chronic and acute loss of COMT can produce dissociable effects on the behavioural effects of cannabinoids. COMT KO mice also demonstrated differential effects of adolescent cannabinoid administration on sociability and anxiety-related behaviour, both confirming and extending earlier reports of COMT×cannabinoid effects on the expression of schizophrenia-related endophenotypes.

  5. Enhanced latent inhibition in high schizotypy individuals

    OpenAIRE

    Granger, Kiri T.; Moran, Paula M.; Buckley, Matthew G.; Haselgrove, Mark

    2016-01-01

    Latent inhibition refers to a retardation in learning about a stimulus that has been rendered familiar by non-reinforced preexposure, relative to a non-preexposed stimulus. Latent inhibition has been shown to be inversely correlated with schizotypy, and abnormal in people with schizophrenia, but these findings are inconsistent. One potential contributing factor to this inconsistency is that many tasks that purport to measure latent inhibition are confounded by alternative effects that also re...

  6. Paired-pulse plasticity in the strength and latency of light-evoked lateral inhibition to retinal bipolar cell terminals.

    Science.gov (United States)

    Vickers, Evan; Kim, Mean-Hwan; Vigh, Jozsef; von Gersdorff, Henrique

    2012-08-22

    Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral IPSCs (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset latencies (∼50-80 and ∼70-150 ms, respectively) that depended on background light adaptation. We observed plasticity in both the synaptic strength and latency of the L-IPSCs. With paired light stimulation, latencies of ON L-IPSCs increased at paired-pulse intervals (PPIs) of 50 and 300 ms, whereas OFF L-IPSC latencies decreased at the 300 ms PPI. ON L-IPSCs showed paired-pulse depression at intervals <1 s, whereas OFF L-IPSCs showed depression at intervals ≤1 s and amplitude facilitation at longer intervals (1-2 s). This biphasic form of L-IPSC plasticity may underlie adaptation and sensitization to surround temporal contrast over multiple timescales. Block of retinal signaling at GABA(A)Rs and AMPARs differentially affected ON and OFF L-IPSCs, confirming that these two types of feedback inhibition are mediated by distinct and convergent retinal pathways with different mechanisms of plasticity. We propose that these plastic changes in the strength and timing of L-IPSCs help to dynamically shape the time course of glutamate release from ON-type BC terminals. Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds.

  7. Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway

    Directory of Open Access Journals (Sweden)

    Jia-Qi Sun

    2016-01-01

    Full Text Available Although Chinese herbal compounds have long been alternatively applied for cancer treatment in China, their treatment effects have not been sufficiently investigated. The Chinese herb Spatholobus suberectus is commonly prescribed to cancer patients. HPLC analysis has shown that the main components of Spatholobus suberectus are flavonoids that can be classified as phytoestrogens, having a structure similar to estrogen. This study was designed to investigate the effects of Spatholobus suberectus column extract (SSCE on the estrogen receptor-positive (ER+ breast cancer cell line MCF-7 and its possible molecular mechanism. In our study, MTT assay was performed to evaluate cell viability. The results show that SSCE (80, 160, and 320 μg/ml significantly decreased the viability of MCF-7 cells. SSCE also triggered apoptosis, arrested the cell cycle at the G0/G1 phase, and inhibited cell migration. A dual-luciferase reporter system showed that SSCE suppressed intranuclear p-ER activity; Western blot analysis confirmed the repressed expression of phosphorylated-ER alpha (p-ERα, ERK1/2, p-ERK1/2, AKT, p-AKT, p-mTOR, PI3K, and p-PI3K, indicating that SSCE suppressed the MAPK PI3K/AKT signaling pathway. Collectively, our results suggest that SSCE causes apoptosis, an arrest in the G0/G1 phase, and a decrease in migration in ER+ MCF-7 cells via hypoactivity of the ER and suppression of the MAPK PI3K/AKT pathway.

  8. Collaborative inhibition in spatial memory retrieval

    National Research Council Canada - National Science Library

    Sjolund, Lori A; Erdman, Matthew; Kelly, Jonathan W

    2014-01-01

    .... Two experiments were designed to explore whether collaborative inhibition, which has heretofore been studied using traditional memory stimuli such as word lists, also characterizes spatial memory retrieval...

  9. Mouse behavioral endophenotypes for schizophrenia.

    Science.gov (United States)

    Amann, Laura C; Gandal, Michael J; Halene, Tobias B; Ehrlichman, Richard S; White, Samantha L; McCarren, Hilary S; Siegel, Steven J

    2010-09-30

    An endophenotype is a heritable trait that is generally considered to be more highly, associated with a gene-based neurological deficit than a disease phenotype itself. Such, endophenotypic deficits may therefore be observed in the non-affected relatives of disease patients. Once endophenotypes have been established for a given illness, such as schizophrenia, mechanisms of, action may then be established and treatment options developed in order to target such measures. The, current paper describes and assesses the merits and limitations of utilizing behavioral and, electrophysiological endophenotypes of schizophrenia in mice. Such endophenotypic deficits include: decreased auditory event related potential (ERP) amplitude and gating (specifically, that of the P20, N40, P80 and P120); impaired mismatch negativity (MMN); changes in theta and gamma frequency, analyses; decreased pre-pulse inhibition (PPI); impaired working and episodic memories (for instance, novel object recognition [NOR], contextual and cued fear conditioning, latent inhibition, Morris and, radial arm maze identification and nose poke); sociability; and locomotor activity. A variety of, pharmacological treatments, including ketamine, MK-801 and phencyclidine (PCP) can be used to, induce some of the deficits described above, and numerous transgenic mouse strains have been, developed to address the mechanisms responsible for such endophenotypic differences. We also, address the viability and validity of using such measures regarding their potential clinical implications, and suggest several practices that could increase the translatability of preclinical data.

  10. Inhibition of the dorsal premotor cortex does not repair surround inhibition in writer's cramp patients.

    Science.gov (United States)

    Veugen, Lidwien C; Hoffland, Britt S; Stegeman, Dick F; van de Warrenburg, Bart P

    2013-03-01

    Writer's cramp is a task-specific form of focal dystonia, characterized by abnormal movements and postures of the hand and arm during writing. Two consistent abnormalities in its pathophysiology are a loss of surround inhibition and overactivity of the dorsal premotor cortex (PMd). This study aimed to assess a possible link between these two phenomena by investigating whether PMd inhibition leads to an improvement of surround inhibition, in parallel with previously demonstrated writing improvement. Fifteen writer's cramp patients and ten controls performed a simple motor hand task during which surround inhibition was measured using transcranial magnetic stimulation. Motor cortical excitability was measured of the active and surround muscles at three phases of the task. Surround inhibition and writing performance were assessed before and after PMd inhibitory continuous theta burst stimulation. In contrast to healthy controls, patients did not show inhibition of the abductor digiti minimi muscle during movement initiation of the first dorsal interosseus muscle, confirming the loss of surround inhibition. PMd inhibition led to an improvement of writing speed in writer's cramp patients. However, in both groups, no changes in surround inhibition were observed. The results confirm a role for the PMd in the pathophysiology of writer's cramp. We show that PMd inhibition does not lead to restoration of the surround inhibition defect in writer's cramp, despite the improvement in writing. This questions the involvement of the PMd in the loss of surround inhibition, and perhaps also the direct link between surround inhibition and dystonia.

