Norepinephrine and Dopamine as Learning Signals
Harley, Carolyn W.
2004-01-01
The present review focuses on the hypothesis that norepinephrine (NE) and dopamine (DA) act as learning signals. Both NE and DA are broadly distributed in areas concerned with the representation of the world and with the conjunction of sensory inputs and motor outputs. Both are released at times of novelty and uncertainty, providing plausible signal events for updating representations and associations. These catecholamines activate intracellular machinery postulated to serve as a memory-formation cascade. Yet, despite the plausibility of an NE and DA role in vertebrate learning and memory, most evidence that they provide a learning signal is circumstantial. The major weakness of the data available is the lack of a specific description of how the neural circuit modulated by NE or DA participates in the learning being analyzed. Identifying a conditioned stimuli (CS) representation would facilitate the identification of a learning signal role for NE or DA. Describing how the CS representation comes to relate to learned behavior, either through sensory-sensory associations, in which the CS acquires the motivational significance of reward or punishment, thus driving appropriate behavior, or through direct sensory-motor associations is necessary to identify how NE and DA participate in memory creation. As described here, evidence consistent with a direct learning signal role for NE and DA is seen in the changing of sensory circuits in odor preference learning (NE), defensive conditioning (NE), and auditory cortex remodeling in adult rats (DA). Evidence that NE and DA contribute to normal learning through unspecified mechanisms is extensive, but the details of that support role are lacking. PMID:15656268
Striatal norepinephrine efflux in l-DOPA-induced dyskinesia.
Ostock, Corinne Y; Bhide, Nirmal; Goldenberg, Adam A; George, Jessica A; Bishop, Christopher
2018-03-01
l-DOPA remains the primary treatment for Parkinson's disease (PD). Unfortunately, its therapeutic benefits are compromised by the development of abnormal involuntary movements (AIMs) known as l-DOPA-induced dyskinesia (LID). The norepinephrine (NE) system originating in the locus coeruleus is profoundly affected in PD and known to influence dopamine (DA) signaling. However, the effect of noradrenergic loss on l-DOPA-induced striatal monoamine efflux and Parkinsonian motor behavior remains controversial and is frequently overlooked in traditional animal models of LID. Thus, the current study sought to determine whether degeneration of the DA and/or NE system(s) altered l-DOPA-induced striatal monoamine efflux in hemiparkinsonian rats with additional NE loss induced by the potent NE-toxin α DA beta hydroxylase (DBH)-saporin. Sham-, DA-, NE-, and dual DA + NE-lesioned rats were treated with l-DOPA (6 mg/kg, s.c.) for 2 weeks. Thereafter, l-DOPA-mediated striatal monoamine efflux was measured with in vivo microdialysis, and concurrent AIMs testing occurred to determine responsiveness to l-DOPA. Noradrenergic lesions exacerbated parkinsonian motor deficits but did not significantly alter LID expression or corresponding l-DOPA-induced striatal monoamine efflux. Interestingly, l-DOPA-induced striatal NE efflux rather than DA efflux, corresponded more closely with dyskinesia severity. Moreover, marked reductions in striatal NE tissue concentration did not appear to impact l-DOPA-induced striatal NE efflux. The current study implicates l-DOPA-induced striatal NE as an important factor in LID expression and demonstrates the importance of developing treatment strategies that co-modulate the NE and DA systems. Copyright © 2018 Elsevier Ltd. All rights reserved.
Monoamine transporter and receptor interaction profiles of a new series of designer cathinones.
Simmler, L D; Rickli, A; Hoener, M C; Liechti, M E
2014-04-01
Psychoactive β-keto amphetamines (cathinones) are sold as "bath salts" or "legal highs" and recreationally abused. We characterized the pharmacology of a new series of cathinones, including methedrone, 4-methylethcathinone (4-MEC), 3-fluoromethcathinone (3-FMC), pentylone, ethcathinone, buphedrone, pentedrone, and N,N-dimethylcathinone. We investigated norepinephrine (NE), dopamine (DA), and serotonin (5-HT) uptake inhibition using human embryonic kidney 293 (HEK 293) cells that express the respective human monoamine transporter, the drug-induced efflux of NE, DA, and 5-HT from monoamine-preloaded cells, and binding affinity to monoamine transporters and receptors. All of the cathinones were potent NE uptake inhibitors but differed in their DA vs. 5-HT transporter inhibition profiles and monoamine release effects. Methedrone was a more potent 5-HT than DA transporter inhibitor and released NE and 5-HT similar to para-methoxymethamphetamine (PMMA), para-methoxyamphetamine (PMA), 4-methylthioamphetamine (4-MTA), and 3,4-methylenedioxymethamphetamine (MDMA). 4-MEC and pentylone equipotently inhibited all of the monoamine transporters and released 5-HT. Ethcathinone and 3-FMC inhibited NE and DA uptake and released NE, and 3-FMC also released DA similar to N-ethylamphetamine and methamphetamine. Pentedrone and N,N-dimethylcathinone were non-releasing NE and DA uptake inhibitors as previously shown for pyrovalerone cathinones. Buphedrone preferentially inhibited NE and DA uptake and also released NE. None of the cathinones bound to rodent trace amine-associated receptor 1, in contrast to the non-β-keto-amphetamines. None of the cathinones exhibited relevant binding to other monoamine receptors. In summary, we found considerable differences in the monoamine transporter interaction profiles among different cathinones and compared with related amphetamines. Copyright © 2013 Elsevier Ltd. All rights reserved.
Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula
Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo
2015-01-01
The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845
Dundon, Carolyn M; Rellini, Alessandra H
2012-10-01
Research suggests that there are three interrelated, yet distinct, emotion-motivation brain systems for human love (lust, romantic love, and attachment), each associated with a unique catecholaminergic and hormonal profile. Of interest for the current study are norepinephrine (NE) and dopamine (DA), which have a hypothesized connection with romantic love. As NE and DA are also known to facilitate sexual arousal, it is plausible that NE and DA may have a greater positive association with the sexual arousal responses of women in romantic love compared with women in lust. This study investigated if the effects of NE and DA activity on sexual arousal responses would differ depending on emotion-motivation state (Lust or Romantic). Physiological sexual arousal was assessed by photoplethysmography and subjective sexual arousal was assessed with a participant-controlled lever. Seventeen women were included in the Lust group and 29 in the Romantic group. All participants provided a urine sample (to assess NE and DA) and completed a psychophysiological assessment. Elevated NE was positively and significantly associated with greater subjective and physiological sexual arousal for the Lust group, but not for the Romantic group. Similarly, elevated DA was positively and significantly associated with greater subjective sexual arousal for the Lust group, but not for the Romantic group. The sexual arousal responses of women in the Lust group, but not in the Romantic group, were positively and significantly associated with elevated NE and DA. It is feasible that, when women are seeking a partner (Lust), NE and DA may facilitate attention toward sexually relevant stimuli. © 2012 International Society for Sexual Medicine.
Chen, Joyce C; Tsai, Houng-Wei; Yeh, Kuei-Ying; Tai, Mei-Yun; Tsai, Yuan-Feen
2008-07-01
The correlation between dopamine (DA) and norepinephrine (NE) levels in the bed nucleus of the stria terminalis (BNST) and male sexual behavior was examined in middle-aged rats. Male rats (18-19 months) were divided into: (a) Group MIE, consisting of rats showing mounts, intromissions, and ejaculations; (b) Group MI, composed of rats showing mounts and intromissions, but no ejaculation; and (c) Group NC, consisting of noncopulators. Young adult rats (4-5 months) displaying complete copulatory behavior were used as the control. Tissue levels of DA, NE, and DA metabolites in the BNST were measured by high-pressure liquid chromatography. DA, but not NE, levels in MIE rats were significantly lower than those in young controls. DA and NE levels in MIE rats were significantly higher than those in NC rats. These results suggest that DA and NE in the BNST might play an important role in the control of male sexual behavior in middle-aged rats.
Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan
2015-01-01
We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Since decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage-treated daily with excipient vehicle, AGN (5 mg per mouse) or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA and their common metabolite decursinol indicated similar retention from AGN vs. D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN-and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN-and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal-transition, invasion-metastasis and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. PMID:26116406
Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan
2015-09-01
We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Because decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage treated daily with excipient vehicle, AGN (5 mg per mouse), or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA, and their common metabolite decursinol indicated similar retention from AGN versus D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN- and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN- and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed that AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell-cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal transition, invasion-metastasis, and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. ©2015 American Association for Cancer Research.
Ye, Nengsheng; Li, Jian
2014-08-01
A novel capillary electrochromatography method was developed for the determination of dopamine (DA), epinephrine (EP), and norepinephrine (NE) by using a graphene oxide (GO) molecularly imprinted polymers (MIPs) coated capillary. In this article, GO was introduced as supporting matrix to synthesize MIPs in the presence of DA as template molecule. Then GO MIPs were used as the stationary phase in electrochromatography for the determination of DA, EP, and NE. The separation of these three analytes was achieved under the optimal conditions with a satisfactory correlation coefficients (R(2) ) > 0.9957 in the range of 5.0-200.0 μg/mL for EP and NE, and 20.0-200.0 μg/mL for DA, respectively. The RSDs for the determination of three analytes were <6.19%, and the detection limits were 1.25 μg/mL for EP and NE, and 10.0 μg/mL for DA, respectively. Finally, this method was used for the determination of DA, EP, and NE in human serum and DA hydrochloride injection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bradley, T.; Hjemdahl, P.; DiBona, G.F.
1987-02-01
The renal overflow of norepinephrine (NE) and dopamine (DA) to plasma from the innervated kidney was studied at rest and during sympathetic nervous system activation by bilateral carotid artery occlusion (BCO) in vagotomized dogs under barbiturate or barbiturate/nitrous oxide anesthesia. BCO elevated arterial pressure and the arterial plasma concentration of NE, DA, and epinephrine (Epi). Renal vascular resistance (renal arterial pressure kept constant) increased by 15 +/- 7% and the net renal venous outflows (renal veno-arterial concentration difference x renal plasma flow) of NE and DA were enhanced. To obtain more correct estimates of the renal contribution to the renalmore » venous catecholamine outflow, they corrected for the renal extraction of arterial catecholamines, assessed as the extractions of (/sup 3/H)NE, (/sup 3/H)DA, or endogenous Epi. The (/sup 3/H)NE corrected renal NE overflow to plasma increased from 144 +/- 40 to 243 +/- 64 pmol-min/sup -1/ during BCO, which, when compared with a previous study of the (/sup 3/H)NE corrected renal NE overflow to plasma evoked by electrical renal nerve stimulation, corresponds to a 40% increase in nerve impulse frequency from approx. 0.6 Hz. If the renal catecholamine extraction was not taken into account the effect of BCO was underestimated. The renal DA overflow to plasma was about one-fifth of the NE overflow both at rest and during BCO, indicating that there was no preferential activation of noradrenergic or putative dopaminergic nerves by BCO.« less
Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun
2016-01-01
Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. PMID:26790349
The effects of four major chlorotriazine metabolites on the constitutive synthesis of the catecholamines dopamine (DA) and norepinephrine (NE) were examined using undifferentiated PC12 cells. NE release and intracellular DA and NE concentrations were quantified following treatme...
Lin, Chen-Cheng; Tung, Che-Se; Lin, Pin-Hsuan; Huang, Chuen-Lin; Liu, Yia-Ping
2016-09-01
Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun
2016-06-15
Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.
Russell, V; Allie, S; Wiggins, T
2000-12-20
Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.
Monoaminc and metabolite levels in the cerebrospinal fluid of hibernating and euthermic marmots.
Reid; Kilduff; Romero; Florant; Dement; Heller
1992-03-01
Cerebrospinal fluid from yellow-bellied marmots, Marmota flaviventris, was analysed for monoamine and monoamine metabolite content during euthermia and deep hibernation. Dopamine (DA) levels were decreased, while DA metabolite levels, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were dramatically increased in hibernating marmots. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels were also greatly enhanced during hibernation while norepinephrine (NE) levels were only moderately increased. These findings demonstrate that cerebrospinal monoamine levels are dynamically altered during hibernation, such that DA versus 5-HT and NE levels undergo opposite changes. Therefore, these data indicate that DA, 5-HT and NE neuronal systems are differentially altered during hibernation in mammals.
Chen, Joyce C; Tsai, Houng-Wei; Yeh, Kuei-Ying; Tai, Mei-Yun; Tsai, Yuan-Feen
2007-12-12
The correlation between male sexual behavior and catecholamine levels in the medial preoptic area (MPOA) and arcuate nucleus (ARN) was studied in middle-aged rats. Male rats (18-19 months) were assigned to three groups: (1) Group MIE, consisting of rats showing mounts, intromissions, and ejaculations; (2) Group MI, consisting of rats showing mounts and intromissions, but no ejaculation; and (3) Group NC, consisting of non-copulators showing no sexual behavior. Young adult rats (4-5 months) displaying complete copulatory behavior were used as the control group. Dopamine (DA) and norepinephrine (NE) tissue levels in the MPOA and ARN were measured by high pressure liquid chromatography with electrochemical detection. There were no differences between MIE rats and young controls in DA or NE tissue levels in these two brain areas. Furthermore, no differences were found between the MI and NC groups in DA or NE tissue levels in either the MPOA or ARN. DA tissue levels in the MPOA and ARN in the MI and NC groups were significantly lower than those in the MIE group. NE tissue levels in the MPOA of the NC group were significantly lower than those in the MIE group, but no differences in NE tissue levels in the ARN were seen between the four groups. These results suggest that, in male rats, complete male sexual performance is related to tissue levels of DA, but not of NE, in the MPOA and/or ARN. Furthermore, ejaculatory behavior might be associated with critical DA tissue levels in the MPOA and/or ARN in middle-aged rats.
The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity
Ferrucci, Michela; Giorgi, Filippo S; Bartalucci, Alessia; Busceti, Carla L; Fornai, Francesco
2013-01-01
The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters. PMID:23814540
Huang, Mei; Kwon, Sunoh; Oyamada, Yoshihiro; Rajagopal, Lakshmi; Miyauchi, Masanori; Meltzer, Herbert Y
2015-11-01
Blonanserin is a novel atypical antipsychotic drug (APD), which, unlike most atypical APDs, has a slightly higher affinity for dopamine (DA) D2 than serotonin (5-HT)2A receptors, and is an antagonist at both, as well as at D3 receptors. The effects of atypical APDs to enhance rodent cortical, hippocampal, limbic, and dorsal striatal (dSTR) DA and acetylcholine (ACh) release, contribute to their ability to improve novel object recognition (NOR) in rodents treated with sub-chronic (sc) phencyclidine (PCP) and cognitive impairment associated with schizophrenia (CIAS). Here we determined the ability of blonanserin, the D3 antagonist NGB 2904, and the typical APD, haloperidol, a D2 antagonist, to enhance neurotransmitter efflux in the medial prefrontal cortex (mPFC) and dSTR of mice, and to ameliorate the scPCP-induced deficit in NOR in rats. Blonanserin, 10mg/kg, i.p., increased DA, norepinephrine (NE), and ACh efflux in mPFC and dSTR. NGB 2904, 3mg/kg, increased DA and ACh, but not NE, efflux in mPFC, and DA, but not ACh, efflux in dSTR. Haloperidol increased DA and NE efflux in dSTR only. The selective D3 agonist PD 128907 partially blocked the blonanserin-induced cortical ACh, DA, NE and striatal DA efflux. NGB 2904, 3mg/kg, like blonanserin, 1mg/kg, and the combination of sub-effective doses of NGB 2904 and blonanserin (both 0.3mg/kg), ameliorated the scPCP-induced NOR deficit in rats. These results suggest that D3 receptor blockade may contribute to the ability of blonanserin to increase cortical DA and ACh efflux, as well as to restore NOR and improve CIAS. Copyright © 2015 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liang, N.Y.; Hower, J.A.; Borchardt, R.T.
1985-09-01
Inhibitors of phenylethanolamine N-methyltransferase (PNMT) and amphetamine were evaluated for their effects on the uptake of (TH)-norepinephrine (TH-NE) and the release of endogenous NE and dopamine (DA) from chopped rat brain tissues. Unlike amphetamine, all of PNMT inhibitors tested produced only slight inhibition of (TH)-NE uptake into chopped cerebral cortex. 2,3-Dichloro-alpha-methylbenzylamine (DCMB) and 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF64139), but not 2-cyclooctyl-2-hydroxyethylamine (CONH) and 1-aminomethylcycloundecanol (CUNH) produced slight release of endogenous NE and DA from chopped hypothalami, but their effects were less pronounced than those produced by amphetamine.
Antihistamine effect on synaptosomal uptake of serotonin, norepinephrine and dopamine
NASA Technical Reports Server (NTRS)
Brown, P. A.; Vernikos, J.
1980-01-01
A study on the effects of five H1 and H2 antihistamines on the synaptosomal uptake of serotonin (5HT), norepinephrine (NE), and dopamine (DA) is presented. Brain homogenates from female rats were incubated in Krebs-Ringer phosphate buffer solution in the presence of one of three radioactive neurotransmitters, and one of the five antihistamines. Low concentrations of pyrilamine competitively inhibited 5HT uptake, had little effect on NE uptake, and no effect on DA uptake. Promethazine, diphenhydramine, metiamide, and cimetidine had no effect on 5HT or DA uptake at the same concentration. Diphenhydramine had a small inhibitory effect on NE uptake. It is concluded that pyrilamine is a selective and potent competitive inhibitor of 5HT uptake at concentrations between .05 and .5 micromolars.
Defining and Assessing the Impact to the Combat/Weapon Systems of a Ship Post Major Overhaul
2013-06-01
vig ati on...ch Ra da r ( SP S‐6 7) Un ne ce ss ary fo r M iss ion 0 Lik e t o h av e 0.2 5 FA LS E 0 0 Na vig ati on Da ta (W SN ‐7 ) Ne ce ss ar y 0.5...E 0 0 Na vig ati on Di str ibu tio n ( NA VS SI) Ne ce ss ar y 0.5 Ne ce ss ary 0.5 FA LS E 0 0 Cr itic al Na vig ati on D ist rib ut ion
1993-01-01
INSTITUTE I cIEINTIFIC•IEPOET SR93-16 Effects of S-2-(3-Methylaminopropylamino)ethyl Phosphorothioic Acid (WR-3689), Alone or Combined with Caffeine...and 220 pg/mg and 69 and 94 pg/mg of hypothalamic tissue, respectively. WR- 3689 had no effect on the content of NE and DA. In contrast, NE increased...increased to 142 ± 13 pg/mg (P < 0.05) 4 hr after injection of 40 mg/kg of caffeine. The combination of WR-3689 and caffeine had no effect on NE and DA
Latagliata, Emanuele Claudio; Puglisi-Allegra, Stefano; Ventura, Rossella; Cabib, Simona
2018-01-01
Previous findings from this laboratory demonstrate: (1) that different classes of addictive drugs require intact norepinephrine (NE) transmission in the medial pre Frontal Cortex (mpFC) to promote conditioned place preference and to increase dopamine (DA) tone in the nucleus accumbens shell (NAc Shell); (2) that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3) that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances. PMID:29434542
Norepinephrine and Stimulant Addiction
Sofuoglu, Mehmet; Sewell, R. Andrew
2008-01-01
No pharmacotherapies are approved for stimulant use disorders, which are an important public health problem. Stimulants increase synaptic levels of the monoamines dopamine (DA), serotonin (5-HT), and norepinephrine (NE). Stimulant reward is attributable mostly to increased DA in the reward circuitry, although DA stimulation alone cannot explain the rewarding effects of stimulants. The noradrenergic system, which uses NE as the main chemical messenger, serves multiple brain functions including arousal, attention, mood, learning, memory, and stress response. In preclinical models of addiction, NE is critically involved in mediating stimulant effects including sensitization, drug discrimination, and reinstatement of drug seeking. In clinical studies, adrenergic blockers have shown promise as treatments for cocaine abuse and dependence, especially in patients experiencing severe withdrawal symptoms. Disulfiram, which blocks NE synthesis, increased the number of cocaine-negative urines in five randomized clinical trials. Lofexidine, an α2-adrenergic agonist, reduces the craving induced by stress and drug cues in drug users. In addition, the norepinephrine transporter (NET) inhibitor atomoxetine attenuates some of d-amphetamine’s subjective and physiological effects in humans. These findings warrant further studies evaluating noradrenergic medications as treatments for stimulant addiction. PMID:18811678
Effect of temperature stress on circulating biogenic amines in bovine.
Davis, T P; Johnson, H D; Gehrke, C W
1984-01-01
A sensitive, simple and selective chromatographic method using high performance liquid chromatography was developed to measure circulating levels of histamine (HI), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) as indicators of response to thermal stress in two breeds of cattle. Duplicate exposures for 8 hr to 13 degrees C resulted in significantly elevated plasma NE and DA in longhorns but not in Herefords and suggest a relatively greater sensitivity to the cold (13 degrees C) in the longhorn. Environmental temperatures of 32 and 42 degrees C significantly increased rectal temperatures of both breeds with much higher rectal temperatures in Herefords. The 32 and 42 degrees C effects on circulating NE and DA of Herefords were highly significant but not in the longhorn. However, heat stress significantly elevated HI and 5-HT in the longhorn which may account for their relatively greater heat tolerance based on their lower rectal temperatures.
Gingerich, W.H.; Drottar, K.R.
1989-01-01
The effects of surgery and anesthesia on concentrations of plasma epinephrine (E), norepinephrine (NE), and dopamine (DA) were investigated in rainbow trout fitted with dorsal aorta cannulae. Baseline catecholamines (CA) concentrations, established in resting rainbow trout, were 1.55 ± 0.90 ϱmol/ml (X ± SD) for E, 2.07 ± 1.26 for NE, and 1.33 ± 0.87 for DA. These values were based on the pooled analyses of five individual fish taken over seven different sampling periods. The E:NE ratio in resting fish was always less than 1.0. In a second experiment, fish were subjected to dorsal aorta cannulation and sequential blood samples were taken immediately after surgery, and 6, 24, and 48 hr later. Plasma E concentrations were 36 times greater than baseline values in the first sample; NE was 15 times greater and DA was 41 times greater. After surgery, plasma concentrations of all CAs fell rapidly but values were still higher than baseline 6 hr after surgery, then were near baseline at 24 and 48 hr after surgery. The E:NE ratio was about 3.0 immediately after surgery, dropped to 1.8 at 6 hr, and was about 1.0 at 24 and 48 hr. In a third experiment, plasma CAs were determined in a group of five animals anesthetized with tricaine methanesulfonate (100 mg/ml) to advanced anesthesia, and then allowed to recover in flowing well water over a 12-hr observation period. Plasma E and NE concentrations in the fish during early anes-thesia (1.14 ± 0.14 min) were not significantly different from preanesthesia values. During advanced anesthesia (2.31 ± 0.21 min), values for E and NE were significantly greater and continued to be elevated during the 12-hr recovery period. The E:NE ratio exceeded 1.0 during advanced anesthesia and for the rest of the experiment.
Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency
NASA Technical Reports Server (NTRS)
Kim, Chun-Hyung; Zabetian, Cyrus P.; Cubells, Joseph F.; Cho, Sonhae; Biaggioni, Italo; Cohen, Bruce M.; Robertson, David; Kim, Kwang-Soo
2002-01-01
Norepinephrine (NE), a key neurotransmitter of the central and peripheral nervous systems, is synthesized by dopamine beta-hydroxylase (DBH) that catalyzes oxidation of dopamine (DA) to NE. NE deficiency is a congenital disorder of unknown etiology, in which affected patients suffer profound autonomic failure. Biochemical features of the syndrome include undetectable tissue and circulating levels of NE and epinephrine, elevated levels of DA, and undetectable levels of DBH. Here, we report identification of seven novel variants including four potentially pathogenic mutations in the human DBH gene (OMIM 223360) from analysis of two unrelated patients and their families. Both patients are compound heterozygotes for variants affecting expression of DBH protein. Each carries one copy of a T-->C transversion in the splice donor site of DBH intron 1, creating a premature stop codon. In patient 1, there is a missense mutation in DBH exon 2. Patient 2 carries missense mutations in exons 1 and 6 residing in cis. We propose that NE deficiency is an autosomal recessive disorder resulting from heterogeneous molecular lesions at DBH. Copyright 2002 Wiley-Liss, Inc.
76 FR 76337 - Television Broadcasting Services; Lincoln, NE
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-07
... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-192, RM-11646; DA 11-1924] Television Broadcasting Services; Lincoln, NE AGENCY: Federal Communications Commission. ACTION: Proposed..., 2012, and reply comments on or before January 23, 2012. ADDRESSES: Federal Communications Commission...
Madec, Morgan; Pecheux, François; Gendrault, Yves; Rosati, Elise; Lallement, Christophe; Haiech, Jacques
2016-10-01
The topic of this article is the development of an open-source automated design framework for synthetic biology, specifically for the design of artificial gene regulatory networks based on a digital approach. In opposition to other tools, GeNeDA is an open-source online software based on existing tools used in microelectronics that have proven their efficiency over the last 30 years. The complete framework is composed of a computation core directly adapted from an Electronic Design Automation tool, input and output interfaces, a library of elementary parts that can be achieved with gene regulatory networks, and an interface with an electrical circuit simulator. Each of these modules is an extension of microelectronics tools and concepts: ODIN II, ABC, the Verilog language, SPICE simulator, and SystemC-AMS. GeNeDA is first validated on a benchmark of several combinatorial circuits. The results highlight the importance of the part library. Then, this framework is used for the design of a sequential circuit including a biological state machine.
Thakare, Vishnu N; Aswar, Manoj K; Kulkarni, Yogesh P; Patil, Rajesh R; Patel, Bhoomika M
2017-10-01
Silymarin is a polyphenolic flavonoid of Silybum marianum, exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique. Wistar rats were administered with silymarin at a dose of 100mg/kg and 200mg/kg, by per oral in OBX and sham operated rats. Behavioral (ambulatory and rearing activity and immobility time), neurochemical [serotonin (5-HT), dopamine (DA), norepinephrine (NE) and brain derived neurotrophic factor (BDNF) level], biochemical (MDA formation, IL-6, TNF-α and antioxidants) changes in hippocampus and cerebral cortex along with serum corticosterone were investigated. Rats subjected to OBX elicited significant increase in immobility time, ambulatory and rearing behaviors, reduced BDNF level, 5-HT, DA, NE and antioxidant parameters along with increased serum corticosterone, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex compared to sham operated rats. Administration of with silymarin significantly attenuated immobility time, ambulatory and rearing behaviors, serum corticosterone and improved BDNF expression, 5-HT, DA, NE and antioxidant paradigms in cerebral cortex as well as hippocampus. In addition, silymarin attenuated IL-6, and TNF-α significantly in hippocampus and cerebral cortex in OBX rats. Thus, silymarin exhibits anti-depressant-like activity in OBX rats due to alterations in several neurotransmitters, endocrine and immunologic systems, including BDNF, 5-HT, DA, NE, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex as well as serum corticosterone. Copyright © 2017 Elsevier Inc. All rights reserved.
Billes, Sonja K; Cowley, Michael A
2007-04-01
Although originally developed as an antidepressant, long-term bupropion (BUP) treatment was recently shown to cause 5-8% weight loss over placebo in clinical trials with obese adults. BUP's antidepressant properties probably stem from its ability to increase extracellular brain dopamine (DA) and norepinephrine (NE) levels by inhibiting their reuptake, although the mechanism of BUP-induced weight loss is unknown. Consequently, the acute effects of DA and NE reuptake inhibition on energy homeostasis were determined by measuring food intake and body weight in mice following peripheral (intraperitoneal (i.p.)) administration of either BUP, a selective DA (GBR12783), or a selective NE (nisoxetine (NIS)) reuptake inhibitor. BUP, GBR12783, and NIS all dose-dependently decreased acute food intake in fasted lean mice. The ability of BUP to decrease food intake was independent of its ability to cause a temporary increase in locomotor activity. The inhibitory effects of acute GBR12783 and NIS on short-term food intake were additive. Subchronic (via mini-osmotic pump) administration of GBR12783 and NIS produced a transient nonadditive effect on food intake, but produced an additive reduction in body weight (8-10%). Because obesity can affect catecholaminergic signaling, we determined the effects of i.p. BUP, GBR12783, and NIS on short-term food intake in obese mice. Acute BUP, GBR12783, and NIS dose-dependently reduced acute food intake, and the additive effect of GBR12783 and NIS on acute food intake was preserved in obese mice. These results demonstrate that combined DA and NE reuptake inhibition produces additive effects on energy balance in lean and obese mice on both standard and high-fat diet, providing a foundation for further research on the effects of BUP and similar compounds on energy balance in mice.
Clozapine response and plasma catecholamines and their metabolites.
Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J
1993-02-01
The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.
Haloperidol response and plasma catecholamines and their metabolites.
Green, A I; Alam, M Y; Boshes, R A; Waternaux, C; Pappalardo, K M; Fitzgibbon, M E; Tsuang, M T; Schildkraut, J J
1993-06-01
Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.
Zhang, Qiyang; Gong, Maojun
2016-06-10
Flow-gated capillary electrophoresis (CE) coupled with microdialysis has become an important tool for in vivo bioanalytical measurements because it is capable of performing rapid and efficient separations of complex biological mixtures thus enabling high temporal resolution in chemical monitoring. However, the limit of detection (LOD) is often limited to a micro- or nano-molar range while many important target analytes have picomolar or sub-nanomolar levels in brain and other tissues. To enhance the capability of flow-gated CE for catecholamine detection, a novel and simple on-line sample preconcentration method was developed exclusively for fluorescent derivatives of catecholamines that were fluorogenically derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide. The effective preconcentration coupled with the sensitive laser-induced fluorescence (LIF) detection lowered the LOD down to 20pM for norepinephrine (NE) and 50pM for dopamine (DA) at 3-fold of S/N ratio, and the signal enhancement was estimated to be over 100-fold relative to normal injection when standard analytes were dissolved in artificial cerebrospinal fluid (aCSF). The basic focusing principle is novel since the sample plug contains borate while the background electrolyte (BGE) is void of borate. This strategy took advantage of the complexation between diols and borate, through which one negative charge was added to the complex entity. The sample derivatization mixture was electrokinetically injected into a capillary via the flow-gated injection, and then NE and DA derivatives were selectively focused to a narrow zone by the reversible complexation. Separation of NE and DA derivatives was executed by incoming surfactants of cholate and deoxycholate mixed in the front BGE plug. This on-line preconcentration method was finally applied to the detection of DA in rat cerebrospinal fluid (CSF) via microdialysis and on-line derivatization. It is anticipated that the method would be valuable for in vivo monitoring of DA and NE in various brain regions of live animals on flow-gated CE or microchip platforms. Published by Elsevier B.V.
Huang, Hui; Gao, Yuan; Shi, Fanping; Wang, Guannan; Shah, Syed Mazhar; Su, Xingguang
2012-03-21
In this paper, a sensitive water-soluble fluorescent conjugated polymer biosensor for catecholamine (dopamine DA, adrenaline AD and norepinephrine NE) was developed. In the presence of horse radish peroxidase (HRP) and H(2)O(2), catecholamine could be oxidized and the oxidation product of catecholamine could quench the photoluminescence (PL) intensity of poly(2,5-bis(3-sulfonatopropoxy)-1,4-phenylethynylenealt-1,4-poly(phenylene ethynylene)) (PPESO(3)). The quenching PL intensity of PPESO(3) (I(0)/I) was proportional to the concentration of DA, AD and NE in the concentration ranges of 5.0 × 10(-7) to 1.4 × 10(-4), 5.0 × 10(-6) to 5.0 × 10(-4), and 5.0 × 10(-6) to 5.0 × 10(-4) mol L(-1), respectively. The detection limit for DA, AD and NE was 1.4 × 10(-7) mol L(-1), 1.0 × 10(-6) and 1.0 × 10(-6) mol L(-1), respectively. The PPESO(3)-enzyme hybrid system based on the fluorescence quenching method was successfully applied for the determination of catecholamine in human serum samples with good accuracy and satisfactory recovery. The results were in good agreement with those provided by the HPLC-MS method.
[Effect of bitumen fume on neurotransmitter and ultrastructure in mice brain].
Li, Hai-Ling; Guo, Xiang-Yun; Feng, San-Wei; Liu, Chang-Hai
2006-12-01
To observe the effects of bitumen fume on neurotransmitter and ultrastructure of mice brain and to investigate the toxicity of bitumen fume on nerve system of mice brain. The experimental mice were forced to inhale the bitumen fume at different exposure level and in different time periods. The contents of the three transmitters dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT) in mice brain were measured by the fluorescence meanwhile ultrastructure of mice brain was observed by electronic microscope. The ultrastructure of mice brain was observed under transmission electron microscopy. The contents of DA, NE and 5-HT in all groups decreased with the increasing of dose and prolonging of time (after 8 week, with the increasing of exposure lever, the content of DA, NE, 5-HT was respectively 2.194, 2.190, 2.181, 2.178 microg/g and 1.148, 1.138, 1.135 and 1.407, 1.403, 1.395 microg), but the results did not show significant differences. The structure of the mitochondria changes included the swollen mitochondria, chromatin margination, pyknosis and apoptosis in neuro cells and the processes of swollen astrocyte cells. The bitumen fume could induce changes of the ultrastructure of mice brain and affect the contents of neurotransmitter of mice brain.
Kim, Tae-Hyun; Choi, Juhee
2014-01-01
A simple and rapid liquid chromatography tandem mass spectrometry method has been developed for the determination of BH4, DA, 5-HT, NE, EP, Glu, and GABA in mouse brain using epsilon-acetamidocaproic acid and isotopically labeled neurotransmitters as internal standards. Proteins in the samples were precipitated by adding acetonitrile, and then the supernatants were separated by a Sepax Polar-Imidazole (2.1 mm × 100 mm, i.d., 3 μm) column by adding a mixture of 10 mM ammonium formate in acetonitrile/water (75 : 25, v/v, 300 μl/min) for BH4 and DA. To assay 5-HT, NE, EP, Glu, and GABA; a Luna 3 μ C18 (3.0 mm × 150 mm, i.d., 3 μm) column was used by adding a mixture of 1% formic acid in acetonitrile/water (20 : 80, v/v, 350 μl/min). The total chromatographic run time was 5.5 min. The method was validated for the analysis of samples. The calibration curve was linear between 10 and 2000 ng/g for BH4 (r2 = 0.995) , 10 and 5000 ng/g for DA (r2 = 0.997) , 20 and 10000 ng/g for 5-HT (r2 = 0.994) , NE (r2 = 0.993) , and EP (r2 = 0.993) , and 0.2 and 200 μg/g for Glu (r2 = 0.996) and GABA (r2 = 0.999) in the mouse brain tissues. As stated above, LC-MS/MS results were obtained and established to be a useful tool for the quantitative analysis of BH4, DA, 5-HT, NE, EP, Glu, and GABA in the experimental rodent brain. PMID:25258696
Numerical Analysis of Parasitic Crossing Compensation with Wires in DA$$\\Phi$$NE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Valishev, A.; Shatilov, D.; Milardi, C.
2015-06-24
Current-bearing wire compensators were successfully used in the 2005-2006 run of the DAΦNE collider to mitigate the detrimental effects of parasitic beam-beam interactions. A marked improvement of the positron beam lifetime was observed in machine operation with the KLOE detector. In view of the possible application of wire beam-beam compensators for the High Luminosity LHC upgrade, we revisit the DAΦNE experiments. We use an improved model of the accelerator with the goal to validate the modern simulation tools and provide valuable input for the LHC upgrade project.
Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.
Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K
2010-09-01
Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.
Liu, B; Jiao, J; Li, Y
1990-04-01
In this study, the authors, by means of fluorescence spectrophotometry, observed the variations of blood contents of monoamine neuro-transmitters (5-hydroxytamine 5-HT; norepinephrine NE; dopamine DA) in 68 subjects before and after adoption of Qigong exercises. A comparison of pre- and post-exercise showed a general reduction in 5-HT, varying from 0.43 +/- 0.21 to 0.21 +/- 0.13 microgram/ml (P less than 0.001). Variations in NE and DA tended to go up, NE being from 0.27 +/- 0.13 to 0.35 +/- 0.27 microgram/ml, DA from 0.86 +/- 0.69 to 1.19 +/- 0.81 micrograms/ml (P less than 0.02). Effects of Qigong exercises on different diseases: Subjects in each group showed reduction in blood 5-HT content after they had practised Qigong exercise. (1) Cardiovascular disease: 0.47 +/- 0.34 to 0.16 +/- 0.11 microgram/ml (n = 13); (2) gastric diseases: 0.37 +/- 0.19 to 0.22 +/- 0.13 microgram/ml (n = 20); (3) joint system diseases: 0.44 +/- 0.21 to 0.18 +/- 0.13 microgram/ml (n = 10); (4) respiratory system diseases: 0.40 +/- 0.22 to 0.22 +/- 0.12 microgram/ml (n = 8); (5) other diseases (neuroasthenia, neurosis, etc.): 0.46 +/- 0.22 to 0.25 +/- 0.14 microgram/ml (n = 13). In all these groups except the fourth group, variations in 5-HT content in comparison with the pre-exercise values were respectively P less than 0.01, less than 0.01, less than 0.05, less than 0.05. The difference was obvious. The post-exercise blood content of DA in various groups rose up remarkably.(ABSTRACT TRUNCATED AT 250 WORDS)
Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok
2016-03-01
The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.
Propagation Limitations of Navigation and Positioning Systems
1977-02-01
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Thakare, Vishnu N; Patil, Rajesh R; Oswal, Rajesh J; Dhakane, Valmik D; Aswar, Manoj K; Patel, Bhoomika M
2018-02-01
Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The present study was undertaken to explore the antidepressant potential of silymarin in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to find out its probable mechanism(s) of action, mainly neurogenesis, neuroinflammation, and/or oxidative stress. The mice were subjected to CUMS for 28 days (4 weeks) and administered with silymarin (100 mg/kg and 200 mg/kg), or fluoxetine or vehicle from days 8 to 28 (3 weeks simultaneously). Animals were evaluated for behavioral changes, such as anhedonia by sucrose preference test, behavioral despair by forced swim test, and exploratory behaviors by an open field test. In addition, neurobiochemical alterations, mainly monoamines, 5-HT, NE, DA, neurotrophic factor BDNF, and cytokines, IL-6, TNF-α, oxidant-antioxidant parameters by determining the malondialdehyde formation (an index of lipid peroxidation process), superoxide dismutase (SOD) and catalase (CAT) activity in hippocampus and cerebral cortex along with serum corticosterone were investigated. Our findings reveal that mice subjected to CUMS exhibited lower sucrose preference, increase immobility time without affecting general locomotion of the animals, and reduce BDNF, 5-HT, NE, and DA level, increased serum corticosterone, IL-6 and TNF-α along with an oxidant-antioxidant imbalance in the hippocampus and cerebral cortex. Silymarin significantly reversed the CUMS-induced changes in the hippocampus and cerebral cortex in mice. Thus, the possible mechanism involved in the antidepressant-like activity of silymarin is correlated to the alleviation of monoaminergic, neurogenesis (enhancing 5-HT, NE, and BDNF levels), and attenuation of inflammatory cytokines system and oxidative stress by modulation of corticosterone response, restoration of antioxidant defense system in cerebral cortex and hippocampus.
The effects of mind-body training on stress reduction, positive affect, and plasma catecholamines.
Jung, Ye-Ha; Kang, Do-Hyung; Jang, Joon Hwan; Park, Hye Yoon; Byun, Min Soo; Kwon, Soo Jin; Jang, Go-Eun; Lee, Ul Soon; An, Seung Chan; Kwon, Jun Soo
2010-07-26
This study was designed to assess the association between stress, positive affect and catecholamine levels in meditation and control groups. The meditation group consisted of 67 subjects who regularly engaged in mind-body training of "Brain-Wave Vibration" and the control group consisted of 57 healthy subjects. Plasma catecholamine (norepinephrine (NE), epinephrine (E), and dopamine (DA)) levels were measured, and a modified form of the Stress Response Inventory (SRI-MF) and the Positive Affect and Negative Affect Scale (PANAS) were administered. The meditation group showed higher scores on positive affect (p=.019) and lower scores on stress (p<.001) compared with the control group. Plasma DA levels were also higher in the meditation (p=.031) than in the control group. The control group demonstrated a negative correlation between stress and positive affects (r=-.408, p=.002), whereas this correlation was not observed in the meditation group. The control group showed positive correlations between somatization and NE/E (r=.267, p=.045) and DA/E (r=.271, p=.042) ratios, whereas these correlations did not emerge in the meditation group. In conclusion, these results suggest that meditation as mind-body training is associated with lower stress, higher positive affect and higher plasma DA levels when comparing the meditation group with the control group. Thus, mind-body training may influence stress, positive affect and the sympathetic nervous system including DA activity. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Kim, Nahyun; Hughes, Tonda L.; Park, Chang G.; Quinn, Laurie
2016-01-01
Abstract The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ2-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t =−6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents. PMID:26849530
Simulation of Crab Waist Collisions In DA$$\\Phi$$NE With KLOE-2 Interaction Region
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zobov, M.; Drago, A.; Gallo, A.
2015-06-24
After the successful completion of the SIDDHARTA experiment run with crab waist collisions, the electron-positron collider DAΦNE has started routine operations for the KLOE-2 detector. The new interaction region also exploits the crab waist collision scheme, but features certain complications including the experimental detector solenoid, compensating anti-solenoids, and tilted quadrupole magnets. We have performed simulations of the beam-beam collisions in the collider taking into account the real DAΦNE nonlinear lattice. In particular, we have evaluated the effect of crab waist sextupoles and beam-beam interactions on the DAΦNE dynamical aperture and energy acceptance, and estimated the luminosity that can be potentiallymore » achieved with and without crab waist sextupoles in the present working conditions. A numerical analysis has been performed in order to propose possible steps for further luminosity increase in DAΦNE such as a better working point choice, crab sextupole strength optimization, correction of the phase advance between the sextupoles and the interaction region. The proposed change of the e- ring working point was implemented and resulted in a significant performance increase.« less
Effects of perch access on physiological parameters in caged White Leghorn pullets
USDA-ARS?s Scientific Manuscript database
The neuroendocrine system controls animals' adaptability to their environments by releasing psychotropic compounds such as catecholamines [epinephrine (EP), norepinephrine (NE), and dopamine (DA)], corticosterone (CORT), and serotonin (5-HT). Changes of these neuroendocrine compounds have been used ...
High-Resolution Spectroscopy of [Ne II] Emission from AA Tau and GM Aur
NASA Astrophysics Data System (ADS)
Najita, Joan R.; Doppmann, Greg W.; Bitner, Martin A.; Richter, Matthew J.; Lacy, John H.; Jaffe, Daniel T.; Carr, John S.; Meijerink, Rowin; Blake, Geoffrey A.; Herczeg, Gregory J.; Glassgold, Alfred E.
2009-05-01
We present high-resolution (R = 80,000) spectroscopy of [Ne II] emission from two young stars, GM Aur and AA Tau, which have moderate to high inclinations. The emission from both sources appears centered near the stellar velocity and is broader than the [Ne II] emission measured previously for the face-on disk system TW Hya. These properties are consistent with a disk origin for the [Ne II] emission we detect, with disk rotation (rather than photoevaporation or turbulence in a hot disk atmosphere) playing the dominant role in the origin of the line width. In the non-face-on systems, the [Ne II] emission is narrower than the CO fundamental emission from the same sources. If the widths of both diagnostics are dominated by Keplerian rotation, this suggests that the [Ne II] emission arises from larger disk radii on average than does the CO emission. The equivalent width of the [Ne II] emission we detect is less than that of the spectrally unresolved [Ne II] feature in the Spitzer spectra of the same sources. Variability in the [Ne II] emission or the mid-infrared continuum, a spatially extended [Ne II] component, or a very (spectrally) broad [Ne II] component might account for the difference in the equivalent widths. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministrio da Cincia e Tecnologia (Brazil), and SECYT (Argentina).
Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R
2015-04-01
Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Vesicular monoamine transporter 2 (Vmat2) knockdown elicits anxiety-like behavior in zebrafish.
Wang, Yali; Li, Siyue; Liu, Wenwen; Wang, Fen; Hu, Li-Fang; Zhong, Zhao-Min; Wang, Han; Liu, Chun-Feng
2016-02-19
Vesicular monoamine transporter 2 (Vmat2) is widely distributed in the central nervous system, and responsible for uptaking transmitters into the vesicles. However, whether Vmat2-deficiency is related to the anxiety is rarely investigated, especially in zebrafish. Here, we reported Vmat2 heterzygous mutant zebrafish displayed anxiety-like behavior. The mutants spent less time in the top area and took longer latency to the top in the novel tank test. Consistently, they showed dark avoidance in the light/dark box test, with longer duration in the light zone and increased number of crossing between the two zones. Monoamine concentration analysis showed that the levels of monoamine neurotransmitters including dopamine (DA), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE), as well as their metabolites were decreased in VMAT mutants. Taken together, these findings suggest that Vmat2 heterzygous mutant zebrafish may serve as a new model of anxiety, which may be related with the low level of DA, 5-HT and NE. Copyright © 2016 Elsevier Inc. All rights reserved.
Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat
NASA Technical Reports Server (NTRS)
Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.
1986-01-01
The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.
Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat.
Robinson, S E; Maher, J R; Wallace, M J; Kunko, P M
1997-01-01
On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.
Differential effects of dietary fats on sympathetic nervous system activity in the rat.
Young, J B; Walgren, M C
1994-01-01
Fat feeding stimulates sympathetic nervous system (SNS) activity in rats. To determine if fats vary in their potency as stimulants of the SNS, [3H]norepinephrine ([3H]NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of animals fed lab chow diets supplemented with safflower oil, coconut oil, or medium-chain triglycerides (MCT). At 5 days, all three fats accelerated [3H]NE turnover in heart and did so equally, but only when the fat supplement represented an increase in energy intake. However, after 14 days, safflower oil and coconut oil but not MCT increased [3H]NE turnover in heart compared with turnover rates obtained in animals fed isoenergetic amounts of chow. Furthermore, the stimulatory effect of safflower oil on [3H]NE turnover was statistically greater than that seen in animals fed equivalent amounts of coconut oil. In vivo synthesis of NE assessed by accumulation of dopamine (DA) in heart following inhibition of dopamine-beta-hydroxylase (D beta H) was likewise highest in safflower oil-fed rats and lowest in those fed MCT. Thus, sympathetic activation by dietary fat varies among different fats, suggesting a role for fatty acid intake in dietary regulation of the SNS.
Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S
2013-08-01
The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.
NASA Technical Reports Server (NTRS)
Kohl, R. L.; Chelen, W. E.
1992-01-01
Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.
New approaches to evaluate sympathoadrenal system activity in experiments on Earth and in space
NASA Astrophysics Data System (ADS)
Kvetnansky, R.; Noskov, V. B.; Blazicek, P.; Macho, L.; Grigoriev, A. I.; Goldstein, D. S.; Kopin, I. J.
In previous studies the activity of the sympathoadrenal system (SAS) in cosmonauts during space flights was evaluated by measuring plasma catecholamines (CA) levels and urinary CA and their metabolites concentrations. Plasma CA levels are accepted indicators of SAS activity, however, they are determined by the plasma clearances as well as the rates of CA release (spillover-SO) into the bloodstream. Nowadays methods are available which evaluate not only plasma levels of CA but also their release, spillover, uptake, reuptake, degradation and also CA synthesis in vivo measured by plasma levels of dihydroxyphenylalanine (DOPA). Plasma concentrations of DOPA, the CA noradrenaline (NE), adrenaline (ADR), and dopamine (DA), the deaminated catechol metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), and the O-methylated metabolites methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured during immobilization stress (IMO) in conscious rats. Radiotracer methods were used to measure NE SO. IMO markedly increased arterial NE levels but NE SO was less elevated bacause the NE clearance was slightly reduced in IMO rats. Simultaneous measurements of plasma CA and their metabolites provide another means to obtain information about SAS function. For instance, dissociation between changes of plasma DHPG and NE levels can indicate changes in neuronal reuptake of NE. We found marked parallel increases in plasma NE and DHPG levels during acute IMO; however after repeated IMO, plasma NE levels were increased but DHPG responses were less pronounced suggesting a reduced NE reuptake. DOPA, the CA precursor, circulates in plasma at a concentration higher than NE. During stress, increased sympathoneural outflow stimulates DOPA synthesis and release into the circulation supporting the view that changes in plasma DOPA levels during stress reflect in vivo changes in the rate of CA synthesis. We propose to measure the new plasma indicators of SAS activity in cosmonauts and/or in animals before, during and after space flights.
ERIC Educational Resources Information Center
Qi, Zhenghan; Gold, Paul E.
2009-01-01
Intra-amygdala injections of anisomycin produce large increases in the release of norepinephrine (NE), dopamine (DA), and serotonin in the amygdala. Pretreatment with intra-amygdala injections of the beta-adrenergic receptor antagonist propranolol attenuates anisomycin-induced amnesia without reversing the inhibition of protein synthesis, and…
Oosthuizen, Mathys M J; Lambrechts, Hugo
2007-01-01
Hepatoproliferin (HPF) was purified from regenerating rat livers as an oligomeric entity (big-HPF) from which the monomeric form (small-HPF) could be obtained using disaggregating conditions. By using a solid-phase ion-exchange method, small-HPF was forced to dissociate into two charged ionic species, namely norepinephrine (NE) and a sulfonated disaccharide with a molecular structure consisting of D-glucuronic acid bound to glucosamine 2,6-disulfate by a beta-glycosidic linkage having a beta, 1 --> 4 configuration. Monomeric HPF stemmed from the formation of three electrostatic bonds between the protonated amine groups of three norepinephrines, of which two bind to the deprotonated sulfonic groups of glucosamine 2,6-disulfate and one to the deprotonated carboxylic group of glucuronic acid, to constitute a tightly associated complex with a molecular mass of 1046 Da. This represents one of the two purified isoforms of small-HPF. The other isoform, which has a lower molecular mass of 877 Da, lack one NE, leaving the weaker carboxylic group of glucuronic acid unoccupied, to constitute a more acidic form of HPF.
Diricks, Margo; De Bruyn, Frederik; Van Daele, Paul; Walmagh, Maarten; Desmet, Tom
2015-10-01
Sucrose synthase (SuSy) catalyzes the reversible conversion of sucrose and a nucleoside diphosphate into fructose and nucleotide (NDP)-glucose. To date, only SuSy's from plants and cyanobacteria, both photosynthetic organisms, have been characterized. Here, four prokaryotic SuSy enzymes from the nonphotosynthetic organisms Nitrosomonas Europaea (SuSyNe), Acidithiobacillus caldus (SuSyAc), Denitrovibrio acetiphilus (SusyDa), and Melioribacter roseus (SuSyMr) were recombinantly expressed in Escherichia coli and thoroughly characterized. The purified enzymes were found to display high-temperature optima (up to 80 °C), high activities (up to 125 U/mg), and high thermostability (up to 15 min at 60 °C). Furthermore, SuSyAc, SuSyNe, and SuSyDa showed a clear preference for ADP as nucleotide, as opposed to plant SuSy's which prefer UDP. A structural and mutational analysis was performed to elucidate the difference in NDP preference between eukaryotic and prokaryotic SuSy's. Finally, the physiological relevance of this enzyme specificity is discussed in the context of metabolic pathways and genomic organization.
Jongkees, Bryant J; Hommel, Bernhard; Kühn, Simone; Colzato, Lorenza S
2015-11-01
Consuming the amino-acid tyrosine (TYR), the precursor of dopamine (DA) and norepinephrine (NE), may counteract decrements in neurotransmitter function and cognitive performance. However, reports on the effectiveness of TYR supplementation vary considerably, with some studies finding beneficial effects, whereas others do not. Here we review the available cognitive/behavioral studies on TYR, to elucidate whether and when TYR supplementation can be beneficial for performance. The potential of using TYR supplementation to treat clinical disorders seems limited and its benefits are likely determined by the presence and extent of impaired neurotransmitter function and synthesis. Likewise, the potential of TYR supplementation for enhancing physical exercise seems minimal as well, perhaps because the link between physical exercise and catecholamine function is mediated by many other factors. In contrast, TYR does seem to effectively enhance cognitive performance, particularly in short-term stressful and/or cognitively demanding situations. We conclude that TYR is an effective enhancer of cognition, but only when neurotransmitter function is intact and DA and/or NE is temporarily depleted. Copyright © 2015 Elsevier Ltd. All rights reserved.
Arutjunyan, Alexander; Kozina, Ljudmila; Milyutina, Yulia; Korenevsky, Andrew; Stepanov, Michael; Arutyunov, Vladimir
2012-12-01
Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging. The investigation of epithalamine (a polypeptide preparation from the bovine pineal gland) effect on circadian rhythms disturbed by the neurotoxic compound DMH has shown a recovery of the diurnal dynamics of NE in MPA. In addition, NE was found to decrease from 9:30 till 11 o'clock, Circadian Time (CT), which was typical of control animals. Epitalon (Ala-Glu-Asp-Gly) proved to be more effective in ME-Arc. This peptide prevents the xenobiotic caused disturbance of DA diurnal rhythm, keeping this metabolite low at 5 o'clock (CT) with it having increased by 11 o'clock (CT). The data obtained suggest that the pineal gland is important for the circadian signal normalization needed for gonadoliberin surge on the day of proestrus. Melatonin and peptides of the pineal gland can be considered as effective protectors of female reproductive system from xenobiotics and premature aging.
Yu, Z J; Wecker, L
1994-07-01
The objective of these experiments was to determine whether the chronic administration of nicotine, at a dose regimen that increases the density of nicotine binding sites, alters the nicotine-induced release of [3H]-dopamine ([3H]DA), [3H]norepinephrine ([3H]NE), [3H]-serotonin ([3H]5-HT), or [3H]acetylcholine ([3H]ACh) from rat striatal slices. For these experiments, rats received subcutaneous injections of either saline or nicotine bitartrate [1.76 mg (3.6 mumol)/kg, dissolved in saline] twice daily for 10 days, and neurotransmitter release was measured following preloading of the tissues with [3H]DA, [3H]NE, [3H]5-HT, or [3H]choline. Chronic nicotine administration did not affect the accumulation of tritium by striatal slices, the basal release of radioactivity, or the 25 mM KCl-evoked release of neurotransmitter. Superfusion of striatal slices with 1, 10, and 100 microM nicotine increased [3H]DA release in a concentration-dependent manner, and release from slices from nicotine-injected animals was significantly (p < 0.05) greater than release from saline-injected controls; release from the former increased to 132, 191, and 172% of release from the controls following superfusion with 1, 10, and 100 microM nicotine, respectively. Similarly, [3H]5-HT release increased in a concentration-related manner following superfusion with nicotine, and release from slices from nicotine-injected rats was significantly (p < 0.05) greater than that from controls. [3H]5-HT release from slices from nicotine-injected rats evoked by superfusion with 1 and 10 microM nicotine increased to 453 and 217%, respectively, of release from slices from saline-injected animals. The nicotine-induced release of [3H]NE from striatal slices was also concentration dependent but was unaffected by chronic nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
1989-03-01
Jon s (n)e-"’ z(121) SA+ -jO where N-1 Ck = s(n)s (n - k) k > 0 (122) n=z+k and + =ck = -c~k) (123) Now, to get the digital equivalents of (2),(4) we...Paulo NI. D. M6nica de Oliveira 2 Direcpto do Servi(;o de Instru~ao e Treino Edificjo da Adniinistraqdo Central de Marinha Praoa do Comercio I I...Lisboa Portugal 89 12. Lt. Paulo M. D. NM6nica de Oliveira2 Direc Ao do Servi~o de 1nstruqao e Treino Edificio da Adnistraqo Central de Marinha Praoa do Comercio 1 100 Lisboa Portuoal 89
2010-05-01
s ’ Op ini on Ja nk ov...Inj ur y ( %) Su ffic ien t Da ta? † Ne ur olo gic al Re su lts Au th or s ’ Op ini on Ja nk ov ić et al. , 1 99 8 49 47 19 21 56 NA NA 27 6 50 /9...Ne ur olo gic al Re su lts Au th or s ’ Op ini on Cy bu lsk i e t a l., 19 89 ha nd gu n 0 0 88 29 59 88 NA NA no 47 .5% im pr ov ed w / o p do
Brodnik, Zachary D; Double, Manda; España, Rodrigo A; Jaskiw, George E
2017-09-01
We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated. Published by Elsevier Ltd.
Sensitivity Analysis of a Lagrangian Sea Ice Model
NASA Astrophysics Data System (ADS)
Rabatel, Matthias; Rampal, Pierre; Bertino, Laurent; Carrassi, Alberto; Jones, Christopher K. R. T.
2017-04-01
Large changes in the Arctic sea ice have been observed in the last decades in terms of the ice thickness, extension and drift. Understanding the mechanisms behind these changes is of paramount importance to enhance our modeling and forecasting capabilities. For 40 years, models have been developed to describe the non-linear dynamical response of the sea ice to a number of external and internal factors. Nevertheless, there still exists large deviations between predictions and observations. There are related to incorrect descriptions of the sea ice response and/or to the uncertainties about the different sources of information: parameters, initial and boundary conditions and external forcing. Data assimilation (DA) methods are used to combine observations with models, and there is nowadays an increasing interest of DA for sea-ice models and observations. We consider here the state-of-the art sea-ice model, neXtSIM te{Rampal2016a}, which is based on a time-varying Lagrangian mesh and makes use of the Elasto-Brittle rheology. Our ultimate goal is designing appropriate DA scheme for such a modelling facility. This contribution reports about the first milestone along this line: a sensitivity analysis in order to quantify forecast error to guide model development and to set basis for further Lagrangian DA methods. Specific features of the sea-ice dynamics in relation to the wind are thus analysed. Virtual buoys are deployed across the Arctic domain and their trajectories of motion are analysed. The simulated trajectories are also compared to real buoys trajectories observed. The model response is also compared with that one from a model version not including internal forcing to highlight the role of the rheology. Conclusions and perspectives for the general DA implementation are also discussed. \\bibitem{Rampal2016a} P. Rampal, S. Bouillon, E. Ólason, and M. Morlighem. ne{X}t{SIM}: a new {L}agrangian sea ice model. The Cryosphere, 10 (3): 1055-1073, 2016.
Zhang, Fuping; Zhang, Min; Cheng, Jiongjia; Yang, Li; Ji, Ming; Bi, Shuping
2007-11-01
In this paper, we firstly report the direct voltammetric recognition and determination of dopamine (DA) by using Al(III)-DA complexes at the hanging mercury drop electrode (HMDE). A new sensitive cathodic peak of Al(III)-DA can be detected at -900 mV (vs. SCE) in 0.1 M NH(4)Cl-NH(3).H(2)O-0.1 M KCl buffer solution at pH 8.5. This unique -900 mV cathodic peak arises from the specific interaction between Al(III) and DA on the HMDE, whereas other substances with similar structures, such as L-dopa, epinephrine (EP), norepinephrine (NE), catechols, caffeic acid (CA), trihydric phenols and tiron, do not yield any new peak on the voltammograms in the potential range from -100 to -1200 mV when Al(III) is added. The distinct voltammetric characteristic of the recognition of DA can effectively inhibit the interferences of both ascorbic acid and uric acid in the DA determination by the direct electrochemistry, which is a major difficulty when a solid electrode is used. The proposed method can be anticipated as an effective means for the recognition of DA in the elucidation of the mechanisms of Parkinson's disease (PD) and Alzheimer's disease (AD) in the presence of Al(III).
Balasubramanian, Priya; Sirivelu, Madhu P; Weiss, Kathryn A; Wagner, James G; Harkema, Jack R; Morishita, Masako; Mohankumar, P S; Mohankumar, Sheba M J
2013-05-01
Acute exposure to airborne pollutants, especially particulate matter (PM2.5) is known to increase hospital admissions for cardiovascular conditions, increase cardiovascular related mortality and predispose the elderly and obese individuals to cardiovascular conditions. The mechanisms by which PM2.5 exposure affects the cardiovascular system is not clear. Since the autonomic system plays an important role in cardiovascular regulation, we hypothesized that PM2.5 exposure most likely activates the paraventricular nucleus (PVN) of the hypothalamus to cause an increase in sympathetic nervous system and/or stress axis activity. We also hypothesized that these changes may be sustained in obese rats predisposing them to higher cardiovascular risk. To test this, adult male Brown Norway (BN) rats were subjected to one day or three days of inhalation exposures to filtered air (FA) or concentrated air particulate (CAP) derived from ambient PM2.5. Corpulent JCR-LA rats were exposed to FA or CAP for four days. Animals were sacrificed 24h after the last inhalation exposure. Their brains were removed, frozen and sectioned. The PVN and median eminence (ME) were microdissected. PVN was analyzed for norepinephrine (NE), dopamine (DA) and 5-hydroxy-indole acetic acid (5-HIAA) levels using HPLC-EC. ME was analyzed for corticotrophin releasing hormone (CRH) levels by ELISA. One day exposure to CAP increased NE levels in the PVN and CRH levels in the ME of BN rats. Repeated exposures to CAP did not affect NE levels in the PVN of BN rats, but increased NE levels in JCR/LA rats. A similar pattern was observed with 5-HIAA levels. DA levels on the other hand, were unaffected in both BN and JCR/LA strains. These data suggest that repeated exposures to PM2.5 continue to stimulate the PVN in obese animals but not lean rats. Copyright © 2012 Elsevier Inc. All rights reserved.
Kolta, M G; Holson, R; Duffy, P; Hart, R W
1989-05-01
The present study examines the changes in central monoamines and their metabolites in aged male and female rats after long-term caloric restriction. Fischer 344 rats of both sexes (n = 5-10/group) were maintained on one of two dietary regimens: ad libitum NIH 31 diet or 60% by weight of the ad lib. intake (restricted), supplemented with vitamins and minerals. Animals received these diets from the age of 14 weeks until killed at 22.25 months of age. Caudate nucleus (CN), hypothalamus (HYPO), olfactory bulb (OB) and nucleus accumbens (NA) were assayed for content of norepinephrine (NE), dopamine (DA) and its metabolites (dihydroxyphenylacetic acid, DOPAC, and homovanillic acid, HVA) and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) using HPLC/EC. Relative to the ad lib. group, restricted rats of both sex showed significant decreases in NE content in CN, HYPO and OB. DA and 5-HT content were decreased significantly in the CN and HYPO. No significant changes were found in the levels of DA metabolites in all brain regions studied. While the 5-HIAA level was significantly reduced in the HYPO and NA of the female restricted rats, it was increased several-fold in the OB of the male restricted animals. These preliminary results suggest that long-term caloric restriction alters brain monoamine concentrations, an effect which may in turn modify the normal rate of aging.
Anticipatory responses of catecholamines on muscle force production.
French, Duncan N; Kraemer, William J; Volek, Jeff S; Spiering, Barry A; Judelson, Daniel A; Hoffman, Jay R; Maresh, Carl M
2007-01-01
Few data exist on the temporal relationship between catecholamines and muscle force production in vivo. The purpose of this study was to examine the influence of preexercise arousal on sympathoadrenal neurohormones on muscular force expression during resistance exercise. Ten resistance-trained men completed two experimental conditions separated by 7 days: 1) acute heavy resistance exercise protocol (AHREP; 6 x 10 repetitions parallel squats, 80% 1 repetition maximum) and 2) control (Cont; rest). Peak force (F(peak)) was recorded during a maximal isometric squat preceding each set and mean force (F(mean)) was measured during each set. Serial venous blood samples were collected before the AHREP and immediately preceding each set. Blood collection times were matched during Cont. Preexercise epinephrine (Epi), norepinephrine (NE), and dopamine (DA) increased (P
Arnsten, Amy F T
2007-09-01
Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal levels of DA D1 receptor stimulation decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive levels of catecholamine release during stress impair working memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental illnesses are associated with extracellular changes in these pathways: Attention Deficit Hyperactivity Disorder is linked to genetic changes that reduce catecholamine transmission to suboptimal levels and is treated with agents that increase catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is associated with amplified noradrenergic transmission that impairs PFC but strengthens amygdala function. PTSD is now treated with agents that block alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, schizophrenia and bipolar disorder, are associated with genetic changes in molecules regulating intracellular signaling pathways activated by stress. Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein signaling 4 inhibits PI signaling. Loss of function in these genes may render patients vulnerable to profound stress-induced PFC dysfunction including symptoms of thought disorder.
Mariappan, Subramanian; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel
2013-09-01
In a stressful situation, greater short-nosed fruit bats (Cynopterus sphinx) emit audible vocalization either to warn or to inform conspecifics. We examined the effect of distress calls on bats emitting the call as well as the bats receiving the distress signal through analysis of the hypothalamic-pituitary-adrenal axis and catacholaminargic systems. We measured the levels of neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)] and stress hormones [(adrenocorticotropic hormone (ACTH) and corticosterone (CORT)]. Our results showed that distress call emission elevated the level of ACTH and CORT, as well as 5-HT, DA and NE in the amygdala, for both the call emitting bat and the responding bat. Subsequently, we observed increased activity of glucocorticoid receptor and its steroid receptor co-activator (SRC-1). An expression of SRC-1 was up-regulated in the distress call emitter only, whereas it was at a similar level in both the call responder and silent bats. These findings suggest that bats emitting distress calls and also bats responding to such calls have similar neurotransmitter expression patterns, and may react similarly in response to stress.
Caffeine and the olfactory bulb.
Hadfield, M G
1997-08-01
Caffeine, a popular CNS stimulant, is the most widely used neuroactive drug. Present in coffee, tea, chocolate, and soft drinks as well as over-the-counter and prescription medications, it influences millions of users. This agent has achieved recent notoriety because its dependency consequences and addictive potential have been re-examined and emphasized. Caffeine's central actions are thought to be mediated through adenosine (A) receptors and monoamine neurotransmitters. The present article suggests that the olfactory bulb (OB) may be an important site in the brain that is responsible for caffeine's central actions in several species. This conclusion is based on the extraordinarily robust and selective effects of caffeine on norepinephrine (NE), dopamine (DA), and particularly serotonin (5HT) utilization in the OB of mice. We believe that these phenomena should be given appropriate consideration as a basis for caffeine's central actions, even in primates. Concurrently, we review a rich rodent literature concerned with A, 5HT, NE, and DA receptors in the OB and related structures along with other monoamine parameters. We also review a more limited literature concerned with the primate OB. Finally, we cite the literature that treats the dependency and addictive effects of caffeine in humans, and relate the findings to possible olfactory mechanisms.
Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S
2013-06-01
The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.
Zhao, Longshan; Zheng, Shuning; Su, Guangyue; Lu, Xiumei; Yang, Jingyu; Xiong, Zhili; Wu, Chunfu
2015-04-15
A sensitive and versatile, ultra-high performance, liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method coupled to pre-column derivatization for the simultaneous determination of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), γ-aminobutyric acid (GABA) and glutamic acid (Glu) was developed and validated in rat plasma. The analytes were dansylated under strong alkaline conditions after protein precipitation extraction, which were analyzed on a BEH C18 column using a gradient elution. The lower limit of quantification (LLOQ) values for 5-HT, 5-HIAA, DA, NE, HVA, GABA and Glu were 1.00, 1.00, 0.991, 0.992, 1.02, 1000, and 5030 pmol/mL, respectively. Good linearity was obtained (r > 0.99) and the intra- and inter-day precisions of the method (relative standard deviation, RSD%) were lower than 12%. The method was novel, sensitive and specific which can provide an alternative method for the quantification of neurotransmitters and their metabolites in plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.
Abdel Moneim, Ahmed E
2012-09-01
Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both man and animals. Here, the neuroprotective effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg) induced alternation in monoamines and brain oxidative stress was examined in rats. The levels of lead, dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation, nitrite/nitrate (NO), and glutathione (GSH) were determined; also, the activity of acetylcholinesterase (AChE) and Na(+)-K(+)-ATPase were estimated on different brain regions of adult male albino rats. The level of lead was markedly elevated in different brain regions of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in AChE activity and GSH level. In addition, the levels of DA, NE, and 5-HT were decreased in the brain. These findings were associated with BAX over expression. Treatment of rats with flaxseed oil induced a marked improvement in most of the studied parameters as well as the immunohistochemistry features. These data indicated that dietary flaxseed oil provide protection against lead-induced oxidative stress and neurotoxic effects.
Cornil, Charlotte A; Dejace, Christel; Ball, Gregory F; Balthazart, Jacques
2005-08-30
In rats, dopamine (DA) facilitates male sexual behavior through its combined action on D1- and D2-like receptors, in the medial preoptic area (MPOA) as well as other brain areas. In Japanese quail, systemic injections of dopaminergic drugs suggested a similar pharmacology but central injections have never been performed. Recent electrophysiological experiments demonstrated that DA effects in the MPOA of quail are mediated mainly through the activation of alpha2-noradrenergic receptors. Previous studies of DA action on behavior used specific dopaminergic agonists/antagonists and therefore unintentionally avoided the potential cross-reaction with alpha2-receptors. The present study was thus designed to investigate directly the effects of DA on male sexual behavior and to test whether the interaction of DA with heterologous receptors affects this behavior. Intracerebroventricular (i.c.v.) injection of DA or NE inhibited copulation in a dose-dependent manner. Systemic injections of yohimbine, an alpha2-noradrenergic antagonist, modulated copulation in a bimodal manner depending on the dose injected. Interestingly, a behaviorally ineffective dose of yohimbine markedly reduced the inhibitory effects of DA when injected 15min before. Together, these results show for the first time that i.c.v. injections of DA itself inhibit male sexual behavior in quail and suggest that the interaction of DA with alpha2-receptors has behavioral significance.
Masilamoni, Gunasingh Jeyaraj; Groover, Olivia; Smith, Yoland
2017-04-01
There is anatomical and functional evidence that ventral midbrain dopaminergic (DA) cell groups and the subthalamic nucleus (STN) receive noradrenergic innervation in rodents, but much less is known about these interactions in primates. Degeneration of NE neurons in the locus coeruleus (LC) and related brainstem NE cell groups is a well-established pathological feature of Parkinson's disease (PD), but the development of such pathology in animal models of PD has been inconsistent across species and laboratories. We recently demonstrated 30-40% neuronal loss in the LC, A5 and A6 NE cell groups of rhesus monkeys rendered parkinsonian by chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, we used dopamine-beta-hydroxylase (DβH) immunocytochemistry to assess the impact of this neuronal loss on the number of NE terminal-like varicosities in the substantia nigra pars compacta (SNC), ventral tegmental area (VTA), retrorubral field (RRF) and STN of MPTP-treated parkinsonian monkeys. Our findings reveal that the NE innervation of the ventral midbrain and STN of normal monkeys is heterogeneously distributed being far more extensive in the VTA, RRF and dorsal tier of the SNC than in the ventral SNC and STN. In parkinsonian monkeys, all regions underwent a significant (~50-70%) decrease in NE innervation. At the electron microscopic level, some DβH-positive terminals formed asymmetric axo-dendritic synapses in VTA and STN. These findings demonstrate that the VTA, RRF and SNCd are the main ventral midbrain targets of ascending NE inputs, and that these connections undergo a major break-down in chronically MPTP-treated parkinsonian monkeys. This severe degeneration of the ascending NE system may contribute to the pathophysiology of ventral midbrain and STN neurons in PD. Copyright © 2017 Elsevier Inc. All rights reserved.
Naccarato, Attilio; Gionfriddo, Emanuela; Sindona, Giovanni; Tagarelli, Antonio
2014-01-31
The work aims at developing a simple and rapid method for the quantification of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in human urine. The urinary levels of these biogenic amines can be correlated with several pathological conditions concerning heart disease, stress, neurological disorders and cancerous tumors. The proposed analytical approach is based on the use of solid phase microextraction (SPME) combined with gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS) after a fast derivatization of both aliphatic amino and phenolic moieties by propyl chloroformate. The variables influencing the derivatization reaction were reliably optimized by the multivariate approach of "Experimental design". The optimal conditions were obtained by performing derivatization with 100μL of propyl chloroformate and 100μL of pyridine. The extraction ability of five commercially available SPME fibers was evaluated in univariate mode and the best results were obtained using the polyacrylate fiber. The variables affecting the efficiency of SPME analysis were again optimized by the multivariate approach of "Experimental design" and, in particular, a central composite design (CCD) was applied. The optimal values were extraction in 45min at room temperature, desorption temperature at 300°C, no addition of NaCl. Assay of derivatized analytes was performed by using a gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS) system in selected reaction monitoring (SRM) acquisition. An evaluation of all analytical parameters demonstrates that the developed method provides satisfactory results. Indeed, very good linearities were achieved in the tested calibration range with correlation coefficient values of 0.9995, 0.9999 and 0.9997 for DA, 5-HT and NE, respectively. Accuracies and RSDs calculated for between-run and tested at concentrations of 30, 200, and 800μg L(-1) were in the range from 92.8% to 103.0%, and from 0.67 to 4.5%, respectively. Finally, the LOD values obtained can be considered very good (0.587, 0.381 and 1.23μg L(-1) for DA, 5-HT and NE, respectively). Copyright © 2013 Elsevier B.V. All rights reserved.
Bala, Madhu; Gupta, Vanita; Prasad, Jagdish
2017-12-01
Effects of a radioprotective, standardized leaf extract (code SBL-1) from traditional medicinal plant, sea buckthorn [Hippophae rhamnoides L. (Elaeagnaceae)], on neurotransmitters and brain injuries in rats showing radiation-induced conditioned taste aversion (CTA), are not known. Understanding CTA in rats is important because its process is considered parallel to nausea and vomiting in humans. This study investigated the levels of neurotransmitters, antioxidant defences and histological changes in rats showing radiation CTA, and their modification by SBL-1. The inbred male Sprague-Dawley rats (age 65 days, weighing 190 ± 10 g) were used. Saccharin-preferring rats were selected using standard procedure and divided into groups. Group I (untreated control) was administered sterile water, group II was 60 Co-γ-irradiated (2 Gy), and group III was administered SBL-1 before irradiation. Observations were recorded up to day 5. Irradiation (2 Gy) caused (i) non-recoverable CTA (≥ 64.7 ± 5.0%); (ii) degenerative changes in cerebral cortex, amygdala and hippocampus; (iii) increases in brain dopamine (DA, 63.4%), norepinephrine (NE, 157%), epinephrine (E, 233%), plasma NE (103%) and E (160%); and (iv) decreases in brain superoxide dismutase (67%), catalase (60%) and glutathione (51%). SBL-1 treatment (12 mg/kg body weight) 30 min before irradiation (i) countered brain injuries, (ii) reduced CTA (38.7 ± 3.0%, day 1) and (iii) normalized brain DA, NE, E, superoxide dismutase, catalase and CTA from day 3 onwards. Radiation CTA was coupled with brain injuries, disturbances in neurotransmitters and antioxidant defences. SBL-1 pretreatment countered these disturbances, indicating neuroprotective action.
Abundância química de simbióticas na direção do bojo galáctico
NASA Astrophysics Data System (ADS)
Luna, G. J. M.; Costa, R. D. D.
2003-08-01
O estudo da distribuição de metalicidades de gigantes K no Bojo indica um largo intervalo com valores entre 0.1 a 10 vezes o valor solar. As razões elementais Ca/Fe, Si/Fe, Mg/Fe são típicas de estrelas do halo, apontando para um processo rápido de enriquecimento, via estrelas masssivas (SN's tipo II). No entanto, este cenário não combina com os resultados derivados de nebulosas planetárias do bojo tais como os de Ratag et al. (1992, A&A,255,270), Cuisinier et al.(2000, A&A,353, 543), Escudero e Costa (2001, A&A,380, 300),que obtêm abundâncias análogas às do disco. Neste cenário, o estudo de estrelas simbióticas possibilita uma abordagem particularmente apropriada para o problema das abundâncias químicas de estrelas de massa intermediária em estágios avançados da evoluçao estelar. Apresentamos aqui os resultados da determinacão das abundâncias do grupo do CNO numa extensa amostra de simbióticas do bojo. Aliás, com a disponibilidade de espectros no visível determinamos também abundâncias de Ar, Ne, S e He, fundamentais para analisar os processos de enriquecimento químico ocorridos ao longo da evolução estelar, bem como a evolução química do meio interestelar. Com os espectros UV do satelite IUE obtivemos abundâncias de C, necessárias no estudo da evolução dos sistemas. As relaçoes C/N-O/N mostram que o material nebular é produto do vento da componente gigante e não dos eventos de nova que às vezes acontecem nestes sistemas, como foi mostrado por Nussbaumer et al (1988,A&A,198,179). As abundâncias de Ar, S, Ne e O são compativeis com resultados de fontes no disco e bojo, seguindo o gradiente proposto por muitos autores na literatura a partir de diferentes objetos como cefeidas, nebulosas planetárias e anãs G. (CAPES,FAPESP,CNPq)
Aboul Ezz, H S; Khadrawy, Y A; Ahmed, N A; Radwan, N M; El Bakry, M M
2013-07-01
The use of mobile phones is rapidly increasing all over the world. Few studies deal with the effect of electromagnetic radiation (EMR) on monoamine neurotransmitters in the different brain areas of adult rat. The aim of the present study was to investigate the effect of EMR on the concentrations of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the hippocampus, hypothalamus, midbrain and medulla oblongata of adult rats. Adult rats were exposed daily to EMR (frequency 1800 MHz, specific absorption rate 0.843 W/kg, power density 0.02 mW/cm2, modulated at 217 Hz) and sacrificed after 1, 2 and 4 months of daily EMR exposure as well as after stopping EMR for 1 month (after 4 months of daily EMR exposure). Monoamines were determined by high performance liquid chromatography coupled with fluorescence detection (HPLC-FD) using their native properties. The exposure to EMR resulted in significant changes in DA, NE and 5-HT in the four selected areas of adult rat brain. The exposure of adult rats to EMR may cause disturbances in monoamine neurotransmitters and this may underlie many of the adverse effects reported after EMR including memory, learning, and stress.
Ikegami, Taro; Takemura, Akihiro; Choi, Eunjung; Suda, Atsushi; Tomonaga, Shozo; Badruzzaman, Muhammad; Furuse, Mitsuhiro
2015-10-01
Fish are faced with a wide range of hydrostatic pressure (HP) in their natural habitats. Additionally, freshwater fish are occasionally exposed to rapid changes in HP due to heavy rainfall, flood and/or dam release. Accordingly, variations in HP are one of the most important environmental cues for fish. However, little information is available on how HP information is perceived and transmitted in the central nervous system of fish. The present study examined the effect of HP (water depth of 1.3 m) on the quantities of monoamines and their metabolites in the telencephalon, optic tectum, diencephalon, cerebellum (including partial mesencephalon) and vagal lobe (including medulla oblongata) of the goldfish, Carassius auratus, using high-performance liquid chromatography. HP affected monoamine and metabolite contents in restricted brain regions, including the telencephalon, cerebellum and vagal lobe. In particular, HP significantly increased the levels of dopamine (DA) in the telencephalon at 15 min and that of norepinephrine (NE) in the cerebellum at 30 min. In addition, HP also significantly increased locomotor activity at 15 and 30 min after HP treatment. It is possible that HP indirectly induces locomotion in goldfish via telencephalic DA and cerebellar NE neuronal activity.
Warren, Christopher M.; Holroyd, Clay B.
2012-01-01
We applied the event-related brain potential (ERP) technique to investigate the involvement of two neuromodulatory systems in learning and decision making: The locus coeruleus–norepinephrine system (NE system) and the mesencephalic dopamine system (DA system). We have previously presented evidence that the N2, a negative deflection in the ERP elicited by task-relevant events that begins approximately 200 ms after onset of the eliciting stimulus and that is sensitive to low-probability events, is a manifestation of cortex-wide noradrenergic modulation recruited to facilitate the processing of unexpected stimuli. Further, we hold that the impact of DA reinforcement learning signals on the anterior cingulate cortex (ACC) produces a component of the ERP called the feedback-related negativity (FRN). The N2 and the FRN share a similar time range, a similar topography, and similar antecedent conditions. We varied factors related to the degree of cognitive deliberation across a series of experiments to dissociate these two ERP components. Across four experiments we varied the demand for a deliberative strategy, from passively watching feedback, to more complex/challenging decision tasks. Consistent with our predictions, the FRN was largest in the experiment involving active learning and smallest in the experiment involving passive learning whereas the N2 exhibited the opposite effect. Within each experiment, when subjects attended to color, the N2 was maximal at frontal–central sites, and when they attended to gender it was maximal over lateral-occipital areas, whereas the topology of the FRN was frontal–central in both task conditions. We conclude that both the DA system and the NE system act in concert when learning from rewards that vary in expectedness, but that the DA system is relatively more exercised when subjects are relatively more engaged by the learning task. PMID:22493568
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bleavins, M.R.; Bursian, S.J.; Brewster, J.S.
1984-01-01
In the initial trial, adult mink and ferrets were administered hexachlorobenzene (HCB) via the feed at concentrations of 1, 5, or 25 ppm for 47 wk. Animals receiving 125 and 625 ppm HCB in the diet died before termination of the experiment, with female ferrets at the 125 ppm level displaying abnormal aggressiveness and hyperexcitability just prior to death. Hypothalamic serotonin (5-HT) was significantly elevated at all dose levels in mink, and cerebellar 5-HT was significantly elevated at 1 ppm in the ferret. Regional brain biogenic amine concentrations were also determined in the offspring of the female mink that weremore » administered 1 and 5 ppm HCB. Hypothalamic dopamine (DA) concentrations were significantly depressed by 1 and 5 ppm in these kits. In a second study, adult male and female ferrets were administered 250 or 500 ppm HCB via the diet for 7 wk. Two animals at the 250-ppm level and 3 animals at the 500-ppm level died before termination of the experiment without showing behavioral changes. Of the remaining animals, 3 ferrets at 250 ppm and 1 ferret at 500 ppm showed slight aggressiveness and hyperexcitability during the last week of the experiment. Concentrations of 5-HT were significantly elevated at 500 ppm in the cerebral hemispheres and at 250 ppm in the midbrain of male ferrets, while in the females, 5-HT was elevated in the cerebral hemispheres at 250 ppm and in the hypothalamus at both 250 and 500 ppm. Norepinephrine (NE) concentrations were significantly elevated in the cerebellum of males exposed to 250 and 500 ppm, as were NE concentrations in the midbrain. HCB at 500 ppm caused a significant increase in medullary NE, while 250 ppm caused an increase in hypothalamic NE in males. The only change in regional brain dopamine (DA) concentrations occurred at 500 ppm HCB in the midbrain of males, where there was a significant elevation of this neurotransmitter. 34 references, 7 tables.« less
To, Ho; Suzuki, Takayuki; Kawahara, Fumiya; Uetsuka, Koji; Nagai, Shinya; Nunoya, Tetsuo
2017-02-28
Necrotic enteritis (NE) is one of the most important bacterial diseases in terms of economic losses. Clostridium perfringens necrotic enteritis toxin B, NetB, was recently proposed as a new key virulent factor for the development of NE. The goal of this work was to develop a necrotic enteritis model in chickens by using a Japanese isolate of C. perfringens. The Japanese isolate has been found to contain netB gene, which had the same nucleotide and deduced amino acid sequences as those of prototype gene characterized in Australian strain EHE-NE18, and also expressed in vitro a 33-kDa protein identified as NetB toxin by nano-scale liquid chromatographic tandem mass spectrometry. In the challenge experiment, broiler chickens fed a commercial chicken starter diet for 14 days post-hatch were changed to a high protein feed mixed 50:50 with fishmeal for 6 days. At day 21 of age, feed was withheld for 24 hr, and each chicken was orally challenged twice daily with 2 ml each of C. perfringens culture (10 9 to 10 10 CFU) on 5 consecutive days. The gross necrotic lesions were observed in 90 and 12.5% of challenged and control chickens, respectively. To our knowledge, this is the first study that demonstrated that a netB-positive Japanese isolate of C. perfringens is able to induce the clinical signs and lesions characteristic of NE in the experimental model, which may be useful for evaluating the pathogenicity of field isolates, the efficacy of a vaccine or a specific drug against NE.
Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si
NASA Astrophysics Data System (ADS)
Wallace, J. B.; Aji, L. B. Bayu; Shao, L.; Kucheyev, S. O.
2018-05-01
The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ˜-30 ° C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ˜0.1 eV , independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ˜0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.
Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si.
Wallace, J B; Aji, L B Bayu; Shao, L; Kucheyev, S O
2018-05-25
The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ∼-30 °C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ∼0.1 eV, independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ∼0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.
Interaction of organic cation transporter 3 (SLC22A3) and amphetamine
Zhu, Hao-Jie; Appel, David I.; Gründemann, Dirk; Markowitz, John S.
2013-01-01
The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. Relative to wild-type (WT) animals, Oct3 knockout (KO) mice have displayed altered behavioral and neurochemical responses to psychostimulants such as amphetamine (AMPH) and methamphetamine. In the present study, both in vitro and in vivo approaches were utilized to explore potential mechanisms underlying the disparate neuropharmacological effects observed following AMPH exposure in Oct3 KO mice. In vitro uptake studies conducted in OCT3 transfected cells indicated that dextroamphetamine (d-AMPH) is not a substrate of OCT3. However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT). Inhibition studies demonstrated that d-AMPH exerts relatively weak inhibitory effects on the OCT3-mediated uptake of DA, NE, 5-HT, and the model OCT3 substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide. The IC50 values were determined to be 41.5 ± 7.5 and 24.1 ± 7.0 μM for inhibiting DA and 5-HT uptake, respectively, while 50% inhibition of NE and 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide uptake was not achieved by even the highest concentration of d-AMPH applied (100 μM). Furthermore, the disposition of d-AMPH in various tissues including the brain, liver, heart, kidney, muscle, intestine, spleen, testis, uterus, and plasma were determined in both male and female Oct3 KO and WT mice. No significant difference was observed between either genotypes or sex in all tested organs and tissues. Our findings suggest that OCT3 is not a prominent factor influencing the disposition of d-AMPH. Additionally, based upon the inhibitory potency observed in vitro, d-AMPH is unlikely to inhibit the uptake of monoamines mediated by OCT3 in the brain. Differentiated neuropharmacological effects of AMPHs noted between Oct3 KO and WT mice appear to be due to the absence of Oct3 mediated uptake of neurotransmitters in the KO mice. PMID:20402963
Interaction of organic cation transporter 3 (SLC22A3) and amphetamine.
Zhu, Hao-Jie; Appel, David I; Gründemann, Dirk; Markowitz, John S
2010-07-01
The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. Relative to wild-type (WT) animals, Oct3 knockout (KO) mice have displayed altered behavioral and neurochemical responses to psychostimulants such as amphetamine (AMPH) and methamphetamine. In the present study, both in vitro and in vivo approaches were utilized to explore potential mechanisms underlying the disparate neuropharmacological effects observed following AMPH exposure in Oct3 KO mice. In vitro uptake studies conducted in OCT3 transfected cells indicated that dextroamphetamine (d-AMPH) is not a substrate of OCT3. However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT). Inhibition studies demonstrated that d-AMPH exerts relatively weak inhibitory effects on the OCT3-mediated uptake of DA, NE, 5-HT, and the model OCT3 substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide. The IC(50) values were determined to be 41.5 +/- 7.5 and 24.1 +/- 7.0 microM for inhibiting DA and 5-HT uptake, respectively, while 50% inhibition of NE and 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide uptake was not achieved by even the highest concentration of d-AMPH applied (100 microM). Furthermore, the disposition of d-AMPH in various tissues including the brain, liver, heart, kidney, muscle, intestine, spleen, testis, uterus, and plasma were determined in both male and female Oct3 KO and WT mice. No significant difference was observed between either genotypes or sex in all tested organs and tissues. Our findings suggest that OCT3 is not a prominent factor influencing the disposition of d-AMPH. Additionally, based upon the inhibitory potency observed in vitro, d-AMPH is unlikely to inhibit the uptake of monoamines mediated by OCT3 in the brain. Differentiated neuropharmacological effects of AMPHs noted between Oct3 KO and WT mice appear to be due to the absence of Oct3 mediated uptake of neurotransmitters in the KO mice.
Operating Room Utilization at Frederick Memorial Hospital
2007-07-01
nepose, including the tie for reviewin t uctiom ne t ing da o athering and ntlal8 t a e aid copletift md reviewing thin collecin of enfation Send...the continuous efforts of James Thomas , Kristen Malone, and Keith Hawkins at FMH, as their continuous efforts to gather data used in this study. James... Thomas was also essential in developing my understanding of the processes within the OR that lead to the data used to make this study meaningful
Steps Toward an Empirical Evaluation of Robust Regression Applied to Reaction-Time Data.
1986-11-01
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Duncan, M W; Smythe, G A; Clezy, P S
1985-03-01
Synthesis of deuterated (2H4)salsolinol from (2H4)dopamine via a Pictet-Spengler condensation is described. This (2H4)salsolinol is an ideal internal standard to determine picomole (ng) amounts of salsolinol (SAL) in a variety of sample types including urine, plasma, beverages and fruits. The deuterated standard is completely free of contamination by the non-deuterated species. The extraction procedure described is fast, highly efficient and does not lead to artifactual salsolinol formation even in the face of high dopamine concentrations. As well as SAL the method described allows simultaneous determination of norepinephrine (NE), dopamine (DA) and its two metabolites dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylethanol (DOPET). Each of the analytes is measured as its trifluoroacetyl derivative. Using trifluoroacetic anhydride in conjunction with trifluoroethanol allows simultaneous one-step derivatization of the acid function of DOPAC. All compounds were measured in the single ion monitoring (SIM) mode and quantified using appropriate deuterated internal standards. SAL, DA, DOPET, DOPAC and NE have been quantified in a variety of food and beverage sources. Soy sauce and dried banana have been identified as rich dietary sources of SAL. These data suggest diet should be considered a potentially important source of 'mammalian alkaloids' such as SAL, and the presence of SAL in mammalian systems is not necessarily evidence for an in vivo Pictet-Spengler condensation.
Effect of hypoxia and hypercapnia on catecholamine content in cat carotid body.
Fitzgerald, R S; Garger, P; Hauer, M C; Raff, H; Fechter, L
1983-05-01
The purpose of this study was to determine the content of catecholamines (CA) in the cat carotid body before and after 0.5 h exposures to normoxic normocapnia [arterial O2 partial pressure (Pao2) 126 +/- 28 Torr, arterial CO2 partial pressure (Paco2) 36.4 +/- 1.5 Torr], hypoxic normocapnia (Pao2 25 +/- 3 Torr, Paco2 36.7 +/- 3.3 Torr), and normoxic hypercapnia (Pao2 132 +/- 13 Torr, Paco2 = 98.2 +/- 7.6 Torr). CA synthesis was blocked using alpha-methylparatyrosine methyl ester (AMPT) prior to alterations in the inspired air. There was a significant decrease in carotid body content of dopamine (DA), norepinephrine (NE), and epinephrine (E) 1 h after AMPT administration. Analysis of variance and Duncan new multiple range procedures revealed that during the subsequent 0.5-h exposures to normoxia, hypoxia, or hypercapnia, only the decrease in DA during hypoxia was significantly greater than that during normoxia; the loss during hypercapnia was not. The decreases in NE during the three exposures were indistinguishable among themselves as were the decreases in E. The decrease in CA content is probably attributable to increased release. The data reveal that the release of CAs during the chemoreception of hypoxia is different from that during the chemoreception of hypercapnia and support the concept of different mechanisms for the chemoreception of hypoxia and hypercapnia.
Effects of Mind-Body Training on Cytokines and Their Interactions with Catecholamines.
Jang, Joon Hwan; Park, Hye Yoon; Lee, Ui Soon; Lee, Kyung-Jun; Kang, Do-Hyung
2017-07-01
Mind-body training (MBT) may control reactions to stress and regulate the nervous and immune systems. The present study was designed to assess the effects of MBT on plasma cytokines and their interactions with catecholamines. The study group consisted of 80 subjects who practice MBT and a control group of 62 healthy subjects. Plasma catecholamine (norepinephrine, NE; epinephrine, E; and dopamine, DA) and cytokine (TNF-alpha, IL-6, IFN-gamma, and IL-10) levels were measured, and the differences between the MBT and control groups and the interactions of cytokines with catecholamines were investigated. A significant increase in IL-10+IFN-gamma was found in females of the MBT group compared with controls. Also, a significant increase of IL-10 (anti-inflammatory cytokine) in the MBT group was shown in a specific condition in which TNF-alpha and IL-6 (pro-inflammatory cytokines) are almost absent (≤1 ng/L) compared with controls. In the MBT group, significant positive correlations were found between IL-10 and the NE/E ratio and between IL-10 and the DA/E ratio, whereas the control group did not show any such correlations. MBT may increase IL-10, under specific conditions such as a decrease of pro-inflammatory cytokines or E, which may regulate the stress response and possibly contribute to effective and beneficial interactions between the nervous and immune systems.
Davidson, M; Kahn, R S; Stern, R G; Hirschowitz, J; Apter, S; Knott, P; Davis, K L
1993-02-01
Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients. However, the mechanism mediating this unique efficacy has not been fully elucidated. This study examined the effect of clozapine on pHVA concentrations in schizophrenic patients. Since clozapine potently binds to alpha 2-adrenergic receptors, plasma norepinephrine (pNE) concentrations were also measured. Twenty-eight treatment-refractory schizophrenic patients (24 men, 4 women) were treated with clozapine (up to 600 mg/day) for 5 weeks, after a minimum 1-week drug-free period. Symptomatology and pHVA and pNE concentrations were measured at the last drug-free day and weekly for 5 weeks. Fourteen patients responded to clozapine treatment, while an equal number did not. Mean pHVA concentrations did not significantly change during treatment with clozapine. Although clozapine tended to lower pHVA concentrations in treatment responders, the effect was small and not significant. Clozapine treatment significantly raised pNE concentrations, but this did not differentiate responders from nonresponders to clozapine. These findings suggest that clozapine's effect on DA turnover is small and that clozapine may be effective in treatment-refractory schizophrenia by mechanisms other than, or in addition to, dopamine receptor blockade. However, since about one-third of NE is metabolized into HVA, the clozapine-induced increase in pNE may have overshadowed a possible lowering effect of clozapine on pHVA.
Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs.
Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R; McIntosh, J Michael; Brunzell, Darlene H; Cannon, Jason R; Drenan, Ryan M
2014-04-01
α6β2* nicotinic acetylcholine receptors (nAChRs)s in the ventral tegmental area to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9'S mice) that are hypersensitive to nicotine and endogenous acetylcholine. Evoked extracellular dopamine (DA) levels were enhanced in α6L9'S NAc slices compared to control, non-transgenic (non-Tg) slices. Extracellular DA levels in both non-Tg and α6L9'S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by acetylcholine plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9'S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9'S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to non-Tg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid, and norepinephrine (NE) were unchanged in α6L9'S compared to non-Tg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9'S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels. © 2013 International Society for Neurochemistry.
1989-04-12
ext. 2783 or 2264 EDUCATION: Sept. 1971 - June 1975 Knox College Galesburg, Ill. 60540 B.A. Chemistry Sept. i977 - March 1979 Rush University...a field-related effect on the daily rhythms for NE and the main metabolite of DA. The rhythms for the serotonergic system were not significantly...USA, 74, 2993-2997. Singer, S.J. and Nicolson, G.L. (1972). A fluid mosaic model of the structure of the membrane. Science, 175:720. Zagyansky, Y.A
Z.J. Wang; J.Y. Zhu; Ronald S. Jr. Zalesny; K.F. Chen
2012-05-01
Dilute acid (DA) and Sulfite Pretreatment to Overcome Recalcitrance of Lignocelluloses (SPORL) pretreatments were directly applied to wood chips of four poplar wood samples of different genotypes (hereafter referred to as poplars; Populus tremuloides Michx. ânative aspen collectionâ; Populus deltoides Bartr. ex Marsh x Populus nigra L. âNE222â and âDN5â; P. nigra x...
Wakamatsu, Kazumasa; Tanaka, Hitomi; Tabuchi, Keisuke; Ojika, Makoto; Zucca, Fabio A; Zecca, Luigi; Ito, Shosuke
2014-06-16
Neuromelanin (NM) is produced in dopaminergic neurons of the substantia nigra (SN) and in noradrenergic neurons of the locus coeruleus (LC). The synthesis of NM in those neurons is a component of brain aging and there is the evidence that this pigment can be involved in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. NM is believed to derive from the oxidative polymerization of dopamine (DA) or norepinephrine (NE) with the participation of cysteine, dolichols and proteins. However, there are still unknown aspects in the chemical structure of NM from SN (SN-NM) and LC (LC-NM). In this study, we designed a new method to synthesize o-aminophenol compounds as putative degradation products of catecholamines and their metabolites which may be incorporated into NM. Those compounds are aminohydroxyphenylethylamine (AHPEA) isomers, aminohydroxyphenylacetic acid (AHPAA) isomers and aminohydroxyethylbenzene (AHEB) isomers, which are expected to arise from DA or NE, 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylmandelic acid (DOMA) and 3,4-dihydroxyphenylethanol (DOPE) or 3,4-dihydroxyphenylethyleneglycol (DOPEG), respectively. These o-aminophenol compounds were synthesized by the nitration of phenol derivatives followed by reduction with hydroiodic acid (HI), and they could be identified by HPLC in HI hydrolysates of SN-NM and LC-NM. This degradative approach by HI hydrolysis allows the identification of catecholic precursors unique to SN-NM and LC-NM, which are present in catecholaminergic neurons.
Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur
2017-01-05
The 5-HT 1A/1B -receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT 1A/1B -receptor activation decreases impulsive choice, but increases impulsive action. Copyright © 2016 Elsevier B.V. All rights reserved.
Pérez-Valenzuela, Catherine; Gárate-Pérez, Macarena F.; Sotomayor-Zárate, Ramón; Delano, Paul H.; Dagnino-Subiabre, Alexies
2016-01-01
Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague–Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle-treated animals. These results indicate that NE has a key role in A1 and attention of stressed rats during tone discrimination. PMID:28082872
Angulo, Daniela; Bustos, Edson; Sánchez, Andrés; Barja, Salesa
2016-07-19
Introducción: la rehabilitación de la alimentación por vía oral (RVO) es compleja en pacientes que han recibido nutrición enteral (NE) prolongada. Objetivo: describir este proceso en niños con enfermedades respiratorias crónicas y sonda nasoenteral (SNE) o gastrostomía (GT).Pacientes y métodos: estudio retrospectivo con revisión de registros clínicos de niños con NE mayor a dos meses, ingresados entre 2005 y 2014 al Hospital Josefina Martínez.Resultados: Se incluyeron 116 pacientes, con mediana de edad 10 meses (Rango: 3 a 101), 56% hombres. Diagnóstico: 34,5% Daño pulmonar crónico postinfeccioso (DPC), 29,3% Insuficiencia respiratoria por enfermedad neuromuscular, 19% Displasia broncopulmonar y 17,2% enfermedad de la vía aérea. Con traqueostomía: 82,8%. Eran usuarios de GT 89,7% y de SNG 10,3%, instaladas con mediana de edad 6 meses (0 a 74), por ingesta insuficiente (6,6%) o trastorno de deglución (92,4%). Del grupo total, 36,2% (42/116) tenía indicación de RVO, los cuales habían recibido NE durante 12,2 meses (2 a 41); de estos 50% (21/42) logró alimentarse exclusivamente por vía oral (91% SNG y 35,4% GT, Chi2 p = 0,023), 14% parcialmente y 36% no lo logró. El tiempo para lograr la vía oral exclusiva fue de 9,75 meses (0,5 a 47), sin diferencia por edad, sexo, vía de acceso, duración NE ni presencia de enfermedad neurológica.Conclusión: en pacientes con enfermedades respiratorias crónicas graves y NE prolongada, la RVO es un proceso lento pero posible: 64% lo logra de modo completo o parcial.
The influence of microwave radiation from cellular phone on fetal rat brain.
Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui
2012-03-01
The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (P<0.05) found in the contents of SOD, GSH-Px, and MDA in GM and GH; the contents of SOD and GSH-Px decreased and the content of MDA increased. The significant content differences of NE and DA were found in fetal rat brains in GL and GH groups, with the GL group increased and the GH group decreased. Through this study, we concluded that receiving a certain period of microwave radiation from cellular phones during pregnancy has certain harm on fetal rat brains.
Dhanda, Saurabh; Sandhir, Rajat
2015-06-01
The present study was designed to evaluate the role of biogenic amines in behavioral alterations observed in rat model of hepatic encephalopathy (HE) following bile duct ligation (BDL). Male Wistar rats subjected to BDL developed biliary fibrosis after four weeks which was supported by altered liver function tests, increased ammonia levels and histological staining (Sirius red). Animals were assessed for their behavioral performance in terms of cognitive, anxiety and motor functions. The levels of dopamine (DA), serotonin (5-HT), epinephrine and norepinephrine (NE) were estimated in different regions of brain viz. cortex, hippocampus, striatum and cerebellum using HPLC along with activity of monoamine oxidase (MAO). Cognitive assessment of BDL rats revealed a progressive decline in learning, memory formation, retrieval, exploration of novel environment and spontaneous locomotor activity along with decrease in 5-HT and NE levels. This was accompanied by an increase in MAO activity. Motor functions of BDL rats were also altered which were evident from decrease in the time spent on the rotating rod and higher foot faults assessed using narrow beam walk task. A global decrease was observed in the DA content along with an increase in MAO activity. Histopathological studies using hematoxylin-eosin (H&E) and cresyl violet exhibited marked neuronal degeneration, wherein neurons appeared more pyknotic, condensed and damaged. The results reveal that dopaminergic and serotonergic pathways are disturbed in chronic liver failure post-BDL which may be responsible for behavioral impairments observed in HE. Copyright © 2015 Elsevier B.V. All rights reserved.
Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats.
Sahu, Surajit; Ray, Koushik; Yogendra Kumar, M S; Gupta, Shilpa; Kauser, Hina; Kumar, Sanjeev; Mishra, Kshipra; Panjwani, Usha
2012-07-15
The present study was performed to investigate the effects of Valeriana wallichi (VW) aqueous root extract on sleep-wake profile and level of brain monoamines on Sprague-Dawley rats. Electrodes and transmitters were implanted to record EEG and EMG in freely moving condition and the changes were recorded telemetrically after oral administration of VW in the doses of 100, 200 and 300 mg/kg body weight. Sleep latency was decreased and duration of non-rapid eye movement (NREM) sleep was increased in a dose dependent manner. A significant decrease of sleep latency and duration of wakefulness were observed with VW at doses of 200 and 300 mg/kg. Duration of NREM sleep as well as duration of total sleep was increased significantly after treatment with VW at the doses of 200 and 300 mg/kg. VW also increased EEG slow wave activity during NREM sleep at the doses of 200 and 300 mg/kg. Level of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and hydroxy indole acetic acid (HIAA) were measured in frontal cortex and brain stem after VW treatment at the dose of 200mg/kg. NE and 5HT level were decreased significantly in both frontal cortex and brain stem. DA and HIAA level significantly decreased only in cortex. DOPAC level was not changed in any brain region studied. In conclusion it can be said that VW water extract has a sleep quality improving effect which may be dependent upon levels of monoamines in cortex and brainstem. Copyright © 2012 Elsevier GmbH. All rights reserved.
1992-10-29
cosiofdynamic mujnkinisloniwg with adn 125 r ,, of such CB1 AirForce-widle. But peneliuz believe dmtd munmt daMl bepudwabove 50 F - r, duis, ue dw...much the levels of carbon dioxide in the body. The harm doesn’t come same for a patient with pneumonia or tuberculosis . For from taking in too much...sputum.aon iedby wit tuberculosisy-c resent blosthesam ed smputom. I there is a loss of acid and an increase in the pH factor whichO ne w ith tuberculosis m oy
1985-12-01
mounted in one NVG barrel, which he styles an NVG head up display (HUD). A similar result could be obtained by using NVGs already equipped with beam...extrietcr. La perception du relief ne peut se faire par mise en eu de le stroscopie seuls los facteur corticaux da cotta parcaption 5O. utili’c4s...r6alit,ý op6rationnelle, contr616 at idantique pour tous los sujets. Pour ce faire , dos prises do vues ont 6t r~alis~es au magn~toscope lors do vol
Turnover of Biogenic Amines in the Hypothalamus of Rats during Pyrogen Fever
NASA Technical Reports Server (NTRS)
Penn, P. E.; Williams, B. A.
1979-01-01
Many pharmacological studies have implicated the biogenic amines in the hypothalamus as playing a role in the production of fever, but few investigations of endogenous neurochemicals have been made during fever. Turnover rates of transmitters utilizing radioactive precursors may be one of the most accurate measurements of activity in brain regions. The present study was designed to measure the turnover of 5-hydroxytryptamine (5-HT) norepinephrine (NE) and dopamine (DA) in the hypothalamus of rats during pyrogen fever. Salmonella typhosa (Wyeth, 8 units) was previously found in our laboratory to produce a significant hyperthermia in most rats by 2.5 hours. This pyrogen (N = l2) or saline control (N = 8) was injected intraperitoneally and the rats killed 2.75 hours later. Rectal temperatures (Tr) were monitored continuously with thermocouples taped to the tail and recorded automatically every 3 minutes. Half of each group received an injection of radioactive precursors, (3)H-tryptophan (0.5 mCi) and (3)H-tryptophan (1.0 mCi), via an indwelling jugular catheter 60 minutes before killing, and the other half at 90 minutes. The rats were killed by near freezing in liquid nitrogen and the brains dissected in the cold. Turnover was measured by the method of Lane (Life Sci 21, 1101, 1977). At the time of killing most of the pyrogen group showed a significant (p < .02) increase (mean +/- s.e.m.) in Tr above pre injection levels (0.75 +/- 0.13 C, N = 10). The saline group showed no change (-0.025 +/- 0.16, N = 8), and the difference between groups was also significant. No significant differences were found in the levels of the amines between the pyrogen and saline groups. A significant difference was found in the specific activity of NE between the 60 minute pyrogen and saline groups (4.41 +/- 0.41 vs 2.6 +/- 0.51 dpm/pmole) but no change in turnover. This suggests an increased accumulation of (3)H-NE in the pyrogen group, but no change in utilization. An increased turnover of DA for the pyrogen group (44.5 vs 19.2 pmole/mg protein/hr) was found. However, DA is mainly a precursor in the hypothalamus and measurement was near the limit of sensitivity for the assay; these limitations Must be considered in interpreting this data. The most significant finding was an increase in the turnover of 5-HT in the pyrogen group (41.3 vs 7.3 pmole/mg protein/hr), indicating a resynthetization rate of 77% of the total pool per hour. These results suggest that at the time point measured, an increase in the utilization of 5-HT in the hypothalamus is-correlated with pyrogen fever.
Fischer, David J.; Hulvey, Matthew K.; Regel, Anne R.; Lunte, Susan M.
2012-01-01
The fabrication and evaluation of different electrode materials and electrode alignments for microchip electrophoresis with electrochemical (EC) detection is described. The influences of electrode material, both metal and carbon-based, on sensitivity and limits of detection (LOD) were examined. In addition, the effects of working electrode alignment on analytical performance (in terms of peak shape, resolution, sensitivity, and LOD) were directly compared. Using dopamine (DA), norepinephrine (NE), and catechol (CAT) as test analytes, it was found that pyrolyzed photoresist electrodes with end-channel alignment yielded the lowest limit of detection (35 nM for DA). In addition to being easier to implement, end-channel alignment also offered better analytical performance than off-channel alignment for the detection of all three analytes. In-channel electrode alignment resulted in a 3.6-fold reduction in peak skew and reduced peak tailing by a factor of 2.1 for catechol in comparison to end-channel alignment. PMID:19802847
Farrand, Ariana Q; Helke, Kristi L; Gregory, Rebecca A; Gooz, Monika; Hinson, Vanessa K; Boger, Heather A
Parkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. To assess therapeutic potential of VNS in a PD model. To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.
Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M
2016-10-01
Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice. The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated. Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.
Chauhan, Nishant Ranjan; Kapoor, Medha; Prabha Singh, Laxmi; Gupta, Rajinder Kumar; Chand Meena, Ramesh; Tulsawani, Rajkumar; Nanda, Sarita; Bala Singh, Shashi
2017-09-01
Heat Stress (HS) induces diverse pathophysiological changes, which include brain ischemia, oxidative stress and neuronal damage. The present study was undertaken with the objective to ascertain whether neuroinflammation in Hypothalamus (HTH) caused under HS affects monoamine levels and hence, its physiological role in thermoregulation. Rats were exposed to HS in a heat simulation environmental chamber (Ambient temperature, Ta=45±0.5°C and Relative Humidity, RH=30±10%) with real-time measurement of core temperature (Tc) and skin temperature (Ts). Animals were divided into two subgroups: Moderate HS (MHS) (Tc=40°C) and Severe HS (SHS)/Heat stroke (Tc=42°C). Rats with MHS showed an increase in Mean Arterial Pressure (MAP) and Heart Rate (HR) while fall in MAP and rise in HR was observed in rats with SHS. In addition, oxidative stress and an increase in pyknotic neurons were observed in HTH. High levels of Adrenocorticotropic-hormone (ACTH), Epinephrine (EPI), Norepinephrine (NE) and Dopamine (DA) in the systemic circulation and progressive increase in EPI and DA levels in HTH were recorded after the thermal insult. Moreover, a substantial increase in Glutamate (Glu) level was observed in HTH as well as in systemic circulation of heat stroke rats. We found a rise in NE whereas a fall in Serotonin (5-HT) level in HTH at MHS, without perturbing inflammatory mediators. However, rats with SHS exhibited significant elevations in NF-kB, IL-1β, COX2, GFAP and Iba1 protein expression in HTH. In conclusion, the data suggest that SHS induces neuroinflammation in HTH, which is associated with monoamines and Glu imbalances, leading to thermoregulatory disruption. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Ali, Elham H A; Elgoly, Amany H Mahmoud
2013-10-01
The aim of this work is to evaluate the impact of butyl paraben (BP) in brain of the pups developed for mothers administered BP from early pregnancy till weaning and its effect on studying the behavior, brain neurotransmitters and brain derived neurotrophic factor BDNF via comparing the results with valproic acid (VA) autistic-rat model preparing by a single oral injection dose of VA (800 mg/kg b.wt) at the 12.5 days of gestation. Butyl paraben was orally and subcutaneously administered (200 mg/kg b.wt) to pregnant rats from gestation day 1 to lactation day 21. The offspring male rats were subjected at the last 3 days of lactation to Morris water maze and three chamber sociability test then decapitated and the brain was excised and dissected to the cortex, hippocampus, cerebellum, midbrain and pons for the determination of norepinephrine, dopamine and serotonin (NE, DA and 5-HT) and cortex amino acids and whole brain BDNF. The results showed similar social and learning and memory behavioral deficits in VA rat model and the butyl paraben offspring in comparison with the controls. Also, some similar alterations were observed in monoamine content, amino acids and BDNF factor in the autistic-like model and butyl paraben offspring in comparison with the controls. The alterations were recorded notably in hippocampus and pons NE, midbrain DA, hippocampus and midbrain 5-HT, and frontal cortex GABA and asparagine. These data suggest that prenatal exposure to butyl paraben induced neuro-developmental disorders similar to some of the neurodevelopmental disorders observed in the VA model of autism. © 2013 Elsevier Inc. All rights reserved.
First Experiments with e-
NASA Astrophysics Data System (ADS)
Kabantsev, A. A.; Thompson, K. A.; Driscoll, C. F.
2017-10-01
Negative Hydrogen ions are produced and confined in a room-temperature electron plasma, causing enhanced mode damping and particle transport effects. We accumulate an H- charge fraction nH-
Antidepressant-like effect of essential oil isolated from Toona ciliata Roem. var. yunnanensis.
Duan, Dongmei; Chen, Liping; Yang, Xiuyan; Tu, Ya; Jiao, Shuang
2015-04-01
Depressive order is one of the most common psychiatric diseases, and Toona ciliata Roem. var. yunnanensis has shown many bioactivities in folk medicine. This study was designed to investigate the antidepressant-like effect of essential oil isolated from T. ciliata Roem. var. yunnanensis. Gas chromatography and mass spectrometry (GC-MS) was used to analyze the compositions of essential oil. The immobility time in the forced swimming test (FST), tail suspending test (TST), and open field test (OFT) were used to evaluate the antidepressive effects of essential oil. Furthermore, chronic mild stress (CMS) rats were established, and contents of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) in the brain were determined by high-performance liquid chromatography-electron capture detector (HPLC-ECD). Western blotting was performed to investigate the effects of essential oil on the expressions of brain-derived neurotrophic factor (BDNF) protein in rats' brain. The GC-MS analysis showed that the main components of essential oil were estragole (6.16 %), β-elemene (24.91 %), β-cubebene (14.29 %), and γ-elemene (8.05 %). The results from the FST and TST demonstrated that the immobility time could be significantly reduced by essential oil (10, 20, 40, and 80 mg/kg), without accompanying changes in ambulation when assessed in the OFT. Additionally, the contents of DA, NE, 5-HT, and BDNF in the hippocampus of CMS rats could be increased by treatment with essential oil at doses of 20, 40, and 80 mg/kg. All these results suggested that essential oil could be considered as a new candidate for curing depressive disorders.
Radioenzymatic analysis of neurotransmitters
DOE Office of Scientific and Technical Information (OSTI.GOV)
Philips, S.R.
Since the late 1960's, radioenzymatic assays have gradually come to replace the less sensitive and less specific spectrofluorometric and bioassay procedures previously used to determine many of the neurotransmitters. These assays provide the means to measure picogram quantities of most of these substances, and have enabled determinations to be made in very small volumes of body fluids, in brain perfusates and individual brain nuclei, and in large individual cells of some simple animals. This paper reviews briefly some of the radioenzymatic techniques presently available for assaying norepinephrine (NE), epinephrine (E), dopamine (DA), serotonin, and the trace amines octopamine (OA), phenylethanolaminemore » (PEOHA), phenylethylamine (PEA), tyramine (TA) and tryptamine (T).« less
Route of steroid-activated macromolecules through nuclear pores imaged with atomic force microscopy.
Oberleithner, H; Schäfer, C; Shahin, V; Albermann, L
2003-02-01
In eukaryotic cells, two concentric membranes, the nuclear envelope (NE), separate the nucleus from the cytoplasm. The NE is punctured by nuclear pore complexes (NPCs; molecular mass 120 MDa) that serve as regulated pathways for macromolecules entering and leaving the nuclear compartment. Transport across NPCs occurs through central channels. Such import and export of macromolecules through individual NPCs can be elicited in the Xenopus laevis oocyte by injecting the mineralocorticoid aldosterone and can be visualized with atomic force microscopy. The electrical NE resistance in intact cell nuclei can be measured in parallel. Resistance increases when macromolecules are engaged with the NPC. This article describe six observations made from these experiments and the conclusions that can be drawn from them. (i) A homogeneous population of macromolecules (approx. 100 kDa) attaches to the cytoplasmic face of the NPC 2 min after aldosterone injection. They are most likely to be aldosterone receptors. After a few minutes, they have disappeared. (ii) Large plugs (approx. molecular mass 1 MDa) appear in the central channels 20 min after hormone injection. They are most likely to be ribonucleoproteins exiting the nucleus. (iii) Electrical resistance measurements in isolated nuclei reveal transient electrical NE resistance peaks: an early (2 min) peak and a late (20 min) peak. Electrical peaks reflect macromolecule interaction with the NPC. (iv) Spironolactone blocks both the early and late peaks. This indicates that classic aldosterone receptors are involved in the pregenomic (early) and post-genomic (late) responses. (v) Actinomycin D and, independently, RNase A block the late electrical peak, confirming that plugs are genomic in nature. (vi) Intracellular calcium chelation blocks both early and late electrical peaks. Thus, the release of calcium from internal stores, which is known to be the first intracellular signal in response to aldosterone, is a prerequisite for the late genomic response.
Guerrero, D; Garrigue, E
2017-01-01
Atopic dermatitis (AD) is the most frequent disease treated at the Avène hydrotherapy center. Children represent a large part of the population due to the high prevalence of AD in early childhood. Avène thermal spring water (ATSW) has been known for its therapeutic effects since the middle of the 18 th century. It has been greatly studied over the last decades, with a comprehensive fundamental, pharmaco-clinical and clinical approach. Cohort studies using the Scoring Atopic Dermatitis (SCORAD) clinical score and the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index [CDLQI]) quality of life scores, allowed to confirm the clinical results obtained from the previous studies. These results were corroborated by clinical trials conducted in atopic patients outside the Avène hydrotherapy center, allowing to demonstrate the specific effect of the ATSW. Pharmacological and pharmaco-clinical studies evidenced several effects that could explain the healing effect of ATSW: effect on histamine release, anti-inflammatory effects on standardized models, immuno-modulation of some cytokines involved in DA physiopathology (interferon [INF], interleukin 2 and 4 [IL-2, IL-4]), improvement of keratinocyte differentiation, effect on the skin microbioma by promoting the development of a diversified non-pathogenic flora. In addition, an original microorganism, Aquaphilus dolomiae, never described in another medium, has very recently been identified in the ATSW. Aquaphilus dolomiae is responsible for significant pharmacological activities on inflammation, pruritus and enhancement of innate immunity. This set of works confirms the medical significance of the hydrotherapy which should be considered as a complementary care in the sometimes difficult management of AD. © 2017 Elsevier Masson SAS. Tous droits réservés.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang Yongqing; Wang Anzhong
2011-05-15
In this paper, we investigate three important issues: stability, ghost, and strong coupling, in the Horava-Melby-Thompson setup of the Horava-Lifshitz theory with {lambda}{ne}1, generalized recently by da Silva. We first develop the general linear scalar perturbations of the Friedmann-Robertson-Walker (FRW) universe with arbitrary spatial curvature and find that an immediate by-product of the setup is that, in all the inflationary models described by a scalar field, the FRW universe is necessarily flat. Applying them to the case of the Minkowski background, we find that it is stable, and, similar to the case {lambda}=1, the spin-0 graviton is eliminated. The vectormore » perturbations vanish identically in the Minkowski background. Thus, similar to general relativity, a free gravitational field in this setup is completely described by a spin-2 massless graviton, even with {lambda}{ne}1. We also study the ghost problem in the FRW background and find explicitly the ghost-free conditions. To study the strong coupling problem, we consider two different kinds of spacetimes, all with the presence of matter: one is cosmological, and the other is static. We find that the coupling becomes strong for a process with energy higher than M{sub pl}|c{sub {psi}|}{sup 5/2} in the flat FRW background and M{sub pl}|c{sub {psi}|}{sup 3} in a static weak gravitational field, where |c{sub {psi}|{identical_to}}|(1-{lambda})/(3{lambda}-1)|{sup 1/2}.« less
Approaches for the Development of Drugs for Treatment of Obesity and Metabolic Syndrome.
Maksimov, Maksim L; Svistunov, Andrey A; Tarasov, Vadim V; Chubarev, Vladimir N; Ávila-Rodriguez, Marco; Barreto, George E; Dralova, Olga V; Aliev, Gjumrakch
2016-01-01
Obesity and metabolic syndrome (MS) are risk factors for diabetes, cancer, some cardiovascular and musculoskeletal diseases. Pharmacotherapy should be used when the body mass index (BMI) exceeds 30 kg/m² or 27 kg/m² with comorbidity. Efficacy and safety of pharmacotherapy depend on the mechanism of action of drugs. In this context, drugs affecting the central and peripheral mediator systems such as cannabinoid receptor antagonists (Rimonabant), neuronal reuptake inhibitor of NE and 5 HT (Sibutramine), neuronal reuptake inhibitor of NE 5-HT DA (Tesofensine), agonist of 5 HT 2C receptors (Lorcaserin) have a high risk of side effects on the central nervous and cardiovascular systems when used for a long period. Apparently, the drugs design targeting obesity should screen safer drugs that affect fat absorption (Orlistat), activate energy metabolism (Adipokines), inhibit MetAP2 (Beloranib) and other peripheral metabolic processes. The use of synergies of anti-obesity drugs with different mechanisms of action is an effective approach for developing new combined pharmaceutical compositions (Contrave®, EmpaticTM, Qsymia et al). The purpose of this article is to review the currently available anti-obesity drugs and some new promising trends in development of anti-obesity therapy.
Dalterio, S; Steger, R; Mayfield, D; Bartke, A
1984-01-01
Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.
Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti
2016-06-01
Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.
NASA Astrophysics Data System (ADS)
Yu, Zhongyuan; Zhang, Peizhen; Min, Wei; Wei, Qinghai; Zhao, Bin
2018-01-01
The Da'an-Dedu Fault Zone (DDFZ) is a major tectonic feature cutting through the Songliao Basin from south to north in NE China. Pulsed compression deformation of DDFZ during the Cenozoic implies a complex geodynamic process, and the latest stage of which occurred in the Quaternary directly influences the present seismicity of the interior basin. Although most of the evidence for Quaternary deformation about the Songliao Basin in the past decades was concentrated in marginal faults, all five earthquake swarms with magnitudes over 5.0 along the buried DDFZ with no surface expression during the past 30 years suggest it is a main seismogenic structure with seismic potential, which should deserve more attention of geologists. However, limited by the coverage of the Quaternary sedimentary and absence of strong historic and instrumental earthquakes records (M > 7), the geometric pattern, Quaternary activity and seismic potential of the DDFZ remain poorly understood. Thus, unlike previous geophysical studies focused on crust/mantle velocity structure across the fault and the aim of exploring possible mineral resources in the basin, in this study we have integrated a variety of the latest seismic data and drilling holes from petroleum explorations and shallow-depth seismic reflection profiles, to recognize the Cenozoic pulsed compression deformation of the DDFZ, and to discuss its implication for earthquake potential. The results show that at least four stages of compression deformation have occurred along the DDFZ in the Cenozoic: 65 Ma, 23 Ma, 5.3 Ma, and 1.8 Ma, respectively, although the geodynamic process behind which still in dispute. The results also imply that the tectonic style of the DDFZ fits well with the occurrence of modern seismic swarms. Moderate earthquake potential (M ≤ 7.0) is suggested along the DDFZ.
The Guadalquivir Diapiric Ridge: Deep Tectonics and Related Gas Structures
NASA Astrophysics Data System (ADS)
Fernández-Puga, M. C.; Somoza, L.; Pinheiro, L. M.; Magalhães, V.; Vázquez, J. T.; Díaz-del-Río, V.; Ivanov, M.
Cooperation between the Spanish TASYO project during the cruises Tasyo/2000, Anastasya/99, Anastasya/00 and Anastasya/01 and the UNESCO-IOC Trainning Trough Research Programme during the TTR9, TTR10 and TTR-11 cruises have per- mitted to identify numerous structures related to hydrocarbon seepages in the Gulf of Cadiz, located between the Africa and Eurasia plate. The interpretation of multibeam bathymetry and a large database of reflection seismic profiles shows two important morphotectonics structures: the Cadiz Diapiric Ridge (CDR) and the Guadalquivir Di- apiric Ridge (GDR). The CDR is a diapiric elongate structure located between 400 and 700m water depth, with a N-S direction. The GDR is an elongated ridge, situated west- ward of this structure and located along the shelf and slope between 300-1100m depth. This highly deformed ridge, formed by several diapirs oriented in NE-SW direction, has been mapped using industrial multifold seismic, core logs, gravity cores, dredge samples and photographs, obtained during the ANASTASYA 01/09 cruise. This data has shown that it is composed of early-middle Miocene blue marls (Maldonado et al, 1999), mud breccias and calcarenites. In fact, this diapiric structure is associated with a complex tectono-sedimentary history related to along slope gravity gliding and tec- tonic compression westward the fronts of the deformed wedges of the SOlistostromic & cedil;allochtonous unitsT (Somoza et al., 1999). According to the observed and sampled structures along the GDR, this ridge can be divided in three areas: (a) The NE area is characterized by the existence of a series of wide single sub-circular mud volcanoes (Anastasya, Tarsis and Pipoca), surrounded by a ring shaped seafloor depression. Mud breccia has been collected from these mud volcanoes (ANAS00-TG5,TG6,TG7,TG8 and ANAS01-TG2); (b) a central sector with long rounded-like crater structures, of unknown origin, from which calcarenites were collected (ANAS01-DA13); and (c) a SW sector, between 8zW and 7z40`W, that is caracterized by a series of mud mounds boundarying the Cadiz channel: Iberico, Cornide and Hormigas. In this area, abundant carbonate chimneys, slab and calcarenites were collected (ANAS00-DA10, ANAS01-DA1,DA2,DA15). All these seabed structures suggest high-pressure expul- sion of methane-enriched muds along thrusting faults. This research has been supported by the "TASYO" project (Tecto-sedimentary transfer 1 from shelf to Horseshoe and Seine abyssal plains in the Gulf of Cadiz) of the Spanish- funded Marine Science and Technology programme (CYTMAR 98-0209) in the frame of the Spanish-Portuguese agreement for scientific co-operation. References: Maldonado, A.,Somoza, L., Pallarés, L., 1999. The Betic orogen and the Iberian- African boundary in the Gulf of Cadiz : geological evolution (Central North Atlantic). Mar. Geol., 155, 9-43. Somoza, L., Maestro, A., Lowrie, A., 1999. Allochtonous Blocks as Hydrocarbon Traps in the Gulf of Cadiz. Offshore Technology Conference OTC 10889, 571-577. 2
Implications of streamlining theory for microbial ecology
Giovannoni, Stephen J; Cameron Thrash, J; Temperton, Ben
2014-01-01
Whether a small cell, a small genome or a minimal set of chemical reactions with self-replicating properties, simplicity is beguiling. As Leonardo da Vinci reportedly said, ‘simplicity is the ultimate sophistication'. Two diverging views of simplicity have emerged in accounts of symbiotic and commensal bacteria and cosmopolitan free-living bacteria with small genomes. The small genomes of obligate insect endosymbionts have been attributed to genetic drift caused by small effective population sizes (Ne). In contrast, streamlining theory attributes small cells and genomes to selection for efficient use of nutrients in populations where Ne is large and nutrients limit growth. Regardless of the cause of genome reduction, lost coding potential eventually dictates loss of function. Consequences of reductive evolution in streamlined organisms include atypical patterns of prototrophy and the absence of common regulatory systems, which have been linked to difficulty in culturing these cells. Recent evidence from metagenomics suggests that streamlining is commonplace, may broadly explain the phenomenon of the uncultured microbial majority, and might also explain the highly interdependent (connected) behavior of many microbial ecosystems. Streamlining theory is belied by the observation that many successful bacteria are large cells with complex genomes. To fully appreciate streamlining, we must look to the life histories and adaptive strategies of cells, which impose minimum requirements for complexity that vary with niche. PMID:24739623
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C.
1996-05-01
There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically puremore » {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.« less
USDA-ARS?s Scientific Manuscript database
NE Trailblazer C-1 (GP-101, PI 672015), NE Trailblazer C0 (GP-100, PI 672014), NE Trailblazer C2 (GP-102, PI 672016), NE Trailblazer C3 (GP-103, PI 672017), NE Trailblazer C4 (GP-104, PI 672018), and NE Trailblazer C5 (GP-105, PI 672019) switchgrass (Panicum virgatum L.) germplasms were released by ...
Solar helium and neon in the Earth
NASA Technical Reports Server (NTRS)
Honda, M.; Mcdougall, I.; Patterson, D. B.
1994-01-01
Neon isotopic compositions in mantle-derived samples commonly are enriched in (20)Ne and (21)Ne relative to (22)Ne compared with atmospheric neon ((20)Ne/(22)Ne and (21)Ne/(22)Ne ratios in atmospheric neon are 9.8 and 0.029, respectively), together with significant primordial (3)He. Such results have been obtained on MORB's, intraplate plume-related oceanic island basalts, backarc basin basalts, mantle xenoliths, ancient diamonds and CO2 well gases (e.g., 1 - 8). The highest (20)Ne/(22)Ne ratio observed in MORB glasses (= 13.6 plus or minus 1.3 is close to the solar value (= 13.6, as observed in solar wind). In order to explain the enrichment of (20)Ne and (21)Ne relative to atmospheric neon for samples derived from the mantle, it is necessary to postulate the presence of at least two distinct non-atmospheric components. The two most likely candidates are solar and nucleogenic ((20)Ne/(22)Ne solar = 13.6 (21)Ne/(22)Ne solar = 0.032, (20)Ne/(22)Ne nucleogenic = 2.5 and (21)Ne/(22)Ne nucleogenic = 32). This is because solar neon is the only known component with a (20)Ne/(22)Ne ratio greater than both the atmospheric value and that observed in samples derived from the mantle. Nucleogenic neon is well known to elevate (21)Ne/(22)Ne ratios. Neon isotopic signatures observed in mantle-derived samples can be accounted for by mixing of the three neon end members: solar, nucleogenic and atmospheric.
Spectroscopic evidence of hippocampal abnormalities in neocortical epilepsy
Mueller, S. G.; Laxer, K. D.; Cashdollar, N.; Lopez, R. C.; Weiner, M. W.
2009-01-01
Lesional neocortical epilepsy (NE) can be associated with hippocampal sclerosis or hippocampal spectroscopic abnormalities without atrophy (dual pathology). In this study, magnetic resonance spectroscopic imaging (MRSI) was used to determine the frequency of hippocampal damage/dysfunction in NE with and without structural lesion. Sixteen patients with NE [seven temporal NE (NE-T), nine extratemporal (NE-ET)] and 16 controls were studied with a 2D MRSI sequence (Repetition time/echo time (TR/TE) = 1800/135 ms) covering both hippocampi. Seven NE patients had MR visible lesions (NE-Les), nine had normal MRI (NE-no). In each hippocampus, 12 voxels were uniformly selected. In controls, mean (± SD) NAA/(Cr + Cho) values for each voxel were calculated and voxels with NAA/(Cr + Cho) ≤ (mean in controls – 2SD in controls) were defined as ‘pathological’ in patients. Eight of 16 NE patients had at least two ‘pathological’ voxel (mean 2.5, range 2–5) in one hippocampus. Four were NE-Les and four NE-no. Three (43%) NE-T patients, had evidence for hippocampal damage/dysfunction and five (56%) had NE-ET. The ipsilateral hippocampus was affected in six of eight NE patients. Evidence for unilateral hippocampal damage/dysfunction was demonstrated in 50% of the NE patients. The type of NE, i.e. NE-Les or NE-no, NE-T or NE-ET, had no influence on the occurrence of hippocampal damage/dysfunction. PMID:16618342
"Normal Planetary" Ne-Q in Chelyabinsk and Mars
NASA Astrophysics Data System (ADS)
Nyquist, L. E.; Park, J.; Nagao, K.; Haba, M. K.; Mikouchi, T.; Kusakabe, M.; Shih, C.-Y.; Herzog, G. F.
2015-07-01
Chelyabinsk contains “Q”-noble gases. Martian shergottite Dhofar 378 contains trapped 20Ne/22Ne = 7.3±0.3, derivable from Q-Ne with 20Ne/22Ne = 10.67 via fractionation by solar wind induced sputtering. Martian juvenile Ne is suggested to be Q-Ne.
Atmospheric 21Ne abundance determined by the Helix-MC Plus mass spectrometer
NASA Astrophysics Data System (ADS)
Honda, M.; Zhang, X.; Phillips, D.; Hamilton, D.; Deerberg, M.; Schwieters, J. B.
2014-12-01
Analyses of noble gas isotopes by multi-collector, high resolution mass spectrometry have the potential to revolutionise applications in the cosmo-geo-sciences. The Helix-MC Plus noble gas mass spectrometer installed at the Australian National University (ANU) is equipped with unique high mass resolution collectors [mass resolution (MR): ~1,800 and mass resolving power (MRP): ~8,000], including fixed axial (Ax), adjustable high mass (H2) and adjustable low mass (L2) detectors. The high mass resolution of the L2, Ax and H2 collectors permits complete separation of 20Ne (measured on L2 detector) from doubly charged interfering 40Ar (required MR of 1,777), 1H19F (MR = 1450), 1H218O (MR = 894) and partial separation of the 21Ne peak (on Ax detector) from interfering 20Ne1H (MR = 3,271), and 22Ne (on H2 detector) from interfering doubly charged CO2 (MR = 6,231). Because of the high MRP of ~8,000, 21Ne can be measured, essentially without interference from 20Ne1H, by setting the magnet position on a 20Ne1H interference-free position. This capability provides an important opportunity to re-evaluate the 21Ne abundance in the atmosphere. Our analyses demonstrate that 20Ne1H contributes ~4% to atmospheric 21Ne measurements, with the corresponding production ratio of 20Ne1H to 20Ne being ~1E-4. We calculate a new atmospheric 21Ne/20Ne ratio of 0.00287 relative to an atmospheric 22Ne/20Ne ratio of 0.102; this new value is distinctly lower than the current IUPAC recommended 21Ne/20Ne value of 0.00298. There are several significant implications ensuing from the newly determined atmospheric 21Ne abundance. For example, in the area of Earth sciences the most critical issue relates to cosmogenic 21Ne surface exposure ages, which involve the calculation of 21Ne concentrations from excess 21Ne, relative to the atmospheric 21Ne/20Ne ratio. For young samples, where cosmogenic 21Ne contents are small and the 21Ne/20Ne ratio is close to the atmospheric value, the revised value could increase cosmogenic 21Ne ages by ~30%.
Ne-20/Ne-22 in the Martian Atmosphere: New Evidence from Martian Meteorites
NASA Technical Reports Server (NTRS)
Park, J.; Nyquist, L. E.; Herzog, G. F.; Nagao, K.; Mikouchi, T.; Kusakabe, M.
2017-01-01
Analyses of Ne trapped in "pods" of impact melt in the Elephant Moraine 79001 (EET 79001) Martian meteorite led to suggest (Ne-20/Ne-22) approx.10 in the Martian atmosphere (MA). In contrast, obtained trapped (Ne-20/Ne-22)Tr approx.7 from an impact melt vein in Yamato 793605 (Y-793605) and concluded that the isotopic composition of Martian Ne remained poorly defined. A "pyroxene-rich" separate from Dhofar 378 (Dho 378) analyzed gave a comparatively high trapped Ne concentration and (Ne-20/Ne-22) = 7.3+/-0.2 in agreement with the Y-793605 value. We explore the hypothesis that Martian Ne was trapped in the Dho 378 meteorite in a manner similar to entrapment of terrestrial Ne in tektites strengthening the "Martian atmosphere" interpretation. We also report new data for Northwest Africa 7034 (NWA 7034) that are consistent with the Ne data for Dho 378.
Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling.
Kristensen, Jacob H; Karsdal, Morten A; Sand, Jannie Mb; Willumsen, Nicholas; Diefenbach, Claudia; Svensson, Birte; Hägglund, Per; Oersnes-Leeming, Diana J
2015-05-03
During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for antibody generation and developed an ELISA assay (EL-NE) for the quantification of NE-degraded elastin. Monoclonal antibodies were developed against 10 NE-specific cleavage sites on elastin. One EL-NE assay was tested for analyte stability, linearity and intra- and inter-assay variation. The NE specificity was demonstrated using elastin cleaved in vitro with matrix metalloproteinases (MMPs), cathepsin G (CatG), NE and intact elastin. Clinical relevance was assessed by measuring levels of NE-generated elastin fragments in serum of patients diagnosed with idiopathic pulmonary fibrosis (IPF, n = 10) or lung cancer (n = 40). Analyte recovery of EL-NE for human serum was between 85% and 104%, the analyte was stable for four freeze/thaw cycles and after 24 h storage at 4°C. EL-NE was specific for NE-degraded elastin. Levels of NE-generated elastin fragments for elastin incubated in the presence of NE were 900% to 4700% higher than those seen with CatG or MMP incubation or in intact elastin. Serum levels of NE-generated elastin fragments were significantly increased in patients with IPF (137%, p = 0.002) and in patients with lung cancer (510%, p < 0.001) compared with age- and sex-matched controls. The EL-NE assay was specific for NE-degraded elastin. The EL-NE assay was able to specifically quantify NE-degraded elastin in serum. Serum levels of NE-degraded elastin might be used to detect excessive lung tissue degradation in lung cancer and IPF.
1991-01-08
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Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni
2017-09-01
CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased. To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopamine in the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Hamilton, D.; Honda, M.; Zhang, X.; Phillips, D.; Matchan, E.
2017-12-01
The Helix-MC Plus multi-collector noble gas mass spectrometer at the Australian National University is uniquely equipped with three high mass resolution collectors on H2, Axial and L2 positions. Their mass resolution and mass resolving power are as high as 1,800 and 8,000, respectively. The Helix-MC Plus can totally separate 20Ne+ from 40Ar++ isobaric interference and also partially separate 21Ne+ from 20NeH+ and 22Ne+ from 12C16O2++. By adjusting collector positions, we are able to measure interference-free Ne isotope intensities and have re-determined the 21Ne abundance in air [1]. Analyses by Honda et al. [1] demonstrated that 20Ne1H contributes approximately 2% to previously determined atmospheric 21Ne values [2], and a new atmospheric 21Ne/20Ne ratio of 0.002906 was calculated. Using the Helix-MC Plus mass spectrometer, we measured Ne abundances in the CREU-1 quartz standard [3] and determined cosmogenic concentrations by subtraction of atmospheric Ne with the new atmospheric 21Ne/20Ne value. The average concentration of cosmogenic 21Ne determined from four repeated analyses is 338 ± 12 × 106 atom/g (2σ). This compares with the average concentration of 348 ± 10 × 106 atom/g (2σ) from 45 analyses determined by several laboratories [3], where Ne isotope analyses were undertaken by conventional low resolution mass spectrometers and atmospheric Ne was subtracted using the conventional atmospheric 21Ne/20Ne [2]. On this basis, for a sample with abundant cosmogenic Ne, like CREU-1 quartz, previously measured by low mass resolution mass spectrometers are likely valid and their geological implications are unaffected. However, for low 21Ne concentration samples, combining new generation of mass spectrometers as well as the new atmospheric ratio may have significance for cosmogenic 21Ne surface exposure dating. References: [1] Honda M., et. al., International Journal of Mass Spectrometry, 387, 1 (2015). [2] Eberhardt P., et. al., Zeitschrift fur Naturforschung, 20a, 623 (1965). [3] Vermeesch P., et. al., Quaternary Geochronology, 26, 20 (2015).
Krichmar, Jeffrey L.
2013-01-01
The vertebrate neuromodulatory systems are critical for appropriate value-laden responses to environmental challenges. Whereas changes in the overall level of dopamine (DA) have an effect on the organism's reward or curiosity-seeking behavior, changes in the level of serotonin (5-HT) can affect its level of anxiety or harm aversion. Moreover, top-down signals from frontal cortex can exert cognitive control on these neuromodulatory systems. The cholinergic (ACh) and noradrenergic (NE) systems affect the ability to filter out noise and irrelevant events. We introduce a neural network for action selection that is based on these principles of neuromodulatory systems. The algorithm tested the hypothesis that high levels of serotonin lead to withdrawn behavior by suppressing DA action and that high levels of DA or low levels of 5-HT lead to curious, exploratory behavior. Furthermore, the algorithm tested the idea that top-down signals from the frontal cortex to neuromodulatory areas are critical for an organism to cope with both stressful and novel events. The neural network was implemented on an autonomous robot and tested in an open-field paradigm. The open-field test is often used to test for models anxiety or exploratory behavior in the rodent and allows for qualitative comparisons with the neurorobot's behavior. The present neurorobotic experiments can lead to a better understanding of how neuromodulatory signaling affects the balance between anxious and curious behavior. Therefore, this experimental paradigm may also be informative in exploring a wide range of neurological diseases such as anxiety, autism, attention deficit disorders, and obsessive-compulsive disorders. PMID:23386829
Determinação da composição química em nebulosas planetárias na direção do anticentro galáctico
NASA Astrophysics Data System (ADS)
Costa, R. D. D.; Uchida, M. M. M.; Maciel, W. J.
2003-08-01
Existe um gradiente radial de abundâncias no disco galáctico, cujo comportamento é razoavelmente bem conhecido para distâncias galactocêntricas entre 3 e 10 kpc. Foi obtido a partir de resultados derivados de nebulosas planetárias, regiões HII e estrelas, como as estrelas quentes de tipo O, B e aglomerados abertos. Com o objetivo de investigar o comportamento deste gradiente radial na região externa do disco, conhecida como anticentro galáctico, reportamos aqui os resultados finais da análise de uma amostra de nebulosas planetárias na direção do anticentro, observadas no LNA e no ESO entre 1995 e 2000. O uso de nebulosas planetárias permite o cálculo das abundâncias de elementos traçadores da evolução química do disco como oxigênio, argônio e neônio com o uso de técnicas de espectroscopia nebular. Os resultados indicam uma distribuição de abundâncias distinta daquela encontrada na vizinhança solar, mostrando que o gradiente radial diminui sensivelmente para distâncias galactocêntricas maiores que 10 kpc. Este resultado está de acordo com os mais recentes modelos de evolução química do disco, que prevêem uma diminuição ou mesmo um desaparecimento do gradiente radial no bordo externo do disco galáctico. (FAPESP/CNPq)
Comparison of the triple-point temperatures of {sup 20}Ne, {sup 22}Ne and normal Ne
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nakano, T.; Tamura, O.; Nagao, K.