  11. Reduced surround inhibition in musicians.

    Science.gov (United States)

    Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

    2012-06-01

    To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

  12. Cellulase Inhibition by High Concentrations of Monosaccharides

    DEFF Research Database (Denmark)

    Hsieh, Chia-Wen; Cannella, David; Jørgensen, Henning

    2014-01-01

    that low free water availability contributes to cellulase inhibition. Of the hydrolytic enzymes involved, those acting on the cellulose substrate, that is, exo- and endoglucanases, were the most inhibited. The β -glucosidases were shown to be less sensitive to high monosaccharide concentrations except...

  13. A Qualitative Approach to Enzyme Inhibition

    Science.gov (United States)

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

  14. Inhibited and Uninhibited Types of Children.

    Science.gov (United States)

    Kagan, Jerome; And Others

    1989-01-01

    Investigates the preservation of inhibited and uninhibited behaviors in 100 children of 14, 20, 32, and 48 months. Children who had been extremely inhibited or uninhibited at 14 and 20 months differed significantly at 4 years of age in behavior and cardiac acceleration. (RJC)

  15. Inhibition: Mental Control Process or Mental Resource?

    Science.gov (United States)

    Im-Bolter, Nancie; Johnson, Janice; Ling, Daphne; Pascual-Leone, Juan

    2015-01-01

    The current study tested 2 models of inhibition in 45 children with language impairment and 45 children with normally developing language; children were aged 7 to 12 years. Of interest was whether a model of inhibition as a mental-control process (i.e., executive function) or as a mental resource would more accurately reflect the relations among…

  16. Quorum Sensing Inhibition, Relevance to Periodontics

    OpenAIRE

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  17. A Qualitative Approach to Enzyme Inhibition

    Science.gov (United States)

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

  18. Quorum sensing inhibition, relevance to periodontics.

    Science.gov (United States)

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  19. Inhibition in Autism: Children with Autism Have Difficulty Inhibiting Irrelevant Distractors but Not Prepotent Responses

    Science.gov (United States)

    Adams, Nena C.; Jarrold, Christopher

    2012-01-01

    Resistance to distractor inhibition tasks have previously revealed impairments in children with autism. However, on the classic Stroop task and other prepotent response tasks, children with autism show intact inhibition. These data may reflect a distinction between prepotent response and resistance to distractor inhibition. The current study…

  20. Inhibition of ethylene production by rhizobitoxine

    Energy Technology Data Exchange (ETDEWEB)

    Owens, L.D.; Lieberman, M.; Kunishi, A.

    1970-01-01

    Rhizobitoxine, an inhibitor of methionine biosynthesis in Salmonella typhimurium, inhibited ethylene production about 75% in light-grown sorghum seedlings and in senescent apple tissue. Ethylene production stimulated by indoleacetic acid and kinetin in sorghum was similarly inhibited. With both apple and sorghum, the inhibition could only be partially relieved by additions of methionine. A methionine analogue, ..cap alpha..-keto-..gamma..-methylthiobutyric acid, which has been suggested as an intermediate between methionine and ethylene, had no effect on the inhibition. Incorporation of /sup 14/C from added methionine-/sup 14/C into ethylene was curtailed by rhizobitoxine to about the same extent as was ethylene production. These results suggest that rhizobitoxine interferes with ethylene biosynthesis by blocking the conversion of methionine to ethylene and not indirectly by inhibiting the biosynthesis of methionine. Ethylene production by Penicillium digitatum, a fungus which produces ethylene via pathways not utilizing methionine as a precursor, was not affected by rhizobitoxine. 16 references, 2 figures, 4 tables.

  1. Habituation, latent inhibition, and extinction.

    Science.gov (United States)

    Jordan, Wesley P; Todd, Travis P; Bucci, David J; Leaton, Robert N

    2015-06-01

    In two conditioned suppression experiments with a latent inhibition (LI) design, we measured the habituation of rats in preexposure, their LI during conditioning, and then extinction over days. In the first experiment, lick suppression, the preexposed group (PE) showed a significant initial unconditioned response (UR) to the target stimulus and significant long-term habituation (LTH) of that response over days. The significant difference between the PE and nonpreexposed (NPE) groups on the first conditioning trial was due solely to the difference in their URs to the conditioned stimulus (CS)-a habituated response (PE) and an unhabituated response (NPE). In the second experiment, bar-press suppression, little UR to the target stimulus was apparent during preexposure, and no detectable LTH. Thus, there was no difference between the PE and NPE groups on the first conditioning trial. Whether the UR to the CS confounds the interpretation of LI (Exp. 1) or not (Exp. 2) can only be known if the UR is measured. In both experiments, LI was observed in acquisition. Also in both experiments, rats that were preexposed and then conditioned to asymptote were significantly more resistant to extinction than were the rats not preexposed. This result contrasts with the consistently reported finding that preexposure either produces less resistance to extinction or has no effect on extinction. The effect of stimulus preexposure survived conditioning to asymptote and was reflected directly in extinction. These two experiments provide a cautionary procedural note for LI experiments and have shown an unexpected extinction effect that may provide new insights into the interpretation of LI.

  2. Fear inhibition in high trait anxiety.

    Science.gov (United States)

    Kindt, Merel; Soeter, Marieke

    2014-01-01

    Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders.

  3. BST2/Tetherin Inhibition of Alphavirus Exit

    Directory of Open Access Journals (Sweden)

    Yaw Shin Ooi

    2015-04-01

    Full Text Available Alphaviruses such as chikungunya virus (CHIKV and Semliki Forest virus (SFV are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles to the cell surface. Alphaviruses have highly organized structures and exclude host membrane proteins from the site of budding, suggesting that their release might be insensitive to tetherin inhibition. Here, we demonstrated that exogenously-expressed tetherin efficiently inhibited the release of SFV and CHIKV particles from host cells without affecting virus entry and infection. Alphavirus release was also inhibited by the endogenous levels of tetherin in HeLa cells. While rubella virus (RuV and dengue virus (DENV have structural similarities to alphaviruses, tetherin inhibited the release of RuV but not DENV. We found that two recently identified tetherin isoforms differing in length at the N-terminus exhibited distinct capabilities in restricting alphavirus release. SFV exit was efficiently inhibited by the long isoform but not the short isoform of tetherin, while both isoforms inhibited vesicular stomatitis virus exit. Thus, in spite of the organized structure of the virus particle, tetherin specifically blocks alphavirus release and shows an interesting isoform requirement.