2013-09-11
At the National Metrology Institute of Japan (NMIJ), the triple points of {sup 20}Ne and {sup 22}Ne were realized using modular sealed cells, Ec3Ne20 and Ec8Ne22, made by the Istituto Nazionale di Ricerca Metrologica (INRiM) in Italy. The difference of the triple-point temperatures of {sup 20}Ne and {sup 22}Ne was estimated by using the sub-range of standard platinum resistance thermometers (SPRTs) calibrated by NMIJ on the International Temperature Scale of 1990 (ITS-90). The melting curves obtained with the Ec3Ne20 and Ec8Ne22 cells show narrow widths (0.1 mK) over a wide range of the inverse of the melted fraction (1/F) frommore » 1/F=1 to 1/F=10. The liquidus point T{sub tp} estimated by the melting curves from F∼0.5 to F∼0.85 using the Ec8Ne22 is 0.146 29 (4) K higher than that using the Ec3Ne20 cell, which is in good agreement with that observed by INRiM using the same cells. After correction of the effect of impurities and other isotopes for Ec3Ne20 and Ec8Ne22 cells, the difference of T{sub tp} between pure {sup 20}Ne and pure {sup 22}Ne is estimated to be 0.146 61 (4) K, which is consistent with the recent results reported elsewhere. The sub-ranges of SPRTs computed by using the triple point of {sup 20}Ne or {sup 22}Ne realized by the Ec3Ne20 cell or the Ec8Ne22 cell in place of the triple point of Ne for the defining fixed point of the ITS-90 are in good agreement with those realized on the basis of the ITS-90 at NMIJ within 0.03 mK, which is much smaller than the non-uniqueness and the sub-range inconsistency of SPRTs.« less
Nishi, Kyoko; Mück-Seler, Dorotea; Hasegawa, Shu; Watanabe, Arata; Diksic, Mirko
2006-10-16
Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) released from nerve terminals in the brain are primarily removed from the synaptic cleft by a reuptake mechanism. In part, the homeostasis is maintained by monoamine oxidase (MAO) deamination achieved primarily intracellularly. The present study's aim was to examine the effect of the acute administration of the MAO inhibitors, moclobemide (a MAO-A inhibitor) and deprenyl (a MAO-B inhibitor), on 5-HT synthesis rates, measured in discrete regions of the rat brain by an autoradiographic method, using alpha-[14C]methyl-l-tryptophan as a tracer. MAO inhibitors have different effects on 5-HT synthesis rates in the cell bodies and areas of the nerve terminals. Moclobemide (10 mg/kg, i.p. 30 min before the tracer injection) and deprenyl (3 mg/kg, i.p. 2 h before the tracer injection) decreased the 5-HT synthesis rates in the dorsal (-18% and -22%) and median (-22% and -33%) raphe, respectively. Moclobemide also significantly decreased 5-HT synthesis in the entire nerve terminal areas investigated. The reductions were between 23% (cingulate cortex) and 50% (locus coeruleus). Deprenyl did not significantly affect 5-HT synthesis in the nerve terminals. The present results suggest that MAO-A, and to a lesser extent, MAO-B, are involved in the regulation of 5-HT synthesis in the rat brain. The mechanism(s) of MAO inhibitors' action on 5-HT synthesis in the raphe nuclei are probably related to an increase in the extraneuronal 5-HT concentration and also to the interaction between the serotonergic and catecholaminergic neurons. The reduction of 5-HT synthesis in the raphe nuclei likely occurs by an action of extracellular 5-HT via the dendritic autoreceptors with a possible contribution from the action of extracellular DA and NE. In the terminal regions, the most likely mechanism is via the presynaptic autoreceptors through which elevated extraneuronal 5-HT acts on synthesis control. However, there is also a possibility that the elevation in intraneuronal 5-HT directly inhibits its synthesis, especially following deprenyl treatment. A great influence of moclobemide on 5-HT synthesis could be related to its antidepressant action.
Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair
Penfield, Lauren; Wysolmerski, Brian; Mauro, Michael; Farhadifar, Reza; Martinez, Michael A.; Biggs, Ronald; Wu, Hai-Yin; Broberg, Curtis; Needleman, Daniel; Bahmanyar, Shirin
2018-01-01
Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) ruptures and repairs in interphase. The duration of NE ruptures depends on lamins; however, the underlying mechanisms and relevance to in vivo events are not known. Here, we use the Caenorhabditis elegans zygote to analyze lamin’s role in NE rupture and repair in vivo. Transient NE ruptures and subsequent NE collapse are induced by weaknesses in the nuclear lamina caused by expression of an engineered hypomorphic C. elegans lamin allele. Dynein-generated forces that position nuclei enhance the severity of transient NE ruptures and cause NE collapse. Reduction of dynein forces allows the weakened lamin network to restrict nucleo–cytoplasmic mixing and support stable NE recovery. Surprisingly, the high incidence of transient NE ruptures does not contribute to embryonic lethality, which is instead correlated with stochastic chromosome scattering resulting from premature NE collapse, suggesting that C. elegans tolerates transient losses of NE compartmentalization during early embryogenesis. In sum, we demonstrate that lamin counteracts dynein forces to promote stable NE repair and prevent catastrophic NE collapse, and thus provide the first mechanistic analysis of NE rupture and repair in an organismal context. PMID:29386297
Neutrophil elastase and proteinase 3 trafficking routes in myelomonocytic cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kaellquist, Linda; Rosen, Hanna; Nordenfelt, Pontus
2010-11-15
Neutrophil elastase (NE) and proteinase 3 (PR3) differ in intracellular localization, which may reflect different trafficking mechanisms of the precursor forms when synthesized at immature stages of neutrophils. To shed further light on these mechanisms, we compared the trafficking of precursor NE (proNE) and precursor PR3 (proPR3). Like proNE [1], proPR3 interacted with CD63 upon heterologous co-expression in COS cells but endogenous interaction was not detected although cell surface proNE/proPR3/CD63 were co-endocytosed in myelomonocytic cells. Cell surface proNE/proPR3 turned over more rapidly than cell surface CD63 consistent with processing/degradation of the pro-proteases but recycling of CD63. Colocalization of proNE/proPR3/CD63 withmore » clathrin and Rab 7 suggested trafficking through coated vesicles and late endosomes. Partial caveolar trafficking of proNE/CD63 but not proPR3 was suggested by colocalization with caveolin-1. Blocking the C-terminus of proNE/proPR3 by creating a fusion with FK506 binding protein inhibited endosomal re-uptake of proNE but not proPR3 indicating 'pro{sub C}'-peptide-dependent structural/conformational requirements for proNE but not for proPR3 endocytosis. The NE aminoacid residue Y199 of a proposed NE sorting motif that interacts with AP-3 [2] was not required for proNE processing, sorting or endocytosis in rat basophilic leukemia (RBL) cells expressing heterologous Y199-deleted proNE; this suggests operation of another AP-3-link for proNE targeting. Our results show intracellular multi-step trafficking to be different between proNE and proPR3 consistent with their differential subcellular NE/PR3 localization in neutrophils.« less
New global electron density observations from GPS-RO in the D- and E-Region ionosphere
NASA Astrophysics Data System (ADS)
Wu, Dong L.
2018-06-01
A novel retrieval technique is developed for electron density (Ne) in the D- and E-region (80-120 km) using the high-quality 50-Hz GPS radio occultation (GPS-RO) phase measurements. The new algorithm assumes a slow, linear variation in the F-region background when the GPS-RO passes through the D- and E-region, and extracts the Ne profiles at 80-130 km from the phase advance signal caused by Ne. Unlike the conventional Abel function, the new approach produces a sharp Ne weighting function in the lower ionosphere, and the Ne retrievals are in good agreement with the IRI (International Reference Ionosphere) model in terms of monthly maps, zonal means and diurnal variations. The daytime GPS-RO Ne profiles can be well characterized by the α-Chapman function of three parameters (NmE, hmE and H), showing that the bottom of E-region is deepening and sharpening towards the summer pole. At high latitudes the monthly GPS-RO Ne maps at 80-120 km reveal clear enhancement in the auroral zones, more prominent at night, as a result of energetic electron precipitation (EEP) from the outer radiation belt. The D-/E-region auroral Ne is strongly correlated with Kp on a daily basis. The new Ne data allow further comprehensive analyses of the sporadic E (Es) phenomena in connection with the background Ne in the E-region. The layered (2-10 km) and fluctuated (<2 km) Es components, namely Ne_Layer than Ne_Pert, are extracted with respect to the background Ne_Region on a profile-by-profile basis. The Ne_Layer component has a strong but highly-refined peak at ∼105 km, with an amplitude smaller than Ne_Region approximately by an order of magnitude. The Ne_Pert component, which was studied extensively in the past, is ∼2 orders of magnitude weaker than Ne_Layer. Both Ne_Layer and Ne_Pert are subject to significant diurnal and semidiurnal variations, showing downward progression with local time in amplitude. The 11-year solar cycle dominates the Ne interannual variations, showing larger Ne_Region and Ne_Layer but smaller Ne_Pert amplitudes in the solar maximum years. Enhanced Ne profiles are often observed in the polar winter, showing good correlation with solar proton events (SPEs) and geomagnetic activity. The new methodology offers great potential for retrieving low Ne in the D-region, where radio propagation and communication blackouts can occur due to enhanced ionization. For space weather applications it is recommended for GPS-RO operations to raise the top of high-rate data acquisition to ∼140 km in the future.
Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats.
McCarty; Pacak; Goldstein; Eisenhofer
1997-12-01
Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nuriya, Mutsuo; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501
Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This primingmore » effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. - Highlights: • Background NE augments the responsiveness of astrocytes to subsequent NE stimulation. • The priming effect is independent of neuronal activity and mediated by βadrenoceptor. • Background subthreshold NE may play gliomodulatory roles in the cerebral cortex.« less
Source of Volatiles in Earth's Deep Mantle from Neon Isotope Systematics in the South Atlantic
NASA Astrophysics Data System (ADS)
Williams, C. D.; Mukhopadhyay, S.
2016-12-01
The noble gases play an important role in understanding Earth's accretion and subsequent evolution. Neon isotopes in particular have the potential to distinguish between distinct sources of Earth's volatiles e.g., acquisition of nebular gas, solar wind implanted materials or chondritic meteorites and their components. The neon isotopic composition of the deep mantle remains subject to debate with the majority of mantle-derived basalts displaying maximum 20Ne/22Ne ratios less than 12.5, similar to values determined for the convective mantle (20Ne/22Ne = 12.49 +/- 0.04; [1]). These values are also much lower than those of solar wind (20Ne/22Ne = 13.8; [2,3]) and estimates of the nebular gas (20Ne/22Ne = 13.4; [4]) but comparable to solar wind implanted meteoritic materials (20Ne/22Ne = 12.5-12.7; [5]). Here we determine the neon isotopic composition of mantle-derived materials from the south Atlantic. These samples display strong linear correlations in 20Ne/22Ne-21Ne/22Ne space with maximum 20Ne/22Ne ratios that are resolvable from and higher than materials derived from the convecting mantle as well as models of solar wind implantation. These results supplement a growing database of mantle materials characterized by 20Ne/22Ne ratios greater than 12.5, challenging the notion that the entire mantle acquired volatiles from solar wind implanted meteoritic materials. In this presentation we will explore alternative origins for these volatiles and provide testable predictions for each scenario. [1] G. Holland, C.J. Ballentine.. Nature 441 (2006), 186-191. [2] A. Gimberg et al. GCA 72 (2008), 626-645. [3] V.S. Heber et al. GCA 73 (2009), 7414-7432. [4] V. S. Heber et al. ApJ 759 (2012), 121. [5] R. Wieler in: D. Porcelli, C.J. Ballentine, R. Wieler (Eds.), Reviews in Mineralogy and Geochemistry 47 (2002), 21-70.
Extracting Exact Answers to Questions Based on Structural Links
2002-01-01
type of asking point and answer point (e.g. NePerson asking point matches NePerson and its sub-types NeMan and NeWoman; ‘how’ matches manner-modifier...NePerson V-S win [John Smith]/ NeMan Some sample results are given in section 4 to illustrate how answer-points are identified based on matching binary
Dev, Dipti A; Carraway-Stage, Virginia; Schober, Daniel J; McBride, Brent A; Kok, Car Mun; Ramsay, Samantha
2017-12-01
National childhood obesity prevention policies recommend that child-care providers educate young children about nutrition to improve their nutrition knowledge and eating habits. Yet, the provision of nutrition education (NE) to children in child-care settings is limited. Using the 2011 Academy of Nutrition and Dietetics benchmarks for NE in child care as a guiding framework, researchers assessed child-care providers' perspectives regarding delivery of NE through books, posters, mealtime conversations, hands-on learning, and sensory exploration of foods to young children (aged 2 to 5 years). Using a qualitative design (realist method), individual, semistructured interviews were conducted until saturation was reached. The study was conducted during 2012-2013 and used purposive sampling to select providers. Final sample included 18 providers employed full-time in Head Start or state-licensed center-based child-care programs in Central Illinois. Child-care providers' perspectives regarding implementation of NE. Thematic analysis to derive themes using NVivo software. Three overarching themes emerged, including providers' motivators, barriers, and facilitators for delivering NE to children. Motivators for delivering NE included that NE encourages children to try new foods, NE improves children's knowledge of healthy and unhealthy foods, and NE is consistent with children's tendency for exploration. Barriers for delivering NE included that limited funding and resources for hands-on experiences and restrictive policies. Facilitators for delivering NE included providers obtain access to feasible, low-cost resources and community partners, providers work around restrictive policies to accommodate NE, and mealtime conversations are a feasible avenue to deliver NE. Providers integrated mealtime conversations with NE concepts such as food-based sensory exploration and health benefits of foods. Present study findings offer insights regarding providers' perspectives on implementing NE in child care. Drawing from these perspectives, registered dietitian nutritionists can train providers about the importance of NE for encouraging healthy eating in children, integrating NE with mealtime conversations, and practicing low-cost, hands-on NE activities that meet the food safety standards for state licensing. Such strategies may improve providers' ability to deliver NE in child-care settings. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.
Nonequilibrium thermodynamic potentials for continuous-time Markov chains.
Verley, Gatien
2016-01-01
We connect the rare fluctuations of an equilibrium (EQ) process and the typical fluctuations of a nonequilibrium (NE) stationary process. In the framework of large deviation theory, this observation allows us to introduce NE thermodynamic potentials. For continuous-time Markov chains, we identify the relevant pairs of conjugated variables and propose two NE ensembles: one with fixed dynamics and fluctuating time-averaged variables, and another with fixed time-averaged variables, but a fluctuating dynamics. Accordingly, we show that NE processes are equivalent to conditioned EQ processes ensuring that NE potentials are Legendre dual. We find a variational principle satisfied by the NE potentials that reach their maximum in the NE stationary state and whose first derivatives produce the NE equations of state and second derivatives produce the NE Maxwell relations generalizing the Onsager reciprocity relations.
Neon produced by solar cosmic rays in ordinary chondrites
NASA Astrophysics Data System (ADS)
Roth, Antoine S. G.; Trappitsch, Reto; Metzler, Knut; Hofmann, Beda A.; Leya, Ingo
2017-06-01
Solar-cosmic-ray-produced Ne (SCR-Ne), in the form of low cosmogenic 21Ne/22Ne ratios (21Ne/22Necos <0.8), is more likely to be found in rare meteorite classes, like Martian meteorites, than in ordinary chondrites. This may be the result of a sampling bias: SCR-Ne is better preserved in meteorites with small preatmospheric radii and these specimens are often only studied if they belong to unusual or rare classes. We measured He and Ne isotopic concentrations and nuclear tracks in 25 small unpaired ordinary chondrites from Oman. Most chondrites have been intensively heated during atmospheric entry as evidenced by the disturbed track records, the low 3He/21Ne ratios, the low 4He concentrations, and the high peak release temperatures. Concentration depth profiles indicate significant degassing; however, the Ne isotopes are mainly undisturbed. Remarkably, six chondrites have low 21Ne/22Necos in the range 0.711-0.805. Using a new physical model for the calculation of SCR production rates, we show that four of the chondrites contain up to 20% of SCR-Ne; they are analyzed in terms of preatmospheric sizes, cosmic ray exposure ages, mass ablation losses, and orbits. We conclude that SCR-Ne is preserved, regardless of the meteorite class, in specimens with small preatmospheric radii. Sampling bias explains the predominance of SCR-Ne in rare meteorites, although we cannot exclude that SCR-Ne is more common in Martian meteorites than it is in small ordinary chondrites.
Dawes, Ryan P.; Madden, Kelley S.
2016-01-01
Activation of the sympathetic nervous system (SNS) drives breast cancer progression in preclinical breast cancer models, but it has yet to be established if neoplastic and stromal cells residing in the tumor are directly targeted by locally released norepinephrine (NE). In murine orthotopic and spontaneous mammary tumors, tyrosine hydroxylase (TH)+ sympathetic nerves were limited to the periphery of the tumor. No TH+ staining was detected deeper within these tumors, even in regions with a high density of blood vessels. NE concentration was much lower in tumors compared to the more densely innervated spleen, reflecting the relative paucity of tumor TH+ innervation. Tumor and spleen NE concentration decreased with increased tissue mass. In mice treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to selectively destroy sympathetic nerves, tumor NE concentration was reduced approximately 50%, suggesting that the majority of tumor NE is derived from local sympathetic nerves. To evaluate NE utilization, NE turnover in orthotopic 4T1 mammary tumors was compared to spleen under baseline and stress conditions. In non-stressed mice, NE turnover was equivalent between tumor and spleen. In mice exposed to a stressor, tumor NE turnover was increased compared to spleen NE turnover, and compared to non-stressed tumor NE turnover. Together, these results demonstrate that NE in mammary tumors is derived from local sympathetic nerves that synthesize and metabolize NE. However, differences between spleen and tumor NE turnover with stressor exposure suggest that sympathetic NE release is regulated differently within the tumor microenvironment compared to the spleen. Local mammary tumor sympathetic innervation, despite its limited distribution, is responsive to stressor exposure and therefore can contribute to stress-induced tumor progression. PMID:26718447
Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.
Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad
2016-01-01
Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.
Nuriya, Mutsuo; Takeuchi, Miyabi; Yasui, Masato
2017-01-29
Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.
Cocaine. Selective regional effects on central monoamines.
Hadfield, M G
1995-01-01
Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice ip. Thirty minutes later, the brains were removed, and nine regions were isolated: olfactory bulbs, olfactory tubercles, prefrontal cortex, septum, striatum, amygdala, hypothalamus, hippocampus, and thalamus. Using high-performance liquid chromatography, concentrations of norepinephrine, dopamine, serotonin, and their major metabolites and the metabolite/neurotransmitter ratios were determined as an indicator of utilization. Serotonergic systems responded most dramatically. 5HIAA/5-HT decreases were seen in all the brain regions, except the septum, hippocampus, and olfactory bulbs. In most instances, the alterations were dose-dependent. The most profound changes were seen in the amygdala, prefrontal cortex, hypothalamus, and thalamus. For noradrenergic systems, significant responses were seen only in the amygdala, prefrontal cortex, and hypothalamus, but then only at the lower dose. The dopaminergic responses were more complex and not always dose-dependent. The DOPAC/DA ratio was decreased only in the amygdala and striatum at the lower dose, and the olfactory tubercles at the higher dose. It was increased in the septum. The HVA/DA ratios were decreased in the amygdala, prefrontal cortex, and hypothalamus, but only at the lower dose (like MHPG/NE). The 3MT/DA ratio was decreased in the thalamus at the lower dose and in the olfactory tubercles at the higher dose, whereas it was increased in the prefrontal cortex at the lower dose. The HVA and DOPAC routes of degradation were both utilized only by the amygdala. Thus, cocaine produced its most comprehensive effects in this nucleus, as well as the greatest absolute percentage changes for all three of the monoamine systems studied.
Increased locomotor and thermogenic activity in mice with targeted ablation of the GHRH gene.
Leone, Sheila; Chiavaroli, Annalisa; Shohreh, Rugia; Ferrante, Claudio; Ricciuti, Adriana; Manippa, Fabio; Recinella, Lucia; Di Nisio, Chiara; Orlando, Giustino; Salvatori, Roberto; Vacca, Michele; Brunetti, Luigi
2015-04-01
Growth hormone (GH) deficiency (GHD) leads to growth failure and changes in body composition, including increased fat accumulation and reduced lean body mass in both humans and rodents. The aim of this study was to examine the factors that contribute to energy imbalance in the GH releasing hormone knock out (GHRHKO) mice, a well established model of GHD. We evaluated food intake (of standard laboratory chow), total body weight (TBW), locomotor activity, body temperature and interscapular brown adipose tissue (BAT) weight in 8 adult male mice homozygous for the GHRHKO allele (-/-) and 8 heterozygous (+/-) animals as controls. The gene expression of uncoupling protein-1 (UCP-1) in BAT and the levels of norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine, 5-HT) in the ventral striatum were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and high performance liquid chromatography (HPLC) analysis, respectively. Throughout 2 months of observation -/- mice consumed approximately 40% more food (normalized to TBW; P<0.001), and showed increased locomotor activity in 24h time compared to controls (P<0.05). Moreover, -/- animals showed increased body temperature (P<0.001), BAT weight (P<0.001), and UCP-1 gene expression (P<0.001), while NE levels in the striatum area were lower (P<0.05) than controls. The present study demonstrates that the increased food intake observed in GHRH ablated animals is associated with increased locomotor and thermogenic activity. Copyright © 2014 Elsevier Ltd. All rights reserved.
Chaudhari, Nirja K; Nampoothiri, Laxmipriya P
2017-02-01
Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.
Norepinephrine is coreleased with serotonin in mouse taste buds.
Huang, Yijen A; Maruyama, Yutaka; Roper, Stephen D
2008-12-03
ATP and serotonin (5-HT) are neurotransmitters secreted from taste bud receptor (type II) and presynaptic (type III) cells, respectively. Norepinephrine (NE) has also been proposed to be a neurotransmitter or paracrine hormone in taste buds. Yet, to date, the specific stimulus for NE release in taste buds is not well understood, and the identity of the taste cells that secrete NE is not known. Chinese hamster ovary cells were transfected with alpha(1A) adrenoceptors and loaded with fura-2 ("biosensors") to detect NE secreted from isolated mouse taste buds and taste cells. Biosensors responded to low concentrations of NE (>or=10 nm) with a reliable fura-2 signal. NE biosensors did not respond to stimulation with KCl or taste compounds. However, we recorded robust responses from NE biosensors when they were positioned against mouse circumvallate taste buds and the taste buds were stimulated with KCl (50 mm) or a mixture of taste compounds (cycloheximide, 10 microm; saccharin, 2 mm; denatonium, 1 mm; SC45647, 100 microm). NE biosensor responses evoked by stimulating taste buds were reversibly blocked by prazosin, an alpha(1A) receptor antagonist. Together, these findings indicate that taste bud cells secrete NE when they are stimulated. We isolated individual taste bud cells to identify the origin of NE release. NE was secreted only from presynaptic (type III) taste cells and not receptor (type II) cells. Stimulus-evoked NE release depended on Ca(2+) in the bathing medium. Using dual biosensors (sensitive to 5-HT and NE), we found all presynaptic cells secrete 5-HT and 33% corelease NE with 5-HT.
Study of the 20,22Ne+20,22Ne and 10,12,13,14,15C+12C Fusion Reactions with MUSIC
NASA Astrophysics Data System (ADS)
Avila, M. L.; Rehm, K. E.; Almaraz-Calderon, S.; Carnelli, P. F. F.; DiGiovine, B.; Esbensen, H.; Hoffman, C. R.; Jiang, C. L.; Kay, B. P.; Lai, J.; Nusair, O.; Pardo, R. C.; Santiago-Gonzalez, D.; Talwar, R.; Ugalde, C.
2016-05-01
A highly efficient MUlti-Sampling Ionization Chamber (MUSIC) detector has been developed for measurements of fusion reactions. A study of fusion cross sections in the 10,12,13,14,15C+12C and 20,22Ne+20,22Ne systems has been performed at ATLAS. Experimental results and comparison with theoretical predictions are presented. Furthermore, results of direct measurements of the 17O(α, n)20Ne, 23Ne(α, p)26Mg and 23Ne(α, n)26Al reactions will be discussed.
Aprikian, A G; Cordon-Cardo, C; Fair, W R; Reuter, V E
1993-06-15
This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma. Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies. NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases. This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.
Hamilton, Matthew B; Tartakovsky, Maria; Battocletti, Amy
2018-05-01
The genetic effective population size, N e , can be estimated from the average gametic disequilibrium (r2^) between pairs of loci, but such estimates require evaluation of assumptions and currently have few methods to estimate confidence intervals. speed-ne is a suite of matlab computer code functions to estimate Ne^ from r2^ with a graphical user interface and a rich set of outputs that aid in understanding data patterns and comparing multiple estimators. speed-ne includes functions to either generate or input simulated genotype data to facilitate comparative studies of Ne^ estimators under various population genetic scenarios. speed-ne was validated with data simulated under both time-forward and time-backward coalescent models of genetic drift. Three classes of estimators were compared with simulated data to examine several general questions: what are the impacts of microsatellite null alleles on Ne^, how should missing data be treated, and does disequilibrium contributed by reduced recombination among some loci in a sample impact Ne^. Estimators differed greatly in precision in the scenarios examined, and a widely employed Ne^ estimator exhibited the largest variances among replicate data sets. speed-ne implements several jackknife approaches to estimate confidence intervals, and simulated data showed that jackknifing over loci and jackknifing over individuals provided ~95% confidence interval coverage for some estimators and should be useful for empirical studies. speed-ne provides an open-source extensible tool for estimation of Ne^ from empirical genotype data and to conduct simulations of both microsatellite and single nucleotide polymorphism (SNP) data types to develop expectations and to compare Ne^ estimators. © 2018 John Wiley & Sons Ltd.
Inaba, Masato; Matsuda, Naoyuki; Banno, Hirotsugu; Jin, Wanchun; Wachino, Jun-Ichi; Yamada, Keiko; Kimura, Kouji; Arakawa, Yoshichika
2016-12-01
The host stress hormone norepinephrine (NE), also called noradrenaline, is reported to augment bacterial growth and pathogenicity, but few studies have focused on the effect of NE on the activity of antimicrobials. The aim of this study was to clarify whether NE affects antimicrobial activity against multidrug-resistant Acinetobacter baumannii (MDR-AB). Time-kill studies of tigecycline (TIG) and colistin (COL) against MDR-AB as well as assays for factors contributing to antibiotic resistance were performed using MDR-AB clinical strains both in the presence and absence of 10 µM NE. In addition, expression of three efflux pump genes (adeB, adeJ and adeG) in the presence and absence of NE was analysed by quantitative reverse transcription PCR. Viable bacterial cell counts in TIG-supplemented medium containing NE were significantly increased compared with those in medium without NE. In contrast, NE had little influence on viable bacterial cell counts in the presence of COL. NE-supplemented medium resulted in an ca. 2 log increase in growth and in bacterial cell numbers adhering on polyurethane, silicone and polyvinylchloride surfaces. Amounts of biofilm in the presence of NE were ca. 3-fold higher than without NE. Expression of the adeG gene was upregulated 4-6-fold in the presence of NE. In conclusion, NE augmented factors contributing to antibiotic resistance and markedly reduced the in vitro antibacterial activity of TIG against MDR-AB. These findings suggest that NE treatment may contribute to the failure of TIG therapy in patients with MDR-AB infections. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Swaab, Hanna; de Vries, Linda S.; Jongmans, Marian J.
2007-01-01
Neonatal encephalopathy (NE) following perinatal asphyxia (PA) is considered an important cause of later neurodevelopmental impairment in infants born at term. This review discusses long-term consequences for general cognitive functioning, educational achievement, neuropsychological functioning and behavior. In all areas reviewed, the outcome of children with mild NE is consistently positive and the outcome of children with severe NE consistently negative. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. With respect to educational achievement, difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, studies of neuropsychological functioning have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Conclusion: Behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE. PMID:17426984
Zhang, Peng; Hiebert, Colin W; McIntosh, Robert A; McCallum, Brent D; Thomas, Julian B; Hoxha, Sami; Singh, Davinder; Bansal, Urmil
2016-03-01
Genetic and mutational analyses of wheat leaf rust resistance gene Lr13 and hybrid necrosis gene Ne2 m indicated that they are the same gene. Hybrid necrosis in wheat characterized by chlorosis and eventual necrosis of plant tissues in certain wheat hybrids is controlled by the interaction of complementary dominant genes Ne1 and Ne2 located on chromosome arms 5BL and 2BS, respectively. Multiple alleles at each locus can be identified by differences in necrotic phenotypes when varieties are crossed with a fixed accession of the other genotype. Some of at least five Ne2 alleles were described as s (strong), m (medium) and w (weak); alleles of Ne1 were similarly described. Ne2m causes moderate necrosis in hybrids with genotypes having Ne1s. Ne2 is located on chromosome arm 2BS in close proximity to Lr13. Most wheat lines with Ne2m carry Lr13, and all wheat lines with Lr13 appear to carry Ne2m. To further dissect the relationship between Lr13 and Ne2m, more than 350 crosses were made between cv. Spica (Triticum aestivum) or Kubanka (T. durum) carrying Ne1s and recombinant inbred lines or doubled haploid lines from three crosses segregating for Lr13. F1 plants from lines carrying Lr13 crossed with Spica (Ne1s) always showed progressive necrosis; those lacking Lr13 did not. Four wheat cultivars/lines carrying Lr13 were treated with the mutagen EMS. Thirty-five susceptible mutants were identified; eight were distinctly less glaucous and late maturing indicative of chromosome 2B or sub-chromosome loss. Hybrids of phenotypically normal Lr13 mutant plants crossed with Spica did not produce symptoms of hybrid necrosis. Thus, Lr13 and one particular Ne2m allele may be the same gene.
Production of Ne Auger electrons by Ne/+/ bombardment of Mg and Al surfaces
NASA Technical Reports Server (NTRS)
Ferrante, J.; Pepper, S. V.
1976-01-01
A description is given of experiments which provide evidence for the production of an inner shell vacancy in the Ne by the asymmetric Ne-Mg and Ne-Al collision. In addition, autoionization states of neutral Ne have been observed. These states are to be distinguished from the more usual case in Auger electron spectroscopy of de-excitation of an ion with a core vacancy. The experiments involved the bombardment of Mg and Al surfaces with Ne(+) ions. A LEED-Auger system equipped with an ion gun and a four-grid retarding potential analyzer operated in the usual dN(E)/dE mode was used.
NASA Astrophysics Data System (ADS)
Curciarello, F.
We present a search for a new light vector boson, carrier of a "dark force" between WIMPs, with the KLOE detector at \\DA$\\Phi$NE. We analyzed $e^+ e^- \\to \\mu^+ \\mu^- \\gamma$ ISR events corresponding to an integrated luminosity of $239$ pb$^{-1}$ to find evidence for the $e^+ e^- \\to U\\gamma ,\\,\\, U\\to\\mu^+\\mu^-$ process. We found no $U$ vector boson signal and set a 90% CL upper limit on the ratio of the U boson and photon coupling constants between 1.6$\\times10^{-5}$ to 8.6$\\times10^{-7}$ in the mass region $520
Chung, Gary Hong Chun; Domart, Marie Charlotte; Peddie, Christopher; Mantell, Judith; Mclaverty, Kieran; Arabiotorre, Angela; Hodgson, Lorna; Byrne, Richard D; Verkade, Paul; Arkill, Kenton; Collinson, Lucy M; Larijani, Banafshe
2018-06-12
Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis, is a highly regulated process but the detailed mechanism still remains incompletely understood. Previous studies have found isolated diacylglycerol (DAG) containing vesicles are essential for completing the fusion of NE in non-somatic cells. We investigated the impact of DAG depletion from cis-Golgi in mammalian cells on NE reassembly. Using advanced electron microscopy, we observed an enriched DAG population of vesicles at the vicinity of the NE gaps of telophase mammalian cells. We applied a miniSOG-C1-domain tag that localized DAG-enriched vesicles at the perinuclear region, which suggested the existence of NE fusogenic vesicles. We quantified the impact of Golgi-DAG depletion by measuring the in situ NE rim curvature of the re-forming NE. The rim curvature in these cells was significantly reduced compared with controls, which indicated a localized defect in NE morphology. Our novel results demonstrate the significance of the role of DAG from cis-Golgi for the regulation of NE assembly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
Dubois, A; Castel, G; Murri, S; Pulido, C; Pons, J-B; Benoit, L; Loiseau, A; Lakhdar, L; Galan, M; Marianneau, P; Charbonnel, N
2018-03-01
Ecoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. In this study, we focused on nephropathia epidemica (NE), which is caused by Puumala hantavirus (PUUV) whose natural reservoir is the bank vole, Myodes glareolus. We questioned the possibility of NE emergence in a French region that is considered to be NE-free but that is adjacent to a NE-endemic region. We first confirmed the epidemiology of these two regions and we demonstrated the absence of spatial barriers that could have limited dispersal, and consequently, the spread of PUUV into the NE-free region. We next tested whether regional immunoheterogeneity could impact PUUV chances to circulate and persist in the NE-free region. We showed that bank voles from the NE-free region were sensitive to experimental PUUV infection. We observed high levels of immunoheterogeneity between individuals and also between regions. Antiviral gene expression (Tnf and Mx2) reached higher levels in bank voles from the NE-free region. During experimental infections, anti-PUUV antibody production was higher in bank voles from the NE-endemic region. These results indicated a lower susceptibility to PUUV for bank voles from this NE-free region, which might limit PUUV persistence and therefore, the risk of NE.
Lee, Ahn R; Che, Nicole; Lovnicki, Jessica M; Dong, Xuesen
2018-01-01
While the use of next-generation androgen receptor pathway inhibition (ARPI) therapy has significantly increased the survival of patients with metastatic prostate adenocarcinoma (AdPC), several groups have reported a treatment-resistant mechanism, whereby cancer cells can become androgen receptor (AR) indifferent and gain a neuroendocrine (NE)-like phenotype. This subtype of castration-resistant prostate cancer has been termed "treatment-induced castration-resistant neuroendocrine prostate cancer" (CRPC-NE). Recent reports indicate that the overall genomic landscapes of castration-resistant tumors with AdPC phenotypes and CRPC-NE are not significantly altered. However, CRPC-NE tumors have been found to contain a NE-specific pattern throughout their epigenome and splicing transcriptome, which are significantly modified. The molecular mechanisms by which CRPC-NE develops remain unclear, but several factors have been implicated in the progression of the disease. Recently, Ser/Arg repetitive matrix 4 (SRRM4), a neuronal-specific RNA splicing factor that is upregulated in CRPC-NE tumors, has been shown to establish a CRPC-NE-unique splicing transcriptome, to induce a NE-like morphology in AdPC cells, and, most importantly, to transform AdPC cells into CRPC-NE xenografts under ARPI. Moreover, the SRRM4-targeted splicing genes are highly enriched in various neuronal processes, suggesting their roles in facilitating a CRPC-NE program. This article will address the importance of SRRM4-mediated alternative RNA splicing in reprogramming translated proteins to facilitate NE differentiation, survival, and proliferation of cells to establish CRPC-NE tumors. In addition, we will discuss the potential roles of SRRM4 in conjunction with other known pathways and factors important for CRPC-NE development, such as the AR pathway, TP53 and RB1 genes, the FOXA family of proteins, and environmental factors. This study aims to explore the multifaceted functions of SRRM4 and SRRM4-mediated splicing in driving a CRPC-NE program as a coping mechanism for therapy resistance, as well as define future SRRM4-targeted therapeutic approaches for treating CRPC-NE or mitigating its development.
Lee, Ahn R.; Che, Nicole; Lovnicki, Jessica M.; Dong, Xuesen
2018-01-01
While the use of next-generation androgen receptor pathway inhibition (ARPI) therapy has significantly increased the survival of patients with metastatic prostate adenocarcinoma (AdPC), several groups have reported a treatment-resistant mechanism, whereby cancer cells can become androgen receptor (AR) indifferent and gain a neuroendocrine (NE)-like phenotype. This subtype of castration-resistant prostate cancer has been termed “treatment-induced castration-resistant neuroendocrine prostate cancer” (CRPC-NE). Recent reports indicate that the overall genomic landscapes of castration-resistant tumors with AdPC phenotypes and CRPC-NE are not significantly altered. However, CRPC-NE tumors have been found to contain a NE-specific pattern throughout their epigenome and splicing transcriptome, which are significantly modified. The molecular mechanisms by which CRPC-NE develops remain unclear, but several factors have been implicated in the progression of the disease. Recently, Ser/Arg repetitive matrix 4 (SRRM4), a neuronal-specific RNA splicing factor that is upregulated in CRPC-NE tumors, has been shown to establish a CRPC-NE-unique splicing transcriptome, to induce a NE-like morphology in AdPC cells, and, most importantly, to transform AdPC cells into CRPC-NE xenografts under ARPI. Moreover, the SRRM4-targeted splicing genes are highly enriched in various neuronal processes, suggesting their roles in facilitating a CRPC-NE program. This article will address the importance of SRRM4-mediated alternative RNA splicing in reprogramming translated proteins to facilitate NE differentiation, survival, and proliferation of cells to establish CRPC-NE tumors. In addition, we will discuss the potential roles of SRRM4 in conjunction with other known pathways and factors important for CRPC-NE development, such as the AR pathway, TP53 and RB1 genes, the FOXA family of proteins, and environmental factors. This study aims to explore the multifaceted functions of SRRM4 and SRRM4-mediated splicing in driving a CRPC-NE program as a coping mechanism for therapy resistance, as well as define future SRRM4-targeted therapeutic approaches for treating CRPC-NE or mitigating its development. PMID:29666783
Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish
Singh, Chanpreet; Oikonomou, Grigorios; Prober, David A
2015-01-01
Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine β-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep, dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons. DOI: http://dx.doi.org/10.7554/eLife.07000.001 PMID:26374985
NASA Technical Reports Server (NTRS)
Pravdivtseva, O.; Zinner, E.; Meshik, A. P.; Hohenberg, C. M.; Walker, R. W.
2004-01-01
Presolar graphite in Murchison has been extensively studied. It is characterized by a unique Ne isotopic composition, known as the Ne-E(L) component. According to studies by Huss and Lewis, the concentration of Ne-E(L) in Orgueil is about one order of magnitude higher than in Murchison, when normalized to the matrix. This could be due to a higher presolar graphite abundance in Orgueil, or due to a higher Ne-E concentrations per grain. The Ne isotopic compositions in individual presolar graphite grains from Murchison have been measured before. It was shown, that a third of the grains have detectable excesses in 22Ne, characteristic of the Ne-E(L) component. One grain in a hundred had a Ne-22 concentration two orders of magnitude higher than blank.
Geochronometry and thermochronometry using nucleogenic 21Ne
NASA Astrophysics Data System (ADS)
Farley, K. A.; Flowers, R. M.; Vasconcelos, P. M.
2011-12-01
Nucleogenic 21Ne is produced by the interaction of α particles with 18O. While the cross section for this reaction is small (about 1 α in 25 million participates), 21Ne excesses can be measured in a variety of minerals, forming the basis of (U-Th)/Ne chronometry. Previous work focused on thermochronometry of U, Th rich trace minerals. For example, Gautheron et al. (2005) studied nucleogenic Ne in zircon and inferred a closure temperature of ~400 C. Our preliminary Ne diffusion data on Durango apatite suggests Tc ~280 C. The method can also be applied to phases with much lower U and Th contents in which the 21Ne is measurable on old and/or large specimens. We have obtained (U-Th)/Ne ages on ~50 mg samples of iron oxides with ppm-level U and Th and Ne ages of 50-500 Ma. For example, hematites from the Neoproterozoic (?) Urucum BIF yield a 21Ne age of 470 ± 15 Ma and post-depositional hydrothermal hematite in the Redwall Limestone in the Grand Canyon yields an age of 251 ± 11 Ma. In both cases (U-Th)/He ages are more than 100 Myr younger. Outstanding issues with this method are 1) the diffusivity of Ne - are we measuring cooling ages or formation ages?, 2) how well known is the production rate?, and 3) in what minerals is the air component sufficiently small to permit precision measurements of 21Ne excesses?
Comparison of energy rationing systems for late gestation ewes: Impacts on ewe and lamb performance.
Campion, F P; McGovern, F M; Lott, S; Fahey, A G; Creighton, P; Boland, T M
2016-08-01
The objectives of this study were 1) to compare the effects of a ME () or a NE () system for rationing ewes during late gestation on ewe and progeny performance and 2) to investigate incremental increases in NE allocation above 100% of recommendation during late gestation on ewe and progeny performance. Fifty-two twin-bearing ewes ( = 13 per treatment) were rationed to either 100% of recommended ME requirements (100% ME) or 100, 110, or 120% of recommended NE requirements (100% NE, 110% NE, and 120% NE) from d 112 of gestation to parturition. Mean energy intake, measured as ME and NE, from Day 112 of gestation to parturition was higher in all NE treatments compared with 100% ME ewes ( = 0.01). Ewes offered the 3 NE treatments had a higher live weight at parturition compared with 100% ME ewes ( = 0.02), with 100% NE and 120% NE ewes still being heavier than 100% ME ewes at 35 d postpartum ( = 0.02). Increasing NE allowance resulted in a linear decrease in the level of BCS loss prepartum ( = 0.01) and a linear increase in the level of BCS loss postpartum ( = 0.01). There was no difference observed between any of the treatments in total colostrum produced to 18 h postpartum ( = 0.29) or in total colostrum intake to 18 h postpartum ( = 0.27). Increasing maternal NE allowance led to a linear increase in lamb serum IgG concentration at 24 h postpartum ( = 0.03). The estimated milk production of 120% NE ewes tended to be higher than all other treatments at wk 6 of lactation ( = 0.08). Colostral SFA levels from 100% ME ewes was lower than that of all 3 NE treatments ( = 0.01), and unsaturated fatty acid (UFA) levels in colostrum of the 100% ME ewes were lower than those of the 100% NE ewes ( = 0.01). Cumulative levels of milk SFA, UFA, and MUFA did not differ between treatments ( = 0.19). Lamb growth rates during the first 5 wk postpartum were unaffected by treatment ( = 0.18) as were days to slaughter ( = 0.34). It can be concluded that both ME and NE systems used in this study are appropriate for formulating ewe diets during late gestation. Increasing NE allocation above 100% altered the pattern of body reserve mobilization during late gestation and early lactation without observed variations in lamb performance during this time.
NASA Astrophysics Data System (ADS)
Pepin, Robert O.; Schlutter, Dennis J.; Becker, Richard H.; Reisenfeld, Daniel B.
2012-07-01
We report compositions and fluxes of light noble gases in the solar wind (SW), extracted by stepped pyrolysis and amalgamation from gold collector materials carried on the Genesis Solar Wind Sample Return Mission. Results are compared with data from other laboratories on SW-He, Ne and Ar distributions implanted in Genesis aluminum, carbon, and silicon collectors and extracted by laser ablation. Corrections for mass-dependent losses (“backscatter”) of impinging SW ions due to scattering from the collector material are substantially larger for gold than for these lower atomic weight targets. We assess such losses by SRIM simulation calculations of SW backscatter from gold which are applied to the measurements to recover the composition of the incident SW. Averaged results of integrated stepped pyrolysis and single-step amalgamation measurements, with 1σ errors, are as follows: for SW-Ne and Ar isotope ratios (3He/4He was not measured), 20Ne/22Ne = 14.001 ± 0.042, 21Ne/22Ne = 0.03361 ± 0.00018, 36Ar/38Ar = 5.501 ± 0.014; for SW element ratios, 4He/20Ne = 641 ± 15, 20Ne/36Ar = 51.6 ± 0.5; and for SW fluxes in atoms cm-2 s-1 at the Genesis L1 station, 4He = 1.14 ± 0.04 × 107, 20Ne = 1.80 ± 0.06 × 104, 36Ar = 3.58 ± 0.11 × 102. Except for the 21Ne/22Ne and 20Ne/36Ar ratios, these values are in reasonable accord (within ∼1-3σ) with measurements on different collector materials reported by one or both of two other Genesis noble gas research groups. We further find, in three stepped pyrolysis experiments on gold foil, that He, Ne and Ar are released at increasing temperatures without elemental fractionation, in contrast to a pyrolytic extraction of a single non-gold collector (Al) where the release patterns point to mass-dependent thermal diffusion. The pyrolyzed gold foils exhibit enhancements, relative to sample totals, in 20Ne/22Ne and 21Ne/22Ne ratios evolved at low temperatures. The absence of elemental fractionation in pyrolytic release from gold implies that these isotope ratio enhancements, involving much smaller mass differences, do not result from preferential diffusive release of the lighter Ne isotopes. This effect, not predicted by SRIM calculations, has also been observed in stepped acid-etch releases from a different Genesis collector material in another laboratory.
Grate, Jay W; Warner, Marvin G; Ozanich, Richard M; Miller, Keith D; Colburn, Heather A; Dockendorff, Brian; Antolick, Kathryn C; Anheier, Norman C; Lind, Michael A; Lou, Jianlong; Marks, James D; Bruckner-Lea, Cynthia J
2009-05-01
A renewable surface biosensor for rapid detection of botulinum neurotoxin serotype A is described based on fluidic automation of a fluorescence sandwich immunoassay, using a recombinant protein fragment of the toxin heavy chain ( approximately 50 kDa) as a structurally valid simulant. Monoclonal antibodies AR4 and RAZ1 bind to separate non-overlapping epitopes of the full botulinum holotoxin ( approximately 150 kDa). Both of the targeted epitopes are located on the recombinant fragment. The AR4 antibody was covalently bound to Sepharose beads and used as the capture antibody. A rotating rod flow cell was used to capture these beads delivered as a suspension by a sequential injection flow system, creating a 3.6 microL column. After perfusing the bead column with sample and washing away the matrix, the column was perfused with Alexa 647 dye-labeled RAZ1 antibody as the reporter. Optical fibers coupled to the rotating rod flow cell at a 90 degrees angle to one another delivered excitation light from a HeNe laser (633 nm) using one fiber and collected fluorescent emission light for detection with the other. After each measurement, the used Sepharose beads are released and replaced with fresh beads. In a rapid screening approach to sample analysis, the toxin simulant was detected to concentrations of 10 pM in less than 20 minutes using this system.
The role of adrenergic activation on murine luteal cell viability and progesterone production.
Wang, Jing; Tang, Min; Jiang, Huaide; Wu, Bing; Cai, Wei; Hu, Chuan; Bao, Riqiang; Dong, Qiming; Xiao, Li; Li, Gang; Zhang, Chunping
2016-09-15
Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating β-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective β-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on β-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating β-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3β-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO. Copyright © 2016 Elsevier Inc. All rights reserved.
Kamath, Pauline L.; Haroldson, Mark A.; Luikart, Gordon; Paetkau, David; Whitman, Craig L.; van Manen, Frank T.
2015-01-01
Effective population size (Ne) is a key parameter for monitoring the genetic health of threatened populations because it reflects a population's evolutionary potential and risk of extinction due to genetic stochasticity. However, its application to wildlife monitoring has been limited because it is difficult to measure in natural populations. The isolated and well-studied population of grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem provides a rare opportunity to examine the usefulness of different Ne estimators for monitoring. We genotyped 729 Yellowstone grizzly bears using 20 microsatellites and applied three single-sample estimators to examine contemporary trends in generation interval (GI), effective number of breeders (Nb) and Ne during 1982–2007. We also used multisample methods to estimate variance (NeV) and inbreeding Ne (NeI). Single-sample estimates revealed positive trajectories, with over a fourfold increase in Ne (≈100 to 450) and near doubling of the GI (≈8 to 14) from the 1980s to 2000s. NeV (240–319) and NeI (256) were comparable with the harmonic mean single-sample Ne (213) over the time period. Reanalysing historical data, we found NeV increased from ≈80 in the 1910s–1960s to ≈280 in the contemporary population. The estimated ratio of effective to total census size (Ne/Nc) was stable and high (0.42–0.66) compared to previous brown bear studies. These results support independent demographic evidence for Yellowstone grizzly bear population growth since the 1980s. They further demonstrate how genetic monitoring of Ne can complement demographic-based monitoring of Nc and vital rates, providing a valuable tool for wildlife managers.
NASA Technical Reports Server (NTRS)
Blakely, Randy D. (Inventor); Robertson, David (Inventor)
2006-01-01
Isolated polynucleotide molecules and peptides encoded by these molecules are used in the analysis of human norepinephrine (NE) transporter variants, as well as in diagnostic and therapeutic applications, relating to a human NE transporter polymorphism. By analyzing genomic DNA or amplified genomic DNA, or amplified cDNA derived from mRNA, it is possible to type a human NE transporter with regard to the human NE transporter polymorphism, for example, in the context of diagnosing and treating NE transport impairments, and disorders associated with NE transport impairments, such as orthostatic intolerance.
Fadul-Pacheco, L; Pellerin, D; Chouinard, P Y; Wattiaux, M A; Duplessis, M; Charbonneau, É
2017-08-01
Nitrogen efficiency (milk N/dietary N; NE) can be used as a tool for the nutritional, economic, and environmental management of dairy farms. The aim of this study was to identify the characteristics of herds with varying NE and assess the effect on farm profitability. One hundred dairy herds located in Québec, Canada, comprising on average 42 ± 18 cows in lactation were visited from October 2014 to June 2015. Feed intake was measured over 24 h. Samples of each feedstuff were taken and sent to a commercial laboratory for analysis of chemical composition. Feeding management and feed prices were recorded. Milk yield was recorded and milk samples were collected over 2 consecutive milkings. Fat, protein, and milk urea N were analyzed. Balances of metabolizable protein (MP; MP supply - MP requirements) and rumen degradable protein (RDP; RDP supply - RDP requirement) were calculated. A hierarchical cluster analysis was conducted and allowed grouping the farms by their NE. Four clusters were identified with an average NE of 22.1 (NE22), 26.9 (NE27), 30.0 (NE30), and 35.8% (NE36). Herds in clusters NE30 and NE36 were fed diets with greater concentrations of starch, net energy for lactation, and nonfiber carbohydrates than those in the other 2 clusters. Moreover, the average proportion of corn silage was lower for herds in cluster NE22 compared with NE30 and NE36 (8.23 vs. 31.8 and 31.3% of total forages, respectively). In addition, crude protein of the diets declined from an average of 16.0 to 14.9% with increasing NE among clusters. Average dry matter intake declined from 26.1 to 22.5 kg/d as NE of clusters increased. Herds in cluster NE22 had lower yields of milk (28.7 vs. 31.8 kg/d), fat (1.15 vs. 1.29 kg/d), and protein (0.94 vs. 1.05 kg/d) than the other clusters. Also, milk urea N was greater for farms in cluster NE22 (13.2 mg/dL) than for farms in the other clusters (11.4 mg/dL). Furthermore, MP and RDP balances decreased from 263.2 to -153.7 g/d and from 594.7 to 486.9 g/d, respectively, with increasing NE among clusters. Income over feed cost increased from $14.3 to $17.3/cow per day (Can$) as NE among clusters augmented. Results from this study showed that some farms were able to achieve high NE by using lower levels of dietary N and having cows with lower DMI while maintaining milk performance. These farms had a potentially lower environmental impact, and they were more profitable. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D
2016-01-15
Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.
KCl stimulation increases norepinephrine transporter function in PC12 cells.
Mandela, Prashant; Ordway, Gregory A
2006-09-01
The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.
NASA Astrophysics Data System (ADS)
Koner, Debasish; Barrios, Lizandra; González-Lezana, Tomás; Panda, Aditya N.
2016-01-01
Initial state selected dynamics of the Ne + NeH+(v0 = 0, j0 = 0) → NeH+ + Ne reaction is investigated by quantum and statistical quantum mechanical (SQM) methods on the ground electronic state. The three-body ab initio energies on a set of suitably chosen grid points have been computed at CCSD(T)/aug-cc-PVQZ level and analytically fitted. The fitting of the diatomic potentials, computed at the same level of theory, is performed by spline interpolation. A collinear [NeHNe]+ structure lying 0.72 eV below the Ne + NeH+ asymptote is found to be the most stable geometry for this system. Energies of low lying vibrational states have been computed for this stable complex. Reaction probabilities obtained from quantum calculations exhibit dense oscillatory structures, particularly in the low energy region and these get partially washed out in the integral cross section results. SQM predictions are devoid of oscillatory structures and remain close to 0.5 after the rise at the threshold thus giving a crude average description of the quantum probabilities. Statistical cross sections and rate constants are nevertheless in sufficiently good agreement with the quantum results to suggest an important role of a complex-forming dynamics for the title reaction.
Chen, Xiaochuan; Green, Alice S.; Macko, Antoni R.; Yates, Dustin T.; Kelly, Amy C.
2013-01-01
Intrauterine growth-restricted (IUGR) fetuses experience prolonged hypoxemia, hypoglycemia, and elevated norepinephrine (NE) concentrations, resulting in hypoinsulinemia and β-cell dysfunction. Previously, we showed that acute adrenergic blockade revealed enhanced insulin secretion responsiveness in the IUGR fetus. To determine whether chronic exposure to NE alone enhances β-cell responsiveness afterward, we continuously infused NE into fetal sheep for 7 days and, after terminating the infusion, evaluated glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-induced insulin secretion (GPAIS). During treatment, NE-infused fetuses had greater (P < 0.05) plasma NE concentrations and exhibited hyperglycemia (P < 0.01) and hypoinsulinemia (P < 0.01) compared with controls. GSIS during the NE infusion was also reduced (P < 0.05) compared with pretreatment values. GSIS and GPAIS were approximately fourfold greater (P < 0.01) in NE fetuses 3 h after the 7 days that NE infusion was discontinued compared with age-matched controls or pretreatment GSIS and GPAIS values of NE fetuses. In isolated pancreatic islets from NE fetuses, mRNA concentrations of adrenergic receptor isoforms (α1D, α2A, α2C, and β1), G protein subunit-αi-2, and uncoupling protein 2 were lower (P < 0.05) compared with controls, but β-cell regulatory genes were not different. Our findings indicate that chronic exposure to elevated NE persistently suppresses insulin secretion. After removal, NE fetuses demonstrated a compensatory enhancement in insulin secretion that was associated with adrenergic desensitization and greater stimulus-secretion coupling in pancreatic islets. PMID:24253046
Tsai, Jeng-Dau; Chen, Hsuan-Ju; Ku, Min-Sho; Chen, Shan-Ming; Hsu, Chih-Chuan; Tung, Min-Che; Lin, Che-Chen; Chang, Hsing-Yi; Sheu, Ji-Nan
2017-12-01
Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present.
Zhang, Heng-Zhu; Li, Yu-Ping; Yan, Zheng-cun; Wang, Xing-dong; She, Lei; Wang, Xiao-dong; Dong, Lun
2014-01-01
Neuroendoscopic (NE) surgery as a minimal invasive treatment for basal ganglia hemorrhage is a promising approach. The present study aims to evaluate the efficacy and safety of NE approach using an adjustable cannula to treat basal ganglia hemorrhage. In this study, we analysed the clinical and radiographic outcomes between NE group (21 cases) and craniotomy group (30 cases). The results indicated that NE surgery might be an effective and safe approach for basal ganglia haemorrhage, and it is also suggested that NE approach may improve good functional recovery. However, NE approach only suits the selected patient, and the usefulness of NE approach needs further randomized controlled trials (RCTs) to evaluate. PMID:24949476
Plate Tectonic Cycling and Whole Mantle Convection Modulate Earth's 3He/22Ne Ratio
NASA Astrophysics Data System (ADS)
Dygert, N. J.; Jackson, C.; Hesse, M. A.; Tremblay, M. M.; Shuster, D. L.; Gu, J.
2016-12-01
3He and 22Ne are not produced in the mantle or fractionated by partial melting, and neither isotope is recycled back into the mantle by subduction of oceanic basalt or sediment. Thus, it is a surprise that large 3He/22Ne variations exist within the mantle and that the mantle has a net elevated 3He/22Ne ratio compared to volatile-rich planetary precursor materials. Depleted subcontinental lithospheric mantle and mid-ocean ridge basalt (MORB) mantle have distinctly higher 3He/22Ne compared to ocean island basalt (OIB) sources ( 4-12.5 vs. 2.5-4.5, respectively) [1,2]. The low 3He/22Ne of OIBs approaches chondritic ( 1) and solar nebula values ( 1.5). The high 3He/22Ne of the MORB mantle is not similar to solar sources or any known family of meteorites, requiring a mechanism for fractionating He from Ne in the mantle and suggesting isolation of distinct mantle reservoirs throughout geologic time. We model the formation of a MORB source with elevated and variable 3He/22Ne though diffusive exchange between dunite channel-hosted basaltic liquids and harzburgite wallrock beneath mid-ocean ridges. Over timescales relevant to mantle upwelling beneath spreading centers, He may diffuse tens to hundreds of meters into wallrock while Ne is relatively immobile, producing a regassed, depleted mantle lithosphere with elevated 3He/22Ne. Subduction of high 3He/22Ne mantle would generate a MORB source with high 3He/22Ne. Regassed, high 3He/22Ne mantle lithosphere has He concentrations 2-3 orders of magnitude lower than undegassed mantle. To preserve the large volumes of high 3He/22Ne mantle required by the MORB source, mixing between subducted and undegassed mantle reservoirs must have been limited throughout geologic time. Using the new 3He/22Ne constraints, we ran a model similar to [3] to quantify mantle mixing timescales, finding they are on the order of Gyr assuming physically reasonable seafloor spreading rates, and that Earth's convecting mantle has lost >99% of its primordial volatile elements. Most significantly, mantle convection is not and cannot have been layered for most of geologic time. [1] Graham (2002), RiMG 74, 247-317. [2] Jalowitzki et al. (2016), EPSL 450, 263-273. [3] Gonnermann & Mukhopadhyay (2009), Nature, 560-563.
NASA Astrophysics Data System (ADS)
Klimchouk, Alexander; Auler, Augusto S.; Bezerra, Francisco H. R.; Cazarin, Caroline L.; Balsamo, Fabrizio; Dublyansky, Yuri
2016-01-01
This study is focused on speleogenesis of the Toca da Boa Vista (TBV) and Toca da Barriguda (TBR), the longest caves in South America occurring in the Neoproterozoic Salitre Formation in the São Francisco Craton, NE Brazil. We employ a multidisciplinary approach integrating detailed speleomorphogenetic, lithostratigraphic and geological structure studies in order to reveal the origin of the caves, their functional organization and geologic controls on their development. The caves developed in deep-seated confined conditions by rising flow. The overall fields of passages of TBV and TBR caves represent a speleogenetically exploited large NE-SW-trending fracture corridor associated with a major thrust. This corridor vertically extends across the Salitre Formation allowing the rise of deep fluids. In the overall ascending flow system, the formation of the cave pattern was controlled by a system of sub-parallel anticlines and troughs with NNE-SSW dominant orientation, and by vertical and lateral heterogeneities in fracture distribution. Three cave-stratigraphic stories reflect the actual hydrostratigraphy during the main phase of speleogenesis. Cavities at different stories are distinct in morphology and functioning. The gross tree-dimensional pattern of the system is effectively organized to conduct rising flow in deep-seated confined conditions. Cavities in the lower story developed as recharge components to the system. A laterally extensive conduit network in the middle story formed because the vertical flow from numerous recharge points has been redirected laterally along the highly conductive unit, occurring below the major seal - a scarcely fractured unit. Rift-like and shaft-like conduits in the upper story developed along fracture-controlled outflow paths, breaching the integrity of the major seal, and served as outlets for the cave system. The cave system represents a series of vertically organized, functionally largely independent clusters of cavities developed within individual ascending flow cells. Lateral integration of clusters occurred due to hydrodynamic interaction between the flow cells in course of speleogenetic evolution and change of boundary conditions. The main speleogenetic phase, during which the gross cave pattern has been established and the caves acquired most of their volume, was likely related to rise of deep fluids at about 520 Ma or associated with rifting and the Pangea break-up in Triassic-Cretaceous. This study highlights the importance of speleogenetic studies for interpreting porosity and permeability features in carbonate reservoirs.
Murillo-Rodríguez, Eric; Di Marzo, Vincenzo; Machado, Sergio; Rocha, Nuno B; Veras, André B; Neto, Geraldo A M; Budde, Henning; Arias-Carrión, Oscar; Arankowsky-Sandoval, Gloria
2017-01-01
The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB 1 and CB 2 ), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep-wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N -arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.
Jacome, Luis F.; Gautreaux, Claris; Inagaki, Tomoko; Mohan, Govini; Alves, Stephen; Lubbers, Laura S.; Luine, Victoria
2010-01-01
Effects of estradiol benzoate (EB), ERα-selective agonist, propyl pyrazole triol (PPT) and ERβ-selective agonists, diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks. Treatments were acute (behavior 4 h later) or sub chronic (daily injections for 2 days with behavior 48 h later). Objects were explored in sample trials (T1), and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2–4 h inter-trial delays. Subjects treated sub chronically with EB, DPN, and C-19, but not PPT, discriminated between old and new objects and objects in old and new locations, suggesting that, at these doses and duration of treatments, estrogenic interactions with ERβ contributes to enhancements in recognition memory. Acute injections of DPN, but not PPT, immediately after T1, also enhanced discrimination for both tasks (C19 was not investigated). Effects of EB, DPN and PPT on anxiety and locomotion, measured on elevated plus maze and open field, did not appear to account for the mnemonic enhancements. Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing. DPN was associated with alterations in monoamines in several brain areas: indexed by the metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the MHPG/norepinephrine (NE) ratio, NE activity was increased by 60–130% in the prefrontal cortex (PFC) and ventral hippocampus, and NE activity was decreased by 40–80% in the v. diagonal bands and CA1. Levels of the dopamine (DA) metabolite, homovanillic acid (HVA), increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment. The metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was increased in the PFC and CA3, by approximately 20%. No monoaminergic changes were noted in striatum or medial septum. Results suggest that ERβ mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur, in part, through alterations in monoaminergic containing systems primarily in PFC and hippocampus. PMID:20828630
Animal Models of Human Disease: Severe and Mild Lead Encephalopathy in the Neonatal Rat*
Michaelson, I. Arthur; Sauerhoff, Mitchell W.
1974-01-01
Inorganic lead produces cerebral dysfunction and clinically definable encephalopathies in man. To date there have been few studies on the biochemical changes in brain following exposure to inorganic lead. Studies correlating toxicity with behavioral and brain neurochemical changes following lead exposure have been hindered because adult laboratory animals are resistant to the central nervous system effects of lead poisoning. Such studies have been impeded by lack of suitable experimental models until Pentschew and Garro showed that brain lesions develop in neonatal rats when a pregnant rat newly delivered of her litter is placed on a 4% lead carbonate containing diet. Lead passes into the developing sucklings via maternal milk. Lead-poisoned new-borns have pronounced retardation of growth and during the fourth week of ilfe develop the severe signs of lead encephalopathy, namely, extensive histological lesions of the cerebellum, brain edema, and paraplegia. There is an approximate 85-fold increase in the lead concentration of both the cerebellum and cerebral cortex relative to controls, but edema and gross vascular changes are confined to the cerebellum. Ingested lead had little effect on RNA, DNA, and protein concentrations of developing rat cerebellum and cerebral cortex. However, there was a reduction of between 10 and 20% in the DNA content of the cerebellum around 3 weeks of age in the lead-exposed sucklings. This suggests a failure of cell multiplication in this part of the brain. A critical evaluation of this experimental approach indicated that under similar dietary conditions experimental lactating rats eat 30% less food than controls resulting in: (a) sustained loss in body weight of nursing mothers and that (b) offsprings who develop paraplegia and cerebellar damage do so after gaining access to lead containing diet. We have studied mothers' food consumption and body weight changes and blood, milk, and brain lead content; and newborns' body and brain weight changes, blood and brain lead content, and brain serotonin (5HT), norepinephrine (NE), dopamine (DA), and γ-aminobutyric acid (GABA). We have found that a lactating mother rat eating 5% lead acetate (2.73% Pb) produced milk containing 25 ppm lead. When the mothers' diet is changed at day 16 from 5% PbAc to one containing 25 ppm Pb, and neonates allowed free access to the solid diet, the sucklings still have retarded body growth but do not develop paraplegia or grossly apparent vascular damage of the cerebellum. However, during the fourth week these animals exhibit a less severe form of “encephalopathy” consisting of hyperactivity, tremors, and stereotype behavior. Pair-fed controls coetaneous to experimental groups do not display such activities. There was no change in brain 5HT, GABA, or NE, but a 15–20% decrease in brain DA. Change in DA relative to other monoamines suggests a relationship between CNS dysfunction due to lead and DA metabolism in the brain. The experimental design as discribed provides a model of CNS dysfunction due to lead exposure without debilitating histopathologies. It is possible that our findings on increased motor activity and changes in brain dopamine may correspond to early responses to lead exposure before recognized overt signs of toxicity. ImagesFIGURE 1.FIGURE 2. PMID:4831141
Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory
2015-10-01
Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.
Patel, Shalaka; Rose, Annkatrin; Meulia, Tea; Dixit, Ram; Cyr, Richard J.; Meier, Iris
2004-01-01
The nuclear envelope (NE) acts as a selective barrier to macromolecule trafficking between the nucleus and the cytoplasm and undergoes a complex reorganization during mitosis. Different eukaryotic kingdoms show specializations in NE function and composition. In contrast with vertebrates, the protein composition of the NE and the function of NE proteins are barely understood in plants. MFP1 attachment factor 1 (MAF1) is a plant-specific NE-associated protein first identified in tomato (Lycopersicon esculentum). Here, we demonstrate that two Arabidopsis thaliana MAF1 homologs, WPP1 and WPP2, are associated with the NE specifically in undifferentiated cells of the root tip. Reentry into cell cycle after callus induction from differentiated root segments reprograms their NE association. Based on green fluorescent protein fusions and immunogold labeling data, the proteins are associated with the outer NE and the nuclear pores in interphase cells and with the immature cell plate during cytokinesis. RNA interference–based suppression of the Arabidopsis WPP family causes shorter primary roots, a reduced number of lateral roots, and reduced mitotic activity of the root meristem. Together, these data demonstrate the existence of regulated NE targeting in plants and identify a class of plant-specific NE proteins involved in mitotic activity. PMID:15548735
Is elevated norepinephrine an etiological factor in some cases of Alzheimer's disease?
Fitzgerald, Paul J
2010-09-01
Loss of norepinephrine (NE) releasing neurons, in the locus coeruleus of the brainstem, is well documented to occur in Alzheimer's disease (AD). However, this process does not necessarily result in decreased release of NE, since compensatory mechanisms may produce increased release of this neurotransmitter. Independent of potential loss of locus coeruleus cells, brain NE levels may be elevated in some persons with AD, both before and during disease progression. Here I examine evidence that elevated, endogenous brain NE is an etiological factor in some cases of AD, and not merely an epiphenomenon of the disease. To explore this etiological hypothesis in AD, I examine the following eight lines of evidence: 1) direct evidence of elevated NE or its metabolites in AD; 2) studies of tricyclic antidepressants, which may principally boost NE; 3) studies of clonidine and other alpha2 adrenergic agonist drugs, which may principally lower the concentration of NE; 4) studies of beta adrenoceptor blocking drugs, including propranolol; 5) comorbidity of AD and bipolar disorder, where both disorders may involve elevated NE; 6) comorbidity of AD and hypertension; 7) comorbidity of AD and obesity; and 8) potential interaction between AD and psychological stress, where stressors are known to release NE. These lines of evidence tend to support the elevated NE etiological hypothesis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koner, Debasish; Panda, Aditya N., E-mail: adi07@iitg.ernet.in; Barrios, Lizandra
2016-01-21
Initial state selected dynamics of the Ne + NeH{sup +}(v{sub 0} = 0, j{sub 0} = 0) → NeH{sup +} + Ne reaction is investigated by quantum and statistical quantum mechanical (SQM) methods on the ground electronic state. The three-body ab initio energies on a set of suitably chosen grid points have been computed at CCSD(T)/aug-cc-PVQZ level and analytically fitted. The fitting of the diatomic potentials, computed at the same level of theory, is performed by spline interpolation. A collinear [NeHNe]{sup +} structure lying 0.72 eV below the Ne + NeH{sup +} asymptote is found to be the most stablemore » geometry for this system. Energies of low lying vibrational states have been computed for this stable complex. Reaction probabilities obtained from quantum calculations exhibit dense oscillatory structures, particularly in the low energy region and these get partially washed out in the integral cross section results. SQM predictions are devoid of oscillatory structures and remain close to 0.5 after the rise at the threshold thus giving a crude average description of the quantum probabilities. Statistical cross sections and rate constants are nevertheless in sufficiently good agreement with the quantum results to suggest an important role of a complex-forming dynamics for the title reaction.« less
Tann, Cally J; Martinello, Kathryn A; Sadoo, Samantha; Lawn, Joy E; Seale, Anna C; Vega-Poblete, Maira; Russell, Neal J; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie; Sobanjo-ter Meulen, Ajoke; Vekemans, Johan; Heath, Paul T; Garcia-Alix, Alfredo; Boo, Nem-Yun; Martinez-Biarge, Miriam; Cheong, Jeanie; Cowan, Frances; de Vries, Linda S; Arca-Diaz, Gemma; Edwards, A David; Ellis, Matthew; Gale, Christopher; Glass, Hannah C; Groenendaal, Floris; Gunn, Alistair; Hayes, Breda; Jacobs, Susan E; Johnson, Clark T; Kali, Gugu; Manne, Manogna; Massaro, An N; Robertson, Nicola J; Shah, Prakeshkumar; Shankaran, Seetha; Tann, Cally J; Thayyil, Sudhin; Thoresen, Marianne; Walsh, Brian H; Wintermark, Pia; Lee, Anne C C
2017-01-01
Abstract Background Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE. Results Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%–.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47–2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births. Conclusions The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts. PMID:29117330
INSM1 is a Sensitive and Specific Marker of Neuroendocrine Differentiation in Head and Neck Tumors.
Rooper, Lisa M; Bishop, Justin A; Westra, William H
2018-05-01
The head and neck is the site of a wide and sometimes bewildering array of neuroendocrine (NE) tumors. Although recognition of NE differentiation may be necessary for appropriate tumor classification and treatment, traditional NE markers such as synaptophysin, chromogranin, and CD56 are not always sufficiently sensitive or specific to make this distinction. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently demonstrated excellent sensitivity and specificity for NE differentiation in various anatomic sites, but has not yet been extensively evaluated in tumors of the head and neck. We performed INSM1 immunohistochemistry on NE tumors (n=97) and non-NE tumors (n=626) across all histologic grades and anatomic subsites of the head and neck. INSM1 was positive in all types of head and neck NE tumors evaluated here (99.0% sensitivity), including middle ear adenoma, pituitary adenoma, paraganglioma, medullary thyroid carcinoma, olfactory neuroblastoma, small cell carcinoma, large cell NE carcinoma, and sinonasal teratocarcinosarcoma. Notably, it was positive in the vast majority of high-grade NE malignancies (95.8% sensitivity). INSM1 also was negative in almost all non-NE tumors (97.6% specificity) with the highest rates of reactivity in alveolar rhabdomyosarcoma and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1 (SMARCB1)-deficient sinonasal carcinoma. These findings confirm that INSM1 may be used as a standalone first-line marker of NE differentiation for tumors of the head and neck.
Yang, Teng-Kai; Huang, Kuo-How; Chen, Shyh-Chyan; Chang, Hong-Chiang; Yang, Hung-Ju; Guo, Ya-Jun
2013-01-01
Children with attention deficit hyperactivity disorder (ADHD) tend to be more vulnerable to various forms of voiding dysfunction and nocturnal enuresis (NE). We attempt to compare the clinical manifestations and attentional performance between ADHD children with NE and those without NE. We consecutively enrolled children diagnosed with ADHD in child and adolescent psychiatric clinics. The questionnaires for evaluation of ADHD symptoms and voiding dysfunction symptoms were administered to all study participants. All participants also received the Test Battery for Attention Performance (TAP) for assessment of attentional function. A total of 53 children were enrolled in this study, comprising 47 boys and six girls. The prevalence rate of NE was 28.3%. Children in the NE group had statistically significant higher dysfunctional voiding symptom score (5.40 ± 3.66 vs.3.16 ± 2.74; p = 0.018) and two subscales of "When I wet myself, my underwear is soaked" (p < 0.001) and "I miss having a bowel movement every day" (p = 0.047). There were no significant differences with regard to all psychiatric evaluations between the NE and non-NE groups. In the TAP test, the NE group showed a significantly shorter reaction time in the domain of inhibitory control, working memory, and auditory sustained attention than the non-NE group. Children with ADHD have a high prevalence of NE. ADHD children with NE had a significantly higher dysfunctional voiding symptom score and shorter reaction time in most domains of the TAP test. Further study is needed to discern the impact of NE on the neuropsychological function of ADHD children. Copyright © 2012. Published by Elsevier B.V.
NASA Astrophysics Data System (ADS)
Leya, Ingo; Wieler, Rainer
1999-07-01
The production of nucleogenic Ne in terrestrial crust and upper mantle by alpha particles from the decay of U and Th was calculated. The calculations are based on stopping powers for the chemical compounds and thin-target cross sections. This approach is more rigorous than earlier studies using thick-target yields for pure elements, since our results are independent of limiting assumptions about stopping-power ratios. Alpha induced reactions account for >99% of the Ne production in the crust and for most of the 20,21Ne in the upper mantle. On the other hand, our 22Ne value for the upper mantle is a lower limit because the reaction 25Mg(n,α)22Ne is significant in mantle material. Production rates calculated here for hypothetical crustal and upper mantle material with average major element composition and homogeneously distributed F, U, and Th are up to 100 times higher than data presented by Kyser and Rison [1982] but agree within error limits with the results by Yatsevich and Honda [1997]. Production of nucleogenic Ne in "mean" crust and mantle is also given as a function of the weight fractions of O and F. The alpha dose is calculated by radiogenic 4He as well as by the more retentive fissiogenic 136Xe. U and Th is concentrated in certain accessory minerals. Since the ranges of alpha particles from the three decay chains are comparable to mineral dimensions, most nucleogenic Ne is produced in U- and Th-rich minerals. Therefore nucleogenic Ne production in such accessories was also calculated. The calculated correlation between nucleogenic 21Ne and radiogenic 4He agrees well with experimental data for Earth's crust and accessories. Also, the calculated 22Ne/4He ratios as function of the F concentration and the dependence of 21Ne/22Ne from O/F for zircon and apatite agree with measurements.
Zheng, Wen; Zhang, Yu-Jiao; Bu, Xiang-Ting; Guo, Xin-Zhu; Hu, Da-Yi; Li, Zhan-Quan; Sun, Jian
2017-11-01
Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the efficacy of persistent treatment in a real-world setting may vary from regions. Routine lipid-lowering therapy in the region with a high prevalence of cardiovascular disease may lead to more failures of goal attainment. We therefore performed a study to observe different lipid-lowering strategies in northeast (NE) China with respect to low-density lipoprotein-cholesterol (LDL-C) reduction and goal attainments.A cross-sectional study (DYSIS-China) was conducted in 2012, involving 25,317 patients from 122 centers across China who were diagnosed with hyperlipidemia and treated with lipid-lowering therapy for at least 3 months. Of these patients, 4559 (18.0%) were assigned to the NE group according to their residential zones.Patients in the NE group tended to be younger, female, overweight, and had more comorbidities and higher blood lipid levels than those in the non-NE group (P < .001). The goal attainment for LDL-C in NE was lower than non-NE (45.3% vs 65.1%, P < .001), and especially lower in high (NE vs non-NE, 38.5% vs 58.6%) and very high (NE vs non-NE, 22.6% vs 43.7%) risk patients. The proportion of high intensity statin was lower in NE than non-NE, and the proportion of combination therapy was similar (∼2%). However, the goal attainment did not increase after administering higher dosages of statins in 2 groups. Logistic regression analysis identified diabetes mellitus (DM), coronary heart disease (CHD), cerebrovascular disease (CBD), being female, body mass index (BMI) >24 kg/m, drinking alcohol, smoking, and being residence in NE China as independent predictors of LDL-C attainment.Despite having received persistent lipid-lowering treatments, the current situation of dyslipidemia patients in NE China is unsatisfactory. The main treatment gap might be related to the choice of statin and effective combination therapy and the control of comorbidities and obesity, especially for high-risk patients.
Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.
Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David
2017-01-01
3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.
Detection of irradiation induced reactive oxygen species production in live cells
NASA Astrophysics Data System (ADS)
Gao, Bo; Zhu, Debin
2006-09-01
Reactive oxygen species (ROS) is thought to play an important role in cell signaling of apoptosis, necrosis, and proliferation. Light irradiation increases mitochondrial reactive oxygen species (ROS) production and mediates its intracellular signaling by adjusting the redox potential in tumor cells. Mitochondria are the main source of ROS in the living cell. Superoxide anions (0 II - are likely the first ROS generated in the mitochondria following radiation damage, and then convert to hydrogen peroxide (H II0 II), hydroxyl radical (•OH), and singlet oxygen (10 II), etc. Conventional methods for research ROS production in mitochondria mostly use isolated mitochondria rather than mitochondria in living cells. In this study, a highly selective probe to detect mitochondrial 0 II - in live cells, MitoSOX TM Red, was applied to quantify the mitochondrial ROS production in human lung adenocarcinoma cells (ASTC-a-1) with laser scanning microscope (LSM) after ultraviolet C (UVC) and He-Ne laser irradiation. Dichiorodihydrofluoresein diacetate (DCFHDA), a common used fluorescent probe for ROS detection without specificity, were used as a comparison to image the ROS production. The fluorescent image of MItoSOX TM Red counterstained with MitoTracker Deep Red 633, a mitochondria selective probe, shows that the mitochondrial ROS production increases distinctly after UVC and He-Ne laser irradiation. DCFH-DA diffuses labeling throughout the cell though its fluorescence increases markedly too. In conclusion, the fluorescent method with MitoSOX TM Red reagent is proved to be a promising technique to research the role of ROS in radiation induced apoptosis.
EUGÈNE'HOM: a generic similarity-based gene finder using multiple homologous sequences
Foissac, Sylvain; Bardou, Philippe; Moisan, Annick; Cros, Marie-Josée; Schiex, Thomas
2003-01-01
EUGÈNE'HOM is a gene prediction software for eukaryotic organisms based on comparative analysis. EUGÈNE'HOM is able to take into account multiple homologous sequences from more or less closely related organisms. It integrates the results of TBLASTX analysis, splice site and start codon prediction and a robust coding/non-coding probabilistic model which allows EUGÈNE'HOM to handle sequences from a variety of organisms. The current target of EUGÈNE'HOM is plant sequences. The EUGÈNE'HOM web site is available at http://genopole.toulouse.inra.fr/bioinfo/eugene/EuGeneHom/cgi-bin/EuGeneHom.pl. PMID:12824408
Is elevated norepinephrine an etiological factor in some cases of epilepsy?
Fitzgerald, Paul J
2010-07-01
It is well established that the neurotransmitter norepinephrine (NE) has anticonvulsant properties. However, NE may also have proconvulsant properties under some conditions, both in animal epilepsy models and in humans. This paper examines the hypothesis that this neurotransmitter has proconvulsant properties, where much of the pharmaceutical evidence comes from rodent models. In assessing the elevated NE epilepsy hypothesis, the following seven lines of evidence are examined that include studies of: (1) antidepressants that raise the level of NE; (2) clonidine and other alpha 2 adrenergic agonist drugs that lower the level of NE; (3) prazosin and other drugs that affect alpha adrenoceptors; (4) propranolol and other drugs that affect beta adrenoceptors; (5) pheochromocytoma, which is a rare cancer of the adrenal glands that can boost NE levels; (6) comorbidity of epilepsy with bipolar disorder, hypertension, and obesity, where all four conditions may involve elevated NE; and (7) psychological stress, which is associated with increased release of NE. The body of evidence supporting the NE proconvulsant hypothesis is consistent with the notion that elevated, endogenous noradrenergic transmission is an etiological factor in some cases of epilepsy. 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
MicroBooNE: The Search For The MiniBooNE Low Energy Excess
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kaleko, David
This thesis describes work towards the search for a low energy excess in MicroBooNE. What MicroBooNE is, what the low energy excess is, and how one searches for the latter in the former will be described in detail.
Yao, Cui-Xia; Zhang, Pei-Yu
2014-07-10
The dynamics of the Ne + D2(+) (v0 = 0-2, j0 = 0) → NeD(+) + D reaction has been investigated in detail by using an accurate time-dependent wave-packet method on the ground 1(2)A' potential energy surface. Comparisons between the Coriolis coupling results and the centrifugal-sudden ones reveal that Coriolis coupling effect can influence reaction dynamics of the NeD2(+) system. Integral cross sections have been evaluated for the Ne + D2(+) reaction and its isotopic variant Ne + H2(+), and a considerable intermolecular isotopic effect has been found. Also obvious is the great enhancement of the reactivity due to the reagent vibrational excitation. Besides, a comparison with previous theoretical results is also presented and discussed.
Rosser, K E
1998-11-01
This paper evaluates the characteristics of ionization chambers for the measurement of absorbed dose to water for medium-energy x-rays. The values of the chamber correction factor, k(ch), used in the IPEMB code of practice for the UK secondary standard (NE2561/NE2611) ionization chamber are derived and their constituent factors examined. The comparison of the chambers' responses in air revealed that of the chambers tested only the NE2561, NE2571 and NE2505 exhibit a flat (within 5%) energy response in air. Under no circumstances should the NACP, Sanders electron chamber, or any chamber that has a wall made of high atomic number material, be used for medium-energy x-ray dosimetry. The measurements in water reveal that a chamber that has a substantial housing, such as the PTW Grenz chamber, should not be used to measure absorbed dose to water in this energy range. The value of k(ch) for an NE2561 chamber was determined by measuring the absorbed dose to water and comparing it with that for an NE2571 chamber, for which k(ch) data have been published. The chamber correction factor varies from 1.023 +/- 0.03 to 1.018 +/- 0.001 for x-ray beams with HVL between 0.15 and 4 mm Cu. The values agree with that for an NE2571 chamber within the experimental uncertainty. The corrections due to the stem, waterproof sleeve and replacement of the phantom material by the chamber for an NE2561 chamber are described.
Tann, Cally J; Martinello, Kathryn A; Sadoo, Samantha; Lawn, Joy E; Seale, Anna C; Vega-Poblete, Maira; Russell, Neal J; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Heath, Paul T
2017-11-06
Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases. We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE. Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%-.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47-2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births. The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Garratt, Luke W; Sutanto, Erika N; Ling, Kak-Ming; Looi, Kevin; Iosifidis, Thomas; Martinovich, Kelly M; Shaw, Nicole C; Buckley, Alysia G; Kicic-Starcevich, Elizabeth; Lannigan, Francis J; Knight, Darryl A; Stick, Stephen M; Kicic, Anthony
2016-03-01
Neutrophil elastase (NE) activity is associated with many destructive lung diseases and is a predictor for structural lung damage in early cystic fibrosis (CF), which suggests normal maintenance of airway epithelium is prevented by uninhibited NE. However, limited data exist on how the NE activity in airways of very young children with CF affects function of the epithelia. The aim of this study was to determine if NE activity could inhibit epithelial homeostasis and repair and whether any functional effect was reversible by antiprotease alpha-1 antitrypsin (α1AT) treatment. Viability, inflammation, apoptosis, and proliferation were assessed in healthy non-CF and CF pediatric primary airway epithelial cells (pAECnon-CF and pAECCF, respectively) during exposure to physiologically relevant NE. The effect of NE activity on pAECCF wound repair was also assessed. We report that viability after 48 hours was significantly decreased by 100 nM NE in pAECnon-CF and pAECCF owing to rapid cellular detachment that was accompanied by inflammatory cytokine release. Furthermore, both phenotypes initiated an apoptotic response to 100 nM NE, whereas ≥ 50 nM NE activity significantly inhibited the proliferative capacity of cultures. Similar concentrations of NE also significantly inhibited wound repair of pAECCF, but this effect was reversed by the addition of α1AT. Collectively, our results demonstrate free NE activity is deleterious for epithelial homeostasis and support the hypothesis that proteases in the airway contribute directly to CF structural lung disease. Our results also highlight the need to investigate antiprotease therapies in early CF disease in more detail.
Kuo, Fu-Shan; Falquetto, Bárbara; Chen, Dawei; Oliveira, Luiz M.; Takakura, Ana C.
2016-01-01
Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes and serve as an integration center for other autonomic centers, including brain stem noradrenergic neurons. Norepinephrine (NE) contributes to respiratory control and chemoreception, and, since disruption of NE signaling may contribute to several breathing disorders, we sought to characterize effects of NE on RTN chemoreception. All neurons included in this study responded similarly to CO2/H+ but showed differential sensitivity to NE; we found that NE activated (79%), inhibited (7%), or had no effect on activity (14%) of RTN chemoreceptors. The excitatory effect of NE on RTN chemoreceptors was dose dependent, retained in the presence of neurotransmitter receptor blockers, and could be mimicked and blocked by pharmacological manipulation of α1-adrenergic receptors (ARs). In addition, NE-activation was blunted by XE991 (KCNQ channel blocker), and partially occluded the firing response to serotonin, suggesting involvement of KCNQ channels. However, in whole cell voltage clamp, activation of α1-ARs decreased outward current and conductance by what appears to be a mixed effect on multiple channels. The inhibitory effect of NE on RTN chemoreceptors was blunted by an α2-AR antagonist. A third group of RTN chemoreceptors was insensitive to NE. We also found that chemosensitive RTN astrocytes do not respond to NE with a change in voltage or by releasing ATP to enhance activity of chemosensitive neurons. These results indicate NE modulates subsets of RTN chemoreceptors by mechanisms involving α1- and α2-ARs. PMID:27306669
Alignment relaxation of Ne*(2pi [J = 1]) atoms in He-Ne* glow discharges
NASA Astrophysics Data System (ADS)
Bahrim, Cristian; Khadilkar, Vaibhav; Matsukuma, Hiraku; Hasuo, Masahiro
2009-11-01
Alignment relaxation of the Ne*(2p5 3p; 2pi [J = 1]) atoms (where i = 2, 5, 7 or 10) induced by collisions with He atoms in glow discharges at 77 K < T < 1,000 K are reported. Close-coupling many-channel quantum calculations using a model potential for the Ne*(2p5 3p) - He system are compared with measurements of the alignment relaxation using the LIFS technique and the Hanle effect. The addition of the dipole polarization potential of the Ne*(2pi [J = 1]) atoms to the spin-orbit coupling and the electrostatic interaction between Ne* and He atoms leads to good agreement between theory and experiment.
Hantavirus disease (nephropathia epidemica) in Belgium: effects of tree seed production and climate.
Tersago, K; Verhagen, R; Servais, A; Heyman, P; Ducoffre, G; Leirs, H
2009-02-01
Recently, human cases of nephropathia epidemica (NE) due to Puumala virus infection in Europe have increased. Following the hypothesis that high reservoir host abundance induces higher transmission rates to humans, explanations for this altered epidemiology must be sought in factors that cause bank vole (Myodes glareolus) abundance peaks. In Western Europe, these abundance peaks are often related to high tree seed production, which is supposedly triggered by specific weather conditions. We evaluated the relationship between tree seed production, climate and NE incidence in Belgium and show that NE epidemics are indeed preceded by abundant tree seed production. Moreover, a direct link between climate and NE incidence is found. High summer and autumn temperatures, 2 years and 1 year respectively before NE occurrence, relate to high NE incidence. This enables early forecasting of NE outbreaks. Since future climate change scenarios predict higher temperatures in Europe, we should regard Puumala virus as an increasing health threat.
Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 C-acclimated hamsters
NASA Technical Reports Server (NTRS)
Jones, S. B.; Musacchia, X. J.
1976-01-01
The relationship of norepinephrine (NE) concentration and endogenous turnover rates in both myocardial and spleen tissues in the golden hamster is examined as a function of chronic exposure to either high or low ambient temperatures. Changes in myocardial and spleen NE turnover values are discussed in terms of functional alterations in sympathetic nerve activity and the importance of such changes in temperature acclimation. It is found that acclimation of hamsters to 7 C for 7-10 weeks results in decreased myocardial NE concentration and an apparent increase in myocardial NE turnover. In contrast, exposure to 34 C for 6-8 weeks results in increased myocardial NE concentration and an apparent decrease in NE turnover in both myocardial and spleen tissues. The implication of altered NE synthesis is that sympathetic nerve activity is reduced with heat acclimation and is enhanced with cold acclimation.
Taniyama, Toshiyuki; Tsuda, Natsumi; Sueda, Shinji
2018-06-15
The nuclear envelope (NE) is a double membrane that segregates nuclear components from the cytoplasm in eukaryotic cells. It is well-known that the NE undergoes a breakdown and reformation during mitosis in animal cells. However, the detailed mechanisms of the NE dynamics are not yet fully understood. Here, we propose a method for the fluorescent labeling of the NE in living cells, which enables the tracing of the NE dynamics during cell division under physiological conditions. In our method, labeling of the NE is accomplished by fixing green fluorescent protein carrying the nuclear localization signal on the inner nuclear membrane based on a unique biotinylation reaction from the archaeon Sulfolobus tokodaii. With this method, we observed HeLa cells during mitosis by confocal laser scanning microscopy and succeeded in clearly visualizing the difference in the timing of the formation of the NE and the nuclear lamina.
Low-lying dipole modes in 26,28Ne in the quasiparticle relativistic random phase approximation
NASA Astrophysics Data System (ADS)
Cao, Li-Gang; Ma, Zhong-Yu
2005-03-01
The low-lying isovector dipole strengths in the neutron-rich nuclei 26Ne and 28Ne are investigated in the quasiparticle relativistic random phase approximation. Nuclear ground-state properties are calculated in an extended relativistic mean field theory plus Bardeen-Cooper-Schrieffer (BCS) method where the contribution of the resonant continuum to pairing correlations is properly treated. Numerical calculations are tested in the case of isovector dipole and isoscalar quadrupole modes in the neutron-rich nucleus 22O. It is found that in the present calculation, low-lying isovector dipole strengths at Ex<10MeV in nuclei 26Ne and 26Ne exhaust about 4.9% and 5.8% of the Thomas-Reiche-Kuhn dipole sum rule, respectively. The centroid energy of the low-lying dipole excitation is located at 8.3 MeV in 26Ne and 7.9 MeV in 28Ne.
The Serotonin Transporter Promoter Polymorphism and Childhood Positive and Negative Emotionality
Hayden, Elizabeth P.; Klein, Daniel N.; Sheikh, Haroon I.; Olino, Thomas M.; Dougherty, Lea R.; Dyson, Margaret W.; Durbin, C. Emily; Singh, Shiva M.
2011-01-01
Association studies of the serotonin transporter promoter polymorphism (5-HTTLPR) and negative emotionality (NE) are inconclusive. However, emerging evidence suggests that the association between this polymorphism and NE may be influenced by levels of another temperament trait, positive emotionality (PE). Therefore, this study examined whether the association between the 5-HTTLPR and NE was moderated by PE. A community sample of 413 three-year-old children completed a standardized battery of laboratory tasks designed to tap temperamental emotionality. Children were also genotyped for the 5-HTTLPR. No direct association between 5-HTTLPR genotype and NE was found. However, the interaction of child PE and NE predicted 5-HTTLPR genotype. Furthermore, children with a short allele who were also low in PE had significantly greater NE than children without a short allele or children with high PE. Our findings suggest that the short allele of the 5-HTTLPR is associated with NE only in the context of low PE. Inconsistent links between NE and this gene in previous research may stem from the failure to consider other temperament traits that moderate associations. PMID:21038952
Almasi, Hadi; Zandi, Mohsen; Beigzadeh, Sara; Haghju, Sara; Mehrnow, Nazila
2016-07-14
Chitosan films were loaded with NE nettle (Urtica dioica L.) extract (NE) at concentrations of 0, 0.5, 1 and 1.5%w/w in the free or nanoliposomal form to obtain active and nanoactive films, respectively. The antioxidant potential of the films containing NE-loaded nanoliposomes was decreased in comparison of free NE incorporated films. Diffusion of NE to soybean oil was enough to delay the induction of the oxidation of soybean oil stored for 60 days in contact with chitosan based films. Release studies indicated that the release rate of NE in 95% ethanol simulant significantly decreased by the nanoencapsulation of NE. The diffusion coefficient (D) for chitosan films containing 1.5%w/w of free and encapsulated NE at 25 °C was 18.80 and 3.68 × 10 -7 cm 2 s -1 , respectively. Moreover, the formation of nanoliposomes diminished the increasing effect of temperature on the release rate as when storage temperature increased from 4 °C to 40 °C.
Lisson, Sarah; Goodell, L Suzanne; Dev, Dipti; Wilkerson, Kristi; Hegde, Archana V; Stage, Virginia C
2016-10-01
The purpose of this study was to provide new insight into common barriers to the availability and use of nutrition education (NE) resources in Head Start preschool programs based on administrator and teacher perceptions. In-depth, semistructured phone interviews (n = 63) were conducted with administrators (n = 31) and teachers (n = 32) from North Carolina-based Head Start programs. Interviews were audio-recorded and transcribed verbatim. Data were analyzed qualitatively using content analysis to identify common themes. Five emergent themes were identified within the areas of NE resource availability and use and barriers to NE resource availability and use. Participants expressed desire for greater organization of existing NE material resources, increased community support, and professional development opportunities for teachers specific to NE. Funding and time constraints were reported as affecting NE resources. Creative strategies for addressing NE resource availability and use and barriers (eg, NE integration with educational standards) in Head Start are needed. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.
The 20Ne(d,p) 21Ne Transfer Reaction in Relation to the s-Process Abundances
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nsangu, C. T.; Laird, A. M.; Parikh, A.
2016-01-01
A study of the Ne-20(d,p)Ne-21 transfer reaction was performed using the Quadrupole Dipole Dipole Dipole (Q3D) magnetic spectrograph in Garching, Germany. The experiment probed excitation energies in Ne-21 ranging from 6.9 MeV to 8.5 MeV. The aim was to investigate the spectroscopic information of Ne-21 within the Gamow window of core helium burning in massive stars. Further information in this region will help reduce the uncertainties on the extrapolation down to Gamow window cross sections of the O-17(alpha,gamma)Ne-21 reaction. In low metallicity stars, this reaction has a direct impact on s-process abundances by determining the fate of O-16 as eithermore » a neutron poison or a neutron absorber. The experiment used a 22-MeV deuteron beam, with intensities varying from 0.5-1 mu A, and an implanted target of Ne-20 of 7 mu g/cm(2) in 40 mu g/cm(2) carbon foils. Sixteen Ne-21 peaks have been identified in the E-x = 6.9-8.5 MeV range, of which only thirteen peaks correspond to known states. Only the previously-known E-x = 7.960 MeV state was observed within the Gamow window.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Andrews, Lester; Liang, Binyong; Li, Jun
2004-02-15
Atomic uranium excited by laser ablation reacts with CO in excess neon to produce the novel CUO molecule, which forms weak complexes CUO(Ne)m with neon and stronger complexes CUO(Ne)x(Ng)n (Ng = Ar, Kr, Xe) when the heavier noble gas atoms are present. The heavier CUO(Ne)m-1(Ng) complexes are identified through the effects of CO isotopic and Ng substitution on the neon matrix infrared spectra and by comparison to DFT frequency calculations on model complexes CUO(Ng) (Ng = Ne, Ar, Kr, Xe). The U-C and U-O stretching frequencies of CUO(Ne)m-1(Ng) complexes are slightly red shifted from 1047 and 872 cm-1 frequencies formore » the 1Sigma+ CUO ground state neon complex, which identifies singlet ground state CUO(Ne)m-1(Ng) complexes in solid neon. The next singlet CUO(Ne)x(Ng)2 complexes in excess neon follow in like manner. However, stretching modes and the isotopic shifts of the higher CUO(Ne)x(Ng)n complex approach those of the pure argon matrix CUO(Ar)n complex, which characterizes triple t ground state complexes by comparison to DFT frequency calculations.« less
Effect of counseling on nutritional status during pregnancy.
Garg, Aashima; Kashyap, Sushma
2006-08-01
To assess the nutritional status and dietary practices among underprivileged pregnant women, identify the lacune, outline implement and assess the effect of nutritional counseling on their dietary intake, anthropometric status and anemia status. Hundred pregnant women belonging to low socio-economic status were interviewed. Based on lacune, nutrition education (NE) was given in the form of simple messages to 50 subjects (NE-group) over 10-16 weeks period, while the remaining 50 formed the comparison group (Non-NE group). Tools used were individual counseling, weekly home visits and group meetings. Anthropometric measurements taken were height and weight. Dietary data was collected using 24-hour recall and food frequency questionnaire. Hemoglobin estimation was done. Effect of intervention was assessed by monitoring changes in dietary practices, weight gain, and nutritional status of the subjects. Baseline findings--low mean maternal body weight (51.05 +/- 7.26 kg), 96.3% anemia prevalence and severely sub-optimal dietary intakes. Post-NE results revealed a significant increase in quality and quantity of the diets consumed. Mean hemoglobin levels significantly increased (Post-NE vs Non-NE = 9.65 +/- 0.97 vs 7.85 +/- 1.58, p < 0.001) and anemia prevalence reduced (Post-NE vs Non-NE = 78.7% vs 96%) in post-NE group. Individual counseling with weekly reinforcement can bring about improvement in nutritional status during pregnancy.
Coutinho, C C; Mercadante, M E Z; Jorge, A M; Paz, C C P; El Faro, L; Monteiro, F M
2015-10-30
The effect of selection for postweaning weight was evaluated within the growth curve parameters for both growth and carcass traits. Records of 2404 Nellore animals from three selection lines were analyzed: two selection lines for high postweaning weight, selection (NeS) and traditional (NeT); and a control line (NeC) in which animals were selected for postweaning weight close to the average. Body weight (BW), hip height (HH), rib eye area (REA), back fat thickness (BFT), and rump fat thickness (RFT) were measured and records collected from animals 8 to 20 (males) and 11 to 26 (females) months of age. The parameters A (asymptotic value) and k (growth rate) were estimated using the nonlinear model procedure of the Statistical Analysis System program, which included fixed effect of line (NeS, NeT, and NeC) in the model, with the objective to evaluate differences in the estimated parameters between lines. Selected animals (NeS and NeT) showed higher growth rates than control line animals (NeC) for all traits. Line effect on curves parameters was significant (P < 0.001) for BW, HH, and REA in males, and for BFT and RFT in females. Selection for postweaning weight was effective in altering growth curves, resulting in animals with higher growth potential.
Kramer, A; Liashkovich, I; Oberleithner, H; Ludwig, S; Mazur, I; Shahin, V
2008-08-12
Apoptosis, a physiologically critical process, is characterized by a destruction of the cell after sequential degradation of key cellular components. Here, we set out to explore the fate of the physiologically indispensable nuclear envelope (NE) in this process. The NE mediates the critical nucleocytoplasmic transport through nuclear pore complexes (NPCs). In addition, the NE is involved in gene expression and contributes significantly to the overall structure and mechanical stability of the cell nucleus through the nuclear lamina, which underlies the entire nucleoplasmic face of the NE and thereby interconnects the NPCs, the NE, and the genomic material. Using the nano-imaging and mechanical probing approach atomic force microscopy (AFM) and biochemical methods, we unveiled the fate of the NE during apoptosis. The doomed NE sustains a degradation of both the mediators of the critical selective nucleocytoplasmic transport, namely NPC cytoplasmic filaments and basket, and the nuclear lamina. These observations are paralleled by marked softening and destabilization of the NE and the detection of vesicle-like nuclear fragments. We conclude that destruction of the cell nucleus during apoptosis proceeds in a strategic fashion. Degradation of NPC cytoplasmic filaments and basket shuts down the critical selective nucleocytoplasmic cross-talk. Degradation of the nuclear lamina disrupts the pivotal connection between the NE and the chromatin, breaks up the overall nuclear architecture, and softens the NE, thereby enabling the formation of nuclear fragments at later stages of apoptosis.
The Malleable Nature of the Budding Yeast Nuclear Envelope: Flares, Fusion, and Fenestrations.
Meseroll, Rebecca A; Cohen-Fix, Orna
2016-11-01
In eukaryotes, the nuclear envelope (NE) physically separates nuclear components and activities from rest of the cell. The NE also provides rigidity to the nucleus and contributes to chromosome organization. At the same time, the NE is highly dynamic; it must change shape and rearrange its components during development and throughout the cell cycle, and its morphology can be altered in response to mutation and disease. Here we focus on the NE of budding yeast, Saccharomyces cerevisiae, which has several unique features: it remains intact throughout the cell cycle, expands symmetrically during interphase, elongates during mitosis and, expands asymmetrically during mitotic delay. Moreover, its NE is safely breached during mating and when large structures, such as nuclear pore complexes and the spindle pole body, are embedded into its double membrane. The budding yeast NE lacks lamins and yet the nucleus is capable of maintaining a spherical shape throughout interphase. Despite these eccentricities, studies of the budding yeast NE have uncovered interesting, and likely conserved, processes that contribute to NE dynamics. In particular, we discuss the processes that drive and enable NE expansion and the dramatic changes in the NE that lead to extensions and fenestrations. J. Cell. Physiol. 231: 2353-2360, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
The Yeast Polo Kinase Cdc5 Regulates the Shape of the Mitotic Nucleus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walters, Alison D.; May, Christopher K.; Dauster, Emma S.
Abnormal nuclear size and shape are hallmarks of aging and cancer. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompassesmore » the nucleolus. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Lastly, even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis, plays a role in regulating nuclear morphology and NE expansion.« less
The Yeast Polo Kinase Cdc5 Regulates the Shape of the Mitotic Nucleus
Walters, Alison D.; May, Christopher K.; Dauster, Emma S.; ...
2014-11-20
Abnormal nuclear size and shape are hallmarks of aging and cancer. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompassesmore » the nucleolus. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Lastly, even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis, plays a role in regulating nuclear morphology and NE expansion.« less
Skrbinšek, Tomaž; Jelenčič, Maja; Waits, Lisette; Kos, Ivan; Jerina, Klemen; Trontelj, Peter
2012-02-01
The effective population size (N(e) ) could be the ideal parameter for monitoring populations of conservation concern as it conveniently summarizes both the evolutionary potential of the population and its sensitivity to genetic stochasticity. However, tracing its change through time is difficult in natural populations. We applied four new methods for estimating N(e) from a single sample of genotypes to trace temporal change in N(e) for bears in the Northern Dinaric Mountains. We genotyped 510 bears using 20 microsatellite loci and determined their age. The samples were organized into cohorts with regard to the year when the animals were born and yearly samples with age categories for every year when they were alive. We used the Estimator by Parentage Assignment (EPA) to directly estimate both N(e) and generation interval for each yearly sample. For cohorts, we estimated the effective number of breeders (N(b) ) using linkage disequilibrium, sibship assignment and approximate Bayesian computation methods and extrapolated these estimates to N(e) using the generation interval. The N(e) estimate by EPA is 276 (183-350 95% CI), meeting the inbreeding-avoidance criterion of N(e) > 50 but short of the long-term minimum viable population goal of N(e) > 500. The results obtained by the other methods are highly consistent with this result, and all indicate a rapid increase in N(e) probably in the late 1990s and early 2000s. The new single-sample approaches to the estimation of N(e) provide efficient means for including N(e) in monitoring frameworks and will be of great importance for future management and conservation. © 2012 Blackwell Publishing Ltd.
Goldstein, David S; Holmes, Courtney; Kaufmann, Horacio; Freeman, Roy
2004-12-01
Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA). In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS. Plasma L-DOPS peaked at 1.9 microg/ml (9 micromol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2-3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS. The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from LDOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves.
Modi, Kshitij D.; Foster, Thomas H.
2013-01-01
Abstract. We demonstrate the use of an enzyme-activatable fluorogenic probe, Neutrophil Elastase 680 FAST (NE680), for in vivo imaging of neutrophil elastase (NE) activity in tumors subjected to photodynamic therapy (PDT). NE protease activity was assayed in SCC VII and EMT6 tumors established in C3H and BALB/c mice, respectively. Four nanomoles of NE680 was injected intravenously immediately following PDT irradiation. 5 h following administration of NE680, whole-mouse fluorescence imaging was performed. At this time point, levels of NE680 fluorescence were at least threefold greater in irradiated versus unirradiated SCC VII and EMT6 tumors sensitized with Photofrin. To compare possible photosensitizer-specific differences in therapy-induced elastase activity, EMT6 tumors were also subjected to 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-PDT. NE levels measured in HPPH-PDT-treated tumors were twofold higher than in unirradiated controls. Ex vivo labeling of host cells using fluorophore-conjugated antibodies and confocal imaging were used to visualize Gr1+ cells in Photofrin-PDT-treated EMT6 tumors. These data were compared with recently reported analysis of Gr1+ cell accumulation in EMT6 tumors subjected to HPPH-PDT. The population density of infiltrating Gr1+ cells in treated versus unirradiated drug-only control tumors suggests that the differential in NE680 fold enhancement observed in Photofrin versus HPPH treatment may be attributed to the significantly increased inflammatory response induced by Photofrin-PDT. The in vivo imaging of NE680, which is a fluorescent reporter of NE extracellular release caused by neutrophil activation, demonstrates that PDT results in increased NE levels in treated tumors, and the accumulation of the cleaved probe tracks qualitatively with the intratumor Gr1+ cell population. PMID:23897439
Helium and neon isotopes in the mantle: constraints on the origin of volatiles on Earth
NASA Astrophysics Data System (ADS)
Moreira, M. A.
2005-12-01
It is now obvious that the mantle neon is solar-like. The possibility that the origin of this solar flavor is due to incorporation of irradiated parent bodies during accretion (e.g. gas rich meteorites) has been evoked by Trieloff and collaborators. The main argument is the fact there are no precise 20Ne/22Ne measured ratios above 13 in oceanic basalts, whereas the solar wind has a 20Ne/22Ne of 13.8 and the "neon B" neon shows a ratio of 12.6-12.8. The second argument for an irradiated origin is the air-like 38Ar/36Ar in mantle-derived samples (the "neon B" argon is close to air), distinct from the solar argon. Here we present another argument for an irradiated origin of the rare gases in the Earth. The global correlation in oceanic basalts (MORB and OIB) between 4He/3He and 21Ne/22Ne (corrected for air contamination) gives a mixing hyperbolae with a r parameter (r=(3He/22Ne)MORB/(3He/22Ne)PM) close to 10. It is now clear that 3He/22Ne ratio in the MORB source is around 7, giving for the primitive mantle (PM) a 3He/22Ne of 0.7. The solar 3He/22Ne ratio is estimated at 5-6 whereas the gas rich meteorites show a ratio of 0.3. Therefore, the global correlation in oceanic basalts between the helium and neon isotopic ratios suggests that (some) parent bodies of the Earth were gas rich meteorites, irradiated by an energetic solar wind during the planetary accretion.
Detection of neuroendocrine tumors using promoter-specific secreted Gaussia luciferase.
Tseng, Alan Wei-Shun; Akerstrom, Victoria; Chen, Chiachen; Breslin, Mary B; Lan, Michael S
2016-01-01
Accurate detection of neuroendocrine (NE) tumors is critically important for better prognosis and treatment outcomes in patients. To demonstrate the efficacy of using an adenoviral vector for the detection of NE tumors, we have constructed a pair of adenoviral vectors which, in combination, can conditionally replicate and release Gaussia luciferase into the circulation after infecting the NE tumors. The expression of these two vectors is regulated upstream by an INSM1-promoter (insulinoma-associated-1) that is specifically active in NE tumors and developing NE tissues, but silenced in normal adult tissues. In order to retain the tumor-specificity of the INSM1 promoter, we have modified the promoter using the core insulator sequence from the chicken β-globin HS4 insulator and the neuronal restrictive silencing element (NRSE). This modified INSM1-promoter can retain NE tumor specificity in an adenoviral construct while driving a mutated adenovirus E1A gene (∆24E1A), the Metridia, or Gaussia luciferase gene. The in vitro cell line and mouse xenograft human tumor studies revealed the NE specificity of the INSM1-promoter in NE lung cancer, neuroblastoma, medulloblastoma, retinoblastoma, and insulinoma. When we combined the INSM1-promoter driven Gaussia luciferase with ∆24E1A, the co-infected NE tumor secreted higher levels of Gaussia luciferase as compared to the INSM1p-Gaussia virus alone. In a mouse subcutaneous xenograft tumor model, the combination viruses secreted detectable level of Gaussia luciferase after infecting an INSM1-positive NE lung tumor for ≥12 days. Therefore, the INSM1-promoter specific conditional replicating adenovirus represents a sensitive diagnostic tool to aid clinicians in the detection of NE tumors.
Hare, Matthew P; Nunney, Leonard; Schwartz, Michael K; Ruzzante, Daniel E; Burford, Martha; Waples, Robin S; Ruegg, Kristen; Palstra, Friso
2011-06-01
Effective population size (N(e)) determines the strength of genetic drift in a population and has long been recognized as an important parameter for evaluating conservation status and threats to genetic health of populations. Specifically, an estimate of N(e) is crucial to management because it integrates genetic effects with the life history of the species, allowing for predictions of a population's current and future viability. Nevertheless, compared with ecological and demographic parameters, N(e) has had limited influence on species management, beyond its application in very small populations. Recent developments have substantially improved N(e) estimation; however, some obstacles remain for the practical application of N(e) estimates. For example, the need to define the spatial and temporal scale of measurement makes the concept complex and sometimes difficult to interpret. We reviewed approaches to estimation of N(e) over both long-term and contemporary time frames, clarifying their interpretations with respect to local populations and the global metapopulation. We describe multiple experimental factors affecting robustness of contemporary N(e) estimates and suggest that different sampling designs can be combined to compare largely independent measures of N(e) for improved confidence in the result. Large populations with moderate gene flow pose the greatest challenges to robust estimation of contemporary N(e) and require careful consideration of sampling and analysis to minimize estimator bias. We emphasize the practical utility of estimating N(e) by highlighting its relevance to the adaptive potential of a population and describing applications in management of marine populations, where the focus is not always on critically endangered populations. Two cases discussed include the mechanisms generating N(e) estimates many orders of magnitude lower than census N in harvested marine fishes and the predicted reduction in N(e) from hatchery-based population supplementation. ©2011 Society for Conservation Biology.
Thomas, Lydia; Zakir, Foziyah; Mirza, Mohd Aamir; Anwer, Md Khalid; Ahmad, Farhan Jalees; Iqbal, Zeenat
2017-08-01
In the present study, various nanoemulsions were prepared using Labrafac PG+Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032±0.023nm, viscosity 78.23±22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1-3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88μg/cm 2 /h as compared to NE2 (76.05μg/cm 2 /h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75±88μg) is significantly higher than NE2 (771.25±67μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.
Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W
2016-01-01
Emotional arousal enhances perception and memory of high-priority information but impairs processing of other information. Here, we propose that, under arousal, local glutamate levels signal the current strength of a representation and interact with norepinephrine (NE) to enhance high priority representations and out-compete or suppress lower priority representations. In our "glutamate amplifies noradrenergic effects" (GANE) model, high glutamate at the site of prioritized representations increases local NE release from the locus coeruleus (LC) to generate "NE hotspots." At these NE hotspots, local glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. In contrast, arousal-induced LC activity inhibits less active representations via two mechanisms: 1) Where there are hotspots, lateral inhibition is amplified; 2) Where no hotspots emerge, NE levels are only high enough to activate low-threshold inhibitory adrenoreceptors. Thus, LC activation promotes a few hotspots of excitation in the context of widespread suppression, enhancing high priority representations while suppressing the rest. Hotspots also help synchronize oscillations across neural ensembles transmitting high-priority information. Furthermore, brain structures that detect stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during, or after encoding enhances synaptic plasticity at NE hotspots, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms promote selective attention and memory under arousal. GANE not only reconciles apparently contradictory findings in the emotion-cognition literature but also extends previous influential theories of LC neuromodulation by proposing specific mechanisms for how LC-NE activity increases neural gain.
Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping
2014-01-01
Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.
Andrade-Silva, Jéssica; Cipolla-Neto, José; Peliciari-Garcia, Rodrigo A
2014-01-01
Although the norepinephrine (NE) synchronization protocol was proved to be an important procedure for further modulating in vitro pineal melatonin synthesis, the maintenance of clock genes under the same conditions remained to be investigated. The aim of this study was to investigate the maintenance of the clock genes expression in pineal gland cultures under standard and NE-synchronized stimulation. The glands were separated into three experimental groups: Control, Standard (acute NE-stimulation), and NE-synchronized. The expression of Bmal1, Per2, Cry2, Rev-erbα, the clock controlled gene Dbp and Arylalkylamine-N-acetyltransferase were investigated, as well as melatonin content. No oscillations were observed in the expression of the investigated genes from the control group. Under Standard NE stimulation, the clock genes did not exhibit a rhythmic pattern of expression. However, in the NE-synchronized condition, a rhythmic expression pattern was observed in all cases. An enhancement in pineal gland responsiveness to NE stimulation, reflected in an advanced synthesis of melatonin was also observed. Our results reinforce our previous hypothesis that NE synchronization of pineal gland culture mimics the natural rhythmic release of NE in the gland, increasing melatonin synthesis and keeping the pineal circadian clock synchronized, ensuring the fine adjustments that are relied in the clockwork machinery. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping
2014-01-01
Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity. PMID:25610478
Koch, J R; Creelman, R A; Eshita, S M; Seskar, M; Mullet, J E; Davis, K R
2000-06-01
Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response.
Koch, Jennifer Riehl; Creelman, Robert A.; Eshita, Steven M.; Seskar, Mirjana; Mullet, John E.; Davis, Keith R.
2000-01-01
Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response. PMID:10859179
On the origin of shape fluctuations of the cell nucleus.
Chu, Fang-Yi; Haley, Shannon C; Zidovska, Alexandra
2017-09-26
The nuclear envelope (NE) presents a physical boundary between the cytoplasm and the nucleoplasm, sandwiched in between two highly active systems inside the cell: cytoskeleton and chromatin. NE defines the shape and size of the cell nucleus, which increases during the cell cycle, accommodating for chromosome decondensation followed by genome duplication. In this work, we study nuclear shape fluctuations at short time scales of seconds in human cells. Using spinning disk confocal microscopy, we observe fast fluctuations of the NE, visualized by fluorescently labeled lamin A, and of the chromatin globule surface (CGS) underneath the NE, visualized by fluorescently labeled histone H2B. Our findings reveal that fluctuation amplitudes of both CGS and NE monotonously decrease during the cell cycle, serving as a reliable cell cycle stage indicator. Remarkably, we find that, while CGS and NE typically fluctuate in phase, they do exhibit localized regions of out-of-phase motion, which lead to separation of NE and CGS. To explore the mechanism behind these shape fluctuations, we use biochemical perturbations. We find the shape fluctuations of CGS and NE to be both thermally and actively driven, the latter caused by forces from chromatin and cytoskeleton. Such undulations might affect gene regulation as well as contribute to the anomalously high rates of nuclear transport by, e.g., stirring of molecules next to NE, or increasing flux of molecules through the nuclear pores.
Morgan, Judith K; Shaw, Daniel S; Olino, Thomas M
2012-08-01
Whereas socialization influences in early childhood have been linked to children's emerging internalizing problems and prosocial behavior, relatively few studies have examined how NE might moderate such associations in both advantageous and maladaptive ways. Furthermore, more research is needed to evaluate the impact of sibling relationships as an influential socialization influence on these child outcomes. In the current study we examined how NE might differentially moderate the associations between quality of relationships with siblings and both internalizing problems and social skills at school entry. NE moderated the effects of positive and destructive sibling relationship quality on child internalizing problems. Specifically, for boys high on NE, more positive sibling relationship quality predicted fewer internalizing problems, but more destructive sibling conflict predicted more internalizing problems. NE also moderated the effects of destructive sibling conflict on child social skills. For boys high on NE, destructive sibling conflict predicted fewer social skills. Boys high on NE appear to show greater susceptibility to the effects of sibling socialization on child outcomes, relative to boys low on NE. The implications of these interactions are discussed with respect to differential susceptibility theory.
Jerobin, Jayakumar; Makwana, Pooja; Suresh Kumar, RS; Sundaramoorthy, Rajiv; Mukherjee, Amitava; Chandrasekaran, Natarajan
2015-01-01
Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7–1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2–2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes. PMID:26491309
Jerobin, Jayakumar; Makwana, Pooja; Suresh Kumar, R S; Sundaramoorthy, Rajiv; Mukherjee, Amitava; Chandrasekaran, Natarajan
2015-01-01
Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7-1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2-2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes.
Nanoemulsion of ethanolic extracts of propolis and its antioxidant activity
NASA Astrophysics Data System (ADS)
Mauludin, R.; Primaviri, D. S.; Fidrianny, I.
2015-09-01
Propolis contains several antioxidant compounds which can be used in topical application to protect skin against free radical and prevent skin cancer and skin aging. Ethanolic extracts of propolis (EEP) provided the greatest antioxidant activity but has very small solubility in water thus was prepared in nanoemulsion (NE). EEP contains steroid/triterpenoid, flavonoid, and saponin. EEP had the value of DPPH scavenging activity 61.14% and IC50 0.41629 ppm. The best NE formulation consisted of 26.25% Kolliphor RH40; 8.75% glycerin; 5% rice bran oil; and 3% EEP. NE was transparent, had particle size of 23.72 nm and polydispersity index of 0.338. Based on TEM morphology, NE was almost spherical and has particle size below 50 nm. NE propolis revealed to be physically stable after stability test within 63 days at 25°C and passed 6 cycles of Freeze and Thaw test without separated. NE propolis reduced around 58% of free radical DPPH similar to antioxidant activity of the original extracts. Antioxidant activity of NE propolis is relatively stable after stored for 6 weeks. NE propolis was proven to be safe by primary irritation test with the value of primary irritation index (OECD) was 0.
A New Giant Stellar Structure in the Outer Halo of M31
NASA Astrophysics Data System (ADS)
Zucker, Daniel B.; Kniazev, Alexei Y.; Bell, Eric F.; Martínez-Delgado, David; Grebel, Eva K.; Rix, Hans-Walter; Rockosi, Constance M.; Holtzman, Jon A.; Walterbos, Rene A. M.; Ivezić, Željko; Brinkmann, J.; Brewington, Howard; Harvanek, Michael; Kleinman, S. J.; Krzesinski, Jurek; Lamb, Don Q.; Long, Dan; Newman, Peter R.; Nitta, Atsuko; Snedden, Stephanie A.
2004-09-01
The Sloan Digital Sky Survey has revealed an overdensity of luminous red giant stars ~3° (40 projected kpc) to the northeast of M31, which we have called Andromeda NE. The line-of-sight distance to Andromeda NE is within ~50 kpc of M31; Andromeda NE is not a physically unrelated projection. Andromeda NE has a g-band absolute magnitude of ~-11.6 and a central surface brightness of ~29 mag arcsec-2, making it nearly 2 orders of magnitude more diffuse than any known Local Group dwarf galaxy at that luminosity. Based on its distance and morphology, Andromeda NE is likely undergoing tidal disruption. Andromeda NE's red giant branch color is unlike that of M31's present-day outer disk or the stellar stream reported by Ibata et al., arguing against a direct link between Andromeda NE and these structures. However, Andromeda NE has a red giant branch color similar to that of the G1 clump; it is possible that these structures are both material torn off of M31's disk in the distant past or that these are both part of one ancient stellar stream.
Shaw, Daniel S.; Olino, Thomas M.
2012-01-01
Whereas socialization influences in early childhood have been linked to children’s emerging internalizing problems and prosocial behavior, relatively few studies have examined how NE might moderate such associations in both advantageous and maladaptive ways. Furthermore, more research is needed to evaluate the impact of sibling relationships as an influential socialization influence on these child outcomes. In the current study we examined how NE might differentially moderate the associations between quality of relationships with siblings and both internalizing problems and social skills at school entry. NE moderated the effects of positive and destructive sibling relationship quality on child internalizing problems. Specifically, for boys high on NE, more positive sibling relationship quality predicted fewer internalizing problems, but more destructive sibling conflict predicted more internalizing problems. NE also moderated the effects of destructive sibling conflict on child social skills. For boys high on NE, destructive sibling conflict predicted fewer social skills. Boys high on NE appear to show greater susceptibility to the effects of sibling socialization on child outcomes, relative to boys low on NE. The implications of these interactions are discussed with respect to differential susceptibility theory. PMID:22366882
Analysis of trace impurities in neon by a customized gas chromatography.
Yin, Min Kyo; Lim, Jeong Sik; Moon, Dong Min; Lee, Gae Ho; Lee, Jeongsoon
2016-09-09
Excimer lasers, widely used in the semiconductor industry, are crucial for analyzing the purity of premix laser gases for the purpose of controlling stable laser output power. In this study, we designed a system for analyzing impurities in pure neon (Ne) base gas by customized GC. Impurities in pure neon (H2 and He), which cannot be analyzed at the sub-μmol/mol level using commercial GC detectors, were analyzed by a customized pulsed-discharge Ne ionization detector (PDNeD) and a pressurized injection thermal conductivity detector using Ne as the carrier gas (Pres. Inj. Ne-TCD). From the results, trace species in Ne were identified with the following detection limits: H2, 0.378μmol/mol; O2, 0.119μmol/mol; CH4, 0.880μmol/mol; CO, 0.263μmol/mol; CO2, 0.162μmol/mol (PDNeD); and He, 0.190μmol/mol (Pres. Inj. Ne-TCD). This PDNeD and pressurized injection Ne-TCD technique thus developed permit the quantification of trace impurities present in high-purity Ne. Copyright © 2016. Published by Elsevier B.V.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jong, M. de; Leiden Institute of Physics, Leiden University, Leiden; Collaboration: KM3NeT Collaboration
2015-07-15
KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure hasmore » started. The prospects of the different phases of the implementation of KM3NeT are summarised.« less
NASA Astrophysics Data System (ADS)
de Jong, M.
2015-07-01
KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure has started. The prospects of the different phases of the implementation of KM3NeT are summarised.
Neutron unbound states in 28 Ne and 25 F
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smith, J. K.; Baumann, T.; Brown, B. A.
2012-11-01
Unbound states in Ne-28 and F-25 were populated in the reaction of a 102 MeV/nucleon Na-29 beam on a beryllium target. The measured decay energy of 32(22) keV in the Ne-27+n system corresponds to an unbound excited state in Ne-28 at 3.86(11) MeV. This is the first measured unbound state of Ne-28. The decay energy of the F-24+n system was measured as 300(170) keV. This places the second measured unbound state of F-25 at 4.66(17) MeV.
Specific memory impairment following neonatal encephalopathy in term-born children.
van Handel, Mariëlle; de Sonneville, Leo; de Vries, Linda S; Jongmans, Marian J; Swaab, Hanna
2012-01-01
This study examines short-term memory, verbal working memory, episodic long-term memory, and intelligence in 32 children with mild neonatal encephalopathy (NE), 39 children with moderate NE, 10 children with NE who developed cerebral palsy (CP), and 53 comparison children, at the age of 9 to 10 years. in addition to a global effect on intelligence, NE had a specific effect on verbal working memory, verbal and visuo-spatial long-term memory, and learning, which was associated with degree of NE. Although these memory problems occurred in children without CP, they were more pronounced when children had also developed CP.
Underwater acoustic positioning system for the SMO and KM3NeT - Italia projects
DOE Office of Scientific and Technical Information (OSTI.GOV)
Viola, S.; Barbagallo, G.; Cacopardo, G.
In the underwater neutrino telescopes, the positions of the Cherenkov light sensors and their movements must be known with an accuracy of few tens of centimetres. In this work, the activities of the SMO and KM3NeT-Italia teams for the development of an acoustic positioning system for KM3NeT-Italia project are presented. The KM3NeT-Italia project foresees the construction, within two years, of 8 towers in the view of the several km{sup 3}-scale neutrino telescope KM3NeT.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Al-Abdullah, T.; Physics Department, Hashemite University, Zarqa 13115; Carstoiu, F.
2010-03-15
The production of {sup 22}Na in ONe novae can be influenced by the {sup 22}Mg(p,gamma){sup 23}Al reaction. To investigate this reaction rate at stellar energies, we have determined the asymptotic normalization coefficient (ANC) for {sup 22}Mg+p->{sup 23}Al through measurements of the ANCs in the mirror nuclear system {sup 22}Ne+n->{sup 23}Ne. The peripheral neutron-transfer reactions {sup 13}C({sup 12}C,{sup 13}C){sup 12}C and {sup 13}C({sup 22}Ne,{sup 23}Ne){sup 12}C were studied. The identical entrance and exit channels of the first reaction make it possible to extract independently the ground-state ANC in {sup 13}C. Our experiment gives C{sub p{sub 1/2}}{sup 2}({sup 13}C)=2.24+-0.11 fm{sup -1}, whichmore » agrees with the value obtained from several previous measurements. The weighted average for all the obtained C{sub p{sub 1/2}}{sup 2} is 2.31+-0.08 fm{sup -1}. This value is adopted to be used in obtaining the ANCs in {sup 23}Ne. The differential cross sections for the reaction {sup 13}C({sup 22}Ne,{sup 23}Ne){sup 12}C leading to the J{sup {pi}}=5/2{sup +} and 1/2{sup +} states in {sup 23}Ne have been measured at 12 MeV/u. Optical model parameters for use in the DWBA calculations were obtained from measurements of the elastic scatterings {sup 22}Ne+{sup 13}C and {sup 22}Ne+{sup 12}C. The extracted ANC for the ground state in {sup 23}Ne, C{sub d{sub 5/2}}{sup 2}=0.86+-0.08+-0.12 fm{sup -1}, is converted to its corresponding value in {sup 23}Al using mirror symmetry to give C{sub d{sub 5/2}}{sup 2}({sup 23}Al)=(4.63+-0.77)x10{sup 3} fm{sup -1}. The astrophysical S factor S(0) for the {sup 22}Mg(p,gamma) reaction was determined to be 0.96+-0.11 keV b. The consequences for nuclear astrophysics are discussed.« less
Stanton, P K; Mody, I; Heinemann, U
1989-01-01
Mechanisms of action of norepinephrine (NE) on dentate gyrus granule cells were studied in rat hippocampal slices using extra- and intracellular recordings and measurements of stimulus and amino acid-induced changes in extracellular Ca2+ and K+ concentration. Bath application of NE (10-50 microM) induced long-lasting potentiation of perforant path evoked potentials, and markedly enhanced high-frequency stimulus-induced Ca2+ influx and K+ efflux, actions blocked by beta-receptor antagonists and mimicked by beta agonists. Enhanced Ca2+ influx was primarily postsynaptic, since presynaptic delta [Ca2+]o in the stratum moleculare synaptic field was not altered by NE. Interestingly, the potentiation of both ionic fluxes and evoked population potentials were antagonized by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). Furthermore, NE selectively enhanced the delta [Ca2+]o delta [K+]o and extracellular slow negative field potentials elicited by iontophoretically applied NMDA, but not those induced by the excitatory amino acid quisqualate. These results suggest that granule cell influx of Ca2+ through NMDA ionophores is enhanced by NE via beta-receptor activation. In intracellular recordings, NE depolarized granule cells (4.8 +/- 1.1 mV), and increased input resistance (RN) by 34 +/- 6.5%. These actions were also blocked by either the beta-antagonist propranolol or specific beta 1-blocker metoprolol. Moreover, the depolarization and RN increase persisted for long periods (93 +/- 12 min) after NE washout. In contrast, while NE, in the presence of APV, still depolarized granule cells and increased RN, APV made these actions quickly reversible upon NE washout (16 +/- 9 min). This suggested that NE induction of long-term, but not short-term, plasticity in the dentate gyrus requires NMDA receptor activation. NE may be enhancing granule cell firing by some combination of blockade on the late Ca2+-activated K+ conductance and depolarization of granule cells, both actions that can bring granule cells into a voltage range where NMDA receptors are more easily activated. Furthermore, NE also elicited activity-independent long-lasting depolarization and RN increases, which required functional NMDA receptors to persist.
1975-01-01
The synthesis and behavior of Amoeba proteus nuclear envelope (NE) phospholipids were studied. Most NE phospholipid synthesis occurs during G2 and little during mitosis or S. (A. proteus has no G1 phase). Autoradiographic observations after implantation of [3-H] choline nuclei into unlabeled cells reveal little turnover of NE phospholipid during interphase but during mitosis all the label is dispersed through the cytoplasm. Beginning at telophase all the label is dispersed through the cytoplasm. Beginning at telophase all the NE phospholipid label returns to the daughter NEs. This observation, along with the finding that no NE phospholipid synthesis occurs during mitosis or S, indicates that no de novo NE phospholipid production is required for newly forming NEs. Similarlyemetine, at concentrations that inhibit 97 percent of protein synthesis, does not prevent the post mitotic formation of NEs, suggesting that previously manufactured proteins are used in making new NEs. If a nucleus containing labeled NE phospholipids is transplanted into an unlabeled nucleate cell and the cell is allowed to grow and divide, the resultant four nuclei are equally labeled. This finding supports, but does not prove (see next paragraph), the conclusion that there probably is no continuity of the A. proteus NE during mitosis. When a phospholipid-labeled nucleus is implanted into a cell in mitosis, the grafted nucleus is not induced to enter mitosis. There is, however, a marked increase in the turnover of that nucleus's NE phospholipids with no apparent breakdown of the NE; this indicated that the mitotic cytoplasm possesses a factor that stimulates NE phospholipid exchange with the cytoplasm. That enhanced turnover is not accompanied by visible structural alteration makes less certain the earlier conclusion that no NE continuity exists during mitosis. Perhaps the most important finding in this study is that there are present, at restricted times in the cell cycle, factors capable of inducing accelerated exchange of structural components without microscopically detectable disruptions of structure. PMID:805790
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jankunas, Justin; Bertsche, Benjamin; Osterwalder, Andreas, E-mail: andreas.osterwalder@epfl.ch
2014-06-28
Two isotopic chemical reactions, Ne{sup *} + NH{sub 3}, and Ne{sup *} + ND{sub 3}, have been studied at low collision energies by means of a merged beams technique. Partial cross sections have been recorded for the two reactive channels, namely, Ne{sup *} + NH{sub 3} → Ne + NH{sub 3}{sup +} + e{sup −}, and Ne{sup *} + NH{sub 3} → Ne + NH{sub 2}{sup +}+ H + e{sup −}, by detecting the NH{sub 3}{sup +} and NH{sub 2}{sup +} product ions, respectively. The cross sections for both reactions were found to increase with decreasing collision energy, E{sub coll},more » in the range 8 μeV < E{sub coll} < 20 meV. The measured rate constant exhibits a curvature in a log(k)-log(E{sub coll}) plot from which it is concluded that the Langevin capture model does not properly describe the Ne{sup *} + NH{sub 3} reaction in the entire range of collision energies covered here. Calculations based on multichannel quantum defect theory were performed to reproduce and interpret the experimental results. Good agreement was obtained by including long range van der Waals interactions combined with a 6-12 Lennard-Jones potential. The branching ratio between the two reactive channels, Γ=([NH{sub 2}{sup +}])/([NH{sub 2}{sup +}]+[NH{sub 3}{sup +}]) , is relatively constant, Γ ≈ 0.3, in the entire collision energy range studied here. Possible reasons for this observation are discussed and rationalized in terms of relative time scales of the reactant approach and the molecular rotation. Isotopic differences between the Ne{sup *} + NH{sub 3} and Ne{sup *} + ND{sub 3} reactions are small, as suggested by nearly equal branching ratios and cross sections for the two reactions.« less
MAP kinase-independent signaling in angiotensin II regulation of neuromodulation in SHR neurons.
Yang, H; Raizada, M K
1998-09-01
Angiotensin II (Ang II), via its interaction with the angiotensin type 1 (AT1) receptor subtype, causes enhanced stimulation of norepinephrine (NE) neuromodulation. This involves increased transcription of NE transporter, tyrosine hydroxylase, and dopamine ss-hydroxylase genes in Wistar-Kyoto rat (WKY) brain neurons. AT1 receptor-mediated regulation of certain signaling events (such as activation of the Ras-Raf-1-mitogen activated protein (MAP) kinase signaling pathway, nuclear translocation of transcription factors such as Fos and Jun, and the interactions of these factors with AP-1 binding sites) is involved in this NE neuromodulation (Lu et al. J Cell Biol. 1996;135:1609-1617). The aim of this study was to compare the signal transduction mechanism of Ang II regulation of NE neuromodulation in WKY and spontaneously hypertensive rat (SHR) brain neurons, in view of the fact that AT1 receptor expression and Ang II stimulation of NE neuromodulation are higher in SHR neurons compared with WKY neurons. Despite this hyperactivity, Ang II stimulation of Ras, Raf-1, and MAP kinase activities was comparable between the neurons from WKY and SHR. Similarly, central injections of Ang II caused a comparable stimulation of MAP kinase in the hypothalamic and brain stem areas of adult WKY and SHR. Inhibition of MAP kinase by either an MAP kinase kinase inhibitor (PD98059) or an MAP kinase antisense oligonucleotide completely attenuated the stimulatory effects of Ang II on [3H]-NE uptake, NE transporter mRNA, and tyrosine hydroxylase mRNA levels in WKY neurons. These treatments resulted in only 43% to 50% inhibition of [3H]-NE uptake and NE transporter and tyrosine hydroxylase mRNAs in SHR neurons. Thus, Ang II stimulation of NE neuromodulation was completely blocked by MAP kinase inhibition in WKY neurons and only partially blocked in the SHR neurons. These observations suggest the presence of an additional signal transduction pathway involved in NE neuromodulation in SHR neurons that is independent of the MAP kinase pathway.
Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice
Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.
2012-01-01
Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542
Origin of Ne emission line of very luminous soft X-ray transient MAXI J0158–744
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ohtani, Yukari; Morii, Mikio; Shigeyama, Toshikazu
2014-06-01
We investigate the mechanism that reproduced notable spectral features at the ignition phase of the nova explosion observed for a super-Eddington X-ray transient source MAXI J0158–744 in the Small Magellanic Cloud. These features include a strong Ne IX emission line at 0.92 keV with large equivalent widths of 0.32{sub −0.11}{sup +0.21} keV and the absence of the Ne X line at 1.02 keV. In this paper, we calculate the radiative transfer using a Monte Carlo code, taking into account the line blanketing effect due to transitions of N, O, Ne, Mg, and Al ions in an accelerating wind emanating frommore » a white dwarf with a structure based on a spherically symmetric stationary model. We found that the strong Ne IX line can be reproduced if the mass fraction of Ne is enhanced to 10{sup –3} or more and if that of O is reduced to ∼5 × 10{sup –9} or less and that the absence of other lines, including Ne X ions at higher energies, can be also reproduced by the line blanketing effect. This enhancement of the Ne mass fraction indicates that the ejecta are enriched by Ne dredged up from the surface of the white dwarf composed of O, Ne, and Mg rather than C and O, as already pointed out in previous work. We argue that the CNO cycle driving this nova explosion converted most of C and O into N and thus reduced the O mass fraction.« less
Parreira, Valeria R.; Marri, Pradeep R.; Rosey, Everett L.; Gong, Joshua; Songer, J. Glenn; Vedantam, Gayatri; Prescott, John F.
2010-01-01
Type A Clostridium perfringens causes poultry necrotic enteritis (NE), an enteric disease of considerable economic importance, yet can also exist as a member of the normal intestinal microbiota. A recently discovered pore-forming toxin, NetB, is associated with pathogenesis in most, but not all, NE isolates. This finding suggested that NE-causing strains may possess other virulence gene(s) not present in commensal type A isolates. We used high-throughput sequencing (HTS) technologies to generate draft genome sequences of seven unrelated C. perfringens poultry NE isolates and one isolate from a healthy bird, and identified additional novel NE-associated genes by comparison with nine publicly available reference genomes. Thirty-one open reading frames (ORFs) were unique to all NE strains and formed the basis for three highly conserved NE-associated loci that we designated NELoc-1 (42 kb), NELoc-2 (11.2 kb) and NELoc-3 (5.6 kb). The largest locus, NELoc-1, consisted of netB and 36 additional genes, including those predicted to encode two leukocidins, an internalin-like protein and a ricin-domain protein. Pulsed-field gel electrophoresis (PFGE) and Southern blotting revealed that the NE strains each carried 2 to 5 large plasmids, and that NELoc-1 and -3 were localized on distinct plasmids of sizes ∼85 and ∼70 kb, respectively. Sequencing of the regions flanking these loci revealed similarity to previously characterized conjugative plasmids of C. perfringens. These results provide significant insight into the pathogenetic basis of poultry NE and are the first to demonstrate that netB resides in a large, plasmid-encoded locus. Our findings strongly suggest that poultry NE is caused by several novel virulence factors, whose genes are clustered on discrete pathogenicity loci, some of which are plasmid-borne. PMID:20532244
Lepp, Dion; Roxas, Bryan; Parreira, Valeria R; Marri, Pradeep R; Rosey, Everett L; Gong, Joshua; Songer, J Glenn; Vedantam, Gayatri; Prescott, John F
2010-05-24
Type A Clostridium perfringens causes poultry necrotic enteritis (NE), an enteric disease of considerable economic importance, yet can also exist as a member of the normal intestinal microbiota. A recently discovered pore-forming toxin, NetB, is associated with pathogenesis in most, but not all, NE isolates. This finding suggested that NE-causing strains may possess other virulence gene(s) not present in commensal type A isolates. We used high-throughput sequencing (HTS) technologies to generate draft genome sequences of seven unrelated C. perfringens poultry NE isolates and one isolate from a healthy bird, and identified additional novel NE-associated genes by comparison with nine publicly available reference genomes. Thirty-one open reading frames (ORFs) were unique to all NE strains and formed the basis for three highly conserved NE-associated loci that we designated NELoc-1 (42 kb), NELoc-2 (11.2 kb) and NELoc-3 (5.6 kb). The largest locus, NELoc-1, consisted of netB and 36 additional genes, including those predicted to encode two leukocidins, an internalin-like protein and a ricin-domain protein. Pulsed-field gel electrophoresis (PFGE) and Southern blotting revealed that the NE strains each carried 2 to 5 large plasmids, and that NELoc-1 and -3 were localized on distinct plasmids of sizes approximately 85 and approximately 70 kb, respectively. Sequencing of the regions flanking these loci revealed similarity to previously characterized conjugative plasmids of C. perfringens. These results provide significant insight into the pathogenetic basis of poultry NE and are the first to demonstrate that netB resides in a large, plasmid-encoded locus. Our findings strongly suggest that poultry NE is caused by several novel virulence factors, whose genes are clustered on discrete pathogenicity loci, some of which are plasmid-borne.
NASA Technical Reports Server (NTRS)
Benson, Robert F.; Fainberg, Joseph; Osherovich, Vladimir A.; Truhlik, Vladimir; Wang, Yongli; Bilitza, Dieter; Fung, Shing F.
2015-01-01
Large magnetic-storm induced changes have been detected in high-latitude topside vertical electron-density profiles Ne(h). The investigation was based on the large database of topside Ne(h) profiles and digital topside ionograms from the International Satellites for Ionospheric Studies (ISIS) program available from the NASA Space Physics Data Facility (SPDF) at http://spdf.gsfc.nasa.gov/isis/isis-status.html. This large database enabled Ne(h) profiles to be obtained when an ISIS satellite passed through nearly the same region of space before, during, and after a major magnetic storm. A major goal was to relate the magnetic-storm induced high-latitude Ne(h) profile changes to solar-wind parameters. Thus an additional data constraint was to consider only storms where solar-wind data were available from the NASA/SPDF OMNIWeb database. Ten large magnetic storms (with Dst less than -100 nT) were identified that satisfied both the Ne(h) profile and the solar-wind data constraints. During five of these storms topside ionospheric Ne(h) profiles were available in the high-latitude northern hemisphere and during the other five storms similar ionospheric data were available in the southern hemisphere. Large Ne(h) changes were observed during each one of these storms. Our concentration in this paper is on the northern hemisphere. The data coverage was best for the northern-hemisphere winter. Here Ne(h) profile enhancements were always observed when the magnetic local time (MLT) was between 00 and 03 and Ne(h) profile depletions were always observed between 08 and 10 MLT. The observed Ne(h) deviations were compared with solar-wind parameters, with appropriate time shifts, for four storms.