  4. A preliminary study of acoustic startle reflex in male patients with chronic schizophrenia%慢性精神分裂症男性患者听觉刺激惊跳反射的初步研究

    Institute of Scientific and Technical Information of China (English)

    王志仁; 周东丰; 谭云龙; 杨甫德; 张五芳; 邹义壮; 宋崇生; 周宇; 李英丽; 张向阳

    2010-01-01

    Objective To explore the deficits of acoustic startle reflex (ASR) that might exist in Chinese patients with schizophrenia and the effects of antipsychotics on ASR. Methods Participants included 25 male patients with chronic schizophrenia treated with typical antipsychotics ( typical group), 25 with atypical antipsychotic clozapine (clozapine group) and 25 healthy male subjects (control group)matched for age and years of education. Startle reflex to acoustic stimuli were examined in all subjects from the three groups. At the same day of startle testing, psychopathological symptoms of the patients were assessed with the Positive and Negative Syndrome Scale (PANSS). Results (1) Startle response(SR) was significantly reduced in typical group than in control group[ (553.6 ±516. 9) mV vs (942. 0 ±447. 3) mV,P =0. 009]. SR of clozapine group [ (755.9 ±439. 4) mV] was greater than that of typical group and less than that of control group, but there was no significant difference between clozapine group and the other two ( P > 0. 05 ). (2) Habituation (HAB) of startle reflex in typical group was significantly lower than in control group [ ( 17. 8 ± 35. 8 ) % vs (44. 9 ± 28.9) %, P = 0. 027 ]. HAB of clozapine group [ (22. 9 ± 34. 1 ) % ]was higher than that of typical group and less than that of control group, but there was no significant difference between clozapine group and the other groups ( P > 0. 05 ). ( 3 ) Compared with healthy controls,patients of typical group exhibited the significant reduction in prepulse inhibition (PPI) of startle reflex (P = 0. 024) when prepulse interval (LI) was 120 ms. PPI of clozapine group was higher than typical group and less than control group, but no significant differences in PPI were found between clozapine group and the other groups. While LI was 30 ms or 120 ms, PPI among the three groups did not show significantly different (P > 0. 05 ). (4) No significant relationship was found between PPI of different LIs and

  5. The IFITMs Inhibit Zika Virus Replication

    Directory of Open Access Journals (Sweden)

    George Savidis

    2016-06-01

    Full Text Available Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.

  6. Reversible Inhibition of Cellular Metabolism by Ribavirin

    Science.gov (United States)

    Larsson, Alf; Stenberg, Kjell; Öberg, Bo

    1978-01-01

    The broad spectrum antiviral drug ribavirin (Virazole, 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 μM ribavirin or 18 h with 2 μM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells. PMID:646339

  7. Revealing the Mechanistic Pathway of Acid Activation of Proton Pump Inhibitors To Inhibit the Gastric Proton Pump: A DFT Study.

    Science.gov (United States)

    Jana, Kalyanashis; Bandyopadhyay, Tusar; Ganguly, Bishwajit

    2016-12-29

    Acid-related gastric diseases are associated with disorder of digestive tract acidification due to the acid secretion by gastric proton pump, H(+),K(+)-ATPase. Omeprazole is one of the persuasive irreversible inhibitor of the proton pump H(+),K(+)-ATPase. However, the reports on the mechanistic pathway of irreversible proton pump inhibitors (PPIs) on the acid activation and formation of disulfide complex are scarce in the literature. We have examined the acid activation PPIs, i.e., timoprazole, S-omeprazole and R-omeprazole using M062X/6-31++G(d,p) in aqueous phase with SMD solvation model. The proton pump inhibitor is a prodrug and activated in the acidic canaliculi of the gastric pump H(+),K(+)-ATPase to sulfenic acid which can either form another acid activate intermediate sulfenamide or a disulfide complex with cysteine amino acid of H(+),K(+)-ATPase. The quantum chemical calculations suggest that the transition state (TS5) for the disulfide complex formation is the rate-determining step of the multistep acid inhibition process by PPIs. The free energy barrier of TS5 is 5.5 kcal/mol higher for timoprazole compared to the S-omeprazole. The stability of the transition state for the formation of disulfide bond between S-omeprazole and cysteine amino acid of H(+),K(+)-ATPase is governed by inter- and intramolecular hydrogen bonding. The disulfide complex for S-omeprazole is thermodynamically more stable by 4.5 kcal/mol in aqueous phase compared to disulfide complex of timoprazole, which corroborates the less efficacy of timoprazole as irreversible PPI for acid inhibition process. It has been speculated that sulfenic acid can either form sulfenamide or a stable disulfide complex with cysteine amino acid residue of H(+),K(+)-ATPase. The M062X/6-31++G(d,p) level of theory calculated results reveal that the formation of tetra cyclic sulfenamide is unfavored by ∼17 kcal/mol for S-omeprazole and 11.5 kcal/mol for timoprazole compared to the disulfide complex formation

  8. Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the vesicular monoamine transporter-2.

    Science.gov (United States)

    Nickell, Justin R; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P

    2010-02-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [(3)H]dihydrotetrabenazine binding, inhibition of [(3)H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (K(i) = 45 nM) inhibiting vesicular [(3)H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC(50) = 0.65 microM; I(max) = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC(50) = 0.42 microM, I(max) = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for

  9. Lobelane Inhibits Methamphetamine-Evoked Dopamine Release via Inhibition of the Vesicular Monoamine Transporter-2S⃞

    Science.gov (United States)

    Nickell, Justin R.; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B.; Zheng, Guangrong; Crooks, Peter A.

    2010-01-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [3H]dihydrotetrabenazine binding, inhibition of [3H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (Ki = 45 nM) inhibiting vesicular [3H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC50 = 0.65 μM; Imax = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC50 = 0.42 μM, Imax = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for the development of a

  10. Inhibition of urinary calculi -- a spectroscopic study

    Science.gov (United States)

    Manciu, Felicia; Govani, Jayesh; Durrer, William; Reza, Layra; Pinales, Luis

    2008-10-01

    Although a considerable number of investigations have already been undertaken and many causes such as life habits, metabolic disorders, and genetic factors have been noted as sources that accelerate calculi depositions and aggregations, there are still plenty of unanswered questions regarding efficient inhibition and treatment mechanisms. Thus, in an attempt to acquire more insights, we propose here a detailed scientific study of kidney stone formation and growth inhibition based on a traditional medicine approach with Rotula Aquatica Lour (RAL) herbal extracts. A simplified single diffusion gel growth technique was used for synthesizing the samples for the present study. The unexpected Zn presence in the sample with RAL inhibitor, as revealed by XPS measurements, explains the inhibition process and the dramatic reflectance of the incident light observed in the infrared transmission studies. Raman data demonstrate potential binding of the inhibitor with the oxygen of the kidney stone. Photoluminescence results corroborate to provide additional evidence of Zn-related inhibition.

  11. Toxicants inhibiting anaerobic digestion: a review.

    Science.gov (United States)

    Chen, Jian Lin; Ortiz, Raphael; Steele, Terry W J; Stuckey, David C

    2014-12-01

    Anaerobic digestion is increasingly being used to treat wastes from many sources because of its manifold advantages over aerobic treatment, e.g. low sludge production and low energy requirements. However, anaerobic digestion is sensitive to toxicants, and a wide range of compounds can inhibit the process and cause upset or failure. Substantial research has been carried out over the years to identify specific inhibitors/toxicants, and their mechanism of toxicity in anaerobic digestion. In this review we present a detailed and critical summary of research on the inhibition of anaerobic processes by specific organic toxicants (e.g., chlorophenols, halogenated aliphatics and long chain fatty acids), inorganic toxicants (e.g., ammonia, sulfide and heavy metals) and in particular, nanomaterials, focusing on the mechanism of their inhibition/toxicity. A better understanding of the fundamental mechanisms behind inhibition/toxicity will enhance the wider application of anaerobic digestion.

  12. Glycerol inhibition of ruminal lipolysis in vitro

    Science.gov (United States)

    Supplemental glycerol inhibits rumen lipolysis, a prerequisite for rumen biohydrogenation, which is responsible for the saturation of dietary fatty acids consumed by ruminant animals. Feeding excess glycerol, however, adversely affects dry matter digestibility. To more clearly define the effect of...