Li, Zhongchao; Liu, Hu; Li, Yakui; Lv, Zhiqian; Liu, Ling; Lai, Changhua; Wang, Junjun; Wang, Fenglai; Li, Defa; Zhang, Shuai
2018-01-01
In the past two decades, a considerable amount of research has focused on the determination of the digestible (DE) and metabolizable energy (ME) contents of feed ingredients fed to swine. Compared with the DE and ME systems, the net energy (NE) system is assumed to be the most accurate estimate of the energy actually available to the animal. However, published data pertaining to the measured NE content of ingredients fed to growing pigs are limited. Therefore, the Feed Data Group at the Ministry of Agricultural Feed Industry Centre (MAFIC) located at China Agricultural University has evaluated the NE content of many ingredients using indirect calorimetry. The present review summarizes the NE research works conducted at MAFIC and compares these results with those from other research groups on methodological aspect. These research projects mainly focus on estimating the energy requirements for maintenance and its impact on the determination, prediction, and validation of the NE content of several ingredients fed to swine. The estimation of maintenance energy is affected by methodology, growth stage, and previous feeding level. The fasting heat production method and the curvilinear regression method were used in MAFIC to estimate the NE requirement for maintenance. The NE contents of different feedstuffs were determined using indirect calorimetry through standard experimental procedure in MAFIC. Previously generated NE equations can also be used to predict NE in situations where calorimeters are not available. Although popular, the caloric efficiency is not a generally accepted method to validate the energy content of individual feedstuffs. In the future, more accurate and dynamic NE prediction equations aiming at specific ingredients should be established, and more practical validation approaches need to be developed.
Beam production of 18Ne with in-flight method for alpha scattering at CRIB
NASA Astrophysics Data System (ADS)
Duy, N. N.; Chae, K. Y.; Cha, S. M.; Yamaguchi, H.; Abe, K.; Bae, S. H.; Binh, D. N.; Choi, S. H.; Hahn, K. I.; Hayakawa, S.; Hong, B.; Iwasa, N.; Kahl, D.; Khiem, L. H.; Kim, A.; Kim, D. H.; Kim, E. J.; Kim, G. W.; Kim, M. J.; Kwak, K.; Kwag, M. S.; Lee, E. J.; Lim, S. I.; Moon, B.; Moon, J. Y.; Park, S. Y.; Phong, V. H.; Shimizu, H.; Yang, L.; Ge, Z.; Hao, T. V. Nhan
2018-07-01
We conducted a measurement of 18Ne + α scattering in inverse kinematics, in order to search for experimental evidence of α-cluster structure in 22Mg above the alpha threshold (Ethr = 8 . 14 MeV) and determine the astrophysical rates of the 18Ne(α, p)21Na reaction under the conditions of break-out from the Hot-CNO cycle. A high intensity 18Ne beam at 2.54 AMeV was successfully produced at CRIB (CNS Radioactive Ion Beam separator) of the Center for Nuclear Study, the University of Tokyo. This paper presents the in-flight production of the radioactive 18Ne beam by using the production reaction 3He(16O, 18Ne)n with a windowed cryogenic gas target, which was employed in the mentioned resonant α-scattering experiment.
Waples, R S
2016-10-01
The relationship between life-history traits and the key eco-evolutionary parameters effective population size (Ne) and Ne/N is revisited for iteroparous species with overlapping generations, with a focus on the annual rate of adult mortality (d). Analytical methods based on populations with arbitrarily long adult lifespans are used to evaluate the influence of d on Ne, Ne/N and the factors that determine these parameters: adult abundance (N), generation length (T), age at maturity (α), the ratio of variance to mean reproductive success in one season by individuals of the same age (φ) and lifetime variance in reproductive success of individuals in a cohort (Vk•). Although the resulting estimators of N, T and Vk• are upwardly biased for species with short adult lifespans, the estimate of Ne/N is largely unbiased because biases in T are compensated for by biases in Vk• and N. For the first time, the contrasting effects of T and Vk• on Ne and Ne/N are jointly considered with respect to d and φ. A simple function of d and α based on the assumption of constant vital rates is shown to be a robust predictor (R(2)=0.78) of Ne/N in an empirical data set of life tables for 63 animal and plant species with diverse life histories. Results presented here should provide important context for interpreting the surge of genetically based estimates of Ne that has been fueled by the genomics revolution.
NASA Astrophysics Data System (ADS)
Zhang, Y. Q.; Wei, H. J.; Yang, H. Q.; Guo, Z. Y.; Xie, S. S.; Gu, H. M.; Guo, X.; Zhu, Z. G.
2013-06-01
Previous studies from our group have demonstrated that glucose solution can induce optical clearing enhancement of esophageal tissues with optical coherence tomography (OCT). The aims of this study were to evaluate the optical clearing effects of ultrasound-mediated optical clearing agents (OCAs) and to find more effective methods to distinguish human normal esophageal tissues (NE) and cancerous esophageal tissues (CE). Here we used the OCT technique to investigate the optical attenuation of NE and CE in vitro after treatment with 30% glycerol alone and glycerol combined with ultrasound, respectively. Experimental results showed that the averaged attenuation coefficient of CE was significantly larger than that of NE. The maximal decreases of averaged attenuation coefficients of NE and CE were approximately 48.7% and 36.2% after treatment with 30% glycerol alone, and they were significantly lower than those treated with 30% glycerol and ultrasound (57.5% in NE and 44.8% in CE). Moreover, after treatment with 30% glycerol alone, the averaged attenuation coefficients of NE and CE reached their minima in about 80 min and 65 min, respectively. The times were much shorter in NE and CE after treatment with glycerol with ultrasound, being about 62 min and 50 min, respectively. The results suggest that there is a significant difference in the optical properties of NE and CE, and that OCT with an ultrasound-OCAs combination has the ability to distinguish CE from NE.
Brownlow, Bill; Nagaraj, Vinay J; Nayel, Amy; Joshi, Megha; Elbayoumi, Tamer
2015-10-01
There is a great need for effective protection against cutaneous pathologies arising from chronic exposure to harmful solar UVB radiations. A promising pharmaceutical strategy to improve the efficacy of chemotherapeutic/preventative natural compounds (e.g., soy isoflavone Genistein, Gen) is to enhance their dermal delivery using nanoemulsion (NE) formulations. This report investigates the development of nanoemulsified tocotrienol(T3)-rich fraction of red palm oil (Tocomin®), to yield an optimal NE delivery system for dermal photoprotection (z-average size <150 nm, ζ-potential ≈ -30 mV, polydispersity index < 0.25). Physicochemical characterization and photostability studies indicate NE formulations utilizing surfactant mixture (Smix) of Solutol® HS-15 (SHS15) blended with vitamin E TPGS (TPGS) as cosurfactant was significantly superior to formulations that utilized Lutrol® F68 (LF68) as the cosurfactant. A ratio of 60:40 of SHS15-TPGS-NE was further identified as lead Tocomin® NE topical platform using in vitro pharmaceutical skin reactivity studies that assess cutaneous irritancy and cytotoxicity. Prototype Tocomin® NE loaded with the antiphotocarcinogenic molecule Gen (Gen-Tocomin® NE) showed slow-release profile in both liquid and cream forms. Gen-Tocomin® NE also showed excellent biocompatibility, and provided substantial UVB protection to cultured subcutaneous L929 fibroblasts, indicating the great potential of our Tocomin® NE warranting further prototype development as topical pharmaceutical platform for skin photoprotection applications. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
BACKWARD ANGLE STRUCTURE IN THE 20Ne+28Si QUASIELASTIC SCATTERING
NASA Astrophysics Data System (ADS)
Sgouros, O.; Soukeras, V.; Pakou, A.; Patronis, N.; Zerva, K.; Keeley, N.; Strojek, I.; Trzcińska, A.; Piasecki, E.; Rusek, K.; Stiliaris, E.; Mazzocco, M.
2013-10-01
New data for the quasielastic scattering of 20Ne from a 28Si target at incident energies of 42.5 MeV and 52.3 MeV and for the 28Si(20Ne, 24Mg)24Mg, 28Si(20Ne, 16O)32S and 28Si(20Ne, 12C)36Ar transfer reactions at 52.3 MeV are reported. Oscillations are observed in the backward angle quasielastic scattering data at 52.3 MeV and the 28Si(20Ne, 12C)36Ar transfer cross-sections are of the same magnitude as those for single-α stripping. Coupled reaction channels (CRC) calculations are unable to describe either the quasielastic or the 28Si(20Ne, 12C)36Ar transfer data assuming a sequential α transfer process with α-particle form factors from the literature. The addition of direct 8Be cluster transfer can provide a reasonable description of both data sets, but only with much larger spectroscopic factors than suggested by simple structure calculations or the large 8Be emission thresholds of 20Ne, 28Si and 36Ar, suggesting that the observed structure is of resonance-like origin. An optical model analysis of the quasielastic scattering data is also reported.
Studies of X-ray burst reactions with radioactive ion beams from RESOLUT
NASA Astrophysics Data System (ADS)
Blackmon, J. C.; Wiedenhöver, I.; Belarge, J.; Kuvin, S. A.; Anastasiou, M.; Baby, L. T.; Baker, J.; Colbert, K.; Deibel, C. M.; de Lucio, O.; Gardiner, H. E.; Gay, D. L.; Good, E.; Höflich, P.; Hood, A. A. D.; Keely, N.; Lai, J.; Laminack, A.; Linhardt, L. E.; Lighthall, J.; Macon, K. T.; Need, E.; Quails, N.; Rasco, B. C.; Rijal, N.; Volya, A.
2018-01-01
Reactions on certain proton-rich, radioactive nuclei have been shown to have a significant influence on X-ray bursts. We provide an overview of two recent measurements of important X-ray burst reactions using in-flight radioactive ion beams from the RESOLUT facility at the J. D. Fox Superconducting Accelerator Laboratory at Florida State University. The 17F(d,n)18Ne reaction was measured, and Asymptotic Normalization Coefficients were extracted for bound states in 18Ne that determine the direct-capture cross section dominating the 17F(p,γ)18Ne reaction rate for T≲ 0.45 GK. Unbound resonant states were also studied, and the single-particle strength for the 4.523-MeV (3+) state was found to be consistent with previous results. The 19Ne(d,n)20Na proton transfer reaction was used to study resonances in the 19Ne(p,γ)20Na reaction. The most important 2.65-MeV state in 20Na was observed to decay by proton emission to both the ground and first-excited states in 19Ne, providing strong evidence for a 3+ spin assignment and indicating that proton capture on the thermally-populated first-excited state in 19Ne is an important contributor to the 19Ne(p,γ)20Na reaction rate.
2013-01-01
Background The use of psychoactive substances to neuroenhance cognitive performance is prevalent. Neuroenhancement (NE) in everyday life and doping in sport might rest on similar attitudinal representations, and both behaviors can be theoretically modeled by comparable means-to-end relations (substance-performance). A behavioral (not substance-based) definition of NE is proposed, with assumed functionality as its core component. It is empirically tested whether different NE variants (lifestyle drug, prescription drug, and illicit substance) can be regressed to school stressors. Findings Participants were 519 students (25.8 ± 8.4 years old, 73.1% female). Logistic regressions indicate that a modified doping attitude scale can predict all three NE variants. Multiple NE substance abuse was frequent. Overwhelming demands in school were associated with lifestyle and prescription drug NE. Conclusions Researchers should be sensitive for probable structural similarities between enhancement in everyday life and sport and systematically explore where findings from one domain can be adapted for the other. Policy makers should be aware that students might misperceive NE as an acceptable means of coping with stress in school, and help to form societal sensitivity for the topic of NE among our younger ones in general. PMID:23777577
Hur, Yoon-Mi; Hwang, Sunyung; Chung, Un-Sun
2015-12-01
Age difference in the etiology of the relationship between childhood negative emotionality (NE) and conduct problems (CP) has not been previously investigated. Mothers of 662 pairs of twins completed questions on the emotionality (NE) scale of the EAS temperament survey and the CP scale of the Strengths and Difficulties Questionnaires (SDQ) via a telephone interview. Twin data were analyzed separately in younger (ages 3 to 7 years; mostly pre-schoolers) and older children (ages 8 to 13 years; mostly elementary school children). The phenotypic correlation between NE and CP increased from 0.33 among younger twins to 0.43 among older twins. Bivariate model-fitting analysis was performed to determine age difference in the etiology of the relationship between NE and CP. Among younger twins, the correlation between NE and CP was entirely explained by additive genetic factors common to NE and CP. Among older children, however, a small but significant amount of unique environmental correlation emerged to account for about 47% of the phenotypic correlation between NE and CP. The remaining 53% of the phenotypic correlation was due to shared additive genetic factors. We speculate that environmental factors associated with school adjustment may exert influences on the relationship between NE and CP among elementary school children.
NASA Astrophysics Data System (ADS)
Nobre, José; Cabral, Tiago; Cabral, João; Gomes, Ana
2014-05-01
The Complex pegmatite - apelitic of Cabecinha corresponds to an isolated ridge that reaches 933 meters, located in the middle zone of transition between the Hesperian massif and the Cova da Beira being located in the NE central part of Portugal, more specifically in the Mountainous region of the province of Beira Alta, council of Sabugal. This complex lies embedded in porphyritic granites with terms of switching to a medium-grained granite rich in sodium feldspars in which they are muscovite granite intrusions. The lodes have pegmatites with NE-SW orientation, presenting phases of predominantly quartz crystallization with multiple parageneses. The inclusions observed are veins filonianian secondary. Some veins have structural discontinuity due to further their training tectonics. The apelitico material is basic in nature engaging in descontinuiddes of pegmatite material, showing no preferred orientation. The petrological characteristics of the area in question provide the appearance of motivating exotic landforms of scientific interest. These landforms, over time, have motivated the popular level the emergence of various myths, thus contributing to the enrichment of the local cultural heritage. This study proceeded to the geological and geomorphological mapping an area of about 6945,350 m2 with a maximum length of 182 m. The huge patent mineralogical, petrological and geomorphological level geodiversity, allied to the structural complexity and associated cultural heritage, allow geoconservation strategies and recovery, using new multimedia technologies including use of QR codes and 3D. All this geological framework and environment becomes an asset for the scientific, educational and economic development of the region. On the other hand, it has the vital Importance in the context of the strategy of forming a geological park, in the point of view of tourism, research and interpretation.
Gioio, Anthony E.
2017-01-01
Abstract Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3′untranslated region (3’UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal. Toward this end, a targeted deletion of the axonal transport sequence element was developed, using the lentiviral delivery of the CRISPR/Cas9 system, and two guide RNA (gRNA) sequences flanking the 50-bp cis-acting regulatory element in rat superior cervical ganglion (SCG) neurons. Deletion of the axonal transport element reduced TH mRNA levels in the distal axons and reduced the axonal protein levels of TH and TH activity as measured by phosphorylation of SER40 in SCG neurons. Moreover, deletion of the zip-code diminished the axonal levels of dopamine (DA) and norepinephrine (NE). Conversely, the local translation of exogenous TH mRNA in the distal axon enhanced TH levels and activity, and elevated axonal NE levels. Taken together, these results provide direct evidence to support the hypothesis that TH mRNA trafficking and local synthesis of TH play an important role in the synthesis of catecholamines in the axon and presynaptic terminal. PMID:28630892
Aschrafi, Armaz; Gioio, Anthony E; Dong, Lijin; Kaplan, Barry B
2017-01-01
Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3'untranslated region (3'UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal. Toward this end, a targeted deletion of the axonal transport sequence element was developed, using the lentiviral delivery of the CRISPR/Cas9 system, and two guide RNA (gRNA) sequences flanking the 50-bp cis- acting regulatory element in rat superior cervical ganglion (SCG) neurons. Deletion of the axonal transport element reduced TH mRNA levels in the distal axons and reduced the axonal protein levels of TH and TH activity as measured by phosphorylation of SER40 in SCG neurons. Moreover, deletion of the zip-code diminished the axonal levels of dopamine (DA) and norepinephrine (NE). Conversely, the local translation of exogenous TH mRNA in the distal axon enhanced TH levels and activity, and elevated axonal NE levels. Taken together, these results provide direct evidence to support the hypothesis that TH mRNA trafficking and local synthesis of TH play an important role in the synthesis of catecholamines in the axon and presynaptic terminal.
Seismic Anisotropy And Upper Mantle Structure In Se Brazil
NASA Astrophysics Data System (ADS)
Heintz, M.; Vauchez, A.; Assumpcao, M.; Egydio-Silva, M.
We present preliminary shear wave splitting measurements performed in south-east Brazil in a quite complex region, from a geological point of view. Seismic anisotropy is the result of a preferred orientation of anisotropic minerals (olivine) in the upper mantle, due to deformation. Splitting parameters Ø (direction of the fastest S wave) are compared to large-scale tectonic structures of the area, in order to infer to which extent the deformations in the upper mantle and in the crust are mechanically coupled. The field of study is a region of 1000 by 1000 km, along the Atlantic coast from São Paulo to 500 km north of Rio de Janeiro. This region is made up of large scale geological units as the southern termination of the São Francisco craton, from archean age, surrounded by two neoproterozoic belts (the Ribeira belt to the east and the Brasilia belt to the west), and the Parana basin, which is a vast flood basalt region. Teleseisms used were acquired by 39 seismological stations well distributed in the region of interest. The results highlight the fact that the orientations of the polarization plane of the fast split shear wave vary a lot in this region, and measurements could be splitted into 5 groups : directions are parallel to the NE-SW trending of the Ribeira belt, some are parallel to the NW-SE trending of the Brasilia belt, in the NE-SW direction of the Transbrasiliano lineament, parallel to the absolute plate maotion (APM) that is EW in this region, or turning around a cylindrical low velocity anomaly imaged in the Parana basin and supposed to be the fossil plume head conduit of the Tristan da Cunha plume head.
Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523.
Tottori, K; Miwa, T; Uwahodo, Y; Yamada, S; Nakai, M; Oshiro, Y; Kikuchi, T; Altar, C A
2001-12-01
The antidepressant-like activity of a novel compound, OPC-14523, was investigated in comparison with the conventional antidepressants, fluoxetine and imipramine. OPC-14523 bound with nanomolar affinities to sigma receptors (IC(50)=47-56 nM), the 5-HT(1A) receptor (IC(50)=2.3 nM), and the 5-HT transporter (IC(50)=80 nM). OPC-14523 inhibited the in vitro reuptake of 3H-5-HT (IC(50)=27 nM), but it showed very weak inhibitory activity on 3H-NE and 3H-DA reuptake. OPC-14523 did not inhibit MAO A or B activities or muscarinic receptors. A single oral administration of OPC-14523 produced a marked antidepressant-like effect in the forced swimming test (FST) with rats (ED(50)=27 mg/kg) and mice (ED(50)=20mg/kg) without affecting the general locomotor activity. In contrast, fluoxetine and imipramine each required at least four days of repeated dosing to show this activity. The acute activity of OPC-14523 was blocked by pretreatment with the sigma receptor antagonist NE-100 or the selective 5-HT(1A) receptor antagonist WAY-100635. The induction of flat body posture by OPC-14523 was blocked by the selective 5-HT(1A) receptor antagonist NAN-190, and forebrain 5-HT biosynthesis was attenuated by OPC-14523 at behaviorally effective doses. In contrast, OPC-14523, unlike fluoxetine, failed to inhibit 5-HT reuptake at oral doses below 100mg/kg. Thus, the acute antidepressant-like action of OPC-14523 is achieved by the combined stimulation of sigma and 5-HT(1A) receptors without inhibition of 5-HT reuptake in vivo.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Etingov, Pavel V.; Makarov, Yuri V.; Wu, Di
The document describes detailed uncertainty quantification (UQ) methodology developed by PNNL to estimate secure ranges of potential dynamic intra-hour interchange adjustments in the ISO-NE system and provides description of the dynamic interchange adjustment (DINA) tool developed under the same contract. The overall system ramping up and down capability, spinning reserve requirements, interchange schedules, load variations and uncertainties from various sources that are relevant to the ISO-NE system are incorporated into the methodology and the tool. The DINA tool has been tested by PNNL and ISO-NE staff engineers using ISO-NE data.
75 FR 29653 - Amendment of Class E Airspace; Beatrice, NE
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-27
... Beatrice, NE. Decommissioning of the Shaw non-directional beacon (NDB) at Beatrice Municipal Airport... airspace for the Beatrice, NE area. Decommissioning of the Shaw NDB and cancellation of the NDB approach at...
78 FR 55731 - Notice of Service Delivery Area Designation for the Wilton Rancheria
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-11
..., Pottawattomie, IA, Sarpy, NE, Stanton, NE, Wayne, NE, Woodbury, IA. Port Gamble Indian Community of the Kitsap, WA. Port Gamble Reservation, Washington. Prairie Band of Potawatomi Nation, Jackson, KS. Kansas...
Lapetina, Diego L; Ptak, Christopher; Roesner, Ulyss K; Wozniak, Richard W
2017-10-02
Interactions occurring at the nuclear envelope (NE)-chromatin interface influence both NE structure and chromatin organization. Insights into the functions of NE-chromatin interactions have come from the study of yeast subtelomeric chromatin and its association with the NE, including the identification of various proteins necessary for tethering subtelomeric chromatin to the NE and the silencing of resident genes. Here we show that four of these proteins-the silencing factor Sir4, NE-associated Esc1, the SUMO E3 ligase Siz2, and the nuclear pore complex (NPC) protein Nup170-physically and functionally interact with one another and a subset of NPC components (nucleoporins or Nups). Importantly, this group of Nups is largely restricted to members of the inner and outer NPC rings, but it lacks numerous others including cytoplasmically and nucleoplasmically positioned Nups. We propose that this Sir4-associated Nup complex is distinct from holo-NPCs and that it plays a role in subtelomeric chromatin organization and NE tethering. © 2017 Lapetina et al.
Web-based provision of information on infectious diseases: a systems study.
Roy, Anjana; Kostkova, Patty; Catchpole, Michael; Carson, Ewart
2006-12-01
The National electronic Library for Health (NeLH) is an Internet medical information resources portal, principally for healthcare professionals, within which the National electronic Library of Infection (NeLI) is one of NeLH Specialist Libraries providing evidence on infectious diseases. In this article, we describe a systems-based evaluation of NeLI based on a soft systems methodology. User feedback and other data for the analysis were obtained using online questionnaires. This evaluation, which is a pilot study aimed at demonstrating proof of concept, provided evidence for improving three systems that are crucial to effective NeLI provision. These are navigation of the site, quality and tagging of information provided by NeLI, and information regarding users and their usage of the system. On the basis of a soft systems analysis, an action plan was formulated identifying areas where improvement is needed. Actions for consideration included simplifying terminologies to improve the navigation, enhancing the provision of research assessments, quality tagging NeLI documents, provided by experts in the field, and attracting a broader cross-section of healthcare professional user.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, J.; Kucharek, H.; Möbius, E.
In this paper we report on a two-year study to estimate the Ne/O abundance ratio in the gas phase of the local interstellar cloud (LIC). Based on the first two years of observations with the Interstellar Boundary Explorer, we determined the fluxes of interstellar neutral (ISN) O and Ne atoms at the Earth's orbit in spring 2009 and 2010. A temporal variation of the Ne/O abundance ratio at the Earth's orbit could be expected due to solar cycle-related effects such as changes of ionization. However, this study shows that there is no significant change in the Ne/O ratio at themore » Earths orbit from 2009 to 2010. We used time-dependent survival probabilities of the ISNs to calculate the Ne/O abundance ratio at the termination shock. Then we estimated the Ne/O abundance ratio in the gas phase of the LIC with the use of filtration factors and the ionization fractions. From our analysis, the Ne/O abundance ratio in the LIC is 0.33 ± 0.07, which is in agreement with the abundance ratio inferred from pickup-ion measurements.« less
NASA Astrophysics Data System (ADS)
Margiotta, A.
2014-04-01
KM3NeT is a deep-sea research infrastructure being constructed in the Mediterranean Sea. It will be installed at three sites: KM3NeT-Fr, offshore Toulon, France, KM3NeT-It, offshore Portopalo di Capo Passero, Sicily (Italy) and KM3NeT-Gr, offshore Pylos, Peloponnese, Greece. It will host the next generation Cherenkov neutrino telescope and nodes for a deep sea multidisciplinary observatory, providing oceanographers, marine biologists, and geophysicists with real time measurements. The neutrino telescope will search for Galactic and extra-Galactic sources of neutrinos, complementing IceCube in its field of view. The detector will have a modular structure and consists of six building blocks, each including about one hundred Detection Units (DUs). Each DU will be equipped with 18 multi-PMT digital optical modules. The first phase of construction has started and shore and deep-sea infrastructures hosting the future KM3NeT detector are being prepared in France near Toulon and in Italy, near Capo Passero in Sicily. The technological solutions for KM3NeT and the expected performance of the detector are presented and discussed.
Sugimura, Niwako; Rudolph, Karen D.; Agoston, Anna M.
2015-01-01
The way in which children cope with peer aggression may determine their subsequent adjustment, but different forms of coping may be more or less effective for particular children. This research examined whether the contribution of children’s coping to subsequent depressive symptoms was contingent on children’s temperament (i.e., level of negative emotionality; NE) and gender. Children (N = 235, 102 boys, 133 girls, M = 7.94 years, SD = .33) reported on exposure to peer victimization. Parents rated children’s NE and depressive symptoms, and teachers rated children’s coping. For girls with high NE, problem solving protected against depressive symptoms whereas seeking retaliation heightened risk for depressive symptoms. Advice seeking protected children with low NE against depressive symptoms whereas ignoring protected children with high NE against depressive symptoms. Humor predicted fewer depressive symptoms in boys with high NE but more depressive symptoms in boys with low NE. This research helps to elucidate individual differences in the effects of coping on adjustment, and has implications for interventions aimed at reducing risk resulting from exposure to peer aggression. PMID:24043360
Lu, Lin; Zhang, Yalin
2018-01-10
The Afrotropical leafhopper genus Dwightla previously included five species: D. acutipennis (Linnavuori Al-Ne'amy), D. alecto (Linnavuori Al-Ne'amy), D. angolana (Linnavuori Al-Ne'amy), D. delongi Zahniser Dietrich and D. hercules (Linnavuori Al-Ne'amy). A new species, Dwightla medleri sp. nov. from Nigeria, is described and illustrated and a checklist and key to species of this genus are provided.
Measurements and analysis of alpha-induced reactions of importance for nuclear astrophysics
NASA Astrophysics Data System (ADS)
de Messieres, Genevieve Escande
2011-11-01
Reactions during stellar helium burning are of primary importance for understanding nucleosynthesis. A detailed understanding of the critical reaction chain 4He(2alpha, gamma)12C( alpha, gamma)16O(alpha, gamma) 20Ne is necessary both because it is the primary energy source and because it determines the ratio of 12C to 16O produced, which in turn significantly effects subsequent nucleosynthesis. Also during Helium burning, the reactions 22Ne(alpha, n)25Mg and 22Ne(alpha, gamma )26Mg are crucial in determining the amount of neutrons available for the astrophysical s-process. This thesis presents new experimental results concerning the 16O(alpha, gamma) 20Ne, 22Ne(alpha, n)25Mg, and 22Ne(alpha, gamma)26Mg reaction rates. These results are then applied to the calculation of the associated stellar reaction rates in order to achieve better accuracy.
NASA Astrophysics Data System (ADS)
John, Cédric Michaël
2003-08-01
This study investigated the slope carbonates of two Miocene carbonate systems: the Maltese Islands (in the Central Mediterranean) and the Marion Plateau (Northeastern Australia, drilled during ODP Leg 194). The aim of the study was to trace the impact of the Miocene cooling steps (events Mi1-Mi6) in these carbonate systems, especially the Mi3 event, which took place around 13.6 Ma and deeply impacted the marine oxygen isotope record. This event also profoundly impacted oceanographic and climatic patterns, eventually leading to the establishment of the modern ice-house world. In particular, East Antarctica became ice covered at that period. The rational behind the present study was to investigate the impact that this event had on shallow water systems in order to complement the deep-sea record and hence acquire a more global perspective on Miocene climate change. The Maltese Islands were investigated for trends in bulk-rock carbon and oxygen isotopes, as well as bulk-rock mineralogy, clay minerals analysis and organic geochemisty. Results showed that the mid Miocene cooling event deeply impacted sedimentation at that location by changing sedimentation from carbonate to clay-rich sediments. Moreover, it was discovered that each phase of Antarctic glaciation, not just the major mid Miocene event, resulted in higher terrigenous input on Malta. Mass accumulation rates revealed that this was linked to increased runoff during periods when Antarctica was glaciated, and thus that the carbonate sediments were “diluted” by clay-rich sediments. The model subsequently developed to explain this implies feedback from Antarctic glaciations creating cold, dense air masses that push the ITCZ Northward, thus increasing precipitation on the North African subcontinent. Increased precipitation (or stronger African monsoon) accelerated continental weathering and runoff, thus bringing more terrigenous sediment to the paleo-location of the slope sediments of Malta. Spectral analysis of carbonate content and organic matter geochemical analysis furthermore suggest that the clay-rich intervals are similar to sapropelic deposits. On the Marion Plateau, trends in oxygen and carbon isotopes were obtained by measuring Cibicidoides spp foraminifers. Moreover, carbonate content was reconstructed using a chemical method (coulometer). Results show that the mid Miocene cooling step profoundly affected this system: a major drop in accumulation rates of carbonates occurs precisely at 13.8 Ma, around the time of the East Antarctic ice sheet formation. Moreover, sedimentation changes occurred at that time, carbonate fragments coming from neritic environments becoming less abundant, planktonic foraminifer content increasing and quartz and reworked glauconite being deposited. Conversely, a surprising result is that the major N12-N14 sea-level fall occurring around 11.5 Ma did not impact the accumulation of carbonates on the slope. This was unexpected since carbonate platform are very sensitive to sea-level changes. The model developed to explain that mass accumulation rates of carbonates diminished around 13.6 Ma (Mi3 Event) instead of 11.5 Ma (N12-N14 event), suggests that oceanic currents were controlling slope carbonate deposition on the Marion Plateau prior to the mid-Miocene, and that the mid Miocene event considerably increase their strength, hence reducing the amount of carbonate being deposited on slope sites. Moreover, by combining results from deep-sea oxygen isotopes with sea-level estimates based on coastal onlaps made during Leg 194, we constrain the amplitude of the N12-N14 sea-level fall to 90 meters. When integrating isotopic results from this study, this amplitude is lowered to 70 meters. A general conclusion of this work is that the mid Miocene climatic shift did impact carbonate systems, at least at the two locations studied. However, the nature of this response was highly dependant on the regional settings, in particular the presence of land mass (Malta) and the absence of a barrier to shelter from the effects of open ocean (Marion Plateau). Im Rahmen dieser Doktorarbeit wurden die Hangkarbonate von zwei miozänen heterozoischen Karbonatsystemen näher untersucht: die Malta Inselgruppe (zentrales Mittelmeer) und das Marion Plateau (Nordost Australien, ODP Leg 194). Die Auswirkungen der mittelmiozänen Abkühlung (Mi3), die auf 13.6 Ma datiert wird und starken Einfluß auf die Sauerstoffisotopenkurve hatte, in den oben genannten Flachwassersystemen stellten das Ziel dieser Arbeit dar. Dieses Abkühlungsereignis beeinflußte außerdem sehr stark die ozeanographischen und klimatischen Muster, die im weiteren Verlauf zum modernen Eishausklima führten. So steht insbesondere die Vereisung von Ostantarktika mit diesem Ereignis in Verbindung. Diese Arbeit untersucht den Einfluß dieses Ereignisses auf Flachwassersysteme, um vorliegende Untersuchungen in Tiefwassersystemen zu ergänzen und so zum globalen Verständnis des miozänen Klimawechsels beizutragen. Die Profile auf der Maltainselgruppe wurden mit Hilfe von Kohlenstoff- und Sauerstoffisotopen Auswertungen im Gesamtgestein, Gesamtgesteinmineralogie, Tonmineralanalyse und organischer Geochemie untersucht. Durch einen Wechsel von karbonatischeren zu tonigeren Sedimenten beeinflußte das mittelmiozäne Abkühlungsereignis die Sedimentation in diesem Gebiet sehr stark. Weiterhin wurde beobachtet, daß jede Phase der antarktischen Vereisung, nicht nur das mittelmiozäne Hauptereignis, zu einem erhöhten terrigenen Eintrag in den Hangsedimenten der Maltainselgruppe führte. Akkumulationsraten zeigen, daß dieser erhöhte terrigene Eintrag den einzelnen Vereisungsperioden zusammenhängt und die karbonatischen Sedimente durch tonreiche Sedimente “verunreinigt” wurden. Das daraufhin entwickelte Modell erklärt diesen erhöhten terrigenen Eintrag mit einer nordwärtigen Verlagerung der innertropischen Konvergenzzone durch die Bildung von kalten, dichten Luftmassen, die zu verstärkten Niederschlägen in Nordafrika führten. Diese verstärkten Niederschläge (oder verstärkter afrikanischer Monsun) beeinflußten die kontinentale Verwitterung und den Eintrag, mit der Folge, daß verstärkt terrigene Sedimente im Bereich der Hangsedimente der Maltainselgruppe abgelagert wurden. Die tonreichen Intervalle weisen Ähnlichkeiten zu sapropelischen Ablagerungen auf, was mit Hilfe der Spektral analyse des Karbonatgehalts und der geochemischen Analyse des organischen Materials gezeigt wurde. Auf dem Marion Plateau wurden die Sauerstoff- und Kohlenstoffisotopenkurven anhand von Foraminiferen der Gattung Cibicidoides spp. rekonstruiert. Der Karbonatgehalt wurde mit Hilfe einer chemischen Methode (Coulometer) ermittelt. Genauso wie die Sedimente der Maltainselgruppe beeinflußte das mittelmiozäne Abkühlungsereignis (Mi3) auch die Sedimente auf dem Marion Plateau. So kam es bei 13,8 Ma, in etwa zur Zeit der Vereisung von Ostantarktika, zu einem Abfall der Karbonatakkumulationsraten. Weiterhin traten Änderungen in der Zusammensetzung der Sedimente auf, so nehmen neritische Karbonatfragmente ab, der planktische Foraminiferengehalt nimmt zu und es wurden verstärkt Quarz und Glaukonit abgelagert. Ein überraschendes Ergebnis ist die Tatsache, daß der große N12-N14 Meeresspiegelabfall um 11,5 Ma die Akkumulationsraten der Karbonate auf dem Hang nicht beeinflußte. Dieses Ergebnis ist umso erstaunlicher, da Karbonatplattformen normalerweise sehr sensitiv auf Meeresspiegeländerungen reagieren. Der Grund, warum sich die Karbonatakkumulationsraten schon um 13,6 Ma (Mi3) und nicht erst um 11,5 Ma (N12-N14) verringerten, liegt in der Tatsache, daß die ozeanischen Strömungen die Karbonatsedimentation auf dem Hang des Marion Plateau schon im Miozän kontrollierten. Das mittelmiozäne Ereignis (Mi3) erhöhte die Stärke diese Strömungen und als eine Ursache wurde die Karbonatakkumulation auf den Hängen reduziert. Die Amplitude des N12-N14 Meeresspiegelabfalls liegt bei 90 m unter der Berücksichtigung der Sauerstoffisotopendaten aus der Tiefsee und Berechnungen des Meeresspiegels anhand des “coastal onlaps”, die während Leg 194 gemacht wurden. Die Isotopendaten dieser Arbeit weisen hingegen auf einen verringerten Meeresspiegelabfall von 70 m hin. Als allgemeine Schlußfolgerung kann gesagt werden, daß der mittelmiozäne Klimaumschwung die Karbonatsysteme zumindest an den beiden untersuchten Lokalitäten beeinflußt hat. Allerdings waren die Auswirkungen sehr von den unterschiedlichen lokalen Gegebenheiten abhängig. Insbesondere wirkten sich die Anwesenheit einer Landmasse (Malta) und die Abwesenheit einer Barriere vor den Einflüssen des offenen Ozeans (Marion Plateau) stark auf die Ablagerung der Karbonate aus.
Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W.
2018-01-01
Long Abstract Existing brain-based emotion-cognition theories fail to explain arousal’s ability to both enhance and impair cognitive processing. In the Glutamate Amplifies Noradrenergic Effects (GANE) model outlined in this paper, we propose that arousal-induced norepinephrine (NE) released from the locus coeruleus (LC) biases perception and memory in favor of salient, high priority representations at the expense of lower priority representations. This increase in gain under phasic arousal occurs via synaptic self-regulation of NE based on glutamate levels. When the LC is phasically active, elevated levels of glutamate at the site of prioritized representations increase local NE release, creating “NE hot spots.” At these local hot spots, glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. This excitatory effect contrasts with widespread NE suppression of weaker representations via lateral and auto-inhibitory processes. On a broader scale, hot spots increase oscillatory synchronization across neural ensembles transmitting high priority information. Furthermore, key brain structures that detect or pre-determine stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during or after encoding enhances synaptic plasticity at sites of high glutamate activity, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms increase perceptual and memory selectivity under arousal. Beyond explaining discrepancies in the emotion-cognition literature, GANE reconciles and extends previous influential theories of LC neuromodulation by highlighting how NE can produce such different outcomes in processing based on priority. PMID:26126507
Cryan, John F.; O'Leary, Olivia F.; Jin, Sung-Ha; Friedland, Julie C.; Ouyang, Ming; Hirsch, Bradford R.; Page, Michelle E.; Dalvi, Ashutosh; Thomas, Steven A.; Lucki, Irwin
2004-01-01
Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine β-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh–/– mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh+/– mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh–/– mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using l-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh–/– mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh–/– mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs. PMID:15148402
NASA Astrophysics Data System (ADS)
Themens, David R.; Jayachandran, P. T.; Bilitza, Dieter; Erickson, Philip J.; Häggström, Ingemar; Lyashenko, Mykhaylo V.; Reid, Benjamin; Varney, Roger H.; Pustovalova, Ljubov
2018-02-01
In this study, we present a topside model representation to be used by the Empirical Canadian High Arctic Ionospheric Model (E-CHAIM). In the process of this, we also present a comprehensive evaluation of the NeQuick's, and by extension the International Reference Ionosphere's, topside electron density model for middle and high latitudes in the Northern Hemisphere. Using data gathered from all available incoherent scatter radars, topside sounders, and Global Navigation Satellite System Radio Occultation satellites, we show that the current NeQuick parameterization suboptimally represents the shape of the topside electron density profile at these latitudes and performs poorly in the representation of seasonal and solar cycle variations of the topside scale thickness. Despite this, the simple, one variable, NeQuick model is a powerful tool for modeling the topside ionosphere. By refitting the parameters that define the maximum topside scale thickness and the rate of increase of the scale height within the NeQuick topside model function, r and g, respectively, and refitting the model's parameterization of the scale height at the F region peak, H0, we find considerable improvement in the NeQuick's ability to represent the topside shape and behavior. Building on these results, we present a new topside model extension of the E-CHAIM based on the revised NeQuick function. Overall, root-mean-square errors in topside electron density are improved over the traditional International Reference Ionosphere/NeQuick topside by 31% for a new NeQuick parameterization and by 36% for a newly proposed topside for E-CHAIM.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Somogyi, G.T.; de Groat, W.C.
Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activationmore » of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.« less
Semple, Bridgette D; Trivedi, Alpa; Gimlin, Kayleen; Noble-Haeusslein, Linda J
2015-02-01
While neutrophil elastase (NE), released by activated neutrophils, is a key mediator of secondary pathogenesis in adult models of brain ischemia and spinal cord injury, no studies to date have examined this protease in the context of the injured immature brain, where there is notable vulnerability resulting from inadequate antioxidant reserves and prolonged exposure to infiltrating neutrophils. We thus reasoned that NE may be a key determinant of secondary pathogenesis, and as such, adversely influence long-term neurological recovery. To address this hypothesis, wild-type (WT) and NE knockout (KO) mice were subjected to a controlled cortical impact at post-natal day 21, approximating a toddler-aged child. To determine if NE is required for neutrophil infiltration into the injured brain, and whether this protease contributes to vasogenic edema, we quantified neutrophil numbers and measured water content in the brains of each of these genotypes. While leukocyte trafficking was indistinguishable between genotypes, vasogenic edema was markedly attenuated in the NE KO. To determine if early pathogenesis is dependent on NE, indices of cell death (TUNEL and activated caspase-3) were quantified across genotypes. NE KO mice showed a reduction in these markers of cell death in the injured hippocampus, which corresponded to greater preservation of neuronal integrity as well as reduced expression of heme oxygenase-1, a marker of oxidative stress. WT mice, treated with a competitive inhibitor of NE at 2, 6 and 12h post-injury, likewise showed a reduction in cell death and oxidative stress compared to vehicle-treated controls. We next examined the long-term behavioral and structural consequences of NE deficiency. NE KO mice showed an improvement in long-term spatial memory retention and amelioration of injury-induced hyperactivity. However, volumetric and stereological analyses found comparable tissue loss in the injured cortex and hippocampus independent of genotype. Further, WT mice treated acutely with the NE inhibitor showed no long-term behavioral or structural improvements. Together, these findings validate the central role of NE in both acute pathogenesis and chronic functional recovery, and support future exploration of the therapeutic window, taking into account the prolonged period of neutrophil trafficking into the injured immature brain. Copyright © 2014 Elsevier Inc. All rights reserved.
Semple, Bridgette D; Trivedi, Alpa; Gimlin, Kayleen; Noble-Haeusslein, Linda J
2014-01-01
While neutrophil elastase (NE), released by activated neutrophils, is a key mediator of secondary pathogenesis in adult models of brain ischemia and spinal cord injury, no studies to date have examined this protease in the context of the injured immature brain, where there is notable vulnerability resulting from inadequate antioxidant reserves and prolonged exposure to infiltrating neutrophils. We thus reasoned that NE may be a key determinant of secondary pathogenesis, and as such, adversely influence long-term neurological recovery. To address this hypothesis, wild-type (WT) and NE knockout (KO) mice were subjected to a controlled cortical impact at post-natal day 21, approximating a toddler-aged child. To determine if NE is required for neutrophil infiltration into the injured brain, and whether this protease contributes to vasogenic edema, we quantified neutrophil numbers and measured water content in the brains of each of these genotypes. While leukocyte trafficking was indistinguishable between genotypes, vasogenic edema was markedly attenuated in the NE KO. To determine if early pathogenesis is dependent on NE, indices of cell death (TUNEL and activated caspase-3) were quantified across genotypes. NE KO mice showed a reduction in these markers of cell death in the injured hippocampus, which corresponded to greater preservation of neuronal integrity as well as reduced expression of heme oxygenase-1, a marker of oxidative stress. WT mice, treated with a competitive inhibitor of NE at 2, 6 and 12 h post-injury, likewise showed a reduction in cell death and oxidative stress compared to vehicle-treated controls. We next examined the long-term behavioral and structural consequences of NE deficiency. NE KO mice showed an improvement in long-term spatial memory retention and amelioration of injury-induced hyperactivity. However, volumetric and stereological analyses found comparable tissue loss in the injured cortex and hippocampus independent of genotype. Further, WT mice treated acutely with the NE inhibitor showed no long-term behavioral or structural improvements. Together, these findings validate the central role of NE in both acute pathogenesis and chronic functional recovery, and support future exploration of the therapeutic window, taking into account the prolonged period of neutrophil trafficking into the injured immature brain. PMID:25497734
Milligan, James; Lee, Joseph; McMillan, Colleen; Klassen, Hilary
2012-01-01
Résumé Objectif Sensibiliser davantage les médecins de famille à la dysréflexie autonome (DA) chez les patients victimes d’une lésion médullaire (LM) et proposer certaines interventions. Sources de l’information On a fait une recension dans MEDLINE de 1970 à juillet 2011 à l’aide des expressions en anglais autonomic dysreflexia et spinal cord injury, ainsi que family medicine ou primary care. On a aussi passé en revue et utilisé d’autres ressources et guides de pratique pertinents. Message principal Il arrive souvent que les médecins de famille ne se sentent pas confiants de traiter des patients ayant une LM dont les problèmes sont complexes et exigent beaucoup de temps. Les médecins de famille ont l’impression de n’avoir pas la formation nécessaire pour répondre à leurs besoins. Pourtant, ils offrent une composante essentielle des soins à de tels patients et il est important qu’ils comprennent les problèmes médicaux particuliers aux LM. La dysréflexie autonome est un important et fréquent problème potentiellement sérieux que connaissent mal de nombreux médecins de famille. Cet article passe en revue les signes et les symptômes de la DA et présente certaines options de prise en charge aiguë, ainsi que des stratégies de prévention à l’intention des médecins de famille. Conclusion Les médecins de famille devraient savoir quels patients traumatisés médullaires sont susceptibles d’avoir une DA et surveiller ceux qui sont touchés par ce problème. Une explication est donnée dans cet article quant à l’approche à suivre pour la prise en charge aiguë. Les médecins de famille jouent un rôle essentiel dans la prévention de la DA, notamment par l’éducation (du patient et des autres professionnels de la santé) et la consignation dans le dossier médical de stratégies comme les soins appropriés de la vessie, de l’intestin et de la peau, d’avertissements et de plans de prise en charge.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hayes, E.F.; Siu, A.K.Q.; Chapman, F.M. Jr.
1976-09-01
A potential energy surface for the Ne--H/sub 2//sup +/ reaction has been obtained in the LCAO--MO--SCF approximation. Analysis of the surface indicates that the reaction Ne+H/sub 2//sup +/..-->..NeH/sup +/+H should proceed with an endoergicity of 12 kcal/mole, in agreement with the experimental results of Chupka and Russell. Several procedures for parameterizing a diatomics-in-molecules (DIM) representation of the NeH/sub 2//sup +/ surface are considered. The results show that an accurate representation of the SCF surface can be obtained from the DIM model using a minimum of diatomic and triatomic data. (AIP)
Interaction of excited He and Ne rare gas metastable atoms with the CHF2Cl molecule
NASA Astrophysics Data System (ADS)
Chérid, M.; Ben Arfa, M.; Driss Khodja, M.
2005-06-01
We studied the Penning ionization of the CHF2Cl molecule with He and Ne metastable atoms (He* and Ne*). We measured the electron kinetic energy and the time-of-flight mass spectra; we also determined the branching ratio for the parent ion and charged CHF+2, CHFCl+, HCF+/CF+ and Cl+ fragments. These data led us to discuss the dissociation channels for all the energetically-accessible electronic states of the ionized molecule. We evidenced a marked contrast in the fragment ion proportions for Ne*-CHF2Cl and He*-CHF2Cl systems, and related it to the difference in polarizability and internal energy of the He* and Ne* atoms.
15O(alpha,gamma)19Ne breakout reaction and impact on X-ray bursts.
Tan, W P; Fisker, J L; Görres, J; Couder, M; Wiescher, M
2007-06-15
The breakout reaction 15O(alpha,gamma)19Ne, which regulates the flow between the hot CNO cycle and the rp process, is critical for the explanation of the burst amplitude and periodicity of x-ray bursters. We report on the first successful measurement of the critical alpha-decay branching ratios of relevant states in 19Ne populated via 19F(3He,t)19Ne. Based on the experimental results and our previous lifetime measurements of these states, we derive the first experimental rate of 15O(alpha,gamma)19Ne. The impact of our experimental results on the burst pattern and periodicity for a range of accretion rates is analyzed.
18Ne Excited States Two-Proton Decay
NASA Astrophysics Data System (ADS)
de Napoli, M.; Rapisarda, E.; Raciti, G.; Cardella, G.; Amorini, F.; Giacoppo, F.; Sfienti, C.
2008-04-01
Two-proton radioactivity studies have been performed on excited states of 18Ne produced by 20Ne fragmentation at the FRS of the Laboratori Nazionali del Sud and excited via Coulomb excitation on a 209Pb target. The 18Ne levels decay has been studied by complete kinematical reconstruction. In spite of the low statistic, the energy and angular correlations of the emitted proton pairs indicate the presence of 2He emission toghether with the democratic decay.
NASA Technical Reports Server (NTRS)
Ducas, T. W.; Feld, M. S.; Ryan, L. W., Jr.; Skribanowitz, N.; Javan, A.
1972-01-01
Observation results are presented on the optical hyperfine structure in Ne-21 obtained with the aid of laser-induced line-narrowing techniques. The output from a long stabilized single-mode 1.15-micron He-Ne laser focused into an external sample cell containing Ne-21 was used in implementing these techniques. Their applicability is demonstrated for optical hyperfine structure observation in systems whose features are ordinarily masked by Doppler broadening.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Szulagyi, Judit; Pascucci, Ilaria; Abraham, Peter
Mid-infrared atomic and ionic line ratios measured in spectra of pre-main-sequence stars are sensitive indicators of the hardness of the radiation field impinging on the disk surface. We present a low-resolution Spitzer IRS search for [Ar II] at 6.98 {mu}m, [Ne II] at 12.81 {mu}m, and [Ne III] 15.55 {mu}m lines in 56 transitional disks. These objects, characterized by reduced near-infrared but strong far-infrared excess emission, are ideal targets to set constraints on the stellar radiation field onto the disk, because their spectra are not contaminated by shock emission from jets/outflows or by molecular emission lines. After demonstrating that wemore » can detect [Ne II] lines and recover their fluxes from the low-resolution spectra, here we report the first detections of [Ar II] lines toward protoplanetary disks. We did not detect [Ne III] emission in any of our sources. Our [Ne II]/[Ne III] line flux ratios combined with literature data suggest that a soft-EUV or X-ray spectrum produces these gas lines. Furthermore, the [Ar II]/[Ne II] line flux ratios point to a soft X-ray and/or soft-EUV stellar spectrum as the ionization source of the [Ar II] and [Ne II] emitting layer of the disk. If the soft X-ray component dominates over the EUV, then we would expect larger photoevaporation rates and, hence, a reduction of the time available to form planets.« less
Stress hormonal changes in the brain and plasma after acute noise exposure in mice.
Jin, Sang Gyun; Kim, Min Jung; Park, So Young; Park, Shi Nae
2017-06-01
To investigate the effects of acute noise stress on two amine stress hormones, norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain and plasma of mice after noise exposure. Mice were grouped into the control and noise groups. Mice in the noise group were exposed to white noise of 110dB sound pressure level for 60min. Auditory brainstem response thresholds, distortion product otoacoustic emissions, the organ of Corti grading scores, western blots of NE/5-HIAA in the whole brain and hippocampus, and the plasma levels of NE/5-HIAA were compared between the two groups. Significant hearing loss and cochlear damage were demonstrated in the noise group. NE and 5-HIAA in the hippocampus were elevated in the noise group (p=0.019/0.022 for NE/5-HIAA vs. the control). Plasma levels of NE and 5-HIAA were not statistically different between the groups (p=0.052/0.671 for NE/5-HIAA). Hearing loss with outer hair cell dysfunction and morphological changes of the organ of Corti after noise exposure in C57BL/6 mice proved the reliability of our animal model as an acute noise stress model. NE and 5-HIAA are suggested to be the potential biomarkers for acute noise stress in the hippocampus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Detection of Ne VIII in an Intervening Multiphase Absorption System Toward 3C 263
NASA Astrophysics Data System (ADS)
Narayanan, Anand; Wakker, Bart P.; Savage, Blair D.
2009-09-01
We report the detection of Ne VIII in an intervening multiphase absorption line system at z = 0.32566 in the Far Ultraviolet Spectroscopic Explorer spectrum of the quasar 3C 263 (zem = 0.646). The Ne VIII λ770 Å detection has a 3.9σ significance. At the same velocity, we also find absorption lines from C IV, O III, O IV, and N IV. The line parameter measurements yield log [N(Ne VIII) cm-2] = 13.98+0.10 -0.13 and b = 49.8 ± 5.5 km s-1. We find that the ionization mechanism in the gas phase giving rise to the Ne VIII absorption is inconsistent with photoionization. The absorber has a multiphase structure, with the intermediate ions produced in cool photoionized gas and the Ne VIII most likely in a warm collisionally ionized medium in the temperature range (0.5-1.0) × 106 K. This is the second ever detection of an intervening Ne VIII absorption system. Its properties resemble the previous Ne VIII absorber reported by Savage and colleagues. Direct observations of H I and O VI are needed to better constrain the physical conditions in the collisionally ionized gas phase of this absorber. Based on observations with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer operated by Johns Hopkins University, supported by NASA contract NAS5-32985.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Browning, R.A.; Rigler-Daugherty, S.K.; Long, G.
1986-03-01
GEP rats are characterized by an enhanced susceptibility to seizures caused by a variety of stimuli, most notably sound. Pharmacological treatments that reduce the synaptic concentration of NE increase seizure severity in GEP rats while elevations in NE have the opposite effect. GEP rats also display a widespread deficit in brain NE concentration suggesting that their increased seizure susceptibility is related to a deficit in noradrenergic transmission. The authors have compared the kinetics of /sup 3/H-NE uptake in the P/sub 2/ synaptosomal fraction isolated from the cerebral cortex of normal and GEP-rats. Although the apparent Kms were not significantly differentmore » (Normal +/- SEM:0.37 +/- 0.13..mu..M; GEP +/- SEM: 0.29 +/- 0.07..mu..M), the Vmax for GEP rats was 48% lower than that of normal rats (Normal +/- SEM: 474 +/- 45 fmole/mg/4min; GEP +/- SEM: 248 +/- 16 fmole/mg/4min). Because of the possible role of the inferior colliculus (IC) in the initiation of sound-induced seizures in GEP rats, the authors measured synaptosomal NE uptake in the IC using a NE concentration of 50 nM. The IC synaptosomal NE uptake was found to be 35% lower in GEP than in normal rats. These findings are consistent with the hypothesis that a deficit in noradrenergic transmission is related to the increased seizure susceptibility of GEP rats.« less
Co-sleeping and childhood enuresis in China.
Ma, Jun; Li, Shenghui; Jiang, Fan; Jin, Xingming; Shen, Xiaoming; Li, Fei
2014-01-01
Co-sleeping is associated with disturbance of the natural sleep pattern, including sleep fragmentation and daytime sleepiness. Nocturnal enuresis (NE) or bed-wetting, although benign, is a significant cause of distress to affected children and their caregiver(s). This study investigated the relationship between co-sleeping and NE in primary school children from China. Data from a previous sleep study of primary school children from 8 cities across China were analyzed. Multivariable regression analysis was performed to assess the relationship between co-sleeping and NE while controlling for a number of confounding factors. The prevalence of NE in co-sleeping and non-co-sleeping children in different age groups was evaluated. The prevalence of co-sleeping and NE in children aged 5 to 12 years was 22.8% and 4.6%, respectively. Co-sleeping was associated with a higher prevalence of NE in primary school age children (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.27-1.77; p < .001) after adjusting for confounding factors. The differences in the prevalence of NE between co-sleepers and non-co-sleepers were significant in the 9-year age group (OR, 1.49; 95% CI, 1.06-2.11; p = .025) and 11- to 12-year age group (OR, 3.16; 95% CI, 2.19-4.57; p < .001). Co-sleeping may increase the risk of NE in primary school children, particularly in those aged 11 to 12 years.
Measurement of 17F(d ,n )18Ne and the impact on the 17F(p ,γ )18Ne reaction rate for astrophysics
NASA Astrophysics Data System (ADS)
Kuvin, S. A.; Belarge, J.; Baby, L. T.; Baker, J.; Wiedenhöver, I.; Höflich, P.; Volya, A.; Blackmon, J. C.; Deibel, C. M.; Gardiner, H. E.; Lai, J.; Linhardt, L. E.; Macon, K. T.; Rasco, B. C.; Quails, N.; Colbert, K.; Gay, D. L.; Keeley, N.
2017-10-01
Background: The 17F(p ,γ )18Ne reaction is part of the astrophysical "hot CNO" cycles that are important in astrophysical environments like novas. Its thermal reaction rate is low owing to the relatively high energy of the resonances and therefore is dominated by direct, nonresonant capture in stellar environments at temperatures below 0.4 GK. Purpose: An experimental method is established to extract the proton strength to bound and unbound states in experiments with radioactive ion beams and to determine the parameters of direct and resonant capture in the 17F(p ,γ )18Ne reaction. Method: The 17F(d ,n )18Ne reaction is measured in inverse kinematics using a beam of the short-lived isotope 17F and a compact setup of neutron, proton, γ -ray, and heavy-ion detectors called resoneut. Results: The spectroscopic factors for the lowest l =0 proton resonances at Ec .m .=0.60 and 1.17 MeV are determined, yielding results consistent within 1.4 σ of previous proton elastic-scattering measurements. The asymptotic normalization coefficients of the bound 21+ and 22+ states in 18Ne are determined and the resulting direct-capture reaction rates are extracted. Conclusions: The direct-capture component of the 17F(p ,γ )18Ne reaction is determined for the first time from experimental data on 18Ne.
2014-01-01
Background Healthy university students have been shown to use psychoactive substances, expecting them to be functional means for enhancing their cognitive capacity, sometimes over and above an essentially proficient level. This behavior called Neuroenhancement (NE) has not yet been integrated into a behavioral theory that is able to predict performance. Job Demands Resources (JD-R) Theory for example assumes that strain (e.g. burnout) will occur and influence performance when job demands are high and job resources are limited at the same time. The aim of this study is to investigate whether or not university students’ self-reported NE can be integrated into JD-R Theory’s comprehensive approach to psychological health and performance. Methods 1,007 students (23.56 ± 3.83 years old, 637 female) participated in an online survey. Lifestyle drug, prescription drug, and illicit substance NE together with the complete set of JD-R variables (demands, burnout, resources, motivation, and performance) were measured. Path models were used in order to test our data’s fit to hypothesized main effects and interactions. Results JD-R Theory could successfully be applied to describe the situation of university students. NE was mainly associated with the JD-R Theory’s health impairment process: Lifestyle drug NE (p < .05) as well as prescription drug NE (p < .001) is associated with higher burnout scores, and lifestyle drug NE aggravates the study demands-burnout interaction. In addition, prescription drug NE mitigates the protective influence of resources on burnout and on motivation. Conclusion According to our results, the uninformed trying of NE (i.e., without medical supervision) might result in strain. Increased strain is related to decreased performance. From a public health perspective, intervention strategies should address these costs of non-supervised NE. With regard to future research we propose to model NE as a means to reach an end (i.e. performance enhancement) rather than a target behavior itself. This is necessary to provide a deeper understanding of the behavioral roots and consequences of the phenomenon. PMID:24904687
Wolff, Wanja; Brand, Ralf; Baumgarten, Franz; Lösel, Johanna; Ziegler, Matthias
2014-01-01
Healthy university students have been shown to use psychoactive substances, expecting them to be functional means for enhancing their cognitive capacity, sometimes over and above an essentially proficient level. This behavior called Neuroenhancement (NE) has not yet been integrated into a behavioral theory that is able to predict performance. Job Demands Resources (JD-R) Theory for example assumes that strain (e.g. burnout) will occur and influence performance when job demands are high and job resources are limited at the same time. The aim of this study is to investigate whether or not university students' self-reported NE can be integrated into JD-R Theory's comprehensive approach to psychological health and performance. 1,007 students (23.56 ± 3.83 years old, 637 female) participated in an online survey. Lifestyle drug, prescription drug, and illicit substance NE together with the complete set of JD-R variables (demands, burnout, resources, motivation, and performance) were measured. Path models were used in order to test our data's fit to hypothesized main effects and interactions. JD-R Theory could successfully be applied to describe the situation of university students. NE was mainly associated with the JD-R Theory's health impairment process: Lifestyle drug NE (p < .05) as well as prescription drug NE (p < .001) is associated with higher burnout scores, and lifestyle drug NE aggravates the study demands-burnout interaction. In addition, prescription drug NE mitigates the protective influence of resources on burnout and on motivation. According to our results, the uninformed trying of NE (i.e., without medical supervision) might result in strain. Increased strain is related to decreased performance. From a public health perspective, intervention strategies should address these costs of non-supervised NE. With regard to future research we propose to model NE as a means to reach an end (i.e. performance enhancement) rather than a target behavior itself. This is necessary to provide a deeper understanding of the behavioral roots and consequences of the phenomenon.
Tripathi, Chandra Bhushan; Parashar, Poonam; Arya, Malti; Singh, Mahendra; Kanoujia, Jovita; Kaithwas, Gaurav; Saraf, Shubhini A
2018-05-10
Breast cancer is the most common cancer of occurrence in women and has the highest mortality incidence rate therein. The present study envisaged to develop doxorubicin (Dox) loaded folate functionalized nanoemulsion (NE) for profound therapeutic activity against mammary gland cancer. NE was prepared using pseudo-ternary phase diagrams utilizing α-linolenic acid (ALA) as lipid phase, to further enhance the anticancer potential of Dox. Box-Behnken design was employed to systematically develop the NE. Optimized NE (f-Dox-NE) was evaluated for in vitro and in vivo performance. f-Dox-NE, with globule size 55.2 ± 3.3 nm, zeta potential - 31 ± 2 mV, entrapment 92.51 ± 3.62%, drug loading 0.42 ± 0.08% and percent drug release 94.86 ± 1.87% in 72 h, was capable of reducing cell viability in MCF-7 cell lines vis-à-vis pure and marketed drug. Further, mechanistic studies in MCF-7 cell lines demonstrated that f-Dox-NE induces cellular apoptosis by reactive oxygen species generated and mitochondrial membrane mediated apoptosis. The antitumor effect was evaluated in 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland tumor in female Albino Wistar rats. f-Dox-NE exhibited enhanced antitumor targeting potential, therapeutic safety and efficacy vis-à-vis pure and marketed drug, as revealed by tumor volume, animal survival, weight variation, cardiotoxicity and biodistribution studies. f-Dox-NE restored the biochemical parameters viz., SOD, catalase, TBARS and protein carbonyl, towards normal levels in comparison to DMBA induced animal group. f-Dox-NE displayed downregulation of anti-apoptotic (Bcl-2 and MMP-9) proteins and upregulation of pro-apoptotic proteins (caspase-9 and BAX). The experimental results suggest that ALA augmented folate functionalized NE are able to overcome the challenges of developing safe and effective delivery system with enhanced potential for mammary gland carcinoma therapy.
Jongsma, Johan; Oomen, Monique H; Noordzij, Marinus A; Van Weerden, Wytske M; Martens, Gerard J M; van der Kwast, Theodorus H; Schröder, Fritz H; van Steenbrugge, Gert J
2002-03-01
Neuroendocrine (NE) cells are androgen-independent cells and secrete growth-modulating peptide hormones via a regulated secretory pathway (RSP). We studied NE differentiation after long-term androgen withdrawal in the androgen-dependent human prostate cancer xenograft PC-310. Tumor-bearing nude mice were killed at 0, 2, 5, 7, 14, 21, 47, 84, and 154 days after castration. The half-life of the PC-310 tumor was 10 days, with a stable residual tumor volume of 30--40% after 21 days and longer periods of androgen deprivation. Proliferative activity and prostate-specific antigen serum levels decreased to zero after castration, whereas cell-cycle arrest was manifested by increased p27(kip1) expression. A temporary downregulation of androgen receptor (AR) expression was noted after androgen deprivation. The expression of chromogranin A, secretogranin III, and secretogranin V (7B2) increased 5 days after castration and later. Subsequently, pro-hormone convertase 1 and peptidyl alpha--amidating monooxygenase as well as vascular endothelial growth factor were expressed from 7 days after castration on. Finally, such growth factors as gastrin-releasing peptide and serotonin were expressed in a small part of the NE cells 21 days after castration, but strong expression was induced late during androgen deprivation, that is, 84 and 154 days after castration, respectively. Androgen deprivation of the NE-differentiated PC-310 model induced the formation of NE-differentiated AR(minus sign) and non-NE AR(+) tumor residues. The NE-differentiated cells actively produced growth factors via an RSP that may lead to hormone-refractory disease. The dormant non-NE AR(+) tumor cells were shown to remain androgen sensitive even after long-term androgen deprivation. In the PC-310 xenograft, time-dependent NE differentiation and subsequent maturation were induced after androgen depletion. The androgen-dependent PC-310 xenograft model constitutes an excellent model for studying the role of NE cells in the progression of clinical prostate cancer. Copyright 2002 Wiley-Liss, Inc.
Joch, Michael; Hegele, Mathias; Maurer, Heiko; Müller, Hermann; Maurer, Lisa Katharina
2017-07-01
The error (related) negativity (Ne/ERN) is an event-related potential in the electroencephalogram (EEG) correlating with error processing. Its conditions of appearance before terminal external error information suggest that the Ne/ERN is indicative of predictive processes in the evaluation of errors. The aim of the present study was to specifically examine the Ne/ERN in a complex motor task and to particularly rule out other explaining sources of the Ne/ERN aside from error prediction processes. To this end, we focused on the dependency of the Ne/ERN on visual monitoring about the action outcome after movement termination but before result feedback (action effect monitoring). Participants performed a semi-virtual throwing task by using a manipulandum to throw a virtual ball displayed on a computer screen to hit a target object. Visual feedback about the ball flying to the target was masked to prevent action effect monitoring. Participants received a static feedback about the action outcome (850 ms) after each trial. We found a significant negative deflection in the average EEG curves of the error trials peaking at ~250 ms after ball release, i.e., before error feedback. Furthermore, this Ne/ERN signal did not depend on visual ball-flight monitoring after release. We conclude that the Ne/ERN has the potential to indicate error prediction in motor tasks and that it exists even in the absence of action effect monitoring. NEW & NOTEWORTHY In this study, we are separating different kinds of possible contributors to an electroencephalogram (EEG) error correlate (Ne/ERN) in a throwing task. We tested the influence of action effect monitoring on the Ne/ERN amplitude in the EEG. We used a task that allows us to restrict movement correction and action effect monitoring and to control the onset of result feedback. We ascribe the Ne/ERN to predictive error processing where a conscious feeling of failure is not a prerequisite. Copyright © 2017 the American Physiological Society.
Comparison of electromagnetic and nuclear dissociation of 17Ne
NASA Astrophysics Data System (ADS)
Wamers, F.; Marganiec, J.; Aksouh, F.; Aksyutina, Yu.; Alvarez-Pol, H.; Aumann, T.; Beceiro-Novo, S.; Bertulani, C. A.; Boretzky, K.; Borge, M. J. G.; Chartier, M.; Chatillon, A.; Chulkov, L. V.; Cortina-Gil, D.; Emling, H.; Ershova, O.; Fraile, L. M.; Fynbo, H. O. U.; Galaviz, D.; Geissel, H.; Heil, M.; Hoffmann, D. H. H.; Hoffman, J.; Johansson, H. T.; Jonson, B.; Karagiannis, C.; Kiselev, O. A.; Kratz, J. V.; Kulessa, R.; Kurz, N.; Langer, C.; Lantz, M.; Le Bleis, T.; Lehr, C.; Lemmon, R.; Litvinov, Yu. A.; Mahata, K.; Müntz, C.; Nilsson, T.; Nociforo, C.; Ott, W.; Panin, V.; Paschalis, S.; Perea, A.; Plag, R.; Reifarth, R.; Richter, A.; Riisager, K.; Rodriguez-Tajes, C.; Rossi, D.; Savran, D.; Schrieder, G.; Simon, H.; Stroth, J.; Sümmerer, K.; Tengblad, O.; Typel, S.; Weick, H.; Wiescher, M.; Wimmer, C.
2018-03-01
The Borromean drip-line nucleus 17Ne has been suggested to possess a two-proton halo structure in its ground state. In the astrophysical r p -process, where the two-proton capture reaction 15O(2 p ,γ )17Ne plays an important role, the calculated reaction rate differs by several orders of magnitude between different theoretical approaches. To add to the understanding of the 17Ne structure we have studied nuclear and electromagnetic dissociation. A 500 MeV/u 17Ne beam was directed toward lead, carbon, and polyethylene targets. Oxygen isotopes in the final state were measured in coincidence with one or two protons. Different reaction branches in the dissociation of 17Ne were disentangled. The relative populations of s and d states in 16F were determined for light and heavy targets. The differential cross section for electromagnetic dissociation (EMD) shows a continuous internal energy spectrum in the three-body system 15O+2 p . The 17Ne EMD data were compared to current theoretical models. None of them, however, yields satisfactory agreement with the experimental data presented here. These new data may facilitate future development of adequate models for description of the fragmentation process.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-29
..., Takeoff Minimums and Obstacle DP, Amdt 3 Harvard, NE, Harvard State, RNAV (GPS) RWY 35, Orig Harvard, NE, Harvard State, Takeoff Minimums and Obstacle DP, Orig Harvard, NE, Harvard State, VOR/DME RNAV OR GPS RWY...
KM3NeT/ARCA sensitivity to point-like neutrino sources
NASA Astrophysics Data System (ADS)
Trovato, A.;
2017-09-01
KM3NeT is network of deep-sea neutrino telescopes in the Mediterranean Sea aiming at the discovery of cosmic neutrino sources (ARCA) and the determination of the neutrino mass hierarchy (ORCA). The geographical location of KM3NeT in the Northern hemisphere allows to observe most of the Galactic Plane, including the Galactic Centre. Thanks to its good angular resolution, prime targets of KM3NeT/ARCA are point-like neutrino sources and in particular galactic sources.
Vibrational Relaxation and Collision-Induced Dissociation of Xenon Fluoride by Neon
1989-03-01
potential energy surface, which consists of a Morse function for the XeF interaction and Lennard - Jones functions for the NeXe and NeF interactions. Rate...interaction and a Lennard - Jones function for the NeXe and the NeF interactions. The values of the Morse potential parameters for XeF are taken from...interactions are calculated using the theoretical data provided by Svehla.59 The parameters for the Morse potential and the Lennard - Jones potentials are listed
NASA Astrophysics Data System (ADS)
John, T. L.
1996-04-01
Free-free absorption coefficients of the negative neon ion are calculated by the phase-shift approximation based on multiconfiguration Hartree-Fock continuum wave functions. These wave functions accurately account for electron-neon correlation and polarization, and yield scattering cross-sections in excellent agreement with the latest experimental values. The coefficients are expected to give the best current estimates of Ne^- continuous absorption. We find that Ne^- makes only a small contribution (less than 0.3 per cent) to stellar opacities, including hydrogen-deficient stars with enhanced Ne abundances.
Sympathetic Nerves in Breast Cancer: Angiogenesis and Antiangiogenic Therapy
2013-02-01
directly regulate 4T1 growth through ARs. Using in vitro conditions that yielded NE-mediated functional effects in other cell lines (1), we assessed...Therefore we propose that 4T1 is a good model for examining the effects of NE-induced effects on stromal cell populations in the absence of direct NE... effects analysis or by Holm-Sidak multiple comparison test. RESULTS 4T1 Tumor Cells Do Not Respond to NE In Vitro or Signal via AR To determine
NASA Astrophysics Data System (ADS)
Aguilar-Arevalo, A. A.; Anderson, C. E.; Bartoszek, L. M.; Bazarko, A. O.; Brice, S. J.; Brown, B. C.; Bugel, L.; Cao, J.; Coney, L.; Conrad, J. M.; Cox, D. C.; Curioni, A.; Djurcic, Z.; Finley, D. A.; Fleming, B. T.; Ford, R.; Garcia, F. G.; Garvey, G. T.; Green, C.; Green, J. A.; Hart, T. L.; Hawker, E.; Imlay, R.; Johnson, R. A.; Karagiorgi, G.; Kasper, P.; Katori, T.; Kobilarcik, T.; Kourbanis, I.; Koutsoliotas, S.; Laird, E. M.; Linden, S. K.; Link, J. M.; Liu, Y.; Liu, Y.; Louis, W. C.; Mahn, K. B. M.; Marsh, W.; Martin, P. S.; McGregor, G.; Metcalf, W.; Meyer, H.-O.; Meyers, P. D.; Mills, F.; Mills, G. B.; Monroe, J.; Moore, C. D.; Nelson, R. H.; Nguyen, V. T.; Nienaber, P.; Nowak, J. A.; Ouedraogo, S.; Patterson, R. B.; Perevalov, D.; Polly, C. C.; Prebys, E.; Raaf, J. L.; Ray, H.; Roe, B. P.; Russell, A. D.; Sandberg, V.; Sands, W.; Schirato, R.; Schofield, G.; Schmitz, D.; Shaevitz, M. H.; Shoemaker, F. C.; Smith, D.; Soderberg, M.; Sorel, M.; Spentzouris, P.; Stancu, I.; Stefanski, R. J.; Sung, M.; Tanaka, H. A.; Tayloe, R.; Tzanov, M.; Van de Water, R.; Wascko, M. O.; White, D. H.; Wilking, M. J.; Yang, H. J.; Zeller, G. P.; Zimmerman, E. D.; MiniBooNE Collaboration
2009-02-01
The MiniBooNE neutrino detector was designed and built to look for ν→ν oscillations in the (sin 2θ,Δm) parameter space region where the LSND experiment reported a signal. The MiniBooNE experiment used a beam energy and baseline that were an order of magnitude larger than those of LSND so that the backgrounds and systematic errors would be completely different. This paper provides a detailed description of the design, function, and performance of the MiniBooNE detector.
Frequency measurement of the 260-THz (1. 15-. mu. m) He--Ne laser
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jennings, D.A.; Petersen, F.R.; Evenson, K.M.
1979-05-01
Absolute infrared frequency measurement has been extended to 260 THz with the measurement of the strong 1.15-..mu..m laser line in /sup 20/Ne. The frequency was synthesized in nonlinear crystals of CdGeAs/sub 2/ and Ag/sub 3/AsS/sub 3/ from stabilized CO/sub 2/ lasers and the 1.5-..mu..m laser line in /sup 20//sub Ne.Themeasuredfrequencyis/..nu..20/sub Ne,1.15mum/ =260.103 284 (30) THz.
Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A.
2010-01-01
Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5 min decreased [3H]NE uptake capacity, an effect characterized by a robust decrease in the Vmax of the transport of [3H]NE. As expected, reserpine did not displace the binding of [3H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [3H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [3H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca2+/Ca2+-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [3H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, α-methyl-p-tyrosine, increased [3H]NE uptake and eliminated the inhibitory effects of reserpine on [3H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca2+-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. PMID:20176067
Wolff, Wanja; Sandouqa, Yaser; Brand, Ralf
2016-05-01
Epidemiological research indicates that the use of prescription drugs to enhance cognitive functioning is prevalent in Western countries, however, research on this phenomenon in Arab countries is lacking. Our study aimed to investigate the frequency of neuroenhancement (NE) using prescription drugs in a sample of employees in Jordan. A sample of 1186 employees (37.11±8.37 years old, 495 female), of whom 723 (35.65±7.53 years old, 396 female) served as teachers, completed a paper-pencil questionnaire. The single sample count technique (SSC) was used in order to secure confidential, self-reporting of prescription drug NE. The 12-month prevalence of NE, estimated with the SSC was 15.43%. At 26.16%, the prevalence estimate was markedly higher in the subsample of teachers compared to non-teachers, 0.29%. Surprisingly, 336 participants did not use the SSC and directly affirmed or denied prescription drug NE. These direct responses yielded a prevalence of 11.57% for the full sample, 9.73% for the teachers and 15.60% for the non-teachers. This is the first study of the frequency of NE in an Arab sample. Results indicate that the use of prescription drug NE is not limited to Western countries and that teachers in Jordan might constitute a high-risk population. Further, participants seem to differ in their use of indirect estimation methods for reporting prescription drug NE. For future research, it might be useful to triangulate standard self-reports and indirect estimation methods to assess NE. Possible cultural differences and specific high-risk populations for NE should be investigated further. Copyright © 2015 Elsevier B.V. All rights reserved.
Wolff, Wanja; Baumgarten, Franz; Brand, Ralf
2013-12-06
Neuroenhancement (NE), the use of psychoactive substances in order to enhance a healthy individual's cognitive functioning from a proficient to an even higher level, is prevalent in student populations. According to the strength model of self-control, people fail to self-regulate and fall back on their dominant behavioral response when finite self-control resources are depleted. An experiment was conducted to test the hypothesis that ego-depletion will prevent students who are unfamiliar with NE from trying it. 130 undergraduates, who denied having tried NE before (43% female, mean age = 22.76 ± 4.15 years old), were randomly assigned to either an ego-depletion or a control condition. The dependent variable was taking an "energy-stick" (a legal nutritional supplement, containing low doses of caffeine, taurine and vitamin B), offered as a potential means of enhancing performance on the bogus concentration task that followed. Logistic regression analysis showed that ego-depleted participants were three times less likely to take the substance, OR = 0.37, p = .01. This experiment found that trying NE for the first time was more likely if an individual's cognitive capacities were not depleted. This means that mental exhaustion is not predictive for NE in students for whom NE is not the dominant response. Trying NE for the first time is therefore more likely to occur as a thoughtful attempt at self-regulation than as an automatic behavioral response in stressful situations. We therefore recommend targeting interventions at this inter-individual difference. Students without previous reinforcing NE experience should be provided with information about the possible negative health outcomes of NE. Reconfiguring structural aspects in the academic environment (e.g. lessening workloads) might help to deter current users.
Nasu, Makoto; Takata, Nozomu; Danjo, Teruko; Sakaguchi, Hideya; Kadoshima, Taisuke; Futaki, Sugiko; Sekiguchi, Kiyotoshi; Eiraku, Mototsugu; Sasai, Yoshiki
2012-01-01
In the mammalian cortex, the dorsal telencephalon exhibits a characteristic stratified structure. We previously reported that three-dimensional (3D) culture of mouse ES cells (mESCs) can efficiently generate cortical neuroepithelium (NE) and layer-specific cortical neurons. However, the cortical NE generated in this mESC culture was structurally unstable and broke into small neural rosettes by culture day 7, suggesting that some factors for reinforcing the structural integrity were missing. Here we report substantial supporting effects of the extracellular matrix (ECM) protein laminin on the continuous formation of properly polarized cortical NE in floating aggregate culture of mESCs. The addition of purified laminin and entactin (a laminin-associated protein), even at low concentrations, stabilized the formation of continuous cortical NE as well as the maintenance of basement membrane and prevented rosette formation. Treatment with the neutralizing ß1-integrin antibody impaired the continuous NE formation. The stabilized cortical NE exhibited typical interkinetic nuclear migration of cortical progenitors, as seen in the embryonic cortex. The laminin-treated cortical NE maintained a continuous structure even on culture days 12 and 15, and contained ventricular, basal-progenitor, cortical-plate and Cajal-Retzius cell layers. The cortical NE in this culture was flanked by cortical hem-like tissue. Furthermore, when Shh was added, ventral telencephalic structures such as lateral ganglionic eminence–like tissue formed in the region adjacent to the cortical NE. Thus, our results indicate that laminin-entactin ECM promotes the formation of structurally stable telencephalic tissues in 3D ESC culture, and supports the morphogenetic recapitulation of cortical development. PMID:23300850
Li, Zhiping; Oben, Jude A; Yang, Shiqi; Lin, Huizhi; Stafford, Elizabeth A; Soloski, Mark J; Thomas, Steven A; Diehl, Anna Mae
2004-08-01
It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of ob/ob mice promotes depletion of liver NKT cells, thereby sensitizing ob/ob livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic NKT cells were quantified in wild-type mice before and after treatment with NE inhibitors, and in dopamine beta-hydroxylase knockout mice (which cannot synthesize NE) and ob/ob mice before and after 4 weeks of NE supplementation. Decreasing NE activity consistently reduces liver NKT cells, while increasing NE has the opposite effect. Analysis of hepatic and thymic NKT cells in mice of different ages demonstrate an age-related accumulation of hepatic NKT cells in normal mice, while liver NKT cells become depleted after birth in ob/ob mice, which have increased apoptosis of hepatic NKT cells. NE treatment inhibits apoptosis and restores hepatic NKT cells. In ob/ob mice with reduced hepatic NKT cells, hepatic T and NKT cells produce excessive T helper (Th)-1 proinflammatory cytokines and the liver is sensitized to LPS toxicity. NE treatment decreases Th-1 cytokines, increases production of Th-2 cytokines, and reduces hepatotoxicity. Studies of CD1d-deficient mice, which lack the receptor required for NKT cell development, demonstrate that they are also unusually sensitive to LPS hepatotoxicity. In conclusion, low NE activity increases hepatic NKT cell apoptosis and depletes liver NKT cells, promoting proinflammatory polarization of hepatic cytokine production that sensitizes the liver to LPS toxicity. Copyright 2004 American Association for the Study of Liver Diseases
Agnostic stacking of intergalactic doublet absorption: measuring the Ne VIII population
NASA Astrophysics Data System (ADS)
Frank, Stephan; Pieri, Matthew M.; Mathur, Smita; Danforth, Charles W.; Shull, J. Michael
2018-05-01
We present a blind search for doublet intergalactic metal absorption with a method dubbed `agnostic stacking'. Using a forward-modelling framework, we combine this with direct detections in the literature to measure the overall metal population. We apply this novel approach to the search for Ne VIII absorption in a set of 26 high-quality COS spectra. We probe to an unprecedented low limit of log N>12.3 at 0.47≤z ≤1.34 over a path-length Δz = 7.36. This method selects apparent absorption without requiring knowledge of its source. Stacking this mixed population dilutes doublet features in composite spectra in a deterministic manner, allowing us to measure the proportion corresponding to Ne VIII absorption. We stack potential Ne VIII absorption in two regimes: absorption too weak to be significant in direct line studies (12.3 < log N < 13.7), and strong absorbers (log N > 13.7). We do not detect Ne VIII absorption in either regime. Combining our measurements with direct detections, we find that the Ne VIII population is reproduced with a power-law column density distribution function with slope β = -1.86 ^{+0.18 }_{ -0.26} and normalization log f_{13.7} = -13.99 ^{+0.20 }_{ -0.23}, leading to an incidence rate of strong Ne VIII absorbers dn/dz =1.38 ^{+0.97 }_{ -0.82}. We infer a cosmic mass density for Ne VIII gas with 12.3 < log N < 15.0 of Ω _{{{Ne {VIII}}}} = 2.2 ^{+1.6 }_{ _-1.2} × 10^{-8}, a value significantly lower that than predicted by recent simulations. We translate this density into an estimate of the baryon density Ωb ≈ 1.8 × 10-3, constituting 4 per cent of the total baryonic mass.
Young, Daniel L; Shen, Jay J; Estocado, Nancy; Landers, Merrill R
2012-04-01
The NE1 Wound Assessment Tool (NE1 WAT; Medline Industries, Inc, Mundelein, Illinois), previously called the N.E. One Can Stage, was shown to significantly improve accuracy of pressure ulcer (PrU) staging. Improved PrU staging has many potential benefits, including improved care for the patient and better reimbursement. Medicare has incentivized good care and accurate identification of PrUs in the acute care hospital through an additional payment, the Medicare Severity-Diagnosis Related Group (MS-DRG). This article examines the financial impact of NE1 WAT use on the acute care hospital relative to MS-DRG reimbursement. PrU staging accuracy with and without use of the NE1 WAT from previous data was compared with acute care hospital PrU rates obtained from the 2006 National Inpatient Sample. Hill-Rom International Pressure Ulcer Prevalence Survey data were used to estimate the number of MS-DRG-eligible PrUs. There are between 390,000 and 130,000 MS-DRG-eligible PrUs annually. Given current PrU staging accuracy, approximately $209 million in MS-DRG money is being collected. With the improved staging afforded by the NE1 WAT, this figure is approximately $763.9 million. Subtracting the 2 reveals $554.9 million in additional reimbursement that could be generated by using the NE1 WAT. There is a tremendous financial incentive to improve PrU staging. The NE1 WAT has been shown to improve PrU staging accuracy significantly. This improvement has the potential to improve the financial health of acute care hospitals caring for patients with PrUs.
Error-related brain activity and error awareness in an error classification paradigm.
Di Gregorio, Francesco; Steinhauser, Marco; Maier, Martin E
2016-10-01
Error-related brain activity has been linked to error detection enabling adaptive behavioral adjustments. However, it is still unclear which role error awareness plays in this process. Here, we show that the error-related negativity (Ne/ERN), an event-related potential reflecting early error monitoring, is dissociable from the degree of error awareness. Participants responded to a target while ignoring two different incongruent distractors. After responding, they indicated whether they had committed an error, and if so, whether they had responded to one or to the other distractor. This error classification paradigm allowed distinguishing partially aware errors, (i.e., errors that were noticed but misclassified) and fully aware errors (i.e., errors that were correctly classified). The Ne/ERN was larger for partially aware errors than for fully aware errors. Whereas this speaks against the idea that the Ne/ERN foreshadows the degree of error awareness, it confirms the prediction of a computational model, which relates the Ne/ERN to post-response conflict. This model predicts that stronger distractor processing - a prerequisite of error classification in our paradigm - leads to lower post-response conflict and thus a smaller Ne/ERN. This implies that the relationship between Ne/ERN and error awareness depends on how error awareness is related to response conflict in a specific task. Our results further indicate that the Ne/ERN but not the degree of error awareness determines adaptive performance adjustments. Taken together, we conclude that the Ne/ERN is dissociable from error awareness and foreshadows adaptive performance adjustments. Our results suggest that the relationship between the Ne/ERN and error awareness is correlative and mediated by response conflict. Copyright © 2016 Elsevier Inc. All rights reserved.
Chen, Guojun; Jaskula-Sztul, Renata; Harrison, April; Dammalapati, Ajitha; Xu, Wenjin; Cheng, Yiqiang; Chen, Herbert; Gong, Shaoqin
2016-08-01
Neuroendocrine (NE) cancers can cause significant patient morbidity. Besides surgery, there are no curative treatments for NE cancers and their metastases, emphasizing the need for the development of other forms of therapy. In this study, multifunctional unimolecular micelles were developed for targeted NE cancer therapy. The unimolecular micelles were formed by multi-arm star amphiphilic block copolymer poly(amidoamine)-poly(valerolactone)-poly(ethylene glycol) conjugated with KE108 peptide and Cy5 dye (abbreviated as PAMAM-PVL-PEG-KE108/Cy5). The unimolecular micelles with a spherical core-shell structure exhibited a uniform size distribution and excellent stability. The hydrophobic drug thailandepsin-A (TDP-A), a recently discovered HDAC inhibitor, was physically encapsulated into the hydrophobic core of the micelles. KE108 peptide, a somatostatin analog possessing high affinity for all five subtypes of somatostatin receptors (SSTR 1-5), commonly overexpressed in NE cancer cells, was used for the first time as an NE cancer targeting ligand. KE108 exhibited superior targeting abilities compared to other common somatostatin analogs, such as octreotide, in NE cancer cell lines. The in vitro assays demonstrated that the TDP-A-loaded, KE108-targeted micelles exhibited the best capabilities in suppressing NE cancer cell growth. Moreover, the in vivo near-infrared fluorescence imaging on NE-tumor-bearing nude mice showed that KE108-conjugated micelles exhibited the greatest tumor accumulation due to their passive targeting and active targeting capabilities. Finally, TDP-A-loaded and KE108-conjugated micelles possessed the best anticancer efficacy without detectable systemic toxicity. Thus, these novel TDP-A-loaded and KE108-conjugated unimolecular micelles offer a promising approach for targeted NE cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Zhang, Xuemin; Qian, Jiadong; Shen, Xuhui
2014-05-01
The solar cycle variations of electron density (Ne) in the topside ionosphere are presented by observations around local time 22:30 from Detection of Electro-Magnetic Emissions Transmitted from Earthquake Regions (DEMETER) satellite during 2006-2008 in the low solar activity, in which the revisited orbits are selected to construct Ne time sequences at different points. The results show that electron density (Ne) reduced 50-100% since 2006 to 2008 at equatorial area and middle latitudes, with much bigger maximal Ne in 2006 but even no yearly peak in 2007 and 2008 around 30° latitude. The seasonal asymmetry is revealed by the yearly maxima of Ne in December over Southern Hemisphere always being larger than those in June over Northern Hemisphere. Furthermore, the equinoctial asymmetry is found around the magnetic equator and high northern latitudes under the low solar activity, and the latter one has not been revealed in other research. Ne from IRI2012 is close to the actual observation by DEMETER in 2008, even better than those in 2006 and 2007, indicating the great improvement of this empirical ionospheric model in this extremely low solar minimum. After comparison with the fitted results by indices of F10.7 and EUV combined with the first five periods in Ne, EUV is a little better to describe the variations in Ne during this solar minimum. By discussing the relationship among nighttime Ne and molecules in upper atmosphere, the [O/N2] density ratio is the key factor at high latitude, while [O] density plays a certain role to electron density around the equator.
Schachter, J B; Yasuda, R P; Wolfe, B B
1995-09-01
Studies were undertaken in an effort to discern possible mechanisms by which the A1 adenosine receptor agonist cyclopentyladenosine (CPA) enhances the norepinephrine-stimulated (NE-stimulated) hydrolysis of phosphoinositides in DDT1-MF2 cells. Measurements of arachidonic acid release revealed similar behaviours to those observed in measurements of phosphoinositide hydrolysis. In the presence of NE, both second messenger responses were potentiated by the addition of CPA, whereas in the absence of NE, CPA had little or no effect on either second messenger. The stimulation and potentiation of both second messenger responses were enhanced in the presence of extracellular calcium, and in each case these effects were persistent over time. For either second messenger system the stimulation by NE and the potentiation by CPA appeared to utilize separate mechanisms as evidenced by the fact that the potentiations by CPA were selectively antagonized by a cAMP analogue or by pertussis toxin, whereas the stimulations by NE were essentially unaffected by these agents. Inhibition of phospholipase A2 (PLA2) also blocked the potentiation of PLC by CPA, without affecting NE-stimulated phosphoinositide hydrolysis. Furthermore, in the presence of CPA, the exogenous administration of PLA2 was found to stimulate phosphoinositide hydrolysis in these cells. These data are consistent with a hypothesis whereby the apparent potentiation of NE-stimulated phosphoinositide hydrolysis by CPA is actually due to the stimulation by CPA of a second pathway of phospholipase C activity which is additive to that of NE. The activation of PLC and PLA2 by NE produces phospholipid products which may play a permissive role in the pathway coupling adenosine A1 receptors to these phospholipases. The formation of lysophosphatidic acid is suggested as one possible mediator of this permissive effect.
Tampin, Brigitte; Briffa, Noelle Kathryn; Goucke, Roger; Slater, Helen
2013-12-01
The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain has proposed a grading system for the presence of neuropathic pain (NeP) using the following categories: no NeP, possible, probable, or definite NeP. To further evaluate this system, we investigated patients with neck/upper limb pain with a suspected nerve lesion, to explore: (i) the clinical application of this grading system; (ii) the suitability of 2 NeP questionnaires (Leeds Assessment of Neuropathic Symptoms and Signs pain scale [LANSS] and the painDETECT questionnaire [PD-Q]) in identifying NeP in this patient cohort; and (iii) the level of agreement in identifying NeP between the NeuPSIG classification system and 2 NeP questionnaires. Patients (n = 152; age 52 ± 12 years; 53% male) completed the PD-Q and LANSS questionnaire and underwent a comprehensive clinical examination. The NeuPSIG grading system proved feasible for application in this patient cohort, although it required considerable time and expertise. Both questionnaires failed to identify a large number of patients with clinically classified definite NeP (LANSS sensitivity 22%, specificity 88%; PD-Q sensitivity 64%, specificity 62%). These lowered sensitivity scores contrast with those from the original PD-Q and LANSS validation studies and may reflect differences in the clinical characteristics of the study populations. The diagnostic accuracy of LANSS and PD-Q for the identification of NeP in patients with neck/upper limb pain appears limited. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Cluster folding analysis of 20Ne+16O elastic transfer
NASA Astrophysics Data System (ADS)
Hamada, Sh.; Keeley, N.; Kemper, K. W.; Rusek, K.
2018-05-01
The available experimental data for the 20Ne+16O system in the energy range where the effect of α -cluster transfer is well observed are reanalyzed using the cluster folding model. The cluster folding potential, which includes both real and imaginary terms, reproduces the data at forward angles and the inclusion of the 16O(20Ne,16O)20Ne elastic transfer process provides a satisfactory description of the backward angles. The spectroscopic factor for the 20Ne→16O+α overlap was extracted and compared with other values from the literature. The present results suggest that the (20Ne,16O ) reaction might be an alternative means of exploring the α -particle structure of nuclei.
Könnecke, Mark; Akeroyd, Frederick A; Bernstein, Herbert J; Brewster, Aaron S; Campbell, Stuart I; Clausen, Björn; Cottrell, Stephen; Hoffmann, Jens Uwe; Jemian, Pete R; Männicke, David; Osborn, Raymond; Peterson, Peter F; Richter, Tobias; Suzuki, Jiro; Watts, Benjamin; Wintersberger, Eugen; Wuttke, Joachim
2015-02-01
NeXus is an effort by an international group of scientists to define a common data exchange and archival format for neutron, X-ray and muon experiments. NeXus is built on top of the scientific data format HDF5 and adds domain-specific rules for organizing data within HDF5 files, in addition to a dictionary of well defined domain-specific field names. The NeXus data format has two purposes. First, it defines a format that can serve as a container for all relevant data associated with a beamline. This is a very important use case. Second, it defines standards in the form of application definitions for the exchange of data between applications. NeXus provides structures for raw experimental data as well as for processed data.
Gelatin contains collagen, which is one of the materials that make up cartilage and bone. This is why some people think ... Collagen Hydrolysate, Collagène Dénaturé, Collagène Hydrolysé, Collagène Marin Hydrolysé, Denatured Collagen, Gelatina, Gelatine, Gélatine, Gélatine Hydrolysée, Hydrolised ...
Ficts and facts of epinephrine and norepinephrine stability in injectable solutions.
Hoellein, Ludwig; Holzgrabe, Ulrike
2012-09-15
Epinephrine (EPI) and norepinephrine (NE) play an important role in emergency medicine and acute treatment of hypotension and shocks in the intensive care unit. Injectable solutions can either be provided as proprietary medicinal products or as individually prepared dilutions. Due to the chemical structure of EPI and NE, the stability of the corresponding solutions is limited. Thus, most manufacturers of EPI and NE injectable solutions use sulfites and nitrogen for stabilization, Nevertheless, storage conditions such as temperature and light have to be considered, but are often neglected in the daily hospital routine. In addition, hospital pharmacies prepare EPI and NE solutions and dilute commercially available solutions for individual therapy, especially on ICUs. Since the influence of dilution and the presence of excipients and other preservatives are not systematically explored, we collected published data and investigations on stability on the potency of EPI and NE injectable solutions in order to deduce storage recommendations for diluted EPI and NE solutions of different concentration. Copyright © 2012 Elsevier B.V. All rights reserved.
Proposed morphologic classification of prostate cancer with neuroendocrine differentiation.
Epstein, Jonathan I; Amin, Mahul B; Beltran, Himisha; Lotan, Tamara L; Mosquera, Juan-Miguel; Reuter, Victor E; Robinson, Brian D; Troncoso, Patricia; Rubin, Mark A
2014-06-01
On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.
Yen, T T; Fuller, R W; Broderick, C L; Hemrick-Luecke, S K; Perry, K W
1988-08-01
ONO-2235 [(E)-3-carboxymethyl-5-[(2E)-2-methyl-3-phenyl-propenylidene]rhodanine], an ARI, was reported to prevent significantly the decrease of norepinephrine (NE) turnover in three tissues of streptozotocin (STZ)-diabetic rats (1). To examine whether the partial restoration of NE turnover by ONO-2235 is related to its ARI activity, the effect of another ARI, AL-1576 [spiro(2,7-difluoro-9H-fluoren-9, 4'-imidazoline)-2'5'-dione], on NE turnover in STZ rats was investigated. STZ caused an accumulation of sorbitol in the lens and decreased NE turnover in interscapular brown adipose tissue (IBAT), heart and pancreas. AL-1576 totally prevented the accumulation of sorbitol in the lens but had no effect on the decreased NE turnover in all three tissues. These results suggest that the partial prevention of NE turnover decrease by ONO-2235 may not have been mediated by its ARI activity.
Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase.
Warren, Christopher M; van den Brink, Ruud L; Nieuwenhuis, Sander; Bosch, Jos A
2017-04-01
It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy adult participants in a double-blind, placebo-controlled cross-over design. Atomoxetine administration significantly increased SAA secretion and concentrations at 75-180min after treatment (more than doubling baseline levels). Consistent with evidence that elevation in central NE is a co-determinant of hypothalamic-pituitary-adrenal axis activity, salivary cortisol also approximately doubled at the same time points. Moreover, changes in salivary cortisol positively correlated with SAA (0.44
Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior.
McCall, Jordan G; Siuda, Edward R; Bhatti, Dionnet L; Lawson, Lamley A; McElligott, Zoe A; Stuber, Garret D; Bruchas, Michael R
2017-07-14
Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms.
CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety
McCall, Jordan G.; Al-Hasani, Ream; Siuda, Edward R.; Hong, Daniel Y.; Norris, Aaron J.; Ford, Christopher P.; Bruchas, Michael R.
2015-01-01
Summary The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. PMID:26212712
Noble gases in Mars atmosphere: new precise analysis with Paloma
NASA Astrophysics Data System (ADS)
Sarda, Ph.; Paloma Team
2003-04-01
The Viking mission embarked a mass spectrometer designed by Alfred O. Nier that yielded the first determination of the elemental and isotopic composition of noble gases in Mars atmosphere. For example, the 40Ar/36Ar ratio in martian air is roughly 10 fold that in terrestrial air. This extraordinary accomplishment, however, has furnished only partial results with large analytical uncertainties. For example, we do not know the isotopic composition of helium, and only very poorly that of Ne, Kr and Xe. In planetary science, it is fundamental to have a good knowledge of the atmosphere because this serves as a reference for all further studies of volatiles. In addition, part of our present knowledge of Mars atmosphere is based on the SNC meteorites, and again points to important differences between the atmospheres of Earth and Mars. For example the 129Xe/132Xe ratio of martian atmosphere would be twice that of terrestrial air and the 36Ar/38Ar ratio strongly different from the terrestrial or solar value. There is a need for confirming that the atmospheric components found in SNC meteorites actually represents the atmosphere of Mars, or to determine how different they are. Paloma is an instrument designed to generate elemental and isotopic data for He, Ne, Ar, Kr and Xe (and other gases) using a mass spectrometer with a purification and separation line. Gas purification and separation did not exist on the Vicking instrument. Because Paloma includes purification and separation, we expect strong improvement in precision. Ne, Ar and Xe isotope ratios should be obtained with an accuracy of better than 1%. Determination of the presently unknown ^3He/^4He ratio is also awaited from this experiment. Knowledge of noble gas isotopes in Mars atmosphere will allow some insight into major planetary processes such as degassing (^3He/^4He, 40Ar/36Ar, 129Xe/130Xe, 136Xe/130Xe), gravitational escape to space (^3He/^4He, 20Ne/22Ne), hydrodynamic escape and/or impact erosion of the atmosphere (20Ne/22Ne, 21Ne/22Ne, 38Ar/36Ar, Xe isotopes), input of solar wind and galactic comic rays (^3He/^4He, 20Ne/22Ne, 21Ne/22Ne). Comparison with the Earth may also shed light on long standing problems such as the large isotopic mass fractionation of the Xe isotopes and the so-called missing xenon problem. Possible variations of Kr and Xe abundances due to adsorption phenomena related to the climatic cycle will be searched for by measuring along at least one martian year.
L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.
Goldstein, David S
2006-01-01
L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.
Direct measurement of neon production rates by (α,n) reactions in minerals
NASA Astrophysics Data System (ADS)
Cox, Stephen E.; Farley, Kenneth A.; Cherniak, Daniele J.
2015-01-01
The production of nucleogenic neon from alpha particle capture by 18O and 19F offers a potential chronometer sensitive to temperatures higher than the more widely used (U-Th)/He chronometer. The accuracy depends on the cross sections and the calculated stopping power for alpha particles in the mineral being studied. Published 18O(α,n)21Ne production rates are in poor agreement and were calculated from contradictory cross sections, and therefore demand experimental verification. Similarly, the stopping powers for alpha particles are calculated from SRIM (Stopping Range of Ions in Matter software) based on a limited experimental dataset. To address these issues we used a particle accelerator to implant alpha particles at precisely known energies into slabs of synthetic quartz (SiO2) and barium tungstate (BaWO4) to measure 21Ne production from capture by 18O. Within experimental uncertainties the observed 21Ne production rates compare favorably to our predictions using published cross sections and stopping powers, indicating that ages calculated using these quantities are accurate at the ∼3% level. In addition, we measured the 22Ne/21Ne ratio and (U-Th)/He and (U-Th)/Ne ages of Durango fluorapatite, which is an important model system for this work because it contains both oxygen and fluorine. Finally, we present 21Ne/4He production rate ratios for a variety of minerals of geochemical interest along with software for calculating neon production rates and (U-Th)/Ne ages.
Element Abundance Ratios in the Quiet Sun Transition Region
NASA Astrophysics Data System (ADS)
Young, P. R.
2018-03-01
Element abundance ratios of magnesium to neon (Mg/Ne) and neon to oxygen (Ne/O) in the transition region of the quiet Sun have been derived by re-assessing previously published data from the Coronal Diagnostic Spectrometer on board the Solar and Heliospheric Observatory in the light of new atomic data. The quiet Sun Mg/Ne ratio is important for assessing the effect of magnetic activity on the mechanism of the first ionization potential (FIP) effect, while the Ne/O ratio can be used to infer the solar photospheric abundance of neon, which cannot be measured directly. The average Mg/Ne ratio is found to be 0.52 ± 0.11, which applies over the temperature region 0.2–0.7 MK, and is consistent with the earlier study. The Ne/O ratio is, however, about 40% larger, taking the value 0.24 ± 0.05 that applies to the temperature range 0.08–0.40 MK. The increase is mostly due to changes in ionization and recombination rates that affect the equilibrium ionization balance. If the Ne/O ratio is interpreted as reflecting the photospheric ratio, then the photospheric neon abundance is 8.08 ± 0.09 or 8.15 ± 0.10 (on a logarithmic scale for which hydrogen is 12), according to whether the oxygen abundances of M. Asplund et al. or E. Caffau et al. are used. The updated photospheric neon abundance implies a Mg/Ne FIP bias for the quiet Sun of 1.6 ± 0.6.
Infrared and Microwave Spectra of Ne-WATER Complex
NASA Astrophysics Data System (ADS)
Liu, Xunchen; Thomas, Javix; Xu, Yunjie; Hou, Dan; Li, Hui
2016-06-01
The binary complex of rare gas atom and water is an ideal model to study the anisotropic potential energy surface of van der Waals interaction and the large amplitude motion. Although Xe-H_2O, Kr-H_2O, Ar-H_2O, Ar-D_2O and even Ne-D_2O complexes were studied by microwave or high resolution infrared spectroscopy, the lighter Ne-H_2O complex has remained unidentified. In this talk, we will present the theoretical and experimental investigation of the Ne-H_2O complex. A four-dimension PES for H_2O-Ne which only depended on the intramolecular (Q2) normal-mode coordinate of H2O monomer was calculated in this work to determine the rovibrational energy levels and mid-infrared transitions. Aided with the calculated transitions, we were able to assigned the high resolution mid-infrared spectra of both 20Ne-H_2O and 22Ne-H_2O complexes that are generated with a pulsed supersonic molecular beam in a multipass direct absorption spectrometer equiped with an external cavity quantum cascade laser at 6 μm. Several bands of both para and ortho Ne-H2O were assigned and fitted using the Hamiltonian with strong Coriolis and angular-radical coupling terms. The predicted groud state energy levels are then confirmed by the J=1-0 and J=2-1 transitions measurement using a cavity based Fourier transform microwave spectrometer.
Hemofagocitinė limfohistiocitozė: literatūros apžvalga
Bereikienė, Simona; Rascon, Jelena
2017-01-01
Hemofagocitinė limfohistiocitozė – tai sindromas, besivystantis dėl sutrikusios imuninio atsako aktyvacijos ir slopinimo pusiausvyros. Išskiriama pirminė (genetinė arba šeiminė) sindromo forma, nulemta genų, dalyvaujančių imuninių ląstelių sąveikoje, mutacijų; ir antrinė (sporadinė) forma, besivystanti dėl infekcijos, navikinio, autoimuninio proceso ar metabolinių sutrikimų. Antrinės hemofagocitinės limfohistiocitozės genetinis pagrindas kol kas nežinomas. Pirminei ir antrinei formoms būdingas toks pats specifinis hiperuždegiminių reakcijų bei klinikinių simptomų kompleksas, kuriuo grindžiama patologijos diagnostika. Tačiau pirminės ir antrinės formų atskyrimas dažnai tampa iššūkiu dėl patologijos retumo, plataus klinikinių požymių spektro, dėl riboto specifinių testų prieinamumo ir, svarbiausia, gydymo taktikos ypatumų. Etiopatogenetinis pirminės formos gydymas yra skubi alogeninė kraujodaros kamieninių ląstelių transplantacija, be kurios išeitis neišvengiamai fatali. Antrinės formos gydymas priklauso nuo klinikinės išraiškos ir ją sukėlusios infekcijos pobūdžio. Labai svarbi laiku atlikta diagnostika norint kuo skubiau pradėti tinkamą gydymą bei pagerinti išgyvenamumą. Hemofagocitinės limfohistiocitozės gydymą komplikuoja didelis su gydymu susijęs mirtingumo dažnis bei ligos polinkis recidyvuoti. PMID:28630593
Evolution of superconducting gap and metallic ground state in cuprates from transport
NASA Astrophysics Data System (ADS)
Taillefer, Louis
2006-03-01
We report on fundamental characteristics of the ground state of cuprates in the limit of T=0, for both normal and superconducting states, obtained from transport measurements on high-quality single crystals of YBCO and Tl-2201, as a function of hole concentration. The superconducting gap is extracted from thermal conductivity; it is found to scale with the superconducting transition temperature throughout the overdoped regime, with a gap-to-Tc ratio of 5 [1]. The normal state is accessed by suppressing superconductivity with magnetic fields up to 60 T and is characterized by the limiting behavior of its electrical resistivity; while carrier localization is observed in YBCO at low temperature for carrier concentrations p below 0.1 hole/planar Cu, at p=0.1 and above the material remains highly metallic down to T=0 [2]. This shows that the non-superconducting state of underdoped cuprates, deep in the pseudogap phase, is remarkably similar to that of strongly overdoped cuprates, e.g. at p=0.3. We compare these results with similar measurements on other cuprates and discuss their implication for our understanding of the cuprate phase diagram. [1] In collaboration with: D.G. Hawthorn, S.Y. Li, M. Sutherland, E. Boaknin, R.W. Hill, C. Proust, F. Ronning, M. Tanatar, J. Paglione, D. Peets, R. Liang, D.A. Bonn, W.N. Hardy, and N.N. Kolesnikov. [2] In collaboration with: C. Proust, M. Sutherland, N. Doiron- Leyraud, S.Y. Li, R. Liang, D.A. Bonn, W.N. Hardy, N.E. Hussey, S. Adachi, S. Tajima, J. Levallois, and M. Narbone.
Liu, Wei; Lang, Ming; Youdim, Moussa B H; Amit, Tamar; Sun, Yewei; Zhang, Zaijun; Wang, Yuqiang; Weinreb, Orly
2016-10-01
Current novel therapeutic approach suggests that multifunctional compounds with diverse biological properties and a single bioavailability and pharmacokinetic metabolism, will produce higher significant advantages in treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Based on this rational, a new class of cholinesterase (ChE)-monoamine oxidase (MAO) inhibitors were designed and synthesized by amalgamating the propargyl moiety of the irreversible selective MAO-B inhibitor, neuroprotective/neurorestorative anti-Parkinsonian drug, rasagiline, into the "N-methyl" position of the ChE inhibitor, anti-AD drug rivastigmine. Initially, we examined the MAO and ChE inhibitory effect of these novel compounds, MT series in vitro and in vivo. Among MT series, MT-031 exhibited higher potency as a dual MAO-A and ChE inhibitor compared to other compounds in acute-treated mice. Additionally, MT-031 was found to increase the striatal levels of dopamine (DA), serotonin (5-HT) and norepinephrine (NE), and prevent the metabolism of DA and 5-HT. Finally, we have demonstrated that MT-031 exerted neuroprotective effect against H2O2-induced neurotoxicity and reactive oxygen species generation in human neuroblastoma SH-SY5Y cells. These findings provide evidence that MT-031 is a potent brain permeable novel multifunctional, neuroprotective and MAO-A/ChE inhibitor, preserves in one molecule entity some of the beneficial properties of its parent drugs, rasagiline and rivastigmine, and thus may be indicated as novel therapeutic approach for AD. Copyright © 2016 Elsevier Ltd. All rights reserved.
Measurement of a Neutrino-Induced Charged Current Single Neutral Pion Cross Section at MicroBooNE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hackenburg, Ariana
Micro Booster Neutrino Experiment (MicroBooNE) is a Liquid Argon Time Projection Chamber (LArTPC) operating in the Booster Neutrino Beamline at Fermi National Accelerator Laboratory. MicroBooNE's physics goals include studying short baslinemore » $$\
Early Energetic Particle Irradiation of the HED Parent Body Regolith
NASA Technical Reports Server (NTRS)
Bogard, D. D.; Garrison, D. H.; Rao, M. N.
1996-01-01
Previous studies have shown that many individual grains within the dark phase of the Kapoeta howardite were irradiated with energetic particles while residing on the surface of the early HED regolith. Particle tracks in these grains vary in density by more than an order of magnitude and undoubtedly were formed by energetic heavy (Fe) ions associated with early solar flares. Early Irradiation of HED Regolith: Concentrations of excess Ne alone are not sufficient to decide between competing galactic and solar irradiation models. However, from recent studies of depth samples of oriented lunar rocks, we have shown that the cosmogenic 21-Ne/22-Ne ratio produced in feldspar differs substantially between Galactic Cosmic Radiation (GCR) and solar protons, and that this difference is exactly that predicted from cross-section data. Using Ne literature data and new isotopic data we obtained on acid-etched, separated feldspar from both the light and dark phases of Kapoeta, we derive 21-Ne/22-Ne = 0.80 for the recent GCR irradiation and 21-Ne/22-Ne = 0.68 for the early regolith irradiation. This derived ratio indicates that the early Ne production in the regolith occurred by both galactic and solar protons. If we adopt a likely one-component regolith model in which all grains were exposed to galactic protons but individual grains had variable exposure to solar protons, we estimate that this early GCR irradiation lasted for about 3-6 m.y. More complex two-component regolith models involving separate solar and galactic irradiation would permit this GCR age to be longer. Higher-energy solar protons would permit the GCR to be longer. Higher-energy solar protons would permit the GCR age to be shorter. Further, cosmogenic 126(Xe) in Kapoeta dark is no more than a factor of about 2 higher than that observed in Kapoeta light. Because 126(Xe) can only be formed by galactic protons and not solar protons, these data support a short GCR irradiation for the HED regolith. This would also be the maximum time peRiod for the solar irradiation. Various asteroidal regolith models, based on Monte Carlo modeling of impact rates as a function of size and on irradiation features of meteorites, predict surface exposure times of about 0.1 to 10 m.y., and depend on such factors as gravity, rock mechanical properties, and micrometeoroid flux. Because the depth at which solar Fe tracks are produced (is much less than 1 micrometer) is much less than the depth at which Solar Cosmic Rays (SCR) Ne is produced (about 1 cm), for a reasonably well-stirred HED regolith the "surface exposure time" for SCR 21-Ne production should be significantly longer than that for solar tracks and some other surface irradiation features. Enhanced Solar Proton Irradiation: For bulk samples of Kapoeta dark feldspar and a one-component regolith model, the derived ratio of 21-Ne/22-Ne = 0.68 implies that the early production ratio of SCR 21-Ne to GCR 21-Ne was about 0.5-1.5. This ratio is independent of any assumptions about the fraction of dark grains that are irradiated or of the variability in the degree of solar irradiation among grains. The 21-Ne SCR/GCR ratio indirectly derived from bulk Kapoeta pyroxene is somewhat larger, as is the ratio derived for simple two-component regolith models. Individual feldspar grains that were extensively solar irradiated would require even larger 21-Ne SCR/GCR production ratios. In contrast, the theoretical SCR/GCR production ratio for lunar feldspar with 0 g/CM2 shield ing is is less than or equal to 2, and the lowest ratio observed in near-surface samples of lunar anorthosites is less than or equal to 1. Considering the greater solar distance of Vesta (compared to the Moon), the likelihood that SCR 21-Ne was acquired under some shielding where production rates are lower, and the likelihood that the exposure time to galactic protons exceeded the exposure time to solar protons because of their very different penetration depths, the 21-Ne SCR/GCR production ratio on the HED parent body was probably < 0.1. The relatively large difference between the derived 21-Ne SCR/GCR ratio in Kapoeta dark feldspar and the estimated production ratio strongly indicates that the early solar irradiation involved a flux -20-50x the recent solar flux. This enhanced proton flux was probably associated with an overall greater solar activity in the first approximately 10(exp 7) to 10(exp 8) years of solar history.
50 CFR 648.87 - Sector allocation.
Code of Federal Regulations, 2014 CFR
2014-10-01
... sector's allocation of the overall ACL available to all vessels issued a limited access NE multispecies... the GB cod ACL available to all vessels issued a limited access NE multispecies permit, that sector... this example, if the overall GB cod ACL available to all vessels issued a limited access NE...
76 FR 16530 - Establishment of Class E Airspace; Creighton, NE
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-24
...-1170; Airspace Docket No. 10-ACE-13] Establishment of Class E Airspace; Creighton, NE AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes Class E airspace... Federal Register a notice of proposed rulemaking to establish Class E airspace for Creighton, NE, creating...
75 FR 64971 - Proposed Establishment of Class E Airspace; Central City, NE
Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-21
...-0837; Airspace Docket No. 10-ACE-10] Proposed Establishment of Class E Airspace; Central City, NE...: This action proposes to establish Class E airspace at Central City, NE. Controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAP) at Central City Municipal--Larry...
A simple kinetic model of a Ne-H2 Penning-plasma laser
NASA Astrophysics Data System (ADS)
Petrov, G. M.; Stefanova, M. S.; Pramatarov, P. M.
1995-09-01
A simple kinetic model of the Ne-H2 Penning-Plasma Laser (PPL) (NeI 585.3 nm) is proposed. The negative glow of a hollow cathode discharge at intermediate pressures is considered as the active medium. The balance equations for the upper and lower laser levels, electrons, ions and electron energy are solved. The dependences of the laser gain on the discharge conditions (Ne and H2 partial pressures, discharge current) are calculated and measured. The calculated values are in a good agreement with the experimental data.
NASA Astrophysics Data System (ADS)
Capdeville, H.; Pédoussat, C.; Pitchford, L. C.
2002-02-01
The work presented in the article is a study of the heavy particle (ion and neutral) energy flux distributions to the cathode in conditions typical of discharges used for luminous signs for advertising ("neon" signs). The purpose of this work is to evaluate the effect of the gas mixture on the sputtering of the cathode. We have combined two models for this study: a hybrid model of the electrical properties of the cathode region of a glow discharge and a Monte Carlo simulation of the heavy particle trajectories. Using known sputtering yields for Ne, Ar, and Xe on iron cathodes, we estimate the sputtered atom flux for mixtures of Ar/Ne and Xe/Ne as a function of the percent neon in the mixture.
Study of Electromagnetic Interactions with the MicroBooNE Detector
NASA Astrophysics Data System (ADS)
Caratelli, David; MicroBooNE Collaboration
2017-01-01
MicroBooNE is an experiment which employs the Liquid Argon Time Projection Chamber (LArTPC) detector technology to study neutrinos produced with the Fermilab Booster Neutrino Beam. As for any accelerator-based detector interested in studying neutrino oscillations, it is essential to be able to identify and reconstruct the kinematic properties of electrons and photons produced in μν and νe interactions. We report current progress in reconstructing electron and photon electromagnetic (EM) showers using data from the MicroBooNE LArTPC. These studies cover EM showers in the tens to hundreds of MeV energy range; they lay the foundation for MicroBooNE's investigation of the excess of low-energy EM events reported by MiniBooNE, and are of interest to the wider LArTPC neutrino community.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Könnecke, Mark; Akeroyd, Frederick A.; Bernstein, Herbert J.
2015-01-30
NeXus is an effort by an international group of scientists to define a common data exchange and archival format for neutron, X-ray and muon experiments. NeXus is built on top of the scientific data format HDF5 and adds domain-specific rules for organizing data within HDF5 files, in addition to a dictionary of well defined domain-specific field names. The NeXus data format has two purposes. First, it defines a format that can serve as a container for all relevant data associated with a beamline. This is a very important use case. Second, it defines standards in the form of application definitionsmore » for the exchange of data between applications. NeXus provides structures for raw experimental data as well as for processed data.« less
Focal mechanisms and the stress regime in NE and SW Tanzania, East Africa
NASA Astrophysics Data System (ADS)
Brazier, Richard A.; Nyblade, Andrew A.; Florentin, Juliette
2005-07-01
We report 12 new focal mechanisms from earthquakes in NE and SW Tanzania where the stress regime within the East African rift system is not well constrained. Focal mechanisms for events at the intersection of the Lake Tanganyika and Rukwa rifts in SW Tanzania indicate a complicated stress pattern with possible dextral strike-slip motion on some faults but oblique motion on others (either sinistral on NW striking faults or dextral on NE striking faults). Within the Rukwa rift, focal mechanisms indicate normal dip-slip motion with NE-SW opening. In NE Tanzania where the Eastern rift impinges on the margin of the Tanzania Craton, fault motions are consistent with a zone of distributed block faults and sub E-W extension. All twelve earthquakes likely nucleated within the crust.
Könnecke, Mark; Akeroyd, Frederick A.; Bernstein, Herbert J.; ...
2015-01-30
NeXus is an effort by an international group of scientists to define a common data exchange and archival format for neutron, X-ray and muon experiments. NeXus is built on top of the scientific data format HDF5 and adds domain-specific rules for organizing data within HDF5 files, in addition to a dictionary of well defined domain-specific field names. The NeXus data format has two purposes. First, it defines a format that can serve as a container for all relevant data associated with a beamline. This is a very important use case. Second, it defines standards in the form of application definitionsmore » for the exchange of data between applications. As a result, NeXus provides structures for raw experimental data as well as for processed data.« less
Online platforms to teach Nutrition Education to children: a non-systematic review.
Domínguez Rodríguez, Alejandro; Cebolla Marti, Ausiàs Josep; Oliver-Gasch, Elia; Baños-Rivera, Rosa María
2016-11-29
Childhood obesity is now considered a worldwide problem. Nutrition Education (NE) has been identified as a key factor in preventing overweight and obesity in children. In recent years, there has been an increase in the interest in innovative ways to teach this knowledge to children, mainly through the use of the Internet. Review and analyze the available evidence about programs focused on NE for children through the use of the Internet. Three different ways were found to deliver NE over the Internet to children: platforms designed to communicate with other peers or professionals; platforms designed to provide NE through the contents included in the web tool; and platforms designed to provide NE through the contents included in the web tool and automated feedback. Most of these programs were effective in achieving the objectives established. Although the use of Internet platforms to teach NE to children has been shown to be effective, the amount of evidence is still scarce. Some of the main advantages the Internet provides are: the opportunity to put the children in contact with education and health professionals; children can keep a record of the food consumed; and it is a more attractive and interesting way for children to learn NE, compared to traditional methods.
Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas; Okonogi, Siriporn
2017-01-01
Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO.
Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas
2017-01-01
Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO. PMID:29190663
Peterson, Amanda D; Goodell, L Suzanne; Hegde, Archana; Stage, Virginia C
2017-05-01
To develop a theory that explains the process of how teachers' perception of multilevel policies may influence nutrition education (NE) teaching strategies in Head Start preschools. Semistructured telephone interviews. North Carolina Head Start preschools. Thirty-two Head Start teachers. All interviews were transcribed verbatim. Following a grounded theory approach, authors coded interview data for emergent themes. Two primary themes emerged during analysis, including teachers' policy perceptions and teacher-perceived influence of policy on NE. A theoretical model was developed to explain how teachers' perceptions of policies influenced NE (eg, teaching strategies) in the classroom. Teachers discussed multiple policy areas governing their classrooms and limiting their ability to provide meaningful and consistent NE. How teachers perceived the level of regulation in the classroom (ie, high or low) influenced the frequency with which they used specific teaching strategies. Despite federal policies supporting the provision of NE, teachers face competing priorities in the classroom (eg, school readiness vs NE) and policies may conflict with standardized NE curricula. To understand how Head Start centers develop local policies, additional research should investigate how administrators interpret federal and state policies. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.
Parmer, Sondra M; Salisbury-Glennon, Jill; Shannon, David; Struempler, Barbara
2009-01-01
To examine the effects of a school garden on children's fruit and vegetable knowledge, preference, and consumption. Self-report questionnaires, interview-style taste and rate items, lunchroom observations. An elementary school. Second-grade students (n = 115). Participants were assigned to one of 3 groups: (1) nutrition education and gardening (NE+G) treatment group, (2) nutrition education only (NE) treatment group, or (3) control group (CG). Both treatment groups received classroom instruction, and the NE+G group also received a school gardening experience. Fruit and vegetable knowledge, preference, and consumption. Analyses of variance (alpha = .05). Participants in the NE+G and NE treatment groups exhibited significantly greater improvements in nutrition knowledge and taste ratings than did participants in the CG. Moreover, the NE+G group was more likely to choose and consume vegetables in a lunchroom setting at post-assessment than either the NE or CG groups. School gardens as a component of nutrition education can increase fruit and vegetable knowledge and cause behavior change among children. These findings suggest that school administrators, classroom teachers, and nutrition educators should implement school gardens as a way to positively influence dietary habits at an early age.
Kessenbrock, Kai; Fröhlich, Leopold; Sixt, Michael; Lämmermann, Tim; Pfister, Heiko; Bateman, Andrew; Belaaouaj, Azzaq; Ring, Johannes; Ollert, Markus; Fässler, Reinhard; Jenne, Dieter E.
2008-01-01
Neutrophil granulocytes form the body’s first line of antibacterial defense, but they also contribute to tissue injury and noninfectious, chronic inflammation. Proteinase 3 (PR3) and neutrophil elastase (NE) are 2 abundant neutrophil serine proteases implicated in antimicrobial defense with overlapping and potentially redundant substrate specificity. Here, we unraveled a cooperative role for PR3 and NE in neutrophil activation and noninfectious inflammation in vivo, which we believe to be novel. Mice lacking both PR3 and NE demonstrated strongly diminished immune complex–mediated (IC-mediated) neutrophil infiltration in vivo as well as reduced activation of isolated neutrophils by ICs in vitro. In contrast, in mice lacking just NE, neutrophil recruitment to ICs was only marginally impaired. The defects in mice lacking both PR3 and NE were directly linked to the accumulation of antiinflammatory progranulin (PGRN). Both PR3 and NE cleaved PGRN in vitro and during neutrophil activation and inflammation in vivo. Local administration of recombinant PGRN potently inhibited neutrophilic inflammation in vivo, demonstrating that PGRN represents a crucial inflammation-suppressing mediator. We conclude that PR3 and NE enhance neutrophil-dependent inflammation by eliminating the local antiinflammatory activity of PGRN. Our results support the use of serine protease inhibitors as antiinflammatory agents. PMID:18568075
Stahl, Jutta; Gibbons, Henning
2007-03-01
The aim of the present study was to investigate the functional significance of error (related) negativity Ne/ERN and individual differences in human action monitoring. A response-conflict model of Ne/ERN should be tested applying a stop-signal paradigm. After a few modifications of Ne/ERN response-conflict theory (Yeung N, Botvinick MM, Cohen JD. The neural basis of error detection: conflict monitoring and the error-related negativity. Psychological Review 2004:111(4);931-959), strength and time course of response conflict could be modeled as a function of stop-signal delay. In Experiment 1, 35 participants performed a visual two-choice response-time task but tried to withhold the response if an auditory stop signal was presented. Probability of stopping errors was held at 50% using variable delays between visual and auditory stimuli. Experiment 2 (n=10) employed both auditory go and stop signals and confirmed that Ne/ERN effects are due to conflict induced by the auditory stop signal, and not the mere presence or absence of an additional stimulus. As predicted, amplitudes of both the stimulus-locked and response-locked Ne/ERN were largest for non-stopped responses, followed by successfully stopped and go responses. However, independently of response type Ne/ERN also increased with increasing stop-signal delay. Since longer delay invokes stronger response conflict, results specifically support the notion of Ne/ERN reflecting response-conflict monitoring. Furthermore, individual differences related to measures of response control and behavioral control were observed. Both low response control estimated from stop-task performance and high psychometric impulsivity were accompanied by smaller Ne/ERN amplitude on stop trials, suggesting reduced response-conflict monitoring. The present study supported the response-conflict view of Ne/ERN. Furthermore, the observed relationship between impulsivity and Ne/ERN amplitude suggested that individuals with low behavioral control were characterized by lower activity in anterior cingulate cortex, the neural generator of Ne/ERN, in situations of strong response conflict. The present study, for the first time, employed a stop-signal paradigm to verify predictions regarding the temporal dynamics of response-conflict processing as derived from response-conflict theory of ERN.
Rengaraj, Deivendran; Truong, Anh Duc; Ban, Jihye; Lillehoj, Hyun S.; Hong, Yeong Ho
2017-01-01
Objective Despite an increasing number of investigations into the pathophysiology of necrotic enteritis (NE) disease, etiology of NE-associated diseases, and gene expression profiling of NE-affected tissues, the microRNA (miRNA) profiles of NE-affected poultry have been poorly studied. The aim of this study was to induce NE disease in the genetically disparate Fayoumi chicken lines, and to perform non-coding RNA sequencing in the intestinal mucosal layer. Methods NE disease was induced in the Fayoumi chicken lines (M5.1 and M15.2), and non-coding RNA sequencing was performed in the intestinal mucosal layer of both NE-affected and uninfected chickens to examine the differential expression of miRNAs. Next, quantitative real-time polymerase chain reaction (real-time qPCR) was performed to further examine four miRNAs that showed the highest fold differences. Finally, bioinformatics analyses were performed to examine the four miRNAs target genes involvement in the signaling pathways, and to examine their interaction. Results According to non-coding RNA sequencing, total 50 upregulated miRNAs and 26 downregulated miRNAs were detected in the NE-induced M5.1 chickens. While 32 upregulated miRNAs and 11 downregulated miRNAs were detected in the NE-induced M15.2 chickens. Results of real-time qPCR analysis on the four miRNAs (gga-miR-9-5p, gga-miR-20b-5p, gga-miR-196-5p, and gga-let-7d) were mostly correlated with the results of RNAseq. Overall, gga-miR-20b-5p was significantly downregulated in the NE-induced M5.1 chickens and this was associated with the upregulation of its top-ranking target gene, mitogen-activated protein kinase, kinase 2. Further bioinformatics analyses revealed that 45 of the gene targets of gga-miR-20b-5p were involved in signal transduction and immune system-related pathways, and 35 of these targets were predicted to interact with each other. Conclusion Our study is a novel report of miRNA expression in Fayoumi chickens, and could be very useful in understanding the role of differentially expressed miRNAs in a NE disease model. PMID:28111433
NASA Astrophysics Data System (ADS)
Amari, Sachiko
2008-05-01
There are several isotopically distinct noble gas components in meteorites. Of them, Ne-E(L), heavily enriched in 22Ne, is carried by graphite with a range of density (1.6 - 2.2 g/cm3). Bulk (=aggregates) noble gas analysis of graphite separates from the Murchison meteorite indicate that a dominant source of 22Ne is 22Na (T1/2 = 2.6 a) with varying proportions of 22Ne via 14N(α,γ)18F(e+ν)18O(α,γ)22Ne with density. Low-density graphite grains, from their isotopic signatures, are believed to have formed in supernovae. Examinations of both bulk and single-grain analyses of low-density graphite grains (Amari et al., 1995; Nichols et al., 1994) indicate that all 22Ne in low-density graphite grains is from the decay of 22Na that was produced in the O/Ne zone in supernovae. One may argue why implanted 20,22Ne was not observed in the grains, considering the fact that the mass fraction of 20Ne is 5 orders of magnitude larger than that of 22Na. Croat et al. (2003) observed TiC subgrains inside low-density graphite grains have amorphous rims with the thickness of 3 to 15 nm, indicating atom bombardment from the surrounding gas. Assuming the gas is He, they estimated the velocity is 50 km/s or less. If the relative velocities between the Ne and the graphite grains are in that range, the penetration depth into the graphite grains is 2nm. Such shallow surface layers would be sputtered once the grains hit the reverse shock and keep traveling into the hot H-rich region (Nozawa et al, 2007). It remains to be seen whether or not 22Na in higher-density graphite is from supernovae or novae, or both. Amari, S. et al. 1995, Geochim. Cosmochim. Acta, 59, 1411 Croat, T.K. et al. 2003, Geochim. Cosmochim. Acta, 67, 4705 Nichols R.H. et al. 1994, Meteoritics, 29, 510 Nozawa, T. et al. 2007 ApJ, 666, 955
Neutrino-nucleus neutral current elastic interactions measurement in MiniBooNE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Perevalov, Denis
2009-12-01
The MiniBooNE experiment at the Fermi National Accelerator Laboratory (Fermilab) was designed to search for v μ → v e neutrino oscillations at Δm 2 ~ 1 eV 2 using an intense neutrino flux with an average energy E v ~ 700 MeV. From 2002 to 2009 MiniBooNE has accumulated more than 1.0 x 10 21 protons on target (POT) in both neutrino and antineutrino modes. MiniBooNE provides a perfect platform for detailed measurements of exclusive and semiinclusive neutrino cross-sections, for which MiniBooNE has the largest samples of events up to date, such as neutral current elastic (NCE), neutral currentmore » π 0, charged current quasi-elastic (CCQE), charged current π +, and other channels. These measured cross-sections, in turn, allow to improve the knowledge of nucleon structure. This thesis is devoted to the study of NCE interactions. Neutrino-nucleus neutral current elastic scattering (vN → vN) accounts for about 18% of all neutrino interactions in MiniBooNE. Using a high-statistics, high purity sample of NCE interactions in MiniBooNE, the flux-averaged NCE differential cross-section has been measured and is being reported here. Further study of the NCE cross-section allowed for probing the structure of nuclei. The main interest in the NCE cross-section is that it may be sensitive to the strange quark contribution to the nucleon spin, Δs, this however requires a separation of NCE proton (vp → vp) from NCE neutron (vn → vn) events, which in general is a challenging task. MiniBooNE uses a Cherenkov detector, which imposes restrictions on the measured nucleon kinematic variables, mainly due to the impossibility to reconstruct the nucleon direction below the Cherenkov threshold. However, at kinetic energies above this threshold MiniBooNE is able to identify NCE proton events that do not experience final state interactions (FSI). These events were used for the Δs measurement. In this thesis MiniBooNE reports the NCE (n+p) cross-section, the measurement of the axial mass, M A, and the Δs parameter from the NCE data.« less
Measurement of the reaction 18O(α,n)21Ne
NASA Astrophysics Data System (ADS)
Best, A.; Falahat, S.; Görres, J.; Couder, M.; deBoer, R.; Güray, R. T.; Kontos, A.; Kratz, K.-L.; LeBlanc, P. J.; Li, Q.; O'Brien, S.; Özkan, N.; Sonnabend, K.; Talwar, R.; Uberseder, E.; Wiescher, M.
2013-04-01
Background: The reaction 18O(α,n)21Ne is a part of the reaction chains leading to the production of 19F and 22Ne during He burning in low-mass and massive AGB stars, respectively. Additionally, it has been observed as a strong background source in the measurement of other (α,n) reactions.Purpose: Previously low-energy 18O(α,n)21Ne cross section data have only been available in a non-peer-reviewed form. An improved measurement of this reaction has been done to both clarify its astrophysical influence as well as to provide background yield data for future (α,n) experiments.Method: The 18O(α,n(0+1)) reaction has been measured with a moderating neutron detector. In addition the (α,n1γ) channel has been measured independently by observation of the characteristic 350.7 keV γ transition in 21Ne. The reaction cross section at energies above Eα=1100 keV was determined by a simultaneous R-matrix fit to both channels. The strengths of the two lowest-energy resonances at Eα=959 keV and Eα=1066 keV were analyzed separately using individual Breit-Wigner fits.Results: The cross section of both reaction channels, 18O(α,n0)21Ne and 18O(α,n1γ)21Ne, was determined from the threshold energies at 851 keV and 1280 keV, respectively, to 2300 keV. A new reaction rate has been deduced for the temperature range of 0.1 GK to 10 GK. A previously reported resonance at Eα=888 keV is explained as background from the contaminant reaction 17O(α,n)20Ne.Conclusions: In general, our reaction rate is slightly lower than the reaction rates in recent compilations. At temperatures below 0.2 GK the present rate is significantly lower because it could be shown that the lowest reported resonance is background from the reaction 17O(α,n)20Ne that has been wrongly assigned to 18O(α,n)21Ne.
Neutrino-nucleus neutral current elastic interactions measurement in MiniBooNE
NASA Astrophysics Data System (ADS)
Perevalov, Denis
The MiniBooNE experiment at the Fermi National Accelerator Laboratory (Fermilab) was designed to search for numu → nu e neutrino oscillations at Deltam 2 ˜ 1 eV2 using an intense neutrino flux with an average energy Enu ˜ 700 MeV. From 2002 to 2009 MiniBooNE has accumulated more than 1.0x1021 protons on target (POT) in both neutrino and antineutrino modes. MiniBooNE provides a perfect platform for detailed measurements of exclusive and semi-inclusive neutrino cross-sections, for which MiniBooNE has the largest samples of events up to date, such as neutral current elastic (NCE), neutral current pi 0, charged current quasi-elastic (CCQE), charged current pi +, and other channels. These measured cross-sections, in turn, allow to improve the knowledge of nucleon structure. This thesis is devoted to the study of NCE interactions. Neutrino-nucleus neutral current elastic scattering (nuN → nu N) accounts for about 18% of all neutrino interactions in MiniBooNE. Using a high-statistics, high purity sample of NCE interactions in MiniBooNE, the flux-averaged NCE differential cross-section has been measured and is being reported here. Further study of the NCE cross-section allowed for probing the structure of nuclei. The main interest in the NCE cross-section is that it may be sensitive to the strange quark contribution to the nucleon spin, Deltas, this however requires a separation of NCE proton (nup → nu p) from NCE neutron (nun → nun ) events, which in general is a challenging task. MiniBooNE uses a Cherenkov detector, which imposes restrictions on the measured nucleon kinematic variables, mainly due to the impossibility to reconstruct the nucleon direction below the Cherenkov threshold. However, at kinetic energies above this threshold MiniBooNE is able to identify NCE proton events that do not experience final state interactions (FSI). These events were used for the Deltas measurement. In this thesis MiniBooNE reports the NCE (n+p) cross-section, the measurement of the axial mass, MA, and the Delta s parameter from the NCE data.
Parental perception and factors associated with treatment strategies for primary nocturnal enuresis.
Tai, Thomson T; Tai, Brent T; Chang, Yu-Jun; Huang, Kuo-Hsuan
2017-06-01
The aim was to investigate the factors influencing parents seeking reasonable managements for their child and their overall outlook toward primary nocturnal enuresis (PNE). We recruited 93 children with PNE from enuresis clinics and requested their parents to complete questionnaires regarding their child's medical history and behavior, their methods for coping with PNE, and their perception of enuresis. Logistic regression models were applied to investigate factors influencing the parents to adopt a positive approach toward enuresis and to subsequently seek a medical consultation. One-third of the parents had an encouraging attitude toward children with PNE, whereas slightly less than half reacted with anger. The more educated the father or the younger the child with NE, the larger the possibility of the parents utilizing a positive approach, such as encouragement, for coping with NE. Factors that influenced parents to seek medical consultation for NE were socioeconomic status, maternal educational level, and the age and birth order of their child. From our results, angry and frustrated parents (43.0%) were significantly more likely to punish their child for bedwetting than were parents who approached NE positively (comfort and encouragement; 33.3%). A lack of encouragement may negatively affect the self-esteem of children with NE. Moreover, an individual's self-esteem or confidence, both of which can help them eliminate NE, determines the person's behavioral response to bedwetting. In our study, approximately 50% of the parents who approached NE positively (comfort and encouragement) or inconsistently (ambivalence) reported that they comforted their child after bedwetting. Nearly half the parents reacted angrily to children with NE, and some parents even punished their child. The parents' socioeconomic background, education, and the age and birth order of the child were the factors associated with their seeking active treatment for NE. A father's education and young age of the child were factors that influenced parents who preferred positive approaches, such as encouragement, for coping with NE. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Latagliata, Emanuele Claudio; Saccoccio, Pamela; Milia, Chiara; Puglisi-Allegra, Stefano
2016-03-01
Drug-associated cues exposure to induce extinction is a useful strategy to contrast cue-induced drug seeking. Treatments aimed at reducing motivational properties of cues are considered highly promising since they could decrease their ability to induce drug-conditioned behaviors. Norepinephrine (NE) in the medial prefrontal cortex (mPFC) is critical for attribution of motivational salience to highly salient stimuli, suggesting a major role in prelimbic (PL) mpFC to modulate the motivational properties of drug-related cues, invigorating them, and consequently, delaying extinction. To investigate if NE in PL fosters the maintenance of drug-seeking behavior, we assessed its role on amphetamine-induced conditioned place preference (CPP). Moreover, to affirm the specificity of NE in PL, we also assessed the role of NE in the infralimbic (IL) mPFC. The effects of selective NE depletion in the PL or in the IL of C57BL/6J mice were assessed on the expression of amphetamine-induced CPP before and after extinction procedure. NE-depleted mice in PL extinguished preference for Amph-paired chamber long before sham animals. By contrast, IL-depleted animals maintained place preference for more than 4 weeks after the procedure of extinction, having at that moment interrupted the test. Inactivation of NE in PL cortex blunts amphetamine-induced CPP, thus fostering extinction and showing to be critical for the maintenance of conditioned Amph-seeking behavior. Opposite effects of NE depletion in IL, seemingly in agreement with literature on extinction, are discussed in terms of balance of activity between PL and IL in extinction.
Mahata, S K; Mandal, A; Ghosh, A
1988-01-01
A single intraperitoneal (IP) melatonin injection (0.5 mg/100 g body wt.) caused an increase in norepinephrine (NE) fluorescence and elevation of NE content in newly-hatched pigeons (Columba livia), but a reduction of NE fluorescence and depletion of NE content in the adrenal medulla of newly-hatched crows (Corvus splendens) after 0.5 h of treatment. In contrast, in adults melatonin caused increase in NE fluorescence and elevation of NE content only in the parakeet (Psittacula krameri). Half an hour of IP melatonin treatment (0.5 mg/100 g body wt.) induced release of epinephrine (E) from the adrenal medulla of newly-hatched pigeon and parakeet. In contrast, in the adults melatonin caused more than a two-fold increase in E in the pigeon, and a significant increase in the crow. Single IP melatonin injection (0.5 mg/100 g body wt.) caused hypoglycemia in the newly-hatched parakeet and adult pigeon, and hyperglycemia in newly-hatched pigeon after 0.5 h of treatment. Melatonin failed to regulate glucose homoeostasis in newly-hatched and adult crow. Splanchnic denervation of the left adrenal gland was performed in the adult pigeon. The right adrenal served as the innervated gland. Melatonin-induced modulation of catecholamines following a single IP injection (0.5 mg/100 g body wt.) revealed significant increases in NE fluorescence and NE content at 4 and 12 h after treatment in the denervated gland only, which gradually approached normal levels 9 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
NASA Astrophysics Data System (ADS)
Matchan, Erin L.; Honda, Masahiko; Barrows, Timothy T.; Phillips, David; Chivas, Allan R.; Fifield, L. Keith; Fabel, Derek
2018-01-01
In this study we investigate the cosmogenic neon component in olivine samples from a vertical profile in order to quantify muogenic 21Ne production in this mineral. Samples were collected from an 11 m thick Eocene basalt profile in the Eastern Highlands of southeastern Australia. An eruption age of 54.15 ± 0.36 Ma (2σ) was determined from 40Ar/39Ar step-heating experiments (n = 6) on three whole-rock samples. A 36Cl profile on the section indicated an apparent steady state erosion rate of 4.7 ± 0.5 m Ma-1. The eruption age was used to calculate in situ produced radiogenic 4He and nucleogenic 3He and 21Ne concentrations in olivine. Olivine mineral separates (n = 4), extracted from the upper two metres of the studied profile, reveal cosmogenic 21Ne concentrations that attenuate exponentially with depth. However, olivine (Fo68) extracted from below 2 m does not contain discernible 21Ne aside from magmatic and nucleogenic components, with the exception of one sample that apparently contained equal proportions of nucleogenic and muogenic neon. Modelling results suggest a muogenic neon sea-level high-latitude production rate of 0.02 ± 0.04 to 0.9 ± 1.3 atoms g-1 a-1 (1σ), or <2.5% of spallogenic cosmogenic 21Ne production at Earth's surface. These data support a key implicit assumption in the literature that accumulation of muogenic 21Ne in olivine in surface samples is likely to be negligible/minimal compared to spallogenic 21Ne.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-27
... for addenda to the FY 2010 sector operations plans and contracts, and the supplemental environmental... sector operations plans and contracts and allocations of annual catch entitlement (ACE) for 17 NE... addenda to FY 2010 NE multispecies sector operations plans and contracts that would add certain exemptions...