  13. Meis1: effects on motor phenotypes and the sensorimotor system in mice

    Directory of Open Access Journals (Sweden)

    Aaro V. Salminen

    2017-08-01

    Full Text Available MEIS1 encodes a developmental transcription factor and has been linked to restless legs syndrome (RLS in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and has a substantial impact on the quality of life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the system with the most potential for modeling RLS in animals. We used heterozygous Meis1-knockout mice to study the effects of Meis1 haploinsufficiency on mouse behavioral and neurological phenotypes, and to relate the findings to human RLS. We exposed the Meis1-deficient mice to assays of motor, sensorimotor and cognitive ability, and assessed the effect of a dopaminergic receptor 2/3 agonist commonly used in the treatment of RLS. The mutant mice showed a pattern of circadian hyperactivity, which is compatible with human RLS. Moreover, we discovered a replicable prepulse inhibition (PPI deficit in the Meis1-deficient animals. In addition, these mice were hyposensitive to the PPI-reducing effect of the dopaminergic receptor agonist, highlighting a role of Meis1 in the dopaminergic system. Other reported phenotypes include enhanced social recognition at an older age that was not related to alterations in adult olfactory bulb neurogenesis previously shown to be implicated in this behavior. In conclusion, the Meis1-deficient mice fulfill some of the hallmarks of an RLS animal model, and revealed the role of Meis1 in sensorimotor gating and in the dopaminergic systems modulating it.

  14. Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.

    Science.gov (United States)

    Iwayama, Yoshimi; Hattori, Eiji; Maekawa, Motoko; Yamada, Kazuo; Toyota, Tomoko; Ohnishi, Tetsuo; Iwata, Yasuhide; Tsuchiya, Kenji J; Sugihara, Genichi; Kikuchi, Mitsuru; Hashimoto, Kenji; Iyo, Masaomi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Iwata, Nakao; Nanko, Shinichiro; Iwamoto, Kazuya; Okazaki, Yuji; Kato, Tadafumi; Yoshikawa, Takeo

    2010-03-05

    Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such as schizophrenia and bipolar disorder. To unravel PPI-controlling mechanisms, we previously performed quantitative trait loci (QTL) analysis in mice, and identified Fabp7, that encodes a brain-type fatty acid binding protein (Fabp), as a causative gene. In that study, human FABP7 showed genetic association with schizophrenia. FABPs constitute a gene family, of which members FABP5 and FABP3 are also expressed in the brain. These FABP proteins are molecular chaperons for polyunsaturated fatty acids (PUFAs) such as arachidonic and docosahexaenoic acids. Additionally, the involvement of PUFAs has been documented in the pathophysiology of schizophrenia and mood disorders. Therefore in this study, we examined the genetic roles of FABP5 and 3 in schizophrenia (N = 1,900 in combination with controls) and FABP7, 5, and 3 in bipolar disorder (N = 1,762 in the case-control set). Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease. Each FABP is relatively small and it is assumed that there are multiple regulatory elements that control gene expression. Therefore, future identification of unknown regulatory elements will be necessary to make a more detailed analysis of their genetic contribution to mental illnesses.

  15. Environmental Enrichment Ameliorates Behavioral Impairments Modeling Schizophrenia in Mice Lacking Metabotropic Glutamate Receptor 5.

    Science.gov (United States)

    Burrows, Emma L; McOmish, Caitlin E; Buret, Laetitia S; Van den Buuse, Maarten; Hannan, Anthony J

    2015-07-01

    Schizophrenia arises from a complex interplay between genetic and environmental factors. Abnormalities in glutamatergic signaling have been proposed to underlie the emergence of symptoms, in light of various lines of evidence, including the psychotomimetic effects of NMDA receptor antagonists. Metabotropic glutamate receptor 5 (mGlu5) has also been implicated in the disorder, and has been shown to physically interact with NMDA receptors. To clarify the role of mGlu5-dependent behavioral expression by environmental factors, we assessed mGlu5 knockout (KO) mice after exposure to environmental enrichment (EE) or reared under standard conditions. The mGlu5 KO mice showed reduced prepulse inhibition (PPI), long-term memory deficits, and spontaneous locomotor hyperactivity, which were all attenuated by EE. Examining the cellular impact of genetic and environmental manipulation, we show that EE significantly increased pyramidal cell dendritic branching and BDNF protein levels in the hippocampus of wild-type mice; however, mGlu5 KO mice were resistant to these alterations, suggesting that mGlu5 is critical to these responses. A selective effect of EE on the behavioral response to the NMDA receptor antagonist MK-801 in mGlu5 KO mice was seen. MK-801-induced hyperlocomotion was further potentiated in enriched mGlu5 KO mice and treatment with MK-801 reinstated PPI disruption in EE mGlu5 KO mice only, a response that is absent under standard housing conditions. Together, these results demonstrate an important role for mGlu5 in environmental modulation of schizophrenia-related behavioral impairments. Furthermore, this role of the mGlu5 receptor is mediated by interaction with NMDA receptor function, which may inform development of novel therapeutics.

  16. Sex-dependent changes in social behaviors in motor pre-symptomatic R6/1 mice.

    Directory of Open Access Journals (Sweden)

    Susanna Pietropaolo

    Full Text Available BACKGROUND: The R6/1 mouse line is one of the most widely employed models of Huntington Disease (HD, a complex syndrome characterized by motor and non-motor deficits. Surprisingly, its behavioral phenotype during the early phases of the pathology when the motor impairments are not manifest yet has been poorly investigated. It is also not clear whether the expression of HD-like symptoms at the pre-motor stage in this mouse model differs between the two sexes. METHODS: Male and female 12 weeks-old R6/1 mice and their wild-type littermates were tested on a battery of tests modeling some of the major neuropsychiatric non-motor symptoms of HD: alterations in social interest, social interaction and communication, as well as disturbances in prepulse inhibition of the acoustic startle response (PPI and circadian patterns of activity. The lack of motor symptoms was confirmed during the entire experimental period by means of the tail test for clasping. RESULTS: R6/1 mice displayed marked alterations in all social behaviors which were mainly observed in males. Male R6/1 animals were also the only ones showing reduced body weight. Both male and female transgenic mice displayed mild alterations in the circadian activity patterns, but no deficits in PPI. CONCLUSIONS: These results demonstrate the validity of the R6/1 mouse in mimicking selected neuropsychiatric symptoms of HD, the social deficits being the clearest markers of the pre-motor phase of the pathology. Furthermore, our data suggest that male R6/1 mice are more suitable for future studies on the early stages of HD.

  17. Pharmacological insights into the role of P2X4 receptors in behavioral regulation: lessons from ivermectin

    Science.gov (United States)

    Bortolato, Marco; Yardley, Megan; Khoja, Sheraz; Godar, Sean C; Asatryan, Liana; Finn, Deborah A.; Alkana, Ronald L.; Louie, Stan G.; Davies, Daryl L.