Cytosolic DNA sensing genes expression in the intestinal mucosa of necrotic enteritis chickens
USDA-ARS?s Scientific Manuscript database
Poultry farms often report necrotic enteritis (NE) outbreaks as a result of the inappropriate use of antibiotics in the feed. Several studies have reported that the genes related to intestine and immune system are significantly altered in response to NE. We induce NE in two chicken lines that are ...
Cosmogenic Ne-21 Production Rates in H-Chondrites Based on Cl-36 - Ar-36 Ages
NASA Technical Reports Server (NTRS)
Leya, I.; Graf, Th.; Nishiizumi, K.; Guenther, D.; Wieler, R.
2000-01-01
We measured Ne-21 production rates in 14 H-chondrites in good agreement with model calculations. The production rates are based on Ne-21 concentrations measured on bulk samples or the non-magnetic fraction and Cl-36 - Ar-36 ages determined from the metal phase.
U.S. Nuclear Engineering Education: Status and Prospects.
ERIC Educational Resources Information Center
National Academy of Sciences - National Research Council, Washington, DC. Commission on Engineering and Technical Systems.
This study examines the status of and outlook for nuclear engineering (NE) in the United States. The study resulted from a concern about the downward trends in student enrollments in NE, in both graduate and undergraduate programs. Concerns have also been expressed about the declining number of U.S. university NE departments and programs, the…
USDA-ARS?s Scientific Manuscript database
Necrotic enteritis (NE) is a re-emerging disease as a result of an increased restriction on the use of antibiotics in poultry. However, the molecular mechanisms underlying the pathology of NE are unclear. Therefore, we carried out small RNA transcriptome analysis in an experimentally induced NE m...
Noble Gases in the Hamlet Meteorite (LL4)
NASA Astrophysics Data System (ADS)
Amari, S.; Sabe, Y.; Shiraishi, T.; Matsuda, J.
2014-09-01
We analyzed noble gases in a bulk sample and an HF-HCl residue of Hamlet (LL4). The Xe composition of the residue shows that no diamond is contained in the residue. The 20Ne/22Ne ratio of Hamlet Ne-Q has been determined to be 11.0 ± 0.5.
Rotifer neuropharmacology--III. Adrenergic drug effects on Brachionus plicatilis.
Keshmirian, J; Nogrady, T
1987-01-01
Norepinephrine (NE) induces three pharmacological effects in Brachionus plicatilis. As a result of excitation the rate of ciliary motion and swimming increases, and the animals flip their foot constantly at a rapid rate. This rapid foot flipping was used as a specific model to measure adrenergic effects in B. plicatilis. Phenylephrine induces the same effect at identical efficacy, while isoproterenol and salbutamol, two beta-agonists, show one-half and one-tenth NE efficacy. The beta blocker propranolol and the alpha blocker tolazoline both antagonize foot flipping induced by NE. However, propranolol shows antagonism because it causes foot paralysis by itself. Timolol, another beta blocker but without the membrane effect of propranolol, does not antagonize the alpha receptor mediated NE effect, nor does it cause foot paralysis. Propranolol, timolol and tolazoline also show agonist activity, inducing foot flipping. NE does not antagonize the foot paralysis induced by propranolol, only its anesthetic effect by delaying its onset. These results indicate that the foot flipping induced by NE is a receptor-mediated alpha adrenergic effect, while the foot paralysis is caused by membrane phenomena.
Goniakowska-Witalińska, L; Zaccone, G; Fasulo, S; Mauceri, A; Licata, A; Youson, J
1995-01-01
Neuroendocrine (NE) cells were localized by electron microscopy and immunocytochemistry in the gill epithelium of bowfin Amia calva. The NE cells are dispersed in whole epithelium of the gill as solitary cells without intraepithelial innervation. All the observed NE cells do not reach the surface of the epithelium. The NE cells are characterized by a large nucleus with patches of condensed chromatin, numerous mitochondria, a well developed Golgi apparatus and a few dense core vesicles of various size scattered in the cytoplasm. Dense core vesicles range from 100 to 560 nm in diameter, while a clear space between the electron dense core ant the limiting membrane ranges from 20 to 240 nm. Immunocytochemical observations reveal the presence of general neuroendocrine markers such as neuro-specific enolase and bioactive substances: serotonin, leu-enkephalin and met-enkephalin. we demonstrated the presence of endothelin - for the first time in fish - and suggested a local paracrine role for the NE cells. Some ultrastructural aspects and the immunocytochemical characteristics of NE cells of bowfin gills are common with those encountered in such cells of other lower vertebrate species.
Megha; Hasan, Gaiti
2017-04-15
Successful completion of animal development is fundamentally reliant on nutritional cues. Surviving periods of nutritional insufficiency requires adaptations that are coordinated, in part, by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation if either insulin signaling or IP 3 /Ca 2+ signaling were downregulated in NE cells. Moreover, an IP 3 R (inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by overexpression of either InR (insulin receptor) or IP 3 R in NE cells of the mutant, suggesting that the two signaling pathways might be functionally compensatory. Furthermore, cultured IP 3 R mutant NE cells, but not neurons, exhibited reduced protein translation. Thus cell-specific regulation of protein synthesis by IP 3 R in NE cells influences protein metabolism. We propose that this regulation helps developing animals survive in poor nutritional conditions. © 2017. Published by The Company of Biologists Ltd.
CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.
McCall, Jordan G; Al-Hasani, Ream; Siuda, Edward R; Hong, Daniel Y; Norris, Aaron J; Ford, Christopher P; Bruchas, Michael R
2015-08-05
The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing, we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin-releasing hormone(+) (CRH(+)) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
Laser Interferometric Measurements of the Physical Properties for He, ne Gases and Their Mixture
NASA Astrophysics Data System (ADS)
Abdel-Moniem, N. M.; El-Masry, M. M.; El-Bradie, B.; El-Mekawy, F. M.
2010-04-01
A Mach-Zehner interferometer MZI illuminated with He-Ne Laser 632.8nm is used for measuring the refractive index for He, Ne gases and their mixture HeNe. The measurements are carried out at different pressures and temperatures. The error factors of the refractive index measurements for He, Ne and HeNe gases are equal to ±1.7×10-5, ±9.5×10-6 and ±7.25×10-5 respectively. Some calculations of the electrical properties are carried out such as the optical permittivity dielectric susceptibility and specific refractivity from the determination of the refractive index. Also, the molecular radii of the gases under investigation are computed then the transport coefficients (diffusion. viscosity and thermal conductivity) are calculated. All of these calculations are carried out at different pressures and temperatures. The experimental results of refractive index for the above mixture are compared with the results estimated using one of the mixing rules and a good agreement is achieved. Also, some physical parameters are compared with other values in another literatures.
Ptak, Christopher; Roesner, Ulyss K.
2017-01-01
Interactions occurring at the nuclear envelope (NE)–chromatin interface influence both NE structure and chromatin organization. Insights into the functions of NE–chromatin interactions have come from the study of yeast subtelomeric chromatin and its association with the NE, including the identification of various proteins necessary for tethering subtelomeric chromatin to the NE and the silencing of resident genes. Here we show that four of these proteins—the silencing factor Sir4, NE-associated Esc1, the SUMO E3 ligase Siz2, and the nuclear pore complex (NPC) protein Nup170—physically and functionally interact with one another and a subset of NPC components (nucleoporins or Nups). Importantly, this group of Nups is largely restricted to members of the inner and outer NPC rings, but it lacks numerous others including cytoplasmically and nucleoplasmically positioned Nups. We propose that this Sir4-associated Nup complex is distinct from holo-NPCs and that it plays a role in subtelomeric chromatin organization and NE tethering. PMID:28883038
Three New Low-Energy Resonances in the 22Ne(p, γ )23Na Reaction
NASA Astrophysics Data System (ADS)
Cavanna, Francesca; Depalo, Rosanna
The neon-sodium (NeNa) cycle drives the synthesis of the elements between 20Ne and 27Al, through a series of proton capture reactions that start from 20Ne, to end with sodium synthesis. This cycle is active in red giant stars (RGB), asymptotic giant branch stars (AGB), in novae as well as in type Ia supernovae. In order to reproduce the observed elemental abundances, the cross sections of the reactions involved in the nucleosynthesis process should be accurately known. The 22Ne(p, γ )23Na reaction rate was very uncertain because of a large number of unobserved resonances lying in the Gamow window. For proton energies below 400 keV, in the literature there were only upper limits for the resonance strengths. A new direct study of the 22Ne(p, γ )23Na reaction has been performed at the Laboratory for Underground Nuclear Astrophysics (LUNA) in Gran Sasso using a windowless gas target and two high-purity germanium detectors. Several resonances have been observed for the first time in a direct experiment.
Angiotensin receptors and norepinephrine neuromodulation: implications of functional coupling.
Gelband, C H; Sumners, C; Lu, D; Raizada, M K
1997-10-31
The objective of this review is to examine the role of neuronal angiotensin II (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have been identified in cardiovascularly relevant areas of the brain: the AT1 and the AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1 and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE) neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor-mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and ultimately leads to an increase in NE transporter, tyrosine hydroxylase and dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+ channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors will be discussed.
Angiotensin receptors and norepinephrine neuromodulation: implications of functional coupling.
Gelband, C H; Sumners, C; Lu, D; Raizada, M K
1998-02-27
The objective of this review is to examine the role of neuronal angiotensin II (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have been identified in cardiovascularly relevant areas of the brain: the AT1 and the AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1 and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE) neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor-mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and ultimately leads to an increase in NE transporter, tyrosine hydroxylase and dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+ channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors will be discussed.
Characterization of the ETEL and HZC 3-inch PMTs for the KM3NeT project
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bormuth, R.; Samtleben, D.; Classen, L., E-mail: kalekin@physik.uni-erlangen.de
2014-11-18
The KM3NeT collaboration constructs a multi-cubic-kilometer scale neutrino telescope in the Mediterranean Sea. The telescope’s detection units, deployed in the deep sea, will be instrumented with facet like Digital Optical Modules (DOMs), each housing 31 three-inch photomultiplier tubes (PMTs) and readout electronics inside of 17-inch pressure resistant glass sphere. Two companies, ET Enterprises Ltd (ETEL) from UK and HZC from China developed new 3-inch PMTs to meet KM3NeT requirements. 126 PMTs of types D783KFLA, D792KFLA, and D793KFLA from ETEL and 7 PMTs of type XP53 from HZC have been delivered to KM3NeT and tested by the KM3NeT groups of NIKHEF-Amsterdammore » and ECAP-Erlangen. Tests have been performed to measure the main PMT parameters listed in the KM3NeT specifications, such as gain, transit time spread, dark rate, fraction of spurious pulses, and quantum efficiency. Methods and results are presented in this report.« less
Cost of non-renewable energy in production of wood pellets in China
NASA Astrophysics Data System (ADS)
Wang, Changbo; Zhang, Lixiao; Liu, Jie
2013-06-01
Assessing the extent to which all bio-fuels that are claimed to be renewable are in fact renewable is essential because producing such renewable fuels itself requires some amount of non-renewable energy (NE) and materials. Using hybrid life cycle analysis (LCA)—from raw material collection to delivery of pellets to end users—the energy cost of wood pellet production in China was estimated at 1.35 J/J, of which only 0.09 J was derived from NE, indicating that only 0.09 J of NE is required to deliver 1 J of renewable energy into society and showing that the process is truly renewable. Most of the NE was consumed during the conversion process (46.21%) and delivery of pellets to end users (40.69%), during which electricity and diesel are the two major forms of NE used, respectively. Sensitivity analysis showed that the distance over which the pellets are transported affects the cost of NE significantly. Therefore the location of the terminal market and the site where wood resources are available are crucial to saving diesel.
Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior
McCall, Jordan G; Siuda, Edward R; Bhatti, Dionnet L; Lawson, Lamley A; McElligott, Zoe A; Stuber, Garret D; Bruchas, Michael R
2017-01-01
Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms. DOI: http://dx.doi.org/10.7554/eLife.18247.001 PMID:28708061
Composite Overview and Composite Aerocover Overview
NASA Technical Reports Server (NTRS)
Caraccio, Anne; Tate, LaNetra; Dokos, Adam; Taylor, Brian; Brown, Chad
2014-01-01
Materials Science Division within the Engineering Directorate tasked by the Ares Launch Vehicle Division (LX-V) and the Fluids Testing and Technology Development Branch (NE-F6) to design, fabricate and test an aerodynamic composite shield for potential Heavy Lift Launch Vehicle infusion and a composite strut that will serve as a pathfinder in evaluating calorimeter data for the CRYOSTAT (cryogenic on orbit storage and transfer) Project. ATP project is to carry the design and development of the aerodynamic composite cover or "bracket" from cradle to grave including materials research, purchasing, design, fabrication, testing, analysis and presentation of the final product. Effort consisted of support from the Materials Testing & Corrosion Control Branch (NE-L2) for mechanical testing, the Prototype Development Branch (NE-L3) for CAD drawing, design/analysis, and fabrication, Materials & Processes Engineering Branch (NE-L4) for project management and materials selection; the Applied Physics Branch (NE-LS) for NDE/NDI support; and the Chemical Analysis Branch (NE-L6) for developmental systems evaluation. Funded by the Ares Launch Vehicle Division and the Fluids Testing and Technology Development Branch will provide ODC
Differentiated norepinephrine spillover in human skeletal muscle.
Karlsson, A K; Elam, M; Lönnroth, P; Sullivan, L; Friberg, P
1997-07-01
Most neurophysiological studies have shown similar sympathetic outflow to arm and leg. However, some direct microneurographic recordings indicate differentiated sympathetic outflow to limbs both at rest and during mental stress. Hence, differentiated levels of norepinephrine (NE) spillover could prevail. By steady-state infusion of [3H]NE and body composition determination by dual-energy X-ray absorptiometry-scan, we simultaneously assessed arm and leg NE spillover related to 100 g tissue and total limb weight. NE spillover was lower in leg than arm (0.26 vs. 1.51 pmol.min-1.100 g-1, P < 0.05), and the difference remained when expressed as a function of total limb weight (66 vs. 137 pmol/min, P < 0.05). Fractional extraction of [3H]NE was similar in arm and leg. Neuronal uptake blockade by desipramine was more effective in leg than arm; fractional extraction in leg decreased by 32% (P < 0.05) but was unaltered in arm. Thus a lower NE spillover was observed from leg than arm, possibly reflecting a lower sympathetic outflow and a more neuronally dependent reuptake.
Ferrara, P; Ianniello, F; Romani, L; Fabrizio, G C; Gatto, A; Chiaretti, A
2014-01-01
Nocturnal enuresis (NE) is a very common pediatric disorder. The aim of this study was to evaluate the characteristics of patients with NE or urinary incontinence (UI) during a period of 5 years to increase the knowledge on these conditions and optimize their diagnosis and treatment. We enrolled 278 children with NE or UI referred to the pediatric nephrology ambulatory, 'A. Gemelli' University Hospital of Rome, from December 2006 to December 2011. We observed that heredity, parasomnias, left-handedness, polythelia and constipation are correlated to NE and UI. We wanted to clarify the definition of NE and UI and describe our experience on the main characteristics of these conditions by referring to the latest knowledge reported in the literature. 2013 S. Karger AG, Basel.
NASA Astrophysics Data System (ADS)
Greene, Amy
2013-04-01
MicroBooNE is a neutrino experiment at Fermilab designed to investigate the 3σ low-energy electron candidate events measured by the MiniBooNE experiment. Neutrinos from the Booster Neutrino Beam are detected by a 89-ton liquid argon time projection chamber, which is expected to start taking data in 2014. MicroBooNE measures both the ionization electrons and scintillation light produced by neutrino interactions in the liquid argon. The scintillation light is collected by an array of 30 PMTs located at one side of the detector. This array can be calibrated using Michel electrons from stopping cosmic ray muons, by fitting the measured PMT response with the theoretical expectation. I will report on the progress of the PMT calibration software that has been developed using the MicroBooNE Monte Carlo.
Reconstructing Michel Electrons in the MicroBooNE Detector
NASA Astrophysics Data System (ADS)
Caratelli, David
2016-03-01
MicroBooNE is a Liquid Argon Time Projection Chamber (LArTPC) neutrino detector located in the Booster Neutrino Beamline at Fermilab which began collecting neutrino data in October 2015. MicroBooNE aims to explore the low-energy excess in the νe spectrum reported by MiniBooNE as well as perform ν-Ar cross-section measurements. In this talk, we present the current status of reconstructing Michel electrons from cosmic ray muons in the MicroBooNE detector. These Michel electrons are distributed uniformly inside the detector, and serve as a natural and powerful calibration source to study the detector's response for low energy (10s of MeV) interactions as a function of position. We have developed a reconstruction software tool to successfully identify such Michel electrons which could be of benefit to LArTPC experiments generically.
Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A
2010-01-01
Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5min decreased [(3)H]NE uptake capacity, an effect characterized by a robust decrease in the V(max) of the transport of [(3)H]NE. As expected, reserpine did not displace the binding of [(3)H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [(3)H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [(3)H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca(2+)/Ca(2+)-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [(3)H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, alpha-methyl-p-tyrosine, increased [(3)H]NE uptake and eliminated the inhibitory effects of reserpine on [(3)H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca(2+)-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.
Is there any electrophysiological evidence for subliminal error processing?
Shalgi, Shani; Deouell, Leon Y
2013-08-29
The role of error awareness in executive control and modification of behavior is not fully understood. In line with many recent studies showing that conscious awareness is unnecessary for numerous high-level processes such as strategic adjustments and decision making, it was suggested that error detection can also take place unconsciously. The Error Negativity (Ne) component, long established as a robust error-related component that differentiates between correct responses and errors, was a fine candidate to test this notion: if an Ne is elicited also by errors which are not consciously detected, it would imply a subliminal process involved in error monitoring that does not necessarily lead to conscious awareness of the error. Indeed, for the past decade, the repeated finding of a similar Ne for errors which became aware and errors that did not achieve awareness, compared to the smaller negativity elicited by correct responses (Correct Response Negativity; CRN), has lent the Ne the prestigious status of an index of subliminal error processing. However, there were several notable exceptions to these findings. The study in the focus of this review (Shalgi and Deouell, 2012) sheds new light on both types of previous results. We found that error detection as reflected by the Ne is correlated with subjective awareness: when awareness (or more importantly lack thereof) is more strictly determined using the wagering paradigm, no Ne is elicited without awareness. This result effectively resolves the issue of why there are many conflicting findings regarding the Ne and error awareness. The average Ne amplitude appears to be influenced by individual criteria for error reporting and therefore, studies containing different mixtures of participants who are more confident of their own performance or less confident, or paradigms that either encourage or don't encourage reporting low confidence errors will show different results. Based on this evidence, it is no longer possible to unquestioningly uphold the notion that the amplitude of the Ne is unrelated to subjective awareness, and therefore, that errors are detected without conscious awareness.
NASA Astrophysics Data System (ADS)
Behling, Hermann; W. Arz, Helge; Pätzold, Jürgen; Wefer, Gerold
2000-06-01
Late Quaternary paleoenvironments from northeastern (NE) Brazil have been studied by pollen analysis of marine sediment. The studied core GeoB 3104-1 (3°40' S, 37°43' W, 767 m b.s.l.) from the upper continental slope off NE Brazil is 517 cm long and >42,000 14C yr BP old. Chronological control was obtained by 12 radiocarbon (AMS) dates from individuals of the foraminiferal species Globigerinoides sacculifer. Modern pollen analogs were received from 15 river, lake and forest soil surface samples from NE Brazil. Marine pollen dates indicate the predominance of semi-arid caatinga vegetation in NE Brazil during the recorded period between >42,000 and 8500 14C yr BP. The increased fluvial input of terrigenous material, with high concentrations of pollen and specially fern spores, into the marine deposits, about 40,000, 33,000 and 24,000 14C yr BP and between 15,500 and 11,800 14C yr BP, indicate short-term periods of strong rainfall on the NE Brazilian continent. The expansion of mountain, floodplain and gallery forests characterize the interval between 15,500 and 11,800 14C yr BP as the wettest recorded period in NE Brazil, which allowed floristic exchanges between Atlantic rain forest and Amazonian rain forest, and vice versa. The paleodata from core GeoB 3104-1 confirm the, in general, dry pre-Last Glacial Maximum (LGM) and LGM conditions and the change to wet Lateglacial environments in tropical South America. The annual movement of the intertropical convergence zone over NE Brazil, the strong influence of the Antarctic cold fronts and changes of the high-pressure cell over the southern Atlantic, may explain the very wet Lateglacial period in NE Brazil. The documented NE Brazilian short-term signals correlate with the documented Dansgaard-Oeschger cycles and Heinrich events from the northern Hemisphere and suggest strong teleconnections.
2013-01-01
Background Neuroenhancement (NE), the use of psychoactive substances in order to enhance a healthy individual’s cognitive functioning from a proficient to an even higher level, is prevalent in student populations. According to the strength model of self-control, people fail to self-regulate and fall back on their dominant behavioral response when finite self-control resources are depleted. An experiment was conducted to test the hypothesis that ego-depletion will prevent students who are unfamiliar with NE from trying it. Findings 130 undergraduates, who denied having tried NE before (43% female, mean age = 22.76 ± 4.15 years old), were randomly assigned to either an ego-depletion or a control condition. The dependent variable was taking an “energy-stick” (a legal nutritional supplement, containing low doses of caffeine, taurine and vitamin B), offered as a potential means of enhancing performance on the bogus concentration task that followed. Logistic regression analysis showed that ego-depleted participants were three times less likely to take the substance, OR = 0.37, p = .01. Conclusion This experiment found that trying NE for the first time was more likely if an individual’s cognitive capacities were not depleted. This means that mental exhaustion is not predictive for NE in students for whom NE is not the dominant response. Trying NE for the first time is therefore more likely to occur as a thoughtful attempt at self-regulation than as an automatic behavioral response in stressful situations. We therefore recommend targeting interventions at this inter-individual difference. Students without previous reinforcing NE experience should be provided with information about the possible negative health outcomes of NE. Reconfiguring structural aspects in the academic environment (e.g. lessening workloads) might help to deter current users. PMID:24314053
Tan, Cheng Seng; Hassan, Maizom; Mohamed Hussein, Zeti Azura; Ismail, Ismanizan; Ho, Kok Lian; Ng, Chyan Leong; Zainal, Zamri
2018-02-01
Geraniol degradation pathway has long been elucidated in microorganisms through bioconversion studies, yet weakly characterised in plants; enzyme with specific nerol-oxidising activity has not been reported. A novel cDNA encodes nerol dehydrogenase (PmNeDH) was isolated from Persicaria minor. The recombinant PmNeDH (rPmNeDH) is a homodimeric enzyme that belongs to MDR (medium-chain dehydrogenases/reductases) superfamily that catalyses the first oxidative step of geraniol degradation pathway in citral biosynthesis. Kinetic analysis revealed that rPmNeDH has a high specificity for allylic primary alcohols with backbone ≤10 carbons. rPmNeDH has ∼3 fold higher affinity towards nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) than its trans-isomer, geraniol. To our knowledge, this is the first alcohol dehydrogenase with higher preference towards nerol, suggesting that nerol can be effective substrate for citral biosynthesis in P. minor. The rPmNeDH crystal structure (1.54 Å) showed high similarity with enzyme structures from MDR superfamily. Structure guided mutation was conducted to describe the relationships between substrate specificity and residue substitutions in the active site. Kinetics analyses of wild-type rPmNeDH and several active site mutants demonstrated that the substrate specificity of rPmNeDH can be altered by changing any selected active site residues (Asp 280 , Leu 294 and Ala 303 ). Interestingly, the L294F, A303F and A303G mutants were able to revamp the substrate preference towards geraniol. Furthermore, mutant that exhibited a broader substrate range was also obtained. This study demonstrates that P. minor may have evolved to contain enzyme that optimally recognise cis-configured nerol as substrate. rPmNeDH structure provides new insights into the substrate specificity and active site plasticity in MDR superfamily. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
NASA Astrophysics Data System (ADS)
Martínez-Paredes, M.; Bruzual, G.; Meléndez, M.; González-Martín, O.
2017-11-01
The optical diagnostic diagram te{BPT81, VO87} allow us to discriminate between the different excitation mechanism, like that produce by young stars and that produce by the AGN during the accretion of matter onto the super massive black hole. This kind of tool are important because allow us to study the connection between starburst and AGN. However, despite the great success, the identification of the most heavily dust-obscured systems remains a challenge for optical diagrams. Mid-infrared diagnostic are more suitable to study dust-enshrouded systems, where the effect of dust obscuration can hamper the interpretation of traditional optical diagnostics, since in this spectral range we have access to low-ionization lines (as [Ne II]12.8μm) typical of star forming regions and high ionization lines typical of active galaxies ([OIV]25.9μm), while intermediate ionization-lines ([Ne III]15.3μm) provide a unique scenario where the AGN coexist with active star formation in the host galaxy. In a previous work te{Melendez14} we have carried out extensive and detailed photoionization modeling to successfully separate the different excitation mechanism in the mid-infrared diagnostic diagrams proposed by te{Weaver10}. We successfully modelled the AGN and starburst galaxies ratios lines of [NeIII]/[NeII] Vs [OIV]/[NeIII]. However, we failed in modelling the observed ratio lines in galaxies with a normal star formation activity ([NeIII]/[NeII]<1 and [OIV]/[NeIII]<1). These results suggest the presence of a more complex excitation mechanism in these galaxies. In this project we are using the update stellar population models from te{BC17} that include massive stars, and the update photoionization models from CLOUDY from te{Ferland17}, to characterize the properties of the stellar population that produce the high ionization conditions in these galaxies.
Yu, Meng; Ma, Huixian; Lei, Mingzhu; Li, Nan; Tan, Fengping
2014-09-01
Topical skin treatment was limited due to the lack of suitable delivery system with significant cutaneous localization and systemic safety. The aim of this study was to develop and optimize a nanoemulsion (NE) to enhance targeting localization of metronidazole (MTZ) in skin layers. In vitro studies were used to optimize NE formulations, and a series of experiments were carried in vitro and in vivo to validate the therapeutic efficacy of MTZ-loaded optimal NE. NE type selection and D-optimal design study were applied to optimize NE formulation with maximum skin retention and minimum skin penetration. Three formulation variables: Oil X1 (Labrafil), Smix X2 (a mixture of Cremophor EL/Tetraethylene glycol, 2:1 w/w) and water X3 were included in D-design. The system was assessed for skin retention Y1, cumulative MTZ amount after 24 h Y2 and droplet size Y3. Following optimization, the values of formulation components (X1, X2 and X3) were 4.13%, 16.42% and 79.45%, respectively. The optimized NE was assessed for viscosity, droplet size, morphological study and in vitro permeation in pig skin. Distributions of MTZ were validated by confocal laser scanning microscopy (CLSM). Active agent of NE transferred into deeper skin and localized in epidermal/dermal layers after 24 h, which showed significant advantages of the optimal NE over Gel. The skin targeting localization and minimal systemic escape of optimal NE was further proved by in vivo study on rat skin. Current in vitro-in vivo correlation (IVIVC) enabled the prediction of pharmacokinetic profile of MTZ from in vitro permeation results. Further, the in vivo anti-rosacea efficacy of optimal formulation was investigated by pharmacodynamics study on mice ear. Copyright © 2014 Elsevier B.V. All rights reserved.
Viral-genetic tracing of the input-output organization of a central noradrenaline circuit.
Schwarz, Lindsay A; Miyamichi, Kazunari; Gao, Xiaojing J; Beier, Kevin T; Weissbourd, Brandon; DeLoach, Katherine E; Ren, Jing; Ibanes, Sandy; Malenka, Robert C; Kremer, Eric J; Luo, Liqun
2015-08-06
Deciphering how neural circuits are anatomically organized with regard to input and output is instrumental in understanding how the brain processes information. For example, locus coeruleus noradrenaline (also known as norepinephrine) (LC-NE) neurons receive input from and send output to broad regions of the brain and spinal cord, and regulate diverse functions including arousal, attention, mood and sensory gating. However, it is unclear how LC-NE neurons divide up their brain-wide projection patterns and whether different LC-NE neurons receive differential input. Here we developed a set of viral-genetic tools to quantitatively analyse the input-output relationship of neural circuits, and applied these tools to dissect the LC-NE circuit in mice. Rabies-virus-based input mapping indicated that LC-NE neurons receive convergent synaptic input from many regions previously identified as sending axons to the locus coeruleus, as well as from newly identified presynaptic partners, including cerebellar Purkinje cells. The 'tracing the relationship between input and output' method (or TRIO method) enables trans-synaptic input tracing from specific subsets of neurons based on their projection and cell type. We found that LC-NE neurons projecting to diverse output regions receive mostly similar input. Projection-based viral labelling revealed that LC-NE neurons projecting to one output region also project to all brain regions we examined. Thus, the LC-NE circuit overall integrates information from, and broadcasts to, many brain regions, consistent with its primary role in regulating brain states. At the same time, we uncovered several levels of specificity in certain LC-NE sub-circuits. These tools for mapping output architecture and input-output relationship are applicable to other neuronal circuits and organisms. More broadly, our viral-genetic approaches provide an efficient intersectional means to target neuronal populations based on cell type and projection pattern.
GPS, BDS and Galileo ionospheric correction models: An evaluation in range delay and position domain
NASA Astrophysics Data System (ADS)
Wang, Ningbo; Li, Zishen; Li, Min; Yuan, Yunbin; Huo, Xingliang
2018-05-01
The performance of GPS Klobuchar (GPSKlob), BDS Klobuchar (BDSKlob) and NeQuick Galileo (NeQuickG) ionospheric correction models are evaluated in the range delay and position domains over China. The post-processed Klobuchar-style (CODKlob) coefficients provided by the Center for Orbit Determination in Europe (CODE) and our own fitted NeQuick coefficients (NeQuickC) are also included for comparison. In the range delay domain, BDS total electrons contents (TEC) derived from 20 international GNSS Monitoring and Assessment System (iGMAS) stations and GPS TEC obtained from 35 Crust Movement Observation Network of China (CMONC) stations are used as references. Compared to BDS TEC during the short period (doy 010-020, 2015), GPSKlob, BDSKlob and NeQuickG can correct 58.4, 66.7 and 54.7% of the ionospheric delay. Compared to GPS TEC for the long period (doy 001-180, 2015), the three ionospheric models can mitigate the ionospheric delay by 64.8, 65.4 and 68.1%, respectively. For the two comparison cases, CODKlob shows the worst performance, which only reduces 57.9% of the ionospheric range errors. NeQuickC exhibits the best performance, which outperforms GPSKlob, BDSKlob and NeQuickG by 6.7, 2.1 and 6.9%, respectively. In the position domain, single-frequency stand point positioning (SPP) was conducted at the selected 35 CMONC sites using GPS C/A pseudorange with and without ionospheric corrections. The vertical position error of the uncorrected case drops significantly from 10.3 m to 4.8, 4.6, 4.4 and 4.2 m for GPSKlob, CODKlob, BDSKlob and NeQuickG, however, the horizontal position error (3.2) merely decreases to 3.1, 2.7, 2.4 and 2.3 m, respectively. NeQuickG outperforms GPSKlob and BDSKlob by 5.8 and 1.9% in vertical component, and by 25.0 and 3.2% in horizontal component.
Transition from a warm and dry to a cold and wet climate in NE China across the Holocene
NASA Astrophysics Data System (ADS)
Zheng, Yanhong; Pancost, Richard D.; Naafs, B. David A.; Li, Qiyuan; Liu, Zhao; Yang, Huan
2018-07-01
Northeast (NE) China lies in the northernmost part of the East Asian Summer monsoon (EASM) region. Although a series of Holocene climatic records have been obtained from lakes and peats in this region, the Holocene hydrological history and its controls remain unclear. More specifically, it is currently debated whether NE China experienced a dry or wet climate during the early Holocene. Here we reconstruct changes in mean annual air temperature and peat soil moisture across the last ∼13,000 year BP using samples from the Gushantun and Hani peat, located in NE China. Our approach is based on the distribution of bacterial branched glycerol dialkyl glycerol tetraethers (brGDGTs) and the abundance of the archaeal isoprenoidal (iso)GDGT crenarchaeol. Using the recently developed peat-specific MAATpeat temperature calibration we find that NE China experienced a relatively warm early Holocene (∼5-7 °C warmer than today), followed by a cooling trend towards modern-day values during the mid- and late Holocene. Moreover, crenarchaeol concentrations, brGDGT-based pH values, and the distribution of 6-methyl brGDGTs, all indicate an increase in soil moisture content from the early to late Holocene in both peats, which is largely consistent with other data from NE China. This trend towards increasing soil moisture/wetter conditions across the Holocene in NE China records contrasts with the trends observed in other parts of the EASM region, which exhibit an early and/or mid-Holocene moisture/precipitation maximum. However, the Holocene soil moisture variations and temperature-moisture relationships (warm-dry and cold-wet) observed in NE China are similar to those observed in the core area of arid central Asia which is dominated by the westerlies. We therefore propose that an increase in the intensity of the westerlies across the Holocene, driven by increasing winter insolation, expanding Arctic sea ice extent and the enhanced Okhotsk High, caused an increase in moisture during the late Holocene in NE China.
Wieczorek, Marek; Dunn, Adrian J.
2007-01-01
Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo–pituitary–adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1β (1 μg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2–4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1β injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1β also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1β-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1β-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1. PMID:16330180
Chen, Yunjie; Roux, Benoît
2014-09-21
Hybrid schemes combining the strength of molecular dynamics (MD) and Metropolis Monte Carlo (MC) offer a promising avenue to improve the sampling efficiency of computer simulations of complex systems. A number of recently proposed hybrid methods consider new configurations generated by driving the system via a non-equilibrium MD (neMD) trajectory, which are subsequently treated as putative candidates for Metropolis MC acceptance or rejection. To obey microscopic detailed balance, it is necessary to alter the momentum of the system at the beginning and/or the end of the neMD trajectory. This strict rule then guarantees that the random walk in configurational space generated by such hybrid neMD-MC algorithm will yield the proper equilibrium Boltzmann distribution. While a number of different constructs are possible, the most commonly used prescription has been to simply reverse the momenta of all the particles at the end of the neMD trajectory ("one-end momentum reversal"). Surprisingly, it is shown here that the choice of momentum reversal prescription can have a considerable effect on the rate of convergence of the hybrid neMD-MC algorithm, with the simple one-end momentum reversal encountering particularly acute problems. In these neMD-MC simulations, different regions of configurational space end up being essentially isolated from one another due to a very small transition rate between regions. In the worst-case scenario, it is almost as if the configurational space does not constitute a single communicating class that can be sampled efficiently by the algorithm, and extremely long neMD-MC simulations are needed to obtain proper equilibrium probability distributions. To address this issue, a novel momentum reversal prescription, symmetrized with respect to both the beginning and the end of the neMD trajectory ("symmetric two-ends momentum reversal"), is introduced. Illustrative simulations demonstrate that the hybrid neMD-MC algorithm robustly yields a correct equilibrium probability distribution with this prescription.
NASA Astrophysics Data System (ADS)
Chen, Yunjie; Roux, Benoît
2014-09-01
Hybrid schemes combining the strength of molecular dynamics (MD) and Metropolis Monte Carlo (MC) offer a promising avenue to improve the sampling efficiency of computer simulations of complex systems. A number of recently proposed hybrid methods consider new configurations generated by driving the system via a non-equilibrium MD (neMD) trajectory, which are subsequently treated as putative candidates for Metropolis MC acceptance or rejection. To obey microscopic detailed balance, it is necessary to alter the momentum of the system at the beginning and/or the end of the neMD trajectory. This strict rule then guarantees that the random walk in configurational space generated by such hybrid neMD-MC algorithm will yield the proper equilibrium Boltzmann distribution. While a number of different constructs are possible, the most commonly used prescription has been to simply reverse the momenta of all the particles at the end of the neMD trajectory ("one-end momentum reversal"). Surprisingly, it is shown here that the choice of momentum reversal prescription can have a considerable effect on the rate of convergence of the hybrid neMD-MC algorithm, with the simple one-end momentum reversal encountering particularly acute problems. In these neMD-MC simulations, different regions of configurational space end up being essentially isolated from one another due to a very small transition rate between regions. In the worst-case scenario, it is almost as if the configurational space does not constitute a single communicating class that can be sampled efficiently by the algorithm, and extremely long neMD-MC simulations are needed to obtain proper equilibrium probability distributions. To address this issue, a novel momentum reversal prescription, symmetrized with respect to both the beginning and the end of the neMD trajectory ("symmetric two-ends momentum reversal"), is introduced. Illustrative simulations demonstrate that the hybrid neMD-MC algorithm robustly yields a correct equilibrium probability distribution with this prescription.
Wieczorek, Marek; Dunn, Adrian J
2006-09-01
Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.
Zonal NePhRO scoring system: a superior renal tumor complexity classification model.
Hakky, Tariq S; Baumgarten, Adam S; Allen, Bryan; Lin, Hui-Yi; Ercole, Cesar E; Sexton, Wade J; Spiess, Philippe E
2014-02-01
Since the advent of the first standardized renal tumor complexity system, many subsequent scoring systems have been introduced, many of which are complicated and can make it difficult to accurately measure data end points. In light of these limitations, we introduce the new zonal NePhRO scoring system. The zonal NePhRO score is based on 4 anatomical components that are assigned a score of 1, 2, or 3, and their sum is used to classify renal tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of the tumor, and (O)rganization of the tumor. In this retrospective study, we evaluated patients exhibiting clinical stage T1a or T1b who underwent open partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) score, and a blinded reviewer used the same preoperative imaging study to obtain both scores. Additional data points gathered included age, clamp time, complication rate, urine leak rate, intraoperative blood loss, and pathologic tumor size. One hundred sixty-six patients underwent open partial nephrectomy. There were 37 perioperative complications quantitated using the validated Clavien-Dindo system; their occurrence was predicted by the NePhRO score on both univariate and multivariate analyses (P = .0008). Clinical stage, intraoperative blood loss, and tumor diameter were all correlated with the zonal NePhRO score on univariate analysis only. The zonal NePhRO scoring system is a simpler tool that accurately predicts the surgical complexity of a renal lesion. Copyright © 2014 Elsevier Inc. All rights reserved.
Satellite derived forest phenology and its relation with nephropathia epidemica in Belgium.
Barrios, José Miguel; Verstraeten, Willem W; Maes, Piet; Clement, Jan; Aerts, Jean-Marie; Haredasht, Sara Amirpour; Wambacq, Julie; Lagrou, Katrien; Ducoffre, Geneviève; Van Ranst, Marc; Berckmans, Daniel; Coppin, Pol
2010-06-01
The connection between nephropathia epidemica (NE) and vegetation dynamics has been emphasized in recent studies. Changing climate has been suggested as a triggering factor of recently observed epidemiologic peaks in reported NE cases. We have investigated whether there is a connection between the NE occurrence pattern in Belgium and specific trends in remotely sensed phenology parameters of broad-leaved forests. The analysis of time series of the MODIS Enhanced Vegetation Index revealed that changes in forest phenology, considered in literature as an effect of climate change, may affect the mechanics of NE transmission.
Satellite Derived Forest Phenology and Its Relation with Nephropathia Epidemica in Belgium
Barrios, José Miguel; Verstraeten, Willem W.; Maes, Piet; Clement, Jan; Aerts, Jean-Marie; Haredasht, Sara Amirpour; Wambacq, Julie; Lagrou, Katrien; Ducoffre, Geneviève; Van Ranst, Marc; Berckmans, Daniel; Coppin, Pol
2010-01-01
The connection between nephropathia epidemica (NE) and vegetation dynamics has been emphasized in recent studies. Changing climate has been suggested as a triggering factor of recently observed epidemiologic peaks in reported NE cases. We have investigated whether there is a connection between the NE occurrence pattern in Belgium and specific trends in remotely sensed phenology parameters of broad-leaved forests. The analysis of time series of the MODIS Enhanced Vegetation Index revealed that changes in forest phenology, considered in literature as an effect of climate change, may affect the mechanics of NE transmission. PMID:20644685
Role of neutrophil elastase in lung injury induced by burn-blast combined injury in rats.
Chai, Jia-ke; Cai, Jian-hua; Deng, Hu-ping; Zou, Xiao-fang; Liu, Wei; Hu, Qing-gang; Shen, Chuan-an; Yin, Hui-nan; Zhang, Xi-bo; Chi, Yun-fei; Ma, Li; Feng, Rui
2013-06-01
Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats. One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury. In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes. Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.
Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure.
Tsutamoto, Takayoshi; Nishiyama, Keizo; Sakai, Hiroshi; Tanaka, Toshinari; Fujii, Masanori; Yamamoto, Takashi; Yamaji, Masayuki; Horie, Minoru
2008-12-01
No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF). To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF. We measured haemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF. During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273+/-276 vs. 472+/-433 pg/mL, p<0.0001), NT-proBNP (417+/-700 vs. 928+/-1093 pg/mL, p<0.0001) and NE (114+/-160 vs. 473+/-992 pg/mL, p<0.0001) were significantly higher in non-survivors than survivors. After adjustment for clinical variables associated with CHF including haemodynamics and neurohumoral factors, the transcardiac gradient of NE (p<0.0001) and plasma log NT-proBNP (p<0.0001) were independent prognostic predictors. Among 67 patients in whom 123I-metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE was correlated with the washout rate (r=0.398, p=0.0009) and was a superior predictor of mortality than MIBG parameters on stepwise multivariable Cox proportional hazards regression analyses. The transcardiac increase in NE is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients.
Lu, Angela H; Dickin, Katherine; Dollahite, Jamie
2014-01-01
To develop and apply a framework exploring the extent of involvement in promoting environmental changes to prevent obesity by a group of nutrition educators (NE). Cross-sectional, mixed methods: qualitative interviews informed framework development; survey applied framework to describe NE's involvement in environmental changes. Cooperative Extension in New York State. Interviewees (n = 7) selected to vary in environmental change activities and rural/urban location. Survey response rate was 100% (n = 58). Dimensions and degree of NE's involvement in promoting environmental change. Thematic analysis of qualitative data, triangulated with descriptive analyses of NE's performance of tasks in various settings. NE's promotion of environmental changes was characterized using framework based on settings and tasks, dimensions that emerged from qualitative analysis. NE's actions varied across these dimensions and ranged from low to high intensity of collaboration and leadership for environmental change. Most NE surveyed reported actions limited to providing information and recommendations on healthy eating and physical activity. Few reported intensive engagement in developing, implementing, and evaluating plans to change environments for obesity prevention. Framework identifies the levels of engagement in promoting environmental changes and supports future research and practice of community nutrition professionals by providing a roadmap for assessing their involvement on multiple levels to prevent obesity. Copyright © 2014 Society for Nutrition Education and Behavior. All rights reserved.
NASA Astrophysics Data System (ADS)
Seo, Jeong Hyun; Jeong, Heui Seob; Lee, Joo Yul; Yoon, Cha Keun; Kim, Joong Kyun; Whang, Ki-Woong
2000-08-01
We measured the time integrated vacuum ultraviolet (VUV) emission spectra of He-Ne-Xe gas mixture from a surface type alternating current (ac) plasma display panel cell. The measured emission lines are the resonance line (147 nm) from Xe*(1s4), the first continuum (150 nm) and the second continuum (173 nm) from Xe dimer excited states. The relative intensities of VUV spectral lines from Xe* and Xe2* are dependent on the He/Ne mixing ratio as well as the Xe partial and total pressure. The intensity of 147 nm VUV increases with the Ne content increase and Xe2* molecular emission increases with the He content increase. Infrared (IR) spectra and the time variation of VUV were measured to explain the reaction pathway and the effect of the mixing ratio of He/Ne on the spectral intensity. A detailed study for the decay time shows that the decay time of 147 nm has two time constants and the radiation of 150 and 173 nm results mainly from Xe*(1s5). The IR spectra shows that the contribution from Xe**(>6 s) to Xe*(1s5) and Xe*(1s4) in He-Xe is different from that of Ne-Xe. The change of IR intensity explains the spectral intensity variations of He-Xe and Ne-Xe discharge.
Distinct roles for key karyogamy proteins during yeast nuclear fusion.
Melloy, Patricia; Shen, Shu; White, Erin; Rose, Mark D
2009-09-01
During yeast mating, cell fusion is followed by the congression and fusion of the two nuclei. Proteins required for nuclear fusion are found at the surface (Prm3p) and within the lumen (Kar2p, Kar5p, and Kar8p) of the nuclear envelope (NE). Electron tomography (ET) of zygotes revealed that mutations in these proteins block nuclear fusion with different morphologies, suggesting that they act in different steps of fusion. Specifically, prm3 zygotes were blocked before formation of membrane bridges, whereas kar2, kar5, and kar8 zygotes frequently contained them. Membrane bridges were significantly larger and occurred more frequently in kar2 and kar8, than in kar5 mutant zygotes. The kinetics of NE fusion in prm3, kar5, and kar8 mutants, measured by live-cell fluorescence microscopy, were well correlated with the size and frequency of bridges observed by ET. However the kar2 mutant was defective for transfer of NE lumenal GFP, but not diffusion within the lumen, suggesting that transfer was blocked at the NE fusion junction. These observations suggest that Prm3p acts before initiation of outer NE fusion, Kar5p may help dilation of the initial fusion pore, and Kar2p and Kar8p act after outer NE fusion, during inner NE fusion.
The Spitzer Infrared Nearby Galaxies Survey: A High-Resolution Spectroscopy Anthology
NASA Astrophysics Data System (ADS)
Dale, Daniel A.; SINGS Team
2009-05-01
Results from high resolution mid-infrared spectroscopy are presented for 155 nuclear and extranuclear regions from SINGS. The SINGS sample shows a wide range in the ratio of [SIII]18.71/[SIII]33.48, but the average ratio of the ensemble indicates a typical interstellar electron density of 300--400 cm-3 on 23"x15" scales and 500--600 cm-3 using 11"x9" apertures, independent of whether the region probed is a star-forming nuclear, a star-forming extranuclear, or an AGN environment. Evidence is provided that variations in gas-phase metallicity play an important role in driving variations in radiation field hardness, as indicated by [NeIII]15.56/[NeII]12.81, for regions powered by star formation. Conversely, the radiation hardness for galaxy nuclei powered by accretion around a massive black hole is independent of metal abundance. Furthermore, for metal-rich environments AGN are distinguishable from star-forming regions by significantly larger [NeIII]15.56/[NeII]12.81 ratios. Finally, [FeII]25.99/[NeII]12.81 versus [SiII]34.82/[SIII]33.48 also provides an empirical method for discerning AGN from normal star-forming sources. However, similar to [NeIII]15.56/[NeII]12.81, these mid-infrared line ratios lose their AGN/star-formation diagnostic powers for very low metallicity star-forming systems with hard radiation fields.
Specifying the ISS Plasma Environment
NASA Technical Reports Server (NTRS)
Minow, Joseph I.; Diekmann, Anne; Neergaard, Linda; Bui, Them; Mikatarian, Ronald; Barsamian, Hagop; Koontz, Steven
2002-01-01
Quantifying the spacecraft charging risks and corresponding hazards for the International Space Station (ISS) requires a plasma environment specification describing the natural variability of ionospheric temperature (Te) and density (Ne). Empirical ionospheric specification and forecast models such as the International Reference Ionosphere (IN) model typically only provide estimates of long term (seasonal) mean Te and Ne values for the low Earth orbit environment. Knowledge of the Te and Ne variability as well as the likelihood of extreme deviations from the mean values are required to estimate both the magnitude and frequency of occurrence of potentially hazardous spacecraft charging environments for a given ISS construction stage and flight configuration. This paper describes the statistical analysis of historical ionospheric low Earth orbit plasma measurements used to estimate Ne, Te variability in the ISS flight environment. The statistical variability analysis of Ne and Te enables calculation of the expected frequency of occurrence of any particular values of Ne and Te, especially those that correspond to possibly hazardous spacecraft charging environments. The database used in the original analysis included measurements from the AE-C, AE-D, and DE-2 satellites. Recent work on the database has added additional satellites to the database and ground based incoherent scatter radar observations as well. Deviations of the data values from the IRI estimated Ne, Te parameters for each data point provide a statistical basis for modeling the deviations of the plasma environment from the IRI model output.
Pasternak, K; Dabrowski, W; Dobija, J; Wrońskal, J; Rzecki, Z; Biernacka, J
2006-06-01
It is well known that magnesium (Mg) plays an important role in many physiological processes such as regulation of blood catecholamine concentrations, particularly epinephrine (E) and norepinephrine (NE). The complex character of extracorporeal circulation (ECC) with intraoperative normovolemic haemodilution (NH) may alter blood Mg levels, which is likely to result in disorders of E and NE. The aim of this study was to analyze the influence of preoperative Mg supplementation on E and NE in patients undergoing CABG. Forty male patients undergoing CABG under general anaesthesia were included. Patients were randomly divided into two groups: A--the patients receiving pre-operative magnesium supplementation and B--patients without pre-operative magnesium supplementation. The Mg, E and NE blood concentrations were measured in five stages: 1) before anesthesia after the radial artery cannulation, 2) during NH and ECC, 3) immediately after surgery, 4) in the morning of the 1st postoperative day, 5) in the morning of the 2nd postoperative day. The Mg levels were determined by spectrophotometric methods, E and NE were measured by radioimmunoassay methods. The CABG caused a decrease of Mg and an increase of E and NE in both groups, but the changes were significantly higher in group B. 1) CABG causes a decrease of Mg and an increase of E and NE; 2) Preoperative, oral supplementation of Mg substantially reduces intra- and postoperative disorders.
NASA Astrophysics Data System (ADS)
Ziv, A.; Katzir, Y.; Avigad, D.; Garfunkel, Z.
2010-06-01
The general trend of both fold axes and stretching lineation in the Cycladic Blueschist Unit is NE-SW to NNE-SSW. This orientation forms a large angle (almost perpendicular) with respect to the Hellenic trend that is inferred from the main thrusts on mainland Greece. Thus, the kinematic significance of the stretching parallel folding in the Cycladic Blueschist Unit is non-trivial. Since within the western Cyclades, the NE-trending folds are best exposed on the island of Andros, it is a key locality for understanding the timing, style and kinematic significance of folding. Here we show that the NE-trending folds on Andros formed within the stability field of glaucophane, after the peak high-pressure metamorphism and simultaneously with the early stage of retrogression. The axes-parallel stretching was non-rotational; it started during the NE folding at blueschist-facies conditions, and continued long afterward and well into the retrograde greenschist overprint. Furthermore, we present the result of a finite strain calculation which shows that the large NE folds could not have been reoriented at ~ 90° as previously thought. Instead it is suggested that these folds formed under constrictional strain regime during regional NE-SW extension, and represent coeval transverse NW-SE shortening and vertical thinning. This implies that NE extension and southwest directed rollback of the active margin prevailed in the western Aegean between the Eocene and early Miocene.
Page, M E; Abercrombie, E D
1997-06-01
The locus coeruleus (LC) noradrenergic system is activated by a range of arousing and stressful stimuli. The serotonergic inputs to this structure have been shown to attenuate LC activation under some conditions. The present study examined the effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) known to be a clinically effective antidepressant, on basal and stress-induced norepinephrine (NE) release. Basal and stress-induced NE efflux in the rat hippocampus were assessed using in vivo microdialysis techniques. The effect of a 30 minute tailpinch stressor on extracellular concentration of NE was compared in rats treated with fluoxetine either once prior to tailpinch or twice daily for 14 days and, respectively, in unhandled controls and vehicle-treated control animals. A single fluoxetine injection prior to tailpinch did not significantly alter the tailpinch-induced increase of extracellular NE as compared to naive controls. However, there was an enhanced NE response to tailpinch in chronic fluoxetine versus chronic vehicle-treated control rats. Thus, acute blockade of 5-HT uptake by fluoxetine does not affect NE release in response to tailpinch stress. Chronic fluoxetine administration, however, results in a potentiated evoked response of the LC-NE system. One action of chronic fluoxetine, which may relate to therapeutic efficacy, is an increase in responsivity of LC neurons.
Sterile Neutrino Searches in MiniBooNE and MicroBooNE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ignarra, Christina M.
Tension among recent short baseline neutrino experiments has pointed toward the possible need for the addition of one or more sterile (non-interacting) neutrino states into the existing neutrino oscillation framework. This thesis fi rst presents the motivation for sterile neutrino models by describing the short-baseline anomalies that can be addressed with them. This is followed by a discussion of the phenomenology of these models. The MiniBooNE experiment and results are then described in detail, particularly the most recent antineutrino analysis. This will be followed by a discussion of global fits to world data, including the anomalous data sets. Lastly, futuremore » experiments will be addressed, especially focusing on the MicroBooNE experiment and light collection studies. In particular, understanding the degradation source of TPB, designing the TPB-coated plates for MicroBooNE and developing lightguide collection systems will be discussed. We find an excess of events in the MiniBooNE antineutrino mode results consistent with the LSND anomaly, but one that has a di fferent energy dependence than the low-energy excess reported in neutrino mode. This disagreement creates tension within global fi ts which include up to three sterile neutrinos. The low-energy excess will be addressed by the MicroBooNE experiment, which is expected to start taking data in early 2015. Tension among existing experiments calls for additional, more decisive future experiments.« less
Goldstein, Brandon L; Shankman, Stewart A; Kujawa, Autumn; Torpey-Newman, Dana C; Dyson, Margaret W; Olino, Thomas M; Klein, Daniel N
2018-04-24
Depression is characterized by low positive emotionality (PE) and high negative emotionality (NE), as well as asymmetries in resting electroencephalography (EEG) alpha power. Moreover, frontal asymmetry has itself been linked to PE, NE, and related constructs. However, little is known about associations of temperamental PE and NE with resting EEG asymmetries in young children and whether this association changes as a function of development. In a longitudinal study of 254 three-year old children, we assessed PE and NE at age 3 using a standard laboratory observation procedure. Frontal EEG asymmetries were assessed at age 3 and three years later at age 6. We observed a significant three-way interaction of preschool PE and NE and age at assessment for asymmetry at F3-F4 electrode sites, such that children with both low PE and high NE developed a pattern of increasingly lower relative left-frontal cortical activity over time. In addition, F7-F8 asymmetry was predicted by a PE by time interaction, such that the frontal asymmetry in children with high PE virtually disappeared by age 6. Overall, these findings suggest that early temperament is associated with developmental changes in frontal asymmetry, and that the combination of low PE and high NE predicts the development of the pattern of frontal symmetry that is associated with depression.
77 FR 68714 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-16
...-1055; Directorate Identifier 2012-NE-33-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce... ``Docket No. FAA-2012-1055; Directorate Identifier 2012-NE-33-AD'' at the beginning of your comments. We...H): Docket No. FAA- 2012-1055; Directorate Identifier 2012-NE-33-AD. (a) Comments Due Date We must...
Validation of NE-TWIGS for tolerant hardwood stands in Ontario
Jacek Bankowski; Daniel C. Dey; Eric Boysen; Murray Woods; Jim Rice
1996-01-01
The individual-tree, distance-independent stand growth simulator NE-TWIGS has been tested for Ontario's tolerant hardwood stands using data from long-term permanent sample plots. NE-TWIGS provides reliable short-term (5-year) predictions of stand basal area (modelling efficiency from 77% to 99%), but in longer projections the efficiency of the model drops...
HIMU-type Mid-Ocean Ridge Basalts Incorporate a Primitive Component
NASA Astrophysics Data System (ADS)
Tucker, J.; Mukhopadhyay, S.; Schilling, J. E.
2011-12-01
Samples from 5°N to 7°S along the MAR axis span a range of compositions from depleted MORB (La/SmN ~0.5, 206Pb/204Pb ~18) to very enriched MORB (La/SmN ~3, 206Pb/204Pb ~20). The measured 206Pb/204Pb in the enriched samples are among the highest measured MORB values and are thought to represent a HIMU type mantle (high μ where μ is the U/Pb ratio). Therefore, the enriched samples provide a unique opportunity to characterize the heavy noble gas composition of the HIMU mantle. If HIMU mantle is related to recycled crust, then the noble gas measurements can also provide insights into recycling of atmospheric noble gases back into the mantle. Additionally, the depleted equatorial samples provide an opportunity to characterize the Ar and Xe composition of the N-MORB source for comparison to the 14°N E-MORB popping rock. Finally, the large variations in lithophile isotopes over a geographically short distance affords the opportunity to study the nature of coupling between the noble gases and lithophile tracers, and understand the origin of the heterogeneities in the MORB source. Stepwise crushing and rare gas analysis (He, Ne, Ar, Xe) was undertaken for both enriched and depleted samples. Many of the crushing steps yielded 20Ne/22Ne > 12, and good correlations between Ne, Ar, and Xe isotopes allow for mantle source compositions of Ar and Xe to be determined by extrapolating the measured values to a mantle 20Ne/22Ne of 12.5. The highest measured values of Ar and Xe in a depleted N-MORB are comparable to measured values of the E-MORB popping rock (40Ar/36Ar ~28,000, 129Xe/130Xe ~7.7). When extrapolated to a mantle 20Ne/22Ne of 12.5, the depleted MORB sample indicates a 40Ar/36Ar of ~43,000 (higher than popping rock) and 129Xe/130Xe of ~7.8. Enriched MORB samples from this suite, thought to represent the HIMU mantle, have the same He and Ne characteristics as HIMU basalts from the Cook and Austral Islands; more radiogenic He than MORBs is accompanied by less nucleogenic Ne than MORBs. Additionally, the enriched MORB samples also constrain the HIMU mantle 40Ar/36Ar to ~20,000 and 129Xe/130Xe ~7.3-7.5, significantly lower than the depleted MORBs. Like the HIMU basalts from the Cook and Austral Islands, a less degassed reservoir than the MORB source must be invoked to explain the He and Ne systematics in the HIMU-type MORBs. If HIMU represents recycled crust, then it must have entrained or been entrained by a less degassed mantle from the deep interior. This less degassed reservoir would also explain the good correspondence between low 21Ne/22Ne, low 40Ar/36Ar and low 129Xe/130Xe in the HIMU-type samples. While we cannot rule out recycling of atmospheric noble gases to explain the low 40Ar/36Ar and 129Xe/130Xe, involvement of a source less degassed in He and Ne would also be accompanied by a less degassed Ar and Xe isotopic signature. Therefore the simplest explanation of the covariation between the noble gases and lithophile isotopes involves a mixture of a less processed and hence more primitive component, a degassed recycled component, and depleted MORB mantle beneath the equatorial Mid-Atlantic Ridge.
NASA Astrophysics Data System (ADS)
Xiao, Yuling; Jaskula-Sztul, Renata; Javadi, Alireza; Xu, Wenjin; Eide, Jacob; Dammalapati, Ajitha; Kunnimalaiyaan, Muthusamy; Chen, Herbert; Gong, Shaoqin
2012-10-01
A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers.A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers. Electronic supplementary information (ESI) available: Additional flow cytometry histogram profiles of DOX fluorescence and ASCL1 knockdown results. See DOI: 10.1039/c2nr31853a
Spin exchange optical pumping of neon and its applications
NASA Astrophysics Data System (ADS)
Ghosh, Rajat K.
Hyperpolarized noble gases are used in a variety of applications including medical diagnostic lung imaging, tests of fundamental symmetries, spin filters, atomic gyroscopes, and atomic magnetometers. Typically 3He is utilized because large 3He polarizations on the order of 80% can be achieved. This is accomplished by optically pumping an alkali vapour which polarizes a noble gas nucleus via spin exchange optical pumping. One hyperpolarized noble gas application of particular importance is the K-3He co-magnetometer. Here, the alkali atoms optically pump a diamagnetic noble gas. The magnetic holding field for the alkali and noble gas is reduced until both species are brought into hybrid magnetic resonance. The co-magnetometer exhibits many useful attributes which make it ideal for tests of fundamental physics, such as insensitivity to magnetic fields. The co-magnetometer would demonstrate increased sensitivity by replacing 3He with polarized 21Ne gas. Tests of CPT violation using co-magnetometers would be greatly improved if one utilizes polarized 21Ne gas. The sensitivity of the nuclear spin gyroscope is inversely proportional to the gyromagnetic ratio of the noble gas. Switching to neon would instigate an order of magnitude gain in sensitivity over 3He. In order to realize these applications the interaction parameters of 21Ne with alkali metals must be measured. The spin-exchange cross section sigmase, and magnetic field enhancement factor kappa0 are unknown, and have only been theoretically calculated. There are no quantitative predictions of the neon-neon quadrupolar relaxation rate Gammaquad. In this thesis I test the application of a K-3He co-magnetometer as a navigational gyroscope. I discuss the advantages of switching the buffer gas to 21Ne. I discuss the feasibility of utilizing polarized 21Ne for operation in a co-magnetometer, and construct a prototype 21Ne co-magnetometer. I investigate polarizing 21Ne with optical pumping via spin exchange collisions and measure the spin exchange rate coefficient of K and Rb with Ne to be 2.9 x 10-20cm 3/s and 0.81 x 10-19cm3/s. We measure the magnetic field enhancement factor kappa0 to be 30.8 +/- 2.7, and 35.7 +/- 3.7 for the K-Ne, and the Rb-Ne pair. We measure the quadrupolar relaxation coefficient to be 214 +/- 10 Amagat˙s. Furthermore the spin destruction cross section of Rb, and K with 21 Ne is measured to be 1.9 x 10-23cm2 and 1.1 x 10-23cm2.
NASA Astrophysics Data System (ADS)
Velez-Gonzalez, Mariano; Urrea-Arbelaez, Alejandro; Nicolas, M.; Serra-Baldrich, E.; Perez, J. L.; Pavesi, M.; Camarasa, J. M.; Trelles, Mario A.
1996-01-01
Sixty patients (greater than 16 yrs old) suffering primary or relapse genital herpes simplex viruses (HSV) and relapse labial HSV were appointed for this study. Three or more relapses were experienced per year. Patients (under treatment) were divided into two groups (distribution areas), corresponding to either labial herpes or genital herpes. These groups were sub-divided into 3 groups. The total number of labial or facial HSV patients was 36 (10 in group 1, 12 in group 2, 14 in group 3) and 24 for genital, buttocks, or 'area pudenda' HSV patients (6 in group 1, 8 in group 2, 10 in group 3). The design was a randomized, double- blind study. The setting was hospital and outpatient. The patients diagnosed as having the HVS disease were sent to the dermatology department and were assigned to a group at random. Treatment was begun as follows: During the treatment signs and symptoms were assessed and after the treatment, the relapses were also assessed (biochemical and hematological tests before and after the treatment) and the diagnosis of the HSV type I and II. The statistical evaluation of the results was performed and carried out with the SPSS and BMDP program. The relapses of the herpes infection in the lips and the face were significantly reduced (p less than 0.026) in patients treated with laser He-Ne and laser He-Ne plus Acyclovir. The interim between the relapses also increased significantly (p less than 0.005) in relation with the group treated with Acyclovir. The duration of the herpetic eruptions was clearly reduced in all locations in patients treated with laser He-Ne plus Acyclovir. No differences were noted between patients treated with laser He-Ne only or Acyclovir only. Therefore it is probable that therapeutic synergism took place. In relation with this, laser He-Ne shows the same therapeutic efficacy as Acyclovir taken orally. The association of Acyclovir and laser Ne-Ne could be an alternative method for the treatment of HSV in the face. The number of relapses of the herpes infection in the genital, buttocks or 'area pudenda' and the interim between the relapses were not substantially modified with the treatment of laser He-Ne or laser Ne-Ne plus Acyclovir. Although a little difference exists in comparison with the patients treated with Acyclovir alone, a survey or an increased number of patients should be necessary.
Bielinska, Anna U; Makidon, Paul E; Janczak, Katarzyna W; Blanco, Luz P; Swanson, Benjamin; Smith, Douglas M; Pham, Tiffany; Szabo, Zsuzsanna; Kukowska-Latallo, Jolanta F; Baker, James R
2014-03-15
Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1- and Th-17-balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell-mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.
Latini, Roberto; Masson, Serge; Anand, Inder; Judd, Dianne; Maggioni, Aldo P; Chiang, Yann-Tong; Bevilacqua, Maurizio; Salio, Monica; Cardano, Paola; Dunselman, Peter H J M; Holwerda, Nicolaas J; Tognoni, Gianni; Cohn, Jay N
2002-11-05
Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known. Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or beta-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (+/-SEM) BNP increased from baseline by 23+/-5 pg/mL in the placebo group (n=1979) but decreased by 21+/-5 pg/mL (n=1940) in the valsartan group (P<0.0001). NE increased by 41+/-6 pg/mL (n=1979) and 12+/-6 pg/mL (n=1941) for placebo and valsartan, respectively (P=0.0003). Concomitant therapy with both ACE inhibitors and beta-blockers significantly reduced the effect of valsartan on BNP but not on NE (P for interaction=0.0223 and 0.2289, respectively). In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT.
Gavin, Amy; Pham, Jimmy TH; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A
2015-01-01
Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. PMID:25759580
Gao, Limei; Li, Yongfeng; Shen, Zhihua; Han, Rong
2018-05-01
UV-B acclimation effects and UV-B damage repair induced by a 632.8-nm He-Ne laser were investigated in Arabidopsis thaliana plants in response to supplementary UV-B stress. There was an increasing trend in growth parameters in the combination-treated plants with He-Ne laser and UV-B light compared to those stressed with enhanced UV-B light alone during different developmental stages of plants. The photosynthetic efficiency (Pn) and survival rates of seedlings were significantly higher in the combination treatments than UV-B stress alone. The expression of UVR8, phytochrome B (PhyB), and their mediated signal responsive genes such as COP1, HY5, and CHS were also significantly upregulated in plants with the laser irradiation compared with other groups without the laser. Levels of flavonol accumulation in leaves and capsule yield of He-Ne laser-treated plants were increased. The phyB-9 mutants were more sensitive to enhanced UV-B stress and had no obvious improvements in plant phenotypic development and physiological damage caused by enhanced UV-B stress after He-Ne laser irradiation. Our results suggested that UVR8 and its mediated signaling pathway via interaction with COP1 can be induced by He-Ne laser, and these processes were dependent on cytoplasmic PhyB levels in plant cells, which might be one of the most important mechanisms of He-Ne laser on UV-B protection and UV-B damage repair. These current data have also elucidated that the biostimulatory effects of He-Ne laser on Arabidopsis thaliana plants would happen not only during the early growth stage but also during the entire late developmental stage.
Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B
2015-01-01
Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.
NASA Astrophysics Data System (ADS)
Hussain, T.; Muzahid, S.; Narayanan, A.; Srianand, R.; Wakker, B. P.; Charlton, J. C.; Pathak, A.
2015-01-01
We report the detection of Ne VIII in a zabs = 0.599 61 absorber towards the QSO PG1407+265 (zem= 0.94). Besides Ne VIII, absorption from H I Lyman series lines (H I λ1025-λ915), several other low (C II, N II, O II and S II), intermediate (C III, N III, N IV, O III, S IV and S V) and high (S VI, O VI and Ne VIII) ionization metal lines are detected. Disparity in the absorption line kinematics between different ions implies that the absorbing gas comprises of multiple ionization phases. The low and the intermediate ions (except S V) trace a compact (˜410 pc), metal-rich (Z ˜ Z⊙) and overdense (log nH ˜ -2.6) photoionized region that sustained star formation for a prolonged period. The high ions, Ne VIII and O VI, can be explained as arising in a low density (-5.3 ≤ log nH ≤ -5.0), metal-rich (Z ≳ Z⊙) and diffuse (˜180 kpc) photoionized gas. The S V, S VI and C IV [detected in the Faint Object Spectrograph (FOS) spectrum] require an intermediate photoionization phase with -4.2 < log nH < -3.5. Alternatively, a pure collisional ionization model, as used to explain the previous known Ne VIII absorbers, with 5.65 < log T < 5.72, can reproduce the S VI, O VI and Ne VIII column densities simultaneously in a single phase. However, even such models require an intermediate phase to reproduce any observable S V and/or C IV. Therefore, we conclude that when multiple phases are present, the presence of Ne VIII is not necessarily an unambiguous indication of collisionally ionized hot gas.
Elevated Neutrophil Elastase in Tears of Ocular Graft-Versus-Host Disease Patients.
Arafat, Samer N; Robert, Marie-Claude; Abud, Tulio; Spurr-Michaud, Sandra; Amparo, Francisco; Dohlman, Claes H; Dana, Reza; Gipson, Ilene K
2017-04-01
To investigate the levels of neutrophil elastase (NE), matrix metalloproteinases (MMPs), and myeloperoxidase (MPO) in tear washes of patients with ocular graft-vs-host disease (oGVHD). Case-control study. Based on established criteria, oGVHD patients (n = 14; 28 eyes) and age-/sex-matched healthy controls (n = 14; 28 eyes) were enrolled. Tear washes were collected and analyzed for NE using a single-analyte enzyme-linked immunosorbent assay (ELISA). MMPs (1, 2, 3, 7, 8, 9, 12), MPO, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were analyzed using multianalyte bead-based ELISA assays. Total MMP activity was measured using a fluorimetric assay. Correlation studies were performed between NE, MMP-8, MMP-9, and MPO within study groups. NE, MMP-8, MMP-9, and MPO levels were elevated in oGVHD tears when compared with controls (P < .0001). NE was the most elevated analyte. MMP activity was higher and TIMP-1 levels were lower in oGVHD than in control (P < .0001). In oGVHD, NE significantly correlated with MMP-8 (r = 0.92), MMP-9 (r = 0.90), and MPO (r = 0.79) (P < .0001). MMP-8 correlated with MMP-9 (r = 0.96, P < .0001), and MPO (r = 0.60, P = .001). MMP-9 correlated with MPO (r = 0.55, P = .002). In controls, NE, MMP-9, and MPO significantly correlated with each other (P < .0001). The marked increase in NE in oGVHD tears that correlated strongly with elevated MMP-8, MMP-9, and MPO suggests a common neutrophilic source and provides evidence of neutrophil activity on the ocular surface of oGVHD patients. Copyright © 2017 Elsevier Inc. All rights reserved.
Constraining the Active Galactic Nucleus Contribution in a Multiwavelength Study of Seyfert Galaxies
NASA Technical Reports Server (NTRS)
Melendez, M.; Kraemer, S.B.; Schmitt, H.R.; Crenshaw, D.M.; Deo, R.P.; Mushotzky, R.F.; Bruhweiler, F.C.
2008-01-01
We have studied the relationship between the high- and low-ionization [O IV] (lambda)25.89 microns, [Ne III] (lambda)15.56 microns, and [Ne II] (lambda)12.81 microns emission lines with the aim of constraining the active galactic nuclei (AGNs) and star formation contributions for a sample of 103 Seyfert galaxies.We use the [O IV] and [Ne II] emission as tracers for the AGN power and star formation to investigate the ionization state of the emission-line gas.We find that Seyfert 2 galaxies have, on average, lower [O IV]/[Ne II] ratios than Seyfert 1 galaxies. This result suggests two possible scenarios: (1) Seyfert 2 galaxies have intrinsically weaker AGNs, or (2) Seyfert 2 galaxies have relatively higher star formation rates than Seyfert 1 galaxies. We estimate the fraction of [Ne II] directly associated with the AGNs and find that Seyfert 2 galaxies have a larger contribution from star formation, by a factor of approx.1.5 on average, than what is found in Seyfert 1 galaxies. Using the stellar component of [Ne II] as a tracer of the current star formation, we found similar star formation rates in Seyfert 1 and Seyfert 2 galaxies.We examined the mid- and far-infrared continua and found that [Ne II] is well correlated with the continuum luminosity at 60 microns and that both [Ne III] and [O IV] are better correlated with the 25 micron luminosities than with the continuum at longer wavelengths, suggesting that the mid-infrared continuum luminosity is dominated by the AGN, while the far-infrared luminosity is dominated by star formation. Overall, these results test the unified model of AGNs and suggest that the differences between Seyfert galaxies cannot be solely due to viewing angle dependence.
Seyedi, N; Maruyama, R; Levi, R
1999-08-01
We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.
Kawai, Miho; Harada, Naoaki; Takeyama, Hiromitsu; Okajima, Kenji
2010-06-01
Neutrophil elastase (NE) decreases the endothelial production of prostacyclin (PGI(2)) through the inhibition of endothelial nitric oxide synthase (NOS) activation and thereby contributes to the development of ischemia/reperfusion (I/R)-induced liver injury. We previously demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons increases the insulin-like growth factor- I (IGF-I) production and thereby reduces I/R-induced liver injury. Because PGI(2) is capable of stimulating sensory neurons, we hypothesized that NE contributes to the development of I/R-induced liver injury by decreasing IGF-I production. In the present study, we examined this hypothesis in rats subjected to hepatic I/R. Ischemia/reperfusion-induced decreases of hepatic tissue levels of CGRP and IGF-I were prevented significantly by NE inhibitors, sivelestat, and L-658, 758, and these effects of NE inhibitors were reversed completely by the nonselective cyclooxygenase inhibitor indomethacin (IM) and the nonselective NOS inhibitor L-NAME but not by the selective inducible NOS inhibitor 1400W. I/R-induced increases of hepatic tissue levels of caspase-3, myeloperoxidase and the number of apoptotic cells were inhibited by NE inhibitors, and these effects of NE inhibitors were reversed by IM and L-NAME but not by 1400W. Administration of iloprost, a stable PGI(2) analog, produced effects similar to those induced by NE inhibitors. Taken together, these observations strongly suggest that NE may play a critical role in the development of I/R-induced liver injury by decreasing the IGF-I production through the inhibition of sensory neuron stimulation, which may lead to an increase of neutrophil accumulation and hepatic apoptosis through activation of caspase-3 in rats.
Ghosh, Abhinaba; Purchase, Nicole C.; Chen, Xihua; Yuan, Qi
2015-01-01
Early odor preference learning in rodents occurs within a sensitive period [≤postnatal day (P)10–12], during which pups show a heightened ability to form an odor preference when a novel odor is paired with a tactile stimulation (e.g., stroking). Norepinephrine (NE) release from the locus coeruleus during stroking mediates this learning. However, in older pups, stroking loses its ability to induce learning. The cellular and circuitry mechanisms underpinning the sensitive period for odor preference learning is not well understood. We first established the sensitive period learning model in mice – odor paired with stroking induced odor preference in P8 but not P14 mice. This learning was dependent on NE-β-adrenoceptors as it was prevented by propranolol injection prior to training. We then tested whether there are developmental changes in pyramidal cell excitability and NE responsiveness in the anterior piriform cortex (aPC) in mouse pups. Although significant differences of pyramidal cell intrinsic properties were found in two age groups (P8–11 and P14+), NE at two concentrations (0.1 and 10 μM) did not alter intrinsic properties in either group. In contrast, in P8–11 pups, NE at 0.1 μM presynaptically decreased miniature IPSC and increased miniature EPSC frequencies. These effects were reversed with a higher dose of NE (10 μM), suggesting involvement of different adrenoceptor subtypes. In P14+ pups, NE at higher doses (1 and 10 μM) acted both pre- and postsynaptically to promote inhibition. These results suggest that enhanced synaptic excitation and reduced inhibition by NE in the aPC network may underlie the sensitive period. PMID:26635530
Silverman, A J; Hou-Yu, A; Oldfield, B J
1983-09-01
Since many peptidergic cell groups receive a diverse and complex monoaminergic innervation, we have developed a double-label procedure to visualize a peptide and a catecholamine in the same ultrathin section. Radiolabeled norepinephrine (NE) is applied locally and its reuptake into NE terminals is demonstrated by ultrastructural radioautography. Controls in this and other studies demonstrate that the NE labels only NE (and possibly epinephrine) terminals and not dopaminergic or serotonergic terminals. In the same tissue, vasopressin is localized by immunocytochemistry on unembedded sections that are subsequently embedded in epoxy resins for thin sectioning. The procedure as described here shows that NE terminals in the periventricular zone of the paraventricular nucleus of the hypothalamus innervate both vasopressin-positive and vasopressin-negative structures. This technique is useful in determining the chemical connectivity of the hypothalamus.
Nup155 regulates nuclear envelope and nuclear pore complex formation in nematodes and vertebrates
Franz, Cerstin; Askjaer, Peter; Antonin, Wolfram; Iglesias, Carmen López; Haselmann, Uta; Schelder, Malgorzata; de Marco, Ario; Wilm, Matthias; Antony, Claude; Mattaj, Iain W
2005-01-01
Nuclear envelope (NE) formation during cell division in multicellular organisms is a central yet poorly understood biological process. We report that the conserved nucleoporin Nup155 has an essential function in NE formation in Caenorhabditis elegans embryos and in Xenopus laevis egg extracts. In vivo depletion of Nup155 led to failure of nuclear lamina formation and defects in chromosome segregation at anaphase. Nup155 depletion inhibited accumulation of nucleoporins at the nuclear periphery, including those recruited to chromatin early in NE formation. Electron microscopy analysis revealed that Nup155 is also required for the formation of a continuous nuclear membrane in vivo and in vitro. Time-course experiments indicated that Nup155 is recruited to chromatin at the time of NE sealing, suggesting that nuclear pore complex assembly has to progress to a relatively late stage before NE membrane assembly occurs. PMID:16193066
NASA Astrophysics Data System (ADS)
Clairon, A.; Dahmani, B.; Acef, O.; Granveaud, M.; Domnin, Yu S.; Pouchkine, S. B.; Tatarenkov, V. M.; Felder, R.
1988-01-01
Comparison of the VNIIFTRI and LPTF frequency multiplication chains has been carried out through the measurement of the frequency of a portable VNIIFTRI (He-Ne)/CH4 laser. Agreement is within 100 Hz (1.1 parts in 1012) and is secured by the very good medium-term frequency repeatability of the (He-Ne)/CH4 VNIIFTRI portable laser (a few parts in 1013). On the same occasion a measurement of the frequency of the BIPM (He-Ne)/CH4 reference laser (B.3) has been performed at LPTF. Other experiments carried out on the BIPM laser show that the reproducibility of the (He-Ne)/CH4 system could be improved by a systematic study and then by a better control of the various perturbing factors which influence the shape of the methane-saturated absorption peak.
Coulomb and nuclear excitations of narrow resonances in 17Ne
Marganiec, J.; Wamers, F.; Aksouh, F.; ...
2016-05-25
New experimental data for dissociation of relativistic 17Ne projectiles incident on targets of lead, carbon, and polyethylene targets at GSI are presented. Special attention is paid to the excitation and decay of narrow resonant states in 17Ne. Distributions of internal energy in the 15O+p +p three-body system have been determined together with angular and partial-energy correlations between the decay products in different energy regions. The analysis was done using existing experimental data on 17Ne and its mirror nucleus 17N. The isobaric multiplet mass equation is used for assignment of observed resonances and their spins and parities. A combination of datamore » from the heavy and light targets yielded cross sections and transition probabilities for the Coulomb excitations of the narrow resonant states. Finally, the resulting transition probabilities provide information relevant for a better understanding of the 17Ne structure.« less
Outer nuclear membrane protein Kuduk modulates the LINC complex and nuclear envelope architecture
Ding, Zhao-Ying; Huang, Yu-Cheng; Lee, Myong-Chol; Tseng, Min-Jen; Chi, Ya-Hui
2017-01-01
Linker of nucleoskeleton and cytoskeleton (LINC) complexes spanning the nuclear envelope (NE) contribute to nucleocytoskeletal force transduction. A few NE proteins have been found to regulate the LINC complex. In this study, we identify one, Kuduk (Kud), which can reside at the outer nuclear membrane and is required for the development of Drosophila melanogaster ovarian follicles and NE morphology of myonuclei. Kud associates with LINC complex components in an evolutionarily conserved manner. Loss of Kud increases the level but impairs functioning of the LINC complex. Overexpression of Kud suppresses NE targeting of cytoskeleton-free LINC complexes. Thus, Kud acts as a quality control mechanism for LINC-mediated nucleocytoskeletal connections. Genetic data indicate that Kud also functions independently of the LINC complex. Overexpression of the human orthologue TMEM258 in Drosophila proved functional conservation. These findings expand our understanding of the regulation of LINC complexes and NE architecture. PMID:28716842
Diffusion of neon in white dwarf stars.
Hughto, J; Schneider, A S; Horowitz, C J; Berry, D K
2010-12-01
Sedimentation of the neutron rich isotope 22Ne may be an important source of gravitational energy during the cooling of white dwarf stars. This depends on the diffusion constant for 22Ne in strongly coupled plasma mixtures. We calculate self-diffusion constants D(i) from molecular dynamics simulations of carbon, oxygen, and neon mixtures. We find that D(i) in a mixture does not differ greatly from earlier one component plasma results. For strong coupling (coulomb parameter Γ> few), D(i) has a modest dependence on the charge Z(i) of the ion species, D(i)∝Z(i)(-2/3). However, D(i) depends more strongly on Z(i) for weak coupling (smaller Γ). We conclude that the self-diffusion constant D(Ne) for 22Ne in carbon, oxygen, and neon plasma mixtures is accurately known so that uncertainties in D(Ne) should be unimportant for simulations of white dwarf cooling.
Reinforcement Learning for Constrained Energy Trading Games With Incomplete Information.
Wang, Huiwei; Huang, Tingwen; Liao, Xiaofeng; Abu-Rub, Haitham; Chen, Guo
2017-10-01
This paper considers the problem of designing adaptive learning algorithms to seek the Nash equilibrium (NE) of the constrained energy trading game among individually strategic players with incomplete information. In this game, each player uses the learning automaton scheme to generate the action probability distribution based on his/her private information for maximizing his own averaged utility. It is shown that if one of admissible mixed-strategies converges to the NE with probability one, then the averaged utility and trading quantity almost surely converge to their expected ones, respectively. For the given discontinuous pricing function, the utility function has already been proved to be upper semicontinuous and payoff secure which guarantee the existence of the mixed-strategy NE. By the strict diagonal concavity of the regularized Lagrange function, the uniqueness of NE is also guaranteed. Finally, an adaptive learning algorithm is provided to generate the strategy probability distribution for seeking the mixed-strategy NE.
Nitric oxide, stress, and depression.
McLeod, T M; López-Figueroa, A L; López-Figueroa, M O
2001-01-01
Stress and depression have a significant impact on modern society. Even though their symptomatology is well characterized, little is known about the molecular mechanisms underlying these disturbing disorders. While the role of neurotransmitters such as serotonin, norepinephrine (NE), dopamine (DA), corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) has been extensively studied, new evidence suggests a role for the unique neurotransmitter nitric oxide (NO). This highly diffusible and reactive molecule is synthesized by at least three enzyme subtypes of NO synthase (NOS). The commonly known neuronal NOS subtype is localized in areas of the brain related to stress and depression. The limbic-hypothalamic-pituitary-adrenal (LHPA) axis is the core of this system. These interrelated pathways have in common the production, and negative feedback, of glucocorticoids. Within these areas, NO is suggested to play a role in modulating the release of other neurotransmitters, acting as a cellular communicator in plasticity and development, and/or acting as a vasodilator in regulation of blood flow. This article summarizes some of the recent advances in the understanding of the role of NO in stress and depression.
ERIC Educational Resources Information Center
Kiel, Don; And Others
Instructional applications for NeXT computers were developed by nine faculty members from the biology, mathematics and computer science, fine arts, chemistry, physics and astronomy, and geology departments as part of a grant awarded to the California State University at Los Angeles. These notes provide a schedule of events and reports from a 2-day…
Nuclear envelope rupture: little holes, big openings.
Hatch, Emily M
2018-06-01
The nuclear envelope (NE), which is a critical barrier between the DNA and the cytosol, is capable of extensive dynamic membrane remodeling events in interphase. One of these events, interphase NE rupture and repair, can occur in both normal and disease states and results in the loss of nucleus compartmentalization. NE rupture is not lethal, but new research indicates that it could have broad impacts on genome stability and activate innate immune responses. These observations suggest a new model for how changes in NE structure could be pathogenic in cancer, laminopathies, and autoinflammatory syndromes, and redefine the functions of nucleus compartmentalization. Copyright © 2018 Elsevier Ltd. All rights reserved.
Breaching the nuclear envelope in development and disease
Hatch, Emily
2014-01-01
In eukaryotic cells the nuclear genome is enclosed by the nuclear envelope (NE). In metazoans, the NE breaks down in mitosis and it has been assumed that the physical barrier separating nucleoplasm and cytoplasm remains intact during the rest of the cell cycle and cell differentiation. However, recent studies suggest that nonmitotic NE remodeling plays a critical role in development, virus infection, laminopathies, and cancer. Although the mechanisms underlying these NE restructuring events are currently being defined, one common theme is activation of protein kinase C family members in the interphase nucleus to disrupt the nuclear lamina, demonstrating the importance of the lamina in maintaining nuclear integrity. PMID:24751535
Efremov, V V; Parenskiĭ, V A
2004-04-01
Using Parensky's approach for estimating the number of breeding pairs, we determined effective subpopulation size Ne in early-run sockeye salmon Oncorhynchus nerka from Azabach'e Lake (Kamchatka) in 1977 through 1981. On average (over years and populations), biased sex ratio decreased Ne by 7% as compared to the number of fish on the spawning sites (Ni). High density reduced the Ne/Ni ratio by 62-66% because some fish were excluded from spawning. Dominance polygyny as compared to monogamy and random union of gametes could reduce Ne by about 17%.
Ironson, G; O'Cleirigh, C; Kumar, M; Kaplan, L; Balbin, E; Kelsch, C B; Fletcher, M A; Schneiderman, N
2015-08-01
Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Katori, Teppei
2008-12-01
The Mini-Booster neutrino experiment (MiniBooNE) at Fermi National Accelerator Laboratory (Fermilab) is designed to search for v μ → v e appearance neutrino oscillations. Muon neutrino charged-current quasi-elastic (CCQE) interactions (v μ + n → μ + p) make up roughly 40% of our data sample, and it is used to constrain the background and cross sections for the oscillation analysis. Using high-statistics MiniBooNE CCQE data, the muon-neutrino CCQE cross section is measured. The nuclear model is tuned precisely using the MiniBooNE data. The measured total cross section is σ = (1.058 ± 0.003 (stat) ± 0.111 (syst)) x 10more » -38 cm 2 at the MiniBooNE muon neutrino beam energy (700-800 MeV). v e appearance candidate data is also used to search for Lorentz violation. Lorentz symmetry is one of the most fundamental symmetries in modern physics. Neutrino oscillations offer a new method to test it. We found that the MiniBooNE result is not well-described using Lorentz violation, however further investigation is required for a more conclusive result.« less
Leisure Activities, Caregiving Demands, and Catecholamine Levels in Dementia Caregivers
Chattillion, Elizabeth A.; Mausbach, Brent T.; Roepke, Susan K.; von Känel, Roland; Mills, Paul J.; Dimsdale, Joel E.; Allison, Matthew; Ziegler, Michael G.; Patterson, Thomas L.; Ancoli-Israel, Sonia; Grant, Igor
2012-01-01
This study examined whether satisfaction from leisure activities moderates the relationship between caregiving demands (i.e., hours per day spent caring for a spouse with dementia) and resting levels of the catecholamines norepinephrine (NE) and epinephrine (EPI). Spousal caregivers (N=107; mean age 73.95±8.12 years) were assessed in home for plasma levels of NE and EPI, amount of care provided, and leisure satisfaction. Regression was used to determine whether leisure satisfaction moderated the relationship between hours providing care per day and catecholamine levels. A significant interaction was found between hours caregiving and leisure satisfaction for NE, but not for EPI. Post hoc regressions were conducted for both NE and EPI. At low leisure satisfaction, time spent caring for a spouse was positively associated with plasma NE (β = .41; p = .005) and EPI (β = .44; p = .003). In contrast, at high levels of satisfaction, time caregiving was not significantly associated with plasma NE (β = −.08; p = .57) or EPI (β = .23; p = .12). These findings suggest that leisure satisfaction may protect caregivers from increases in catecholamines, which have been implicated in cardiovascular risk. Further support for these findings may impact psychological treatments for distressed caregivers. PMID:22149759
Abundance ratios of oxygen, neon, and magnesium in solar active regions and flares: The FIP effect
NASA Technical Reports Server (NTRS)
Widing, K. G.; Feldman, U.
1995-01-01
Relative abundances of oxygen, neon, and magnesium have been derived for a sample of nine solar active regions, flares, and an erupting prominance by combining plots of the ion differential emission measures. The observations were photographed in the 300-600 A range by the Naval Research Laboratory (NRL) spectroheliograph on Skylab. Methods for deriving the Mg/Ne abundance ratio-which measures the separation between the low- first ionization potential (FIP) and high-FIP abundnace plateaus-have been described in previous papers. In this paper we describe the spectroscopic methods for deriving the O/Ne abundance ratio, which gives the ratio between two high-FIP elements. The plot of the O/Ne ratio versus the Mg/Ne ratio in the sample of nine Skylab events is shown. The variation in the Mg/Ne ratio by a factor of 6 is associated with a much smaller range in the O/Ne ratio. This is broadly consistent with the presence of the standard FIP pattern of abundances in the outer atmosphere of the Sun. However, a real change in the relative abundances of oxygen and neon by a factor of 1.5 cannot be excluded.
The isotropic condition of energetic particles emitted from a large solar flare. Ph.D. Thesis
NASA Technical Reports Server (NTRS)
Spalding, J.
1983-01-01
Isotope abundance ratios for 5 to 50 MeV/nuc nuclei from a large solar flare were measured. The measurements were made by the heavy isotope spectrometer telescope (HIST) on the ISEE-3 satellite orbiting the Sun near an Earth-Sun liberation point approximately one million miles sunward of the Earth. Finite values for the isotope abundance ratios C-13/C-12, N-15/N-14, O-18/O-16, Ne-22/Ne-20, Mg-25/Mg-24, and Mg-26/Mg-24, and upper limits for the isotope abundance ratios He-3/He-4, C-14/C-12, O-17/O-16 and Ne-21/Ne-20 were reported. Element abundances and spectra were measured to compare the flare with other reported flares. The flare is a typical large flare with low Fe/O abundance or = to 0.1). For C-13/C-12, N-15/N-14, O-18/O-16, Mg-25/Mg-24 and Mg-26/Mg-24 isotope abundance ratios agree with the solar system abundance ratios. Measurement for Ne-22/Ne-20 agree with the isotopic composition of the meteoritic component neon-A.
Dinan, David; Daneman, Alan; Guimaraes, Carolina V; Chauvin, Nancy A; Victoria, Teresa; Epelman, Monica
2014-12-01
Findings of neonatal encephalopathy (NE) and specifically those of hypoxic-ischemic injury are frequently evident on magnetic resonance imaging (MRI). Although MRI has become more widely used and has gained widespread acceptance as the study of choice for the evaluation of NE in recent years, its costs are high and access to MRI is sometimes limited for extremely sick neonates. Therefore, head sonography (US) continues to be the first-line imaging modality for the evaluation of the brain in neonates with NE; furthermore, in many of these infants, the diagnosis of NE may have first been made or suggested using head US. US is noninvasive, inexpensive, and portable, allowing examinations to be performed without moving the infant. However, many of the telltale signs of NE on US are subtle and may be easily overlooked, contributing to diagnostic delay or misdiagnosis. We aim to illustrate the spectrum of US findings in NE, with emphasis on those findings that may be easily overlooked on US. Recognition of these findings could potentially improve detection rates, reduce errors, and improve patient management. Copyright © 2014 Elsevier Inc. All rights reserved.
Beyond standard model searches in the MiniBooNE experiment
Katori, Teppei; Conrad, Janet M.
2014-08-05
Tmore » he MiniBooNE experiment has contributed substantially to beyond standard model searches in the neutrino sector. he experiment was originally designed to test the Δ m 2 ~ 1 eV 2 region of the sterile neutrino hypothesis by observing ν e ( ν - e ) charged current quasielastic signals from a ν μ ( ν - μ ) beam. MiniBooNE observed excesses of ν e and ν - e candidate events in neutrino and antineutrino mode, respectively. o date, these excesses have not been explained within the neutrino standard model ( ν SM); the standard model extended for three massive neutrinos. Confirmation is required by future experiments such as MicroBooNE. MiniBooNE also provided an opportunity for precision studies of Lorentz violation. he results set strict limits for the first time on several parameters of the standard-model extension, the generic formalism for considering Lorentz violation. Most recently, an extension to MiniBooNE running, with a beam tuned in beam-dump mode, is being performed to search for dark sector particles. In addition, this review describes these studies, demonstrating that short baseline neutrino experiments are rich environments in new physics searches.« less
Regulation of period 1 expression in cultured rat pineal
NASA Technical Reports Server (NTRS)
Fukuhara, Chiaki; Dirden, James C.; Tosini, Gianluca
2002-01-01
The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE - or forskolin - stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal. Copyright 2002 S. Karger AG, Basel.
Martynova, Ekaterina V; Valiullina, Aygul H; Gusev, Oleg A; Davidyuk, Yuriy N; Garanina, Ekaterina E; Shakirova, Venera G; Khaertynova, Ilsiyar; Anokhin, Vladimir A; Rizvanov, Albert A; Khaiboullina, Svetlana F
2016-01-01
Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE. The objectives of this study were to evaluate changes in serum total cholesterol, high density cholesterol (HDCL), and triglycerides. In addition to evaluation of serum cytokine activation associations, changes in lipid profile and cytokine activation were determined for gender, thrombocyte counts, and VEGF. Elevated levels of triglycerides and decreased HDCL were observed in NE, while total cholesterol did not differ from controls. High triglycerides were associated with both the lowest thrombocyte counts and high serum VEGF, as well as a high severity score. Additionally, there were higher levels of triglycerides in male than female NE patients. Low triglycerides were associated with upregulation of IFN- γ and IL-12, suggesting activation of Th1 helper cells. Furthermore, levels of IFN- γ and IL-12 were increased in patients with lower severity scores, suggesting that a Th1 type immune response is playing protective role in NE. These combined data advance the understanding of NE pathogenesis and indicate a role for high triglycerides in disease severity.
Valiullina, Aygul H.; Gusev, Oleg A.; Davidyuk, Yuriy N.; Garanina, Ekaterina E.; Shakirova, Venera G.; Khaertynova, Ilsiyar
2016-01-01
Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE. The objectives of this study were to evaluate changes in serum total cholesterol, high density cholesterol (HDCL), and triglycerides. In addition to evaluation of serum cytokine activation associations, changes in lipid profile and cytokine activation were determined for gender, thrombocyte counts, and VEGF. Elevated levels of triglycerides and decreased HDCL were observed in NE, while total cholesterol did not differ from controls. High triglycerides were associated with both the lowest thrombocyte counts and high serum VEGF, as well as a high severity score. Additionally, there were higher levels of triglycerides in male than female NE patients. Low triglycerides were associated with upregulation of IFN-γ and IL-12, suggesting activation of Th1 helper cells. Furthermore, levels of IFN-γ and IL-12 were increased in patients with lower severity scores, suggesting that a Th1 type immune response is playing protective role in NE. These combined data advance the understanding of NE pathogenesis and indicate a role for high triglycerides in disease severity. PMID:28053993
Ohtomo, Yoshiyuki
2017-02-01
Recent studies have shown that incontinence and attention-deficit/hyperactivity disorder (ADHD) coexist and there is an interaction between them. The treatment for nocturnal enuresis (NE) and ADHD, however, has not been established. At the first visit to the outpatient clinic, physical examination and history taking were carried out in 265 new patients with NE. After excluding the possibility of comorbid ADHD and related disorders, patients with monosymptomatic NE (MNE) were treated with desmopressin and/or alarm, and those with non-monosymptomatic NE (NMNE) were treated with anti-cholinergics and/or alarm. This 12 week treatment did not work in 65 patients, and they were re-assessed for comorbid ADHD. A total of 24 were diagnosed with ADHD, and they were treated with atomoxetine (1.8 mg/kg/day) in addition to ongoing therapy for NE. After 8 weeks of atomoxetine, the average wet nights per months was significantly decreased: 18.5-4.6 in the MNE group (P = 0.001), and 22.1-12.4 in the NMNE group (P = 0.0251). Overall, atomoxetine was beneficial in 19 of 24 patients. Atomoxetine may be a suitable option for refractory NE with comorbid ADHD. © 2016 Japan Pediatric Society.
Diagnostic usefulness of dermoscopy in differentiating lichen aureus from nummular eczema.
Suh, Kee Suck; Park, Jong Bin; Yang, Myeong Hyeon; Choi, Soo Young; Hwangbo, Hyun; Jang, Min Soo
2017-05-01
Lichen aureus (LA) is a variant of pigmented purpuric dermatosis that is characterized clinically by rust macules, papules or plaques, mainly on the legs. In some cases, LA can be difficult to be distinguished from nummular eczema (NE) with the naked eye. Dermoscopy can be applied to skin lesions, revealing additional features that can be highly valuable for correct diagnosis. This study was conducted to investigate characteristic dermoscopic findings of LA and to identify distinctive features that can differentiate it from NE. Fourteen LA patients and 14 NE patients diagnosed by skin biopsy were enrolled. Skin lesions were evaluated via polarized dermoscopy. On dermoscopy, "coppery orange diffuse coloration of background", "round to oval red globules", "gray dots", and "networks of brownish to gray interconnected lines" were more commonly seen in LA (100%, 92.9%, 42.9% and 64.3%, respectively) compared with NE. "Scales", "shiny yellow clods" and "irregularly distributed brownish-red globules" were more commonly seen in NE (100%, 85.7% and 57.1%, respectively) compared with LA. Dermoscopy provides valuable information for diagnosis of LA and aids in differentiating it from NE. © 2016 Japanese Dermatological Association.
Nucleon resonance structure in the finite volume of lattice QCD
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Jia -Jun; Kamano, H.; Lee, T. -S. H.
An approach for relating the nucleon resonances extracted from πN reaction data to lattice QCD calculations has been developed by using the finite-volume Hamiltonian method. Within models of πN reactions, bare states are introduced to parametrize the intrinsic excitations of the nucleon. We show that the resonance can be related to the probability P N*(E) of finding the bare state, N*, in the πN scattering states in infinite volume. We further demonstrate that the probability P V N*(E) of finding the same bare states in the eigenfunctions of the underlying Hamiltonian in finite volume approaches P N*(E) as the volumemore » increases. Our findings suggest that the comparison of P N*(E) and P V N*(E) can be used to examine whether the nucleon resonances extracted from the πN reaction data within the dynamical models are consistent with lattice QCD calculation. We also discuss the measurement of P V N*(E) directly from lattice QCD. Furthermore, the practical differences between our approach and the approach using the Lüscher formalism to relate LQCD calculations to the nucleon resonance poles embedded in the data are also discussed.« less
Nucleon resonance structure in the finite volume of lattice QCD
Wu, Jia -Jun; Kamano, H.; Lee, T. -S. H.; ...
2017-06-19
An approach for relating the nucleon resonances extracted from πN reaction data to lattice QCD calculations has been developed by using the finite-volume Hamiltonian method. Within models of πN reactions, bare states are introduced to parametrize the intrinsic excitations of the nucleon. We show that the resonance can be related to the probability P N*(E) of finding the bare state, N*, in the πN scattering states in infinite volume. We further demonstrate that the probability P V N*(E) of finding the same bare states in the eigenfunctions of the underlying Hamiltonian in finite volume approaches P N*(E) as the volumemore » increases. Our findings suggest that the comparison of P N*(E) and P V N*(E) can be used to examine whether the nucleon resonances extracted from the πN reaction data within the dynamical models are consistent with lattice QCD calculation. We also discuss the measurement of P V N*(E) directly from lattice QCD. Furthermore, the practical differences between our approach and the approach using the Lüscher formalism to relate LQCD calculations to the nucleon resonance poles embedded in the data are also discussed.« less
Childhood negative emotionality predicts biobehavioral dysregulation 15 years later
Hagan, Melissa J.; Luecken, Linda J.; Modecki, Kathryn L.; Sandler, Irwin N.; Wolchik, Sharlene A.
2016-01-01
The temperamental trait of negative emotionality (NE) plays an important role in maladaptation among adults experiencing significant life stress. However, the prospective relation between childhood NE and subsequent inter-related behavioral, emotional, and biological dysregulation in later life has not yet been established among children who experience early adversity. Using a longitudinal sample of youth who experienced parental divorce during childhood (N = 160; 53% male; 83% White), we tested the hypothesis that childhood NE would predict physiological, emotional, and behavioral dysregulation 15 years later. NE was assessed by maternal report when youth were between 9-12 years old. Fifteen years later, young adults (mean age = 25.55 years) participated in a psychosocial stress task to assess cortisol reactivity and reported on internalizing symptoms and problematic alcohol use. Structural equation modeling revealed that higher childhood NE predicted significantly greater alcohol use, internalizing symptoms, and total cortisol output during a stress task 15 years later. Importantly, these findings held adjusting for childhood internalizing symptoms. In addition, problematic alcohol use was associated with greater cortisol reactivity and internalizing symptoms. Findings suggest that childhood NE is a critical risk marker for interrelated forms of dysregulation in young adulthood among at-risk youth. PMID:27100364
Solar Control of Earth's Ionosphere: Observations from Solar Cycle 23
NASA Astrophysics Data System (ADS)
Doe, R. A.; Thayer, J. P.; Solomon, S. C.
2005-05-01
A nine year database of sunlit E-region electron density altitude profiles (Ne(z)) measured by the Sondrestrom ISR has been partitioned over a 30-bin parameter space of averaged 10.7 cm solar radio flux (F10.7) and solar zenith angle (χ) to investigate long-term solar and thermospheric variability, and to validate contemporary EUV photoionization models. A two stage filter, based on rejection of Ne(z) profiles with large Hall to Pedersen ratio, is used to minimize auroral contamination. Resultant filtered mean Ne(z) compares favorably with subauroral Ne measured for the same F10.7 and χ conditions at the Millstone Hill ISR. Mean Ne, as expected, increases with solar activity and decreases with large χ, and the variance around mean Ne is shown to be greatest at low F10.7 (solar minimum). ISR-derived mean Ne is compared with two EUV models: (1) a simple model without photoelectrons and based on the 5 -- 105 nm EUVAC model solar flux [Richards et al., 1994] and (2) the GLOW model [Solomon et al., 1988; Solomon and Abreu, 1989] suitably modified for inclusion of XUV spectral components and photoelectron flux. Across parameter space and for all altitudes, Model 2 provides a closer match to ISR mean Ne and suggests that the photoelectron and XUV enhancements are essential to replicate measured plasma densities below 150 km. Simulated Ne variance envelopes, given by perturbing the Model 2 neutral atmosphere input by the measured extremum in Ap, F10.7, and Te, are much narrower than ISR-derived geophysical variance envelopes. We thus conclude that long-term variability of the EUV spectra dominates over thermospheric variability and that EUV spectral variability is greatest at solar minimum. ISR -- model comparison also provides evidence for the emergence of an H (Lyman β) Ne feature at solar maximum. Richards, P. G., J. A. Fennelly, and D. G. Torr, EUVAC: A solar EUV flux model for aeronomic calculations, J. Geophys. Res., 99, 8981, 1994. Solomon, S. C., P. B. Hays, and V. J. Abreu, The auroral 6300 Å emission: Observations and Modeling, J. Geophys. Res., 93, 9867, 1988. Solomon, S. C. and V. J. Abreu, The 630 nm dayglow, J. Geophys. Res., 94, 6817, 1989.
NASA Astrophysics Data System (ADS)
Lee, S.; Cheon, Y.; Lee, Y.; Son, M.
2017-12-01
The Geumseongsan caldera provides an opportunity to understand the structural evolution of volcanic collapse and the role of paleostress. We focus on structural elements of the exhumed caldera floor to interpret the collapse mechanism. The caldera shows an NNW-trending elliptical shape (8×12 km). Basaltic and rhyolitic rocks are situated in the central high of the caldera, while pre-volcanic sedimentary rocks in the perimetric lowland of the volcanic rocks. Stratal attitudes change sharply from the outside to the inside of caldera bounded with a sub-vertical ring fault. The outside strata show a homocline toward SE about 15°, whereas the inside is divided into four structural domains (NE-, NW-, SE-, and SW-domains) based on the changing attitudes. The strata in NW- and SE-domains dip toward SE and NW, respectively, making an overall synclinal fold. While NE- and SW-domains comprise re-oriented, folded strata, which generally have NE- and SW-trending axes plunging toward the center. In addition, extensional and contractional structures occur distinctively in NW- and SE-domains and in NE- and SW-domains, respectively, indicating an axisymmetric deformation around NE-SW axis. The results indicate that higher horizontal mass movement toward the center occurred in NW- and SE-domains than in NE- and SW-domains while vertical mass movement was more active in the latter. This axisymmetric deformation could be produced by regional stress during the volcanic activity, which affected the collapse pattern of caldera floor. The regional stress field during the late Cretaceous is known as NW-SE horizontal maximum and NE-SW horizontal minimum stresses due to the oblique subduction of proto-Pacific Plate underneath Eurasian Plate. NNW-trending elliptical shape of the caldera is interpreted to have formed under the influence of this stresses, like a tension gash. The NW-SE maximum stress possibly acted to resist vertical displacement along the marginal fault of NW- and SE-domains, whereas the NE-SW minimum stress enabled easier vertical movement along that of NE- and SW-domains. This differential movement is interpreted to have caused a great quantity of mass transportation toward NW and SE, which concentrated the extensional and contractional structures in NW- and SE-domains and in NE- and SW-domains, respectively.
Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D
1971-03-01
Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.
NASA Astrophysics Data System (ADS)
Kudrenickis, I.; Klavs, G.
2013-12-01
Utilisation of biomass is an important factor in reducing emission of greenhouse gases (GHG); at the same time, high efficiency of biomass combustion technologies is to be ensured to minimise the methane (CH4) emission thus achieving the most efficient reduction in the total GHG emission. The authors analyse the GHG emission breakdown in Latvia among the sectors not included in the EU Emissions Trading Scheme (ETS), and, in the context of emission reduction, evaluate the energy supply in the Latvian household sector, the types of combustion technologies and the used fuels. The trend is considered for the CH4 emission factor during 1990-2010 in the household sector of EU countries, and the numerical index is calculated which illustrates decoupling the consumption of biomass fuel from CH4 emission. To evaluate the perspective of CH4 emission reduction in the Latvian household sector, two scenarios are investigated for efficiency improvement as related to the central heating equipment based on wood fuel. Biomasas izmantošana ir viens no principiālajiem virzieniem siltumnīcefekta gāzu (SEG) emisiju samazināšanā. Maksimāla SEG emisiju samazinājuma panākšanai ir nepieciešams nodrošināt biomasas sadedzināšanas iekārtu augstu efektivitāti, lai minimizētu ar biomasas kurināmā patēriņu saistīto metāna (CH4) emisiju pieaugumu. Autori raksturo Eiropas Savienības (ES) Emisiju kvotu tirdzniecības sistēmas (ETS) un tajā neietilpstošo sektoru (ne-ETS) nozīmi Latvijas SEG emisiju veidošanā, SEG emisiju relatīvo sadalījumu atbilstoši dažādiem ne- ETS sektoriem un SEG emisiju samazināšanas kontekstā analizē Latvijas mājsaimniecību sektora energoapgādi, patērēto kurināmo un izmantotās kurināmā sadedzināšanas tehnoloģijas. Rakstā ir demonstrēta SEG emisiju inventarizācijā pielietotā CH4 emisiju specifiskā faktora mājsaimniecību sektora koksnes kurināmajam skaitlisko vērtību dinamika 1990-2010 gados dažādās ES valstīs. Salīdzinot kurināmā patēriņa un CH4 emisiju apjoma izmaiņas, ir aprēķināts skaitliskais rādītājs, kas raksturo biomasas kurināmā patēriņa un CH4 emisiju "atsaisti" ES valstīs analizējamā laika posmā. Lai kvantitatīvi novērtētu CH4 emisiju samazināšanas perspektīvu Latvijas mājsaimniecību sektorā, autori analizē divus attīstības scenārijus, kas paredz dažādus mājsaimniecību centrālajā apkurē izmantoto koksnes sadedzināšanas iekārtu efektivitātes pieaugumus.
Dong, Wen-Xin; Ni, Xiang-Lian
2002-01-01
To investigate the pre-synaptic metabolism of norepinephrine (NE), judged by variations in plasma concentration of 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxymandelic acid (DOMA). Pithed and electrically stimulated (2.5 Hz) rats were given intravenous infusion of exogenous NE (6 nmol . kg-1 . min-1). Plasma NE, DHPG, DOMA, and the activities of mono- amine oxidases (MAO) were measured with the radio-enzymatic assay. Exogenous NE induces an about 100-fold increase in plasma NE concentration while blood pressure remained within normal limits. A 12-fold increase in plasma DHPG and 1.2-fold increase for DOMA were observed. When NE transportation across the pre-synaptic membrane was inhibited by desipramine (2 mg/kg, iv), a great reduction in plasma DHPG concentration (about 25 % of control) was observed while DOMA remained unchanged. When MAO-A activity was inhibited to 25 % of control by clorgyline (2 mg/kg, iv) and MAO-B to 30 % by deprenyl, the plasma DHPG and DOMA concentrations were reduced to 15 % and 70 % of controls, and to 26 % and 76 % of controls, respectively. When clorgyline and deprenyl were combined, plasma DHPG was vanished (less than 2 % of control) while plasma DOMA remained in the same range (72 % of control). The metabolizing system of NE in pre-synapse, associating with the pre-synaptic reuptake plus oxidative deamination on the external membrane of mitochondria, is predominant for the reduction to DHPG.
Effects of Carbidopa and Entacapone on the Metabolic Fate of the Norepinephrine Prodrug L-DOPS
Goldstein, David S.; Holmes, Courtney; Sewell, LaToya; Pechnik, Sandra; Kopin, Irwin J.
2016-01-01
Background L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson’s disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic aminoacid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect. Methods Twelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured. Results L-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 ± 8 and 24 ± 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 ± 0.11 nmol/L) averaged less than 1/15 000th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS. Conclusions After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation. PMID:20220040
Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.
Goldstein, David S; Holmes, Courtney; Sewell, LaToya; Pechnik, Sandra; Kopin, Irwin J
2011-01-01
L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect. Twelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured. L-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 ± 8 and 24 ± 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 ± 0.11 nmol/L) averaged less than 1/15,000 th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS. After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation.
Antitumor activity of fermented noni exudates and its fractions
LI, JINHUA; CHANG, LENG-CHEE; WALL, MARISA; WONG, D.K.W.; YU, XIANZHONG; WEI, YANZHANG
2013-01-01
Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention. PMID:24649140
Antitumor activity of fermented noni exudates and its fractions.
Li, Jinhua; Chang, Leng-Chee; Wall, Marisa; Wong, D K W; Yu, Xianzhong; Wei, Yanzhang
2013-01-01
Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention.
Hyperfine quenching of the 2s2 2p5 3 s3P2 state of Ne-like ions
NASA Astrophysics Data System (ADS)
Safronova, U. I.; Stafford, A.; Safronova, A. S.
2017-04-01
The many-body perturbation theory (RMBPT) is used to calculate energies and multipole matrix elements to evaluate hyperfine quenching of the 2s2 2p5 3 s 3P2 state in Ne-like ions. In particular, the 3P2 excited state decays to the 1S0 ground state by M2 emission, while both 1P1 and 3P1 states decay to the ground-state by E1 emission, which is substantially faster. For odd-A nuclei, the hyperfine interaction induces admixtures of 3P1 and 1P1 states into the 3P2 state, resulting in an increase of the 3P2 transition rate and a corresponding reduction of the 3P2 lifetime. We consider 22 Ne like ions with Z = 14 - 94 and nuclear moment I =1/2. We found that the largess hyperfine quenching contribution by a factor of 2 are for Ne-like 31P and 203Tl. The smallest (less than 1%) induced contribution are the following Ne-like ions: 57Fe, 107Ag, 109Ag, 183W, and 187Os ions. For another 15 Ne-like ions the hyperfine quenching contribution is between 15% and 35%. Applications to x-ray line polarization of Ne-like lines is considered. This work is supported by the Department of Energy, National Nuclear Security Administration, under Award Number DE-NA0002954.
Sosorev, Andrey Yu; Parashchuk, Olga D; Zapunidi, Sergey A; Kashtanov, Grigoriy S; Golovnin, Ilya V; Kommanaboyina, Srikanth; Perepichka, Igor F; Paraschuk, Dmitry Yu
2016-02-14
In some donor-acceptor blends based on conjugated polymers, a pronounced charge-transfer complex (CTC) forms in the electronic ground state. In contrast to small-molecule donor-acceptor blends, the CTC concentration in polymer:acceptor solution can increase with the acceptor content in a threshold-like way. This threshold-like behavior was earlier attributed to the neighbor effect (NE) in the polymer complexation, i.e., next CTCs are preferentially formed near the existing ones; however, the NE origin is unknown. To address the factors affecting the NE, we record the optical absorption data for blends of the most studied conjugated polymers, poly(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV) and poly(3-hexylthiophene) (P3HT), with electron acceptors of fluorene series, 1,8-dinitro-9,10-antraquinone (), and 7,7,8,8-tetracyanoquinodimethane () in different solvents, and then analyze the data within the NE model. We have found that the NE depends on the polymer and acceptor molecular skeletons and solvent, while it does not depend on the acceptor electron affinity and polymer concentration. We conclude that the NE operates within a single macromolecule and stems from planarization of the polymer chain involved in the CTC with an acceptor molecule; as a result, the probability of further complexation with the next acceptor molecules at the adjacent repeat units increases. The steric and electronic microscopic mechanisms of NE are discussed.
Injured nerve-derived COX2/PGE2 contributes to the maintenance of neuropathic pain in aged rats.
Ma, Weiya; Chabot, Jean-Guy; Vercauteren, Freya; Quirion, Remi
2010-07-01
Neuropathic pain (NeP) is a debilitating disease afflicting mostly the aged population. Inflammatory responses in injured nerves play a pivotal role in the pathogenesis of NeP. Injured nerve derived cyclooxygenase 2/prostaglandin E2 (COX2/PGE2) contributes to the genesis of NeP at the early stage in young rats. Here we show that COX2/PGE2 is involved in the maintenance of NeP at a chronic stage in aged rats. Eighteen months after partial sciatic nerve ligation (PSNL), NeP remained prominent in aged rats. COX2 expressing macrophages and PGE2 levels were increased in injured nerves. PGE2 receptors (EP1 and EP4) and pain-related ion channel transient receptor potential vanilloid-1 (TRPV1) were increased in the ipsilateral dorsal root ganglion (DRG) neurons of aged PSNL rats. Perineural injection of a selective COX2 inhibitor NS-398 relieved NeP, reversed PSNL increased expression of EP1, EP4 and TRPV1 and suppressed the levels of pain-related peptide substance P and calcitonin gene-related peptide in DRG neurons. These data suggest that injured nerve-derived PGE2 contributes to the maintenance of NeP at the chronic stage in aged rats. Chronically facilitating the synthesis of pain-related molecules in nociceptive DRG neurons is a novel mechanism underpinning the contribution of PGE2. Copyright 2008 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hyung Lee; Rich Johnson, Ph.D.; Kimberlyn C. Moussesau
2011-12-01
The Nuclear Energy - Knowledge base for Advanced Modeling and Simulation (NE-KAMS) is being developed at the Idaho National Laboratory in conjunction with Bettis Laboratory, Sandia National Laboratories, Argonne National Laboratory, Oak Ridge National Laboratory, Utah State University and others. The objective of this consortium is to establish a comprehensive knowledge base to provide Verification and Validation (V&V) and Uncertainty Quantification (UQ) and other resources for advanced modeling and simulation (M&S) in nuclear reactor design and analysis. NE-KAMS will become a valuable resource for the nuclear industry, the national laboratories, the U.S. NRC and the public to help ensure themore » safe operation of existing and future nuclear reactors. A survey and evaluation of the state-of-the-art of existing V&V and M&S databases, including the Department of Energy and commercial databases, has been performed to ensure that the NE-KAMS effort will not be duplicating existing resources and capabilities and to assess the scope of the effort required to develop and implement NE-KAMS. The survey and evaluation have indeed highlighted the unique set of value-added functionality and services that NE-KAMS will provide to its users. Additionally, the survey has helped develop a better understanding of the architecture and functionality of these data and knowledge bases that can be used to leverage the development of NE-KAMS.« less
Tracing tetraether lipids from source to sink in the Rhône River system (NW Mediterranean)
NASA Astrophysics Data System (ADS)
Kim, Jung-Hyun; Ludwig, Wolfgang; Buscail, Roselyne; Dorhout, Denise; Sinninghe Damste, Jaap
2015-06-01
In this study, we investigated soils and river suspended particulate matter (SPM) collected in the Rhône and its tributary basins as well as marine surface sediments taken in the Rhône prodelta (Gulf of Lions, NW Mediterranean). Thereby, we traced the signal of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from the source to sink via the Rhône River and its tributaries and identified sources of brGDGTs in rivers and marine sediments. Soil pH rather than the mean annual air temperature (MAAT) explains most of the observed variances of the brGDGT distribution in our soil dataset. The observed changes in the distribution of brGDGTs in the river SPM indicate that brGDGTs brought by the river to the sea are primarily derived from the lower Rhône and its tributary soils, even though in situ production in the river itself cannot be excluded. In marine surface sediments, it appears that the input of riverine brGDGTs is the primary source of brGDGTs in the Rhône prodelta, although the brGDGT composition may be further modified by the in situ production in the marine environment. More work is required to assess fully whether brGDGTs can be used to reconstruct the terrestrial paleoenvironmental changes using marine sediment cores taken in the Rhône prodelta close to the river mouth.
Giollo, Manuel; Martin, Alberto J M; Walsh, Ian; Ferrari, Carlo; Tosatto, Silvio C E
2014-01-01
The rapid growth of un-annotated missense variants poses challenges requiring novel strategies for their interpretation. From the thermodynamic point of view, amino acid changes can lead to a change in the internal energy of a protein and induce structural rearrangements. This is of great relevance for the study of diseases and protein design, justifying the development of prediction methods for variant-induced stability changes. Here we propose NeEMO, a tool for the evaluation of stability changes using an effective representation of proteins based on residue interaction networks (RINs). RINs are used to extract useful features describing interactions of the mutant amino acid with its structural environment. Benchmarking shows NeEMO to be very effective, allowing reliable predictions in different parts of the protein such as β-strands and buried residues. Validation on a previously published independent dataset shows that NeEMO has a Pearson correlation coefficient of 0.77 and a standard error of 1 Kcal/mol, outperforming nine recent methods. The NeEMO web server can be freely accessed from URL: http://protein.bio.unipd.it/neemo/. NeEMO offers an innovative and reliable tool for the annotation of amino acid changes. A key contribution are RINs, which can be used for modeling proteins and their interactions effectively. Interestingly, the approach is very general, and can motivate the development of a new family of RIN-based protein structure analyzers. NeEMO may suggest innovative strategies for bioinformatics tools beyond protein stability prediction.
Steuber, Nelson; Vo, Kathy; Wadhwa, Ritambhara; Birch, Jordan; Iacoban, Paulina; Chavez, Pedro; Elbayoumi, Tamer A
2016-10-26
Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted δ-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70:30 wt % surfactant mix of Lutrol F-127:VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-potential = -35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-T3 NE produced superior cytotoxicity profiles, in concentration- and time-dependent manners ( p ≤ 0.05), at least three to four folds lower IC 50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.
The plasminogen activator system modulates sympathetic nerve function.
Schaefer, Ulrich; Machida, Takuji; Vorlova, Sandra; Strickland, Sidney; Levi, Roberto
2006-09-04
Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA-null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P<0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)-null mice released much more NE (i.e., a 275% increase; P<0.05). Furthermore, vasa deferentia from t-PA-null mice were hyporesponsive to EFS (P<0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1-null mice were much more responsive (P<0.05). Coronary NE overflow from hearts subjected to ischemia/reperfusion was much smaller in t-PA-null than in WT control mice (P<0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P<0.05) in t-PA-null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.
NASA Astrophysics Data System (ADS)
Mojtahedin, Elham; Hadavi, Fatemeh; Lak, Razyeh
2015-02-01
High abundances of coccoliths have been observed in surface sediment samples from near the coasts of the Oman Sea in February 2011. At the end of the NE monsoon, the locally observed high Gephyrocapsa oceanica production is hypothesized to respond to local injections of nutrient-rich deep water into the surface water due to sea-surface cooling leading to convection. The most abundant coccolithophore species are G. oceanica followed by Emiliania huxleyi, Helicosphaera carteri, Calcidiscus leptoporus. Some species, such as Gephyrocapsa muellerae, Gephyrocapsa ericsonii, Umbilicosphaera sibogae, Umbellosphaera tenuis and Florisphaera profunda, are rare. The G. oceanica suggested a prevalence of upwelling conditions or high supply of nutrients in the Oman Sea (especially West Jask) at the end of the NE monsoon. E. huxleyi showed low relative abundances at the end of the NE monsoon. Due to the location of the Oman Sea in low latitudes with high temperatures, we have observed low abundances of G. muellerae in the study area. Additionally, we have identified low abundances of G. ericsonii at the end of the NE monsoon. Helicosphaera carteri showed a clear negative response with decreasing amounts (relative abundances) at the end of the NE monsoon. C. leptoporus, U. sibogae and U. tenuis have very low relative abundances in the NE monsoon and declined extremely at the end of the NE monsoon. F. profunda, which is known to inhabit the lower photic zone (<100 m depht) was rarely observed in the samples.
Mapanao, Ratchaneegorn; Kuo, Hsin-Wei; Chang, Chin-Chuan; Liu, Kuan-Fu; Cheng, Winton
2018-03-01
L-3,4-Dihydroxyphenylalanine (l-DOPA) is a precursor for dopamine (DA) synthesis. Assessments were conducted to analyze the effects of l-DOPA on mediating regulation of neuroendocrinological, immunological, and physiological parameters in the shrimp, Litopenaeus vannamei when they were individually injected with 0.01 N HCl or l-DOPA at 0.5 or 1.0 μmol shrimp -1 for 60, 120, and 240 min. For catecholamine synthesis evaluation, tyrosine hydroxylase (TH) and DA beta hydroxylase (DBH) activities, l-DOPA, DA, and norepinephrine (NE) levels in hemolymph were determined. The total hemocyte count (THC), differential hemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, phagocytic activity, and clearance efficiency in response to the pathogen, Vibrio alginolyticus were assessed for immune responses, and plasma glucose and lactate levels were for physiological response. Results showed that the TH activity, THC, hyaline cells (HCs), and semigranular cells (SGCs) at 120 min, DA levels at 60-240 min, PO activity in hemocytes per 50 μL of hemolymph at 60-120 min, and PO activity per granulocyte (granular cells (GCs) + SGCs) at 60 min significantly increased, but TH activity, l-DOPA levels, GCs, SGCs, and respiratory bursts in hemocytes per 10 μL of hemolymph at 60 min, respiratory bursts per hemocyte and SOD activity at 120 min, phagocytic activity at 60-240 min, and the clearance efficiency at 60-120 min significantly decreased in shrimp injected with l-DOPA at 1.0 μmol shrimp -1 . In another experiment, 60 min after shrimp had received l-DOPA at 0.5 or 1.0 μmol shrimp -1 , they were challenged with an injection of V. alginolyticus at 2 × 10 5 colony-forming units (cfu) shrimp -1 . The injection of l-DOPA at 1.0 μmol shrimp -1 also significantly increased the cumulative mortality of shrimp by 16.7%, compared to the HCl-challenged control after 120 h. These results suggest that l-DOPA administration at 1.0 μmol shrimp -1 can mediate the transient regulation of neuroendocrinological, immunological, and physiologic responses resulting in immunosuppression, which in turn promoted the susceptibility of L. vannamei to V. alginolyticus. Copyright © 2018 Elsevier Ltd. All rights reserved.
Flemming, Bonnie; Rameika, Gina
2018-05-18
On Monday, June 23, 2014 the MicroBooNE detector -- a 30-ton vessel that will be used to study ghostly particles called neutrinos -- was transported three miles across the Fermilab site and gently lowered into the laboratory's Liquid-Argon Test Facility. This video documents that move, some taken with time-lapse camerad, and shows the process of getting the MicroBooNE detector to its new home.
Broad NE 8 lambda 774 emission from quasars in the HST-FOS snapshot survey (ABSNAP)
NASA Technical Reports Server (NTRS)
Hamann, Fred; Zuo, Lin; Tytler, David
1995-01-01
We discuss the strength and frequency of broad Ne VIII lambda 774 emission from quasars measured in the Hubble Space Telescope Faint Object Spectrograph (HST-FOS) snapshot survey (Absnap). Five sources in the survey have suitable redshifts (0.86 less than or equal to Z(sub em) less than or equal to 1.31), signal-to-noise ratios and no Lyman limit absorptions. Three of the five sources have a strong broad emission line near 774 A (rest), and the remaining two sources have a less securely measured line near this wavelength. We identify these lines with Ne VIII lambda 774 based on the measured wavelengths and theoretical estimates of various line fluxes (Hamann et al. 1995a). Secure Ne VIII detections occur in both radio-loud and radio-quiet sources. We tentatively conclude that broad Ne VIII lambda 774 emission is common in quasars, with typical strengths between approximately 25% and approximately 200% of O VI lambda 1034. These Ne VIII lambda 774 measurements imply that the broad emission line regions have a much hotter and more highly ionized component than previously recognized. They also suggest that quasar continua have substantial ionizing flux out to energies greater than 207 eV (greater than 15.2 ryd, lambda less than 60 A). Photoionization calculations using standard incident spectra indicate that the Ne VIII emission requires ionization parameters U greater than or = 5, total column densities N(sub H) greater than or = 10(sub 22)/sq cm and covering factors greater than or = 25%. The temperatures could be as high as approximately 10(exp 5) K. If the gas is instead collisionally ionized, strong Ne VIII would imply equilibrium temperatures in the range approximately 400,000 less than or approximately = T(sub e) less than or approximately = 10(exp 6) K. In either case, the highly ionized Ne VIII emission regions would appear as X-ray 'warm absorbers' if they lie along our line of sight to the X-ray continuum source.
Bonhommeau, D; Lewerenz, M; Halberstadt, N
2008-02-07
We report a theoretical study of the effect induced by a helium nanodroplet environment on the fragmentation dynamics of a dopant. The dopant is an ionized neon cluster Ne(n) (+) (n=4-6) surrounded by a helium nanodroplet composed of 100 atoms. A newly designed mixed quantum/classical approach is used to take into account both the large helium cluster zero-point energy due to the light mass of the helium atoms and all the nonadiabatic couplings between the Ne(n) (+) potential-energy surfaces. The results reveal that the intermediate ionic dopant can be ejected from the droplet, possibly with some helium atoms still attached, thereby reducing the cooling power of the droplet. Energy relaxation by helium atom evaporation and dissociation, the other mechanism which has been used in most interpretations of doped helium cluster dynamics, also exhibits new features. The kinetic energy distribution of the neutral monomer fragments can be fitted to the sum of two Boltzmann distributions, one with a low kinetic energy and the other with a higher kinetic energy. This indicates that cooling by helium atom evaporation is more efficient than was believed so far, as suggested by recent experiments. The results also reveal the predominance of Ne(2) (+) and He(q)Ne(2) (+) fragments and the absence of bare Ne(+) fragments, in agreement with available experimental data (obtained for larger helium nanodroplets). Moreover, the abundance in fragments with a trimeric neon core is found to increase with the increase in dopant size. Most of the fragmentation is achieved within 10 ps and the only subsequent dynamical process is the relaxation of hot intermediate He(q)Ne(2) (+) species to Ne(2) (+) by helium atom evaporation. The dependence of the ionic fragment distribution on the parent ion electronic state reached by ionization is also investigated. It reveals that He(q)Ne(+) fragments are produced only from the highest electronic state, whereas He(q)Ne(2) (+) fragments originate from all the electronic states. Surprisingly, the highest electronic states also lead to fragments that still contain the original ionic dopant species. A mechanism is conjectured to explain this fragmentation inhibition.
Office of Nuclear Energy Knowledge Management Program Situational Analysis Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kimberlyn C. Mousseau
2011-12-01
Knowledge management (KM) has been a high priority for the Department of Energy (DOE) Office of Nuclear Energy (NE) for the past several years. NE Programs are moving toward well-established knowledge management practices and a formal knowledge management program has been established. Knowledge management is being practiced to some level within each of the NE programs. Although it continues to evolve as NE programs evolve, a formal strategic plan that guides the implementation of KM has been developed. Despite the acceptance of KM within DOE NE, more work is necessary before the NE KM program can be considered fully successful.more » Per Dr. David J. Skyrme[1], an organization typically moves through the following evolutionary phases: (1) Ad-hoc - KM is being practiced to some level in some parts of the organization; (2) Formal - KM is established as a formal project or program; (3) Expanding - the use of KM as a discipline grows in practice across different parts of the organization; (4) Cohesive - there is a degree of coordination of KM; (5) Integrated - there are formal standards and approaches that give every individual access to most organizational knowledge through common interfaces; and (6) Embedded - KM is part-and-parcel of everyday tasks; it blends seamlessly into the background. According to the evolutionary phases, the NE KM program is operating at the two lower levels, Ad-hoc and Formal. Although KM is being practiced to some level, it is not being practiced in a consistent manner across the NE programs. To be fully successful, more emphasis must be placed on establishing KM standards and processes for collecting, organizing, sharing and accessing NE knowledge. Existing knowledge needs to be prioritized and gathered on a routine basis, its existence formally recorded in a knowledge inventory. Governance to ensure the quality of the knowledge being used must also be considered. For easy retrieval, knowledge must be organized according to a taxonomy that mimics nuclear energy programs. Technologies need to be established to make accessing the knowledge easier for the user. Finally, knowledge needs to be used as part of a well defined work process.« less
Hughes, K.L.H.; Masterlark, Timothy; Mooney, W.D.
2010-01-01
The M9.2 Sumatra-Andaman earthquake (SAE) occurred three months prior to the M8.7 Nias earthquake (NE). We propose that the NE was mechanically triggered by the SAE, and that poroelastic effects were a major component of this triggering. This study uses 3D finite element models (FEMs) of the Sumatra-Andaman subduction zone (SASZ) to predict the deformation, stress, and pore pressure fields of the SAE. The coseismic slip distribution for the SAE is calibrated to near-field GPS data using FEM-generated Green's Functions and linear inverse methods. The calibrated FEM is then used to predict the postseismic poroelastic contribution to stress-triggering along the rupture surface of the NE, which is adjacent to the southern margin of the SAE. The coseismic deformation of the SAE, combined with the rheologic configuration of the SASZ produces two transient fluid flow regimes having separate time constants. SAE coseismic pore pressures in the relatively shallow forearc and volcanic arc regions (within a few km depth) dissipate within one month after the SAE. However, pore pressures in the oceanic crust of the down-going slab persist several months after the SAE. Predictions suggest that the SAE initially induced MPa-scale negative pore pressure near the hypocenter of the NE. This pore pressure slowly recovered (increased) during the three-month interval separating the SAE and NE due to lateral migration of pore fluids, driven by coseismic pressure gradients, within the subducting oceanic crust. Because pore pressure is a fundamental component of Coulomb stress, the MPa-scale increase in pore pressure significantly decreased stability of the NE fault during the three-month interval after the SAE and prior to rupture of the NE. A complete analysis of stress-triggering due to the SAE must include a poroelastic component. Failure to include poroelastic mechanics will lead to an incomplete model that cannot account for the time interval between the SAE and NE. Our transient poroelastic model explains both the spatial and temporal characteristics of triggering of the NE by the SAE. ?? 2010 Elsevier B.V.
NASA Astrophysics Data System (ADS)
Wen, T.; Castro, M. C.; Ellis, B. R.; Hall, C. M.; Lohmann, K. C.; Bouvier, L.
2014-12-01
Recent studies in the Michigan Basin looked at the atmospheric and terrigenic noble gas signatures of deep brines to place constraints on the past thermal history of the basin and to assess the extent of vertical transport processes within this sedimentary system. In this contribution, we present noble gas data of shale gas samples from the Antrim shale formation in the Michigan Basin. The Antrim shale was one of the first economic shale-gas plays in the U.S. and has been actively developed since the 1980's. This study pioneers the use of noble gases in subsurface shale gas in the Michigan Basin to clarify the nature of vertical transport processes within the sedimentary sequence and to assess potential variability of noble gas signatures in shales. Antrim Shale gas samples were analyzed for all stable noble gases (He, Ne, Ar, Kr, Xe) from samples collected at depths between 300 and 500m. Preliminary results show R/Ra values (where R and Ra are the measured and atmospheric 3He/4He ratios, respectively) varying from 0.022 to 0.21. Although most samples fall within typical crustal R/Ra range values (~0.02-0.05), a few samples point to the presence of a mantle He component with higher R/Ra ratios. Samples with higher R/Ra values also display higher 20Ne/22Ne ratios, up to 10.4, and further point to the presence of mantle 20Ne. The presence of crustally produced nucleogenic 21Ne and radiogenic 40Ar is also apparent with 21Ne/22Ne ratios up to 0.033 and 40Ar/36Ar ratios up to 312. The presence of crustally produced 4He, 21Ne and 40Ar is not spatially homogeneous within the Antrim shale. Areas of higher crustal 4He production appear distinct to those of crustally produced 21Ne and 40Ar and are possibly related the presence of different production levels within the shale with varying concentrations of parent elements.
Louw, Adriaan; Diener, Ina; Landers, Merrill R; Puentedura, Emilio J
2014-08-15
Multicenter, randomized, controlled trial on preoperative pain neuroscience education (NE) for lumbar radiculopathy. To determine if the addition of NE to usual preoperative education would result in superior outcomes with regard to pain, function, surgical experience, and health care utilization postsurgery. One in 4 patients after lumbar surgery (LS) for radiculopathy experience persistent pain and disability, which is nonresponsive to perioperative treatments. NE focusing on the neurophysiology of pain has been shown to decrease pain and disability in populations with chronic low back pain. Eligible patients scheduled for LS for radiculopathy were randomized to receive either preoperative usual care (UC) or a combination of UC plus 1 session of NE delivered by a physical therapist (verbal one-on-one format) and a NE booklet. Sixty-seven patients completed the following outcomes prior to LS (baseline), and 1, 3, 6, and 12 months after LS: low back pain (numeric rating scale), leg pain (numeric rating scale), function (Oswestry Disability Index), various beliefs and experiences related to LS (10-item survey with Likert scale responses), and postoperative utilization of health care (utilization of health care questionnaire). At 1-year follow-up, there were no statistical differences between the experimental and control groups with regard to primary outcome measure of low back pain (P = 0.183), leg pain (P = 0.075), and function (P = 0.365). In a majority of the categories regarding surgical experience, the NE group scored significantly better: better prepared for LS (P = 0.001); preoperative session preparing them for LS (P < 0.001) and LS meeting their expectations (P = 0.021). Health care utilization post-LS also favored the NE group (P = 0.007) resulting in 45% less health care expenditure compared with the control group in the 1-year follow-up period. NE resulted in significant behavior change. Despite a similar pain and functional trajectory during the 1-year trial, patients with LS who received NE viewed their surgical experience more favorably and used less health care facility in the form of medical tests and treatments. 2.
Is there any electrophysiological evidence for subliminal error processing?
Shalgi, Shani; Deouell, Leon Y.
2013-01-01
The role of error awareness in executive control and modification of behavior is not fully understood. In line with many recent studies showing that conscious awareness is unnecessary for numerous high-level processes such as strategic adjustments and decision making, it was suggested that error detection can also take place unconsciously. The Error Negativity (Ne) component, long established as a robust error-related component that differentiates between correct responses and errors, was a fine candidate to test this notion: if an Ne is elicited also by errors which are not consciously detected, it would imply a subliminal process involved in error monitoring that does not necessarily lead to conscious awareness of the error. Indeed, for the past decade, the repeated finding of a similar Ne for errors which became aware and errors that did not achieve awareness, compared to the smaller negativity elicited by correct responses (Correct Response Negativity; CRN), has lent the Ne the prestigious status of an index of subliminal error processing. However, there were several notable exceptions to these findings. The study in the focus of this review (Shalgi and Deouell, 2012) sheds new light on both types of previous results. We found that error detection as reflected by the Ne is correlated with subjective awareness: when awareness (or more importantly lack thereof) is more strictly determined using the wagering paradigm, no Ne is elicited without awareness. This result effectively resolves the issue of why there are many conflicting findings regarding the Ne and error awareness. The average Ne amplitude appears to be influenced by individual criteria for error reporting and therefore, studies containing different mixtures of participants who are more confident of their own performance or less confident, or paradigms that either encourage or don't encourage reporting low confidence errors will show different results. Based on this evidence, it is no longer possible to unquestioningly uphold the notion that the amplitude of the Ne is unrelated to subjective awareness, and therefore, that errors are detected without conscious awareness. PMID:24009548
Mitrano, Darlene A; Jackson, Kelsey; Finley, Samantha; Seeley, Allison
2018-02-10
The α1-adrenergic receptors (α1ARs) have been implicated in numerous actions of the brain, including attention and wakefulness. Additionally, they have been identified as contributing to disorders of the brain, such as drug addiction, and recent work has shown a role of these receptors in relapse to psychostimulants. While some functionality is known, the actual subcellular localization of the subtypes of the α1ARs remains to be elucidated. Further, their anatomical relationship to receptors for other neurotransmitters, such as dopamine (DA), remains unclear. Therefore, using immunohistochemistry and electron microscopy techniques, this study describes the subcellular localization of the α1b-adrenergic receptor (α1bAR), the subtype most tied to relapse behaviors, as well as its relationship to the D1-dopamine receptor (D1R) in both the shell and core of the rat nucleus accumbens (NAc). Overall, α1bARs were found in unmyelinated axons and axon terminals with some labeling in dendrites. In accordance with other studies of the striatum, the D1R was found mainly in dendrites and spines; therefore, colocalization of the D1R with the α1bAR was rare postsynaptically. However, in the NAc shell, when the receptors were co-expressed in the same neuronal elements there was a trend for both receptors to be found on the plasma membrane, as opposed to the intracellular compartment. This study provides valuable anatomical information about the α1bAR and its relationship to the D1R and the regulation of DA and norepinephrine (NE) neurotransmission in the brain which have been examined previously. Published by Elsevier Ltd.
Tian, Huan; Yang, Fei-Fei; Liu, Chun-Yu; Liu, Xin-Min; Pan, Rui-Le; Chang, Qi; Zhang, Ze-Sheng; Liao, Yong-Hong
2017-01-21
Daylily flowers, the flower and bud parts of Hemerocallis citrina or H. fulva, are well known as Wang-You-Cao in Chinese, meaning forget-one's sadness plant. However, the major types of active constituents responsible for the neurological effects remain unclear. This study was to examine the protective effects of hydroalcoholic extract and fractions and to identify the active fractions. The extract of daylily flowers was separated with AB-8 resin into different fractions containing non-phenolic compounds, phenolic acid derivatives and flavonoids as determined using UPLC-DAD chromatograms. The neuroprotective activity was measured by evaluating the cell viability and lactate dehydrogenase release using PC12 cell damage models induced by corticosterone and glutamate. The neurological mechanisms were explored by determining their effect on the levels of dopamine (DA), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), noradrenaline (NE) and acetylcholine (ACh) in the cell culture medium measured using an LC-MS/MS method. Pretreatment of PC12 cells with the extract and phenolic fractions of daylily flowers at concentrations ranging from 0.63 to 5 mg raw material/mL significantly reversed corticosterone- and glutamate-induced neurotoxicity in a dose-dependent manner. The fractions containing phenolic acid derivatives (0.59% w/w in the flowers) and/or flavonoids (0.60% w/w) exerted similar dose-dependent neuroprotective effect whereas the fractions with non-phenolic compounds exhibited no activity. The presence of phenolic acid derivatives in the corticosterone- and glutamate-treated PC12 cells elevated the DA level in the cell culture medium whereas flavonoids resulted in increased ACH and 5-HT levels. Phenolic acid derivatives and flavonoids were likely the active constituents of daylily flowers and they conferred a similar extent of neuroprotection, but affected the release of neurotransmitters in a different manner.