    2012-01-01

    Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate (ATP). In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioral functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioral organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg, i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviors in the tail-suspension and forced swim tests. The agent induced no significant behavioral changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by prepulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gating. PMID:23174033

  18. Cysteamine treatment ameliorates alterations in GAD67 expression and spatial memory in heterozygous reeler mice.

    Science.gov (United States)

    Kutiyanawalla, Ammar; Promsote, Wanwisa; Terry, Alvin; Pillai, Anilkumar

    2012-09-01

    Brain-derived neurotrophic factor (BDNF) signalling through its receptor, TrkB is known to regulate GABAergic function and glutamic acid decarboxylase (GAD) 67 expression in neurons. Alterations in BDNF signalling have been implicated in the pathophysiology of schizophrenia and as a result, they are a potential therapeutic target. Interestingly, heterozygous reeler mice (HRM) have decreased GAD67 expression in the frontal cortex and hippocampus and they exhibit many behavioural and neurochemical abnormalities similar to schizophrenia. In this study, we evaluated the potential of cysteamine, a neuroprotective compound to improve the deficits in GAD67 expression and cognitive function in HRM. We found that cysteamine administration (150 mg/kg.d, through drinking water) for 30 d significantly ameliorated the decreases in GAD67, mature BDNF and full-length TrkB protein levels found in frontal cortex and hippocampus of HRM. A significant attenuation of the increased levels of truncated BDNF in frontal cortex and hippocampus, as well as truncated TrkB in frontal cortex of HRM was also observed following cysteamine treatment. In behavioural studies, HRM were impaired in a Y-maze spatial recognition memory task, but not in a spontaneous alternation task or a sensorimotor, prepulse inhibition (PPI) procedure. Cysteamine improved Y-maze spatial recognition in HRM to the level of wide-type controls and it improved PPI in both wild-type and HRM. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in GAD67 expression suggesting that TrkB signalling plays an important role in GAD67 regulation by cysteamine.

  19. Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Eells

    Full Text Available Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%, genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/- mice and wild-type (+/+ mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

  20. Neomycin inhibits angiogenin-induced angiogenesis

    OpenAIRE

    1998-01-01

    A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, an...

  1. Neomycin inhibits angiogenin-induced angiogenesis

    OpenAIRE

    Hu, Guo-fu

    1998-01-01

    A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, an...

  2. Inhibited solid propellant composition containing beryllium hydride

    Science.gov (United States)

    Thompson, W. W. (Inventor)

    1978-01-01

    An object of this invention is to provide a composition of beryllium hydride and carboxy-terminated polybutadiene which is stable. Another object of this invention is to provide a method for inhibiting the reactivity of beryllium hydride toward carboxy-terminated polybutadiene. It was found that a small amount of lecithin inhibits the reaction of beryllium hydride with the acid groups in carboxy terminated polybutadiene.

  3. The inhibition of monoamine oxidase by esomeprazole

    OpenAIRE

    2013-01-01

    Virtual screening of a library of drugs has suggested that esomeprazole, the S-enantiomer of omeprazole, may possess binding affinities for the active sites of the monoamine oxidase (MAO) A and B enzymes. Based on this finding, the current study examines the MAO inhibitory properties of esomeprazole. Using recombinant human MAO-A and MAO-B, IC50 values for the inhibition of these enzymes by esomeprazole were experimentally determined. To examine the reversibility of MAO inhibition by esomepra...

  4. Piperine, a dietary phytochemical, inhibits angiogenesis

    OpenAIRE

    2012-01-01

    Angiogenesis plays an important role in tumor progression. Piperine, a major alkaloid constituent of black pepper, has diverse physiological actions including killing of cancer cells; however, the effect of piperine on angiogenesis is not known. Here we show that piperine inhibited the proliferation and G1/S transition of human umbilical vein endothelial cells (HUVECs) without causing cell death. Piperine also inhibited HUVEC migration and tubule formation in vitro, as well as collagen-induce...

  5. Inhibition of Heme Peroxidases by Melamine

    Directory of Open Access Journals (Sweden)

    Pattaraporn Vanachayangkul

    2012-01-01

    Full Text Available In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP, lactoperoxidase (LPO, and cyclooxygenase-1 and -2 (COX-1 and -2. Melamine exhibited noncompetitive inhibition of HRP (9.5±0.7mM, and LPO showed a mixed model of inhibition (14.5±4.7mM. The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.

  6. Scale Inhibition of Green Inhibitor Polyepoxysuccinic Sodium

    Institute of Scientific and Technical Information of China (English)

    Feng Hui-xia; Wang Yi; Yu Shu-rong; Liang Bao-feng

    2004-01-01

    Polyepoxysuccinic acid (PESA) is the green water treatment agents recognized all over the world[1-3]. It is found that when PESA is used alone, it had good scale inhibition. PESA should be included in the category of green scale inhibitor.PESA is synthesized with maleicanhydride in the presence of catalysts. The effect on scale-in-hibiting property of the product from amount and feed times of catalyst, the reaction temperature, the reaction time were investigated. The optimum reaction conditions are as follows:n(maleic anhydride):n(Ca(OH)2):n(NaOH)=1:0.05-0.2:0.5, reaction temperature 95C, reaction time 4h.In all the references about PESA, PESA is researched as a kind of highly effective scale inhibitor or chelate. In this paper, the performance of scale inhibition of PESA is evaluated by scale static inhibitor.The results are shown in Figture1.It is evident from our experimental data (Figture1) that when inhibition for CaCO3.With the increase of PESA dosage, scale inhibition increases. When dosage is more than 6mg/L, inhibition efficiency is over 50%. The formulas give scale inhibition efficiency more than 95% at 12mg/L of total dosage.

  7. Spatially reciprocal inhibition of inhibition within a stimulus selection network in the avian midbrain.

    Science.gov (United States)

    Goddard, C Alex; Mysore, Shreesh P; Bryant, Astra S; Huguenard, John R; Knudsen, Eric I

    2014-01-01

    Reciprocal inhibition between inhibitory projection neurons has been proposed as the most efficient circuit motif to achieve the flexible selection of one stimulus among competing alternatives. However, whether such a motif exists in networks that mediate selection is unclear. Here, we study the connectivity within the nucleus isthmi pars magnocellularis (Imc), a GABAergic nucleus that mediates competitive selection in the midbrain stimulus selection network. Using laser photostimulation of caged glutamate, we find that feedback inhibitory connectivity is global within the Imc. Unlike typical lateral inhibition in other circuits, intra-Imc inhibition remains functionally powerful over long distances. Anatomically, we observed long-range axonal projections and retrograde somatic labeling from focal injections of bi-directional tracers in the Imc, consistent with spatial reciprocity of intra-Imc inhibition. Together, the data indicate that spatially reciprocal inhibition of inhibition occurs throughout the Imc. Thus, the midbrain selection circuit possesses the most efficient circuit motif possible for fast, reliable, and flexible selection.

  8. [Behavioral and neurobiological abnormalities induced by social isolation as a useful animal model of schizophrenia].

    Science.gov (United States)

    Lei, Ming; Luo, Lu; Ma, Shi-Qi; Zhang, Yan; Wu, Xi-Hong; Li, Liang

    2013-02-25

    Social isolation influences the development of the brain, causing dysfunctions at behavioral, cellular and molecular levels. The present paper summarizes the abnormalities induced by social isolation in behaviors, neurotransmitters and cell apoptosis. At the behavioral level, social isolation induces hyperlocomotion, abnormalities in startle reflex and prepulse inhibition (PPI), and dysfunctions in conditioned learning, reversal learning and memory. Moreover, social isolation causes changes of neurotransmitters, such as the increase of dopamine in the nucleus accumbens, the amygdala and other brain regions in the limbic system, the decrease of dopamine in medial prefrontal cortex, the decrease of 5-HT in the nucleus accumbens and the hippocampus, and changes of glutamine in the prefrontal cortex. Finally, social isolation affects cell apoptosis in different brain areas, such as the medial prefrontal cortex, amygdala, nucleus accumbens, and hippocampus. Both the changes in neurotransmitters and cell apoptosis may contribute to the behavioral dysfunctions in social isolated rats. Since schizophrenic patients have similar abnormalities in behaviors and neurotransmitters, isolation rearing can be used as a useful animal model of schizophrenia.

  9. Effect of Hallucinogens on Unconditioned Behavior.

    Science.gov (United States)

    Halberstadt, Adam L; Geyer, Mark A

    2017-02-22

    Because of the ethical and regulatory hurdles associated with human studies, much of what is known about the psychopharmacology of hallucinogens has been derived from animal models. However, developing reliable animal models has proven to be a challenging task due to the complexity and variability of hallucinogen effects in humans. This chapter focuses on three animal models that are frequently used to test the effects of hallucinogens on unconditioned behavior: head twitch response (HTR), prepulse inhibition of startle (PPI), and exploratory behavior. The HTR has demonstrated considerable utility in the neurochemical actions of hallucinogens. However, the latter two models have clearer conceptual bridges to human phenomenology. Consistent with the known mechanism of action of hallucinogens in humans, the behavioral effects of hallucinogens in rodents are mediated primarily by activation of 5-HT2A receptors. There is evidence, however, that other receptors may play secondary roles. The structure-activity relationships (SAR) of hallucinogens are reviewed in relation to each model, with a focus on the HTR in rats and mice.

  10. The effects of breeding protocol in C57BL/6J mice on adult offspring behaviour.

    Directory of Open Access Journals (Sweden)

    Claire J Foldi

    Full Text Available Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10-12 days and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH. The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM. Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI of the acoustic startle response. We found that length of sire exposure (LSE had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour.

  11. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    Science.gov (United States)

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  12. Habituation of the startle reflex depends on attention in cannabis users.

    Science.gov (United States)

    Kedzior, Karina K; Wehmann, Eileen; Martin-Iverson, Mathew

    2016-10-26

    Cannabis use is associated with an attention-dependent deficit in prepulse inhibition of the startle reflex (PPI). The aim of the current study was to investigate startle habituation in cannabis users and healthy controls during two attentional tasks. Auditory startle reflex was recorded from orbicularis oculi muscle while participants (12 controls and 16 regular cannabis users) were either attending to or ignoring 100 dB startling pulses. Startle habituation was measured as the absolute reduction in startle magnitude on block 2 (last nine trials) vs. block 1 (first nine trials). Startle habituation with moderate effect sizes was observed in controls and cannabis users only while they were ignoring the startling pulses but not while they were attending to them. Similar results were also observed in controls (lifetime non-users of cannabis) and cannabis users with lifetime cannabis use disorders (CUD). Startle habituation appears to depend on selective attention but not on cannabis use. Startle habituation was present when attention was directed away from auditory startling pulses in healthy controls and cannabis users. Such a similar pattern of results in both groups suggests that at least a trend exists towards presence of startle habituation regardless of cannabis use or CUD in otherwise healthy members of the general population.

  13. Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug

    Directory of Open Access Journals (Sweden)

    Williams Michael T

    2011-10-01

    Full Text Available Abstract Rationale Whether selective serotonin reuptake inhibitors (SSRIs exposure during adolescent brain development causes lasting effects remains unresolved. Objective Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Methods Male Sprague-Dawley littermates (41 litters were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day, paroxetine (3, 10 or, 17 mg/kg/day, or water; half were tested while on-drug (21 litters and half after 60 days off-drug (20 litters. Results The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N = 20/group. No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI although a trend (p Conclusions The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.

  14. Toll-like receptor 9 deficiency impacts sensory and motor behaviors.

    Science.gov (United States)

    Khariv, Veronika; Pang, Kevin; Servatius, Richard J; David, Brian T; Goodus, Matthew T; Beck, Kevin D; Heary, Robert F; Elkabes, Stella

    2013-08-01

    Toll-like receptors (TLRs) mediate the induction of the innate immune system in response to pathogens, injury and disease. However, they also play non-immune roles and are expressed in the central nervous system (CNS) during prenatal and postnatal stages including adulthood. Little is known about their roles in the CNS in the absence of pathology. Several members of the TLR family have been implicated in the development of neural and cognitive function although the contribution of TLR9 to these processes has not been well defined. The current studies were undertaken to determine whether developmental TLR9 deficiency affects motor, sensory or cognitive functions. We report that TLR9 deficient (TLR9(-/-)) mice show a hyper-responsive sensory and motor phenotype compared to wild type (TLR9(+/+)) controls. This is indicated by hypersensitivity to thermal stimuli in the hot plate paw withdrawal test, enhanced motor-responsivity under anxious conditions in the open field test and greater sensorimotor reactivity in the acoustic startle response. Prepulse inhibition (PPI) of the acoustic startle response was also enhanced, which indicates abnormal sensorimotor gating. In addition, subtle, but significant, gait abnormalities were noted in the TLR9(-/-) mice on the horizontal balance beam test with higher foot slip numbers than TLR9(+/+) controls. In contrast, spatial learning and memory, assessed by the Morris water maze, was similar in the TLR9(-/-) and TLR9(+/+) mice. These findings support the notion that TLR9 is important for the appropriate development of sensory and motor behaviors.

  15. Neomycin inhibits angiogenin-induced angiogenesis.

    Science.gov (United States)

    Hu, G F

    1998-08-18

    A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.

  16. Aspartate inhibits Staphylococcus aureus biofilm formation.

    Science.gov (United States)

    Yang, Hang; Wang, Mengyue; Yu, Junping; Wei, Hongping

    2015-04-01

    Biofilm formation renders Staphylococcus aureus highly resistant to conventional antibiotics and host defenses. Four D-amino acids (D-Leu, D-Met, D-Trp and D-Tyr) have been reported to be able to inhibit biofilm formation and disassemble established S. aureus biofilms. We report here for the first time that both D- and L-isoforms of aspartate (Asp) inhibited S. aureus biofilm formation on tissue culture plates. Similar biofilm inhibition effects were also observed against other staphylococcal strains, including S. saprophyticus, S. equorum, S. chromogenes and S. haemolyticus. It was found that Asp at high concentrations (>10 mM) inhibited the growth of planktonic N315 cells, but at subinhibitory concentrations decreased the cellular metabolic activity without influencing cell growth. The decreased cellular metabolic activity might be the reason for the production of less protein and DNA in the matrix of the biofilms formed in the presence of Asp. However, varied inhibition efficacies of Asp were observed for biofilms formed by clinical staphylococcal isolates. There might be mechanisms other than decreasing the metabolic activity, e.g. the biofilm phenotypes, affecting biofilm formation in the presence of Asp.

  17. Matrix metalloproteinase inhibition in atherosclerosis and stroke.

    Science.gov (United States)

    Roycik, M D; Myers, J S; Newcomer, R G; Sang, Q-X A

    2013-09-01

    Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc-dependent proteases that degrade extracellular matrix (ECM), cell surface, and intracellular proteins. Vascular remodeling, whether as a function of normal physiology or as a consequence of a myriad of pathological processes, requires degradation of the ECM. Thus, the expression and activity of many MMPs are up-regulated in numerous conditions affecting the vasculature and often exacerbate vascular dysfunction. A growing body of evidence supports the rationale of using MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic vascular dementia. This manuscript will examine promising targets for MMP inhibition in atherosclerosis and stroke, reviewing findings in preclinical animal models and human patient studies. Strategies for MMP inhibition have progressed beyond chelating the catalytic zinc to functional blocking antibodies and peptides that target either the active site or exosites of the enzyme. While the inhibition of MMP activity presents a rational therapeutic avenue, the multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors that cause unintended side-effects hinder full realization of MMP inhibition as therapy for vascular disease. For optimal therapeutic effects to be realized, specific targets for MMP inhibition in these pathologies must first be identified and then attacked by potent and selective agents during the most appropriate timepoint.

  18. Genistein inhibits differentiation of primary human adipocytes.

    Science.gov (United States)

    Park, Hea Jin; Della-Fera, Mary Anne; Hausman, Dorothy B; Rayalam, Srujana; Ambati, Suresh; Baile, Clifton A

    2009-02-01

    Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.

  19. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

    Science.gov (United States)

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-08

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

  20. The role of (dis)inhibition in creativity: decreased inhibition improves idea generation.

    Science.gov (United States)

    Radel, Rémi; Davranche, Karen; Fournier, Marion; Dietrich, Arne

    2015-01-01

    There is now a large body of evidence showing that many different conditions related to impaired fronto-executive functioning are associated with the enhancement of some types of creativity. In this paper, we pursue the possibility that the central mechanism associated with this effect might be a reduced capacity to exert inhibition. We tested this hypothesis by exhausting the inhibition efficiency through prolonged and intensive practice of either the Simon or the Eriksen Flanker task. Performance on another inhibition task indicated that only the cognitive resources for inhibition of participants facing high inhibition demands were impaired. Subsequent creativity tests revealed that exposure to high inhibition demands led to enhanced fluency in a divergent thinking task (Alternate Uses Task), but no such changes occurred in a convergent task (Remote Associate Task; studies 1a and 1b). The same manipulation also led to a hyper-priming effect for weakly related primes in a Lexical Decision Task (Study 2). Together, these findings suggest that inhibition selectively affects some types of creative processes and that, when resources for inhibition are lacking, the frequency and the originality of ideas was facilitated.

  1. Structural basis for transcription inhibition by tagetitoxin.

    Science.gov (United States)

    Vassylyev, Dmitry G; Svetlov, Vladimir; Vassylyeva, Marina N; Perederina, Anna; Igarashi, Noriyuki; Matsugaki, Naohiro; Wakatsuki, Soichi; Artsimovitch, Irina

    2005-12-01

    Tagetitoxin (Tgt) inhibits transcription by an unknown mechanism. A structure at a resolution of 2.4 A of the Thermus thermophilus RNA polymerase (RNAP)-Tgt complex revealed that the Tgt-binding site within the RNAP secondary channel overlaps that of the stringent control effector ppGpp, which partially protects RNAP from Tgt inhibition. Tgt binding is mediated exclusively through polar interactions with the beta and beta' residues whose substitutions confer resistance to Tgt in vitro. Importantly, a Tgt phosphate, together with two active site acidic residues, coordinates the third Mg(2+) ion, which is distinct from the two catalytic metal ions. We show that Tgt inhibits all RNAP catalytic reactions and propose a mechanism in which the Tgt-bound Mg(2+) ion has a key role in stabilization of an inactive transcription intermediate. Remodeling of the active site by metal ions could be a common theme in the regulation of catalysis by nucleic acid enzymes.

  2. Mapuche herbal medicine inhibits blood platelet aggregation.

    Science.gov (United States)

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM : MeOH 1 : 1) and Cestrum parqui (DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  3. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

    Directory of Open Access Journals (Sweden)

    Laurent Meijer

    2008-10-01

    Full Text Available Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dualspecificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

  4. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  5. Complete corrosion inhibition through graphene defect passivation.

    Science.gov (United States)

    Hsieh, Ya-Ping; Hofmann, Mario; Chang, Kai-Wen; Jhu, Jian Gang; Li, Yuan-Yao; Chen, Kuang Yao; Yang, Chang Chung; Chang, Wen-Sheng; Chen, Li-Chyong

    2014-01-28

    Graphene is expected to enable superior corrosion protection due to its impermeability and chemical inertness. Previous reports, however, demonstrate limited corrosion inhibition and even corrosion enhancement of graphene on metal surfaces. To enable the reliable and complete passivation, the origin of the low inhibition efficiency of graphene was investigated. Combining electrochemical and morphological characterization techniques, nanometer-sized structural defects in chemical vapor deposition grown graphene were found to be the cause for the limited passivation effect. Extremely fast mass transport on the order of meters per second both across and parallel to graphene layers results in an inhibition efficiency of only ∼50% for Cu covered with up to three graphene layers. Through selective passivation of the defects by atomic layer deposition (ALD) an enhanced corrosion protection of more than 99% was achieved, which compares favorably with commercial corrosion protection methods.

  6. Mesoporous silica nanoparticles inhibit cellular respiration.

    Science.gov (United States)

    Tao, Zhimin; Morrow, Matthew P; Asefa, Tewodros; Sharma, Krishna K; Duncan, Cole; Anan, Abhishek; Penefsky, Harvey S; Goodisman, Jerry; Souid, Abdul-Kader

    2008-05-01

    We studied the effect of two types of mesoporous silica nanoparticles, MCM-41 and SBA-15, on mitochondrial O 2 consumption (respiration) in HL-60 (myeloid) cells, Jurkat (lymphoid) cells, and isolated mitochondria. SBA-15 inhibited cellular respiration at 25-500 microg/mL; the inhibition was concentration-dependent and time-dependent. The cellular ATP profile paralleled that of respiration. MCM-41 had no noticeable effect on respiration rate. In cells depleted of metabolic fuels, 50 microg/mL SBA-15 delayed the onset of glucose-supported respiration by 12 min and 200 microg/mL SBA-15 by 34 min; MCM-41 also delayed the onset of glucose-supported respiration. Neither SBA-15 nor MCM-41 affected cellular glutathione. Both nanoparticles inhibited respiration of isolated mitochondria and submitochondrial particles.

  7. Quantifying hydrate formation and kinetic inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Sloan, E.D.; Subramanian, S.; Matthews, P.N.; Lederhos, J.P.; Khokhar, A.A. [Colorado School of Mines, Golden, CO (United States). Center for Hydrate Research

    1998-08-01

    In the Prausnitz tradition, molecular and macroscopic evidence of hydrate formation and kinetic inhibition is presented. On the microscopic level, the first Raman spectra are presented for the formation of both uninhibited and inhibited methane hydrates with time. This method has the potential to provide a microscopic-based kinetics model. Three macroscopic aspects of natural gas hydrate kinetic inhibition are also reported: (1) The effect of hydrate dissociation residual structures was measured, which has application in decreasing the time required for subsequent formation. (2) The performance of a kinetic inhibitor (poly(N-vinylcaprolactam) or PVCap) was measured and correlated as a function of PVCap molecular weight and concentrations of PVCap, methanol, and salt in the aqueous phase. (3) Long-duration test results indicated that the use of PVCap can prevent pipeline blockage for a time exceeding the aqueous phase residence time in some gas pipelines.

  8. Inhibition of aluminum corrosion using Opuntia extract

    Energy Technology Data Exchange (ETDEWEB)

    El-Etre, A.Y

    2003-11-01

    The inhibitive action of the mucilage extracted from the modified stems of prickly pears, toward acid corrosion of aluminum, is tested using weight loss, thermometry, hydrogen evolution and polarization techniques. It was found that the extract acts as a good corrosion inhibitor for aluminum corrosion in 2.0 M HCl solution. The inhibition action of the extract was discussed in view of Langmuir adsorption isotherm. It was found that the adsorption of the extract on aluminum surface is a spontaneous process. The inhibition efficiency (IE) increases as the extract concentration is increased. The effect of temperature on the IE was studied. It was found that the presence of extract increases the activation energy of the corrosion reaction. Moreover, the thermodynamic parameters of the adsorption process were calculated. It was found also that the Opuntia extract provides a good protection to aluminum against pitting corrosion in chloride ion containing solutions.

  9. Silver-Palladium Surfaces Inhibit Biofilm Formation

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Schroll, Casper; Hilbert, Lisbeth Rischel

    2009-01-01

    Undesired biofilm formation is a major concern in many areas. In the present study, we investigated biofilm-inhibiting properties of a silver-palladium surface that kills bacteria by generating microelectric fields and electrochemical redox processes. For evaluation of the biofilm inhibition...... efficacy and study of the biofilm inhibition mechanism, the silver-sensitive Escherichia coli J53 and the silver-resistant E. coli J53[pMG101] strains were used as model organisms, and batch and flow chamber setups were used as model systems. In the case of the silver-sensitive strain, the silver......-palladium surfaces killed the bacteria and prevented biofilm formation under conditions of low or high bacterial load. In the case of the silver-resistant strain, the silver-palladium surfaces killed surface-associated bacteria and prevented biofilm formation under conditions of low bacterial load, whereas under...

  10. Neural inhibition enables selection during language processing.

    Science.gov (United States)

    Snyder, Hannah R; Hutchison, Natalie; Nyhus, Erika; Curran, Tim; Banich, Marie T; O'Reilly, Randall C; Munakata, Yuko

    2010-09-21

    Whether grocery shopping or choosing words to express a thought, selecting between options can be challenging, especially for people with anxiety. We investigate the neural mechanisms supporting selection during language processing and its breakdown in anxiety. Our neural network simulations demonstrate a critical role for competitive, inhibitory dynamics supported by GABAergic interneurons. As predicted by our model, we find that anxiety (associated with reduced neural inhibition) impairs selection among options and associated prefrontal cortical activity, even in a simple, nonaffective verb-generation task, and the GABA agonist midazolam (which increases neural inhibition) improves selection, whereas retrieval from semantic memory is unaffected when selection demands are low. Neural inhibition is key to choosing our words.

  11. Pyrilamine inhibits nicotine-induced catecholamine secretion.

    Science.gov (United States)

    Kim, Dong-Chan; Yun, So Jeong; Park, Yong-Soo; Jun, Dong-Jae; Kim, Dongjin; Jiten Singh, N; Kim, Sanguk; Kim, Kyong-Tai

    2014-07-01

    Function of nicotine, which induces activation of all parts of the body including our brain, has been receiving much attention for a long period of time and also been actively studied by researchers for its pharmacological actions in the central nervous system. The modulation of nicotine concentration and the inhibition of nicotine binding on target receptors in the brain are the key factors for smoking addiction therapy. In previous studies showed that influx of nicotine at the blood-brain barrier was through the pyrilamine-sensitive organic cation transporters. But the direct interacting mechanism of pyrilamine on the nicotine binding target receptors has not yet been clarified. The aim of the present study is to investigate the direct binding mechanisms of a pyrilamine on the nicotinic acetylcholine receptors (nAChRs). We found that pyrilamine shares the same ligand binding pocket of nicotine (NCT) on nAChRs but interacts with more amino acid residues than NCT does. The extended part of pyrilamine interacts with additional residues in the ligand binding pocket of nAChRs which are located nearby the entrance of the binding pocket. The catecholamine (CA) secretion induced by nAChR agonist (NCT') was significantly inhibited by the pyrilamine pretreatment. Real time carbon-fiber amperometry confirmed the inhibition of the NCT'-induced exocytosis by pyrilamine in a single cell level. We also found that pyrilamine inhibited the NCT'-induced [Ca(2+)]i. In contrast, pyrilamine did not affect the increase in calcium induced by high K(+). Overall, these data suggest that pyrilamine directly docks into the ligand binding site of nAChRs and specifically inhibits the nAChR-mediated effects thereby causing inhibition of CA secretion. Therefore, pyrilamine may play an important role to explore new treatments to aid smoking cessation.

  12. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  13. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    DEFF Research Database (Denmark)

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... of endocrine disruption. Results: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis and it was correlated with a reduced testosterone production. The inhibition of PG synthesis occurs...

  14. Inhibition of spinach bolting by growth regulators

    Directory of Open Access Journals (Sweden)

    Jan Borkowski

    2015-06-01

    Full Text Available Spinach (Spinacia oleracea L. plants must be harvested during a short period of time because they bolt just after producing some edible leaves. Maleic hydrazide (MH and its commercial preparation "Antyrost" were found to inhibit bolting very strongly. The preparation Off-shoot-O showed very weak activity in suppressing bolting but diminished markedly the resistance of spinach plants to fungus diseases. Triiodobenzoic acid stimulated bolting, and the retardant succinic acid-2-2-dimethylhydrazide (SADH did not affect bolting. Application of MH to inhibit spinach bolting cannot be recommended in practice before investigating the residues of this compound in leaves.

  15. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    OpenAIRE

    Alicja Zajdel; Adam Wilczok; Ludmiła Węglarz; Zofia Dzierżewicz

    2013-01-01

    Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the deca...

  16. Cerebellar cortical inhibition and classical eyeblink conditioning.

    Science.gov (United States)

    Bao, Shaowen; Chen, Lu; Kim, Jeansok J; Thompson, Richard F

    2002-02-01

    The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

  17. Hawthorn extract inhibits human isolated neutrophil functions.

    Science.gov (United States)

    Dalli, Ernesto; Milara, Javier; Cortijo, Julio; Morcillo, Esteban J; Cosín-Sales, Juan; Sotillo, José Francisco

    2008-06-01

    Hawthorn extract is a popular herbal medicine given as adjunctive treatment for chronic heart failure. In contrast to the cardiac properties of hawthorn extract, its anti-inflammatory effect has been scarcely investigated. This study examines the effects of a dry extract of leaves and flowers of Crataegus laevigata on various functional outputs of human neutrophils in vitro. Incubation of human neutrophils obtained from peripheral blood of healthy donors with C. laevigata extract (0.75-250 microg/ml) inhibited N-formyl-Met-Leu-Phe (FMLP)-induced superoxide anion generation, elastase release and chemotactic migration with potency values of 43.6, 21.9, and 31.6 microg/ml, respectively. By contrast, serum-opsonized zymosan-induced phagocytosis was unaltered by plant extract. C. laevigata extract (125 microg/ml) reduced FMLP-induced leukotriene B(4) production and lipopolysaccharide-induced generation of tumour necrosis factor-alpha and interleukin-8. Extract inhibited FMLP-induced intracellular calcium signal with potency of 17.4 microg/ml. Extract also markedly inhibited the extracellular calcium entry into calcium-depleted neutrophils, and the thapsigargin-induced intracellular calcium response. In conclusion, C. laevigata extract inhibited various functional outputs of activated human neutrophils which may be relevant to the pathophysiology of cardiac failure.

  18. Stress kinase inhibition modulates acute experimental pancreatitis